Developmental toxicity of 1,2-dichloropropane (PDC) in rats and rabbits following oral gavage.
1,2-Dichloropropane (PDC) was evaluated for its potential to cause embryonal/fetal toxicity and teratogenicity in pregnant rats and rabbits. PDC was administered via oral gavage at dose levels of 0, 10, 30, or 125 mg/kg/day on Days 6 through 15 of gestation (rats) or 0, 15, 50, or 150 mg/kg/day on gestation Days 7 through 19 (rabbits). Fetuses were examined on Gestation Day 20 (rats) or Day 28 (rabbits). Maternal toxicity was observed in both rats and rabbits at the high dose levels. Rats given 125 mg/kg/day of PDC showed clinical signs of toxicity and decreased body weight and body weight gain. Rabbits given 150 mg/kg/day PDC showed changes in hematologic parameters and decreased body weight gain. Although maternal toxicity was apparent, no indication of teratogenicity was observed in rat or rabbit fetuses at any dose level. Significant increases in the incidence of delayed ossification of skull bones, considered secondary to decreased maternal body weight gain, were observed in rats given 125 mg/kg/day and in rabbits given 150 mg/kg/day. No maternal or developmental effects were observed in rats given 10 or 30 mg/kg/day or in rabbits given 15 or 50 mg/kg/day of PDC. Based on the results of these studies the maternal and developmental NOELs in rats and rabbits were 30 and 50 mg/kg/day, respectively.
Kirk
H D
HD
Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Berdasco
N M
NM
Breslin
W J
WJ
Hanley
T R
TR
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005324:Fetal Movement / Q000187:drug effects; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000473:pathology; D007441:Intubation, Gastrointestinal; D008297:Male; D011247:Pregnancy; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D013045:Species Specificity; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D012997:Solvents; D013723:Teratogens; C004765:propylene dichloride; D011407:Propane