Risk assessment and immunotoxicology

Citation
H. Van Loveren et al., Risk assessment and immunotoxicology, TOX LETT, 103, 1998, pp. 261-265
Citations number
11
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY LETTERS
ISSN journal
03784274 → ACNP
Volume
103
Year of publication
1998
Pages
261 - 265
Database
ISI
SICI code
0378-4274(199812)103:<261:RAAI>2.0.ZU;2-L
Abstract
In general toxicity testing, maximal acceptable concentrations are derived from no-observed adverse effect levels (NOAEL) in rodents. Risk assessment then considers safety factors for the interspecies difference, and intraspe cies variability. This approach can be used for assessing maximal acceptabl e concentrations for chemicals inducing direct immunotoxicity, resulting in e.g. reduced resistance to infections. As for predictive testing of chemic als in terms of sensitization, laboratory animal data are mostly used for r isk assessment as well. Generally, the assessment of risk for chemicals tha t induce contact sensitivity is limited to hazard identification, and risk management is restricted to labeling. An alternative type of evaluation of the risk of adverse effects due to exposure to immunotoxic chemicals may be the so called parallellogram approach. In this parallellogram there are fo ur cornerstones, one of which is the health effect of exposure to a chemica l, assessed as an endpoint (e.g. infection model) in experimental animals, and another the quantitative prediction of this endpoint in humans. The oth er cornerstones are assays of parameters that are relevant to the mechanism of the adverse effect in experimental animals and humans, and are used for species comparison. Species comparisons between the animal species used fa r hazard identification and humans are crucial for extrapolation of animal data to the human situation. This approach can be used to provide relevant information on the dose-response relationship in humans. In concert with in formation on actual exposure, such data can then be used for the characteri zation of risk for adverse health effects in humans. Such approaches have b een used for chemicals that exert direct immunotoxic activity (bis(tri-n-bu tyltin)oxide (TBTO)), and may hold promise for the risk evaluation of chemi cals that exert skin sensitizing properties. (C) 1998 Elsevier Science Irel and Ltd. All rights reserved.