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Toxicological information

Carcinogenicity

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Description of key information

No carcinogenicity study is available for 1,3-BDDMA. Data are available for the alcohol metabolite 1,3 -Butanediol and the metabolite donor substance of the methacrylate metabolite methacrylic acid, namely methyl methacrylate. More details on the metabolism are available in the read-across justification document.

 

1,3-Butanediol:

Rats, oral, 2 yrs: negative (Scala & Paynter 1967)

Dogs, oral, 2 yrs: negative (Scala & Paynter 1967)

 

Methyl methacrylate:

Rats, inhalation, 2 yrs: negative (NTP 1986)

Mice, inhalation, 2 yrs: negative (NTP 1986)

Rats, inhalation, 2 yrs: negative (Lomax 1992)

 

Rats, oral, 2 yrs: negative (Borzelleca, 1964, limited reliability)

 

In summary there is no evidence of carcinogenicity of the ester hydrolyses products of 1,3-BDDMA and therefore no carcinogenicity is expected for 1,3-BDDMA itself.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data give no concern on carcinogenic properties of the test substance. Thus, classification of 1,3 -BDDMA as carcinogenic is not required according to Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008 and therefore labelling is not necessary.

Additional information

No carcinogenicity study is available for 1,3-BDDMA. Data are available for the alcohol metabolite 1,3 -Butanediol and the metabolite donor substance of the methacrylate metabolite methacrylic acid, namely methyl methacrylate. More details on the metabolism are available in the chapter Toxicokinetics and in the read-across justification document.

 

1,3-Butanediol:

NTP (1996) stated as follows: “Sprague-Dawley rats (30 males and 30 females per group) received 1%, 3%, or 10% 1,3-BD in feed, and dogs (four males and four females per group) received 0.5%, 1%, or 3% 1,3-butanediol in feed for 2 years. Blood and urine samples were collected from rats at six time points and from dogs at eight time points during the study. Blood samples were evaluated for hematology parameters, and urine was analyzed for specific gravity, pH, glucose, protein, and porphyrins. After 1 year of chemical exposure, 10 rats and 2 dogs from each group were evaluated; after 2 years of chemical exposure, the surviving animals were evaluated. At necropsy, organ weights were taken and all major tissues were fixed and prepared for histopathologic examination. No adverse effects were observed during the study, and there were no gross or microscopic lesions attributable to chemical exposure (Scala and Paynter, 1967).”

 

Methylmethacrylate

Rats & mice, inhalation

Groups of 50 male F344/N rats were exposed to methyl methacrylate (purity >99%; containing 0.04 mg/1 equivalent to 10 ppm monomethylethylether of hydroquinone as an inhibitor of polymerization) by inhalation at ca. 0, 2.05 and 4.1 mg/L (equivalent to 500 or 1000 ppm), female F344/N rats at ca. 0, 1.03 or 2.05 mg/L (equivalent to 250 or 500 ppm) and male and female B6C3F1 mice at ca. 2.05 or 4.1 mg/L (equivalent to 500 or 1000 ppm), 6 hours a day, 5 days a week for 102 weeks (NTP, 1986).

No significant differences of the survival rates were observed between any groups of rats and mice. Reductions in mean body weights of high dosed animals were considered as secondary effects based on the observed inflammations and degenerations of the olfactory epithelium in all MMA treatments. The marginal increase in the incidence of mononuclear-cell leukaemia observed in female rats (control 11/50; low-dose 13/50; high-dose 20/50) fell within the range of values seen in historical controls. Both in mice and rats no treatment-related tumors were observed.

The combined chronic toxicity and carcinogenicity study on methyl methacrylate of Rohm and Haas (1979a, re-evaluated by Lomax, 1992; Lomax et al. 1997) did not reveal any significant incidence of tumors or increase of tumor incidence. One male each out of a total of 49, respectively 47 males exposed to 100 and 400 ppm methyl methacrylate had a small solitary polypoid mass attached to the lateral wall of one side of the anterior nasal cavity. Both masses were composed of well differentiated pseudoglandular structures arising from respiratory epithelium diagnosed as adenomas. Both animals had chronic inflammation of the respiratory epithelial region. An association of the nasal adenomas to methyl methacrylate inhalation were considered to be unlikely, because the incidence was not significantly increased in comparison to controls without any nasal tumor and the findings were not confirmed by other studies. However, historical data show that adenomas from respiratory epithelium are very rare tumors in rats with a spontaneous rate of 0-0.1 % for F344 male and female rats.

 

Rats, oral

An early 2-year chronic study on rats treated orally with MMA revealed no adverse effect other than slightly elevated kidney weights in high-dose female rats (Borzelleca et al., 1964).

 

In summary there is no evidence of carcinogenicity of the ester hydrolyses products of 1,3-BDDMA and therefore no carcinogenicity is expected for 1,3-BDDMA itself.

There is no concern for mutagenicity or genotoxicity at physiologically relevant levels. Although in single in vitro mutagenicity assays there was some evidence of mutagenicity, the analogous substance 1,4-BDDMA substance was non-mutagenic in vivo.

Available data give no concern on carcinogenic properties of the test substance. Carcinogenicity in humans is not expected. In addition TREGDMA, another member of the category of multifunctional methacrylates, has been investigated in a dermal carcinogenicity study and there was no increase in tumor frequency.

 

 

Compliance to REACh requirements

Not applicable: No carcinogenicity study is required.