Risk Assessment and Immunotoxicity
- PDF / 379,135 Bytes
- 5 Pages / 504 x 720.24 pts Page_size
- 81 Downloads / 273 Views
0092-8615197
Copyright 0 1997 Dmg Information Association Inc.
F’rinted in the USA. All rights reserved.
RISK ASSESSMENT AND IMMUNOTOXICITY HENKVAN LOVEREN, JOHANGARSSEN, CEESDE HEER, AND JOSEPHG . VOS Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, Bilthoven, the Netherlands
Effects of a drug on the immune system can be assessed in humans but whether such effects result in decreased resistance to infections cannot easily be assessed in a direct sense. Extrapolation of data on immunotoxicity of agents resulting in decreased resistance to infections gathered from experiments with rodents to the human situation is, therefore, an important step for risk evaluation. This report describes the so-called parallellogram approach that can be used for this purpose. In this parallellogram there are four cornerstones, of which one is the health effect of exposure to a chemical, assessed as an endpoint (ie, infection model) in experimental animals, and another is the quantitative prediction of this endpoint in humans. The other cornerstones are assays that can be carried out both in experimental animals and humans or materials obtained from experimental animals and humans, and that are used for species comparison. For the immunotoxic agent ultaviolet light B radiation, and the environmental contaminant 2,3,7&tetrachLomdibenzo-p-dioxin this approach was used. Such studies may direct risk evaluation for immunotoxicity of drugs. Key Words: Immunotoxicology; Risk assessment; Parallellogram approach
INTRODUCTION HUMAN DATA ON immunotoxicity may be derived from epidemiological studies following exposure, from human volunteer studies, or from studies on human cells or tissues. Each of these approaches has drawbacks. With epidemiological studies, information only becomes available after the product has been marketed. For volunteer studies, immunotoxic endpoints are limited, as studies are primarily confined to body fluids, predomiPresented at the DIA Workshop “lmmunotoxicity of Pharmaceuticals: Current Knowledge, Testing Strategies, Risk Evaluation & Consequences for Human Health,” October 2 4 , 1996, Montreux, Switzerland. Reprint address: Dr. Henk van Loveren, Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, P.O.Box 1, 3720 BA Bilthoven, The Netherlands.
nantly peripheral blood, and occasionally biopsy material. In in vitro studies, there is uncertainty about the generation of the appropriate metabolites, the relevance of the concentrations used, and the lack of complexity of the system, as compared to the in vivo situation. For these reasons, risk assessment is often based on animal studies that then have to be extrapolated to the human situation. Risk assessment comprises four steps: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Direct toxicity of chemicals, drugs, or other agents can readily be identified in experimental animals. The consequences of such immunotoxicity in
Data Loading...
