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Key value for chemical safety assessment

Additional information

Gene mutation in bacteria

Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate was not mutagenic in a standard plate test and in a pre-incubation Ames test with and without metabolicactivation. In the standard plate test, concentration up to 5000 μg/plate were tested in Salmonella typhimurium strainsTA1535, TA 1537, TA 98 and TA 100 and E.coli WP2 uvrA. For the pre-incubation test, E.coli were also exposued to up to 5000µg/plate, while up to 2500µg/plate were used with TA tester strains. S9 fraction was prepared from the liver of male Sprague-Dawley rats, treated with a single dose of phenobarbital and β-naphthoflavone. Cytotoxicity was observed at and above 2500µg/plate in the standard plate test and at and above 333µg/plate in the pre-incubation assay, depending on test strain and test conditions.

Gene mutation in mammalian cells

Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate was also not mutagenic in a HPRT assay using chinese hamster V79 cells. Duplicate cell cultures were exposed to the test substance for either 4 hours (with and without S9) or 24 hours (without S9). The dose range was limited by the cytotoxic properties of the test substance to 0.3 - 2.5µg/plate (without S9) and 40 - 300µg/plate (with S9). After an expression phase of 7 days and a selection period of 8 days, mutant colonies were counted. S9 fraction was prepared from the liver of male Sprague-Dawley rats, treated with a single dose of phenobarbital and β-naphthoflavone.

Genetic toxicity in vivo - cytogenicity studies

No cytogenetic studies exist for Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate, but three studies according to OECD guidelines and GLP are available for the structurally similar substance Propylidynetrimethanol, ethoxylated, esters with acrylic acid (CAS28961 -43 -5).

This substance did not induce chromosomal damage (clastogenicíty) or spindle poison effects (aneugenic activity) in the micronucleus test method according to OECD guideline 474 and GLP (BASF, 2002), when administered once orally in DMSO to NMRI mice at dose levels of 500 mg/kg, 1,000 mg/kg and 2,000 m g/kg body weight. The administration of the test substance was tolerated by all animals without any clinical signs. The animals were sacrificed and the bone marrow of the two femora was prepared 24 and 48 hours after administration in the highest dose group of 2,000 mg/kg body weight and in the vehicle controls. The animals exposed to 1,000 mg/kg or 500 mg/kg body weight and those of the positive control group were all sacrificed after 24 hours. 2000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normocytes with and without micronuclei occurring per 2,000 polychromatic erythrocytes were also recorded. All dose groups showed rates of micronuclei, that were close to the range of the concurrent negative control and within the range of the historical control data. No inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected. Both of the positive control chemicals, i .e. cyclophosphamide for clastogenicity and vincristine for spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei.

This negative result was confirmed in two further MNT studies in vivo according to OECD 474 and GLP (CrayValley 2001, Cytec 2006), in which the substance was administered intraperitoneally in doses up to 250mg/kg b.w. to NMRI or Crl:CD-l(ICR)BR mice, respectively. The first study showed a slight decreases in the ratio of polychromatic to normochromatic erythrocytes at the 48 hours sampling time in mice treated with 250mg/kg. In the second study clinical signs (hunched posture and ptosis) were seen in mice treated with 100mg/kg b.w., the highest dose used in that study. Especially the observation from the first study imply systemic uptake of the test substance and that it reaches the bone marrow cells of mice.

Read across justification

Propylidynetrimethanol, ethoxylated, esters with acrylic acid (CAS28961 -43 -5) is structurally similar toOxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate (CAS118800 -30 -9). Both molecules show no acute toxicity after oral or dermal exposure and did not induce gene mutations in bacteria or mammalian cells. In a developmental toxicity study using the read across substancePropylidynetrimethanol, ethoxylated, esters with acrylic acidat 1000mg/kg b.w., poor general state and weight loss were observed in maternal animals, presumably as the result of local irritation of the gastrointestinal tract. Erosions in the stomach accompanied by weight loss within one week were also observed in a range finding test conducted with Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate using 600 and 1000mg/kg b.w.

The missing propoxy elements in CAS28961 -43 -5 shorten the chain between the propylidynetrimethanol and the acrylic acid groups, leading to a lower molecular weight of app. 433g/mol and lower logPow of 2.89. It is reasonable to assume, that this also leads to a higher reactivity (i.e., an eye irritating and skin sensitizing potential, which is not observed for CAS118800 -30 -9), since the not ethoxylated Trimethylolpropane triacrylate (moleculare weight 296mg/mol, logPow 0.67) shows a further increased sensitizing potential in addition to eye and skin irritation, while also not being acutely toxic or mutagenic. Thus using data from 28961 -43 -5 is a reasonable worst case approach to cover the endpoints required for Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate.


Short description of key information:
Ames: negative (OECD 471, GLP, BASF 2012)
HPRT: negative (OECD 476, GLP, BASF 2012)
MNT in vivo: negativ (OECD 474, GLP, BASF 2002)
MNT in vivo: negativ (OECD 474, GLP, CrayValley 2001)
MNT in vivo: negativ (OECD 474, GLP, Cytec 2006)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Oxirane, methyl-, polymer with oxirane, ether with 2-ethyl-2-(hydroxymethyl)-1,3 -propanediol (3:1), 2 -propenoate did not induce gene mutations in bacteriy or mammalian cells.

Thus, the substance has not to be classified according to EU criteria (67/548/EEC) or CLP/EU-GHS.