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Carcinogenicity

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Description of key information

Data are available for the corresponding sodium salt of the substance, docusate sodium. These data are used for read-across to the substance registered. Docusate sodium was tested up to 1% dietary concentrations in standard rats  for 2 years and in a special rat model for colorectal carcinogenesis for 20 weeks . Both models did not result in increased tumour findings Docusate sodium was tested up to 1% dietary concentrations in standard rats  for 2 years and in a special rat model for colorectal carcinogenesis for 20 weeks . Both models did not result in increased tumor findings up to at a slight toxic dose level  of 1% showing decreased body weight. NOAEL for toxicity was 0.5% dietary concentration (250 mg/kg bw/day) and NOAEL for tumorigenicity was 1% in the diet (500 mg/kg bw/day).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day

Additional information

Data are available for the corresponding sodium salt of the substance, docusate sodium. These data are used for read-across to the substance registered.

A literature study was available, where Docusate sodium was tested for 2 years in rats at concentrations of 0.25, 0.5 and 1% in the diet (Literature: Fitzhugh and Nelson, 1948). At 1%, there were no effects on mortality, but there was a significant (p<0.001) difference in body weight gain between the control group and the 1% dose group. No effects were observed at the 0.5% dose level, corresponding with 250 mg/kg bw/day. There were no dose related changes in tumour incidences up to 1%, corresponding with at least 500 mg/kg bw/day.

Secondly, a review also memntioned a study of Docusate sodium (DSS) in the 1,2-dimethylhydrazine (DMH) rodent model for colorectal carcinogenesis to explore the effect of on carcinogenesis. Inbred male F344 rats were divided into two groups of 84 each and fed the following diets: ground chow and 5% corn oil (control group) and ground chow, 5% corn oil, and 1% DSS (experimental group). All rats received high-dose DMH base, 20 mg/kg/week sc for 20 weeks. Twenty rats per group were killed after 3, 4, 5, and 6 months. Duodenum, small intestine, colon, and rectum were dissected out. Each tumor was measured for size and location and evaluated histologically. The percentage of rats bearing tumors in the control and experimental groups did not differ significantly. In each rat there were fewer gastrointestinal tumors in the DSS-fed group of all histologic types combined, at all organ sites, at 5 and 6 months. This difference between the control and DSS-fed rats reached the level of statistical significance for tumors of the duodenum, colon, and rectum and for total gastrointestinal tumors at the 5th month.

In summary, Docusate sodium was tested up to 1% dietary concentrations in standard rats for 2 years and in a special rat model for colorectal carcinogenesis for 20 weeks. Both models did not result in increased tumor findings up to at a slight toxic dose level of 1% showing decreased body weight. NOAEL for toxicity was 0.5% dietary concentration (250 mg/kg bw/day) and NOAEL for tumorigenicity was 1% in the diet (500 mg/kg bw/day). The absence of tumorigenicity confirmed the negative genetic toxicity potential of Docusate sodium described in section 7.6.

Justification for classification or non-classification

As there were no tumours observed, classification is not warranted.