Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

Rennen, M.A.J.
Nordheim, K.
Houben, G.F.
de Heer, C.
Instituut CIVO-Toxicologie en Voeding TNO

2002

Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in route-to-route extrapolation is the occurrence of local effects. Often, the results of acute irritation studies are used to assess the likelihood of the occurrence of local effects also following repeated exposure and thereby the validity of route-to-route extrapolation. We questioned this working practice and considered whether local effects observed in a given study are of any predictive value with respect to the occurrence of local effects after repeated exposure. Our database analysis indicates that substances inducing skin and/or eye irritation frequently induce local effects after repeated respiratory exposure. In contrast, observations made in any type of study show little or no positive predictive value for the occurrence of local effects after repeated dermal exposure. Notably, the absence of any indication of local effects in any type of study does not exclude the occurrence of local effects on repeated dermal or respiratory exposure. We conclude that the presumed reliability of route-to-route extrapolation in the absence of route-specific toxicity data can be questioned. © 2002 Elsevier Science (USA). Chemicals/CAS: Irritants

Nutrition
Administration, Cutaneous
Animals
Databases, Factual
Disease Models, Animal
Humans
Inhalation Exposure
Irritants
Models, Theoretical
Occupational Exposure
Predictive Value of Tests
Respiratory System
Risk Assessment
Skin
Toxicity Tests

http://resolver.tudelft.nl/uuid:df095719-2715-43a7-99b8-5b2203b978fd

https://doi.org/10.1006/rtph.2002.1582

72874

0273-2300

Regulatory Toxicology and Pharmacology, 36 (3), 253-261

article