Propane, 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 March 2004 to 01 March 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline-conform study under GLP without deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)propane

EC Number:

609-534-4

Cas Number:

382-26-3

Molecular formula:

C5H4F8O

IUPAC Name:

1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)propane

Details on test material:

- Name of test material (as cited in study report):Octafluoroisobutyl methyl ether
- Substance type: pure substance
- Physical state: liquid
- Analytical purity: > 86%
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: n.a.
- Purity test date: not reported
- Lot/batch No.: 161 (20/01/04)
- Expiration date of the lot/batch: 2006
- Storage condition of test material: in original, tighly closed container, in a refrigerator at approximately 4°C (accepted range 2 - 8°C), protected from direct sunlight. During atmosphere generation for Dose Group 4, the test item supply reservoir was cooled in water ice.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Sampling of test atmosphere was performed 4 times during the inhalation exposure period of groups 1, 2, 3 and twice during the inhalation exposure period of group 4. Samples were analyzed by GC-MS.

Duration of exposure:

4 h

Concentrations:

ca. 20 mg/L air (19.63 mg/L air)
ca. 2 mg/L air (2.197 mg/L air)
ca. 0.5 mg/L air (0.827 mg/L air)
ca. 0.2 mg/L air (0.178 mg/L air)

No. of animals per sex per dose:

10 (5 males + 5 females)

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.06 mg/L air

Based on:

act. ingr.

95% CL:

> 0.64 - < 2.42

Exp. duration:

4 h

Any other information on results incl. tables

For calculation of the LC50 estimates, mean chemically determined concentrations of the test item in the test atmosphere samples of Group 1 (0.178 mg/L air), Group 2 (0.827 mg/L air), Group 3 (2.197 mg/L air) were used. The no toxic effect level was set at 0.178 mg/L air, as there were no deaths, no clinical signs and no macroscopic pathology findings at this atmosphere concentration.

One of ten animals died in Group 2 (0.827 mg/L air) and all animals died in Group 3 (2.197 mg/L air) and 4 (19.63 mg/L air).

Clinical signs were only seen in decedent animals and comprised effects on breathing in Groups 2, 3 and 4, in addition to decreased spontaneous activity, ventral recumbency and ruffled fur in Group 3, and somnolence in Group 4.

Mortality and clinical signs were attributed to treatment with the test item. Whether or not transient retardation in body weight gain or transient body weight losses in several male and female survivoers of Groups 1 and 2 were attributable to the treatment remained unclear.

Necropsy revealed dark red or reddish discoloration of the lungs in the one decedent animal of Group 2 and all animals of Groups 3 and 4, in addition to an isolated grey white focus of 2 mm diameter in the lungs of the one affected animal of Group 2.A relationship of the finding of lung discoloration to treatment remained unclear. The single incidence of an isolated grey white focus was not attributed to the treatment.

There was no indication of relevant sex-related differences in toxicity of the test item.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The LC50 of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane for acute inhalation toxicity (4h) in male and female rats observed for a period of 15 days was estimated to be:
LC50 = 1.06 mg/L air (0.64 - 2.42 mg/L air)

Executive summary:

The study has been conducted in accordance with OECD 403 guideline Acute Inhalation toxicity.

Four groups, each of five male and five female Wistar rats, were treated with nebulized Octafluoroisobutyl Methyl Ether at concentration of ca. 20 mg/L air, ca. 2 mg/L air, ca. 0.5 mg/L air mg/kg, ca. 0.2 mg/L air.

Calculation of the saturation point of the test item, revealed that virtually all of the test atmosphere was a vapour at any of the atmosphere concentrations tested in the present study.

The following groups were treated and percentage of mortality was observed:

	Analytical Concentration	Mortality    (Both genders)	Mortality (Males Only)	Mortality (Females Only)
GROUP 1	0.178 mg/L air	0 %	0 %	0 %
GROUP 2	0.827 mg/L air	10 %	20 %	0 %
GROUP 3	2.197 mg/L air	100 %	100 %	100 %
GROUP 4	19.63 mg/L air	100 %	100 %	100 %

 

The no toxic effect level was set at 0.178 mg/L air, as there were no deaths, no clinical signs and no macroscopic pathology findings at this atmosphere concentration. One of ten animals died in Group 2 (0.827 mg/L air) and all animals died in Group 3 (2.197 mg/L air) and 4 (19.63 mg/L air). Clinical signs were only seen in decedent animals and comprised effects on breathing in Groups 2, 3 and 4, in addition to decreased spontaneous activity, ventral recumbency and ruffled fur in Group 3, and somnolence in Group 4. Mortality and clinical signs were attributed to treatment with the test item. Whether or not transient retardation in body weight gain or transient body weight losses in several male and female survivoers of Groups 1 and 2 were attributable to the treatment remained unclear. Necropsy revealed dark red or reddish discoloration of the lungs in the one decedent animal of Group 2 and all animals of Groups 3 and 4, in addition to an isolated grey white focus of 2 mm diameter in the lungs of the one affected animal of Group 2.A relationship of the finding of lung discoloration to treatment remained unclear. The single incidence of an isolated grey white focus was not attributed to the treatment. The was no indication of relevant sex-related differences in toxicity of the test item.

The LC50 of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane for acute inhalation toxicity (4h) in male and female rats observed for a period of 15 days was estimated to be:

LC50 = 1.06 mg/L air (0.64 - 2.42 mg/L air)