Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
The skin sensitization potential of enzymes has recently been reviewed by Basketter et al. and HERA revealing that enzymes should not be considered skin sensitizers. In addition, there is an unequivocal statement from AMFEP (www.amfep.org) on this topic showing that enzymes do not have skin sensitizing potential. The lack of skin sensitizing potential is substantiated by evidence from robust human experimental data and extensive in-use human studies performed with detergents containing enzymes [Bannan et. Al., Griffith at. Al, Rodrigues et al.]. All of these studies confirmed that the presence of enzymes in the detergents did not result in contact skin sensitization, including those conducted with atopic individuals.

However, in spite of clear evidence that enzymes should not be considered skin sensitizers, animal skin sensitization models might give rise to positive results. This is because, just like the previously used guinea pig skin sensitization models, the Local Lymph Node Assay (LLNA), (OECD Test Guideline 429) is inappropriate for the assessment of proteins. These animal models are validated for the testing of small chemicals, not for water soluble protein-based materials, known to be human respiratory allergens. The LLNA does not discriminate between chemical and respiratory sensitizers [Kimber et al., leading to the real risk of false-positive results with proteins, particularly those already known to be sensitizing by the respiratory route, such as enzymes. Indeed, in our experience, all foreign proteins can be made to generate skin reactions in suitably treated animals, including the OECD recognized guinea pig tests and the LLNA [Festersen et al.]. This makes the available animal models inappropriate when used with proteins. Therefore, the assessment of enzymes in any of the existing animal models can be predicted not to provide new and useful knowledge. This conclusion is based on the following considerations:

• The results of predictive testing in man demonstrate that enzymes do not have skin sensitization potential for man.

• In clinical settings, enzymes have only very rarely been suggested as a possible cause of allergic contact dermatitis (ACD). Even in these few cases, a causal relationship has never been proven. Further, several clinical studies have demonstrated that enzymes are not a cause of ACD [Griffith et al., White et al.].

• ACD has never been reported in the detergent enzyme industries where there has been extensive occupational enzyme exposure which, in the past, led to respiratory sensitization and/or irritant dermatitis. For more than 40 years, billions of consumers have had regular, often daily, skin exposure to enzymes during laundry by hand but there is no evidence that this exposure has given rise to skin sensitization.

• The available skin sensitization test methods are not suitable for enzymes. No animal model has been developed or validated for assessing proteins as contact skin sensitizers. So far, no in vitro models exist either.

Since enzyme products are well documented not to be skin sensitizers in man and because no suitable animal model or in vitro assay for protein skin sensitization exists, we consider testing enzymes in animal models developed for chemical contact allergens as both scientifically and ethically unjustified. Finally, the precautions recommended in the material safety data sheets should be sufficient to prevent even a theoretical hazard of skin sensitization

References
Enzyme REACH consortium: data waiving argumentation for technical enzymes
HERA Human and environmental risk assessment on ingredients of household cleaning products - alpha-amylases, cellulases and lipases. 2005.
Basketter,D.A., English,J.S., Wakelin,S.H., and White,I.R. (2008) Enzymes, detergents and skin: facts and fantasies. British journal of dermatology 158, 1177-1181
Bannan,E.A., Griffith,J.F., Nusair,T.L., and L.J.Sauers (1983) Skin testing of laundered fabrics in the dermal safety assessment of enzyme containing detergents. Journal of Toxicology - Cutaneous and Ocular Toxicology 11, 327-339
Griffith,J.F., Weaver,J.E., Whitehouse,H.S., Poole,R.L., and Newmann EANixon,G.A. (1969) SAFETY EVALUATION OF ENZYME DETERGENTS ORAL AND CUTANEOUS TOXICITY IRRITANCY AND SKIN SENSITIZATION STUDIES. Food and Cosmetics Toxicology 7, 581-593
Rodriguez,C., Calvin,G., Lally,C., and LaChapelle,J.M. (1994) Skin effects associated with wearing fabrics washed with commercial laundry detergents. Journal of Toxicology - Cutaneous and Ocular Toxicology 13, 39-45
White,I.R., Lewis,J., and el,A.A. (1985) Possible adverse reactions to an enzyme-containing washing powder. Contact Dermatitis 13, 175-179
Kimber,I., Agius,R., Basketter,D.A., Corsini,E., Cullinan,P., Dearman,R.J., Gimenez-Arnau,E., Greenwell,L., Hartung,T., Kuper,F., Maestrelli,P., Roggen,E., and Rovida,C. (2007) Chemical respiratory allergy: opportunities for hazard identification and characterisation. The report and recommendations of ECVAM workshop 60. Altern Lab Anim 35, 243-265
Festersen,U., Rasmussen,C., Kjaer,T.M.R., Soni,N.K., Roggen,E.L., and Berg,N.W. (2008) Alternative application route in the LLNA provides crucial environmental enrichment and broadens the usability of vehicles. AATEX 14, 433-436

(source: Enzymes REACH Consortium, ERC Data waiving argumentation for technical enzymes)
Migrated from Short description of key information: enzymes should not be considered skin sensitizers Justification for selection of skin sensitisation endpoint: Based on Literature review, there are no indication that enzymes are skin sensitizers.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion