NOAEL Studies
UV Filter / Sunscreen
Enzacamene (4-Methylbenzylidene Camphor) NOAEL Studies
INCI: ENZACAMENE
CAS: 36861-47-9
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
SCCS_vision_codex 88 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | - | NOAEL study | {"effect":"in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_007"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | - | NOAEL study | {"effect":"in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_007"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | - | NOAEL study | {"effect":"in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_007"} |
| SCCS_vision_codex | NOAEL | =1 | - | - | oral | - | NOAEL study | {"effect":"in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_007"} |
| SCCS_vision_codex | NOAEL | =4 | - | - | - | - | NOAEL study | {"effect":"Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_032"} |
| SCCS_vision_codex | NOAEL | =4 | - | - | - | - | NOAEL study | {"effect":"Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_032"} |
| SCCS_vision_codex | NOAEL | =4 | - | - | - | - | NOAEL study | {"effect":"Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_032"} |
| SCCS_vision_codex | NOAEL | =4 | - | - | - | - | NOAEL study | {"effect":"Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_032"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | - | - | Developmental | developmental toxicity | {"dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_013"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | - | - | Developmental | developmental toxicity | {"dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_013"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | - | - | Developmental | developmental toxicity | {"dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_013"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | - | - | Developmental | developmental toxicity | {"dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_013"} |
| SCCS_vision_codex | NOAEL | =25 | - | rat | oral | - | NOAEL study | {"effect":"information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","page":3,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 90-day | genotoxicity | {"dose":"At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.","effect":"___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an","page":7,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_003"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | dermal | subchronic | repeated dose toxicity | {"dose":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).","effect":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation","page":8,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_004"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg | rat | dermal | - | NOAEL study | {"dose":"Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.","effect":"sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.","effect":"ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | - | rat | oral | - | NOAEL study | {"effect":"information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","page":3,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 90-day | genotoxicity | {"dose":"At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.","effect":"___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an","page":7,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_003"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | dermal | subchronic | repeated dose toxicity | {"dose":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).","effect":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation","page":8,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_004"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg | rat | dermal | - | NOAEL study | {"dose":"Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.","effect":"sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | - | rat | oral | - | NOAEL study | {"effect":"information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","page":3,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 90-day | genotoxicity | {"dose":"At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.","effect":"___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an","page":7,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_003"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | dermal | subchronic | repeated dose toxicity | {"dose":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).","effect":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation","page":8,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_004"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg | rat | dermal | - | NOAEL study | {"dose":"Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.","effect":"sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.","effect":"ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.","effect":"ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_005"} |
| SCCS_vision_codex | NOAEL | =25 | - | rat | oral | - | NOAEL study | {"effect":"information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","page":3,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_001"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 90-day | genotoxicity | {"dose":"At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.","effect":"___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an","page":7,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_003"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | - | dermal | subchronic | repeated dose toxicity | {"dose":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).","effect":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation","page":8,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_004"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg | rat | dermal | - | NOAEL study | {"dose":"Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.","effect":"sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors","page":10,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.","effect":"ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_005"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 17-day | NOAEL study | {"dose":"At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.","effect":"SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control","page":6,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_002"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"citation":"Ref.: Gleich et al","dose":"The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.","effect":"xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_017"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 17-day | NOAEL study | {"dose":"At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.","effect":"SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control","page":6,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_002"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 17-day | NOAEL study | {"dose":"At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.","effect":"SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control","page":6,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_002"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"citation":"Ref.: Gleich et al","dose":"The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.","effect":"xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_017"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"citation":"Ref.: Gleich et al","dose":"The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.","effect":"xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_017"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | oral | 17-day | NOAEL study | {"dose":"At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.","effect":"SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control","page":6,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_002"} |
| SCCS_vision_codex | NOAEL | =30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"citation":"Ref.: Gleich et al","dose":"The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.","effect":"xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi","page":25,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_017"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc","page":22,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_008"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | {"dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","effect":"t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio","page":38,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_022"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc","page":22,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_008"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | {"dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","effect":"t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio","page":38,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_022"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc","page":22,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_008"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | {"dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","effect":"t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio","page":38,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_022"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc","page":22,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_008"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | {"dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","effect":"t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio","page":38,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_022"} |
| SCCS_vision_codex | NOAEL | =66 | mg/kg bw/day | human | dermal | - | NOAEL study | {"dose":"(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.","effect":"ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_020"} |
| SCCS_vision_codex | NOAEL | =66 | mg/kg bw/day | human | dermal | - | NOAEL study | {"dose":"(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.","effect":"ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_020"} |
| SCCS_vision_codex | NOAEL | =66 | mg/kg bw/day | human | dermal | - | NOAEL study | {"dose":"(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.","effect":"ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_020"} |
| SCCS_vision_codex | NOAEL | =66 | mg/kg bw/day | human | dermal | - | NOAEL study | {"dose":"(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.","effect":"ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte","page":32,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_020"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.","effect":"he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (","page":9,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | {"dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","effect":"toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg","page":18,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | 90d | reproductive toxicity | {"dose":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_007"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.","effect":"he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (","page":9,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.","effect":"he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (","page":9,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | {"dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","effect":"toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg","page":18,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | 90d | reproductive toxicity | {"dose":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_007"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | {"dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","effect":"toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg","page":18,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | 90d | reproductive toxicity | {"dose":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_007"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | - | - | developmental | developmental toxicity | {"dose":"A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.","effect":"he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (","page":9,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | {"dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","effect":"toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg","page":18,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | 90d | reproductive toxicity | {"dose":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_007"} |
| SCCS_vision_codex | NOAEL | =400 | - | rat | oral | - | NOAEL study | {"dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","effect":"ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","page":22,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_008"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 90d | reproductive toxicity | {"dose":"The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_006"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw /day | - | oral | 90-day | NOAEL study | {"dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","page":24,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | - | rat | oral | - | NOAEL study | {"dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","effect":"ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","page":22,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_008"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | - | rat | oral | - | NOAEL study | {"dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","effect":"ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","page":22,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_008"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 90d | reproductive toxicity | {"dose":"The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_006"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw /day | - | oral | 90-day | NOAEL study | {"dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","page":24,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 90d | reproductive toxicity | {"dose":"The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_006"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw /day | - | oral | 90-day | NOAEL study | {"dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","page":24,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | - | rat | oral | - | NOAEL study | {"dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","effect":"ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","page":22,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_008"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg/day | rat | dermal | 90 day | NOAEL study | {"dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","effect":"bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_011"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | oral | 90d | reproductive toxicity | {"dose":"The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","effect":"e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside","page":21,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_006"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw /day | - | oral | 90-day | NOAEL study | {"dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","page":24,"pdf":"sccs_o_262.pdf","row_type":"noael_study","study_id":"sccs_o_262_noael_011"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.","effect":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.","effect":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.","effect":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_010"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.","effect":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the","page":24,"pdf":"sccp_o_075.pdf","row_type":"noael_study","study_id":"sccp_o_075_noael_010"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 46 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | - | - | oral | - | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=unclear:in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.; EFFECT=in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"","duration":"","effect":"in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"","noael_value":"unclear:in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; 3) a clear NOAEL obtained in a relevant species; 4) exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products.","page":10,"route":"oral","species":"","study_id":"sccp_o_075_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 4 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=unclear:Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the; EFFECT=Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"","duration":"","effect":"Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"","noael_value":"unclear:Table 4: Lines of evidence for endocrine activity via T modality*: According to data of Schlum | pf et al. ( | 2001) The NOEL | (estrogenic a | ctivity) of 4 | -MBC in the","page":32,"route":"","species":"","study_id":"sccs_o_262_noael_032"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | - | rat | oral | - | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=unclear:information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t; EFFECT=information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"","duration":"","effect":"information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"","noael_value":"unclear:information then available, the SCCNFP adopted on 25 May 2004 opinion SCCNFP/0779/04, where it stated that because of the very low MOS (Margin of Safety) which can be derived from currently available information, it is requested that the … data should be provided as a matter of urgency. Following data has been requested: complete physico-chemical data; data on dermal penetration according to current guidelines, including the study of the different factors affecting the quantitative outcome of the results; a clear NOAEL obtained in a relevant species; exposure data on other uses (cosmetic and non-cosmetic) and on oral intake when used in e.g. lip products. In May 2004 the SCCNFP received submissions from Merck KGaA on estrogenic potential of this UV-filter, a reproduction toxicity study in rats and data on toxicokinetics. 2. TERMS OF REFERENCE 1. On the basis of provided data the SCCP is asked to assess the risk to consumers when 4- MBC is used in sunscreen products? 2. Does the SCCP recommend any further restrictions for t","page":3,"route":"oral","species":"rat","study_id":"sccp_o_075_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | mg/kg | rat | dermal | - | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=25; DOSE=Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.; EFFECT=sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats.","duration":"","effect":"sults to human pathophysiology, the present findings in rats cannot be disregarded without a proper understanding of the mechanisms involved. As goitrogenesis is not a trivial process but is in general associated with increased possibility for thyroid autonomy or thyroid carcinoma, disturbances of the thyroid hormone axis should be considered with great caution. Risk assessment is further hampered by the lack of adequate data on dermal penetration and the fact that 25 mg/kg body weight/day is a LOAEL rather than a NOAEL in rats. 4-Methylbenzylidene Camphor is presently widely used in cosmetic sunscreen products and has been available to the consumer for many years. However, reassessment of the available data has raised issues of concern about its safe use in cosmetic sunscreen products. For a better evaluation of these potential effects, the following additional information is required: 1) complete physico-chemical data; 2) a dermal penetration study according to current guidelines, including the study of the different factors","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg","noael_value":"25","page":10,"route":"dermal","species":"rat","study_id":"sccp_o_075_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=ese studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.; EFFECT=ese studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. SCCS has evaluated the original publications and found them difficult to evaluate. For example, it is not fully clear how many original studies were performed and if data from different studies were investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence from all the data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured, and results were uneven and often not clearly dose-dependent. The studies showed that 4-MBC affected gene expression and protein levels of endocrine-related receptors and growth factors in the brain, prostate and uterus. Patterns were not always consistent between mRNA and protein levels. Gene expression patterns in the prostate differed between the dorsal and ventral sites, whereas the effects of 4-MBC were more pronounced in the dorsolateral; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"ese studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.","duration":"","effect":"ese studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. SCCS has evaluated the original publications and found them difficult to evaluate. For example, it is not fully clear how many original studies were performed and if data from different studies were investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence from all the data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured, and results were uneven and often not clearly dose-dependent. The studies showed that 4-MBC affected gene expression and protein levels of endocrine-related receptors and growth factors in the brain, prostate and uterus. Patterns were not always consistent between mRNA and protein levels. Gene expression patterns in the prostate differed between the dorsal and ventral sites, whereas the effects of 4-MBC were more pronounced in the dorsolateral","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":24,"route":"","species":"","study_id":"sccs_o_262_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | mg/kg bw/day | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g.; EFFECT=, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g.","duration":"90-day","effect":", 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":24,"route":"oral","species":"","study_id":"sccs_o_262_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | mg/kg bw/day | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher.; EFFECT=vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. The effects of 4-MBC observed on the thyroid were demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. After dermal exposure, thyroid effects occur at higher exposure doses: e.g. 400 mg/kg bw /day. This Opinion did not address the potential impact of 4-MBC on the environment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher.","duration":"90-day","effect":"vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. The effects of 4-MBC observed on the thyroid were demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. After dermal exposure, thyroid effects occur at higher exposure doses: e.g. 400 mg/kg bw /day. This Opinion did not address the potential impact of 4-MBC on the environment.","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":41,"route":"oral","species":"","study_id":"sccs_o_262_noael_031"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =30 | mg/kg bw/day | rat | oral | 17-day | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT== 30; DOSE=At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.; EFFECT=SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂.","duration":"17-day","effect":"SCCP/1042/06 Opinion on 4-Methylbenzylidene camphor ____________________________________________________________________________________________ 6 8 17-day oral study with the Wistar rat, dosages of 0, 30 & 300 mg 4-MBC/kg bw/day. At 300 mg/kg bw/day: - TSH increase 1.7 times for ♂ and 7.5 times for ♀ at top dose, - increased thyroid gland weight at top dose, - endothelial hypertrophy of thyroid glands at top dose, - dose-related decrease in prostate weight in ♂. Proposed oral NOAEL by authors = 30 mg/kg bw/day. 8 28-day oral study with the Wistar rat at dosages of 0 and 1000 mg 4-MBC/kg bw/day. At 1000 mg/kg bw/day: - increased relative liver weight, - decreased absolute and relative prostate weight in ♂, - reduced absolute thymus weight, - increased absolute and relative thyroid gland weight, - increase in thyroxine (T4) plasma levels, - significant fall in triiodothyronine (T3) plasma levels, - marked pattern of stimulation of the thyroid gland, though different from the positive control","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 30","page":6,"route":"oral","species":"rat","study_id":"sccp_o_075_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 66 | mg/kg bw/day | human | dermal | - | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=66; DOSE=(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.; EFFECT=ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"(2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day.","duration":"","effect":"ersion Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 32 The SCCNFP noticed that the assay deviated from the OECD guideline proposal and several methodological shortcomings were noticed. Furthermore, in vivo potency of the UV-filters is importantly lower than the one observed for the positive control. According to data of Schlumpf et al. (2001) The NOEL (estrogenic activity) of 4-MBC in the in vivo is 66 mg/kg bw/day. The SCCNFP concluded that, based on the actual scientific knowledge, organic UV-filters used in cosmetic sunscreen products, including 4-MBC, which are allowed on the EU market today have no estrogenic effects that could potentially affect human health. Human data From SCCP/1042/06 A number of human tests for the effect on thyroid and pituitary hormones following cutaneous application were described. In the largest (double-blind) study, 24 volunte","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"66","page":32,"route":"dermal","species":"human","study_id":"sccs_o_262_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg/day | rat | dermal | 90 day | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=100; DOSE=The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.; EFFECT=s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","duration":"90 day","effect":"s 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations conta","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":24,"route":"dermal","species":"rat","study_id":"sccp_o_075_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg/day | rat | dermal | 90 day | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=100; DOSE=The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.; EFFECT=levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations containing 6% of 4-MBC), no plasma levels were provided either. Moreover, in rat studies with higher; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","duration":"90 day","effect":"levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not available, which makes relevant comparison impossible. Human data were introduced earlier in the submission that was leading to opinion XXIV/1377/96 on 21 January 1998. But although 24 volunteers were exposed dermally for 14 days (twice per day, 5g formulations containing 6% of 4-MBC), no plasma levels were provided either. Moreover, in rat studies with higher","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":24,"route":"dermal","species":"rat","study_id":"sccp_o_075_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg/day | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study.; EFFECT=rs, out of which the "carryover" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of the 90d dermal toxicity study, based upon thyroid effects occurring at higher levels. • the application of 2mg/cm² of a sunscreen formulation can be considered as a worst-case scenario As such, following the toxicokinetic expert's opinion and accepting that the toxicokinetic part of the MoS can be reduced from 4 to 1, a MoS of 25; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study.","duration":"90-day","effect":"rs, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of the 90d dermal toxicity study, based upon thyroid effects occurring at higher levels. • the application of 2mg/cm² of a sunscreen formulation can be considered as a worst-case scenario As such, following the toxicokinetic expert's opinion and accepting that the toxicokinetic part of the MoS can be reduced from 4 to 1, a MoS of 25","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":18,"route":"dermal","species":"rat","study_id":"sccs_o_262_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg/day | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study.; EFFECT=the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of the 90d dermal toxicity study, based upon thyroid effects occurring at higher levels. • the application of 2mg/cm² of a sunscreen formulation can be considered as a worst-case scenario As such, following the toxicokinetic expert's opinion and accepting that the toxicokinetic part of the MoS can be reduced from 4 to 1, a MoS of 25 needs to be achieved. No new data was submitted in 2019. SCCS comment When comparing the human and rat toxicokinetic data, the AUC and Cmax values in human are lower than in rats, s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study.","duration":"90-day","effect":"the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of the 90d dermal toxicity study, based upon thyroid effects occurring at higher levels. • the application of 2mg/cm² of a sunscreen formulation can be considered as a worst-case scenario As such, following the toxicokinetic expert's opinion and accepting that the toxicokinetic part of the MoS can be reduced from 4 to 1, a MoS of 25 needs to be achieved. No new data was submitted in 2019. SCCS comment When comparing the human and rat toxicokinetic data, the AUC and Cmax values in human are lower than in rats, s","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":18,"route":"dermal","species":"rat","study_id":"sccs_o_262_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg bw/day | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher.; EFFECT=en taking all lines of evidence into account, the SCCS concurs with the ECHA, that there is sufficient evidence that 4-MBC may act as an endocrine disruptor and has effects on both the thyroid and estrogen systems. Effects on the androgen system are not so evident, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. The effects of 4-MBC observed on the thyroid were demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. After dermal exposure, thyroid effects occur at higher exposure doses: e.g. 400 mg/kg bw /day. This Opinion did not address the potential impact of 4-MBC on the environment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher.","duration":"90-day","effect":"en taking all lines of evidence into account, the SCCS concurs with the ECHA, that there is sufficient evidence that 4-MBC may act as an endocrine disruptor and has effects on both the thyroid and estrogen systems. Effects on the androgen system are not so evident, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system, found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. The effects of 4-MBC observed on the thyroid were demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. After dermal exposure, thyroid effects occur at higher exposure doses: e.g. 400 mg/kg bw /day. This Opinion did not address the potential impact of 4-MBC on the environment.","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":41,"route":"oral","species":"","study_id":"sccs_o_262_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =400 | - | rat | oral | - | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=unclear:ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der; DOSE=As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.; EFFECT=ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","duration":"","effect":"ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"","noael_value":"unclear:ice of all animals of the high dosage group. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After der","page":22,"route":"oral","species":"rat","study_id":"sccp_o_075_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =400 | - | rat | oral | - | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=unclear:oup. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After dermal application of 4-MBC to the rat, th; DOSE=As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.; EFFECT=oup. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After dermal application of 4-MBC to the rat, th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application.","duration":"","effect":"oup. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After dermal application of 4-MBC to the rat, th","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"","noael_value":"unclear:oup. The authors also state that gross necropsy, microscopy, clinical biochemistry and haematology (with special attention for thyroid hormone levels) did not reveal any test substance related abnormalities. As far as toxicokinetics are concerned, the test item is reported to be absorbed in a dose- dependent manner and metabolized into its two major metabolites after dermal application. Based upon the test results, the authors have established the following values: - dermal NOAEL = 400 mg 4-MBC/kg bw/day - dermal NOEL = 100 mg 4-MBC/kg bw/day 3.2.5 Toxicokinetic-based Margin of Safety for the use of 4-MBC in sunscreen formulations In this document, the following argumentation is taken into account by the authors: 8 After oral administration of 4-MBC to the rat, 3-(4-carboxybenzylidene)-camphor was identified as the major metabolite in the plasma. 4-MBC was found at very low level and the 3-(4-carboxybenzylidene)-6-hydroxycamphor concentration fell below its limit of detection. After dermal application of 4-MBC to the rat, th","page":22,"route":"oral","species":"rat","study_id":"sccp_o_075_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 400 | mg/kg/day | rat | dermal | 90 day | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=400; DOSE=The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.; EFFECT=bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","duration":"90 day","effect":"bstance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg/day","noael_value":"400","page":24,"route":"dermal","species":"rat","study_id":"sccp_o_075_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 400 | mg/kg/day | rat | dermal | 90 day | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=400; DOSE=The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.; EFFECT=inistration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not availabl; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day.","duration":"90 day","effect":"inistration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the rat. The presented 90 day dermal toxicity study with the rat results in a NOAEL value of 400 mg/kg/day. However, among the effects noted at that dosage level, perturbations of the thyroid system are included. Since the latter belong to the major concerns with regard to the toxicological profile of 4-MBC, it is preferable to use the NOEL value of 100 mg/kg/day for further calculations. Although the plasma concentrations for a NOEL of 100 mg 4-MBC/kg/day are available in the 90d dermal study in the rat, the corresponding plasma levels in man after repeated dermal administration are not availabl","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg/day","noael_value":"400","page":24,"route":"dermal","species":"rat","study_id":"sccp_o_075_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 400 | mg/kg bw /day | - | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=400; DOSE=In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.; EFFECT=or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","duration":"90-day","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal-repeat dose-toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g. 400 mg/kg bw /day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies at levels lower than the current NOAEL","endpoint":"","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw /day","noael_value":"400","page":24,"route":"oral","species":"","study_id":"sccs_o_262_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2000 | mg/kg bw/day | rat | - | chronic | - | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=2000; DOSE=0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.; EFFECT=0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics.","duration":"chronic","effect":"0, 2000 mg/kg bw/day - As described by Renwick and Lazarus [1998], the interspecies factor of 10 can be subdivided in a factor 4.0 for toxicokinetics and a factor 2.5 for toxicodynamics. The toxicokinetic factor takes into account individual differences between the external and the internal dose and thus reflects the chronic blood concentration or the body burden of the substance under study. In order to set this factor to 1, plasma levels are measured in rats after repeated administration of the substance at its NOAEL and are compared with plasma levels measured in humans after repeated administration of the compound under in-use conditions. More specifically, these plasma concentrations are plotted as a function of time and in case the obtained areas under the curve show to be significantly lower in humans than in the rat, the factor 4.0 becomes 1 and a MoS of 25 might be considered. Unfortunately the current submission lacks the plasma levels for the repeated administration of 25 mg 4-MBC/kg/day (proposed NOAEL-value) in the","endpoint":"","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2000","page":24,"route":"","species":"rat","study_id":"sccp_o_075_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | mg/kg bw/day | - | - | Developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=10; DOSE=3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.; EFFECT=SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","duration":"Developmental","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data o","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":25,"route":"","species":"","study_id":"sccs_o_262_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | mg/kg bw/day | rat | - | Developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=10; DOSE=3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats wer; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","duration":"Developmental","effect":"SCCS-rejected applicant NOAEL: ________________________________________________________ 25 could be associated with any adverse effects on reproduction that have not been demonstrated in earlier studies conducted under standardised and controlled protocols. 3.3.5.2 Developmental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats wer","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":25,"route":"","species":"rat","study_id":"sccs_o_262_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 10 | mg/kg bw/day | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=10; DOSE=mental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: mental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats were dosed with the test substance at dose levels of 0, 10, 30 and 100 mg/kg/day by oral gavage between days 6 to 15 of gestation (Gleich 1988). These females were killed on day 20 of gestation and the uterine contents examined in detail to evalua; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"mental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: mental Toxicity From XXIV/1377/96 A teratogenicity study revealed a NOAEL value for developmental effects of 10 mg/kg bw/day, based upon the observation of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats were dosed with the test substance at dose levels of 0, 10, 30 and 100 mg/kg/day by oral gavage between days 6 to 15 of gestation (Gleich 1988). These females were killed on day 20 of gestation and the uterine contents examined in detail to evalua","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":25,"route":"oral","species":"rat","study_id":"sccs_o_262_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 25 | mg/kg bw/day | - | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.; EFFECT=studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossification is due to reduced body weight gains in dams. From the SCCS point of view, this conclusion is questionable, since maternal toxicity does not necessarily lead to reduced ossification (Nitzsche, 2017). The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.; CITATION=Ref: Lichtensteiger et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Lichtensteiger et al; DETAILS_JSON={"cas_number":"36861-47-9","citation":"Ref: Lichtensteiger et al","dose":"The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.","duration":"developmental","effect":"studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossification is due to reduced body weight gains in dams. From the SCCS point of view, this conclusion is questionable, since maternal toxicity does not necessarily lead to reduced ossification (Nitzsche, 2017). The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":25,"route":"","species":"","study_id":"sccs_o_262_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=30; DOSE=The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.; EFFECT=xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi; CITATION=Ref.: Gleich et al; CITATION_NUMBERS=[]; REFERENCE=Ref.: Gleich et al; DETAILS_JSON={"cas_number":"36861-47-9","citation":"Ref.: Gleich et al","dose":"The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species.","duration":"developmental","effect":"xtremities seen in foetuses from this treatment group. Since a level of maternal toxicity was seen in this treatment group (slightly reduced weight gain), this incidence of reduced ossification was considered to be secondary to this effect on the dams. The dose-dependent increase of rudimentary lumbar ribs in both sexes of foetuses from Groups 3 and 4 (30 and 100 mg/kg/day) was also attributed to stress in the dams being sufficient to express the developmental instability inherent in the species. Consequently, the NOAEL for both maternal and foetal toxicity in this study was determined to be 30 mg/kg bw/day. Ref.: Gleich et al., 1988 A publication was submitted that described a developmental toxicity study with 4-MBC (Lichtensteiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossi","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":25,"route":"","species":"rat","study_id":"sccs_o_262_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 30 | mg/kg bw/day | rat | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=30; DOSE=The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.; EFFECT=teiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossification is due to reduced body weight gains in dams. From the SCCS point of view, this conclusion is questionable, since maternal toxicity does not necessarily lead to reduced ossification (Nitzsche, 2017). The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.; CITATION=Ref: Lichtensteiger et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Lichtensteiger et al; DETAILS_JSON={"cas_number":"36861-47-9","citation":"Ref: Lichtensteiger et al","dose":"The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.","duration":"developmental","effect":"teiger et al., 2015). In this study, rats were exposed to mixtures of chemicals, including 4-MBC. There were no treatment groups that studied the effects of 4-MBC alone. This study on mixtures was therefore excluded. Ref: Lichtensteiger et al., 2015 SCCS comment The authors considered that the reduced ossification is due to reduced body weight gains in dams. From the SCCS point of view, this conclusion is questionable, since maternal toxicity does not necessarily lead to reduced ossification (Nitzsche, 2017). The NOAEL for maternal and foetal toxicity from this developmental study is 30 mg/kg bw/day, which is higher than the previously reported NOAEL of 25 mg/kg bw/day for 4- MBC.","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":25,"route":"","species":"rat","study_id":"sccs_o_262_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 30 | mg/kg bw/day | - | - | 90-day | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=30; DOSE=The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06).; EFFECT=400 mg/kg bw/day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these facts together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies can be associated with any adverse effects on reproduction that have not been demonstrated in earlier conducted studies with standardised and controlled protocols. A prenatal developmental toxicity study with 4-MBC resulted in a NOAEL for both maternal and foetal toxicity of 30 mg/kg bw/day. Mutagenicity / genotoxicity 4-MBC was tested in one valid bacterial gene mutation study and one valid mammalian gene mutation study with negative results. After re-evaluation of the chromosomal aberration study on 4-MBC from 1986, the SCCS has noted that only 4 h exposure was used with and without S9 mix, which is not in line with current OECD TG 473 recommending using 4 h (-/+ S9) and 24 h (-S9) exposure. Therefore, the study was considered as inconclusiv; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06).","duration":"90-day","effect":"400 mg/kg bw/day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these facts together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies can be associated with any adverse effects on reproduction that have not been demonstrated in earlier conducted studies with standardised and controlled protocols. A prenatal developmental toxicity study with 4-MBC resulted in a NOAEL for both maternal and foetal toxicity of 30 mg/kg bw/day. Mutagenicity / genotoxicity 4-MBC was tested in one valid bacterial gene mutation study and one valid mammalian gene mutation study with negative results. After re-evaluation of the chromosomal aberration study on 4-MBC from 1986, the SCCS has noted that only 4 h exposure was used with and without S9 mix, which is not in line with current OECD TG 473 recommending using 4 h (-/+ S9) and 24 h (-S9) exposure. Therefore, the study was considered as inconclusiv","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":40,"route":"","species":"","study_id":"sccs_o_262_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 100 | mg/kg bw/day | - | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=100; DOSE=A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.; EFFECT=he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported.","duration":"developmental","effect":"he high-dose group. A dose-dependent increase of rudimentary lumbar ribs in foetuses of both sexes of the intermediate- and high-dose was reported. The authors concluded that ’the maternal animal was sufficiently stressed to express the developmental instability inherent in the species’. There was some retardation of ossification in foetuses of the intermediate and high dose groups. There was no evidence of teratogenesis. Because developmental effects were noted at 30 and 100 mg/kg bw/day, it is concluded that the NOAEL for developmental effects is 10 mg/kg bw/day. 8 Fertile hen's eggs : Groups of 20 eggs were treated with doses (mg/egg) of 0, 0.1, 0.5, 1.0, 5.0 and 10.0. Two series were carried out: in the first, the injections were made on the first day of incubation, and in the second, on the fifth day of incubation. There was no evidence of toxic or teratogenic effect in the surviving chicks; a no effect level of 0.1 mg/egg is suggested, whether the injection was made on the first or fifth day of incubation. Toxicokinetics (","endpoint":"developmental toxicity","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":9,"route":"","species":"","study_id":"sccp_o_075_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 100 | mg/kg/day | rat | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=of some retardation of ossification at 30 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats were dosed with the test substance at dose levels of 0, 10, 30 and 100 mg/kg/day by oral gavage between days 6 to 15 of gestation (Gleich 1988). These females were killed on day 20 of gestation and the uterine contents examined in detail to evaluate any potential effects on reproduction and the embryo. Over this treatment regime, the dose levels of 10 and 30 mg/kg/day proved to be non-toxic to the p; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"of some retardation of ossification at 30 mg/kg bw/day.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: of some retardation of ossification at 30 mg/kg bw/day. There was no evidence of teratogenesis. Based on this study, the NOAEL for developmental toxicity was determined as being 10 mg/kg bw/day. From SCCP/1184/08 In the Opinion from 2008 the full developmental toxicity test report from 1988 was studied. This reveals that the effects on which the above-mentioned NOAEL is based are not clearly related to the test substance and the data obtained are not statistically significant. The study cannot be used to derive a NOAEL. Data submitted 2019 Information taken from EFfCI In a prenatal developmental toxicity study, groups of female rats were dosed with the test substance at dose levels of 0, 10, 30 and 100 mg/kg/day by oral gavage between days 6 to 15 of gestation (Gleich 1988). These females were killed on day 20 of gestation and the uterine contents examined in detail to evaluate any potential effects on reproduction and the embryo. Over this treatment regime, the dose levels of 10 and 30 mg/kg/day proved to be non-toxic to the p","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":25,"route":"oral","species":"rat","study_id":"sccs_o_262_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 400 | mg/kg bw/day | - | oral | 90-day | developmental toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=400; DOSE=In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.; EFFECT=or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal repeat dose toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g., 400 mg/kg bw/day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these facts together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies can be associated with any adverse effects on reproduction that have not been demonstrated in earlier conducted studies with standardised and controlled protocols. A prenatal developmental toxicity study with 4-MBC resulted in a NOAEL for both maternal and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher.","duration":"90-day","effect":"or the development of offspring. In the 90-day oral study, 4-MBC induced significant thyroid effects at dose levels of 50 mg/kg bw/day and higher. At exposure levels of 25 mg/ kg bw/day only slight increases in T4 were seen, none of the other thyroid effects were observed at this dose (Hofmann, 1984). Hence, thyroid effects occur at oral exposure levels of 50 mg 4-MBC/kg bw/day. In the dermal repeat dose toxicity study, slight thyroid effects were observed at even higher exposure doses: e.g., 400 mg/kg bw/day. The NOAEL of 25 mg/kg bw/day was based on thyroid effects observed in the 90-day study (SCCNFP/0779/04 and SCCP/1042/06). Taken these facts together, the SCCS is of the opinion that it is not biologically plausible that the molecular parameters measured in these studies can be associated with any adverse effects on reproduction that have not been demonstrated in earlier conducted studies with standardised and controlled protocols. A prenatal developmental toxicity study with 4-MBC resulted in a NOAEL for both maternal and","endpoint":"developmental toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":40,"route":"oral","species":"","study_id":"sccs_o_262_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | =25 | mg/kg/day | rat | oral | 90-day | genotoxicity | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT== 25; DOSE=At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.; EFFECT=___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal.","duration":"90-day","effect":"___________________________________________________________________________________________ 7 - increased T3 values for ♀ and ♂, though for the latter only in the recovery group, - elevated TSH values for ♀, - hypertrophied epithelium of the thyroid gland with increased mitotic activity in the secretory cells in ♂ and ♀ 8 90-day oral study with the Wistar rat, dosages of 0 & 25 mg 4-MBC/kg bw/day. At 25 mg/kg bw/day: - increased T4 values for ♀, - histological examination of the thyroid was normal. Proposed oral NOAEL by authors = 25 mg/kg/day. Phototoxicity and photosensitisation A mice study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any phototoxic effect. A guinea pig study with 5% 4-MBC and a human study with 4% 4-MBC did not reveal any photosensitising potential. (Photo-)mutagenicity The bacterial mutation (Ames) test and the in vitro chromosomal aberration test were both negative. Their photomutagenicity-counterparts also delivered negative results. Dermal absorption 5% of 14C-labelled 4-MBC in an","endpoint":"genotoxicity","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":7,"route":"oral","species":"rat","study_id":"sccp_o_075_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 25 | mg/kg bw/day | - | dermal | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_075; REPORT_TITLE=Opinion on 4-Methylbenzylidene Camphor COLIPA N° S60; OPINION_NUMBER=SCCP/1042/06; COMMITTEE=SCCP; REPORT_DATE=adopted on 12 June 2001; VALUE_TEXT=25; DOSE=______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).; EFFECT=______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers).","duration":"subchronic","effect":"______________________________________________________________________ 8 The thyroid volume was found to be reduced by 1.7% in the treated group and increased by 3.11% in the placebo group (also consisting of 12 ♂ and 12 ♀ volunteers). Although these findings were found to be statistically significant, the authors attribute them to the inaccuracy of the method used rather than to any substance-related effect. Opinion of the SCCNFP of 21/01/1998 The Margin of Safety of 4-MBC was calculated taking into account the NOAEL value of 25 mg/kg bw/day of the subchronic acute toxicity study and the dermal absorption value of 1.9%. Thus a MoS of 110 was obtained and the use of 4-MBC up to 4% in sunscreens was accepted. 3.1.2 Taken from opinion n° SCCNFP/0483/01, adopted on 12 June 2001 As a result of a publication by Schlumpf et al. [2001], in which the potential estrogenic effects of 5 UVB filters (including 4-MBC) were studied, the SCCNFP was requested to reconsider the safety evaluation of the organic UV-filters under investigation","endpoint":"repeated dose toxicity","ingredient":"3-(4-Methylbenzylidene)-camphor","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":8,"route":"dermal","species":"","study_id":"sccp_o_075_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 25 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.; EFFECT=ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day.","duration":"Sub-chronic","effect":"ghtly higher after exposure. No new data was submitted in 2019. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity From SCCNFP/0779/04 and SCCP/1042/06 In oral 28-day and 90-day studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. N","endpoint":"repeated dose toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":21,"route":"oral","species":"rat","study_id":"sccs_o_262_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 25 | mg/kg bw/day | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=10000 mg/kg LD50-oral-rat:; EFFECT=C very rarely caused contact allergies in humans. Acute toxicity LD50-oral-mouse: 10000 mg/kg LD50-oral-rat: 10000 mg/kg LD50-oral-dog: 5000 mg/kg Repeated dose toxicity In 28-day and 90-day oral studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects was derived at 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"10000 mg/kg LD50-oral-rat:","duration":"28-day","effect":"C very rarely caused contact allergies in humans. Acute toxicity LD50-oral-mouse: 10000 mg/kg LD50-oral-rat: 10000 mg/kg LD50-oral-dog: 5000 mg/kg Repeated dose toxicity In 28-day and 90-day oral studies, 4-MBC was administered daily to rats at dosage levels ranging from 25 to 312 mg/kg bw/day. The effects noted were mainly situated at the level of the thyroid axis, with deviations of normal thyroxine (T4), triiodothyronine (T3) and/or thyroid-stimulating hormone (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects was derived at 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors","endpoint":"repeated dose toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":39,"route":"oral","species":"rat","study_id":"sccs_o_262_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the "carryover" values (accumulation) could be calculated.; EFFECT=toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the "carryover" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","duration":"90-day","effect":"toxicokinetic factor from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg","endpoint":"repeated dose toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":18,"route":"dermal","species":"rat","study_id":"sccs_o_262_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg/day | rat | dermal | 90-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the "carryover" values (accumulation) could be calculated.; EFFECT=from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the "carryover" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated.","duration":"90-day","effect":"from 4 to 1, upon request of the SCCP, an external expert in toxicokinetics studied the dossier. Acknowledging the concerns of the Committee, the expert proposed to estimate the repeated dose plasma levels for 4-MBC and its metabolites, based upon the available single dose plasma levels and the amounts still present after 24 hours, out of which the \"carryover\" values (accumulation) could be calculated. Comparing these levels with the plasma levels of 4-MBC and its metabolites in the rat at the NOEL instead of the NOAEL value (worst case), leads to the conclusion that the estimated human values are systematically lower than their rat counterparts, supporting approval of the requested reduction of the toxicokinetic factor from 4 to 1. Nevertheless, this approach is based upon two assumptions, namely: 1) 100 mg/kg/day needs to be the actual NOEL-value for 4-MBC in the 90-day dermal study. 2) The presented human study needs to be considered as a worst-case situation. The SCCP is of the opinion that: • 100 mg/kg/day is the NOEL of t","endpoint":"repeated dose toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":18,"route":"dermal","species":"rat","study_id":"sccs_o_262_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 25 | mg/kg bw/day | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.; EFFECT=• Body weights and oestrous cycles of adult F1 female rat offspring were not affected by 4-MBC. Ref: Faass et al., 2009 CEHOS, 2012 The Danish Centre on Endocrine Disrupters (CEHOS) described reproductive toxicity of 4- MBC. These effects were based on the same studies as described by EFfCI and will not be repeated. Ref: Hass et al., 2012 SCCS comment A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. SCCS has evaluated the original publications and found them difficult to evaluate. For example, it is not fully clear how many original studies were performed and if data from different studies were investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence from all the data and derive a justifiable NOAEL. In these studies, many different molecular p; CITATION=Ref: Faass et al; CITATION_NUMBERS=[]; REFERENCE=Ref: Faass et al; DETAILS_JSON={"cas_number":"36861-47-9","citation":"Ref: Faass et al","dose":"In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.","duration":"","effect":"• Body weights and oestrous cycles of adult F1 female rat offspring were not affected by 4-MBC. Ref: Faass et al., 2009 CEHOS, 2012 The Danish Centre on Endocrine Disrupters (CEHOS) described reproductive toxicity of 4- MBC. These effects were based on the same studies as described by EFfCI and will not be repeated. Ref: Hass et al., 2012 SCCS comment A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. SCCS has evaluated the original publications and found them difficult to evaluate. For example, it is not fully clear how many original studies were performed and if data from different studies were investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence from all the data and derive a justifiable NOAEL. In these studies, many different molecular p","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":24,"route":"","species":"rat","study_id":"sccs_o_262_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 25 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects.; EFFECT=SCCS-rejected applicant NOAEL: in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluation of the data provided, the SCCS is not able to conclude on the genotoxic potential of 4-MBC and therefore a safety evaluation was not performed. It is important to note that the current re-evaluation of 4-MBC also resulted in a change in the SED, which was calculated to be approximately; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluation of the data provided, the SCCS is not able to conclude on the genotoxic potential of 4-MBC and therefore a safety evaluation was not performed. It is important to note that the current re-evaluation of 4-MBC also resulted in a change in the SED, which was calculated to be approximately","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":38,"route":"oral","species":"","study_id":"sccs_o_262_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 25 | mg/kg bw/day | - | dermal | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=1 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL.; EFFECT=1 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. Reproductive toxicity A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence of all data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured and results were uneven and often not clearly dose-dependent. The stu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"1 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL.","duration":"","effect":"1 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. Reproductive toxicity A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence of all data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured and results were uneven and often not clearly dose-dependent. The stu","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":40,"route":"dermal","species":"","study_id":"sccs_o_262_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 25 | mg/kg bw/day | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=25; DOSE=In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.; EFFECT=from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence of all data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured and results were uneven and often not clearly dose-dependent. The studies show that 4-MBC affected gene expression and protein levels of endocrine-related receptors and growth factors in the brain, prostate, and uterus. Patterns were not always consistent between mRNA and protein levels. Gene expression patterns in the prostate differed between the dorsal and ventral sites, whereas the effects of 4-MBC were more pronounced in the dorsolateral pro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included.","duration":"","effect":"from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS and made it difficult to properly assess the weight of evidence of all data and derive a justifiable NOAEL. In these studies, many different molecular parameters were measured and results were uneven and often not clearly dose-dependent. The studies show that 4-MBC affected gene expression and protein levels of endocrine-related receptors and growth factors in the brain, prostate, and uterus. Patterns were not always consistent between mRNA and protein levels. Gene expression patterns in the prostate differed between the dorsal and ventral sites, whereas the effects of 4-MBC were more pronounced in the dorsolateral pro","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"25","page":40,"route":"","species":"","study_id":"sccs_o_262_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 50 | mg/kg/day | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=50; DOSE=This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.; EFFECT=SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day.","duration":"","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 22 did not affect the reproductive function of female rats or the development of offspring. This study points towards a reproduction toxicity NOAEL value of 50 mg/kg/day. Data submitted 2019 Information taken from EFfCI The results of reproduction toxicity studies with 4-MBC were reported in four separate publications; Durrer et al., 2005 and 2007 and Maerkel et al., 2005 and 2007. A treatment regime similar to that in one-generation reproductive toxicity studies with an extended period of treatment given to F1 pups which were raised to adulthood was used. Although the exposure duration was similar to that in a one-generation reproductive toxicity study, exc","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":22,"route":"","species":"rat","study_id":"sccs_o_262_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 50 | mg/kg bw/day | - | oral | 90-day | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=50; DOSE=The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.; EFFECT=t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","duration":"90-day","effect":"t, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on the 90-day exposure study, the NOAEL of 4-MBC was determined to be 25 mg/kg bw/day. From dermal exposure, thyroid effects occur at relatively high exposure doses: e.g. 400 mg/kg bw/day. 3.4 SAFETY EVALUATION (including calculation of the MoS) Based on an evaluatio","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":38,"route":"oral","species":"","study_id":"sccs_o_262_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | rat | dermal | 90d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.; EFFECT=l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","duration":"90d","effect":"l NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not consider any of the observed effects relevant. SCCNFP co","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":21,"route":"dermal","species":"rat","study_id":"sccs_o_262_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | - | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.; EFFECT=SCCS-rejected applicant NOAEL: ies When taking all lines of evidence into account, the SCCS concurs with ECHA that there is sufficient evidence that 4-MBC may act as an endocrine disruptor and have effects on both the thyroid and estrogen system. Effects on the androgen system are not so evident, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher.","duration":"","effect":"SCCS-rejected applicant NOAEL: ies When taking all lines of evidence into account, the SCCS concurs with ECHA that there is sufficient evidence that 4-MBC may act as an endocrine disruptor and have effects on both the thyroid and estrogen system. Effects on the androgen system are not so evident, as only in vitro evidence is available. The in vivo studies that investigated effects of 4-MBC on the estrogen system found effects at exposure levels of 100 mg/kg bw/day and higher. Hence, these effects occur at exposures that are much higher than the NOAEL for 4-MBC. Effects observed in more recent reproduction studies of Schlumpf and co-workers (see section 3.3.5 Reproductive toxicity) were considered not to be biologically plausible to support adverse endocrine effects and as such cannot be used to derive a NOAEL or LOAEL. The effects of 4-MBC observed on the thyroid were consistently demonstrated in several studies. The majority of these studies show that oral exposure levels of 50 mg/kg bw/day of 4-MBC and higher induced significant thyroid effects. Based on th","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":38,"route":"oral","species":"","study_id":"sccs_o_262_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | - | dermal | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=100; DOSE=SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL.; EFFECT=SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. Reproductive toxicity A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS an; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL.","duration":"","effect":"SCCS/1640/21 Final version Opinion on 4-Methylbenzylidene camphor (4-MBC) ___________________________________________________________________________________________ _________________________________________________________________________ 40 considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. Reproductive toxicity A series of publications from Schlumpf and co-workers describe the effects of 4-MBC on reproductive parameters. In these studies, exposure levels below the current NOAEL of 25 mg/kg bw/day were included. It is not fully clear how many original studies have been performed and if data from different studies have been investigated separately or together. These unclarities hampered the interpretation of the results of these studies by the SCCS an","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":40,"route":"dermal","species":"","study_id":"sccs_o_262_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 400 | mg/kg bw/day | rat | oral | 90d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_262; REPORT_TITLE=OPINION on 4-Methylbenzylidene camphor (4-MBC); OPINION_NUMBER=SCCS/1640/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 29 April 2022; VALUE_TEXT=400; DOSE=The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.; EFFECT=e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"36861-47-9","citation":"","dose":"The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day.","duration":"90d","effect":"e (TSH) levels, thyroid gland weight, etc. The oral NOAEL (90d - rat) based upon thyroid effects showed to be 25 mg/kg bw/day. When dermally applied to the rat skin for 90 days at reported dosage levels of 0, 100, 400 and 2000 mg/kg bw/day, some slight thyroid effects were observed at 400 mg/kg bw/day, while the animals of the high-dosage group had to be sacrificed due to the severity of the local effects they experienced (epidermal lesions, wounds, necrosis). The authors considered 400 mg/kg bw/day as the dermal NOAEL of 4-MBC and 100 mg/kg bw/day as its dermal NOEL. No new data was submitted in 2019. 3.3.4.3 Chronic (> 12 months) toxicity No new data was submitted in 2019. 3.3.5 Reproductive toxicity 3.3.5.1 Fertility and reproduction toxicity SCCNFP/0779/04 and SCCP/1184/08 When tested in a one-generation reproduction toxicity study, 4-MBC displayed some minor thyroid effects at the highest dosage levels tested (25 and 50 mg/kg bw/day), though not at the lowest one (12.5 mg/kg bw/day). The study authors did not conside","endpoint":"reproductive toxicity","ingredient":"4-Methylbenzylidene camphor (4-MBC)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":21,"route":"oral","species":"rat","study_id":"sccs_o_262_noael_006"} |
openFDA substances 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 8I3XWY40L9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H22O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8I3XWY40L9"} |
| openFDA substances | FDA UNII substance identifier | 8I3XWY40L9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H22O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8I3XWY40L9"} |
| openFDA substances | FDA UNII substance identifier | 8I3XWY40L9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H22O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8I3XWY40L9"} |