Risks of Allergic Contact Dermatitis Elicited by Nickel, Chromium, and Organic Sensitizers: Quantitative Models Based...

Risks of allergic contact dermatitis (ACD) from consumer products intended for extended (nonpiercing) dermal contact are regulated by E.U. Directive EN 1811 that limits released Ni to a weekly equivalent dermal load of ≤0.5 μg/cm² . Similar approaches for thousands of known organic sensitizers are hampered by inability to quantify respective ACD-elicitation risk levels. To help address this gap, normalized values of cumulative risk for eliciting a positive ("≥+") clinical patch test response reported in 12 studies for a total of n = 625 Ni-sensitized patients were modeled in relation to observed ACD-eliciting Ni loads, yielding an approximate lognormal (LN) distribution with a geometric mean and standard deviation of GM_Ni = 15 μg/cm² and GSD_Ni = 8.0, respectively. Such data for five sensitizers (including formaldehyde and 2-hydroxyethyl methacrylate) were also ∼LN distributed, but with a common GSD value equal to GSD_Ni and with heterogeneous sensitizer-specific GM values each defining a respective ACD-eliciting potency GM_Ni /GM relative to Ni. Such potencies were also estimated for nine (meth)acrylates by applying this general LN ACD-elicitation risk model to respective sets of fewer data. ACD-elicitation risk patterns observed for Cr(VI) (n = 417) and Cr(III) (n = 78) were fit to mixed-LN models in which ∼30% and ∼40% of the most sensitive responders, respectively, were estimated to exhibit a LN response also governed by GSD_Ni . The observed common LN-response shape parameter GSD_Ni may reflect a common underlying ACD mechanism and suggests a common interim approach to quantitative ACD-elicitation risk assessment based on available clinical data.