Evidence That Two Alkyl Ester Quaternary Ammonium Compounds Lack Substantial Human Skin-Sensitizing Potential

Ian R. Jowsey; Albert M. Kligman; Ian R. White; An Goossens; David A. Basketter

Disclosures

Dermatitis. 2007;18(1):32-39. 

In This Article

Discussion

To date, the published information regarding the skin-sensitizing potential of ester quats consists of data from predictive animal methods[1,2]and information from human studies using formulations that contain these actives.[4]The predictive animal studies described in the literature consist of a modified Buehler guinea pig test (for HEQ)[2]and a guinea pig maximization test (for a TEA-Quat).[1]The study reported here presents evidence that the lack of skin-sensitizing potential of two defined ester quats (the dialkyl ester of triethanol ammonium methyl sulphate [TEA-Quat] and the di-[hardened tallow fatty acid] ester of 2,3-dihydroxypropyl-trimethyl ammonium chloride [HEQ]) as predicted by animal models is supported by a lack of substantial skin-sensitizing potential in humans. First, this was shown by examination of each of the compounds in the maximization test. This procedure has proven sufficiently sensitive to detect weak human sensitizers.[10]In separate panels of 25 volunteers, neither compound was associated with any evidence of skin sensitization.

Second, a population of patients with suspected allergic contact dermatitis who were attending major dermatology clinics in London, UK, and Leuven, Belgium, was assessed by diagnostic patch testing to determine if the patients had become sensitized to either TEA-Quat or HEQ. At a relatively high (but subirritant) concentration (2% w/v), neither TEA-Quat nor HEQ were found to elicit any skin reactions among the 183 patients examined. At higher concentrations on the irritant threshold, a number of irritant skin reactions were observed, but again no evidence of contact allergy to TEA-Quat or HEQ was observed. Clearly, the relatively small size of this patch-test population governs the power of the conclusions that can be drawn from the study such that sensitization frequencies of less than 1% are unlikely to be detected. It is nevertheless a snapshot obtained in the most appropriate population that is consistent with the published negative data for these materials in predictive methods and the absence of any evidence to show that extensive use of HEQ and TEA-Quat in fabric conditioners has resulted in contact allergy. Interestingly, the total number of irritant skin reactions observed with 5% TEA-Quat was greater than that observed with HEQ at the same concentration. This observation is consistent with data showing that in a rabbit skin irritation test, TEA-Quat possessed a greater potential for skin irritation than HEQ did. Whereas no evidence of skin irritation was found following a 4-hour exposure to HEQ,[2]undiluted TEA-Quat was found to be an irritant (although this effect was fully reversible).[1]

Finally, we have considered the historical human maximization test data alongside consumer exposure scenarios in the context of a QRA framework. An AEL for HEQ in fabric rinse conditioner was derived from the maximization test data by expressing the concentration of material tested as dose per unit area and reducing this value to account for various sources of uncertainty. Actual exposure to HEQ through the wearing of fabrics and through hand washing was calculated according to guidelines in the HERA technical guidance document for risk assessments relating to household cleaning products.[13]This treatment clearly demonstrates that exposure to HEQ resulting from its use in fabric conditioner is more than an order of magnitude lower than the AEL that can be derived from the available human maximization test data. It is also noteworthy that the NESIL derived here is considered to be stringent as it was based on negative data from the human maximization test rather than on an extrapolation from positive data obtained in the less sensitive human repeat insult patch test.

Taken together with data published previously by Rodriguez and colleagues,[4]the current study provides supporting evidence that these ester quats lack significant skin-sensitizing potential in humans and is consistent with the clinical literature on allergic contact dermatitis, which does not report these materials as skin-sensitizing chemicals.


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