Activity of 1,1,1- and 1,1,3-trichloroacetones in a chromosomal aberration assay in CHO cells and the micronucleus and spermhead abnormality assays in mice.
1,1,1- and 1,1,3-trichloroacetones (TCA) result from the disinfection of municipal water supplies with chlorine, and are direct-acting mutagens in the Ames/Salmonella assay. The objective of this study was to further investigate the genotoxicity of these compounds in mammalian cells using an in vitro chromosomal aberration assay in Chinese hamster ovary (CHO) cells and the micronucleus and spermhead abnormality assays in mice. Both compounds induced significant increases in structural chromosomal aberrations in CHO cells in the presence and in the absence of rat S9 metabolic activation (MA). 1,1,3-TCA was more cytotoxic to CHO cells but 1,1,1-TCA resulted in a higher proportion of cells with aberrations. The clastogenic activities of both compounds were reduced in assays conducted with MA. Neither compound resulted in the induction of a significant increase in micronucleated polychromatic erythrocytes from bone marrow of Swiss-Webster mice when administered by oral gavage; nor were effects seen on the incidence of sperm with head-shape abnormalities, testis weight, or epididymal sperm concentration in B6C3F1 mice 21 or 35 days after treatment. These data indicate that the drinking water contaminants 1,1,1- and 1,1,3-TCA are clastogenic in vitro, but are not clastogenic to bone marrow cells in vivo, and do not adversely affect several indicators of testicular function in mice.
Blazak
W F
WF
Cellular and Genetic Toxicology Department, SRI International, Menlo Park, CA 94025.
Meier
J R
JR
Stewart
B E
BE
Blachman
D C
DC
Deahl
J T
JT
D000096:Acetone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary; D051381:Rats; D013077:Sperm Head / Q000187:drug effects* / Q000648:ultrastructure; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects; D014873:Water Pollutants / Q000494:pharmacology*; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D009153:Mutagens; D014873:Water Pollutants; D014874:Water Pollutants, Chemical; D000096:Acetone; C058071:1,1,3-trichloroacetone; C058072:1,1,1-trichloroacetone