Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22-APR-1997 to 28-MAY-1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Methods is similar to guideline method, but all the individual animal data are not available in the report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
reduced number of animals per group as only the preliminary study was performed.
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
reduced number of animals per group as only the preliminary study was performed.
GLP compliance:
yes
Test type:
standard acute 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
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rats derived from the Sprague-Dawley strain (Crl: CD(SD)BR)
- Source: Charles River Italia S.p.A. / Via Indipendenza, 11 - 22050 CALCO (Lecco) / ITALY
- Age at study initiation: no more than 3 months old
- Weight at study initiation: 330 to 339 g
- Fasting period before study: no data available
- Housing: 3 animals/cage in an air-conditioned room (grill cages 40.5 x 38.5 x 18h cm with stainless steel feeder)
- Diet: ad libitum (GLP 4RF21 top certificate pelleted diet produced by Charles River italia’s feed licencee Mucedola S.r.L., Settimo Milanese)
- Water: ad libitum (filtered municipal water)
- Acclimation period: > 5 days before the start of the test

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 55 ± 10%
- Air changes: about 20 per hr filtered on HEPA 99.97%
- Photoperiod: 12 hrs dark / 12 hrs light (7 am. - 7 p.m.)

IN-LIFE DATES: From 21-FEB-1997 to 07-MAY-1997

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Preparation of animals skin: approximately 24 hours before the test, fur was clipped from the dorsal and ventral area
- Area of exposure: about 6 x 5 cm of the body dorsal surface (about 10% of the total body surface)
- Type of wrap: the treated area was covered with a porous gauze dressing fixed to the skin with hypoallergenic non-irritating tape. The test site was further covered in a suitable manner in order to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
- At the end of the 24-h exposure period, the residual test substance was not washed, but it was wiped off.

TEST MATERIAL
- Amount(s) applied (volume): 0.15, 0.30 and 0.60 mL/kg of undiluted test material were applied, in order to obtain the doses of 250, 500 and 1000 mg/kg respectively (density 1.6-1.7 g/mL).
Duration of exposure:
About 24 h
Doses:
250, 500 and 1000 mg/kg
No. of animals per sex per dose:
1 per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (clinical signs and mortality): at 30 minutes, 2, 4 and 6 hours on the first day after the administration (day 1) and then twice a day up to termination of the observation period.
- Frequency of body weighing: twice pre-trial (at randomization and on day 1 just before administration) and on days 8 and 15
- Necropsy of survivors performed: gross pathology on animals died before the end of the 14-day observation period and on animals killed at the end of the study
- No histopathology
Statistics:
LD50 was not calculated

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
>= 250 - <= 1 000 mg/kg bw
Based on:
test mat.
Mortality:
Deaths occurred in the male (on day 3) treated with 1000 mg/kg and in the male (on day 4) given the test article at 500 mg/kg. The male treated with 250 mg/kg survived until the end of the 14-d observation period.
Clinical signs:
Sedation/hypoactivity and piloerection were observed in all treated animals (starting 2-6 hours after treatment for animals given 500 and 1000 mg/kg, and on day 2 at the dose level of 250 mg/kg). In addition, hunched posture, hypothermia and skin/mucous pallor were noted in animals at the two higher doses.
All these clinical signs were achieved on day 4 in the rat given 250 mg/kg (at the two higher doses, animals died before day 5).
After removal of the dressing, local skin oedema and cyanosis were observed in all animals. Skin crust was noted in the animal given 250 mg/kg from day 6 up to the end of the observation period.
Body weight:
Body weight of the rat given 250 mg/kg was not affected by the treatment.
Gross pathology:
For the animals which died, lung congestion was noted at the highest dose (1000 mg/kg), and oedema and cyanosis were observed at the treatment site at the two higher doses (500 and 1000 mg/kg).
At the autopsy performed at the end of the observation period, the rat treated with 250 mg/kg displayed focal scab at the application site.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In conclusion, the test article administered by dermal route induced mortality from 500 mg/kg. No mortality was observed at the dose level of 250 mg/kg.
Executive summary:

The purpose of the study was to evaluate the acute dermal toxicity of the test item in Sprague-Dawley Crl: CD(SD) BR rats according to OECD guideline 402 and EU method B.3 and in compliance with good laboratory practices (GLP).

The test item was tested undiluted at the doses of 250, 500 and 1000 mg/kg (at various volumes) administered by dermal route (semi-occlusive) on the body dorsal surface (ca. 6 x 5 cm) of groups of 1 male/dose. The day of treatment was considered as day 1 of the study. At the end of the 24-h exposure period, the residual test article was wiped off. Animals were clinically observed for 14 days following the treatment. Moreover, rats were weighed twice before treatment and on days 8 and 15. Gross pathology evaluation was performed on animals which died before the end of the 14-day observation period and as well as on animals killed on day 15 at the end of the study.

Only the rat given 250 mg/kg survived until the end of the 14-day observation period; rats given higher doses died on days 3-4 after dosing.

Sedation/hypoactivity and piloerection were observed in all animals; hunched posture, hypothermia and skin/mucous pallor were only seen in animals at the two higher doses.

After removal of the dressing, skin oedema and cyanosis were observed at all 3 doses. Skin crust was then noted in the rat given 250 mg/kg from day 6 up to the end of the observation period.

Lung congestion was observed at the autopsy of the animal given 1000 mg/kg; oedema and cyanosis were noted at the treatment site in animals given 500 and 1000 mg/kg.

At the end of the observation period, skin focal scab was seen in the animal given 250 mg/kg.

In this preliminary study, the test article, when administered to rats as a single dose by dermal route, induced mortality at the doses of 500 and 1000 mg/kg. No mortality was observed at 250 mg/kg. Since corrosive effect was noted at the administration site during this preliminary study, no further animal was treated. The test substance is thus classified as Acute Toxicity Category 3 (H311) according to the classification criteria of Regulation (EC) No. 1272/2008 (CLP / EU GHS) and UN GHS.