NOAEL Studies Cosmetic Ingredient

Isopropyl Cloprostenate NOAEL Studies

INCI: ISOPROPYL CLOPROSTENATE

CAS: 157283-66-4

Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.

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SCCS_vision_codex 20 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =0.015 mg/kg bw/d rat dermal 3-month dermal absorption {"dose":"This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.","effect":"e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically","page":32,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_004"}
SCCS_vision_codex NOAEL =0.015 mg/kg bw/d rat dermal 3-month dermal absorption {"dose":"This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.","effect":"e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically","page":32,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_004"}
SCCS_vision_codex NOAEL =0.015 mg/kg bw/d rat dermal 3-month dermal absorption {"dose":"This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.","effect":"e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically","page":32,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_004"}
SCCS_vision_codex NOAEL =0.015 mg/kg bw/d rat dermal 3-month dermal absorption {"dose":"This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.","effect":"e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically","page":32,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_004"}
SCCS_vision_codex NOAEL =0.1 mg/kg bw/day rat oral 28 days reproductive toxicity {"citation":"Ref.: Indrei et al","dose":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).","effect":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr","page":23,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_003"}
SCCS_vision_codex NOAEL =0.1 mg/kg bw/day rat oral 28 days reproductive toxicity {"citation":"Ref.: Indrei et al","dose":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).","effect":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr","page":23,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_003"}
SCCS_vision_codex NOAEL =0.1 mg/kg bw/day rat oral 28 days reproductive toxicity {"citation":"Ref.: Indrei et al","dose":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).","effect":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr","page":23,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_003"}
SCCS_vision_codex NOAEL =0.1 mg/kg bw/day rat oral 28 days reproductive toxicity {"citation":"Ref.: Indrei et al","dose":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).","effect":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr","page":23,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_003"}
SCCS_vision_codex NOAEL =3 - rat oral chronic reproductive toxicity {"effect":"ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","page":40,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_006"}
SCCS_vision_codex NOAEL =3 - rat oral chronic reproductive toxicity {"effect":"ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","page":40,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_006"}
SCCS_vision_codex NOAEL =3 - rat oral chronic reproductive toxicity {"effect":"ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","page":40,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_006"}
SCCS_vision_codex NOAEL =3 - rat oral chronic reproductive toxicity {"effect":"ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","page":40,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_006"}
SCCS_vision_codex NOAEL =3.3 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_002"}
SCCS_vision_codex NOAEL =3.3 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_002"}
SCCS_vision_codex NOAEL =3.3 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_002"}
SCCS_vision_codex NOAEL =3.3 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_002"}
SCCS_vision_codex NOAEL =2004 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_001"}
SCCS_vision_codex NOAEL =2004 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_001"}
SCCS_vision_codex NOAEL =2004 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_001"}
SCCS_vision_codex NOAEL =2004 - rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","effect":"nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","page":22,"pdf":"sccs_o_258.pdf","row_type":"noael_study","study_id":"sccs_o_258_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 6 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 0.015 mg/kg bw/d rat dermal 3-month dermal absorption SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=0.015; DOSE=This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.; EFFECT=e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"157283-66-4","citation":"","dose":"This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg.","duration":"3-month","effect":"e for use. Isopropyl cloprostenate - Applicant #2 lsopropyl cloprostenate is contained in the Long Lashes eyelash serum at 0.007%. A maximum of 0.07 g of the eyelash serum is applied to the lashes per day. This corresponds to an SED of 0.000008 mg/kg bw /d lsopropyl Cloprostenate at a dermal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically","endpoint":"dermal absorption","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.015","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_258_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 0.015 mg/kg bw/d rat dermal 3-month dermal absorption SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=0.015; DOSE=For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats.; EFFECT=rmal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically confirmed the safety of RLA. Highly qualified independent experts have assessed the safety of RLA and concluded in written reports that RLA is safe and that the presence of DDDE in RLA poses no local or ocular safety risk beyond any other cosmetic ingredient. Note by the SCCS: Several wee; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"157283-66-4","citation":"","dose":"For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats.","duration":"3-month","effect":"rmal absorption of 10% and an average body weight of 60 kg. The dermal absorption of 10% was estimated on the basis of a molecular weight of 476 g/mol and a log POW of 5.15 (calculated via QSAR, Episuite 1.0). For cloprostenol, a NOEL of 0.015 mg/kg bw/d was determined during a 3-generation feeding study in rats. Higher NOELs were also determined in 3-month feeding studies of 50 μg/kg bw/d each in rats and marmosets. An ADI value of 0.075 μg/kg bw/d has been established by the EMEA on the basis of the 3-generation NOEL used here for the MOS calculation. This results in a MOS for the lash serum of 916. Dechloro dihydroxy difluoro ethylcloprostenolamide (DDDE) - Applicant #3 Collectively, the biological tests have objectively and scientifically confirmed the safety of RLA. Highly qualified independent experts have assessed the safety of RLA and concluded in written reports that RLA is safe and that the presence of DDDE in RLA poses no local or ocular safety risk beyond any other cosmetic ingredient. Note by the SCCS: Several wee","endpoint":"dermal absorption","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.015","page":32,"route":"dermal","species":"rat","study_id":"sccs_o_258_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 3.3 - rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=unclear:ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment; DOSE=3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.; EFFECT=ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment; CITATION=Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol; CITATION_NUMBERS=[2004]; REFERENCE=Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol; DETAILS_JSON={"cas_number":"157283-66-4","citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","duration":"Sub-chronic","effect":"ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","endpoint":"repeated dose toxicity","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"","noael_value":"unclear:ct. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the data indicate systemic effects caused by very low doses of cloprostenol. This raises concern about the potential for similar effects by other prostaglandin analogues assessed in this Opinion. 3.3.4.3 Chronic (> 12 months) toxicity SCCS comment","page":22,"route":"oral","species":"rat","study_id":"sccs_o_258_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 2004 - rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=unclear:nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the; DOSE=3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.; EFFECT=nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the; CITATION=Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; CITATION_NUMBERS=[2004]; REFERENCE=Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; DETAILS_JSON={"cas_number":"157283-66-4","citation":"Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol","dose":"3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose.","duration":"Sub-chronic","effect":"nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","endpoint":"repeated dose toxicity","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"","noael_value":"unclear:nt drug-related change observed for all the doses tested. This effect was reversible one month after the end of the treatment. Ref.: EMA, 2004 SCCS comment Some experimental data on subcutaneous administration have been provided for cloprostenol; the data show that even low doses of this analogue can exert a systemic effect. 3.3.4.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity In the 3-month oral toxicity study carried out in rats (0, 10, 50, 150 μg/kg bw/day of cloprostenol), 50 μg/kg bw was the NOEL, as ovarian vacuolisation has been observed at the highest dose. In the 3-month oral repeated studies in marmosets (0, 10, 50, 150 μg/kg bw and 0, 10, 20, 50 μg/kg bw/day of cloprostenol), induction of myocardial changes and statistically significant increases in testicular weights were reported at 150 μg/kg bw/day. A NOEL of 50 μg/kg bw/day could be retained. Ref.: EMA, 2004 SCCS comment Some experimental data on sub-chronic oral administration are available for cloprostenol. Although not directly relevant, the","page":22,"route":"oral","species":"rat","study_id":"sccs_o_258_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 0.1 mg/kg bw/day rat oral 28 days reproductive toxicity SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=0.1; DOSE=tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).; EFFECT=tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr; CITATION=Ref.: Indrei et al; CITATION_NUMBERS=[]; REFERENCE=Ref.: Indrei et al; DETAILS_JSON={"cas_number":"157283-66-4","citation":"Ref.: Indrei et al","dose":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001).","duration":"28 days","effect":"tem suggests significant histopathologic modifications in the testis of rats and mice following intraperitoneal exposure to 0.1 mg/kg bw/day for 28 days (Indrei et al., 2001). Ref.: Indrei et al., 2001 In a 3 generation study carried out in rats, the oral administration of doses of 0, 10, 15, 20 and 40 μg of cloprostenol/kg bw did not induce effects on reproductive performance of the animals. The only effects seen were the slight reduction in neonatal viability attributable to the prematurity2 of the offspring. A NOEL of 15 μg/kg bw/day for cloprostenol was retained. In a series of reproductive studies performed with cloprostenol, it was shown that the sensitivity of the rat to termination of pregnancy resulting from luteolysis varies depending on the point in pregnancy when the compound is administered. The oral dose 25 μg/kg bw of cloprostenol did not terminate pregnancy; the most sensitive period to luteolytic action of cloprostenol was just prior to the parturition. Ref.: EMA, 2004 SCCS comment The available data on clopr","endpoint":"reproductive toxicity","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.1","page":23,"route":"oral","species":"rat","study_id":"sccs_o_258_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 3 - rat oral chronic reproductive toxicity SOURCE_SUBDIR=sccs_o_258; REPORT_TITLE=OPINION on Prostaglandins and prostaglandin-analogues used in cosmetic products; OPINION_NUMBER=SCCS/1635/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 3 February 2022; VALUE_TEXT=unclear:ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c; EFFECT=ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"157283-66-4","citation":"","dose":"","duration":"chronic","effect":"ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","endpoint":"reproductive toxicity","ingredient":"Isopropyl Cloprostenate (IPCP)","loael_value":"","noael_unit":"","noael_value":"unclear:ct eye application. Therefore, based on the analysis of available data, the potential of PGAs to cause eye and skin irritation/sensitisation cannot be excluded. 3. The data on acute, chronic, reproductive/developmental toxicity of the PGAs are also very limited and insufficient. The limited available data do not allow drawing conclusions on these endpoints. 4. In the EMA 2004 Report on cloprostenol and R-cloprostenol, an ADI of 0.075 μg/kg bw/day (i.e 4.5 μg/person/day) was established for cloprostenol, based on a NOEL of 15 μg/kg bw/day derived from a rat 3 generation oral reproductive study. The data indicate a potentially very high reproductive activity of the PGAs. Human data The SCCS review of the open literature has indicated that PGAs caused serious adverse effects in ocular and periocular tissues in some glaucoma patients after direct eye applications (Nakakura et al., 2015, Shah et al., 2013; Wang et al., 2014). These data indicate a concern for the manifestation of serious and irreversible histological changes after c","page":40,"route":"oral","species":"rat","study_id":"sccs_o_258_noael_006"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 765298537G UNII - - - chemical {"approval_status":null,"molecular_formula":"C25H35ClO6","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"765298537G"}
openFDA substances FDA UNII substance identifier 765298537G UNII - - - chemical {"approval_status":null,"molecular_formula":"C25H35ClO6","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"765298537G"}
openFDA substances FDA UNII substance identifier 765298537G UNII - - - chemical {"approval_status":null,"molecular_formula":"C25H35ClO6","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"765298537G"}
openFDA substances FDA UNII substance identifier 765298537G UNII - - - chemical {"approval_status":null,"molecular_formula":"C25H35ClO6","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"765298537G"}