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Administrative data

Description of key information

In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day. Duration of administration was 42 days for males and 42-52 days for females.
As a result, NOAEL of PHF was judged to be 60 mg/kg/day since a death in female, clinical signs attributed to central nervous system depression and anesthetic action, decreased body weight and irritative changes in the gastrointestinal tract (chiefly in duodenal mucosa) were observed in both sexes at 300 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
60 mg/kg bw/day
Study duration:
subacute
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day.  Duration of administration was 42 days for males and 42-52 days for females.

As a result, treatment-related changes were chiefly observed at 300 mg/kg. At the dose, clinical signs attributed to central nervous system (CNS) depression and anesthetic action were observed in both sexes, and one of the females died during the delivery following administration on day 24 of gestation. Prior to death, signs of CNS depression were also observed in this dead animal.

In females at 300 mg/kg, body weight and food consumption decreased or tended to decrease in the late of gestation until day 4 of lactation. The body weight of males in this group tended to decrease late in the administration period, but recovered during the recovery period. In addition, food consumption was comparable to that of the control group during the administration period, but it decreased during the recovery period. In the 300 mg/kg group, one male showed erosion of duodenal mucosa and the dead female revealed erosion with hemorrhage in the fundic mucosa and erosion of the duodenal mucosa with hypertrophy of the duodenal glands. According the material safety data sheet, PHF is categorized into corrosive substance. Therefore, erosion in the stomach and duodenal mucosa was considered to be caused by irritability of the test substance.

At 300 mg/kg, hypertrophy of centrilobular hepatocytes was observed in both sexes and liver weight was increased in males at 300 mg/kg. Since there were no fatty degeneration or any increases in liver enzymes indicating liver damage, and it was a reversible change, it was considered to be an adaptive change.

Increased triglyceride was found in the male groups at 60 mg/kg or higher and one female 300 mg/kg. Although relation of the change with the treatment was not clear, it was reversible and not accompanied by any histopathological changes, therefore it was considered not significant.

From the above results, NOAEL for repeated dose toxicity of PHF was judged to be 60 mg/kg/day for males and females based on a death in females, clinical signs attributed to CNS depression and anesthetic action, decreased body weight and irritative changes in the gastrointestinal tract (chiefly in duodenal mucosa) observed in both sexes at 300 mg/kg/day.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: duodenum; neurologic: central nervous system

Justification for classification or non-classification

Duration of treatment for repeated dose toxicity study of PHF with rats was about half of 90 days (42 days for males and 42 -52 days for females). Thus, guidance value for STOT classified into Category 2 is considered to be 20 mg/kg/day < ED <= 200 ma/kg/day. In this repeated dose study, effective dose (LOAEL) was concluded to be 300 mg/kg/day. Since the effective dose is above the guidance value, PHF is not classified for STOT.