2-Butene, 1,1,1,4,4,4-hexafluoro-, (2Z)-

Endpoint summary

Description of key information

Inhalation: OECD 413; rats. NOAEC = 5000 ppm  (33548 mg/m3) in males based on test substance-related reductions in body weight and food consumption at 7500 ppm, and 7500 ppm (50322 mg/m3) in females based on no effects observed at the highest concentration tested. Reliability = 1.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

33 548 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

33 548 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Male and female rats were exposed whole body, 6 hours per day, 5 days per week to 0, 3000, 4000, 5000 or 7500 ppm of the test substance over a 90 day period for a total of 65 exposures. Test substance-related adverse effects on body weight and food consumption were observed in male rats exposed to 7500 ppm. Test substance-related, but non-adverse microscopic findings, were observed in the teeth and femur/knee joints of all male and female rats exposed to the test substance. These changes included incomplete decalcification of enamel in the distal region of the upper incisors; no changes in ameloblasts or dentition were observed in the affected animals. Incomplete decalcification of bone trabeculae in the femur was also present in all males exposed but only in females exposed to 7500 ppm; osteoclasts and osteoblasts were morphologically normal. These microscopic findings are consistent with exposure to a fluorine-containing test substance and were not associated with any histopathological changes suggestive of tissue injury or adverse functional consequences in these tissues and, therefore, were not considered to be adverse. The diagnosis of incomplete decalcification refers to a tissue processing phenomenon indicating that metabolism of the parent material includes production of a free fluoride. Thus, “incomplete decalcification” in this and the supporting 90-day study is not a lesion per se but evidence of fluoride exposure. The conclusion of non-adversity for the teeth and bone observations noted in both 90-day studies was based upon the absence of any clinical (abnormal growth or mottling of teeth) or morphological (damage to bone or tooth structure or degeneration of bone/teeth forming cells) changes suggestive of injury or loss of function of these tissues. Under the conditions of this study, the no-observed-adverse-effect-concentration (NOAEC) for the test substance in male rats was 5000 ppm (33548 mg/m³) based upon test substance-related reductions in body weights and food consumption observed in animals exposed to 7500 ppm. The NOAEC for female rats was 7500 ppm (50322 mg/m³), the highest exposure concentration tested in this study.   

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
OECD guideline, GLP study

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
OECD guideline, GLP study

Justification for classification or non-classification

The NOAEC in male and female rats exposed in a 90-day repeat inhalation toxicity study was 5000 ppm (33548 mg/m³) and 7500 ppm (50322 mg/m³), respectively. Therefore, the substance does not need to be classified for repeated dose toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.