Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-JUL-2001 to 29-OCT-2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1-chloro, 2-(difluoromethoxy) -1,1,2,3,3,3-hexafluoropropane and 2-difluoromethoxy-1,1,1,2,3,3,3-eptafluoro-propane
EC Number:
947-520-2
Cas Number:
60632-00-0
Molecular formula:
Cl-(C3F6O)-CF2-H and C4F9HO
IUPAC Name:
Reaction mass of 1-chloro, 2-(difluoromethoxy) -1,1,2,3,3,3-hexafluoropropane and 2-difluoromethoxy-1,1,1,2,3,3,3-eptafluoro-propane
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Chloro H-Galden
- Physical state: liquid
- Batch. 01
- Storage condition of test material: ambient temperature in the dark
Specific details on test material used for the study:
- Name of test material (as cited in study report): Chloro H-Galden
- Batch No. 01
- Expiration date of the lot/batch: May 2004

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Alpk:APfSD (Wistar-derived) rats (5 males and 5 females, plus 1 spare male)
- Source: Rodent Breeding Unit (UK)
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 239.2 ± 14.04 g for males; 234.8 ± 12.4 g for females
- Fasting period before study: no data available
- Housing: 5 per cage, sexes separately; the additional animal was housed alone.
- Diet: ad libitum, except during exposure (diet (RM1) supplied by Special Diet Services Limited (UK))
- Water: ad libitum, except during exposure
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 30 to 70%
- Air changes: at least 15 air changes per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 24-JUL-2001 to 02-AUG-2001

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 10 polycarbonate tubes (ca. 28-mm diameter) inserted into a PERSPEX exposure chamber covered with an aluminium cone and stood on an aluminium base.
- Exposure chamber volume: internal volume of ca. 27.6 L (i.e., three sections of PERSPEX tubing connected; each tubing having an internal volume of ca. 9.2 L, a diameter of 28 cm and height of 15 cm and one section (sampling port) used for the distribution of the test atmosphere).
- Method of holding animals in test chamber: animals were restrained in polycarbonate tubes supplied by Battelle (Switzerland).
- Source and rate of air: clean, dry air was passed at a nominal flow rate of 25 L/min (at normal temperature and pressure) through the condenser and carried the atmosphere to the exposure chamber. Since diluting air was not employed, the flow rates through the exposure chambers were the same as that employed in the generation of the test atmosphere. Air flows were monitored continuously and recorded at least 3 times using variable area flowmeters (KDG Flowmeters, UK).
- Method of conditioning air: air was dried and filtered using equipment supplied by Atlas-Copco (Sweden).
- System of generating particulates/aerosols: the test atmosphere was generated using a heated (50°C) jacketed glass condenser. The test material was pumped to the condenser using a Watson Marlow peristaltic pump. Before exposure of the test animals, the atmosphere was shown to be acceptably stable over ca. 30 min.
- Method of particle size determination: not applicable
- Treatment of exhaust air: no data available
- Temperature, humidity, pressure in air chamber: 12 air changes per hr; the temperature and relative humidity in each chamber were recorded at least 3 times during exposure using a portable, digital temperature and relative humidity monitor: they were within the range of 20.9 to 21.9°C and 20 to 27%, respectively.

TEST ATMOSPHERE
The test item was tested as supplied.
The atmospheric concentration of the test item was determined for the exposure concentration by gas chromatography analysis of the material collected using a gas tight syringe. The limit of detection was calculated to be ca. 3 ppm (v/v) atmosphere concentration of the test item.
- Samples taken from breathing zone: test atmospheres were sampled from a front-facing port of the relevant exposure chamber, using a 10-mL gas-tight syringe equipped with an integral on-off valve and detachable sampling probe.

VEHICLE
Air.

- Rationale for the selection of concentrations: a maximum atmospheric concentration of 5000 ppm was selected from the results of a trial exposure with a single animal.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentration: 5000 ppm
Achieved concentration: 5080 ± 213 ppm
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: see below
- Necropsy of survivors performed: yes
- Other examinations performed:
* Clinical signs: prior to the start of the study, all rats were examined to ensure that they were physically normal and exhibited normal activity. During exposure, animals were observed frequently. At the end of the 4-hour exposure period, each rat was given a detailed clinical examination. The animals were also subjected to detailed clinical observations, including the finding of "no abnormalities detected", daily during the 14-day observation period.
* Body weight: the body weight of each rat was recorded on day -1 (to ensure animals of one sex were within a similar weight range), 1, 8 and prior to termination on day 15.
* Macroscopic examination: all animals were examined post mortem. This involved an external observation and an internal examination of all thoracic and abdominal viscera.

Results and discussion

Preliminary study:
One male rat was used fir trial exposures to the target concentration.
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 080 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No correction factor applied for the purity of the material.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 54 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other:
Remarks:
Calculated considering an average molecular weight of 260 uma
Mortality:
At the exposure concentration of 5080 ppm, there were no deaths during the exposure or observation periods.
Clinical signs:
other: At the exposure concentration of 5080 ppm, there was no clinical signs indicative of toxicity. During exposure, abnormalities generally associated with restraint-wet fur (all animals), and chromodacryorrhea (some animals) were observed. In addition, all
Body weight:
At an exposure concentration of 5080 ppm, all animals except 2 males had gained weight by day 8 of the study and all animals had gained weight by day 15 of the study.
Gross pathology:
At an exposure concentration of 5080 ppm, there were no macroscopic changes related to the test material.

Any other information on results incl. tables

Table 1: Group mean bodyweight (g)

 

On day 1

On day 8

On day 15

Males

(n = 5)

298 ± 12

312.8 ± 1.8

343.0 ± 14.5

Females

(n = 5)

233.0 ± 13.2

243.6 ± 18.3

255.2 ± 17.8

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information (LC50 > 50 mg/L) Criteria used for interpretation of results: EU
Conclusions:
Nose-only exposure for 4 hours to vapours of the test material at an analytical concentration of 5080 ppm resulted in no deaths. It was thus concluded that the LC50 of the test material was higher than 5080 ppm (corresponding to ca. 54 mg/L, considering an average molecular weight of 260 uma) 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 Alpk:APfSD (Wistar-derived) rats was nose-only exposed for a single 4-hour period to a vapour of the test item at a target concentration of 5000 ppm. Test atmospheres were analysed for total concentration of the test item. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and body weights were recorded throughout the study and at the end of the schedule period; the animals were killed and subjected to a gross examination post-mortem.

 

The achieved test atmospheres had the following characteristics:

 

Target

concentration

(ppm)

Achieved

concentration

(ppm)

5000

5080

 

At an exposure concentration of 5080 ppm, during and immediately after the exposure some clinical signs were observed ( abnormal respiration, salivation, chromodacryorrhea and stains around the snout) in most animals. There were no clinical changes during the remaining 14 day exposure period. All animals had gained weight by day 15 of the study, no macroscopic changes at necroscopy and no deaths.

 

Nose-only exposure for 4 hours to the test material at a concentration of 5080 ppm resulted in no deaths. It was thus concluded that under the conditions of this study the median lethal concentration (LC50) of the test material was higher than 5080 ppm (corresponding ca to 54 mg/L, considering an average molecular weight of 260 g/mol) for male and female rats.