Quantitative Risk Assessment of Diisocyanates Leaching From Wound Dressings Under Physiological Conditions

ABSTRACT Introduction Diisocyanates are potent sensitizers extensively used in polyurethane‐based materials, with numerous case reports linking them to allergic contact dermatitis (ACD). Recent extractables studies have detected residual diisocyanates in medical devices such as wound dressings. However, these assessments typically rely on non‐physiological extraction methods, limiting their relevance to actual skin exposure conditions. Objectives This study aimed to develop and validate a physiologically relevant method for quantifying residual 4,4′‐diphenylmethane diisocyanates (MDI), dicyclohexylmethane‐4,4‐diisocyanates (DMDI), hexamethylene diisocyanates (HDI), toluene diisocyanates (2,4‐ and 2,6‐TDI) and isophorone diisocyanates (IPDI) leaching from wound dressings, and subsequently assess their risk of sensitisation induction and ACD elicitation. Methods Diisocyanate standards were stabilised as di‐lysine adducts in an artificial sweat solution, simulating skin exposure. An optimised LC–MS/MS method was used for quantification. The method was validated across a wide concentration range and subsequently applied to 36 commercial wound dressings. Exposure levels were evaluated against toxicological thresholds for quantitative risk assessments. Results The method proved reliable for all target diisocyanates (except IPDI) at concentrations ≥ 15 ppb. Analysis of the samples revealed that 44% contained quantifiable levels of residual diisocyanates. Notably, over 50% of the HDI‐positive and 20% of MDI‐positive samples exceeded the acceptable exposure level (AEL) for sensitisation induction. Moreover, all samples exceeding the AEL fell above the acceptable non‐eliciting area dose for contact dermatitis (ANEAD). Conclusion We developed and validated a physiologically relevant method to quantify diisocyanate residues leaching from wound dressings, demonstrating that HDI, in particular, poses a significant risk for sensitisation induction and can elicit ACD in individuals who are already sensitised.