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Toxicological information

Carcinogenicity

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Description of key information

HEMA was not found to be genotoxic in a battery of tests in vitro and in vivo.
Read-across to chronic toxicity study data available for methylmethacrylate (MMA), the donor substance of the primary metabolite MAA, and for the other primary metabolite itself, ethylene glycol (EG).

There is no indication of a carcinogenic potential of the primary metabolites.

Key value for chemical safety assessment

Additional information

No chronic exposure toxicity data are available for HEMA.However, there is ample information to indicate that HEMA has a low potential to be carcinogenic and that studies may be waived.

Data are available for potential genotoxicity of HEMA. Additionally, information is available on the carcinogenic potential of methylmethacrylate, a close structural analogue of HEMA. It is concluded that carcinogenicity studies of HEMA are not necessary and may be waived because:

-        HEMA was not found to be genotoxic in a battery of tests in vitro and in vivo.

-        Read-Across to MMA Data. MMA, a close structural analogue of HEMA, has been evaluated in chronic toxicity/carcinogenicity tests in mice and rats and found not to be a carcinogen.

HEMA has been evaluated for genotoxic potential in bacterial cells in culture and were found not to be mutagenic in this assay system. Further, HEMA was found not to be mutagenic in mammalian cells in culture [CHL V79 cell assay], albeit HEMA was evaluated only in the absence of S-9. HEMA was reported to cause chromosomal aberrations in mammalian cells in culture, but an in vivo micronucleus study with HEMA indicated that this material was not clastogenic in vivo. These results are in accord with genotoxicity assay findings for methyl methacrylate (MMA). MMA was not active in bacteria mutation assays but did cause chromosomal aberrations in mammalian cells in culture, an effect not observed in vivo. On balance, it is clear that HEMA is not a genotoxic material.

MMA as a member of the chemical class of short-chain alkyl esters of methacrylic acid has been evaluated for carcinogenic potential in long-term toxicity studies in mice and rats. There is no indication of a potential for carcinogenicity.

NTP (1986) conducted a carcinogenicity study that showed no treatment-related tumors in male and female F344/N rats and male and female B6C3F1 mice following inhalation exposure to 500 or 1000 ppm for 102 weeks (6 h/d, 5 d/wk).

Groups of 50 male F344/N rats were exposed to methyl methacrylate (purity >99%; containing 0.04 mg/1 equivalent to 10 ppm monomethylethyl ether 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 tumours were observed.

 

The EU Risk Assessment Report for MMA (2002) concluded that:

There is no relevant concern on carcinogenicity in humans and animals. Epidemiology data on increased tumor rates in exposed cohorts were of limited reliability and cannot be related to MMA as the solely causal agent. Therefore there are no reasons to assume that MMA should be considered to be carcinogenic in humans.

 

Justification for classification or non-classification

There are no data to indicate that HEMA meet EU CLP criteria for classification as a carcinogen.

No carcinogenic potential of MMA was detected in reliable inhalation studies in rats, mice.