Dose‐response assessments of Kathon® biocide (II) Threshold prophetic patch testing

Abstract

Biocidal preservative agents are important in preventing the growth of pathogenic and nonpathogenic organisms in a variety of personal care, household and industrial products. Nearly all effective, commonly used preservative materials possess skin sensitization potential. In a series of 13 prophetic human repeat insult patch tests involving a total of 1450 subjects, no skin sensitization was induced at concentrations of 10 ppm, 6 ppm or 5 ppm (1121 subjects) or at 15 ppm (200 subjects) of a new isothiazolinone preservative mixture (Kathon CG). Delayed contact hypersensitivity was induced in 1 of 84 subjects at 12.5 ppm and in 2 of 45 subjects at 20 ppm. These results add further support to the previously reported conclusion that use of this new biocide at the very low concentrations required for effective preservation of rinse-off products involves an extremely low risk of clinical dermatoses.

The importance of exposure estimation in the assessment of skin sensitization risk

“…Buehler tests produced a threshold positive response at 0.0025% (10), which also calculates out to 2.5 mg/cm 2 under the patch test exposure conditions used in this study. The threshold for induction of sensitization in predictive testing in man was 0.002% (12). This calculates out to approximately 2 mg/cm 2 under the exposure conditions of the patch test.…”

“…Based on human patch test data (in water), the threshold for skin sensitization by MCI/MI is approximately 2 mg/cm 2 , with approximately 1 mg/ cm 2 defined as a no-effect level (12). The weighting factors used to determine a safety factor for MCI/ MI in a shampoo are shown in Table 5.…”

“…The value of 5 was assigned to matrix effects. This number was derived from the fact that the HRIPT conducted on MCI/MI was done in water as the vehicle (12), whereas the shampoo formulation contains surfactant ingredients. This 5X assumption may be appropriate given the known ability of surfactants to increase the skin penetration of chemicals (28,46).…”

“…It is well-known that sensitizing chemicals can be formulated into consumer products at levels that produce acceptably low incidences of sensitization (12,19,20). It is equally well known that these same ingredients are associated with a much higher incidence of ACD when formulated into products at too high a level (21).…”

“…The latter relates to the potential for induction and/or elicitation of allergic contact sensitization under exposure conditions typical of all intended and foreseeable uses of the product. Allergenic chemicals demonstrate dose-response characteristics regardless of whether the sensitization process evolves in an experimental animal model system (9,10), or in human beings (11,12). The dose response for induction and elicitation of skin allergy can be influenced by a variety of factors including, for example, the application vehicle system (13,14), the number (8) and duration (15) of exposures, underlying skin irritation (16,17) and the use of occlusion (18).…”