Document Detail

Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals.
MedLine Citation:
PMID:  12473410     Owner:  NLM     Status:  MEDLINE    
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.
Monique A J Rennen; Kirsti Nordheim; Geert F Houben; Cees de Heer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Regulatory toxicology and pharmacology : RTP     Volume:  36     ISSN:  0273-2300     ISO Abbreviation:  Regul. Toxicol. Pharmacol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-10     Completed Date:  2003-05-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8214983     Medline TA:  Regul Toxicol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-61     Citation Subset:  IM    
Department of Toxicological Risk Assessment, TNO Chemistry, P.O. Box 360, NL-3700 AJ Zeist, The Netherlands.
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MeSH Terms
Administration, Cutaneous
Databases, Factual
Disease Models, Animal
Inhalation Exposure*
Irritants / adverse effects*
Models, Theoretical*
Occupational Exposure*
Predictive Value of Tests
Respiratory System / pathology
Risk Assessment
Skin / pathology
Toxicity Tests
Reg. No./Substance:

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