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Description of key information

Key values were obtained from a chronic oral NCI study with mice  (1978) and the sub-chronic inhalation study with rats (UNEP 2000).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
mouse

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
83 mg/m³
Study duration:
chronic
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

A 14-day study by gavage in CD-1 mice was performed for selecting doses to be used in a 90-day drinking water study in the same mouse species. Doses selected were 20, 200 and 2000 mg/L for the 90-day drinking water study. In the 90-day drinking water study, effects were observed in mouse liver (White et al., 1985). The NOAEL in females was 3.9 mg/kg/day (20 mg/L), based on the reduction of cytochrome P-450 levels and aniline hydroxylase activity. In males, the NOAEL was 4.4 mg/kg/day (20 mg/L), based on reduction of liver glutathione. Histopathological examination was not conducted in this study, limiting the interpretation of the study results. As part of carcinogenicity studies on mouse and rat, chronic effects on bodyweight gain, mortality and clinical signs were examined following administration of substance by gavage (NCI, 1978). NOAEL was derived at 300 mg/kg bw/d in mouse. No NOAEL was derived in the rat study as clinical signs, such as hunched appearance, rough fur, urine stains on the abdominal area, dyspnea and squinted eyes, were observed at the lowest dose tested, i.e. 35 mg/kg bw/d. The latter study was not retained for the key value because only aspecific changes were observed.

Only summaries (UNEP review document, 2000) were available for repeated inhalation exposure studies.

Repeated inhalation exposure (7 hours/day, 5 days/week) to 83 mg of 1,1,2-trichloroethane/m3 air for 6 months did not lead to substance-related histopathological, hematological and biochemical changes in the rat, guinea pig and rabbit. Body weight gain, organ weights and mortality remained unaffected. Therefore, NAOEL was considered to be 83 mg/m3, equivalent to roughly 11.1 mg/kg/day in the rat, 7.43 mg/kg/day in the guinea pig, and 24.9 mg/kg/day in the rabbit.

No relevant dermal exposure toxicology studies were available in literature.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

Considering organ-specific toxicity, no studies were identified which convincingly confirmed a need for classification.

No classification was also deemed necessary by European authorities regarding repeated oral or inhalation exposure.