Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat.
3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10-2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed-adverse-effect level.
Jekat
F W
FW
Institute of Pharmacology and Toxicology, University of Münster, Germany.
Kemper
F H
FH
Winterhoff
H
H
D000505:Alopecia / Q000139:chemically induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D002934:Cinnamates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D004952:Esters; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D006197:Hair / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013473:Sunscreening Agents / Q000633:toxicity*
D002934:Cinnamates; D004952:Esters; D013473:Sunscreening Agents; C077647:3-(4-methoxyphenyl)-2-propenoic acid 3-methylbutyl ester