Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents.
A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18-22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000-ppm group in the form of reduced extragestational weight gain and, during the first week of treatment, decreased body weight gain. Under these conditions, there was no evidence of developmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200- and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200- and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F1 mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study).(ABSTRACT TRUNCATED AT 250 WORDS)
Morrissey
R E
RE
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Schwetz
B A
BA
Hackett
P L
PL
Sikov
M R
MR
Hardin
B D
BD
McClanahan
B J
BJ
Decker
J R
JR
Mast
T J
TJ
D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D008297:Male; D051379:Mice; D009153:Mutagens; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D013077:Sperm Head / Q000187:drug effects / Q000473:pathology
D002070:Butadienes; D009153:Mutagens; C031763:1,3-butadiene