Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is no study available for octadecyl methacrylate but for structural analogue substances dodecyl methacrylate, isotridecyl methacrylate, and a long-chain methacrylate ester (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate).

Based on the results with the structural analogue substances dodecyl methacrylate, isotridecyl methacrylate, and a long-chain methacrylate ester (C16 -C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate the general conclusion

drawn are that there are no compelling animal data to suggest that dodecyl methacrylate (lauryl methacrylate, LMA) as well as octadecyl methacrylate have a significant potential to cause skin sensitisation. The available GPMT data with dodecyl methacrylate are either negative or flawed. The results of the Buehler occluded patch test are not interpretable and provide no evidence for dodecyl methacrylate having skin sensitising potential. The results of a LLNA-test with methacrylic acid ester 13.0 (CAS: 90551-76-1, 2 -propenoic acid, 2-methyl-, C12-16-alkyl esters) according to OECD 429 was negative. The top concentration of the assay was 25% in acetone:olive oil (4 +1). There are two further reliable OECD 429 studies with GLP conducted with isotridecyl methacrylate and a long-chain methacrylate ester (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate) available. Both tests showed negative skin sensitizing results. These three negative LLNA tests are demonstrating the non-sensitizing potential of the whole range of long-chain methacrylate esters from C12 to C22.

There are three GPMT tests conducted independently with dodecyl methacrylate:

The first of these was conducted by Safepharm Laboratories Ltd (UK) and reported in 1999. In this investigation the test material was identified as Empicryl 6047, this being methacrylic acid esters of aliphatic alcohols with a chain length C10 to C16 - with the content of C12 (lauryl) being between 64% and 80%. The study was conducted using a conventional design. Induction was with 25% (id) and 50% (topical). Subsequent challenge was performed with 75% of the test material. There was no evidence of any reactivity and the sensitisation rate was recorded as being 0%. On the basis of these data the conclusion is that Empicryl 6047 (LMA) lacks skin sensitisation potential.

 

A second GPMT was commissioned by Norsolor and reported by Consultox Laboratories Ltd (UK) in 1980. This used an unconventional study design; the most important point being that there is no indication that any control (non-sensitised) animals were challenged. Certainly the report contains no control data. 

Animals were sensitised with the test material using 2% (id), and with an unknown concentration by topical application. Subsequently test animals were challenged with a 10% dispersion of the test material. At 48 hours following challenge 2 of 11 test animals had scores of 1 (scattered mild erythema), and another 2 animals displayed grade 2 reactions (moderate diffuse erythema). This gives an overall sensitisation score of 4/11 (36%). These data should be discounted for two main reasons. First because no control animals were used, and in the absence of such controls it is not possible to conclude that challenge would not have resulted in an equivalent frequency of grade 1 and 2 erythema in naive recipients. This is very poor practice and a lack of appropriate controls is sufficient to invalidate this test. 

However, there is a second issue and this relates to the fact the reactions displayed by 4 of the 11 test animals following challenge were detectable only after 48 hours and had disappeared by 72 hours. A pattern such as this is suggestive of irritation rather than allergic contact dermatitis.

 

Finally, there is a report in the scientific literature of an unconventional GPMT reported by Kanazawa et al (Contact Dermatitis 40: 19-23, 1999). In these studies groups of 5 to 10 guinea pigs were exposed to dodecyl methacrylate over a concentration range of 4 orders of magnitude (from approximately 25ppm to 0.0003ppm). The lowest concentration found to induce a positive response (in 3 of 10 guinea pigs) was equivalent to 0.025ppm. These data are rather strange insofar as they would serve to indicate a very extreme potency that is out of keeping with all other available data and human experience. Against that background, and in view of the fact that: (a) no control animals appear to have been used (very poor practice as indicated above), and (b) no details are supplied of how dermal reactions were assessed, it is reasonable to discount these data as being unreliable.

 

 

Occluded Patch Test of Buehler

 

There is one (modified) Buehler test of LMA available for inspection. This was conducted DuPont Haskell Laboratory (USA) and reported in 1993. This is a largely conventional Buehler study employing 20 test animals and 10 controls. The induction was conducted with undiluted test material, and 75% in mineral oil used for challenge. The study proved difficult to interpret because following first challenge reactions ranging from slight patchy redness (+) to moderate redness (2) were observed in both test and control animals (indicative of primary irritation caused by challenge). In the test group 14 of 20 guinea pigs displayed some grade of reaction at 24 and/or 48 hours, and in the control group each of 10 animals displayed some reaction at one or both time points. It is standard practice in such situations to perform a subsequent re-challenge of both groups of animals, and this was requested by the sponsor. For this purpose a concentration of 50% was used and animals were re-challenged 9 days following the primary challenge. Again there were no differences between the test animals and controls. Thus, 16 of 20 test animals displayed reactions at one or more time points examined (24, 48 and 72 hours) and some of these were sporadic and of low grade intensity. Only 5 control animals were re-challenged and of these 4 of 5 displayed reactions at one or more time points. On the basis of the challenge and re-challenge test data there is no evidence that the test material (LMA) was able to cause skin sensitisation. Although the report attempts to make a case - based on small differences in the observed grades of reaction - that there was some net response in test animals compared with controls, this is not sustainable. The conclusion drawn in the report that "the test article may possibly be a dermal sensitiser in this study" is unjustified.

Local Lymph Node Assays

 

A LLNA was conducted using a conventional protocol (conforming to OECD TG 429) by Harlan GmbH, and reported in 2009. The test article was dodecyl methacrylate delivered in a 4:1 mixture of acetone and olive oil (AOO) with the selected test concentrations being (w/v) 5%, 10% and 25%. At none of these test concentrations was an SI of 3 or greater achieved relative to concurrent vehicle control values (5% = SI of 0.99; 10% = SI of 2.11; 25% = 2.66). On this basis the clear interpretation is that the test article lacks the potential to cause skin sensitisation.

Second LLNA was conducted using a conventional protocol (conforming to OECD TG 429) by Harlan GmbH, and reported in 2010. The test article was isotridecyl methacrylate (purity: 99 %) delivered in a 4:1 mixture of acetone and olive oil (AOO) with the selected test concentrations being (w/v) 12.5 % and 25%. In the group treated with 25% test item concentration on day 1-3, a distinct lymphocyte proliferation was observed (S.I. = 3.06). However, as the response of animals challenged with 25% test item on day 16 (S.I. = 1.43) was lower and not distinctly higher than the primary response obtained with the same test item concentration directly after the sensitization phase, it can be concluded that the induced response does not bear any immunological memory. Thus, the lymphocyte proliferation observed in the sensitization phase is not due to a sensitizing effect but results from irritation caused by the test item as also supported by the ear weight data.

This is also supported by the fact that in the group treated with 12.5% test item concentration (day 1-3), where no relevant increase in ear weights (no irritation) was observed in comparison to the control group, the obtained S.I. was below the threshold of 3. On this basis the clear interpretation is that the test article isotridecyl methacrylate lacks the potential to cause skin sensitisation.

The third LLNA was conducted using a conventional protocol (conforming to OECD TG 429) by RCC-CCR and reported in 2006. The test article was a long-chain methacrylate ester 17.4 (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate) delivered in a 4:1 mixture of acetone and olive oil (AOO) with the selected test concentrations being (w/v) 2.5%, 5% and 10%. At none of these test concentrations was an SI of 3 or greater achieved relative to concurrent vehicle control values (2.5% = SI of 0.9; 5% = SI of 0.9; 10% = 1.9). On this basis the clear interpretation is that methacrylic acid ester 17.4 lacks the potential to cause skin sensitisation.

  

Conclusions

 

The general conclusion drawn from these data is that there is no evidence to suggest that dodecyl methacrylate, isotridecyl methacrylate and octadecyl methacrylate have a significant potential to cause skin sensitisation.


Migrated from Short description of key information:
There is no study available for octadecyl methacrylate but for structural analogue substances dodecyl methacrylate, isotridecyl methacrylate, and a long-chain methacrylate ester (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate).
The available GPMT data with dodecyl methacrylate are either negative or flawed. The results of the Buehler occluded patch test are not interpretable and provide no evidence for dodecyl methacrylate having skin sensitising potential. The negative result of the LLNA with test concentrations of up to 25% of dodecyl methacrylate failing to elicit a positive response confirms the opinion that dodecyl methacrylate has no evidence to cause skin sensitisation. There are two further reliable OECD 429 studies with GLP conducted with isotridecyl methacrylate and a long-chain methacrylate ester (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate) available. Both tests also showed negative skin sensitizing results.
These test results were confirmed based upon the available experience of human exposure to dodecyl methacrylate.
Based on the results with dodecyl methacrylate, isotridecyl methacrylate and the long-chain methacrylate ester (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate) there is no evidence to suggest that dodecyl methacrylate as well as octadecyl methacrylate has the potential to cause skin sensitisation.

Justification for selection of skin sensitisation endpoint:
No single key study has been selected: instead, all available studies have been used in a weight-of-evidence approach.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Respiratory tract sensitisation

 

Due to the very low vapour pressure of the substances and the resulting lack of significant exposure, respiratory tract sensitisation is not considered as relevant.


Migrated from Short description of key information:
Respiratory tract sensitisation: Due to the very low vapour pressure of the substances and the resulting lack of significant exposure, respiratory tract sensitisation is not considered as relevant.

Justification for classification or non-classification

The general conclusion drawn from the available data with the structural analogue dodecyl methacrylate, isotridecyl methacrylate, and a long-chain methacrylate ester 17.4 (C16-C20, main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate)

is that there is no evidence to suggest that octadecyl methacrylate has a significant potential to cause skin sensitisation.

 

The available GPMT data with the structural analogue dodecyl methacrylate are either negative or flawed. The results of the Buehler occluded patch test are not interpretable and provide no evidence for dodecyl methacrylate having skin sensitising potential. The negative result of the LLNA with test concentrations of up to 25% of dodecyl methacrylate failing to elicit a positive response confirms the opinion that dodecyl methacrylate has no evidence to cause skin sensitisation.

Further negative LLNA studies with isotridecyl methacrylate, and a long-chain methacrylate ester 17.4 (C16-C20 main constituents approximately 28 % hexadecyl methacrylate and 65 % octadecyl methacrylate) also demonstrate the non-sensitizing potential of C12 to C20 methacrylic acid esters.

In conclusion, the long-chain alkyl methacrylate esters (C12 – C22) and therewith octadecyl methacrylate are determined as non-sensitising to skin.

According to the available data and CLP criteria, octadecyl methacrylate is not considered to be a skin sensitiser and has therefore not to be classified as a skin sensitiser under 67/548/EEC, according to CLP (1272/2008/EC) and according to UN GHS (2009) requirements.

Thus, no labelling required.