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Description of key information

HPMA was not found to be genotoxic in a battery of tests in vitro and in vivo. Read-across to chronic toxicity study data are available for methyl methacrylate (MMA), the donor substance of the primary metabolite MAA, and for the other primary metabolite itself, propylene glycol (PG): There is no indication of a carcinogenic potential of the primary metabolites and, as a consequence, of the parent ester.  

Key value for chemical safety assessment

Justification for classification or non-classification

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

No carcinogenic potential of metabolites was detected in reliable inhalation studies in rats, mice and dogs.

Additional information

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

Data in animals and in humans are only available for the respective primary metabolite PG and MMA as analogous substance and MAA donor substance.


Read across evaluation according to ECHA’s Read Across Assessment Framework (RAAF)

The metabolism from the category substances to their primary metabolites is well understood. The same is true for the further metabolism pathways of MAA and the alcohol metabolite PG, respectively (see chapter 5.2, ATSDR 1997, NTP 2004b). The endpoint specific “scientific assessment” of the read across for systemic effects is thus “acceptable with at least medium confidence”, see the attached Read Across Justification (2022) and Category document (2019).


Primary Metabolites

MAA (donor substance MMA)

Oral: EU ESR on MMA concluded: “An early 2-year chronic study on dogs and rats treated orally with MMA revealed no adverse effect other than a lower body weight gain in high-dose dogs and elevated kidney weights in high-dose female rats (Borzelleca et al., 1964). In this study two male and two female dogs received gelatin capsules with 10, 100 and 1000 ppm MMA dissolved in corn oil. The high- dose was reduced to 500 ppm on day 2, 0 ppm on day 3-13 and 300 ppm on day 14 due to vomiting, and then increased to 1200 ppm at week 5 and to 1400 ppm at week 7 to 1500 ppm at week 9. 25 male and 25 female rats were administered with 6, 60 and 2000 ppm MMA in the drinking water, the low and medium doses increased to 7 and 70 ppm after five months.

These studies on dogs and rats revealed no increase of neoplastic lesions. However the reliability of these studies is limited due to their non-conformance to current carcinogenicity test guidelines (e.g., histopathological examination was performed on a limited number of organs).”

Inhalation: EU ESR on MMA concluded: “The combined chronic toxicity and carcinogenicity study on methyl methacrylate of Rohm and Haas (1979a, re-evaluated by Lomax, 1992) reported in Section did not reveal any significant incidence of tumours or increase of tumour 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 tumour and the findings were not confirmed by other studies. However, historical data show that adenomas from respiratory epithelium are very rare tumours in rats with a spontaneous rate of 0-0.1 % for F344 male and female rats (Haseman et al., 1990).


Groups of 50 male F344/N rats were exposed to methyl methacrylate (purity > 99 %; containing 0.04 mg/l equivalent to 10 ppm monomethylethyl ether of hydroquinone as an inhibitor of polymerization) by inhalation at 0, 2.1, 4.2 mg/l (equivalent to 500 or 1000 ppm), female F344/N rats at 0, 1.0 or 2.1 mg/l (equivalent to 250 or 500 ppm) and male and female B6C3F1 mice at 2.1 or 4.2 mg/l (equivalent to 500 or 1000 ppm), 6 hours a day, 5 days a week for 102 weeks (NTP, 1986; Chan et al., 1988). Animals were killed at 111-112 weeks (rats) or 113-114 weeks (mice) of age. No significant differences of the survival rates were observed between any groups of rats and mice. During most of the second year of the study, the mean body weights of treated male mice and high-dose female mice were 10-18 % lower than those of the controls. 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.”

No treatment-related increases in tumour incidence occurred in Golden hamsters with groups of 53-56 males and 56-59 females exposed to 0, 25, 100 or 400 ppm (0, 102.5, 410 or 1640 mg/m³) MMA 6 h/d, 5 d/wk for 78 weeks (no interim sacrifice). At the high-dose, body weight decreased and mortality increased in high dose males (Rohm and Haas, 1979c, cited from Chan et al. 1994; Lomax et al., 1997). After week 60, males exposed to 400 ppm and to 25 ppm had significantly lower body weight during some weeks. There were no clinical signs or haematological effects attributable to exposure to methyl methacrylate at either the 52- or 78- week sampling times. No gross haematological changes indicative for a possible exposure-related effect were observed.”

Human data: EU ESR on MMA concluded: “A retrospective mortality study has been conducted among workers exposed to the vapour phase of methyl methacrylate, low percentages of ethyl acrylate (EA) and volatile by-products of the methyl methacrylate and EA polymerization process in acrylic sheet manufacture in two US plants. Detailed analyses of colorectal cancer mortality were performed for each of the three cohorts (cohort I: 3934 white males employed between 1933 and 1945; cohort II: 6548 white males hired between 1946 and 1986; cohort III: 3381 white males hired between 1943 and 1982). Exposure was estimated on the basis of a job-specific semi-quantitative rating scale. Mortality from colon cancer was significantly increased in cohort I and non-significantly increased in cohort III. The risk for colon cancer was highest in the most exposed workers, who worked extensively in the early 1940s. No regular increase according to years elapsed since first exposure or intensity of exposure was observed for colon cancer. The rate for rectal cancer was increased in cohort I (Walker et al., 1991; IARC, 1994). Some evidence of increased death rate from respiratory cancer or non-malignant respiratory disease were reported for cohort III (Rohm and Haas, 1987).


Another retrospective mortality study (Collins et al., 1989) included a cohort of 2671 male workers employed between 1951 (1957 respectively) and 1974 in two acrylic fibre production plants. Exposed to methyl methacrylate were only 1561 men of the cohort at mean concentrations below or equal to 1 ppm. A small excess of respiratory cancer was reported. There was no significant increase in the number of cancer deaths.


In the cohort study of Tomenson (1994) colorectal cancer was as expected (17 observed deaths versus 16.9 expected) and respiratory cancer mortality was lower than expected (SMR=93). Mortality due to stomach cancer was increased by approximately one third.


The epidemiologic data on humans do not provide consistent evidence on the carcinogenic effect in humans. The studies did not allow a strong association of increased tumour rates in a distinct organ or several organs to MMA as the responsible agent.”

Since the completion of the EU ESR on MMA the Tomenson (1994) internal company report was published as Tomenson et al., 2000 and a summary review of the available epidemiology (cancer mortality) studies published by Tomenson et al., 2005. These publications confirm the conclusion of the ESR.


Based on the available data including mutagenicity studies and 2yr toxicity studies in rats and dogs by feeding, “there is no evidence that propylene glycol is carcinogenic in humans or animals.” (ATSDR 1997; attached to the Toxikokinetics endpoint summary for detailed review).



HPMA has been evaluated for genotoxic potential in bacterial cells in culture and was found not to be mutagenic in this assay system. Further, HPMA was found not to be mutagenic in mammalian cells in culture [CHO HGPRT assay]. HPMA was reported to cause chromosomal aberrations in mammalian cells in culture, but anin vivomicronucleus study with HPMA indicated that this material was not clastogenic in vivo. On balance, it is clear that neither HEMA nor HPMA are genotoxic materials.

As there is no concern for mutagenic or genotoxic potential for HPMA there is no concern for carcinogenicity for HPMA.

This conclusion is supported by comprehensive evaluations of the metabolites which states that there is no relevant concern on carcinogenicity for these reference substances (EU ESR for MMA/MAA; ATSDR for PG, respectively).