Publication- Extension of the DST Approach to Incorporate Chemicals Classified as Reactive

Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive
Robert J. Safford , Anne Marie Api, David W. Roberts, Jon F. Lalko,
B-Safe Toxicology Consulting, Northants, United Kingdom; Research Institute for Fragrance Materials, Inc., Woodcliff Lake, United States; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
Regulatory Toxicology and Pharmacology (Volume 72, Issue 3, August 2015), pp 694–701
doi:10.1016/j.yrtph.2015.04.020

article-2

Highlights

• The Dermal Sensitisation Threshold applies TTC principals to skin sensitisation.

•The DST is useful for both non-reactive and protein reactive chemicals.

•The DST along with structural alerts defines a threshold of low sensitisation risk.

Abstract

« The evaluation of chemicals for their skin sensitising potential is an essential step in ensuring the safety of ingredients in consumer products.

Similar to the Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has been demonstrated to provide effective risk assessments for skin sensitisation in cases where human exposure is low. The DST was originally developed based on a Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not considered to be directly reactive to skin proteins, and unlikely to initiate the first mechanistic steps leading to the induction of sensitisation.

Here we have extended the DST concept to protein reactive chemicals. A probabilistic assessment of the original DST dataset was conducted and a threshold of 64 μg/cm2 was derived. In our accompanying publication, a set of structural chemistry based rules was developed to proactively identify highly reactive and potentially highly potent materials which should be excluded from the DST approach. The DST and rule set were benchmarked against a test set of chemicals with LLNA/human data.

It is concluded that by combining the reactive DST with knowledge of chemistry a threshold can be established below which there is no appreciable risk of sensitisation for protein-reactive chemicals. »


Sources :
http://www.sciencedirect.com/science/article/pii/S0273230015000975
http://fragrancematerialsafetyresource.elsevier.com/

Cet article n’engage que son auteur/ This article is the sole responsibility of the author

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