Skin sensitization in chemical risk assessment: report of a WHO/IPCS international workshop focusing on dose-response assessment.
An international workshop was held in 2006 to evaluate experimental techniques for hazard identification and hazard characterization of sensitizing agents in terms of their ability to produce data, including dose-response information, to inform risk assessment. Human testing to identify skin sensitizers is discouraged for ethical reasons. Animal-free alternatives, such as quantitative structure-activity relationships and in vitro testing approaches, have not been sufficiently developed for such application. Guinea pig tests do not generally include dose-response assessment and are therefore not designed for the assessment of potency, defined as the relative ability of a chemical to induce sensitization in a previously naive individual. In contrast, the mouse local lymph node assay does include dose-response assessment and is appropriate for this purpose. Epidemiological evidence can be used only under certain circumstances for the evaluation of the sensitizing potency of chemicals, as it reflects degree of exposure as well as intrinsic potency. Nevertheless, human diagnostic patch test data and quantitative elicitation data have provided very important information in reducing allergic contact dermatitis risk and sensitization in the general population. It is therefore recommended that clinical data, particularly dose-response data derived from sensitized patients, be included in risk assessment.
van Loveren
Henk
H
National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Cockshott
Amanda
A
Gebel
Tom
T
Gundert-Remy
Ursula
U
de Jong
Wim H
WH
Matheson
Joanna
J
McGarry
Helen
H
Musset
Laurence
L
Selgrade
Maryjane K
MK
Vickers
Carolyn
C
D000818:Animals; D002857:Chromium / Q000633:toxicity; D003877:Dermatitis, Contact / Q000453:epidemiology / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007221:Industry; D023441:Local Lymph Node Assay; D016273:Occupational Exposure / Q000009:adverse effects; D010476:Perfume; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D012307:Risk Factors; D017751:Safety Management; D012871:Skin Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology*; D014481:United States; D014484:United States Environmental Protection Agency; D014944:World Health Organization
D010476:Perfume; D002857:Chromium; C074702:chromium hexavalent ion