Development of Short Term Immunotoxicological Assays for Prediction of Chronic Toxicological Responses Induced by Environmental Chemicals
Abstract
The overall goal of the research project was to systematically develop a battery of in vitro functional assays to predict subchronic or chronic toxicologic behavior that would be produced by an in vivo exposure to a chemical. The results of the in vivo exposures were used to determine if the in vitro tests could predict the toxicologic behavior. The in vitro studies were developed along a tier system, using spleen and bone marrow cells. The Tier 1 assays for the spleen cells were the direct cytotoxicity as measured by trypan blue exclusion and changes in cell number over the exposure period. Also in this tier was the effect of chemicals on DNA synthesis. For Tier 2, the lymphocyte response to a T and a B cell mitogen is used, and in Tier 3, the more complex cell-cell interactions involved in a Mishell-Dutton assay, the mixed lymphocyte reaction, and the in vitro growth of stem cells are investigated. The in vivo studies included a complete toxicologic workup in both male and female mice, using trichloroethylene and dexamethasone. The most sensitive indicators of dexamethasone toxicity were changes in body, spleen, and thymus weights, depression of peripheral leukocyte counts, and an increase in the percent of polymorphonuclear leukocytes. Mice exposed to dexamethasone were deficient in humoral and cell-mediated immunity, with minimal effects on the macrophage and bone marrow parameters.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 25, 1986
- Accession Number
- ADA174925
Entities
People
- Albert E. Munson
Organizations
- Virginia Commonwealth University School of Medicine