Developmental toxicity of dimethylacetamide by inhalation in the rat.
Dimethylacetamide (DMAC) is a widely used industrial solvent. It has been reported to be teratogenic when given to rats by injection or following dermal application. Most of these studies employed large single doses and did not examine both the fetal and the maternal response. In this study, groups of pregnant Crl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalation for 6 hr/day from Days 6 through 15 of gestation (day on which copulation plug was detected was termed Day 1G). A control group of chambered pregnant rats was exposed simultaneously to air only. All female rats were euthanized on Day 21G. At 282 ppm, both maternal weight gain during the exposure period and fetal weight were significantly decreased and accompanied by a significant dose-response trend. These effects were not seen in rats inhaling either 32 or 100 ppm. Fetal resorptions were not increased in any of the groups exposed to DMAC. Fetal incidences of external, visceral, or skeletal variations and malformations were similar between the test and control groups. Therefore, both fetal and maternal toxicity were noted at 282 ppm and the no-observed adverse-effect level under these experimental conditions was 100 ppm for both the dam and the conceptus. DMAC was not demonstrated to produce malformations in the rat fetus even at a level that was toxic to the dam.
Solomon
H M
HM
Central Research and Development Department, E.I. duPont de Nemours and Company, Inc., Haskell Laboratory, Newark, Delaware 19714.
Ferenz
R L
RL
Kennedy
G L
GL
Staples
R E
RE
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000081:Acetamides / Q000008:administration & dosage / Q000633:toxicity*; D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D007774:Lactation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens
D000081:Acetamides; D013723:Teratogens; C013959:dimethylacetamide