Development of Allergic Antibody to an Enzyme in a Body Lotion: Results of an 18-Month Clinical Study

Abstract

Use of enzymes in cosmetic products is novel and the safety of these products is not well understood. The safety of a prototype enzyme-containing body moisturizer lotion was tested via measures of skin compatibility and potential to induce protease-specific IgE antibody in a clinical study. Female, atopic subjects (n = 1,100) used body lotion containing 100 ppm protease (Y217L BPN') for 5 consecutive days per month, for 18 months. Regular lotion was used the remaining days of each month. Skin evaluation and skin prick tests (SPT) were conducted every 3 months. Measures of skin hydration were made in a subset of subjects at 3-month intervals: skin biopsies occurred at baseline and at the first 3-month timepoint. Serum from SPT positive subjects was tested for specific IgE in an immunoCAP assay. Clinical evaluation and histopathology showed no skin irritation and increased hydration of the skin over time. Three of 864 subjects completing the study developed IgE antibody to the enzyme: 1 subject after 6 months product use and 2 subjects after 15 months product use. A fourth subject was found with IgE antibody 3 months after study termination. None had allergic symptoms associated with product use. Intermittent exposure to a low level of protease enzyme in a body lotion led to the development of specific IgE antibody in 0.46% of subjects. While this study showed favorable skin compatibility of the protease containing lotion, the occurrence of allergic antibody to the enzyme was unacceptable for product commercialization.

Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH

“…For consumers, a DMEL of 15 ng/m 3 is proposed, but with the recognition that this is the highest tolerable value and is associated with the situation where there is only short term, perhaps frequent, exposure. Where there are circumstances which would lead for example to prolonged intimate exposure, then a lower level would need to be adopted (Human and Environmental Risk Assessment, 2007;Johnson et al, 1999;Kelling et al, 1998;Sarlo et al, 2004).…”

“…This provides evidence of the absence of an adverse effect. In this context, it is very important to note that other published work investigating different uses of detergent enzyme has found evidence of potential problems and in each case this has led to a cessation of the project prior to marketing (Johnson et al, 1999;Kelling et al, 1998;Sarlo et al, 2004). Arguably, some of these tend to indicate that longer exposure may be just as important as high "spot" exposures, but as already mentioned, detailed understanding of these variables is lacking.…”

“…The exposure discussed here for a trigger spray represents frequent, but nevertheless short duration exposure. Where exposure is prolonged and/or more intimate in nature, then experience shows that a careful risk assessment must be undertaken and that such a high level of exposure could not be tolerated (UK Health and Safety Executive, 2009;Johnson et al, 1999;Kelling et al, 1998;Sarlo et al, 2004;Blaikie et al, 1999).…”

“…So, taken together, and in particular with the evidence from a single but comprehensive study that daily consumer exposure at 15 ng/m 3 was not associated with any induction or elicitation effects, then it is suggested that a consumer DMEL of 15 ng/m 3 can be adopted as the starting point for new and existing enzymes which do not have a limit and/or for which there is no other data to indicate that a different value may be more appropriate. However, it is important that, just as for the occupational limit, this value is not taken as assurance of absolute safety in all conceivable exposure situations (Johnson et al, 1999;Kelling et al, 1998;Sarlo et al, 2004).…”

Enzymes in cleaning products: An overview of toxicological properties and risk assessment/management

“…As already indicated, the key to the risk assessment process is a careful and thorough measurement (or estimation/modelling) of potential enzyme exposure. This requires a consideration of both direct and indirect sources of exposure, as for example has been undertaken with spray cleaners (Weeks et al, 2011), bar soap containing enzyme (Kelling et al, 1998), and skin cream with proteolytic enzyme (Sarlo et al, 2004). The reality is that for most consumer uses of enzymes, airborne exposure is typically well below 1 ng/m 3 and thus safe.…”