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Administrative data

Description of key information

Non-proteases lack the potential to be skin and eye irritants

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
There are substantial in vivo animal data on all industrially applied enzyme classes, as well as in vitro data performed before formal validation, for both skin and eye irritancy. These data document that enzymes are not irritating, with the exception of proteases. Monoamine Oxidase is not a protease. Non-proteases lack the potential to be skin and eye irritants but proteases show a range of effects from no irritation to moderate irritation. It is, however, only the most concentrated and reactive samples which show an effect which is transient in nature and commonly is classified as mild irritation (1; 2). This is also the outcome of clinical investigations (3; 4; 5), confirming that enzymes at the product use concentration, even with exaggerated exposures, do not give rise to any occupational or consumer risk of skin or eye irritation. Enzymes are not skin sensitizers, as explained in the AMFEP Position Paper “Lack of Skin Sensitisation Potential”. Mild irritation could in theory occur when handling products containing high concentrations of protease, however there is evidence that for detergent products that enzymes are not responsible for skin complaints (3).

[1] AMFEP. Amfep paper on safety evaluation of technical enzyme products with regards to the REACH legislation. 2009. AMFEP.
[2] HERA Human and environmental risk assessment on ingredients of household cleaning products - alpha-amylases, cellulases and lipases. 2005.
[3] 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
[4] 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
[5] Cormier,E.M., Sarlo,K., Scott,L.A., MacKenzie,D.P., Payne,N.S., Carr,G.J., Smith,L.A., Cua-Lim,F., Bunag,F.C., and Vasunia,K. (2004) Lack of type 1 sensitization to laundry detergent enzymes among consumers in the Philippines: results of a 2-year study in atopic subjects. Annals of Allergy Asthma and Immunology 92, 549-557
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
There are substantial in vivo animal data on all industrially applied enzyme classes, as well as in vitro data performed before formal validation, for both skin and eye irritancy. These data document that enzymes are not irritating, with the exception of proteases. Non-proteases lack the potential to be skin and eye irritants but proteases show a range of effects from no irritation to moderate irritation. It is, however, only the most concentrated and reactive samples which show an effect which is transient in nature and commonly is classified as mild irritation (1; 2). This is also the outcome of clinical investigations (3; 4; 5), confirming that enzymes at the product use concentration, even with exaggerated exposures, do not give rise to any occupational or consumer risk of skin or eye irritation.

[1] AMFEP. Amfep paper on safety evaluation of technical enzyme products with regards to the REACH legislation. 2009. AMFEP.
[2] HERA Human and environmental risk assessment on ingredients of household cleaning products - alpha-amylases, cellulases and lipases. 2005.
[3] 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
[4] 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
[5] Cormier,E.M., Sarlo,K., Scott,L.A., MacKenzie,D.P., Payne,N.S., Carr,G.J., Smith,L.A., Cua-Lim,F., Bunag,F.C., and Vasunia,K. (2004) Lack of type 1 sensitization to laundry detergent enzymes among consumers in the Philippines: results of a 2-year study in atopic subjects. Annals of Allergy Asthma and Immunology 92, 549-557
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification

There are substantial in vivo animal data on all industrially applied enzyme classes, as well as in vitro data performed before formal validation, for both skin and eye irritancy. These data document that enzymes are not irritating, with the exception of proteases. Monoamine Oxidase is not a protease. Non-proteases lack the potential to be skin and eye irritants but proteases show a range of effects from no irritation to moderate irritation. It is, however, only the most concentrated and reactive samples which show an effect which is transient in nature and commonly is classified as mild irritation (1; 2). This is also the outcome of clinical investigations (3; 4; 5), confirming that enzymes at the product use concentration, even with exaggerated exposures, do not give rise to any occupational or consumer risk of skin or eye irritation. Enzymes are not skin sensitizers, as explained in the AMFEP Position Paper “Lack of Skin Sensitisation Potential”. Mild irritation could in theory occur when handling products containing high concentrations of protease, however there is evidence that for detergent products that enzymes are not responsible for skin complaints (3). In fact, many active proteins including enzymes have been observed in human tears (6).


 


Therefore, monoamine oxidase does not meet the criteria for EU CLP classification as either a skin or eye irritant.


 


[1] AMFEP. Amfep paper on safety evaluation of technical enzyme products with regards to the REACH legislation. 2009. AMFEP.


[2] HERA Human and environmental risk assessment on ingredients of household cleaning products - alpha-amylases, cellulases and lipases. 2005.


[3] 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


[4] 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


[5] Cormier,E.M., Sarlo,K., Scott,L.A., MacKenzie,D.P., Payne,N.S., Carr,G.J., Smith,L.A., Cua-Lim,F., Bunag,F.C., and Vasunia,K. (2004) Lack of type 1 sensitization to laundry detergent enzymes among consumers in the Philippines: results of a 2-year study in atopic subjects. Annals of Allergy Asthma and Immunology 92, 549-557


[6] Anderson J.A., Leopold I.H. (1979) Enzymatic Activities Found in Human Tears. In: Hockwin O., Rathbun W.B. (eds) Progress in Anterior Eye Segment Research and Practice. Documenta Ophthalmologica Proceedings Series, vol 18. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-9609-0_38