Kathon biocide: manifestation of delayed contact dermatitis in guinea pigs is dependent on the concentration for induction and challenge.
The potential of Kathon biocide, an aqueous solution containing, as active ingredients (a.i.), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (14.4% a.i.), to produce delayed contact dermatitis, a sensitization response, was evaluated in outbred Hartley guinea pigs by a modified Buehler's occluded epicutaneous patch technique. The relationship of the response as a function of induction/elicitation concentrations was investigated. Groups of guinea pigs received 9 induction doses of the biocide, 3 times a week, at concentrations ranging from 25-2000 ppm a.i. These guinea pigs were challenged with the biocide at concentrations ranging from 20-2000 ppm a.i., and the application sites were scored for erythema 24 and 48 h after the challenge. The incidence of delayed contact dermatitis in induced guinea pigs was dependent on both the induction and challenge concentrations. The EC50 (concentration at which delayed contact dermatitis was seen in 50% of the population) for induction at a challenge concentration of 2000 ppm a.i., a nonirritating concentration, was estimated to be 88 ppm a.i. with a slope of 3.47 probits/unit log concentration. The EC50 for elicitation at an induction concentration of 1000 ppm a.i. was estimated to be 429 ppm a.i. with a slope of 2.74 probits/unit log concentration. These data demonstrate that for Kathon biocide, there is an induction/elicitation concentration dependency for delayed contact dermatitis response, and there is a "no response concentration" zone where the biocide can be used without concern for clinically significant delayed contact dermatitis. In comparison with a previous study, these data also suggest that the number of induction doses may be an important factor in demonstrating the sensitization potential of a chemical.
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D003877:Dermatitis, Contact / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D011310:Preservatives, Pharmaceutical / Q000633:toxicity; D013844:Thiazoles / Q000633:toxicity*
D000890:Anti-Infective Agents; D011310:Preservatives, Pharmaceutical; D013844:Thiazoles; C037057:Kathon 886