Registration Dossier

Administrative data

Description of key information

Subacute and subchronic inhalation studies in rats

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
245 440 mg/m³

Additional information

Groups of 10 male and 10 female Sprague Dawley rats were exposed to 0, 5000, 15000 and 50000 ppm (0, 24544, 73632 and 245440 mg/m3) HFC 125 for 28 days (6 hours/day, 5 days/week).  Two additional groups were exposed to 0 and 50,000 ppm HFC-125 and were allowed to recover for two weeks after the exposure period (Nakayama et al., 1992).

No mortality was observed in this study.  There were no treatment-related clinical signs of toxicity and differences in body weight and food consumption among the treated and the control groups, neither after the exposure nor after the recovery period.  Some effects were observed in the haematology and blood chemistry analysis. 

Neither macroscopic nor microscopic changes were observed during gross pathology and histological examinations, respectively.  Study of peroxisomal proliferation gave equivocal results, since a slightly higher activity of peroxisomal beta-oxidation was measured in the males of the high-dosed group in comparison to control; while a lower activity was measured in the females of the same group.

The toxicological significance of the above effects is not clear.  Because of the equivocal nature of most of the effects, the 50000 ppm concentration was considered the NOAEC of this study.

In 13-week study, groups of 10 male and 10 female Sprague-Dawley rats were exposed to 0, 5000, 15000 and 50000 ppm (0, 24544, 73632 and 245440 mg/m3) HFC 125 (6 hrs/day, 5 days/week).  Additional groups of 10 male and 10 female rats were designated for a 4-week recovery period (Nakayama et al., 1993).  No mortality was found at any dose. There were no treatment-related clinical signs of toxicity or significant differences in body weight gains and food consumption among the control and the treated groups. No statistical differences were observed in haematology, blood biochemistry and urinalysis, in organ weights and in peroxisomal beta-oxidation activities.  No treatment-related changes were observed during the gross pathology and histopathological examinations. 50000 ppm, was considered the NOAEC for this study.

No chronic toxicity study is available. However, the long-term repeated toxicity study can be waived in accordance with Column 2 of REACH Annex X, since:

- no serious or severe effects were observed in the available subacute and subchronic studies up to 50000 ppm v/v;

- the occurrence of toxic effects following chronic exposure to HFC 125 is not to be expected.

- no dangerous properties not detected in the 90-day study are to be expected.

Justification for classification or non-classification

No sign of toxicity observed up to 50000 ppm (245440 mg/m3). No Classification is warranted.