Genetic Toxicity and Carcinogenicity Studies of Kathon
To the Editor: assays, including the L5178Y (mouse lymphoma), in vitro cytogenetic, in vitro unscheduled DNA synthesis, Kathon CG biocide is the trade name of a product manufactured and sold by the Rohm and Haas Com-in vitro cell transformation, along with in vivo cytogenetic, and Drosophila melanogaster assays [Scribner pany for preservation of cosmetic and toiletry products against microbial contamination. The product has been et al., 1983]. It has also been tested in a mouse micronucleus assay [Richardson et al., 1983]. Kathon biocide sold since the late 1970s, and has been successfully registered in over 35 countries around the world where showed negative (nongenotoxic) results in all of these assays, except the mouse lymphoma assay in which formal registration is required, including Japan. In support of our extensive global use, we have assembled the results were positive (much less so in the presence of metabolic activation). Although the mouse and compiled one of the most complete and comprehensive toxicology and clinical databases for a preser-lymphoma assay is currently included in the US EPA testing guidelines, it is only one of three options for vative.
An article recently published by your journal [Con-the required in vitro gene mutation assay. The mouse lymphoma assay has produced false-positive reactions nor et al., 1996] reports on studies in which aqueous dilutions of several cosmetic products preserved with for a number of compounds, including spermine [Bouzyk and Rosiek, 1988], catecholamines [McGregor et Kathon CG biocide, along with aqueous dilutions of Kathon biocide itself, were evaluated in the Ames Sal-al., 1988], salt [Wangenheim and Bolcsfoldi, 1988],
and a number of other nongenotoxic chemicals [Cald-monella assay and were found to be positive for strain TA 100, the only strain tested.
well, 1993]. The EPA Science Advisory Committee for the Federal Insecticide, Fungicide, and Rodenticide These results are not surprising and, in fact, confirm the findings of several previously published reports of Act advised in 1989 that ''mutagenicity in L5178Y
(mouse lymphoma assay) cannot be concluded with a positive results of aqueous dilutions of Kathon biocide in Ames Salmonella strain TA100 without activation, sufficient degree of certainty to be evidence of mutagenicity or of potential hazard'' [CIR, 1992]. It is our since diluted aqueous cosmetic products are only slight modifications of the aqueous vehicles used in the previ-judgment and that of others [CIR, 1992] that the collective genetic toxicity results for Kathon biocide demon-ous studies [Monte et al., 1983; Scribner et al., 1983;Wright et al., 1983]. The collective results of these strates that it is not genotoxic and does not represent a mutagenic hazard to humans.
Ames assays indicate that diluted concentrations of the active ingredients of Kathon biocide produce positive
Although mutagenicity studies are often used to make predictions of carcinogenicity potential in the results in strain TA100 without metabolic activation, negative or greatly attenuated positive results in strain absence of carcinogenic bioassays, it must be emphasized that the definitive test for carcinogenicity is the TA100 with metabolic activation, and negative results in the other commonly tested Ames strains (TA 98, bioassay. As Connor et al. note, the Rohm and Haas
Company previously conducted a 30-month mouse der-TA1535, and TA1537).
The Ames assay is a good early screening tool for mal carcinogenicity study, which indicated that Kathon biocide was not carcinogenic upon dermal application the possibility of carcinogenic potential. It misses some carcinogens (i.e., nongenotoxic carcinogens) and gives [O'Hara et al., 1984;CIR, 1992]. The concerns of Connor et al. with this study were that its design would false-positive results with some essential compounds, such as cysteine and glutathione [Glatt et al., 1983]. It not be adequate to evaluate carcinogenicity potential by today's standards, and that the dose tested, 5 mg/kg should be noted, however, that many scientists, including scientists within the EPA [Fed. Regist., 1988], be-by the authors' calculation, was too low for proper carcinogenicity testing. The Cosmetic Ingredient Re-lieve that bacterial mutagenicity test systems are not appropriate for evaluating the mutagenic potential of view (CIR) Panel, an expert committee that comprises dermatologists, cancer experts, and academic scientists biocides, which are very toxic to bacterial test systems.
As Connor et al. indicated, Kathon biocide has been recognized by the Food and Drug Administration to evaluate the safety of cosmetic ingredients, concluded evaluated in a number of mammalian cell genotoxicity