Quantitative risk assessment for the induction of allergic contact dermatitis: uncertainty factors for mucosal exposures

Abstract

The quantitative risk assessment (QRA) paradigm has been extended to evaluating the risk of induction of allergic contact dermatitis from consumer products. Sensitization QRA compares product-related, topical exposures to a safe benchmark, the sensitization reference dose. The latter is based on an experimentally or clinically determined 'no observable adverse effect level' (NOAEL) and further refined by incorporating 'sensitization uncertainty factors' (SUFs) that address variables not adequately reflected in the data from which the threshold NOAEL was derived. A critical area of uncertainty for the risk assessment of oral care or feminine hygiene products is the extrapolation from skin to mucosal exposures. Most sensitization data are derived from skin contact, but the permeability of vulvovaginal and oral mucosae is greater than that of keratinized skin. Consequently, the QRA for some personal products that are exposed to mucosal tissue may require the use of more conservative SUFs. This article reviews the scientific basis for SUFs applied to topical exposure to vulvovaginal and oral mucosae. We propose a 20-fold range in the default uncertainty factor used in the contact sensitization QRA when extrapolating from data derived from the skin to situations involving exposure to non-keratinized mucosal tissue.

Prospective study of patch testing in patients with vulval pruritus

“…[15][16][17] It has also been suggested that manufacturers may not take into consideration this increased susceptibility to irritant and allergic contact dermatitis of mucosal surfaces when performing pre-marketing testing. 16,17 Although most patients reported using topical corticosteroids, there were only two positive reactions to the corticosteroid allergens tixocortol pivalate and hydrocortisone-17-butyrate. These are representatives from groups A and D of the allergic contact dermatitis cross-reactive groups in corticosteroid patch testing.…”

Anogenital Dermatitis in Patients Referred for Patch Testing

“…4,5,11,14 This finding could be explained by either the frequent use of corticosteroids to treat anogenital conditions or by enhanced penetration. 18,19,32,33 Feldmann and Maibach 34 showed that carbon 14 hydrocortisone penetrates the scrotum at a rate 42 times higher than in the ventral forearm. Similarly, Britz et al 35 showed that 7.7% of topically applied hydrocortisone cream penetrated vulvar epithelium compared with 1.3% used on forearm skin.…”

Assessing the Dermal Safety of Products Intended for Genital Mucosal Exposure

“…They take into account interindividual susceptibility, matrix differences between the intended product formulation and the test solution in the existing testing for contact sensitization, and variations in the skin exposures. More conservative uncertainty factors are recommended for the skin exposure considerations if the ingredient is intended for products that will come into contact with mucous membranes [17].…”