Butane, 1,2,3,4-tetrachloro-1,1,2,3,4,4-hexafluoro-

Endpoint summary

Description of key information

Acute oral toxicity study (OECD guideline 420, GLP): rat LD50 > 2000 mg/kg, no mortality, no clinical signs
Acute dermal toxicity study (OECD guideline 402, GLP): rat LD50 > 2000 mg/kg, no mortality, no remarkable clinical signs

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:

16 January 2003 to 26 June 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

other: Alpk:APfSD (Wistar-derived)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rodend Breeding Unit, Alderley Park, Macclesflied, Cheshire, UK.
- Age at study initiation: Approximately 8-12 weeks.
- Weight at study initiation: 176-235 gr.
- Fasting period before study: overnight immadiately prir to the start of dosing
- Housing: a maximum of 4 rats were housed per cage, in cages suitable for animals of this strain and weight range expected during the course of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: the animals were housed under the experimental conditions for at least 5 days prior to the start of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 22+/-3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): a minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): artificial, giving 12 hours light and 12 hours dark.

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

laboratory test substance reference number: Y00790/014

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mg/bw

DOSAGE PREPARATION: a measured amount of the test substance was formulated in corn oil and was thoroughly mixed.

- Rationale for the selection of the starting dose:
the main phase was preceded by a sighting phase. Initially, a single female was dosed with 300 mg/Kg bw of the test substance. The animal survived and showed no evident toxicity. To further investigate potential toxicity, an additional female was dosed with 2000 mg/kg bw. The animal survived and showed no evident toxicity. Based on information from the sighting phase, the fixed dose level for the main phase was selected as 2000 mg/kg bw.

Doses:

Sighting phase: 300 mg/kg, 2000 mg/kg;
Main phase: 2000mg/kg

No. of animals per sex per dose:

300 mg/Kg: 1
2000 mg/kg: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: prior to dosing, all rats were examined to ensure that they were physically normal and behaved normally. The animals were observed for signs of systemic toxicity at least twice following dosing on day 1. Subsequent observations were made daily, up to day 15. The animal were weighted prior to fasting on the day before dosing (day -1), immediately before dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: Animal used for the sighting phase were not examined post mortem. All animals used for the main phase were examined post mortem.

The post mortem examination involved an external observation and an examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.

Preliminary study:

Following a dose of 300 mg/kg bw to one female, the animal survived an showed no signs of evident toxicity.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

no mortality was observed following a dose of 300 or 2000 mg/kg bw.

Clinical signs:

other: no signs of evident toxicity were observed following a dose of 300 or 2000 mg/kg bw.

Body weight:

other body weight observations

Remarks:

All animals treated with 2000 mg/kg showed an overall body weight gain during the study

Gross pathology:

no macroscopic abnormalities

Other findings:

none

Interpretation of results:

GHS criteria not met

Conclusions:

The highest fixed dose of 1,2,3,4-tetrachloro-1,1,2,3,4,4-hexafluorobutane administred in this test without causing any lethality (i.e. discriminating dose-level) was 2000 mg/kg to female rats.

Executive summary:

The study has been conducted in accordance with OECD 420 guideline: Acute Oral Toxicity - Fixed Dose procedure.

Dose-levels are chosen from a number of pre-set doses, taking into account the known toxicity of the test substance.

In a sighting ohase, two female rats received a single oral dose of 300 or 2000 mg/kg of 1,2,3,4-tetrachloro-hexafluorobutane and were assessed daily for the following 14 days for any signs of systemic toxicity.

From the results of the sighting phase of the study, a single fixed dose level of 2000 mg/kg was selected for the main phase of the study.

In the main phase, a group of four female Alpk:APfSD (Winstar-derived) rats was dosed and assessed daily for the following 14 days for any signs of systemic toxicity. Their bodyweights were recordered at intervals during the study. At the end of the study all the animals were killed and examinated post mortem. The initial female dosed with 2000mg/kg was included in the main phase of the study, to give a total group size of five animals.

Following a dose of 300mg/kg to one female rat, the animal survived and showed no evident toxicity. The animal showed an overall bodyweight gain during the study. There were no macroscopic abnormalities at examination post mortem.

Following a dose of 2000mg/kg to five females rats, none of the animals died and there was no evident toxicity. All animals showed an overall bodyweight gain during the study. There were no macroscopic abnormalities at examinationpost mortem.

The highest fixed dose of 1,2,3,4-tetrachloro-hexafluorobutane administred in this test without causing any lethality was 2000 mg/kg to female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

16 January 2003 to 26 June 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Alpk:APfSD (Wistar-derived)

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight, macroscopic examination

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality observed

Body weight:

other body weight observations

Remarks:

All the males and 4 females gained weight during the study. One female lost weight throughout the study (-6,5% compared to initial bw) Mean body weights were increased at the end of the observation period.

Gross pathology:

no abnormalities at macroscopic examination.
One male had pelvic dilatation of the kidney and a speckled thymus. As these are common spontaneous findings they were considered incidental.

Other findings:

the tests substance stained the skin brown on all animals following application.
Signs of slight skin irritation were seen in all animals, but cleared by day 13.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose of 1,2,3,4-tetrachloro-hexafluorobutane is estimated to be in excess of 2000mg/kg to male and female.

Executive summary:

A group of five males and five female Alpk: APfSD (Wistar-derived) rats received a single dermal application of 2000 mg/kg of 1,2,3,4-tetrachloro-hexafluorobutane.

The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals during the study. At the end of the study all the animals were killed and examinated post mortem.

None of the animals died and there were no signs of systemic toxicity. All animals gained weight throughout the study. Signs of slight skin irritation were seen in three males and all females but it had completely resolved within 9 days. There were no macroscopic abnormalities at examination post mortem.

The acute dermal median lethal dose of 1,2,3,4-tetrachloro-hexafluorobutane is estimated to be in excess of 2000mg/kg to male and female.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

An oral toxicity study, performed on the test item 1,2,3,4 -tetrachloro-hexafluorobutane according to OECD guideline 420, and a dermal toxicity study, performed according to OECD guideline 402, are reported.

In the oral acute toxicity study, the highest fixed dose of 1,2,3,4 -tetrachloro-hexafluorobutane administered to female rats without causing any lethality was 2000 mg/kg.

The acute dermal median lethal dose of 1,2,3,4 -tetrachloro-hexafluorobutane was estimated to be in excess of 2000mg/kg to male and female rats.

Justification for classification or non-classification

According to Regulation EC No. 1272/2008, the substance does not meet the classification criteria for oral and dermal acute toxicity.