Trifluoro(trifluoromethyl)oxirane

Neurotoxicity

Description of key information

Inhalation: OECD 422; rats. NOAEC = 1000/500 ppm (6800/3400 mg/m3). No statistically significant effects were observed in neurobehavioral parameters examined at the highest concentration tested. Reliability = 1.

Key value for chemical safety assessment

Effect on neurotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: sub-chronic inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 422

Deviations:

yes

Remarks:

Study included FOB and motor activity endpoints

Qualifier:

according to guideline

Guideline:

other: EPA OPPTS 870.3650 (2000)

Deviations:

yes

Remarks:

Study included FOB and motor activity endpoints

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Route of administration:

inhalation: gas

Vehicle:

other: other: filtered and conditioned air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Exposures for males and females were conducted for the 14 day premating period. Subsequently, males and non-pregnant females were exposed through to the terminal sacrifice. Exposures for females with evidence of mating were conducted during the cohabitation period (up to 2 weeks in duration) and during gestation days 0–19. Gestating P1 females were not exposed after gestation day 19.

Premating period - 14 days exposure
Cohabitation - Up to 14 days exposure

Postcohabitation Exposure:
Males - Up to test days 36–37
Females with no evidence of mating - 19 days (approximate)
Gestation - (GD 0-19)
Lactation - No exposure (LD 0-4)

Frequency of treatment:

All exposures were conducted for 6 hours/day, 5 days/week during the premating period. Beginning at the mating (cohabitation) period, exposures were conducted for 6 hours/day, 7 days per week. Lactating dams were not exposed.

Remarks:

Doses / Concentrations:
0, 50, 250, 1000/500 ppm (the high level concentration was reduced to 500 ppm on test day 9 [exposure #7])
Basis:
nominal conc.

No. of animals per sex per dose:

12 animals/sex/dose

Control animals:

yes, concurrent vehicle

Behaviour (functional findings):

effects observed, treatment-related

Details on results:

There were no test substance-related effects or statistically significant differences on forelimb grip strength in either males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects on hindlimb grip strength in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects or statistically significant effects for any behavioral parameter evaluated in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. A test substance-related decrease in total duration of movement and total number of movements was observed in females in the 1000/500 ppm group at the premating evaluation. Although not statistically significant, the decreases were 26% and 25% lower compared to the control values for total duration of movement and total number of movements, respectively. There were no test substance-related or statistically significant effects on duration of movement or number of movements in males exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance.

Refer to Section 7.5.2 Repeated dose toxicity: inhalation: DI.K1.28Day.InhGas.RD/REPRO/DEV.R.D-20964.KD for additional details of repeated dose systemic toxicity findings.  Refer to Section 7.8.1 Toxicity to reproduction: DI.K1.1Gen.Screen.RD/REPRO/DEV.R.D-20964.KD for reproductive toxicity findings.  Refer to Section 7.8.2 Developmental toxicity/teratogenicity: DI.K1.DEV.Screen.RD/REPRO/DEV.R.D-20964.KD for developmental toxicity findings.

Dose descriptor:

NOEC

Remarks:

neurobehavioural

Effect level:

250 ppm (nominal)

Sex:

female

Basis for effect level:

other: Test substance-related decreases in motor activity were observed in 1000/500 ppm females.

Remarks on result:

other:

Dose descriptor:

NOEC

Remarks:

neurobehavioural

Effect level:

>= 500 ppm (nominal)

Sex:

male

Basis for effect level:

other: No effects were observed at 100/500 ppm, the highest concentration tested.

Remarks on result:

other:

Conclusions:

Test substance-related decreases in motor activity were observed in 1000/500 ppm females.

Executive summary:

A combined repeated dose toxicity study with reproduction/developmental toxicity screening test was conducted with the test substance. Crl:CD(SD) rats (12/sex/concentration) were exposed whole body to 0, 50, 250, or 1000/500 ppm. Due to excessive toxicity, the 1000 ppm concentration was reduced to 500 ppm beginning on exposure 7 (test day 9).  Exposures for males and females were conducted for 6 hours per day, 5 days per week from the initiation of the study through the 14 day premating period.  Subsequently, males and non-pregnant females were exposed 7 days a week through the terminal sacrifice.  Exposures for females with evidence of mating were conducted for 6 hours per day, 7 days per week during the cohabitation period (up to 2 weeks in duration) and during gestation days 0–19.  Gestating P1 females were not exposed after gestation day 19. An abbreviated neurobehavioral evaluation consisting of a functional observational battery and motor activity was conducted in P1 rats (12/sex/group) once during pretest and prior to cohabitation.  Clinical pathology parameters were measured in P1 rats (5/sex/group) at the end of the premating period (hematology, clinical chemistry) and at terminal sacrifice (coagulation).  All P1 rats were given a gross pathological examination and selected tissues were weighed and collected from all adult rats.

There were no test substance-related effects or statistically significant differences on forelimb grip strength in either males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects on hindlimb grip strength in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects or statistically significant effects for any behavioral parameter evaluated in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. A test substance-related decrease in total duration of movement and total number of movements was observed in females in the 1000/500 ppm group at the premating evaluation. Although not statistically significant, the decreases were 26% and 25% lower compared to the control values for total duration of movement and total number of movements, respectively. There were no test substance-related or statistically significant effects on duration of movement or number of movements in males exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

3 400 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

Crl:CD(SD) rats (12/sex/concentration) were exposed whole body to 0, 50, 250, or 1000/500 ppm. Due to excessive toxicity, the 1000 ppm concentration was reduced to 500 ppm beginning on exposure 7 (test day 9). An abbreviated neurobehavioral evaluation consisting of a functional observational battery and motor activity was conducted in P1 rats (12/sex/group) once during pre-test and prior to cohabitation. There were no test substance-related effects or statistically significant differences on forelimb grip strength in either males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects on hindlimb grip strength in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. There were no test substance-related effects or statistically significant effects for any behavioural parameter evaluated in males or females exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance. A non-statistically significant test substance-related decrease in total duration of movement and total number of movements was observed in females in the 1000/500 ppm group at the premating evaluation.There were no test substance-related or statistically significant effects on duration of movement or number of movements in males exposed to inhalation concentrations of 50, 250, or 1000/500 ppm of the test substance.

Justification for classification or non-classification

The test substance did not adversely affect neurobehavioral function. These data do not require classification according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.