Gender differences in the metabolism of 1,3-butadiene in Sprague-Dawley rats following a low level inhalation exposure.
1,3-Butadiene (BD), a compound used extensively in the rubber industry, is carcinogenic in the male and female Sprague-Dawley rats after chronic exposures to 1000 and 8000 p.p.m. In terms of incidence of tumors the majority were in mammary tissue, thus the incidence of tumors in female rats exceeded that in males in chronic carcinogenicity studies. In the present study the production and disposition of butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), mutagenic BD metabolites, were examined in male and female Sprague-Dawley rats following a low level inhalation exposure to BD. The rats were exposed to a target concentration of 62.5 p.p.m. BD by nasal inhalation for 6 h. Immediately after exposure blood, bone marrow, lung and fat samples were removed from all the animals and mammary tissue was removed from females. The samples were prepared by cryogenic-vacuum line distillation and analyzed for the epoxides using multidimensional gas chromatography-mass spectrometry. Levels of BDO in the blood were 25.9 +/- 2.9 and 29.4 +/- 2 pmol/g in male and females respectively. The levels of this metabolite were also similar in males and females in the other tissues examined. The greatest amounts of BDO were in fat (175 +/- 21 and 203 +/- 13 pmol/g in males and females respectively). Levels of BDO2 were approximately 5-fold greater in the blood of female rats compared with male rats. In the other tissues examined BDO2 was also consistently greater in tissues from females. In fat BDO2 was present at a concentration of 7.7 +/- 1.3 and 1.1 +/- 0.1 pmol/g tissue in females and males respectively. Mammary tissue from female rats contained 10.5 +/- 2.4 pmol/g BDO2, a level slightly lower than that observed in blood. The ratios of the two epoxides differed markedly between males and females in all tissues examined. Differences were most pronounced in lung and fat tissues, where BDO/BDO2 ratios were 9 and 0.6 (lung) and 159 and 26 (fat) for males and females respectively. This study is the first to describe a gender difference in the metabolism of BD. The greater production of the highly mutagenic BDO2 in females may play a role in the increased incidence of mammary tumors after chronic exposure to BD.
Thornton-Manning
J R
JR
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185, USA.
Dahl
A R
AR
Bechtold
W E
WE
Griffith
W C
WC
Pei
L
L
Henderson
R F
RF
D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013045:Species Specificity
D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; C031763:1,3-butadiene