Ethane, 1,1,2-trichloro-1-fluoro-2-(trifluoromethoxy)-

Endpoint summary

Description of key information

An oral toxicity study (according to OECD guideline 401)and a dermal toxicity study (according to OECD guideline 402), performed on 1,1,2-tricloro-1-fluoro-2-(trifluoromethoxy)-ethane, are reported. 
According to Regulation EC No. 1272/2008, the substance does not meet the classification criteria for both oral or dermal acute toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 July 1995 to 2 August 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Livestock
- Age at study initiation: 7-9 weeks
- Weight at study initiation: Males: 225-250 g, Female: 200-225 g
- Fasting period before study: 16 hours. Feed was returned to rats three hours after the test article administration.
- Housing: 5 animals/sex/cage in T11 air conditioned room.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Five days before the start of the test. Animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 55 +- 10
- Air changes (per hr): about 20/hour filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 / 12 (7 a.m.- 7 p.m.)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: undiluted
- Amount of vehicle (if gavage): The volume of administration was 1.26 ml/kg in order to obtain the dose of 2000 mg/kg being the density 1.587 g/ml.
- Justification for choice of vehicle: not applicable

MAXIMUM DOSE VOLUME APPLIED: 1.26 mL/Kg bw corrisponding to 2000 dose mg/Kg bw

Doses:

2000 mg/ kg bw

No. of animals per sex per dose:

5 males + 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations of clinical signs: at 30 minutes, 2, 4 and 6 hours on the first day after the administration (day 1) and then twice a day up to termination of the observation period.
- Body weighing: twice pre-trial (at randomization and on day 1 just before administration) and on days 3, 8 and 14. On day 1 the animals were weighted after 16-hour fasting. Volume of administration was based oh day 1 body weight.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology examination.

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the study. The LD50 was not calculated and it was considered higher than 2000mg/kg.

Clinical signs:

other: No clinical signs or behavioral alterations were observed in any animal during the observation period.

Gross pathology:

At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rats.

Other findings:

none.

Interpretation of results:

GHS criteria not met

Remarks:

CLP criteria

Conclusions:

The LD50 of the test article, when administered to rats as a single dose by oral route, is higher than 2000 mg/kg bw.

Executive summary:

 Experimental data from a toxicity study in which Sprague Dawley rats received a single oral administration of the test article at the dosage of 2000 mg/kg bw (5 males and 5 females) are given in this report.

The test method was in accordance with European Economic Community Guidelines B.1 and with OECD guidelines 401.

The test article was administered undiluted at the volume of 1.26 ml/kg in order to give the dose of 2000 mg/kg being the density 1.587 g/ml.

All rats were treated after a 16 hours fasting period. The day of treatment was considered day 1 of the study. The animals were weighted twice before treatment (at randomization and on day 1 just before treatment) and on day 3, 8 and 14. They were clinically observed for 14 days following the treatment. On day 15 all rats were killed (fasted overnight) and submitted to a thorough autopsy.

No animals died during the study. The LD50 was higher than 2000 mg/kg bw.

All treated rats did not show any clinical signs or behavioral alterations during the post-treatment observation period.

Body weight resulted unaffected by treatment.

At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 July 2012 - 22 october 2012

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco (Lecco), Italy
- Date of arrival at the Testing Facilities: 26 July 2012
- Age at the date of arrival: 6 to 8 weeks old
- Weight at the date of arrival: 176 to 200 grams
- Housing: Polysulphone solid bottomed cages measuring 59x38.5x20 cm (during acclimatisation) and 42.5x26.6x18 cm (during the study) with nesting material
- Number of animals/cage: up to 5/cage (during acclimatisation) and individually caged (during study)
- Diet: ad libitum
- Water: Drinking water ad libitum
- Acclimation period: At least 5 days

ALLOCATION TO TREATMENT GROUP:
- Allocation: Random at arrival
- Animal identification: Permanent, following arrival, by a combination of ear notch (units) and tattoo on the hind feet. Males and females were identified by even and odd numbers, respectively.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- A single area was clipped free of hair on the dorsal surfaces of the trunk of each animal (approximately 10% of body surface).
- An aliquot of the supplied test item was spread evenly over an area of approximately 10% of the body surface area. A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.
- After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.

Duration of exposure:

Treatment: once only,for 24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals/sex/group

Control animals:

not required

Details on study design:

IN LIFE OBSERVATIONS:
- Mortality and morbidity: Twice daily.
- Clinical signs: day of dosing (on dosing, approximately 1, 2 and 4 hours after dosing), and daily thereafter (for 14 days)
- Body weight: allocation (Day –1), Days 1, 8 and 15
- Termination: day 15.
- Euthanasia method: Carbon dioxide narcosis.
- Necropsy procedure: Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: No clinical signs were observed in male or female animals after treatment during the observation period.

Gross pathology:

No abnormalities were found at necropsy examination performed on all animals at termination of the study.
No abnormalities were observed on the treated site of any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item, TRICHLOROETHYLIC ADDUCT was assessed in an acute dermal toxicity in rats according to the OECD guideline 402.
The test item has no toxic effect in the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg.
The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Executive summary:

The acute toxicity of TRICHLOROETHYLIC ADDUCT was investigated following dermal administration of a single dose to the rat, and according to the OECD guideline 402.

A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no clinical signs were observed in male or female animals during the observation period.

The body weight changes observed during the study were within the expected range for this species and age of animals.

No abnormalities were found at necropsy in the animals at termination of the study.

No abnormalities were observed at the treated site.

These results indicate that the test item, TRICHLOROETHYLIC ADDUCT, has no toxic effect in the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

No mortality or clinical signs were observed in rats at the limit dose of 2000 mg/kg bw in reliable acute oral and dermal toxicity studies. According to Regulation EC No. 1272/2008, the substance does not meet the classification criteria for both oral and dermal acute toxicity.