Dose‐response assessments of Kathon® biocide (I). Diagnostic use and diagnostic threshold patch testing with sensitized humans

Weaver, James E.; Cardin, Caroline W.; Maibach, Howard I.

doi:10.1111/j.1600-0536.1985.tb01083.x

Cited by 57 publications

(14 citation statements)

References 2 publications

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“…At least 1 of the test products was used at least 1X daily. No skin reactions indicative of allergic contact dermatitis elicitation were observed amongst any of the subjects (93).…”

Section: R III Se-ojfmentioning

confidence: 85%

An update of the risk assessment for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) with focus on rinse‐off products

1999

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Methylchloroisothiazolinone/methylisothiazolinone (MCUMI) has been widely used during the last 20 years for the preservation of aqueous systems in cosmetics, toiletries and in various industrial applications. MCI/MI has a broad spectrum of activity against fungi and bacteria at very low concentrations. The allergic contact potential of MCI/MI has been known for many years. This paper provides a review of pre-clinical and clinical experimental studies as well as experience from dermatology clinics worldwide. This forms the basis for an update of the risk assessment for the use of MCUMI in rinse-off products. The scientific data indicate that the actual sensitization rate observed with a contact allergen is extremely dependent on dose and type of exposure. This review of the data leads to the conclusion that, under normal use conditions, within the current permitted/ recommended use concentrations for MCI/MI of up to 15ppm, the risk of primary sensitization from the use of rinse-off products is negligible, and elicitation of allergic contact dermatitis in MCI/MI-sensitized individuals rare, after exposure to MCUMI-preserved rinse-off products.

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“…At least 1 of the test products was used at least 1X daily. No skin reactions indicative of allergic contact dermatitis elicitation were observed amongst any of the subjects (93).…”

Section: R III Se-ojfmentioning

confidence: 85%

An update of the risk assessment for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) with focus on rinse‐off products

1999

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“…The typical formulation of MCI/MI into shampoo products at 5 ppm produces in-use exposure levels well below that limit. The fact that most sensitized individuals can safely use rinse-off products containing those levels of MCI/MI (12,47) indicates that this combination of in-product concentration and in-use exposure represents an acceptable formulation of this known contact allergen.…”

Section: Exposure-based Risk Assessmentmentioning

confidence: 99%

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

et al. 2000

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The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study.

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“…These products were tested as received or as diluted solutions. The LD, , rates for females were45 and 64 mg/kg a.i., while those for males were 40,41,45,50,56,57,64, and 78.5 mg/kg a.i. These are classified as moderately to highly toxic by the Hodge and Sterner system of cla~sification.…”

Section: Absorption D Istr I B Uti 0 N Metabolism a N D Excretionmentioning

confidence: 96%

“…The investigators suggested that the small and stable prevalence of MVMCI-CG sensitivity and the low rate of new sensitization were reflective of a slight potential for ~ensitization. '~~' H a n n u k~e l a '~~' reported a rapid increase in MVMCI-CG allergy in Finland (Table 10 Weaver et al (56) conducted a diagnostic provocative use test to determine the skin sensitivity of humans to consumer products containing MVMCI-CG. Eighteen subjects who had a known skin hypersensitivity to MVMCI-CG (confirmed through positive reactions to diagnostic patch testing with an aqueous solution containing 100 ppm) were given various prototype products to use in place of their regular brands for periods of three or six weeks.…”

Section: Cosmetic Ingredient Rev1 Ewmentioning

confidence: 99%

6 Final Report on the Safety Assessment of Methylisothiazolinone and Methylchloroisothiazolinone

1992

Journal of the American College of Toxicology

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Methylisothiazolinone and Methylchloroisothiazolinone (MVMCI) are heterocyclic organic compounds that are used in cosmetics as a broad spectrum preservative system.MI/MCI was absorbed after oral administration and then was excreted in the urine or feces; storage in the tissues was minimal. Up to 62% of a single percutaneous dose was bound to the site of application 24 hours after exposure. The MI/MCI-CC bound to the skin had a 13.1 -day half-life.MI/MCI was moderately to highly toxic to rats, and highly toxic to rabbits when administered orally, and moderately toxic when applied dermally. MIIMCI was not a cumulative ocular irritant when tested at 55 ppm. The dermal irritation of MI/MCI was concentration dependent but nonirritating to rabbit skin at 560 ppm concentrations; this nonirritating concentration is well above the maximum recommended use concentration.No treatment-related effects were observed in rats which received MI/MCI in oral doses up to 24.4 mg/kg/day for 2 weeks. Doses of MI/MCI up to 2.8 mg/kg/day applied dermally to rabbits, 5 days per week for 3 weeks, produced moderate irritation at the application site but no systemic toxicity. Dermal application of MIIMCI at doses up to 0.4 mg/kg/day for 3 months produced no systemic toxicity in rabbits. No toxicologically significant treatment-related effects were observed in rats or dogs at doses up to 30 and 28 mgkg/day, respectively. The result of genotoxic testing of MVMCI varied with the assay used. Dermal application of 400 ppm MI/MCI-CG, 3 times per week for 30 months, had no local or systemic tumorigenic effect in male mice.MVMCI administered by gavage to pregnant rabbits and rats at doses up to 13.3 mg/kg/day was toxic to the dam, embryo, and fetus; the compound was not teratogenic. MIIMCI is a sensitizer however, the concentration of MI/MCI in cosmetic products which produced sensitization varies. The available human sensitization test data at concentrations of 50 ppm and above are not in agreement. MUMCI-CG was not a sensitizer or photosensitizer at a concentration of 15 ppm.It is concluded that Methylisothiazolinone/Methylchloroisothiazolinone may be safely used in "rinse-off" products at a concentration not to exceed 15 ppm and in "leave-on" cosmetic products at a concentration not to exceed 7.5 ppm. The stated 75 at PENNSYLVANIA STATE UNIV on November 5, 2014 ijt.sagepub.com Downloaded from 76 COSMETIC INGREDIENT REVIEW safe use concentration refers to a mixture containing 23.3% Methylisothiazolinone and 76.7% Methylchloroisothiazolinone. INTRODUCTION his review on the safety of use of Methylisothiazolinone and Methylchloroisothia-T zolinone includes all the published data, as well as unpublished data submitted to CIR by interested individual cosmetic ingredient suppliers and formulators. Most of the data were developed prior to the start of the review. Other data cited were developed and submitted during the review in response to specific concerns expressed by the CIR Expert Panel.

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Dose‐response assessments of Kathon® biocide (I). Diagnostic use and diagnostic threshold patch testing with sensitized humans

Cited by 57 publications

References 2 publications

An update of the risk assessment for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) with focus on rinse‐off products

An update of the risk assessment for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) with focus on rinse‐off products

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

6 Final Report on the Safety Assessment of Methylisothiazolinone and Methylchloroisothiazolinone

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