Derivation of the no expected sensitization induction level for dermal quantitative risk assessment of fragrance ingredients using a weight of evidence approach.

Some fragrance ingredients may have the potential to induce skin sensitization in humans but can still be safely formulated into consumer products. Quantitative Risk Assessment (QRA) for dermal sensitization is required to determine safe levels at which potential skin sensitizers can be incorporated into consumer products. The no expected sensitization induction level or NESIL is the point of departure for the dermal QRA. Sensitization assessment factors are applied to the NESIL to determine acceptable exposure levels at which no skin sensitization induction would be expected in the general population. This paper details the key steps involved in deriving a weight of evidence (WoE) NESIL for a given fragrance ingredient using all existing data, including in vivo, in vitro, and in silico. Read-across can be used to derive a NESIL for a group of structurally similar materials when data are insufficient. When sufficient target and read-across data are lacking, exposure waiving threshold (the DST) may be used. We outline the process as it currently stands at the Research Institute for Fragrance Materials Inc. (RIFM) and provide examples, but it is dynamic and is bound to change with evolving science as new approach methodologies (NAMs) are actively incorporated.