Ethyl methacrylate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Review epidemiological study

Justification for type of information:

Read across from the methacrylic metabolite donor substance
REPORTING FORMAT FOR THE ANALOGUE APPROACH
see attached category document

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
see attached category document, chapter 1.1

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see attached category document, chapter 1

3. ANALOGUE APPROACH JUSTIFICATION
see attached category document, chapter 5 (Toxikokinetics) and endpoint specific chapters

4. DATA MATRIX
see attached category document, endpoint specific chapters

Data source

Reference

Reference Type:

review article or handbook

Title:

Critical review of the epidemiology literature on the potential cancer risks of methyl methacrylate.

Author:

Tomenson JA, Carpenter AV, Pemberton MA

Year:

2005

Bibliographic source:

International Archives of Occupational and Environmental Health [Int. Arch. Occup. Environ. Health], 78(8): 603-612

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

The review focused on epidemiological studies in those parts of the manufacturing industry which had historically occupational exposure to high concentrations of MMA - manufacturing of cast acrylic sheet. The papers used in the review were mainly identified searching relevant scientific databases, e.g. Medline, but in addition three so far unpublished industrial studies were reviewed - two cohort studies and a nested case-control study.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methyl methacrylate

EC Number:

201-297-1

EC Name:

Methyl methacrylate

Cas Number:

80-62-6

Molecular formula:

C5H8O2

IUPAC Name:

methyl methacrylate

Test material form:

liquid

Results and discussion

Results:

In one cohort of workers occupationally exposed to high concentrations of MMA and ethyl acrylate (EA) (manufacturing of acrylic sheet) the authors reported an increased risk of colorectal cancer. An assessment of cumulative exposure to MMA indicated that the excess of colon cancer occurred primarily in the group with the highest exposure. This was, however, not the only cohort with an excess of colon cancer. Another excess of colon cancer deaths occurred among workers who had at most only marginal occupational exposure to MMA. And also, in large cohorts in other studies, partly with comparably high exposures, no evidence of a causal relationship between colorectal cancer and MMA exposure was found. One other study reported an excess but without relationship to MMA exposure.

The relationship of MMA exposure to other types of cancer was also assessed. Excesses of cancers of the stomach and the respiratory system were observed in some groups. A stringent correlation with high exposure and exposure duration was absent and dietary and lifestyle factors, e.g. smoking, were regarded as the more likely association. These cohorts were not related to the cohorts of acrylic sheet workers who had the apparent increase in colorectal cancer.

Applicant's summary and conclusion

Conclusions:

The objective of the paper was to review and assess available epidemiological information on Methyl methacrylate (MMA). The majority of the data was from publicly available or published sources, but also some unpublished information was used. There were some cohorts of MMA-exposed workers, in which excesses of respiratory, stomach and colorectal cancers had been observed. For all except the cases of colorectal cancer, there was little to suggest that exposure to MMA was responsible. Contributions of lifestyle exposures such as cigarette smoking and diet, which are not accessible for evaluation, are the more likely reason. An excess of colorectal cancer in one group of workers exposed to high levels of MMA and Ethyl acrylate (EA) during the 1930s and 1940s remains unexplained. The review concluded that, because of the lack of consistency in the results of the different studies, the absence of dose response and the absence of carcinogenicity in animal toxicology, there is no convincing evidence that exposure to MMA causes cancer in humans.