Probabilistic derivation of the interspecies assessment factor for skin sensitization

• Published in: Regulatory toxicology and pharmacology 2017-08, Vol.88, p.34-44
• Main Authors: Bil, W., Schuur, A.G., Ezendam, J., Bokkers, B.G.H.
• Format: Article
• Language: English
• Subjects: Allergens - adverse effects; Allergic contact dermatitis; Animals; Cosmetics - chemistry; Dermatitis, Allergic Contact - prevention & control; Dose-response modeling; Dose-Response Relationship, Drug; HMT; Household Products - analysis; HRIPT; Humans; Interspecies sensitization assessment factor; LLNA; Mice; No-Observed-Adverse-Effect Level; Probability distribution; Quantitative risk assessment; Risk Assessment; Skin - drug effects; Skin sensitization; Species Specificity
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2017.05.015

An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization threshold is in good correspondence with that determined in humans. However, on an individual level, the murine and human sensitization thresholds may differ considerably. In this study, the interspecies SAF was quantified by using a probabilistic approach, to be able to take these cases into account. As expected, the geometric means of the probability distributions of murine and human sensitization threshold ratios were close to one, but taking the 95 th percentile of these distributions resulted in an interspecies SAF of 15. By using this value, one is sure that with 95% probability, the sensitization threshold determined in mice does not underestimate the human threshold. It can be concluded that a murine-based NESIL requires the use of an interspecies SAF (of 15) in the QRA for skin sensitization, to correct for the differences between mice and humans. This empirically derived interspecies SAF contributes to refinement of the risk assessment methodology. •On average, the murine sensitization threshold corresponds well with the human threshold.•Deviations of this correspondence, up to two orders of magnitude, can be observed.•An interspecies sensitization assessment factor (SAF) of 15 is proposed.•This SAF is required for LLNA based quantitative risk assessment of sensitizers.