Toxicity and mutagenicity of a mixture of 25 chemicals found in contaminated groundwater.
A defined mixture of 25 chemicals that are often found in contaminated groundwater was prepared as an aqueous solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effects in bone marrow cells of rats and mice. The bacterial mutation and prophage induction tests were negative. Exposure to the mixture in drinking water for two weeks resulted in a concentration-related decrease in water consumption in male and female rats and mice. Concentration-related decreases in weight gain were observed in male and female mice; in rats, only the high-dose groups showed decreased weight gains. A small but significant increase in sister chromatid exchanges was seen in male mice and a similar weak effect on micronucleated polychromatic erythrocytes (PCE) in the bone marrow of males and females. Also in bone marrow of male and female mice, an increase in mitotic index and a decrease in average cell generation time was observed. The %PCE in bone marrow was decreased in female mice only, while the %PCE in peripheral blood was increased in both sexes. In rats, the only effects observed in the cytogenetic studies were increased PCE frequencies in the peripheral blood of males and in the bone marrow of males and females. These results indicate that the 25-chemical mixture studied is not genotoxic in bacteria and that a concentration-dependent effect on its palatability to rodents leads to reduced water consumption, food consumption and weight gain. Although the bone marrow effects may be associated with disruptions of normal erythropoiesis that, in turn, alter the cytogenetic end-points reported, elevations of SCE and MN-PCE in mice suggest the 25-chemical mixture, under the conditions of administration, leads to cytogenetic damage in the bone marrow. Such damage may indicate a potential health hazard.
Shelby
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MD
National Toxicology Program, NIEHS, Research Triangle Park, NC 27709.
Tice
R R
RR
DeMarini
D M
DM
Yang
R S
RS
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002869:Chromosome Aberrations / Q000235:genetics; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D008940:Mitotic Index / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012475:Salmonella / Q000187:drug effects / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D009153:Mutagens; D014874:Water Pollutants, Chemical