Characterization of developmental toxicity of mono-n-benzyl phthalate in rats.
The objective of this study was to characterize the developmental toxicity of mono-n-benzyl phthalate (MBeP), which is one of the major metabolites of n-butyl benzyl phthalate. Pregnant rats were given MBeP by gastric intubation at 250, 375, 500, or 625 mg/kg on days 7 to 9, 10 to 12, or 13 to 15 of pregnancy. A significantly increased incidence of postimplantation loss was found at 500 mg/kg and above regardless of the days of administration. While administration of MBeP on days 7 to 9 or 13 to 15 at 375 mg/kg and above was significantly teratogenic, no evidence of teratogenicity was detected when MBeP was given on days 10 to 12. Deformity of the vertebral column and ribs and dilation of the renal pelvis were frequently observed after administration on days 7 to 9. Cleft palate and fused sternebrae were exclusively found after administration on days 13 to 15. These findings indicate that the susceptibility and spectrum of the developmental toxicity of MBeP vary with the developmental stages at the time of administration.
Ema
M
M
National Institute of Health Sciences, Osaka Branch, Japan.
Harazono
A
A
Miyawaki
E
E
Ogawa
Y
Y
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D010795:Phthalic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012272:Ribs / Q000002:abnormalities / Q000187:drug effects; D013131:Spine / Q000002:abnormalities / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*
D010795:Phthalic Acids; D013723:Teratogens; C103325:mono-benzyl phthalate; C027561:butylbenzyl phthalate