Effects of chemically induced maternal toxicity on prenatal development in the rat.
The hypothesis that chemically induced overt maternal toxicity induces a characteristic syndrome of adverse developmental effects in the rat was investigated. Pregnant animals (Sprague-Dawley strain) were dosed by oral gavage with one of a series of compounds on days 6-15 of gestation. These chemicals were diquat (DIQ), ethylene-bis-isothiocyanate (EBIS), toxaphene (TOX), styrene (STY), 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenol (2,4,5-Tr), triphenyl tin hydroxide (TPTH), and cacodylic acid (CAC). The compounds were chosen because they exhibited little or no developmental toxicity in previous studies. Dosage levels producing maternal weight loss and/or lethality were determined from preliminary toxicity studies. Significant maternal weight reductions were noted during the course of treatment with all compounds except CAC and 2,4,5-Tr. Maternal lethality was produced by EBIS, TOX, 2,4,-D, and 2,4,5-Tr. The main treatment-related developmental toxicity noted in litters at term consisted of increased lethality (EBIS, TPTH) and decreased fetal weight (EBIS and CAC). Treatment-related anomalies were seen in litters treated with 2,4-D and TOX (supernumerary ribs) and with EBIS and STY (enlarged renal pelvis). No significant developmental effects were produced with DIQ, or 2,4,5-Tr. This study indicates that overt maternal toxicity as defined by weight loss or mortality is not always associated with the same defined syndrome of adverse developmental effects in the rat.
Chernoff
N
N
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Setzer
R W
RW
Miller
D B
DB
Rosen
M B
MB
Rogers
J M
JM
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002101:Cacodylic Acid / Q000633:toxicity; D004178:Diquat / Q000633:toxicity; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005315:Fetal Diseases / Q000139:chemically induced*; D017879:Isothiocyanates; D008431:Maternal-Fetal Exchange; D009947:Organotin Compounds / Q000633:toxicity; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000503:physiopathology; D013861:Thiocyanates / Q000633:toxicity; D014112:Toxaphene / Q000633:toxicity
D017879:Isothiocyanates; D009947:Organotin Compounds; D013861:Thiocyanates; D015084:2,4-Dichlorophenoxyacetic Acid; C011812:ethylenebis(isothiocyanate); D014112:Toxaphene; D015085:2,4,5-Trichlorophenoxyacetic Acid; D004178:Diquat; D002101:Cacodylic Acid; C007567:triphenyltin hydroxide