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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05-MAY-1997 to 11-JUL-1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
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/female
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: < 3 months for both sexes
- Weight at study initiation: 347 to 350 g for males and 225 to 300 g for females
- Fasting period before study: yes, about 16 h
- Housing: 5 animals/sex/cage in 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: at least 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 08-MAY-1997 to 22-MAY-1997 for females treated with doses of 83 and 58 mg/kg;
from 14-MAY-1997 to 14-MAY-1997 for females treated with a dose of 120 mg/kg;
from 30-MAY-1997 to 13-JUN-1997 for females treated with a dose of 69 mg/kg;
from 20-MAY-1997 to 03-JUN-1997 for males treated with a dose of 58 mg/kg.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: doses were defined based on a preliminary study (not reported).
0.073, 0.05, 0.041 and 0.035 mL/kg corresponding to 120, 83, 69 and 58 mg/kg, respectively (based on density of 1.65)
Doses:
120, 83, and 69 mg/kg for females only
58 mg/kg for both sexes
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: observations of clinical signs and mortality were performed at 30 min, 2, 4 and 6 h on the first day after administration (day 1) and then twice a day up to termination of the observation period. Bodyweight was monitored twice pre-trial (at randomization and on day 1 just before administration) and on days 3, 8 and 14. On day 1, the animals were weighed after a 16-h fasting period.
- Necropsy of survivors performed: yes, on all animals which died during the observation period and on animals killed (fasted overnight) by excision of the femoral arteries, after i.p. overdosage anaesthesia with 5% sodium pentobarbital, at the end of the observation period. Portions of any abnormal entities found in any of the necropsied animals were collected. The tissue samples were fixed and preserved in 10% buffered formalin. Histologic examination was not performed.
Statistics:
LD50 was calculated by the method of the Probit.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
79.5 mg/kg bw
Based on:
test mat.
95% CL:
>= 70.9 - <= 89.2
Mortality:
5/5 female rats at 120 mg/kg, 3/5 females at 83 mg/kg and 1/5 females at 69 mg/kg died before the end of the observation period. The mortalities were observed within 2 h of dosing at 120 mg/kg and during the first week at 83 mg/kg and 69 mg/kg. No deaths occurred in males and females treated at 58 mg/kg (see in Table 1).
Clinical signs:
Piloerection, hunched posture and increased salivation were observed in animals treated with the various doses, starting 30 min to 2 h after dosing. For animals treated with the higher doses (83 and 120 mg/kg), sedation or hypoactivity and gasping or shallow breathing were seen starting 30 min (120 mg/kg) or 2 h to day 3 after dosing (83 mg/kg). One rat of the group treated with 69 mg/kg also showed transient shallow breathing.
Recovery was achieved on day 8 for the group treated with 83 mg/kg, on day 2 for the group treated with 69 mg/kg and within 6 h for animals from the group treated with 58 mg/kg.
Body weight:
Decrease in bodyweight was observed at day 3 in animals treated with 83 mg/kg. Bodyweight gain had returned to normal by day 8. Normal bodyweight growth was found in animals of the lower dose groups.
Gross pathology:
In animals which died before the end of the observation period, the main macroscopic findings were erosion and congestion of stomach and congestion, catarrhal content and thinning walls of intestine. In single animals, these changes were accompanied by paleness of liver, spleen, kidneys or heart. In addition, cases of congestion of lungs and kidney medulla were seen. These changes were mainly confined to the animals treated with the highest dose (120 mg/kg).
At the final killing, no appreciable post-mortem changes were noted in animals.

Any other information on results incl. tables

Table 1: Mortality

Doses (mg/kg)

58

69

83

120

Number of treated animals

10

(males and females)

5

(females)

5

(females)

5

(females)

Day 1

0

1

0

5

Day 4

0

0

1

0

Day 5

0

0

1

0

Day 7

0

0

1

0

Total (day 14)

0

1

3

5

Total (%)

0

20

60

100

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was estimated to be 79.5 mg/kg bodyweight. The compound mainly induced irritation in the gastrointestinal system in the treated rats, especially at the highest dose.
Executive summary:

The purpose of the study was to evaluate the oral acute toxicity of the test article in Sprague-Dawley Crl: CD(SD) BR rats according to OECD guideline 401 and EU method B.1 and in compliance with good laboratory practices (GLP).

The test item was tested undiluted at the doses of 69, 83 and 120 mg/kg administered by gavage to groups of 5 females per dose and at the dose of 58 mg/kg administered by gavage to 5 males and 5 females. All rats were treated after a 16-h fasting period. The day of treatment was considered as day 1 of the study. Animals were clinically observed for 14 days following the treatment. Moreover, rats were weighed twice before treatment and on days 3, 8 and 14. On day 15, the surviving rats were killed and subjected to a thorough autopsy.

Death occurred in 5/5 female rats at 120 mg/kg, in 3/5 females at 83 mg/kg and in 1/5 females at 69 mg/kg. The mortality occurred within 2 h of dosing at 120 mg/kg and within one week at 83 and 69 mg/kg. No deaths occurred in males and females treated with the dose of 58 mg/kg.

Piloerection, hunched posture and increased salivation were observed in animals treated with the various doses, starting 30 min to 2 h after dosing. For animals treated with the higher doses (83 and 120 mg/kg), sedation or hypoactivity and gasping or shallow breathing were seen starting 30 min (120 mg/kg) or 2 h to day 3 after dosing (83 mg/kg). Recovery was achieved on day 8 for the group treated with 83 mg/kg, on day 2 for the group treated with 69 mg/kg and within 6 h for animals from the group treated with 58 mg/kg.

Decrease in bodyweight was observed at day 3 in animals treated with 83 mg/kg. Bodyweight gain returned to normal by day 8. Normal bodyweight growth was found in animals of the lower dose groups.

In animals which died before the end of the observation period, the main macroscopic findings were erosion and congestion of stomach and congestion, catarrhal content and thinning walls of intestine. In single animals, these changes were accompanied by paleness of liver, spleen, kidneys or heart. In addition, cases of congestion of lungs and kidney medulla were seen. These changes were mainly confined to the animals treated with the highest dose (120 mg/kg).

At the final killing, no appreciable post-mortem changes were noted in animals.

In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was estimated to be 79.5 mg/kg bodyweight. The compound mainly induced irritation in the gastrointestinal system in the treated rats, especially at the highest dose. Therefore, the test substance is classified as Acute Toxicity Category 3 (H301) according to the classification criteria of Regulation (EC) No. 1272/2008 (CLP / EU GHS) and UN GHS.