Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied
David W. Roberts, Anne Marie Api , Robert J. Safford, Jon F. Lalko
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool United Kingdom; Research Institute for Fragrance Materials, Woodcliff Lake, United States; B-Safe Toxicology Consulting, Northants, United Kingdom
Regulatory Toxicology and Pharmacology (Volume 72, Issue 3, August 2015), pp 683–693
• The Dermal Sensitisation Threshold can help protect human health from skin allergens.
• Structural alerts can exclude highly reactive materials from the DST approach.
•A DST with structural alerts defines an exposure threshold of low sensitisation risk.
An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential.
The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally.
Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 lg/cm2 for chemicals assessed as reactive. This would protect against 95 % of chemicals assessed as reactive, but the remaining 5 % would include chemicals with very high potency.
Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST. »
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