Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and lauric acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In vitro gene mutation in bacteria

The bacterial reverse mutation assay was conducted in accordance with OECD guidance 471, EU method B.13/14 and GLP principles. Salmonella typhimurium TA1535, TA1537, TA98, TA100 strains and WP2uvrA were used both in the absence and presence of S9-metabolic activation with concurrent positive controls. The test substance did not induce a significant dose-related increase in the number of revertant (His+) colonies in any of the tester strains. These results were confirmed in an independently repeated experiment. In this study, the negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate, and that the metabolic activation system functioned properly (Wil, 2012).

In vitro gene mutation in mammalian cells

In an in vitro mammalian cell gene mutation test performed according to OECD guideline 476, in compliance with GLP, mouse lymphoma L5178Y TK^+/-(3.7.2C) cells were exposed to the read-across substance 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid in DMSO at concentrations of 0, 46.88, 93.75, 187.5, 375 or 750 μg/mL in RPMI 1640 medium with and without 2% S-9 metabolic activation for a preliminary cytotoxicity test. In the main test, two experiments were performed at the following concentrations:

- Experiment 1 (3 hour exposure): Without (S-9): 0, 0.0977, 0.1953, 0.3906, 0.7813, 1.563, 3.125, 6.25, 12.5, 25 or 50 μg/mL; with (S-9): 0, 3.75, 7.5, 15, 30, 35, 40, 45, 50, 60 or 75 μg/mL

- Experiment 2 (3 hour exposure): Without S-9: 0, 3, 6, 9, 12, 15, 18, 21, 24, 27 or 30 μg/mL; with S-9: 0, 15, 30, 40, 50, 60, 70, 80, 90, 100 or 125 μg/mL

Mutant frequencies in negative control cultures fell within normal ranges and clear increases in mutation were induced by the positive control chemicals 4-nitroquinoline 1-oxide (without S-9) and benzo(a)pyrene (with S-9). In Experiment 1, statistically significant increases in mutant frequency were observed at 12.5 (without S-9) and 60 µg/mL (with S-9). A significant linear trend was observed in the presence of S-9 only. In Experiment 2, a statistically significant increase in mutant frequency was observed at 9 µg/mL in the absence of S-9 only. However, no significant increases were observed following treatment with S-9 and there were no significant linear trends in either the absence or presence of S-9. Further, in both experiments, the increases in mutant frequency at the significant concentrations were all within three times the historical mean value, and the increases were not considered concentration-related or biologically relevant. Under the test conditions, the test substance was not mutagenic in L5178Y cells (Stone, 2010).

 

In vivo cytogenicity

In a mouse bone marrow micronucleus test, performed according to OECD guideline 474, in compliance with GLP, CD-1 (ICR) BR male mice (5/dose) were given a single oral (gavage) dose of the read-across substance Bisphenol A diglycidyl ether diacrylate (BADGEDA) in corn oil at concentrations of 500 and 1000 mg/kg bw and twice, approximately one hour apart, at a concentration of 2000 mg/kg bw (1000 mg/kg/dose, BID). Bone marrow was extracted after 24 or 48 h of exposure and the slides prepared were scanned to determine the frequency of micronuclei in 2000 polychromatic erythrocytes (PCEs) per animal. In addition, the number of PCEs and normochromatic erythrocytes (NCEs) in a population of 500 erythrocytes was determined as a measure of cytotoxicity. A preliminary range-finding test was also conducted on 3 mice/sex/dose at 500, 1000 and 2000 mg/kg bw and animals were observed for 2 days. In this previous test, no mortality and/or toxic signs were recorded. No statistically significant increases in the frequency of micronucleated PCEs were observed at any dose level. A statistically significant decrease in the PCE:NCE ratios at a dose level of 1000 mg/kg bw was observed but was not considered biologically significant as the highest dose of 2000 mg/kg bw did not show a similar trend. Under the test conditions, the read-across substance was not genotoxic in the mouse bone marrow micronucleus test (Yong, 2007).

Justification for classification or non-classification

Based on the results of in vitro and in vivo testing with the test and the read-across substance, no classification for genotoxicity is warranted according to EU CLP regulation (EC 1272/2008) criteria.