Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

In an opinion of the EU scientific committee on cosmetic products and non-food products intended for consumers (SCCNFP) on an analysis of the need for appropriate consumer information and identification of consumer allergens, adopted on 8.12.1999, lysmeral has been identified as one of 24 fragrance ingredients, which corresponds to the most frequently recognized allergens (SCCNFP 1999). However, lysmeral was grouped as less frequently reported and thus less documented consumer allergen.

In animal studies for dermal sensitization, several positive local lymph node assays (LLNA) with lysmeral were reported. Basketter et al. demonstrated a significant increase of stimulation indices, resulting in an EC3 value of 18.7% by application of lysmeral in acetone/olive oil (4:1) (Basketter 2001). Furthermore, lysmeral was applied in a LLNA with 4 different solvents (Lalko 2004). The treatment induced significant increases of stimulation indices, resulting in EC3 values of 2.97% (in ethanol), 4.17 % (in diethyl phthalate), 13.91 % (in 25% ethanol/75% DEP), 8.85% (in 75% ethanol/25% DEP).

 

In contrast, a guinea pig maximization test (GPMT) according to the OECD testing guideline 406, using intradermal/epidermal induction with 5/100% lysmeral and epidermal challenge with 10, 30, 100% lysmeral, led to no dermal reactions in any animal (Givaudan 1990E).

 

Further dermal sensitization studies in guinea pigs,being solely available as short summaries from secondary sources and providing limited information on study details and results, reportcontradicting findings concerning lysmeral and dermal sensitization.

 

Human data are available as various clinical reports of allergic contact dermatitis induced by lysmeral and several multicenter diagnostic patch skin tests have been performed.In this evaluation, main focus is drawn on the multicenter studies, giving indications for sensitization reactions for large collective of individuals. A study performed in 6 dermatological centers acrossincluded 1855 patients with a history of adverse reactions to fragrances (Frosch 2002). Three positive (0.2 %) and 12 doubtful cases were observed in the patients after 2 days dermal exposure to 10% lysmeral.

In another study, 9 out of 1825 patients (0.5%) had positive reactions after a patch test with 5% lysmeral (de Groot 2000).

Within the framework of the IVDK (Information Network of Departments of Dermatology) network, patch tests were performed with 10% lysmeral in consecutive, unselected patients during a 2-year period (Schnuch 2007). In 2004 patients tested, allergic reactions were found in 8 patients, 1 follicular reaction and 3 doubtful or irritant reactions were observed, giving a frequency of sensitization of 0.4%. The few unequivocal (stronger) allergic reactions observed, were discussed as evidence for sensitizing properties of lysmeral.

In another worldwide multicentre investigation, 167 patients suspected of fragrance sensitivity were patch tested with 5% lysmeral and allergic reactions were observed in 2 (1.2%), whereas irritant reactions were observed in 3 patients (1.8%) (Larsen 1996).

 

In a human repeated insult patch test, a total of 119 subjects were treated with nine occlusive 24 hour patches using 25% lysmeral (approx. 30000 µg/cm2) in 3:1 EtOH:DEP (Cocchiara 2003). Following a 2 week rest period, subjects were challenged with a 24 hour patch and readings were performed  24, 48, 72 and 96 hours after patch removal. There was one clear sensitization reaction to the test substance. Testing with an alternative vehicle (3:1 DEP/EtOH) under the same testing conditions resulted in no sensitization reactions (106 subjects investigated).

 

In a human repeated insult patch test conducted on 64 subjects (50 female and 14 male) subjects, 5.5% lysmeral in alcohol SD 39C (approx. 4125 µg/cm2) was applied for 24 hours to the upper arms (9 applications; IFF 1980). After a rest period of approximately 11 days, a challenge application was made for 24 hours and readings were performed 24 and 72 hours after patch removal. Under the conditions of this study, 5.5% lysmeral (approx. 4125 µg/cm2) produced little or no skin irritation and no skin sensitization reactions in any of the subjects tested.

 

A variety of scarcely reported human repeated insult patch tests are available, substantiating, that lysmeral did not provoke skin sensitizing reactions after dermal application at a concentration up to a concentration of 5% .

Respiratory sensitisation

Endpoint conclusion
Additional information:

No data are available addressing the potential of lysmeral for respiratory sensitization.

Justification for classification or non-classification

Overall, contradicting findings concerning dermal sensitization were observed in murine LLNA and guinea pig maximization tests, allowing no consistent conclusion concerning sensitizing properties of lymeral based on animal studies. However, including the human evidence from several multicentric patch test surveys in a weight of evidence, a classification “May cause sensitizing by skin contact”, R43 according to the criteria laid down in 67/548/EEC and classification as skin sensitizer (Category 1) according to 272/2008/EEC, is warranted.

No data are available addressing the potential of lysmeral for respiratory sensitization