CDX-403

Skin sensitisation

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., British Journal of dermatology 158 (2008), HERA alpha-amylases, cellulases and lipases (2005) and HERA Subtilisins (Proteases) (2007) revealing that enzymes should not be considered skin sensitizers. The Association of Manufacturers and Formulators of Enzyme Products (www.amfep.org) performed an evaluation of the safety profile and published a statement 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, E.A., et al., Journal of Toxicology - Cutaneous and Ocular Toxicology 11 (1983); Griffith, J.F., et al., Food and Cosmetics Toxicology 7 (1969); Rodriguez, C., et al., Journal of Toxicology - Cutaneous and Ocular Toxicology 13 (1994); Cormier, E.M., et al., Annals of Allergy Asthma and Immunology 92 (2004); White, I.R., et al., Contact Dermatitis 13 (1985). All of these studies confirmed that the presence of enzymes used in detergents did not result in contact skin sensitization, including those conducted with atopic individuals.
This conclusion is based on the following considerations (references are included on the site):
• 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.
• 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.
The skin sensitizing potential of enzymes has been reviewed in multiple publications and all authors conclude that enzymes in general do not produce dermal sensitization (Collection of information on enzymes, European Commission (2002); Ladics and Sewalt, Regulatory Toxicology and Pharmacology (2018); Basketter et al., Journal of Immunotoxicology (2012)). Furthermore, there is no suitable test for (high molecular weight) proteins such as enzymes. In vivo skin sensitization assays such as the guinea pig maximization test and LLNA are not applicable to enzymes . However, the clinical experience with enzymes used in detergent products clearly shows a lack of contact skin sensitization potential (Basketter, D., et al., Regulatory Toxicology and Pharmacology 64 (2012)).
In conclusion, since enzymes 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, testing enzymes in animal models developed for chemical contact allergens is concluded to be both scientifically and ethically unjustified.