Assessment of the potential in vivo genotoxicity of three trihalomethanes: chlorodibromomethane, bromodichloromethane and bromoform.
Chlorination of drinking water results in the formation of chlorodibromomethane, bromodichloromethane and bromoform. These trihalomethanes have all shown evidence of genotoxicity in bacterial and mammalian cell systems in vitro and some evidence of carcinogenicity in rodents. Chlorodibromomethane and bromodichloromethane have previously been tested in the mouse micronucleus test and did not induce chromosome damage, but results from two previous micronucleus tests on bromoform are somewhat contradictory. In the present study, bromoform was tested in the mouse bone marrow micronucleus test in order to reassess the response in this system; all three compounds were evaluated using the rat liver unscheduled DNA synthesis test. Trihalomethanes are well absorbed by the oral route which was selected for this study as being that most relevant to humans. Bromoform did not induce micronuclei in mouse bone marrow, and chlorodibromomethane, bromodichloromethane and bromoform did not cause unscheduled DNA synthesis in rat liver. These trihalomethanes have not shown any evidence of genotoxicity in vivo and are most unlikely to have any significant genotoxic activity in mammals. Their mode of action as rodent carcinogens remains unexplained.
Stocker
K J
KJ
Department of Cellular Toxicology, Huntingdon Life Sciences Ltd, Cambridgeshire, UK.
Statham
J
J
Howard
W R
WR
Proudlock
R J
RJ
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D005260:Female; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D022882:Trihalomethanes
D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D009153:Mutagens; D022882:Trihalomethanes; C032707:chlorodibromomethane; C025191:bromodichloromethane; D004247:DNA; C015044:bromoform