© 1992 Oxford University Press
research-article |
Risk Assessment in Immunotoxicology
I. Sensitivity and Predictability of Immune Tests
*Systems Toxicity Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, North Carolina 27709
Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, North Carolina 27709
Department of Biostatistics, Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298
Received April 4, 1991; accepted July 24, 1991
We have previously reported on the design and content of a screening battery involving a "tier" approach for detecting potential immunotoxic compounds in mice (Luster et al., 1988, Fundam. Appl. Toxicol. 10, 2–19). This battery has now been utilized to examine a variety of compounds by the NIEHS Immunotoxicology Laboratory, the National Toxicology Programsponsored laboratories, and by the Cell Biology Department at the Chemical Industry Institute of Toxicology. The database generated from these studies, which consists of over 50 selected compounds, has been collected and analyzed in an attempt to improve future testing strategies and provide information to aid in quantitative risk assessment for immunotoxicity. Studies presented here have established the ability of each of the tests or test combinations in the screening battery to detect immunotoxic compounds. Efforts are currently underway using this database to determine the relationships between these immune tests and susceptibility to challenge with infectious agents or transplantable tumor cells. The present analyses indicated that the performance of only two or three immune tests are sufficient to predict immunotoxic compounds in rodents (>90% concordance). The tests that showed the highest association with immunotoxicity were the splenic antibody plaque forming cell response (78%) and cell surface marker analysis (83%). The relationship between immunotoxicity and carcinogenicity, as well as genotoxicity, was also determined. These analyses suggested that potential immunotoxic compounds are likely to be rodent carcinogens (p = 0.019) although for compounds that are not immunotoxic the carcinogenic status is unclear. There was no relationship observed between immunotoxicity and mutagenicity as determined using in vitro genotoxicity tests. The significance of these observations is discussed in terms of the relationship between immunotoxicity tests and biological/toxicological processes concerned with human health (e.g., infectious disease).