Identification and classification of skin sensitizers: identifying false positives and false negatives.
The first step in regulatory evaluation of substances involves the identification of their intrinsic hazards, including the potential for skin sensitization. This is, quite properly, entirely different from assessment of the risks to human health, which might arise from incorporation of substances in products. EU guidance on regulations concerning the classification of skin sensitizers suggests a range of sources of information be deployed in the hazard identification process. These include chemical structure, predictive animal tests, and various types of human data. Where the information is clear-cut, then uncertainties rarely arise. However, for some materials, discordant information arises, perhaps because the substance is on the borderline of test sensitivity and classification (sensitizing materials of insufficient potency do not classified according to the EU scheme), due to conflicting results in predictive tests or for other reasons. In this study, we review data on a number of substances where a classification decision is complicated by such discordances and seek to use these examples to demonstrate how best to make a weight of evidence decision on whether a substance should, or should not, be classified as a skin sensitizer.
Basketter
David A
DA
Safety and Environmental Assurance Centre, Unilever, Sharnbrook, Bedfordshire, UK. david.basketter@unilever.com
McFadden
John
J
Evans
Peter
P
Andersen
Klaus E
KE
Jowsey
Ian
I
D000485:Allergens / Q000009:adverse effects / Q000145:classification*; D000818:Animals; D001548:Benzalkonium Compounds / Q000009:adverse effects; D001622:Betaine / Q000009:adverse effects / Q000031:analogs & derivatives; D053138:Cyclohexenes / Q000009:adverse effects; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D000077222:Limonene; D009570:Nitriles / Q000009:adverse effects; D010226:Parabens / Q000009:adverse effects; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects; D012997:Solvents / Q000009:adverse effects; D013425:Sulfanilic Acids / Q000009:adverse effects; D013501:Surface-Active Agents / Q000009:adverse effects; D013729:Terpenes / Q000009:adverse effects
D000485:Allergens; D001548:Benzalkonium Compounds; D053138:Cyclohexenes; D009570:Nitriles; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D012997:Solvents; D013425:Sulfanilic Acids; D013501:Surface-Active Agents; D013729:Terpenes; D012967:Sodium Dodecyl Sulfate; D001622:Betaine; C077055:cocamidopropyl betaine; D000077222:Limonene; C039411:1,2-dibromo-2,4-dicyanobutane