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Toxicological information

Carcinogenicity

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Description of key information

Structurally similar substance Polyglycidyl ether of substituted glycerine (EPON 562) showed carcinogenic activity in several animal studies. 

Key value for chemical safety assessment

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
There are numerous studies available conducted with structurally similar analogues (epoxides) where the carcinogenic activity was investigated. Therefore, the overall quality of the database is high.

Additional information

The "Patty´s Industrial Hygiene and Toxicology" contains information about Polyglycidyl ether of substituted glycerine (EPON 562) (Hine et al., 1981). There is a study mentioned, in which the skin of mice was painted with the material from once weekly to trice weekly over a period of a year and carcinomas were produced on the skin of mice. However, no tumours were produced in rabbits treated dermally with the substance of interest. In addition, a study is mentioned, where rats were treated subcutaneously with the material and sarcomas were produced. Moreover, a study is mentioned, where the test material was fed in the diet (0.2 %) to A strain of mice with spontaneous pulmonary adenomas, there was no effect on the incidence of occurrence.


Justification for selection of carcinogenicity via dermal route endpoint:
No study is selected since all entries are weight-of evidence data.

Justification for classification or non-classification

According to the profiling results of the OECD QSAR Toolbox (v3.1), the epoxides are binders to DNA via SN2 mechanism. They may react directly with the nucleophilic centres of the DNA (nitrogen atoms in guanine, adenine and cytosine) forming highly mutagenic sites leading to mutations. Therefore, the epoxides are allocated as genotoxic carcinogens which attack DNA fragments directly without enzymatic activation. According to the endpoint specific profilers, the target chemical possess mutagenic and carcinogenic activity. Its nearest analogue polyglycidyl ether of substituted glycerine possesses carcinogenic activity in rats and in mice (Hine et al., 1981). There are numerous studies available for a variety of structurally similar epoxy compounds. The chemicals containing the same glycidyloxy moieties in their structures, and having physico-chemical properties such as water solubility, logPow and vapour pressure are similar to those of the target chemical. Those chemicals caused tumors at many different tissues in different animal species (please refer to read-across statement attached to this IUCLID file). On the other hand, there was no indication of tumorigenic potential of the target substance in workers who were exposed to the finishing agent containing glycerol polyglycidyl ether during a lot of years (Lanes et al., 1994; Watkins et al., 2001). For most causes of death, mortality rates in the cohort were similar to mortality rates in the US population (Lanes et al., 1994). In the follow up study, there were no significant differences in the mortality rates between race and gender groups within the same cohort, compiled by Lanes et al. in 1994 (Watkins et al., 2001). All causes of death and all cancer causes of death were below unity on both national and local (country in which plant is located) standards (Watkins et al., 1994). For white males, there were no statistically significant increases for any cause of death with the exception of benign neoplasms. However, these findings only do not represent a clear evidence of carcinogenic effect of glycerol polyglycidyl ether in humans. Furthermore, the major limitation of the human studies is the lack of work history data allowing classification of employees to the plant operation with exposure of interest. Based on these data, no carcinogenic potential could be attributed for the target substance.

Therefore, according to the European Regulation (EC) No. 1272/2008, classification and labelling is not warranted for this endpoint.