1-[difluoro(trifluoromethoxy)methoxy]-1,2,2-trifluoroethylene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15-FEB-2007 to 11-APR-2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Animals were exposed to a target atmosphere concentration slightly above 20 mg/L air, because the test item rapidly vaporised due to its high saturation concentration at room temperature.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Animals were exposed to a target atmosphere concentration slightly above 20 mg/L air, because the test item rapidly vaporised due to its high saturation concentration at room temperature.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

{difluoro[(1,2,2-trifluoroethenyl)oxy]methoxy}trifluoromethane

EC Number:

615-064-0

Cas Number:

700874-87-9

Molecular formula:

C4F8O2

IUPAC Name:

{difluoro[(1,2,2-trifluoroethenyl)oxy]methoxy}trifluoromethane

Test material form:

liquid: volatile

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 01/06
- Expiration date of the lot/batch: 31-DEC-2010
- Purity test date: 99.24%
- Physical Appearance: Liquid
- Aggregate State at Room Temperature: Liquid / vapour

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test item was stored in the original, tightly closed container, at room temperature (range accepted by RCC: 15-25°C), protected from direct sunlight.
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Stable in Air

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none
- Preliminary purification step (if any): none

Test animals

Species:

rat

Strain:

other: HanRcc:WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Servivces (SWITZERLAND)
- Age at study initiation: 9 weeks for males; 10 weeks for females
- Weight at study initiation: 244.4 to 264.1 g for males; 201.9 to 209.7 g for females
- Fasting period before study: no data available
- Housing: in groups of 5 in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocell", Schill AG / SWITZERLAND)
- Diet: ad libitum, except during exposure (pelleted standard Kliba-Nafag 3433, rat maintenance diet, batch No. 80/06 (Provimi Kliba AG / SWITZERLAND))
- Water: ad libitum, except during exposure (community tap-water from Füllinsdorf, chlorinated to ca. 0.5 ppm)
- Acclimation period: 4 to 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 21.3°C
- Humidity: 30 to 70%
- Air changes: 10 to 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs (fluorescent) light

IN-LIFE DATES: From 16-FEB-2007 to 07-MAR-2007

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

other: nose-only, flow-past exposure

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the inhalation exposure system was located inside a ducted extraction cabinet. The test atmosphere entered the inlet at the top of the nose-only, flow-past exposure chamber under slight positive pressure and was distributed to the entrance of each feed tube. It was then delivered through these tubes to the animal's nose in each exposure tube.
- Exposure chamber volume: no data available
- Method of holding animals in test chamber: animals were restrained in exposure tubes.
- Source and rate of air: see below
- Method of conditioning air: no data available
- System of generating particulates/aerosols: the test item was warmed to 50-52°C by use of a heating jacket, and test item vapour was released from the flask and mixed with a small amount of air at a constant flow by use of two thermal mass flow meters (TMF) connected to an electronic controller. The mixture of test item vapour and a small amount of air estimated to be 0.48 L/min was released by one of the two TMF and was diluted further with compressed filtered air at 12.0 L/min to achieve the atmosphere concentrations required for this study. The airflow rate of the test atmosphere as it arrived at the animal ports was 1.04 L/min/animal port.
- Method of particle size determination: not applicable
- Treatment of exhaust air: the exhaled air was extracted through the gap near each feed tube and left the exposure chamber via its outer cylinder followed by the exhaust tube.
- Temperature, humidity, pressure in air chamber: 20.4 ± 0.06°C, 5.5 ± 0.34% humidity, slight positive pressure, 20.6 Vol% O2

TEST ATMOSPHERE
- Brief description of analytical method used: mean analytical concentration and standard deviation were obtained from double analysis of seven test atmosphere samples collected in gasbags at quite regular intervals during around 3 of the 4-h inhalation exposure period. The samples were then chemically analysed for the test item using gas chromatography.
- Samples taken from breathing zone: yes, at an empty port of the exposure chamber, delivering "fresh" test atmosphere to the animal's nose.

VEHICLE
Not applicable

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

- Nominal concentration: 23.34 mg/L air
- Mean atmosphere concentration: 20.65 ± 0.55 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
* Clinical signs were recorded at approximately 1, 2, 3, and 4 h after exposure start and approximately 1 h after the end of exposure on test day 1. In addition, clinical signs were recorded once daily on test days 2 to 5. Observations included, but were not limited to changes in behaviour, somatomotor activity, body position, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g., tremors or convulsions, reactivity to handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes.
* Body weights were recorded on test days 1 (before exposure), 4, 8, and 15 (day of necropsy).
- Necropsy of survivors performed: yes; all animals were examined for any abnormalities.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 20.65 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No spontaneous deaths occurred in this study. All animals were sacrificed as scheduled on test day 15.

Clinical signs:

other: Examination of each animal during and after exposure did not reveal any clinical signs during the 15-day observation period.

Body weight:

There were no adverse effects on body weight in male animals during the 15-day observation period. Body weight loss, marginal in degree, or retardation in body weight gain was occasionally seen in 3 of 5 female animals (see in Table 2 below in "any other information on results incl. tables"). A relationship of these minor effects on female body weight to the treatment with the test item could not be entirely discounted, although there were no clinical signs or other indications of toxicity during this study and slight physical stress, e.g. during restraint in the exposure tubes, might have contributed to these effects. The body weight gain in the other two female was considered to be within the range of natural background variation occasionally seen in female rats of this strain and age.

Gross pathology:

Examination of each animal on the scheduled necropsy day (test day 15) did not reveal any macroscopic findings.

Any other information on results incl. tables

Table 2: Body weights in male (M) and female (F) rats (gram)

Group	Animal No.	Sex	Test day 1 (treatment)	Test day 4	Test day 8	Test day 15
1 (20.65 mg/L air)	1	M	244.4	254.0	270.8	292.8
	2	M	264.1	280.0	306.1	342.6
	3	M	257.9	264.8	278.4	298.6
	4	M	261.1	278.9	295.8	324.5
	5	M	257.0	273.0	295.0	324.8
Mean ± SD N			256.9 ± 7.5 5	270.1 ± 10.9 5	289.2 ± 14.3 5	316.7 ± 20.6 5
Group	Animal No.	Sex	Test day 1 (treatment)	Test day 4	Test day 8	Test day 15
1 (20.65 mg/L air)	6	F	202.8	204.6	213.6	228.6
	7	F	209.7	209.3	213.7	213.6
	8	F	201.9	204.9	207.0	210.9
	9	F	208.9	208.8	214.7	217.1
	10	F	207.5	208.9	209.4	226.7
Mean ± SD N			206.1 ± 3.5 5	207.3 ± 2.3 5	211.7 ± 3.3 5	219.4 ± 7.9 5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Nose-only exposure for 4 hours to vapours of the test substance at an analytical concentration of 20.65 mg/L resulted in no deaths and no adverse effects. It was thus concluded that the LC50 of the test substance was higher than 20.65 mg/L for male and female rats.

Executive summary:

This acute inhalation toxicity study was conducted according to OECD guideline 403 and in compliance with good laboratory practices (GLP).

 

A group of five male and five female albino rats [HanRcc:WIST(SPF)] was nose-only exposed for a single 4-hour period to a vapour of the test substance at a chemically determined mean atmosphere concentration of 20.65 ± 0.55 mg/L air, equivalent to a nominal concentration of 23.34 mg/L air. All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e., over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8, and 15. On day 15, all animals were sacrificed and necropsied.

 

There were no deaths, no clinical signs and no macroscopic pathology findings. Body weight was not adversely affected in male animals. Body weight loss, marginal in degree, or retardation in body weight gain was occasionally seen in 3 of 5 female rats. A relationship of these minor effects on female body weight to treatment with the test item remained unclear.

 

Nose-only exposure for 4 hours to the test substance at a concentration of 20.65 mg/L resulted in no deaths and no adverse effects. It was thus concluded that under the conditions of this study the median lethal concentration (LC50) of the test substance was higher than 20.65 mg/L for male and female rats, therefore the test substance does not meet the classification criteria of EC Regulation No. 1272/2008 (CLP / EU GHS) and UN GHS for acute inhalation toxicity.