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A multidisciplinary approach to toxicological screening: I. Systemic toxicity

E Berman1, M Schlicht, V C Moser

  • 1Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

Journal of Toxicology and Environmental Health
|June 1, 1995
PubMed
Summary
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This study assessed the toxicity of 10 chemicals in rats, finding that effective doses for systemic toxicity were often a small fraction of the LD50, highlighting the sensitivity of organs like the liver and kidneys to chemical exposure.

Area of Science:

  • Toxicology
  • Environmental Health
  • Pharmacology

Background:

  • Assessing chemical toxicity is crucial for public health and environmental safety.
  • Understanding dose-response relationships helps establish safe exposure limits.
  • Previous toxicity data for some industrial chemicals and pesticides may be incomplete or require further validation.

Purpose of the Study:

  • To evaluate the toxic effects of 10 diverse chemicals (pesticides, solvents, industrial compounds) in female F344 rats.
  • To determine dose-dependent toxicological responses in key organs (liver, kidneys, spleen, thymus, adrenals) after acute and sub-chronic oral exposure.
  • To validate an abbreviated LD50 estimation method and a dose-selection algorithm for toxicity testing.

Main Methods:

  • Oral administration of 4 dose levels, based on estimated acute LD50, to female F344 rats for 1 or 14 days.

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  • Multivariate analysis (MANOVA) and post hoc contrast analysis were used to assess organ toxicity.
  • Histopathological examination of liver, kidneys, spleen, thymus, and adrenals for toxicological endpoints.

    • Main Results:

    • Heptachlor induced splenic and thymic lymphocyte necrosis; Triadimefon altered liver and spleen weights.
    • Dichloromethane and trichloroethylene caused dose-dependent hepatotoxicity, with TCE effects seen at lower doses than previously reported.
    • Phenol exposure led to hepatocellular necrosis and kidney lesions, potentially due to vascular stasis; DEHP induced hepatocellular changes.

    Conclusions:

    • The dose-selection algorithm proved effective for both acute and repeated dosing regimens.
    • For most tested chemicals, systemic toxicity occurred at doses significantly lower than the acute LD50.
    • This study provides valuable toxicological data for pesticides, solvents, and industrial chemicals, informing risk assessment and regulatory guidelines.