Trifluoromethane

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

A group of 20 male and 20 female rats were exposed 6 hours/day for 90 days to 0 or 10000 ppm FKW 23 (also known as HFC-23). The following parameters were assessed: feces, food and water consumption, body weight gain, haematology, clinical biochemistry, urinalysis, sight, hearing, and dentition. Macroscopic and histologic pathologic examinations were performed.

Testing procedures were according to "Principles and Procedures for Evaluating the Toxicity of Household Substance", IV, page 14-19, publication 1138, National Academy of Science - National Research Council, Washington DC, 1984.

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S. Ivanovas GmbH & Co.
- Age at study initiation: 37 days for the males, 39 days for the females
- Weight at study initiation: Between 100 - 105 g
- Fasting period before study: no
- Housing: Animals were kept in groups of 3 or 2 in Macrolon cages (type III)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/- 0.5 deg C (maximum range)
- Humidity (%): 60% +/-3% (maximum range)
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

All this data came from the report not the publication

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION: Air/gas mixture was drawn by shunts from the exposure chamber and was verified via gas chromatography. In preliminary testing, it was checked that a complete and even distribution in the air-flow through the exposure chamber wsa ensured.
- Exposure apparatus: exposure chamber was 3 m3 (length: 3m, width: 1 m, height: 1 m)
- Method of holding animals in test chamber: Macrolon cages of the whole group were transferred to the exposure chamber
- Source and rate of air: Compressed air supply
- Method of conditioning air: Air cleaning with potassium dichromatesulphuric acid, sodium hydroxide, glass wool, and calcium chloride
- System of generating particulates/aerosols: not reported
- Temperature, humidity, pressure in air chamber: 21+/-3 deg C
- Air flow rate: not reported
- Air change rate: not reported
- Method of particle size determination: not reported
- Treatment of exhaust air: not reported

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography.
- Samples taken from breathing zone: yes.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analytical verification was done via gas chromatography. Samples were obtained before the exposure period, and then at intervals of 1 hour until exposure ended. Immediate correction was made if the concentration differed 3% from the nominal values of 10,000 ppm by volume of air.

Duration of treatment / exposure:

90 days

Frequency of treatment:

6 hours/day

Remarks:

Doses / Concentrations:
0
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
10000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

20 per dose/sex

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): not reported

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Once a week (on the same day and at the same time of day)

FOOD CONSUMPTION: Yes
- Time schedule for examinations: Estimated daily by weighing residue (at the same time of day). Presence or absence of feces was noted.

FOOD EFFICIENCY: No

WATER CONSUMPTION: Yes, Intake of drinking water was noted.

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:

HAEMATOLOGY: Yes
- Time schedule for collection of blood: After 13 weeks of treatment
- Anaesthetic used for blood collection: Yes, blood was drawn under light ether anesthesia from the retrobulbar venous plexus
- Animals fasted: No data
- How many animals: all animals
- Parameters checked in Table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Before the first exposure, after 7 test days as well as after 6 and 13 weeks of treatment
- Animals fasted: No data
- How many animals: all animals
- Parameters checked in Table No.2 were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: After 13 weeks of treatment
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked in Table 2 were examined.

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: After 13 weeks of treatment, auditory acuty was checked with a simple noise test. Dentition was inspected.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see Table 3)
HISTOPATHOLOGY: Yes (see Table 3)

Statistics:

Analysis of variance and Student's t-test were carried out. Limit for significance was p <= 0.01.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: No changes were observed in the behavior of the rats administered FKW 23. There were no differences in the external appearance of experimental and control animals. None of the rats died prematurely. Feces appeared normal.

BODY WEIGHT: Body weights were not affected by test substance adminstration.

FOOD CONSUMPTION: Food consumption wsa within the normal range during the entire administration period of 3 months.

WATER CONSUMPTION: Intake of drinking water seemed normal.

OPHTHALMOSCOPIC EXAMINATION: No pathological findings were observed in the eyes of rats after 3 months of administration of HFC 23 by inhalation.

HAEMATOLOGY: After 3 months' administration of HFC 23 by inhalation, the blood picture (haemoglobin, erythrocyte-, leucocyte- and differential count) showed no changes. The determination of haematocrit value, blood clotting time and methaemoglobin as well as reticulocyte- and platelet count revealed no pathological findings. HEINZ bodies were not detected.

CLINICAL CHEMISTRY: During and/or after 3 months of treatment with HFC 23 by inhalation, normal serum levels were found for glucose, total bilirubin and protein, blood urea, sodium, potassium, chloride, calcium, uric acid, creatinine, total cholesterol and total lipids. The activity of the serum alkaline phosphatase (AP) and glutamic oxalo-acetc transaminase (GOT) was not increased. This can also be said for the serum gluatmic pyruvic transaminase (GPT); a significantly increased value in the males on test day 7 was not confirmed in the females or at later dates; according to the experience of the laboratory, this finding wsa classified as an incidental finding. Neither electrophoresis of the serum proteins nor bromsulphthalein test showed definate signs of intolerance phenomena.

URINALYSIS: After treatment of 3 months with HFC 23, no pathological changes which might be attributed to the test chemical were detected in the composition of the urine. Leucocytes in the sediment of one animal were attributed to the sphere of spontaneous pathology.

ORGAN WEIGHTS: The only significant difference was in the thyroid of the females, this organ being reduced in both absolute and relative terms. According to the experience of the laboratory, this finding was said to be without meaning.

HISTOPATHOLOGY: Histology revealed no pathological changes attributable to HFC 23. Areas of focal over-inflation were found to the same extent in the lungs of both experimental and control rats. Individual changes in other organs were regarded as belonging to the domain of spontaneous pathology.

OTHER FINDINGS: A simple noise test did not indicate any impairment of auditory acuity. Dentition was free from pathological changes.

Dose descriptor:

LOAEL

Effect level:

> 10 000 ppm

Sex:

male/female

Basis for effect level:

other: No adverse effects were noted at the highest level tested.

Dose descriptor:

NOAEL

Effect level:

10 000 ppm

Sex:

male/female

Basis for effect level:

other: No adverse effects were noted at the highest level tested.

Critical effects observed:

not specified

No adverse effects were noted in any of the parameters assessed. Histologic examination revealed no compound-related pathologic changes.

Conclusions:

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

No adverse effects were noted in any of the parameters assessed. Histologic examination revealed no compound-related pathologic changes.

Executive summary:

A group of 20 male and 20 female rats were exposed 6 hours/day for 90 days to 0 or 10000 ppm HFC-23. The following parameters were assessed: feces, food and water consumption, body weight gain, haematology, clinical biochemistry, urinalysis, sight, hearing, and dentition. Macroscopic and histologic pathologic examinations were performed. No adverse effects were noted in any of the parameters assessed. Histologic examination revealed no compound-related pathologic changes. The LOAEL and NOAEL were > 10000 ppm HFC-23 (the highest dose tested).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

28 634 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

In a K2 inhalation study, groups of male and female rats were administered the substance at doses of 0 or 10000 ppm by inhalation for approximately 90 days. No substance-related adverse toxicity was observed in male or female rats. Under the conditions of the study, the no-observed-adverse-effect-level (NOAEL) for the substance was 10000 ppm, the highest concentration tested.

An additional 90-day inhalation study was conducted in male and female Beagle dogs at doses of 0 or 5000 ppm. No substance-related adverse toxicity was observed in male or female dogs. Under the conditions of the study, the no-observed-adverse-effect-level (NOAEL) for the substance was 5000 ppm, the highest concentration tested.

Justification for classification or non-classification

Based on the lack of adverse effects up to concentrations of 10000 ppm (28634 mg/m³) in rats and 5000 ppm (14317 mg/m³) in dogs in repeated dose inhalation studies, 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.