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

Results

Human Maximization Tests

We assessed the (human) skin-sensitization potential of the two test materials under the conditions of the maximization test developed by Kligman.[10]A concentration of 15% (w/v) was used throughout for both test materials. Throughout the induction phase, no noteworthy inflammatory reactions were observed other than those associated with the SLS pretreatment or with a slight increase in reactivity due to the application of the test material to the barrier-disrupted skin. In no case were these reactions associated with vesicular or bright erythema, and these inflammatory reactions gradually subsided after successive exposures to the test agent. None of the subjects reported tenderness, itching, or burning. Each of the 25 volunteers were challenged with the test material on a new patch site for 2 days, 10 to 14 days after the final induction patch was removed. Patch sites were read 2 hours and then 2 days after the challenge patch was removed. No allergic inflammatory reactions were found in any subject at any of the readings. For completeness, a second provocative challenge with test material was performed after a further 7 days on three individuals selected at random from each panel of volunteers. The provocative challenge involved the application of the test material (15% w/v) to a new patch site that was treated with 10% SLS for 1 hour immediately prior to the application of the challenge patch. Again, these three volunteers did not experience any allergic skin reaction to this provocative challenge. These data are summarized in Table 1 and provide evidence that both HEQ and TEA-Quat lack substantial skin-sensitizing potential in humans.

Diagnostic Patch Tests

Both HEQ and TEA-Quat had been used in fabric rinse conditioners for years and there was clearly an absence of any evidence to suggest that the use of these materials resulted in contact allergy. Nevertheless, we proceeded to proactively explore whether allergy to these actives could be detected among a small population of clinic patients with suspected allergic contact dermatitis. A small preliminary study was performed to determine the appropriate concentrations of HEQ and TEA-Quat for diagnostic patch testing. This revealed that at a concentration of 2% (w/v), neither test substance was associated with irritant skin reactions. By contrast, a 5% (w/v) concentration was considered to be on the irritation threshold. Thus, for the main study, a total of 183 patients who were attending St. John's Institute of Dermatology in London were patch-tested with both materials at concentrations of 2% and 5%. At the subirritant concentration (2%), no inflammatory skin reactions were observed with either HEQ or TEA-Quat. At the irritant threshold concentration, 31 individuals had reactions to TEA-Quat. Only 12 of these reactions were present at the key scoring 2 days after patch removal. Furthermore, all of the reactions were equivocal or weak and in each case were judged by the clinician to be wholly irritant in nature and unrelated to the patients' eczema. Two individuals had reactions to HEQ, only one of which was present at the key day-2 scoring. Again, these reactions were weak and were considered by the clinician to be irritant in nature. In addition, 56 patients who were attending the Contact Dermatitis Clinic at Leuven University Hospital were patch-tested with both materials at a concentration of 5% (w/v). Five patients had reactions to TEA-Quat; four of these were present at the day-2 reading. Again, all reactions to TEA-Quat were weak or equivocal and were judged by the observer to be irritant in nature. None of the 56 volunteers had reactions to HEQ. These data are summarized in Table 1 .

Exposure-Based Quantitative Risk Assessment

Whereas the data above are consistent with the view that neither HEQ nor TEA-Quat represents a substantial skin-sensitizing hazard, potential scenarios of consumer exposure should also be considered. A quantitative risk assessment (QRA) approach[5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]provides a framework for doing this, and we considered the data obtained for HEQ in this context. This treatment of the data involved (1) calculating the concentration of HEQ in terms of dose per unit area that was found to be insufficient to cause skin sensitization in the human maximization test (the no-expected-sensitization induction level [NESIL]), (2) the assignment of sensitization assessment factors (SAFs) that semiquantitatively represent sources of uncertainty that must be considered when the data obtained in a controlled manner in the human test are related to consumer use of the material in a fabric rinse conditioner, (3) the calculation of an acceptable exposure level (AEL) for HEQ by dividing the NESIL by the SAFs, and (4) comparison of this AEL with actual exposure to HEQ through product use. The equations, parameters, and values used are detailed and described in Table 2 . Further information on the calculation of AELs has been published previously.[8]

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