Developmental effects of di-n-butyl phthalate after a single administration in rats.
The objective of this study was to determine the susceptible day for the developmental toxicity of di-n-butyl phthalate (DBP). Pregnant rats were given a single dose of DBP by gastric intubation at 1500 mg kg(-1) on one of days 6-16 of pregnancy. A significant increase in the incidence of postimplantation loss was found in pregnant rats given DBP on one of days 6-16, except for days 7 and 11. Significant increases in the incidences of fetuses with skeletal malformations, of fetuses with skeletal and internal malformations and of fetuses with external and skeletal malformations were noted after a single dosing of DBP on day 8, on day 9 and on day 15, respectively. Deformity of the cervical vertebrae was frequently observed after administration of DBP on day 8. Deformity of the cervical and thoracic vertebrae and ribs and dilatation of the renal pelvis were predominantly found in fetuses of dams treated with DBP on day 9. Cleft palate and fusion of the sternebrae were exclusively detected after administration of DBP on day 15. It could be concluded that the manifestation of deviant development induced by DBP varies with the developmental stage at the time of administration and that DBP induces two discrete responses from embryos to teratogenicity on days 8 and 9 and on day 15 of pregnancy.
Ema
M
M
National Institute of Health Sciences, Osaka Branch, Japan.
Harazono
A
A
Miyawaki
E
E
Ogawa
Y
Y
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004334:Drug Administration Schedule; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects
D003993:Dibutyl Phthalate