MYELOTOXICITY IN MICE CAUSED BY DRINKING MIXTURE OF GROUNDWATER CONTAMINANTS

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The possible toxicological interaction of the 25-chemical mixture of groundwater contaminants and whole-body irradiation (WBI) on hematopoiesis was investigated. Exposure of the chemical mixture (5% mixture stock) to B6C3F1 mice further reduced bone marrow stem-cell proliferation following radiation injury resulting from repeated WBI at 200 rads. Even 10 weeks after cessation of chemical-mixture treatment when all hematological parameters were normal, a residual effect of the chemical mixture may still be demonstrated as lower bone marrow stem- cell counts following irradiation. There is also an indication that even at 1% mixture stock level an enhancement of radiation injury to hematopoiesis may be detected if the exposure period is long enough. These examples provide a clue that the toxicology of chemical mixtures at environmental levels will probably not involve acute toxic responses. It is most likely an insidious effect(s) disrupting the homeostasis of the organism. The exposed animals may appear totally 'normal' clinically or based on conventional toxicological endpoints. However, such a subclinical state may provide basis for enhancement or potentiation of otherwise mild toxic responses from an acute exposure(s) of chemical, physical and/or biological agents. In this sense, the concept of generic 'promotor or 'enhancer' for any possible toxicity may be advanced for the potential toxicologic consequence of a mixture of environmental pollutants. These findings also raise the possibility of syngergistic interaction between a background long-term, low-level chemical mixture exposure and a subsequent acute dose resulting from accidental exposure of drug intake including alcohol abuse. These results were published in Toxicol, Lett. (1989), 49, 183-197; (1991), 57, 101-111; JEPTO (1992), 11(2), 1-10.