Fragrance Skin Sensitization Evaluation and Human Testing: 30-Year Experience

TLDR

The human repeated insult patch test (HRIPT) is a standard safety assessment in the fragrance industry to confirm absence of skin sensitization at a defined dose. The study aimed to document over 30 years of HRIPT experience in the fragrance industry. The authors retrospectively collated 154 HRIPT studies on 134 substances, each with at least 100 volunteers, totaling 16,512 participants. Across 154 studies, sensitization occurred in only 0.12% of subjects (20/16,512), dropping to 0.03% in the last 11 years, underscoring that de novo sensitization is rare yet highlights limitations of nonhuman predictive methods.

Abstract

The human repeated insult patch test (HRIPT) has a history of use in the fragrance industry as a component of safety evaluation, exclusively to confirm the absence of skin sensitization at a defined dose.The aim of the study was to document the accumulated experience from more than 30 years of conducting HRIPTs.A retrospective collation of HRIPT studies carried out to a consistent protocol was undertaken, with each study comprising a minimum of 100 volunteers.The HRIPT outcomes from 154 studies on 134 substances using 16,512 volunteers were obtained. Most studies confirmed that at the selected induction/challenge dose, sensitization was not induced. In 0.12% of subjects (n = 20), there was induction of allergy. However, in the last 11 years, only 3 (0.03%) of 9854 subjects became sensitized, perhaps because of improved definition of a safe HRIPT dose from the local lymph node assay and other skin sensitization methodologies, as well as more rigorous application of the standard protocol after publication in 2008. This experience with HRIPTs demonstrates that de novo sensitization induction is rare and becoming rarer, but it plays an important role as an indicator that toxicological predictions from nonhuman test methods (in vivo and in vitro methods) can be imperfect.