Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-473-0 | CAS number: 96-05-9
Allyl methacrylate was evaluated in the in vitro Chinese hamster ovary cell/hypoxanthine-guanine-phosphoribosyl transferase(CHO/HGPRT) forward gene mutation assay. The genotoxic potential of the test material was assessed in two separate assays. The test material was assayed at concentrations ranging from 125 to 1000 µg/ml and from 6.3 to 75 µg/ml in the absence and presence of an externally supplied metabolic activation (S-9) system, respectively. The adequacy of the experimental conditions for detection of induced mutation was confirmed by employing positive control chemicals (ethyl methane sulfonate for assay without S-9 and 7,12-dimethylbenz(a)anthracene for assays with S-9). Negative control cultures were treated with the solvent used to dissolve the test material. Based upon the frequency of TGr mutants recovered in cultures treated with the test material, it was concluded that the test material did not induce a mutagenic response in the assay system employed.
For the assessment of the mutagenic potential of Allyl methacrylate several studies are available: two reverse gene mutation assays in bacteria (Ames test), two mammalian cell chromosome aberration assays , one cell gene mutation assay (HPRT test), a mammalian cell gene mutation assay (TK test) s and an in vivo micronucleus test.
The in vitro potential mutagenic activity of the test substance allyl methacrylate was investigated by the Ames test using 5 strains of bacteria Salmonella typhimurium: TA 1535, TA 1537, TA 1538, TA 98 and TA 100. After a preliminary assay to define the concentrations to be used for the mutagenicity study, the test substance was tested on two independent assays. Each assay was carried out both in the absence and in the presence of a metabolie activation system, the S9 mix, prepared from a liver microsomal fraction S9 of rats treated with Aroclor 1254. The method used was the direct plate incorporation method. The concentrations were:
- 100, 500, 1000, 1750 and 2500 µg/plate for the first assay with and without S9 mix and for the second assay without 59 mix
- 10, 50, 100, 500 and 1000 µg/plate for the second assay with S9 mix.
The test substance allyl methacrylate did not induce a significant increase in the revertant number with or without S9 mix in any of the 5 strains. The negative and solvent control results were equivalent to those usually obtained in our Laboratory. The number of revertants induced by the positive controls was higher than the spontaneous one, which demonstrated the sensitivity of this test and the efficacy of the S9 mix throughout this study. In conclusion, under our experimental conditions, the test substance allyl methacylate is not mutagenic in the Ames test (C.I.T., 1991).
In a second study, allyl methacrylate was tested for mutagenic activity in the Salmonella/Mammalian-Microsome Reverse Mutation Assay (Ames Test), Preincubation Method. This assay evaluates the test article and/or its metabolites for their ability to induce reverse mutations at the histidine locus in the genome of specific Salmonella typhimurium tester strains both in the presence and absence of an exogenous metabolic activation system of mammalian microsomal enzymes derived from Aroclorw-induced rat liver. The doses tested in the mutagenicity assay were selected based on the results of a dose range finding study using tester strain TA100 and ten dose levels of test article ranging from 5000 to 6.67 µg per plate, one plate per dose, both in the presence and absence of microsomal enzymes. The tester strains used in this study were TA98, TA100, TA1535 and TA1537. The assay was conducted using three plates per dose level in the presence and absence of microsomal enzymes. Six dose levels of the test article were tested, ranging from 1000 to 10.0 µg per plate in the presence of S9 and from 3330 to 66.7 µg per plate in the absence of S9. The results of the initial mutagenicity assay were confirmed in an independent experiment. The results of this Ames Test, Preincubation Method, indicate that under the conditions of this study, in both an initial and a confirmatory assay, the test article, allyl methacrylate, did not cause positive increases in the number of histidine revertants per plate with and of the tester strains in either the presence or absence of microsomal enzymes prepared from Aroclor-induced rat liver (S9) (Hazleton, 1992).
Chromosome aberration tests:
Allyl methacrylate was also found to be negative in an in vitro mammalian chromosome aberration test with human lymphocytes, when tested at concentration of 2 - 200 µg/mL with and without metabolic activation by liver S9 mix of rats induced with Aroclor 1254 (C.I.T., 1994). The test was conducted in compliance with GLP according to OECD 473.
In a second test, the clastogenic potential of allyl methacrylate was evaluated in an in vitro chromosomal aberration assay utilizing rat lymphocytes. Approximately 48 hours after establishing whole blood cultures, the cells were treated for 4 hours in the presence and absence of an external metabolic activation system (S-9) with 0 (negative control), 0.501, 1.67, 5.01, 16.7, 50.1, 167, and 501 µg allyl methacrylate per mL culture medium. Cultures treated with 0.4 µg/mL mitomycin C and 5.0 µg/mL cyclophosphamide served as positive controls for the non-activation and activation assays, respectively. The cultures were harvested 24 h after termination of treatment. Based upon the mitotic indices, cultures treated with 50.1, 167, and 501 µg/mL from the nonactivation assay and with 16.7, 50.1, and 167 µg/ml from the activation assay were selected for determining the incidence of chromosomal aberrations. No significant increase in the aberration frequency was noticed at any of the treatment levels in this assay when compared to the negative controls. Cultures treated with the positive control chemicals had significantly higher incidences of aberrations. Results of the initial assay , were confirmed in an independent repeat experiment utilizing similar dose levels and an additional culture harvest time (48 h after treatment). It was concluded that allyl methacrylate did not exhibit clastogenic activity in cultured rat lymphocytes under the experimental conditions used.
Allyl methacrylate was evaluated in the in vitro Chinese hamster ovary cell/hypoxanthine-guanine-phosphoribosyl transferase (CHO/HGPRT) forward gene mutation assay. The genotoxic potential of the test material was assessed in two separate assays. The test material was assayed at concentrations ranging from 125 to 1000 µg/mL and from 6.3 to 75 µg/mL in the absence and presence of an externally supplied metabolie activation (S-9) system, respectively. The adequacy of the experimental conditions for detection of induced mutation was confirmed by employing positive control chemicals (ethyl methane sulfonate for assay without S-9 and 7,12dimethylbenz(a)anthracene for assays with S-9). Negative control cultures were treated with the solvent used to dissolve the test material. Based upon the frequency of mutants recovered in cultures treated with the test material, it was concluded that the test material did not induce a mutagenic response in the assay system employed.
Mouse lymphoma test:
Allyl Methacrylate was tested both in the presence and absence of S9-mix in two independent experiments and in the presence of S9-mix only in a further two experiments. Negative results were observed in both the presence and absence of S9-mix with maximum concentrations of 64~g/ml and 750µg/ml respectively. Higher concentrations of Allyl Methacrylate (up to 125µg/ml and 1000µ/ml in the presence and absence of S9-mix respectively) gave rise to excessive toxicity.
It is therefore concluded that, Allyl Methacrylate is non-mutagenic to L5178Y TK+/- cells in either the presence or absence of S9-mix when tested to concentrations (64µg/ml and 750µg/ml in the presence and absence of S9-mix respectively) limited by the toxicity of the test sample.
Mouse micronucelous test in vivo:
Allyl methacrylate was evaluated in the mouse bone marrow micronucleus test. The micronucleus test is capable of detecting agents causing chromosomal aberrations and spindle malfunction. The test material was administered to CD-1 mice by single oral gavage at dose levels of 0 (negative control), 75, 150, and 300 mg/kg body weight (bw). The dose levels for the micronucleus assay were based on the outcome of a range finding assay. The concentrations of the test material in the dosing solutions were verified analytically. Groups of animals were sacrificed at three intervals, viz., 24, 48, and 72 hours after treatment. Mice treated with 80 mg/kg bw cyclophosphamide and sacrificed at 24 hours served as positive controls. There were five animals per sex per dose level per sacrifice time. One thousand polychromatic erythrocytes (PCE) were evaluated from each surviving animal and the frequencies of micronucleated polychromatic erythrocytes (MN-PCE) were recorded. There were no significant increases in the frequencies of MN-PCE in groups treated with the test material as compared to negative controls. The positive control mice showed significant increases in MN-PCE. Under the experimental conditions used, the test material was considered to be negative in the mouse bone marrow micronucleus test.
Based on the available data, there is no indication for a mutagenic potential of the test substance. Thus, no classification is warranted according to 67/548/EEC and Regulation (EC) No 1272/2008 (GHS, CLP), respectively.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again