Male-mediated F1 effects in mice exposed to 1,3-butadiene.
We examined the effects on dominant lethality and the incidence of fetal abnormalities of acute and subchronic exposure of male mice by inhalation to the industrial monomer 1,3-butadiene. Investigation of the effect on tumour incidence in surviving offspring is still in progress. In the acute study, CD-1 mice were exposed to atmospheres containing 0 (n = 25), 1250 (n = 25) or 6250 ppm (n = 50) for 6 h, and each male was caged five days later for one week with two untreated virgin females. One of the females was killed humanely on day 17 of gestation. The other was allowed to deliver and rear her litter; the litters are being monitored for life. The killed female was examined for the number of live fetuses, the number of post-implantation deaths (early and late) and the number and type of any gross malformations. In the subchronic study, males were exposed to 0 (n = 25), 12.5 (n = 25) or 1250 ppm (n = 50) for 6 h per day on 5 days per week for 10 weeks and then mated immediately. Mating and observation were conducted as in the acute study. Acute exposure to butadiene resulted in only a small decrease in implantations; after 10 weeks' subchronic exposure to either the high or the low concentration, however, a wide variety of statistically significant effects was seen. At 1250 ppm, the number of implantations was reduced, dominant lethal mutations were induced, and the incidences of early and late deaths were increased; some of the live fetuses had abnormalities. The low dose also increased the frequency of abnormalities and late deaths, but it did not affect the number of early deaths. Thus, butadiene is mutagenic in the germ cells of male mice, as shown by the induction of dominant lethality at 1250 ppm, and the frequencies of late deaths and congenital abnormalities appear to be increased at the subchronic level of 12.5 ppm.
Anderson
D
D
BIBRA Toxicology International, Carshalton, Surrey, United Kingdom.
Edwards
A J
AJ
Brinkworth
M H
MH
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity*; D013094:Spermatozoa / Q000187:drug effects*
D002070:Butadienes; D009153:Mutagens; C031763:1,3-butadiene