Phase specificity of developmental toxicity after oral administration of mono-n-butyl phthalate in rats.
The objective of this study was to further characterize the developmental toxicity of mono-n-butyl phthalate (MBuP), which is one of the major metabolites of n-butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP). Pregnant rats were given MBuP by gastric intubation at a dose of 500, 625 or 750 mg/kg on days 7-9, days 10-12, or days 13-15 of pregnancy. A significantly increased incidence of postimplantation loss was noted in pregnant rats given MBuP on days 7-9 and days 10-12 at doses of 625 mg/kg and above and on days 13-15 at doses of 500 mg/kg and above. No evidence of teratogenicity was found when MBuP was given on days 10-12 of pregnancy. A significantly increased incidence of fetuses with external malformations was found after treatment with MBuP on days 7-9 and days 13-15 at doses of 625 and 750 mg/kg. A significantly increased incidence of fetuses with skeletal malformations was observed after treatment with MBuP on days 7-9 at doses of 500 mg/kg and above and on days 13-15 at doses of 625 mg/kg and above. Deformity of the cervical vertebrae was predominantly observed following treatment with MBuP on days 7-9. Cleft palate and fusion of the sternebrae were exclusively found following treatment with MBuP on days 13-15. It could be concluded that the manifestation of deviant development induced by MBuP varies with the developmental stage at the time of administration.
Ema
M
M
National Institute of Health Sciences, Osaka Branch, 1-1-43, Hoenzaka, Chuo-ku, Osaka 540, Japan.
Kurosaka
R
R
Harazono
A
A
Amano
H
H
Ogawa
Y
Y
D000284:Administration, Oral; D000818:Animals; D002574:Cervical Vertebrae / Q000187:drug effects / Q000473:pathology; D002972:Cleft Palate / Q000139:chemically induced; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D008297:Male; D008431:Maternal-Fetal Exchange; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D010795:Phthalic Acids; C028577:monobutyl phthalate