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.