Biocides: Characterization of the Allergenic Hazard of Methylisothiazolinone

Biocides used in many every day products often are able to act as haptens and so may cause allergic reactions in the skin. In addition, where exposure of the respiratory tract may occur, they should also be evaluated for their ability to cause respiratory allergy. Here we have used local lymph node assay (LLNA) data to compare the relative potency of four biocides together with cytokine profiling to determine whether these biocides can induce skin and/or respiratory allergy. Formaldehyde, glutaraldehyde, 5‐chloro‐2‐methyl‐4‐isothiazolin‐3‐one and 2‐methyl‐2H‐isothiazol‐3‐one mix (3:1) (CMI/MI), and 2‐methyl‐2H‐isothiazol‐3‐one alone (MI) were tested in the LLNA in two vehicles [acetone:olive oil (AOO) and propylene glycol (PG)]. Their relative allergenic potency was measured by derivation of the EC3 value (the estimated concentration that will induce a stimulation index of 3 following topical application of chemical). In AOO, the EC3 value for the chemicals were ranked as follows: formaldehyde = MI < glutaraldehyde < CMI/MI, CMI/MI thus being the most potent allergen as it has the lowest EC3 figure. In PG, a similar rank order of biocides was achieved but the estimated potency in PG was at least 1 log lower than that in AOO. Data are available indicating that while formaldehyde is a contact allergen, glutaraldehyde is both a contact and respiratory allergen. Cytokine profiling was carried out to determine whether CMI/MI and MI also have the potential to cause sensitization of the respiratory tract. The data obtained for CMI/MI were consistent with behavior as a contact sensitizer. The MI is less strongly sensitizing than CMI/MI, being comparable to formaldehyde, and due to this weaker response it has not been possible to evaluate fully its cytokine profile, an outcome indicating it is unlikely to be a significant chemical respiratory allergen.