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

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3,4-tetrachloro-1,1,2,3,4,4-hexafluorobutane

EC Number:

938-148-1

Cas Number:

375-45-1

Molecular formula:

C4Cl4F6

IUPAC Name:

1,2,3,4-tetrachloro-1,1,2,3,4,4-hexafluorobutane

Details on test material:

- Name of test material (as cited in study report): A1112 Dimer
- Substance type: pure substance
- Physical state: liquid
- Analytical purity: 99%
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: 99% pure substance
- Isomers composition: not applicable
- Purity test date: not reported
- Lot/batch No.: DAD 619
- Expiration date of the lot/batch: 2005

- Storage condition of test material: ambient temperature in the dark

Test animals

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.

Administration / exposure

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.

Results and discussion

Preliminary study:

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

Effect levels

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

Applicant's summary and conclusion

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.