Developmental toxic effects of ethylbenzene or toluene alone and in combination with butyl acetate in rats after inhalation exposure.
First, the developmental toxic potential of n-butyl acetate (BA) was examined in Sprague-Dawley rats following whole body inhalation exposure, 6 h day(-1), from day 6 to 20 of gestation, at concentrations of 0, 500, 1000, 2000 and 3000 ppm. Maternal toxicity was evidenced by significant decreases in body weight gain at 2000 and 3000 ppm, and by reduced food consumption at 1000 ppm and higher concentrations. The effects on prenatal development were limited to a significant decrease in fetal weight at 3000 ppm. Thus, inhaled BA was not a selective developmental toxicant. In the second part of this study, the developmental toxic effects of simultaneous exposures to ethylbenzene (EB) and BA, or to toluene (TOL) and BA were evaluated. Pregnant rats were administered EB (0, 250 or 1000 ppm) and BA (0, 500 or 1500 ppm), or TOL (0, 500 or 1500 ppm) and BA (0, 500, 1500 ppm), separately and in combinations, using a 2 x 2 factorial design. The maternal weight gain was reduced after exposure to 1000 ppm EB, to 1500 ppm BA, or to 1500 ppm TOL, either alone or in binary combinations. A significant reduction of fetal weight was associated with exposure to 1000 ppm EB alone, to either mixtures of EB with BA, or to 1500 ppm TOL alone or combined with BA at either concentration. No embryolethal or teratogenic effects were observed whatever the exposure. There was no evidence of interaction between EB and BA or between TOL and BA in causing maternal or developmental effects.
Saillenfait
Anne-Marie
AM
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP No. 27, 54501 Vandoeuvre, France. anne-marie.saillenfait@inrs.fr
Gallissot
Frédéric
F
Sabaté
Jean-Philippe
JP
Bourges-Abella
Nathalie
N
Muller
Samuel
S
D000014:Abnormalities, Drug-Induced; D000085:Acetates / Q000633:toxicity*; D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D019570:Inhalation Exposure; D008098:Litter Size / Q000187:drug effects; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012997:Solvents / Q000633:toxicity*; D014050:Toluene / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D000085:Acetates; D001555:Benzene Derivatives; D012997:Solvents; D014050:Toluene; C006848:butyl acetate; C004912:ethylbenzene