Evaluation of the developmental toxicity of 4-bromobenzene using frog embryo teratogenesis assay--Xenopus: possible mechanisms of action.
Potential mechanisms of 4-bromobenzene-induced developmental toxicity were evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X, laevis embryos were exposed to 4-bromobenzene in two separate definitive concentration-response tests with and without an exogenous metabolic activation system (MAS) or selectively inhibited MAS. The MAS was treated with carbon monoxide (CO) to modulate P-450 activity, cyclohexene oxide (CHO) to modulate epoxide hydrolase activity, and diethyl maleate (DM) to modulate glutathione conjugation. Addition of the intact MAS, and particularly the CHO- and DM-inhibited MASs, dramatically increased the embryo lethal potential of 4-bromobenzene. Addition of the CO-inhibited MAS decreased the developmental toxicity of activated 4-bromobenzene to levels approximating that of the parent compound. Results from these studies suggested that a highly toxic arene oxide intermediate of 4-bromobenzene formed as the result of mixed function oxidase (MFO)-mediated metabolism may play an important role in the development toxicity of 4-bromobenzene in vitro. Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be responsible for activated 4-bromobenzene detoxification.
Fort
D J
DJ
Laboratory Services Division, Stover Group, Stillwater, Oklahoma 74076, USA.
Propst
T L
TL
Stover
E L
EL
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D001969:Bromobenzenes / Q000493:pharmacokinetics / Q000633:toxicity*; D002248:Carbon Monoxide / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D003510:Cyclohexanes / Q000494:pharmacology; D053138:Cyclohexenes; D005260:Female; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity*; D014981:Xenopus / Q000196:embryology*
D001140:Aroclors; D001969:Bromobenzenes; D002273:Carcinogens; D003510:Cyclohexanes; D053138:Cyclohexenes; D008298:Maleates; D013723:Teratogens; D020111:Chlorodiphenyl (54% Chlorine); C007193:cyclohexene oxide; D002248:Carbon Monoxide; C032036:bromobenzene; C014476:diethyl maleate