3-chloropropane-1,2-diol

Carcinogenicity

Description of key information

Cho (2008) performed a carcinogenicity study according to OECD Guideline 451. There was clear evidence of carcinogenic activity of the test substance in male SD rats, based on the increased incidences of kidney renal tubule carcinomas and Leydig cell tumors. There was some evidence of carcinogenic activity in female SD rats, based on increased incidences of kidney renal tubule adenomas. The substance seems to be a threshold carcinogen and a NOAEL of 8.27 mg/kg bw for males and 10.34 mg/kg bw for females is observed.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

8.27 mg/kg bw/day

Justification for classification or non-classification

The substance is classified as a nongenotoxic carcinogen. These carcinogens act species-specific, and sometimes even strain- or sex-specific. Due to the lack of data on the precise mechanisms causing the carcinogenic effects and due to the lack of evidence of carcinogenic effects in humans, the substance is classified as a Category 3 carcinogen (Xn R40) according to the DSD (Directive 67/548/EEC).

According to CLP, the substance will be classified as a Category 2 carcinogen (H351).

Additional information

Cho (2008) performed a carcinogenicity study according to OECD Guideline 451. 50 male and 50 female Sprague-Dawley rats per dose were exposed orally via drinking water during 100 weeks (males) or 104 weeks (females). The substance was supplied continuously via drinking water at doses of either 25, 100 or 400 ppm. Male average daily intake, based on water consumption, was 1.97, 8.27 and 29.50 mg/kg bw/day and female average intake was 2.68, 10.34 and 37.03 mg/kg bw/day. These doses were selected based on 13 -week toxicity studies conducted in Sprague-Dawley rats. Control animals were observed concurrently. There was clear evidence of the carcinogenic potential activity of the test substance in male SD rats, based on the increased incidences of kidney renal tubule carcinomas and Leydig cell tumors that were observed in the absence of pre-neoplastic lesions such as Leydig cell hyperplasia. There was some evidence of the carcinogenic activity in female SD rats, based on increased incidences of kidney renal tubule adenomas. The substance showed as well to induce renal non-neoplastic and pre-neoplastic lesions in both male and female rats. The substance seems to be a threshold carcinogen and a NOAEL of 8.27 mg/kg bw in males and 10.34 mg/kg bw in females is observed. The NOAEL for males of 8.27 mg/kg bw is the critical value for the CSA as this is the lowest value. In addition, the substance was concluded to be non mutagenic based on in vivo mutagenicity tests despite in vitro mutagenicity. The substance is therefore classified as a nongenotoxic carcinogen.

The exact mechanisms by which the substance induces tumors are not known. However, some suggestions were proposed based on available literature data by the Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (2000)

(non-genotoxic mechanisms involving either cytotoxicity (kidney) or hormonal disturbances) and OEHHA (2010) (suggesting that the carcinogenicity of 3 -MCDP may be due to the formation of glycidol - a genotoxic carcinogen, ability of 3 -MCPD to inhibit glyceraldehyde-3 -phosphate-dehydrogenase (GAPDH) that showed to act as a promotor and an inhibitor of carcinogenesis - however currently there is limited understanding of GAPDH's role in carcinogenesis or suppression of certain immune functions in volved in tumor surveillance or a role for hormonal effects in 3 -MCPD carcinogenesis).

Carcinogenicity: via oral route (target organ): urogenital: kidneys; urogenital: testes