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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a study on acute toxicity by the inhalation route is available

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

vapour pressure

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 18 February 2016 to 09 June 2016.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

Version / remarks:

2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Version / remarks:

2006

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7950 (Vapor Pressure)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Type of method:

static method

Key result

Temp.:

25 °C

Vapour pressure:

120 kPa

Key result

Temp.:

20 °C

Vapour pressure:

97 kPa

Conclusions:

The vapour pressure of the substance MOVE3 at 25°C was determined to be 1.2E02 Pa.

Executive summary:

The vapour pressure was determined using the static method in a GLP study according to EC A.4, OECD 104 and OPPTS 830.7950.

No deviation from the guidelines was observed during the test.

The vapour pressure of the substance at 20°C and at 25°C were determined as the mean of the values obtained in the two experiments performed (between 20 and 50°C).

  

The vapour pressure of MOVE3 at 25°C was determined to be 1.2E02 kPa.

The vapour pressure of MOVE3 at 20°C was determined to be 9.7 E01 kPa.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

boiling point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 18 February 2016 to 09 June 2016.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.2 (Boiling Temperature)

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 103 (Boiling point/boiling range)

Version / remarks:

1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7220 (Boiling Point / Boiling Range)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Type of method:

differential scanning calorimetry

Key result

Boiling pt.:

19.5 °C

Atm. press.:

1 007 hPa

Preliminary test (TGA experiment)

It was observed that the test item (10.9 mg) evaporated very quickly. The weight of the test substance had already been reduced to 1.25 mg at the start of the experiment. DSC experiments were therefore performed up to an end temperature of 75°C.

Main test:

DSC EXPERIMENT 1

An endothermic peak between -60°C and 10°C was observed. The extrapolated onset temperature of the peak was -18.10°C. The effect was most likely obtained due to evaporation of the test substance. After the experiment it was observed that the test substance had evaporated from the sample container. The peak shape showed that the hole drilled in the sample container was too large. The result of Experiment 1 was not used for calculations.

DSC EXPERIMENT 2

In an attempt to obtain a better peak shape, a sample container with a prefabricated hole in the sample pan was used. The extrapolated onset temperature of the evaporation peak was 19.40°C. After the experiment it was observed that the test substance had evaporated from the sample container.

DSC EXPERIMENT 3

The temperature program (as well as the use of a sample container with a prefabricated hole) was similar as the temperature program of Experiment 2. Similar results as with Experiment 2 were obtained. The extrapolated onset of the evaporation peak was 19.67°C. After the experiment it was observed that the test substance had evaporated from the sample container.

The boiling temperature of the substance was calculated as the average boiling temperature obtained from Experiment 2 (19.40°C) and Experiment 3 (19.67°C).

Conclusions:

The boiling temperature of the substance MOVE3 at 1007 hPa was determined to be 19.5°C.

Executive summary:

The boiling temperature was determined using Differential Scanning Calorimetry in a GLP study according to EC A.2, OECD 103 and OPPTS 830.7220.

No deviation from the guideline was observed during the study.

From duplicate experiments using an aluminum sample crucible closed by a lid with a small prefabricated hole, a mean value of 19.5°C was obtained for the boiling temperature of the substance MOVE3 at 1007 hPa.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

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

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.

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.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

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

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

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.

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.

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

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.