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Carcinogenicity

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Description of key information

The carcinogenic potential of 1, 2, 3-trichloropropane was tested in rat and mouse by administering the chemical via gavage for 104 weeks. Testing was done according to a guideline similar to OECD451.
Cancer in multiple tissues was observed in both rats and mice. Target organs in the rats of both sexes were the forestomach and the oral mucosa. Additionally, female rats had an increased incidence of mammary gland and clitoral gland tumors while male rats had an increased incidence of tumors in the pancreas, kidney and preputial gland. The forestomach was also a target organ in mice with additional tumors observed the liver and Harderian gland.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
T25
5.12 mg/kg bw/day

Additional information

A tumorigenic effect was observed in rats and mice following long-term exposure to 1, 2, 3 -trichloropropane. Many of the effects were observed at the lowest dose studied (ca 10% of predicted maximum tolerable dose) and in a dose-dependent manner. The most sensitive endpoint in both species was the forestomach. Other significant increases in tumors were also seen at this dose for oral sq. cell papilloma, forestomach sq. cell papilloma, forestomach sq cell carcinoma, preputial gland carcinoma, pancreas acinar adenoma, clitoral gland adenoma, mammary gland adenocarcinoma.

The relevance of these tumors for the situation of human exposure needs to be differentiated as exposure via oral gavage leads to very high concentrations of 1,2,3-trichloropropane at the portal of entry (oral cavity and gastrointestinal tract). Irritation might play a major role here. Therefore the effects seen in the oral cavity, the forestomach and the pancreas are disproportional as compared to systemic effects at the respective dose. Therefore the increased number of mammary gland adenocarcinoma is regarded as the most critical systemic carcinogenic effect of 1,2,3-trichloropropene indicative for humans exposed to low concentrations or doses of 1,2,3-trichloropropane.

Based on this assumption the start value T25 is calculated to be 5.12 mg/kg bw/d.

Genotoxicity studies done on 1, 2, 3 -trichloropropane indicate that it causes both gene mutations in bacterial and mammalian systems as well as chromosome aberrations.

The incidence of mammary gland adenocarcinoma in rats at 3 mg/kg bw was 6/49 = 12.2 % as compared to 1/ 50 in the control group. So the NOAEL for carcinogenicity is 3.0 mg/Kg bw/d. This finding is the basis for the calculation of a T25 value:

3 mg/kg bodyweight dosed 5 days per week= 3 mg/kg x 5 days/7 days = 2.14 mg/kg bw/day

T25 = (25 %/X) x 2.14 mg/kg bw

X = ((6/49-1/50) / (1-1/50)) x 100 % = 10.454 %

T25 = 5.12 mg/kg bw/d


Carcinogenicity: via oral route (target organ): digestive: pancreas; glandular: mammary gland; glandular: other; urogenital: kidneys

Justification for classification or non-classification

The results of the 2-year carcinogenicity study by NTP are unambiguous, showing the carcinogenicity of 1,2,3-trichloropropane in both mice and rats, where rats are more susceptible. Therefore 1,2,3 -trichloropropane is to be classified as Category 1B (Warning; H350: May cause cancer)according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

This classification is in-line with the assessments of IARC ( IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 63, Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals, 1995, IARC Lyon, France, p. 223 -242; http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php) and SCOEL (Recommendation from the Scientific Committee on Occupational Exposure Limits for 1,2,3-trichloropropane, SCOEL/SUM/170, November 2009, For public consultation).

(Category 1B, presumed to have carcinogenic potential for humans, classification is based on animal evidence.)