Understanding fragrance allergy using an exposure‐based risk assessment approach

Abstract

Conducting a sound skin sensitization risk assessment prior to the introduction of new ingredients and products into the market place is essential. The process by which low-molecular-weight chemicals induce and elicit skin sensitization is dependent on many factors, including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. Specifically, by estimating the exposure to the allergen and its allergenic potency, it is feasible to assess quantitatively the sensitization risk of an ingredient in a particular product type. This paper focuses on applying exposure-based risk assessment tools to understanding fragrance allergy for 2 hypothetical products containing the fragrance allergen cinnamic aldehyde. The risk assessment process predicts that an eau de toilette leave-on product containing 1000 ppm or more cinnamic aldehyde would pose an unacceptable risk of induction of skin sensitization, while a shampoo, containing the same level of cinnamic aldehyde, would pose an acceptable risk of induction of skin sensitization, based on limited exposure to the ingredient from a rinse-off product application.

The local lymph node assay and the assessment of relative potency: status of validation

“…In order to protect human health, chemicals that have the intrinsic property of skin sensitization needed to be identified, characterized, and subjected to appropriate risk assessments and risk management. Risk assessments already make extensive use of information on sensitization potency (40)(41)(42)(43)(44)(45). In contrast, regulatory toxicology currently fails to exploit any information of this sort, despite several recommendations on this subject (38,39,46).…”

“…First, as has already been proposed by both industry (38) and regulatory (39) expert groups, potency data can lead to improvements in hazard classification and thus risk management. Second, potency data can facilitate improved risk assessments for skin sensitization (40)(41)(42)(43)(44). Both of these are in our highly desirable goals, but the details fall outside the remit of this article, which is simply to discuss the status of validation of EC3 potency determinations in the LLNA.…”

Skin sensitization

“…32,36,37 Quantitative information on the potency of the sensitizer can be used as the basis for human risk assessment, with detailed guidelines for how this may be achieved having been promulgated. [38][39][40] In response to the above question, firstly, it is evident that predictive assays in the mouse and the guinea pig have had considerable success in the identification of substances that are known to cause contact allergy in humans. [22][23][24][25]41 There are situations where substances known to cause contact allergy in humans have proven to being negative in predictive tests, but generally these have arisen either because of suspected inadequate test conduct (examples include methyldibromo glutaronitrile and methylisothiazolinone (MI)) or because of substances termed 'non-sensitizers', which in reality represent the examples where the cut-off for regulatory classification and labelling of the sensitizer can be shown to be due to that cut-off representing a higher threshold than that actually found in practice in humans.…”

Utility of murine dendritic cell line DC2.4 for <i>in vitro </i>assay of skin-sensitization potential

“…429;OECD, 2002) as a stand-alone test for skin sensitization. One of the merits of the LLNA is that it provides quantitative information on the sensitization potency of a test chemical in the form of an EC3 value (i.e., the estimated concentration required to induce a 3-fold increase in lymph node cell proliferation), which can be used for the risk assessment of finished products containing that chemical (Gerberick et al, 2001;Griem et al, 2003;Api and Vey, 2008). The LLNA is currently the first-choice method for assessing sensitization potency (Angers-Loustau et al, 2011).…”