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Description of key information

Monochloroacetic acid: Oral repeated dose toxicity: key studies: data obtained from exposure during 16 days, 13 weeks and 2 years both in rats and mice (FDA regulations). 
Monochloroacetic acid: Inhalation repeated dose toxicity: supporting information: data obtained from exposure during 4 months in rats and guinea pigs (no guideline was followed).
Methyl chloroacetate: Inhalation repeated dose toxicity: Key study: 28-day inhalation study conducted according to OECD guideline 412.

Key value for chemical safety assessment

Additional information

Reaction mass of methyl chloroacetate and chloroacetic acid:

1.- Chloroacetic acid: Oral repeated-dose toxicity studies with 16-day and 13-week exposure to monochloroacetic acid were available. Within the limited study design of the 16-day toxicity studies (by gavage), the NOAEL in rats was 60 mg/kg bw/day for males and equal or greater than 120 mg/kg bw/day for females, and in mice 120 mg/kg bw/day, both based on mortality. A NOAEL could not be derived from the results of 13-week repeated-dose toxicity study with rats (by gavage). Changes in the weight of the heart, liver, kidneys, and clinical chemistry values were observed at the lowest dose level tested, i.e., 30 mg/kg bw/day. Dose-related cardiomyopathy was found in both sexes at 60 mg/kg bw/day and above. An increased liver weight and decreased serum cholinesterase activity were observed in mice exposed during 13-weeks by gavage, the NOAEL was 100 mg/kg bw/day.

A NOAEL of 3.5 mg/kg bw/day is also derived from the 2-year drinking water study performed by DeAngelo et al. (1997) in rats. At this level, no effect on survival, body weight, or (non-) neoplastic lesions was found.

Main target organs of monochloroacetic acid after prolonged oral administration are liver in both rats and mice, and heart and kidneys in rats. Additionally, growth depression, decreased survival, and inflammation of the nasal mucosa were observed in the carcinogenicity studies. The effects on the heart disappeared at lower dose levels in repeated-dose toxicity studies with longer study duration. Based on the data available, rats appeared to be more sensitive for the toxic effects of monochloroacetic acid than mice.

The repeated dose inhalation toxicity of monochloroacetic acid was studied experimentally on white rats and guinea pigs for 4 months. The tested dose for rats was 20.8 ( ± 1.0) mg/m3. Chronic inhalation of monochloroacetic acid caused reduction of weight in rats (after 10 weeks of exposure), diminished oxygen uptake (on the 3rd and 15th days of exposure), lowering of rectal temperature (at 2nd and 15th days), reduction of the chloride content in urine (after 2 months of exposure), hemoglobinemia (after 4 months) and inflammatory changes in the respiratory organs. The tested dose for guinea pigs was 5.8 ( ± 0.3) mg/m3. Chronic inhalation of monochloroacetic acid caused reduction of weight in guinea pigs (after 2 weeks of exposure), lowering of rectal temperature (at 2nd and 15 th days), reduction of the chloride content in urine (after 2 months of exposure), hemoglobinemia (after 4 months) and inflammatory changes in the respiratory organs.

 

2.- Methyl chloroacetate: 28-day inhalation study conducted according to OECD guideline 412. The effects observed were clinical signs, retardation of the body weight development and changes in lung weight with no evidence of organ dysfunction.

These effects are considered not to support classification for specific target organ toxicity following repeated exposure.

 

 

 

 

 

 

 

 

 

Justification for classification or non-classification

Based on the results from the repeated dose toxicity studies, neither the substance chloroacetic acid nor the substance methyl chloroacetate are classified. Therefore, the reaction mass of chloroacetic acid and methyl chloroacetate is not classified for repeated dose toxicity.