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MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: I. SYSTEMIC TOXICITY
Citation:
Berman, E. AND M. Schlicht. MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: I. SYSTEMIC TOXICITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/392.
Description:
The toxicity of 10 chemicals (carbaryl, carbon tetrachloride, chlordane, ethylhexylphthalate, dichloromethane, heptachlor, phenol, tetrachloroethylene, triadimefon, and trichloroethylene were examined in the liver, kidney, spleen, thymus, and adrenal of female F-344 rats. cute lethality was estimated using abbreviated methods. ultivariate analyses (MANOVA) of each organ were compared to univariate ANOVA of each measure for their effectiveness to determine the response. ANOVA was more effective in cases where general changes occurred. hen ANOVA was adjusted for repeated testing, it was less sensitive in determining the' lowest effective dose. he strategy of the study was to deliver doses that were a fraction of the LD50-7day, for 1 dose or for 14 daily doses and examine the rats one day after the last dose. he use of fractions of the LD50 as dose-levels worked well in both the 1-day and 14-day regimens. ichloromethane caused increased incidence of necrosis in individual centrilobular hepatocytes at doses as low as 337 mg/kg for 1 or for 14 days. Ethylhexylphthalate caused a 3- to 4-fold increase in mitotic figures in hepatocytes from doses as low as 150 mg/kg for I day; after 14 days of dosing with this same dose-level, hepatocellular cytomegaly was apparent. ingle dose of heptachlor caused necrotic lymphocytes in spleen and thymus at levels as low as 23 mg/kg. he level of toxicity of phenol was apparently dependent on the rate of administration, with no cumulative effects over 14 days. iver and spleen weights were changed by triadimefon, an effect not previously described. richloroethylene was hepatotoxic at 1/10 the levels reported in the literature; this may be a strain or sex-related sensitivity.