1,1,2-trichloroethane

Carcinogenicity

Description of key information

Carcinogenicity study of this chemical by gavage showed hepatocellular carcinomas and pheochromocytomas in mice but no carcinogenicity in rats (NCI, 1978). 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Under the previous DSD Regulation, the EC authorities have classified the substance as Carcinogenic 3 ("Substances which cause concern for humans owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment. There is some evidence from appropriate animal studies, but this is insufficient to place the substance in Category 2."), XnR40, according to the following rationale:

Under CLP regulation, this corresponds to carc. cat.2 H351.

-     The findings of pheochromocytoma in the adrenal glands of the mouse (significantly increased for female animals in the highest dose group.).

-     The (non-significant) occurrence of tumors in treated but not in untreated Osborne-Mendel rats.

-     The significantly increased occurrence of liver foci in the initiation/promotion short term test with Osborne-Mendel rats (unclear significance).

-     Also to be considered is the significantly increased incidence of sarcoma of varying location in the highest dose group of male rats compared with untreated animals, although a significant increase relative to vehicle control and to historical controls was not obtained.

-     The data on genotoxicity is not consistent, but although a genotoxic mechanism cannot be unambiguously confirmed, it cannot be excluded.

In an assessment by USEPA, this chemical is classified to group C, a possible human carcinogen and is indicated to structurally related to 1,2-dichloroethane, a probable human carcinogen. On the other hand, International Agency for Research on Cancer (IARC) had evaluated in 1991 that 1,1,2 -trichloroethane was not classifiable as its carcinogenicity to humans (Group 3) because of limited evidence for the carcinogenicity in experimental animals and no available data in humans.

Additional information

A carcinogenicity study with 1,1,2-trichloroethane given by gavage from 150 mg/kg bw/d for 8 weeks, and then 200 mg/kg bw/d for 70 weeks showed hepatocellular carcinomas and pheochromocytomas in mice (50 per dose group). Nevertheless, the chemical was not carcinogenic in rats (50 per dose group) when given by gavage 70 mg/kg bw/d for 20 weeks and then 100 mg/kg bw/d for 58 weeks (NCI, 1978).

After subcutaneous administration of 15.37 or 46.77 mmol/animal (9.11 or 27.73 mg/kg body weight) to 50 male and 50 female Sprague-Dawley rats once a week for 2 years, there was a significant increase in the sarcoma incidence at various locations in the male rats of the highest dose group compared to untreated animals.  However, these effects were not significantly increased relative to vehicle control (DMSO) and historical control values (Norpoth et al, 1988).

Further possible indications of a carcinogenic activity were also reported (Story et al., 1986).  They were able to establish in this species the formation of liver foci in hepatocytes (GGT* foci assay).  On the basis of the characteristics of these foci (Type II, according to the view of the authors at the time of the investigation presumably not preneoplastic), the significance for hepatocarcinogenicity and a promoting effect of 1,1,2 -trichloroethane cannot be conclusively established.

Carcinogenicity: via oral route (target organ): digestive: liver; glandular: adrenal gland