Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26-MAR-1999 to 30-OCT-2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The concentrations of substance in the atmosphere were not determined (nominal concentrations).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was not designed to be in compliance with any particular guideline. The data were initially generated for internal use. However the method is consistent with standardised methods.
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
[2-Chloro-1,2,2-trifluoro-1-(trifluoromethyl)ethoxy] difluoroacetyl fluoride
EC Number:
917-631-0
Molecular formula:
C5ClF9O2 and C5F10O2
IUPAC Name:
[2-Chloro-1,2,2-trifluoro-1-(trifluoromethyl)ethoxy] difluoroacetyl fluoride
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited (Margate, Kent / ENGLAND)
- Age at study initiation: 7 and 8 weeks old for males and females, respectively
- Weight at study initiation, fasting period before study: no data available
- Housing: by sex in groups of 5, in holding cages (size 35 cm x 53 cm x 25 cm height)
- Diet: ad libitum (except during the 4-h exposure), excess amount of SDS rat and mouse diet (RM1)
- Water: ad libitum (except during the 4-h exposure), tap water
- Acclimation period: at least 5 days before the day of exposure

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 26°C
- Humidity: 45 to 63%
- Air changes: 12 to 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light (artificial light between 07:30 - 19:30 daily)

IN-LIFE DATES: from 15-APR-1999 to 22-Jul-1999

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the vapour generator was designed to produce an atmosphere containing vapour by evaporation of the test substance from a fritted glass disc with a countercurrent of air. All parts of the generator in contact with the test substance were made of glass. The test substance was delivered to the generator at a constant flow rate from a syringe driven by a syringe pump and the air supplied to the generator was dried, filtered and oil free. The snout-only exposure chamber used for the exposures was of cylindrical form (30 cm i.d., 45 cm height) and made of aluminium alloy. The rats were held for exposure in (separate) moulded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. The conditioned test atmosphere entered through a port at the top centre of the chamber and passed out through a port at the base section below the level of the rats.
- Exposure chamber volume: the chambers have an enclosed volume of approximately 30 litres.
- Method of holding animals in test chamber: each rat was restrained in a forward position by an adjustable foamed plastic stopper.
- Source and rate of air: clean dried air at a flow rate of 20 L/min
- Method of conditioning air: no data available
- System of generating test atmosphere: a syringe filled with the test substance was fitted to the syringe pump and connected to the generator with Teflon tubing. The syringe was switched on and the exposure timed for 4 h, following a 5-min equilibration period. The syringe was replaced with a filled syringe as required during the exposure. After 4 h, the syringe pump was switched off and the exposure chamber allowed to clear before rats were removed for examination.
- Treatment of exhaust air: no data available
- Temperature in air chamber: 19.6 to 20.8°C
- Humidity, pressure in air chamber: no data available

TEST ATMOSPHERE
The nominal concentration of the test substance was calculated from the amount of test item delivered to the vapouriser and the total volume of air flowing through the exposure system during the period of generation.

VEHICLE
Not applicable
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
Target concentrations: 1, 5, and 2.5 mg/L for groups 1, 2 and 3, respectively
No. of animals per sex per dose:
5 per sex and per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed continuously fir signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. The clinical signs were recorded prior to the end of the chamber equilibration period, 0.25, 0.5 and 1 h into exposure, then at hourly intervals during the remainder of the exposure. Signs were also recorded immediately after exposure and at 1 and 2 h after exposure. During the 14-d observation period, the clinical signs were recorded once in the morning and then as necessary following later check for clinical signs. All rats were weighed twice during the week prior to exposure, at time 0 (immediately before exposure) and weekly during the observation period.
- Necropsy of survivors performed: yes; all rats were subjected to a detailed macroscopic examination. The lungs (including the larynx and trachea), liver and kidneys were dissected free of surrounding tissue, weighed and the weights recorded. The heads from group 2 rats and one decedent group 3 rat were preserved in neutral buffered formalin. The remaining tissues were then discarded.
- Other examinations performed: the amount of food consumed by each cage of rats was measured from weighday to weighday throughout the study. Moreover, a visual inspection of water bottles was conducted daily.
Statistics:
LD50 was not calculated.

Results and discussion

Preliminary study:
Prior to the exposure of group 1, single rats were exposed to nominal concentrations of 0.088, 0.62 and 1.17 mg/L in order to confirm the survivability of rats up to concentrations of approximately 1 mg/L which is the LC50 for hydrofluoric acid.
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
1.17 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
male/female
Dose descriptor:
other: approximate LC50
Effect level:
> 2.66 - < 5.37 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Four males and one female from group 2 were found dead in the cage on day 1 of the observation period. Two further females from group 2 were found dead in the holding cage, one each on days 2 and 3 of the observation period. Severe lung congestion was seen in all of these animals. One male of group 3 was found in a moribund condition on day 4 of the observation period (see in Table 2).
Clinical signs:
other: During the exposure, exaggerated breathing was seen in all groups. During the observation period, treatment-related observations included signs of respiratory distress in all groups, lethargy, hunched posture and staggering in rats of groups 2 and 3 and p
Body weight:
A treatment-related reduction in bodyweight gain was seen in surviving rats over the observation period (see in Table 3).
Gross pathology:
At the end of the 14-d observation period, pale areas and minimal or moderate congestion was seen in the lungs from surviving rats.
Other findings:
- Organ weights: at the end of the 14-d observation period, no treatment-related effect was seen in surviving rats.
- Food and water consumption: food consumption was reduced concomitant with reduced weight gain. Measurement of water consumption by group 2 was commenced on the day after exposure following gross observation of low consumption. From day 3 of the observation period, water consumption was considered to be normal.

Any other information on results incl. tables

Table 2: Mortality

Group

(nominal concentration

- mg/L)

Mortality

 

 

 

Males

Females

Total

1 (1.17)

0/5      

0/5

0/10

2 (5.37)

4/5      

3/5

7/10

3 (2.66)

1/5

0/5

1/10

 

Table 3: Group mean bodyweights (g)

Group

(nominal concentration - mg/L)

Day of observation

 

 

 

 

 

 

 

-6

-5

-3

-2

0

7

14

1 (1.17)

Males

Females

 

228

198

 

 

255

204

 

 

273

209

 

300

228

 

338

242

2 (5.37)

Males

Females

 

 

230

198

 

 

256

209

 

274

212

 

285

195

 

Death

236

3 (2.66)

Males

Females

 

278

213

 

 

293

216

 

 

310

224

 

306

229

 

354

244

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In this study, the non-lethal exposure level was a nominal concentration of 1.17 mg/L.
Executive summary:

The acute inhalation toxicity of the test item was investigated in compliance with GLP.

Groups of 5 male and 5 female albino rats (Sprague-Dawley in origin) were exposed by nose-only inhalation to a vapour of the test substance in clean dried air at the (calculated) nominal concentrations of 1.17, 2.66 and 5.37 mg/L for a single 4-hour period. Concentrations of test substance in the test atmospheres were not determined. The exposure levels were estimated from test substance usage and were nominal concentrations only. Following exposure, animals were retained without treatment for 14 days. Clinical observations and body weights were recorded throughout the study and at the end of the 14-d observation period. Animals were then killed and given a gross examination post-mortem.

Four males and one female from group 2 (i.e., 5.37 mg/L) were found dead in the cage on day 1 of the observation period. Two further females from group 2 were found dead in the holding cage, one each on days 2 and 3 of the observation period. Severe lung congestion was seen in all of these animals. One male of group 3 (i.e., 2.66 mg/L) was found in a moribund condition on day 4 of the observation period. No death occurred in the group 1 (i.e., 1.17 mg/L).

During the exposure, exaggerated breathing was seen in all groups. During the observation period, treatment-related observations included signs of respiratory distress in all groups, lethargy, hunched posture and staggering in rats of groups 2 and 3 and partially closed eyes and whole-body tremors in group 2 only.

Moreover, a treatment-related reduction in bodyweight gain was seen in surviving rats over the observation period.

At the end of the 14-d observation period, pale areas and minimal or moderate congestion was seen in the lungs from surviving rats but no treatment-related effect on organ weight was seen in surviving rats.

Under the conditions of this study, the non-lethal exposure level (LC0) was a nominal concentration of 1.17 mg/L for male and female rats. Given the number of deaths observed at the concentrations tested (from 1/10 to 7/10), the LC50 of the test substance should be between 2.66 and 5.37 mg/L and therefore the test substance is classified as Acute Toxicity Category 3 (H331) according to the classification criteria of Regulation (EC) No. 1272/2008 (CLP / EU GHS) and UN GHS.