Developmental toxicity of di-isodecyl and di-isononyl phthalates in rats.
The developmental toxicity of di-isodecyl phthalate (DIDP; CAS RN 68515-49-1) and di-isononyl phthalate (DINP; CAS RN 68515-48-0) were investigated in Sprague-Dawley rats. DIDP and DINP were administered by gavage to mated rats at doses of 0, 100, 500, and 1000 mg/kg/d on Gestation Days (GD) 6 through 15. Cesarean sections were performed on GD 21 and the fetuses removed for evaluation. Maternal weight gain and food consumption were significantly reduced at 1000 mg/kg/d during the exposure period. No treatment-related effects were noted at cesarean section, nor were there any fetal morphologic observations except for an increased frequency of seventh cervical and rudimentary lumbar ribs at the maternally toxic exposure level of 1000 mg/kg/d. Under these study conditions, mild maternal and developmental effects were observed at 1000 mg/kg/d. Both maternal and developmental NOAELs were therefore established at 500 mg/kg/d. The results indicate that neither DIDP nor DINP is teratogenic or a selective developmental toxicant.
Waterman
S J
SJ
Exxon Biomedical Sciences, Toxicology Division, East Millstone, NJ 08875, USA. sjwater@fpe.erenj.com
Ambroso
J L
JL
Keller
L H
LH
Trimmer
G W
GW
Nikiforov
A I
AI
Harris
S B
SB
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D010795:Phthalic Acids; C012125:diisononyl phthalate; C042080:diisodecyl phthalate