Fructofuranosidase, β-

Endpoint summary

Description of key information

β-fructofuranosidase is not considered to be a skin sensitiser.

β-fructofuranosidase is considered to be a respiratory sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vitro

Remarks:

skin sensitisation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Information on the skin sensitization potential of technical enzymes was summarized by the Enzyme REACH Consortium (ERC) [1]. The skin sensitization potential of enzymes has been reviewed in several publications [1-8], 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 [1, 9-13, 14-19]. 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.

 

References

[1] Reach - Data waiving argumentation for technical enzymes (December 2017, ERC/18/001)

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

[3] HERA Human and environmental risk assessment on ingredients of household cleaning products - Subtilisins (Proteases). Edition 2.0. 2007.

[4] 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

[5] Andersen,P.H., Bindslev-Jensen,C., Mosbech,H., Zachariae,H., and Andersen,K.E. (1998) Skin symptoms in patients with atopic dermatitis using enzyme-containing detergents. A placebo-controlled study. Acta dermato-venereologica 78, 60-62

[6] Basketter D., Berg N., Broekhuizen C., Fieldsend M., Kirkwood S., Kluin C., Mathieu S. and Rodriguez C. Enzymes in Cleaning Products: An Overview of Toxicological Properties and Risk Assessment/Management. 2012a. Reg. Toxicol. Pharmacol, 64/1: 117-123.

[7] Association Internationale de la Savonnerie et de la Detergence (AISE)/AMFEP, Enzymes: Lack of skin sensitisation potential. 1995.

[8] Basketter D.; N. Berg; F. Kruszewski; K. Sarlo; B. Concoby. The Toxicology and Immunology of Detergent Enzymes. 2012b. J. Immunotox., 9, 320-326.

[9] 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

[10] 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

[11] 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

[12] 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

[13] White,I.R., Lewis,J., and el,A.A. (1985) Possible adverse reactions to an enzyme-containing washing powder. Contact Dermatitis 13, 175-179

[14] Andersen,P.H., Bindslev-Jensen,C., Mosbech,H., Zachariae,H., and Andersen,K.E. (1998) Skin symptoms in patients with atopic dermatitis using enzyme-containing detergents. A placebo-controlled study. Acta dermato-venereologica 78, 60-62

[15] Belsito,D.V., Fransway,A.F., Fowler,J.F., Jr., Sherertz,E.F., Maibach,H.I., Mark,J.G., Jr., Mathias,C.G., Rietschel,R.L., Storrs,F.J., and Nethercott,J.R. (2002) Allergic contact dermatitis to detergents: a multicenter study to assess prevalence. Journal of the American Academy of Dermatology 46, 200-206

[16] Lee,M.Y., Park,K.S., Hayashi,C., Lim,H.H., Lee,K.H., Kwak,I., and Laurie,R.D. (2002) Effects of repeated short-term skin contact with proteolytic enzymes. Contact Dermatitis 46, 75-80

[17] Pepys,J., Wells,I.D., D'souza,M.F., and Greenberg,M. (1973) CLINICAL AND IMMUNOLOGICAL RESPONSES TO ENZYMES OF BACILLUS-SUBTILIS IN FACTORY WORKERS AND CONSUMERS. Clinical Allergy 3, 143-160

[18] Peters,G., Johnson,G.Q., and Golembiewski,A. (2001) Safe use of detergent enzymes in the workplace. Appl.Occup Environ.Hyg. 16, 389-396

[19] Zachariae,H., Thomsen,K., and Rasmussen,O.G. (1973) Occupational enzyme dermatitis. Results of patch testing with Alcalase. Acta dermato-venereologica 53, 145-148

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Enzymes regardless of the catalytic activities are potential respiratory allergens, whereas the weight of human evidence indicates that enzymes are not skin sensitizers [1]. All enzymes must therefore be classified as respiratory sensitizers [2], “H334: Hazard Category 1: May cause allergy or asthma symptoms or breathing difficulties if inhaled” in accordance with the CLP Regulation [1].

There is no animal model available to test and rank respiratory sensitisers. Based upon the currently available information including human data collected for over 40 years it is concluded that potency sub-categorisation for respiratory sensitisers is premature and can potentially be misleading, therefore enzymes should be classified as Respiratory Sensitizer Category 1[1, 3].

Since enzymes are considered repiratory allergens, a DMEL (Derived Minimum Effect Level) for workers and consumers have been established [4, 5].

 

References:

[1] Amfep (2012), Enzymes and criteria of repiratory sensitisers in the second adaption to technical progress to CLP

[2] AMFEP policy on classification of enzymes as “Respiratory Sensitisation Category 1” in accordance with the EU Regulation on classification, labelling and packaging of substances and mixtures (EC No 1272/2008, “CLP Regulation”).

[3] Basketter D.A., Kimber I. (2011) Assessing the potency of respiratory allergens: Uncertainties andchallenges. Regul. Toxicol. Pharmacol.,61, 365-372.[SR1] 

[4] Enzyme REACH Consortium - Data waiving argumentation for technical enzymes (December 2017, ERC/18/001)

[5] Basketter DA, Broekhuizen C, Fieldsend M, Kirkwood S, Mascarenhas R, Maurer K, Pedersen C, Rodriguez C, Schiff HE: Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH. Toxicology. 268:165-170, 2010.

Justification for classification or non-classification

Non- protease enzymes such as β-fructofuranosidase are not considered to be skin sensitizers, but there is evidence that enzymes are a respiratory sensitisers. Therefore, β-fructofuranosidase is concluded to be a Respiratory Sensitizer Category 1 according to Regulation (EC) No. 1272/2008 (CLP).