Comparative developmental toxicity of n-butyl benzyl phthalate and di-n-butyl phthalate in rats.
n-Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) were evaluated and compared for their developmental toxic potential. Pregnant rats were given either BBP or DBP by gastric intubation at a dose of 0.75, 1.0 and 1.25 g/kg on days 7-9, days 10-12 and days 13-15 of pregnancy. Regardless of the days of treatment, a significantly increased incidence of postimplantation loss was found at all doses of BBP and DBP. While treatment with BBP and DBP at doses of 0.75 g/kg and above on days 7-9 or days 13-15 resulted in a significant increase in the incidence of fetuses with malformations, no increase in the incidence of malformed fetuses was found after treatment with BBP and DBP on days 10-12. The incidences of postimplantation loss and malformed fetuses increased as the doses of BBP and DBP were increased. Deformity of the vertebral column and ribs commonly occurred after treatment with BBP and DBP on days 7-9. Cleft palate and fusion of the sternebrae were predominantly observed after treatment with BBP and DBP on days 13-15. The similarity in dependence of gestational days of treatment on the manifestation of developmental toxicity and on the spectrum of fetal malformations caused by BBP and DBP suggests that they may act by the same mechanism, possibly via a common metabolite of these two parent compounds.
Ema
M
M
National Institute of Health Sciences, Osaka, Japan.
Kurosaka
R
R
Amano
H
H
Ogawa
Y
Y
D000014:Abnormalities, Drug-Induced; D000818:Animals; D003993:Dibutyl Phthalate / Q000378:metabolism / Q000633:toxicity*; D020964:Embryo Loss / Q000139:chemically induced*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D010795:Phthalic Acids / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D010795:Phthalic Acids; D003993:Dibutyl Phthalate; C027561:butylbenzyl phthalate