Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive.
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/cm(2) 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.
B-Safe Toxicology Consulting, 31 Hayway, Rushden, Northants NN10 6AG, United Kingdom. Electronic address: bob.safford@bstoxconsult.co.uk.
Robert J
RJ
Safford
Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, United States. Electronic address: amapi@rifm.org.
Anne Marie
AM
Api
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom. Electronic address: d.w.roberts@ljmu.ac.uk.
David W
DW
Roberts
Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, United States. Electronic address: jlalko@rifm.org.
Jon F
JF
Lalko
D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001681:Biological Assay; D016208:Databases, Factual; D017449:Dermatitis, Allergic Contact / Q000208:ethnology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D019055:No-Observed-Adverse-Effect Level; D011506:Proteins / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods*
D000485:Allergens; D011506:Proteins
Dermal Sensitisation Threshold (DST); Local Lymph Node Assay (LLNA); Non-animal methods; Sensitisation risk assessment; Skin sensitisation