Hexafluoropropene, oxidized, oligomers, reduced, fluorinated

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 March 1992 to 9 April 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexafluoropropene, oxidized, oligomers, reduced, fluorinated

EC Number:

500-537-5

EC Name:

Hexafluoropropene, oxidized, oligomers, reduced, fluorinated

Cas Number:

161075-00-9

Molecular formula:

R-O(C3F6O)m-R with R= - CF3, - C2F5, -CF2H

IUPAC Name:

1,1,1,2,3,3-hexafluoro-2,3-bis(1,1,2,2,2-pentafluoroethoxy)propane; 1,1,1,2,3,3-hexafluoro-2-(1,1,2,2,2-pentafluoroethoxy)-3-(trifluoromethoxy)propane; 1,1,1,2,3,3-hexafluoro-3-(1,1,2,2,2-pentafluoroethoxy)-2-(trifluoromethoxy)propane; 1,1,1,2,3,3-hexafluoro-3-{[1,1,1,2,3,3-hexafluoro-3-(trifluoromethoxy)propan-2-yl]oxy}-2-(trifluoromethoxy)propane; 1,1,1,3,3,4,6,6,7,9,9,10,12,12,12-pentadecafluoro-4,7,10-tris(trifluoromethyl)-2,5,8,11-tetraoxadodecane; 1-(difluoromethoxy)-1,1,2,3,3,3-hexafluoro-2-(1,1,2,2,2-pentafluoroethoxy)propane; 2,2,3,5,5,6-hexafluoro-3,6-bis(trifluoromethyl)-1,4-dioxane; 2-(difluoromethoxy)-1,1,1,2,3,3-hexafluoro-3-(1,1,2,2,2-pentafluoroethoxy)propane

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Galden HT 70
- Substance type: Pure substance
- Physical state: liquid
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: not reported
- Purity test date: not reported
- Lot/batch No.: G 30
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: far from heating sources (volatile)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

-TEST ANIMALS
- Source: livestock farming
- Age at study initiation: about 7-9 weeks
- Weight at study initiation: males: 225-250 g, females: 200-225 g
- Fasting period before study: 16 hours. Feed was returned to rats three hours after the administration of the test article.
- Housing: 5 animals/sex/cage in air-conditioned rooms. Grill cages. Cage size (cm):40.5 x 38.5 x 18
- Diet (e.g. ad libitum): Certificated pelleted diet, supplied with vitamins and trace elements. Available ad libitum
- Water (e.g. ad libitum): from municipal water main system, filtered and disrtibuted ad libitum.
- Acclimation period: at least 5 days before the strat of the test. Animals were observed daily to ascertain their fitness for the study.

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

IN-LIFE DATES: From: 25-MAR-1992 To: 9-APR-1992

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose 400 cps water solution, containing 0.4% Polysorbate 80.

Details on oral exposure:

VEHICLE: no details

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

Doses:

2000 mg/kg
5000 mg/kg

No. of animals per sex per dose:

10 (5 males + 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Observation of clinical signs and mortality were performed after 30 minutes, 2, 4 and 6 hours on the first day after the administration and then twice a day up to the termination of the observastion period.
Body weight was detected twice pre-trial (at randomization and on day 1 just before treatment) and on days 3, 8 and 14.
On day 1 the animals were weighted after a 16-hour fasting.
Volume of administration was based on day 1 body weight.

- Necropsy of survivors performed: yes.

- Other examinations performed: clinical signs, body weight, gross pathology at post mortem examination.

Statistics:

Calculation of LD 50 was not possible.

Results and discussion

Preliminary study:

not relevant

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No animals died during the observation period.

Clinical signs:

other: Only piloerection was observed in some treated animals starting from 30 minutes and lasting up to 6 hours. Recovery of all animals was achieved within day 2 of the study.

Gross pathology:

The autoptic examination performed on animals killed at the end of the study did not show any change.

Other findings:

none

Any other information on results incl. tables

CLINICAL SIGNS FREQUENCY (Cumulative)

 

Table a

No. Rats treated:5 males + 5 females
Dose: 2000 mg/kg
Clinical signs	Number of rats affected	Signs observed (time)
		from	to
Piloerection	4	30 minutes	4 hours
Recovery	4	6 hours

 

Table b

No. Rats treated:5 males + 5 females
Dose: 5000 mg/kg
Clinical signs	Number of rats affected	Signs observed (time)
		from	to
Piloerection	4	30 minutes	6 hours
Recovery	4	day  2

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental consitions applied in this study, GALDEN LMW showed an LD50 higher than 5000 mg/kg when administered by oral route to rats. Only transient piloerection was noted in some treated animals.

Executive summary:

The purpose of the study was to evaluate the acute toxicity of the test article GALDEN LMW and to determine the LD 50, its statistical limits and slope, if possible.

The test method was in accordance with OECD guideline 401 (Paris, 1981) and subsequent revisions.

The test article was suspended in 0.5% Methylcellulose 400 cps water solution plus 0.4% Polysorbate 80.

The animals were weighed twice before the trial (at randomization and on day 1 just before treatment) and on day 3, 8 and 14. They were clinically observed for 14 days following administration and killed at the end of the study by excision of the femoral arteries after i.p. overdosage injection of 5% sodium pentobarbital.

A throughout autoptic examination was performed on animals killed at the end of the observation period.

No deaths occurred as consequence of GALDEN LMW oral administration at the dosages applied in this study.

Only piloerection was observed in some animals treated with both dose levels starting from 30 minutes and lasting up to 6 hours.

Recovery of all animals was achieved within 24 hours from treatment.

The body weight gain appeared normal.

At the gross pathology examination no drug-related changes were seen.

In conclusion the test test article GALDEN LMW when administered by oral route to rats under the experimental conditions applied in this study, showed an LD50 higher than 5000 mg/kg.