Teratogenic assessment of 2,4-dichlorophenol in Fischer 344 rats.
The potential maternal, embryotoxic, and teratogenic parameters of 2,4-dichlorophenol (2,4-DCP) were evaluated in Fischer 344 rats following oral administration in corn oil on Days 6 through 15 of gestation. Dose levels were 0, 200, 375, and 750 mg/kg/day. Females were sacrificed on Gestation Day 20 and cesarean sections performed. The fetuses were weighed, sexed, measured for crown-rump length, and examined for external malformations. A skeletal examination was conducted on one-half of the fetuses after staining with alizarin red S. The remaining fetuses were fixed in Bouin's solution and examined for visceral anomalies and developmental variations. Maternal body weight gain inhibition occurred in all 2,4-dichlorophenol-treated groups during the treatment period. Four treatment-related deaths occurred in the 750 mg/kg/day group. Additional indicators of maternal toxicity included urogenital staining of the fur at all levels tested, and an increased incidence of hair loss and respiratory rales at the 750 mg/kg/day level. Fetal examinations did not reveal differences in the incidence of external, visceral, or skeletal fetal malformations in any treatment group, when compared with the control group. A slight increase in early embryonic death occurred in the high-dose group only. Fetal weights were lower in the high-dose group than in the control group. Variations in skeletal structure were expressed among fetuses exposed to 750 mg/kg/day during organogenesis. These included delayed ossification of sternal elements and vertebral arches. The reduced fetal weights, intrauterine survival, and retarded ossification may represent a slight degree of embryotoxicity or fetotoxicity in this group. The test material was not teratogenic at any dose level.
Rodwell
D E
DE
Department of Reproduction and Teratology, WIL Research Laboratories, Inc., Ashland, Ohio 44805-9281.
Wilson
R D
RD
Nemec
M D
MD
Mercieca
M D
MD
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002733:Chlorophenols / Q000633:toxicity*; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens
D002733:Chlorophenols; D013723:Teratogens; C004762:2,4-dichlorophenol