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Administrative data

Description of key information

There is no study available for tetradecyl methacrylate but for structural analogue substances dodecyl methacrylate and isotridecyl methacrylate.

No single key study has been selected: instead, all available studies have been used in a weight-of-evidence approach.


The negative results of the LLNAs with test concentrations of up to 25% of dodecyl methacrylate and isotridecyl methacrylate failing to elicit a positive response confirms the opinion that dodecyl methacrylate and isotridecyl methacrylate have no evidence to cause skin sensitisation.
These test results were confirmed based upon the available experience of human exposure to dodecyl methacrylate.
Based on the results with dodecyl methacrylate and isotridecyl methacrylate there is no evidence to suggest that dodecyl methacrylate, isotridecyl methacrylate as well as tetradecyl methacrylate has the potential to cause skin sensitisation.

Key value for chemical safety assessment

Skin sensitisation

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

Data regarding skin sensitization is available for mixtures containing C12 up to C22 MA, and for pure docosyl methacrylate. These data are covering almost the whole category except for C20 MA which was just tested in a mixture containing ~10% and is assessed within this category approach. For sensitization, the relevant molecular inducing event is the electron accepting capacity of the double bond on the methacrylate moiety leading to reaction with proteins. The adverse outcome pathway is Michael addition of the electrophilic ester to macromolecules in the target cells. In RAAF nomenclature, this approach is described in Scenario 6 (i.e., no variation between category members; different compounds which have the same type of effect). For the long chain methacrylates the reactivity is substantially modulated by the substance specific dermal permeability and metabolism rate in the skin layers. The relevant mode of action for sensitization and metabolism of methacrylates to MAA and the corresponding alcohol are well understood, thus there is low bias that influences the prediction since all category members show the same pattern confirming the common underlying mechanism. The decreasing polarity and resulting decreasing skin permeability reduce the amount of long-chain esters that potentially penetrate through the stratum corneum and could form haptene-proteine complexes to a minimum. Following skin penetration, the esters are rapidly hydrolyzed by esterases (proven for esters up to EHMA (C8) and indicated for LMA (C12); for esters with longer chain length of the alcohol moiety experimental prove is technically not feasible). The primary metabolites MAA and the corresponding alcohols are not sensitizing in animal studies, thus ester cleavage has to be considered as a detoxification pathway in terms of sensitization.

Formally, on the first glance there is some bias influencing the prediction since for few esters there have been (false) positive outcome generated. Various studies of the data set which partly stand against the afore described considerations regarding bioavailability and mode of action were additionally assessed by an external, reputable expert. In single cases, the suspicion of being a skin sensitizer couldn´t be averted on the existing data basis and therefore additional studies according to recent guidelines were conducted.

Today the LLNA is often used as a benchmark, however knowing the accuracy of the LLNA is incomplete (Basketter et al., 2009) a Weight of Evidence evaluation for skin sensitization (Ball, 2011) is recommended for some cases (AOP -OECD, 20XX).

On the basis of the whole dataset, the physicochemical properties of the esters in combination with experimentally proven dermal absorption and metabolism in skin and a further assessment by an external expert the read across using a category approach is done with a high level of confidence.

There is no study available for tetradecyl methacrylate but for structural analogue substances dodecyl methacrylate and isotridecyl methacrylate.

Based on the results with the structural analogue substances dodecyl methacrylate and isotridecyl methacrylate the general conclusions drawn are that there are no compelling animal data to suggest that dodecyl methacrylate (lauryl methacrylate, LMA) as well as tetradecyl methacrylate has a significant potential to cause skin sensitisation.

Local Lymph Node Assays

 

A LLNA was conducted using a conventional protocol (conforming with 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.

Another challenge LLNA was conducted using a conventional protocol (conforming with 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.

  

Conclusions

 

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


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.


Justification for classification or non-classification

The general conclusion drawn from the available data with the structural analogue dodecyl methacrylate and isotridecyl methacrylate is that there is no evidence to suggest that tetradecyl methacrylate has a significant potential to cause skin sensitisation.

 

The negative results of the LLNAs with test concentrations of up to 25% of dodecyl methacrylate and isotridecyl methacrylate failing to elicit a positive response confirms the opinion that dodecyl methacrylate has no evidence to cause skin sensitisation.