NOAEL Studies
UV Filter / Sunscreen
Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (Tinosorb M) NOAEL Studies
INCI: METHYLENE BIS-BENZOTRIAZOLYL TETRAMETHYLBUTYLPHENOL
CAS: 103597-45-1
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
SCCS_vision_codex 24 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw/d | rat | dermal | 90-day | NOAEL study | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","dose":"F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_001"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw | rat | dermal | 90-day | carcinogenicity | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_003"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | pig | dermal | Chronic | NOAEL study | {"citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"luding treated skin samples.","effect":"luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity","page":35,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_005"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | dermal | subchronic | repeated dose toxicity | {"dose":"The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.","effect":"n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.0144 | mg/kg bw/d | rat | dermal | 13-week | dermal absorption | {"dose":"Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;","effect":"study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_008"} |
| SCCS_vision_codex | NOAEL | =59.2 | mg/kg bw/d | rat | dermal | - | dermal absorption | {"dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority","page":53,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_009"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw/d | rat | dermal | 90-day | NOAEL study | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","dose":"F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_001"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw | rat | dermal | 90-day | carcinogenicity | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_003"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | pig | dermal | Chronic | NOAEL study | {"citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"luding treated skin samples.","effect":"luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity","page":35,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_005"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | dermal | subchronic | repeated dose toxicity | {"dose":"The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.","effect":"n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.0144 | mg/kg bw/d | rat | dermal | 13-week | dermal absorption | {"dose":"Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;","effect":"study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_008"} |
| SCCS_vision_codex | NOAEL | =59.2 | mg/kg bw/d | rat | dermal | - | dermal absorption | {"dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority","page":53,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_009"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw/d | rat | dermal | 90-day | NOAEL study | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","dose":"F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_001"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw | rat | dermal | 90-day | carcinogenicity | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_003"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | pig | dermal | Chronic | NOAEL study | {"citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"luding treated skin samples.","effect":"luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity","page":35,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_005"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | dermal | subchronic | repeated dose toxicity | {"dose":"The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.","effect":"n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.0144 | mg/kg bw/d | rat | dermal | 13-week | dermal absorption | {"dose":"Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;","effect":"study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_008"} |
| SCCS_vision_codex | NOAEL | =59.2 | mg/kg bw/d | rat | dermal | - | dermal absorption | {"dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority","page":53,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_009"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw/d | rat | dermal | 90-day | NOAEL study | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","dose":"F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_001"} |
| SCCS_vision_codex | NOAEL | =800 | mg/kg bw | rat | dermal | 90-day | carcinogenicity | {"citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","effect":"SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study","page":32,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_003"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/d | pig | dermal | Chronic | NOAEL study | {"citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"luding treated skin samples.","effect":"luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity","page":35,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_005"} |
| SCCS_vision_codex | NOAEL | =10 | % | rat | dermal | subchronic | repeated dose toxicity | {"dose":"The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.","effect":"n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.0144 | mg/kg bw/d | rat | dermal | 13-week | dermal absorption | {"dose":"Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;","effect":"study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose","page":52,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_008"} |
| SCCS_vision_codex | NOAEL | =59.2 | mg/kg bw/d | rat | dermal | - | dermal absorption | {"dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority","page":53,"pdf":"sccs_o_168.pdf","row_type":"noael_study","study_id":"sccs_o_168_noael_009"} |
ToxValDB_GESTIS_DNEL 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_GESTIS_DNEL | DNEL systemic | =21.16 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15633358_15633359:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_e48b095a1e337957d3f787d7a6e8e628 |
| ToxValDB_GESTIS_DNEL | DNEL systemic | =23.5 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL_dup_-_15633358_15633359:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d8e1ed50e6902b2379344c8a4b4a805e |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 28 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 800 | mg/kg bw/d | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=800; DOSE=F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.; EFFECT=0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,; CITATION=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,; CITATION_NUMBERS=[2005,400,800]; REFERENCE=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","dose":"F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","duration":"90-day","effect":"0 1500 2000 Desquamation 0 0 0 4/5 1/4 3/5 0 2/5 Scabs 0 0 0 0 0 0 0 1/5 Erythema 0 0 0 0 1/4 1/5 0 1/5 Second treatment period (vehicle: ointment) 0 1000 1500 2000 Desquamation 0 0 0 0 0 0 0 0 Scabs 0 0 0 1/5 0 0 2/5 1/5 Erythema 0 0 0 0 0 1/5 1/5 1/5 Third treatment period (vehicle: ointment) 0 100 400 800 Desquamation 0 0 0 0 0 0 0 0 Scabs 1/5 0 0 0 1/5 0 0 1/5 Erythema 0 0 0 0 0 3/5 0 1/5 M: male; F: female Conclusion Under the conditions of this dose range-finding study, the dermal no-observed-effect-level (NOEL) of the formulated micronised UV filter Tinosorb® M was determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed,","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"800","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 800 | mg/kg bw | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=800; DOSE=s determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.; EFFECT=SCCS-rejected applicant NOAEL: s determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a c; CITATION=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL; CITATION_NUMBERS=[2005,400,800]; REFERENCE=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"s determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: s determined to be 800 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a c","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw","noael_value":"800","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg bw/d | pig | dermal | Chronic | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=luding treated skin samples.; EFFECT=luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity; CITATION=Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL; CITATION_NUMBERS=[2006,30,22,5]; REFERENCE=Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"luding treated skin samples.","duration":"Chronic","effect":"luding treated skin samples. In high dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":35,"route":"dermal","species":"pig","study_id":"sccs_o_168_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg bw/d | pig | dermal | Chronic | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=igh dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only.; EFFECT=igh dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity /; CITATION=Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL; CITATION_NUMBERS=[2006,30,22,5]; REFERENCE=Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL","dose":"igh dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only.","duration":"Chronic","effect":"igh dose animals treated at 2000 mg/kg bw/d, detectable plasma concentrations below 30 ng/mL of MBBT (micronised form) were observed in one male and one female only. Test item concentrations in plasma were below the limit of quantitation (< 5 ng/mL) in all other samples taken during the study. Conclusion Under the experimental conditions of this study, no target organ toxicity was identified. Topical application of the test item did not induce a significant systemic exposure. The no-observed-adverse-effect-level (NOAEL) for repeated dermal treatment of mini-pigs with the UV-absorbing ingredient MBBT and the formulated micronised UV filter Tinosorb® M was 1000 mg/kg bw/d and 2000 mg/kg bw/d, respectively. MBBT is not subject to classification for specific target organ toxicity according to Regulation (EC) No. 1272/2008. Ref: CIT (2006a) SCCS comment Some absorption was noted in two animals (30ng/mL), while in all other animals (n=22) levels were below detection limit of 5 ng/mL. 3.3.5.3. Chronic (> 12 months) toxicity /","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":35,"route":"dermal","species":"pig","study_id":"sccs_o_168_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | >1000 | mg/kg bw/d | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.; EFFECT=evels of the test item were below the limit of quantitation (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001); CITATION=Ref.: RCC (2001); CITATION_NUMBERS=[2001]; REFERENCE=Ref.: RCC (2001); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2001)","dose":"Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.","duration":"90-day","effect":"evels of the test item were below the limit of quantitation (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001)","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":69,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | >1000 | mg/kg bw/d | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.; EFFECT=ere below the limit of quantitation (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001); CITATION=Ref.: RCC (2001); CITATION_NUMBERS=[2001]; REFERENCE=Ref.: RCC (2001); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2001)","dose":"Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.","duration":"90-day","effect":"ere below the limit of quantitation (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001)","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":69,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | >1000 | mg/kg bw/d | rat | dermal | 90-day | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.; EFFECT=n (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001); CITATION=Ref.: RCC (2001); CITATION_NUMBERS=[2001]; REFERENCE=Ref.: RCC (2001); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2001)","dose":"Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration.","duration":"90-day","effect":"n (1 ng/mL). Analysis of dose formulations revealed decreasing recoveries with increasing test item concentration. Based on this outcome and in order to improve test item suspension, it was decided to use corn oil as vehicle for the subsequent 90-day dermal study in rats (RCC Ltd., 2002). Conclusion Under the conditions of this study, 1000 mg/kg bw/d of the UV-absorbing ingredient MBBT in non-micronised form was established as the no-observed-effect-level (NOEL). Thus, the dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2001)","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":69,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1000 | mg/kg bw/d | rat | dermal | 13-week | - | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=RCC Ltd., 2002)b | 1000 mg/kg bw/d; EFFECT=Unlabeled table on page 52: NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b | 1000 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"RCC Ltd., 2002)b | 1000 mg/kg bw/d","duration":"13-week","effect":"Unlabeled table on page 52: NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b | 1000 mg/kg bw/d","endpoint":"","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":52,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 800 | mg/kg bw | rat | dermal | 90-day | carcinogenicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=800; DOSE=0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.; EFFECT=SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study; CITATION=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL; CITATION_NUMBERS=[2005,400,800]; REFERENCE=Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL","dose":"0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: 0 mg/kg bw/d in rats, when applied topically on the skin for 29 consecutive days in base ointment. The observed signs of poor local tolerance and pain might be vehicle related since they were not confirmed in a 90-day dermal toxicity study in rats using corn oil as vehicle (RCC Ltd., 2002) up to the high dose level of 1000 mg/kg bw/d. Ref.: CIT (2005) SCCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study","endpoint":"carcinogenicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw","noael_value":"800","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 800 | mg/kg bw | rat | dermal | 39-week | carcinogenicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=800; DOSE=CCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL.; EFFECT=CCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study by dermal route in rats. Moreover, a 39-week dermal study in mini-pigs was provided. There is no convincing evidence that the clinical signs are vehicle related, since the 90-day dermal study that is referred to above was not carried out using nano-sized material. The composition of the base ointment is not specified in the study report. No information; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"CCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL.","duration":"39-week","effect":"CCS comment At 400 and 800 mg/kg body weight minimal local skin reactions were observed, which were not considered in the determination of the NOAEL. Therefore the NOAEL of 800 mg/kg bw (equivalent to 400 mg a.i./kg bw) is based on lack of clinical signs when compared to the higher doses that induced pain and discomfort in the animals during the first and second treatment cycle. Given the changes in the study protocol during the study, the results can only be used as supportive for the risk assessment. An adequate NOAEL cannot be derived. It is noted that this dose range-finding toxicity was performed to provide a scientific basis for dose level setting in a carcinogenicity study by dermal route in rats. Moreover, a 39-week dermal study in mini-pigs was provided. There is no convincing evidence that the clinical signs are vehicle related, since the 90-day dermal study that is referred to above was not carried out using nano-sized material. The composition of the base ointment is not specified in the study report. No information","endpoint":"carcinogenicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw","noael_value":"800","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 0.0144 | mg/kg bw/d | rat | dermal | 13-week | dermal absorption | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=0.0144; DOSE=Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;; EFFECT=study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study;","duration":"13-week","effect":"study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC Ltd., 2002)b 1000 mg/kg bw/d Skin absorption (rat), (RCC Ltd., 2007)a 5.922 % of applied dose","endpoint":"dermal absorption","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0144","page":52,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 59.2 | mg/kg bw/d | rat | dermal | - | dermal absorption | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=59.2; DOSE=SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:; EFFECT=SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED:","duration":"","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 53 SED Rat 59.2 mg/kg bw/d MoS (SED Rat / SED Human) 4112 SED: Systemic exposure dose NOAEL: No-observed-adverse-effect-level MoS: Margin of safety a: 2 SD were added to the mean absorption value b: in this study MBBT was not in nanosized form. Based on the calculations presented above, the MoS for MBBT with a d(0.5) = 95 nm is 4112 based on a comparison of the internal dose between rat and man. It should be noted that the above calculations are highly conservative with regard to the human skin absorption value used. Dermal absorption values were mainly below the limit of quantification and the majority","endpoint":"dermal absorption","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"59.2","page":53,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=Results One mid-dose doe was sacrificed on day 23 after an abortion that was not related to the treatment with the test item.; EFFECT=amined for gross external alterations and sex. Results One mid-dose doe was sacrificed on day 23 after an abortion that was not related to the treatment with the test item. All remaining rabbits survived until scheduled sacrifice. In the dams, no test item-related changes were noted in clinical signs, food consumption, body weights and gross lesions. Caesarean sectioning, litter observations and the foetal gross observations were all within the ranges observed historically. Conclusion A no-observed-effect-level (NOEL) was not derived by the study author. Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d. Dosages of 100, 300 and 1000 mg/kg bw/d were selected for the main developmental toxicity study with MBBT in rabbits. Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guidelin; CITATION=Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guidelin; CITATION_NUMBERS=[2005,75,714]; REFERENCE=Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guidelin; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guidelin","dose":"Results One mid-dose doe was sacrificed on day 23 after an abortion that was not related to the treatment with the test item.","duration":"developmental","effect":"amined for gross external alterations and sex. Results One mid-dose doe was sacrificed on day 23 after an abortion that was not related to the treatment with the test item. All remaining rabbits survived until scheduled sacrifice. In the dams, no test item-related changes were noted in clinical signs, food consumption, body weights and gross lesions. Caesarean sectioning, litter observations and the foetal gross observations were all within the ranges observed historically. Conclusion A no-observed-effect-level (NOEL) was not derived by the study author. Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d. Dosages of 100, 300 and 1000 mg/kg bw/d were selected for the main developmental toxicity study with MBBT in rabbits. Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guidelin","endpoint":"developmental toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":80,"route":"oral","species":"rabbit","study_id":"sccs_o_168_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | mg/kg bw/d | rabbit | oral | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d.; EFFECT=on day 23 after an abortion that was not related to the treatment with the test item. All remaining rabbits survived until scheduled sacrifice. In the dams, no test item-related changes were noted in clinical signs, food consumption, body weights and gross lesions. Caesarean sectioning, litter observations and the foetal gross observations were all within the ranges observed historically. Conclusion A no-observed-effect-level (NOEL) was not derived by the study author. Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d. Dosages of 100, 300 and 1000 mg/kg bw/d were selected for the main developmental toxicity study with MBBT in rabbits. Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guideline: Detection of toxicity to reproduction of medical products GLP: In compliance Test ite; CITATION=Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guideline: Detection of toxici; CITATION_NUMBERS=[2005,75,714]; REFERENCE=Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guideline: Detection of toxici; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guideline: Detection of toxici","dose":"Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d.","duration":"developmental","effect":"on day 23 after an abortion that was not related to the treatment with the test item. All remaining rabbits survived until scheduled sacrifice. In the dams, no test item-related changes were noted in clinical signs, food consumption, body weights and gross lesions. Caesarean sectioning, litter observations and the foetal gross observations were all within the ranges observed historically. Conclusion A no-observed-effect-level (NOEL) was not derived by the study author. Based on the results of this study, the oral NOEL for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was at the high dose level of 1000 mg/kg bw/d. Dosages of 100, 300 and 1000 mg/kg bw/d were selected for the main developmental toxicity study with MBBT in rabbits. Ref.: CR-DDS (2005c) Title: Oral (stomach tube) developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: ICH Harmonised Tripartite Guideline: Detection of toxicity to reproduction of medical products GLP: In compliance Test ite","endpoint":"developmental toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":80,"route":"oral","species":"rabbit","study_id":"sccs_o_168_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 1000 | mg/kg bw/d | rat | dermal | - | genotoxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.; EFFECT=SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with; CITATION=Ref.: RCC (2002) E; CITATION_NUMBERS=[2002]; REFERENCE=Ref.: RCC (2002) E; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2002) E","dose":"The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.","duration":"","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with","endpoint":"genotoxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":71,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 1000 | mg/kg bw/d | rat | dermal | - | genotoxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.; EFFECT=ision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with CGF-C2089 (purity: 99.6 %), i.e. with the UV-absorbing ingredient MBBT in non-micronised form, suspended in corn oil; CITATION=Ref.: RCC (2002) E; CITATION_NUMBERS=[2002]; REFERENCE=Ref.: RCC (2002) E; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2002) E","dose":"The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.","duration":"","effect":"ision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with CGF-C2089 (purity: 99.6 %), i.e. with the UV-absorbing ingredient MBBT in non-micronised form, suspended in corn oil","endpoint":"genotoxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":71,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | >1000 | mg/kg bw/d | rat | dermal | - | genotoxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.; EFFECT=-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with CGF-C2089 (purity: 99.6 %), i.e. with the UV-absorbing ingredient MBBT in non-micronised form, suspended in corn oil at dose; CITATION=Ref.: RCC (2002) E; CITATION_NUMBERS=[2002]; REFERENCE=Ref.: RCC (2002) E; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (2002) E","dose":"The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d.","duration":"","effect":"-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 71 Conclusion Under the conditions of this study, no target organ was identified following repeated dermal treatment of rats with the UV-absorbing ingredient MBBT in non-micronised form. The dermal no-observed-effect-level (NOEL) was established at the high dose level of 1000 mg/kg bw/d. The corresponding dermal no-observed-adverse-effect-level (NOAEL) was > 1000 mg/kg bw/d. Ref.: RCC (2002) E. Mutagenicity/Genotoxicity in vivo Title: Bone marrow micronucleus test by intraperitoneal route in mice Guideline: OECD 474 GLP: In compliance Test item: CGF-C2089 (non-micronised) Batch/lot n°: 001719B0 Methods Three groups of 5 mice per sex [Swiss Ico:OF1(IOPS Caw)] received a first and, 24 hours later, a second intraperitoneal treatment with CGF-C2089 (purity: 99.6 %), i.e. with the UV-absorbing ingredient MBBT in non-micronised form, suspended in corn oil at dose","endpoint":"genotoxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":71,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 10 | % | rat | dermal | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=10; DOSE=The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.; EFFECT=n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin.","duration":"subchronic","effect":"n of a Margin of Safety (MoS) for the dermal route of exposure is provided in the table below. Taking the standardised approach to risk characterisation, the systemic estimated human exposure that could be assumed to result from 10 % microfine MBBT in cosmetic products applied to normal skin is used. The resulting systemic exposure dose in humans (SED Human) is then compared with the systemic exposure dose in rats (SED Rat) estimated from the subchronic dermal repeated dose toxicity study in rats using the in vivo NOAEL and the dermal absorption rate determined in the in vitro penetration study with rat skin. MoS calculations for microfine MBBT based on human skin in vitro study results on normal skin, as provided by the applicant. Parameter Microfine MBBT d(0.5) = 95 nm Adult body weight 60 kg Body surface area 17500 cm² Sunscreen applied (if at 1 mg/cm²) 18 g Microfine MBBT applied (10 %) 1800 mg Skin absorption (human), (RCC Ltd., 2007)a 0.048 % of applied dose SED Human 0.0144 mg/kg bw/d NOAEL (Rat 13-week dermal study; RCC","endpoint":"repeated dose toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"%","noael_value":"10","page":52,"route":"dermal","species":"rat","study_id":"sccs_o_168_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 10 | % | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=10; DOSE=In view of the noted effects in the lung, to ensure the safe use in spray application the following information would be needed: a 28-day repeated dose inhalation study, including tissue distribution and systemic toxicity, determination of an LOAEL and NOAEL and possible recovery.; EFFECT=moment, it cannot be concluded that the use of 10% S79 in spray formulations is safe, because of the uncertainties associated with the repeated exposure of the lung to low doses of S79 and the limited information on actual exposure during use of spray applications. In view of the noted effects in the lung, to ensure the safe use in spray application the following information would be needed: a 28-day repeated dose inhalation study, including tissue distribution and systemic toxicity, determination of an LOAEL and NOAEL and possible recovery. However, due to the Cosmetics regulation animal studies are not allowed anymore. Repeated dose toxicity In a dermal repeated dose range-finding study in rats, some clinical effects (vocalization and pain) were noted at dose levels of 500 mg a.i./kg bw/day and higher when exposed to nano- sized MBBT. These, or other effects were not seen in the 39 week min- pig study, where the animals were exposed to dose levels up to 1000 mg a.i./kg bw/day. No effects were noted in rats in dermal or oral; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"103597-45-1","citation":"","dose":"In view of the noted effects in the lung, to ensure the safe use in spray application the following information would be needed: a 28-day repeated dose inhalation study, including tissue distribution and systemic toxicity, determination of an LOAEL and NOAEL and possible recovery.","duration":"28-day","effect":"moment, it cannot be concluded that the use of 10% S79 in spray formulations is safe, because of the uncertainties associated with the repeated exposure of the lung to low doses of S79 and the limited information on actual exposure during use of spray applications. In view of the noted effects in the lung, to ensure the safe use in spray application the following information would be needed: a 28-day repeated dose inhalation study, including tissue distribution and systemic toxicity, determination of an LOAEL and NOAEL and possible recovery. However, due to the Cosmetics regulation animal studies are not allowed anymore. Repeated dose toxicity In a dermal repeated dose range-finding study in rats, some clinical effects (vocalization and pain) were noted at dose levels of 500 mg a.i./kg bw/day and higher when exposed to nano- sized MBBT. These, or other effects were not seen in the 39 week min- pig study, where the animals were exposed to dose levels up to 1000 mg a.i./kg bw/day. No effects were noted in rats in dermal or oral","endpoint":"repeated dose toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"%","noael_value":"10","page":55,"route":"oral","species":"rat","study_id":"sccs_o_168_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | - | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=In females, no Caesarean-sectioning parameters (numbers of corpora lutea, preimplantation loss, implantations, appearance of placentae and viable versus non-viable embryos) were affected by test item dosages as high as 1000 mg/kg bw/d.; EFFECT=here were no test item-related adverse effects on mating, fertility and other reproductive parameters such as oestrous cycling or male reproductive organ weights and sperm concentration and motility. In females, no Caesarean-sectioning parameters (numbers of corpora lutea, preimplantation loss, implantations, appearance of placentae and viable versus non-viable embryos) were affected by test item dosages as high as 1000 mg/kg bw/d. Conclusions Under the conditions of this study, the oral no-observed-effect-level (NOEL) for parental and reproductive toxicity of the UV-absorbing ingredient MBBT (non-micronised) was set at the high dose level of 1000 mg/kg bw/d. Based on the study results, MBBT does not display adverse effects on reproduction parameters and taking all other data on reprotoxicity into account, it is thus not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005a) Title: Oral (gavage) developmental and perinatal / postnatal reproduction toxicity study of; CITATION=Ref.: CR-DDS (2005a) Title: Oral (gavage) developmental and perinatal / postnatal reproduction toxicity study of; CITATION_NUMBERS=[2005]; REFERENCE=Ref.: CR-DDS (2005a) Title: Oral (gavage) developmental and perinatal / postnatal reproduction toxicity study of; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CR-DDS (2005a) Title: Oral (gavage) developmental and perinatal / postnatal reproduction toxicity study of","dose":"In females, no Caesarean-sectioning parameters (numbers of corpora lutea, preimplantation loss, implantations, appearance of placentae and viable versus non-viable embryos) were affected by test item dosages as high as 1000 mg/kg bw/d.","duration":"developmental","effect":"here were no test item-related adverse effects on mating, fertility and other reproductive parameters such as oestrous cycling or male reproductive organ weights and sperm concentration and motility. In females, no Caesarean-sectioning parameters (numbers of corpora lutea, preimplantation loss, implantations, appearance of placentae and viable versus non-viable embryos) were affected by test item dosages as high as 1000 mg/kg bw/d. Conclusions Under the conditions of this study, the oral no-observed-effect-level (NOEL) for parental and reproductive toxicity of the UV-absorbing ingredient MBBT (non-micronised) was set at the high dose level of 1000 mg/kg bw/d. Based on the study results, MBBT does not display adverse effects on reproduction parameters and taking all other data on reprotoxicity into account, it is thus not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005a) Title: Oral (gavage) developmental and perinatal / postnatal reproduction toxicity study of","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":76,"route":"oral","species":"","study_id":"sccs_o_168_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | rat | oral | Developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 78 Conclusion Under the experimental conditions employed, the oral no-observed-effect-level (NOEL) for general toxicity and for...; EFFECT=SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 78 Conclusion Under the experimental conditions employed, the oral no-observed-effect-level (NOEL) for general toxicity and for adverse effects on development and reproduction in rats of the UV-absorbing ingredient MBBT in non-micronised form was established at the high dose level of 1000 mg/kg bw/d. Therefore and taking all other data on reprotoxicity into account, MBBT is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005b) H. Developmental toxicity H.1. Developmental toxicity in rats Title: Dose range-finding prenatal toxicity study wit; CITATION=Ref.: CR-DDS (2005b) H; CITATION_NUMBERS=[2005]; REFERENCE=Ref.: CR-DDS (2005b) H; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CR-DDS (2005b) H","dose":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 78 Conclusion Under the experimental conditions employed, the oral no-observed-effect-level (NOEL) for general toxicity and for...","duration":"Developmental","effect":"SCCS/1546/15 Revision of opinion on 2,2'-methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol) (nano) _______________________________________________________________________________________________ 78 Conclusion Under the experimental conditions employed, the oral no-observed-effect-level (NOEL) for general toxicity and for adverse effects on development and reproduction in rats of the UV-absorbing ingredient MBBT in non-micronised form was established at the high dose level of 1000 mg/kg bw/d. Therefore and taking all other data on reprotoxicity into account, MBBT is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005b) H. Developmental toxicity H.1. Developmental toxicity in rats Title: Dose range-finding prenatal toxicity study wit","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":78,"route":"oral","species":"rat","study_id":"sccs_o_168_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.; EFFECT=Test item-related effects on survival, clinical appearance, food consumption, body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a); CITATION=Ref.: RCC (1998a); CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998a); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998a)","dose":"Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.","duration":"developmental","effect":"Test item-related effects on survival, clinical appearance, food consumption, body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a)","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":78,"route":"","species":"","study_id":"sccs_o_168_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.; EFFECT=cal appearance, food consumption, body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a); CITATION=Ref.: RCC (1998a); CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998a); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998a)","dose":"Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.","duration":"developmental","effect":"cal appearance, food consumption, body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a)","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":78,"route":"","species":"","study_id":"sccs_o_168_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | >1000 | mg/kg bw/d | - | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.; EFFECT=body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a); CITATION=Ref.: RCC (1998a); CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998a); DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998a)","dose":"Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d.","duration":"developmental","effect":"body weights or macroscopic findings did not occur in any dam. No test item-related reproductive effects (mean numbers of corpora lutea and implantation sites, and percent of pre- and post-implantation loss) were noted. Test item-related foetal effects (external abnormalities, sex ratios and body weights) did not occur. Conclusion Under the condition of this range-finding study, the maternal and developmental no-observed- effect-level (NOEL) was 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Identical dose levels were selected for the main study. Ref.: RCC (1998a)","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":78,"route":"","species":"","study_id":"sccs_o_168_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=The few observed significant differences in the various maternal or foetal parameters assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.; EFFECT=body weights; and stage of development. The few observed significant differences in the various maternal or foetal parameters assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity i; CITATION=Ref.: RCC (1998b) H; CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998b) H; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998b) H","dose":"The few observed significant differences in the various maternal or foetal parameters assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.","duration":"developmental","effect":"body weights; and stage of development. The few observed significant differences in the various maternal or foetal parameters assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity i","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":79,"route":"","species":"rat","study_id":"sccs_o_168_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.; EFFECT=assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity in rabbits Title: Oral (stomach tube) dosage-range developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: Not indicated GLP: In; CITATION=Ref.: RCC (1998b) H; CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998b) H; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998b) H","dose":"assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.","duration":"developmental","effect":"assessed were not considered test item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity in rabbits Title: Oral (stomach tube) dosage-range developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: Not indicated GLP: In","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":79,"route":"oral","species":"rat","study_id":"sccs_o_168_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | >1000 | mg/kg bw/d | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=> 1000; DOSE=item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.; EFFECT=item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity in rabbits Title: Oral (stomach tube) dosage-range developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: Not indicated GLP: In compli; CITATION=Ref.: RCC (1998b) H; CITATION_NUMBERS=[1998]; REFERENCE=Ref.: RCC (1998b) H; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: RCC (1998b) H","dose":"item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response.","duration":"developmental","effect":"item-related since they were within the range of normal biological variability for the strain and age of rat used and/or did not exhibit a dose-response. The concentration, homogeneity and stability of the dose formulations were acceptable in this study. Conclusion Under the condition of this study, the maternal and developmental no-observed-effect-level (NOEL) of the UV-absorbing ingredient MBBT in non-micronised form was the high dose level of 1000 mg/kg bw/d. The corresponding no-observed-adverse-effect-level (NOAEL) for maternal and developmental effects was > 1000 mg/kg bw/d. Based on this outcome and taking all other data on repro-toxicity into account, MBBT does not display adverse effects on development in rats and is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: RCC (1998b) H.2 Developmental toxicity in rabbits Title: Oral (stomach tube) dosage-range developmental toxicity study of Tinosorb® MBBT (FAT 75’714) in rabbits Guideline: Not indicated GLP: In compli","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"> 1000","page":79,"route":"oral","species":"rat","study_id":"sccs_o_168_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1000 | mg/kg bw/d | rabbit | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_168; REPORT_TITLE=OPINION ON 2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3- tetramethylbutyl)phenol) (nano form); OPINION_NUMBER=SCCS/1546/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=1000; DOSE=ty, clinical observations, food consumption and body weights in the does were unaffected by the treatment with the test item at all dose levels.; EFFECT=ty, clinical observations, food consumption and body weights in the does were unaffected by the treatment with the test item at all dose levels. No external, soft tissue or skeletal alterations (malformations or variations) in foetuses were caused by the test item up to and including the high dose level of 1000 mg/kg bw/d. All litter parameters remained unaffected and clinical observations were considered unrelated to the test item. Conclusion Under the conditions of this study, the oral no-observed-effect-level (NOEL) for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was established at 1000 mg/kg bw/d. Thus, MBBT does not display adverse effects on development in rabbits and taking all other data on reprotoxicity into account, it is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005d) In Submission 1, information on photosensitization and phototoxicity of MBBT was submitted. The text below is directly copied fro; CITATION=Ref.: CR-DDS (2005d) In Submission 1, information on photosensitization and phototoxicity of MBBT was submitted; CITATION_NUMBERS=[2005,1]; REFERENCE=Ref.: CR-DDS (2005d) In Submission 1, information on photosensitization and phototoxicity of MBBT was submitted; DETAILS_JSON={"cas_number":"103597-45-1","citation":"Ref.: CR-DDS (2005d) In Submission 1, information on photosensitization and phototoxicity of MBBT was submitted","dose":"ty, clinical observations, food consumption and body weights in the does were unaffected by the treatment with the test item at all dose levels.","duration":"developmental","effect":"ty, clinical observations, food consumption and body weights in the does were unaffected by the treatment with the test item at all dose levels. No external, soft tissue or skeletal alterations (malformations or variations) in foetuses were caused by the test item up to and including the high dose level of 1000 mg/kg bw/d. All litter parameters remained unaffected and clinical observations were considered unrelated to the test item. Conclusion Under the conditions of this study, the oral no-observed-effect-level (NOEL) for maternal and developmental toxicity of the UV-absorbing ingredient MBBT in non-micronised form was established at 1000 mg/kg bw/d. Thus, MBBT does not display adverse effects on development in rabbits and taking all other data on reprotoxicity into account, it is not subject to classification as reproductive toxicant according to Regulation (EC) No. 1272/2008. Ref.: CR-DDS (2005d) In Submission 1, information on photosensitization and phototoxicity of MBBT was submitted. The text below is directly copied fro","endpoint":"reproductive toxicity","ingredient":"codes .................................... 8","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":81,"route":"oral","species":"rabbit","study_id":"sccs_o_168_noael_027"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 8NT850T0YS | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C41H50N6O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8NT850T0YS"} |
| openFDA substances | FDA UNII substance identifier | 8NT850T0YS | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C41H50N6O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8NT850T0YS"} |
| openFDA substances | FDA UNII substance identifier | 8NT850T0YS | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C41H50N6O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8NT850T0YS"} |
| openFDA substances | FDA UNII substance identifier | 8NT850T0YS | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C41H50N6O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"8NT850T0YS"} |