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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Other information : Only secondary literature with no details on test conditions and on results.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Remarks:
Only secondary literature with no details on test conditions and on results.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute inhalation toxicity
GLP compliance:
no
Remarks:
Study performed before GLP compliance
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
no details available
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
no details
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no details
Duration of treatment / exposure:
6 hours/day for 4 weeks (5 days/week)
Frequency of treatment:
daily
Dose / conc.:
0 ppm
Dose / conc.:
10 ppm
Dose / conc.:
50 ppm
Dose / conc.:
150 ppm
No. of animals per sex per dose:
no data
Control animals:
yes
Details on study design:
- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no data
- Post-exposure recovery period in satellite groups: the remaining males were allowed to recover from TFE exposure for about 10 days, and then each was supplied with a different female each week for 5 week, and conception rates were measured.
- Section schedule rationale (if not random): no data
Positive control:
no data
Observations and examinations performed and frequency:
No data
CAGE SIDE OBSERVATIONS: No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data

BODY WEIGHT: Yes
- Time schedule for examinations: no data

FOOD CONSUMPTION: no data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY: no data
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: No data
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood:
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER: effect on reproductive function (see details below)
Sacrifice and pathology:
After 2 and 4 weeks exposure some of the males were sacrificed. All females were sacrificed after 4 weeks.
Other examinations:
effect on reproductive function: testis weight, spermatogenesis, ovary weight, histology of 26 tissues (no details on type of tissues examined), conception rate.
Statistics:
no data
Clinical signs:
no effects observed
Description (incidence and severity):
No differences in appearance or behavior among any of the four groups of animals were observed.
Mortality:
no mortality observed
Description (incidence):
No death during or after exposure and no differences in appearance or behavior among any of the four groups of animals were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Although there was no statistically significant decrease in body weight for any group of males after 4 weeks, subgroups exposed to 50 and 150 ppm of trifluoroethanol were significantly lighter than a control subgroup, which indicated that weight loss for the highly exposed groups was of borderline significance.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
The male rats exposed to 150 ppm of Trifluoroethanol for 2 or 4 weeks had lowered mean testis weights and testis weight/body weight ratios. After 4 weeks of exposure to the test item, male rats exposed to 50 ppm also had decreased testis weights.
Treated females had elevated ovary weights relative to controls, but the difference was significant only for the group exposed to 10 ppm of test item. The ovary weight/body weight ratio increased by similar amounts for all non-control groups, but the increase for rats exposed to 150 ppm was not significant although it was nearly as high as for the other two non-control groups. Thus the gain in ovary weight due to test item appears to be of borderline statistical significance. It occurs rather sharply between 0 and 10 ppm and levels off for higher concentrations.
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Histology of ovary revealed no differences in apperance attributable to the test item. Other tissues (26 types in all) from both males and females did not appear different from those of controls.
Among males sacrificed after both 2 and 4 weeks, those exposed to 50 ppm showed impairment of spermatogenesis and those exposed to 150 ppm showed hypospermatogenesis
Histopathological findings: neoplastic:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
In functional tests, the remaining males were allowed to recover from 2,2,2-trifluoroethanol for about 10 days, and then each was supplied with a different female each week for 5 weeks, and conception rates were measured. For group exposed to 10 ppm, the rate was the same as for controls; for the males exposed to 50 ppm, it was 72% that of controls; and for the group exposed to 150 ppm, no conception occured. For the group exposed to 50 ppm, conception rates were lower than for controls during the first 3 weeks, reaching a minimum during the second week, and preimplantation losses followed an analogous pattern. Males were sacrificed 2 weeks later (for a total recovery period of 57 days) and their testes examined. Males exposed to 50 ppm showed normal spermatogenesis. Males exposed to 150 ppm also showed some recovery and some normal spermatogenesis.
Critical effects observed:
yes
Lowest effective dose / conc.:
150 ppm
System:
male reproductive system
Organ:
seminiferous tubules
testes
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

No other information

Conclusions:
Under the test conditions, a repeated inhalation exposure to 50 and 150 ppm of 2,2,2 trifluoroethanol caused body weight loss of male rats. The treated animals presented also effects on the reproductive systems: decrease of testis weight in male rats, and increase of ovary weight in females. The conception rates were decreased in males exposed to 50 and 150 ppm.
Executive summary:

In a subacute inhalation toxicity study, rats (male and female) were exposed to 0, 10, 50 and 150 ppm of 2,2,2-trifluoroethanol for 6 hours per day, for a period of 4 weeks (5 days/week). There is no detailed information on the exposure conditions, the number of animals in each group, the composition of the test item. The results are also not detailed (Kr.4).

Under the test conditions, a repeated inhalation exposure to 50 and 150 ppm of 2,2,2 trifluoroethanol caused body weight loss of male rats. The treated animals presented also effects on the reproductive systems: decrease of testis weight in male rats, and increase of ovary weight in females. The conception rates were decreased in males exposed to 50 and 150 ppm.

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a functional tests derived from a repeated dose study inhalation, in which male rats were exposed to 0, 10, 50 and 150 ppm concentations of TFE for 6h/day, 5d/week for 4 weeks, some males were allowed to recover from 2,2,2-trifluoroethanol for about 10 days, and then each was supplied with a different non exposed female each week for 5 weeks and then the conception rates were measured.

GLP compliance:
no
Remarks:
Study performed before GLP compliance
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trifluoroethanol, Fluorinol-85 or Fluorinol-50
- Physical state: colorless liquid
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: assumed to be stable during the test (sponsor responsibility)
- Storage condition of test material: no data
- Other: manufactured by Halocarbon Products Corporation

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
no detail availbale

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
not specified
Remarks on MMAD:
No data
Vehicle:
not specified
Details on exposure:
No details
Details on mating procedure:
Male rats were exposed to 0, 10, 50 and 150 ppm concentations of TFE for 6h/day, 5d/week for 4 weeks. Some males were allowed to recover from 2,2,2-trifluoroethanol exposure for about 10 days, and then each was supplied with a different non exposed female each week for 5 weeks and then the conception rates were measured.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No details
Duration of treatment / exposure:
6h/day, 5day/week for 4 week
Frequency of treatment:
5 day/week
Details on study schedule:
No data
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Dose / conc.:
10 ppm
Dose / conc.:
50 ppm
Dose / conc.:
150 ppm
No. of animals per sex per dose:
No data
Control animals:
yes, concurrent no treatment
Details on study design:
In a functional tests derived from a repeated dose study inhalation, in which male rats were exposed to 0, 10, 50 and 150 ppm concentations of TFE for 6h/day, 5d/week for 4 weeks, some males were allowed to recover from 2,2,2-trifluoroethanol for about 10 days, and then each was supplied with a different non exposed female each week for 5 weeks and then the conception rates were measured.
Positive control:
No

Examinations

Parental animals: Observations and examinations:
Conception rate
Oestrous cyclicity (parental animals):
see Robust study summary "Rep. Dose tox. Inh. V4 1978b SILB" in Section 7.5.2.
Sperm parameters (parental animals):
see Robust study summary "Rep. Dose tox. Inh. V4 1978b SILB" in Section 7.5.2.
Litter observations:
no data
Postmortem examinations (parental animals):
see Robust study summary "Rep. Dose tox. Inh. V4 1978b SILB" in Section 7.5.2.
Postmortem examinations (offspring):
no
Reproductive indices:
Conception rate
Offspring viability indices:
Not examined

Results and discussion

Results: P0 (first parental generation)

Reproductive function / performance (P0)

Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
For group exposed to 10 ppm, the conception rate was the same as for controls; for the males exposed to 50 ppm, it was 72% that of controls; and for the group exposed to 150 ppm, no conception occured. For the group exposed to 50 ppm, conception rates were lower than for controls during the first 3 weeks, reaching a minimum during the second week, and preimplantation losses followed an analogous pattern. Males were sacrificed 2 weeks later (for a total recovery period of 57 days) and their testes examined. Males exposed to 50 ppm showed normal spermatogenesis. Males exposed to 150 ppm also showed some recovery and some normal spermatogenesis.

Effect levels (P0)

Dose descriptor:
NOAEC
Effect level:
10 ppm
Based on:
not specified
Sex:
male
Basis for effect level:
reproductive function (sperm measures)
reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:
yes
Lowest effective dose / conc.:
50 ppm
System:
male reproductive system
Organ:
seminiferous tubules
testes
Treatment related:
yes
Dose response relationship:
yes

Applicant's summary and conclusion

Conclusions:
Conception rate was impaired in male rats pre-treated by repeated inhaltion of TFE at 50 ppm. When male rats were exposed to 150 ppm 6h/day, 5day/week for 4 weeks, no conception occured. When males were sacrificed after a total recovery period of 57 days post exposure for testis examination, rats exposed to 50 ppm showed normal spermatogenesis while rats exposed to 150 ppm showed some recovery and some normal spermatogenesis.