Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07-JAN-2000 to 21-MAR-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This GLP-compliant study was conducted in accordance with OECD guideline 401 and EU method B.1.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Substance type: monoconstituent 
- Physical state: colourless liquid
- Analytical purity: 100%
- Density: 1.64
- Lot/batch No.: 6-99
- Manufacturing date: 24 May 1999
- Expiration date of the lot/batch: May 2001
- Storage condition of test material: at room temperature
Specific details on test material used for the study:
- Name of test material (as cited in study report): Perfluorosulfonyl vinyl-ether
- Impurities, purity test date: no data available
- Physical state: colourless liquid
- Lot/batch No.: 6-99
- Manufacturing date: 24 May 1999
- Expiration date of the lot/batch: May 2001
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Sprague Dawley Crl: CD(SD) BR rat
- Source: Charles River Italia S.p.A. / Via Indipendenza. 11 - 23885 CALCO (Lecco) / ITALY
- Age at study initiation: no more than 3 months
- Weight at study initiation: 241-329 g for males and 216-226 g for females
- Fasting period before study: about 16 hours before exposure; feed was returned to rats about 3 hours after the test article administration.
- Housing: 5 animals/cage per sex in grill cages (40.5x38.5x18h cm) with stainless steel feeder, in air-conditioned room.
- Diet: ad libitum, GLP 4RF21 top certificate pelleted diet (Charles River Italia’s feed licencee Mucedola S.r.l., Settimo Milanese) supplemented by the producer with vitamins and trace elements
- Water: ad libitum, filtered water from municipal water main system
- Acclimation period: at least 5 days before the start of the test

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 55 ± 10%
- Air changes: about 15-20 per hour filtered on HEPA 99.97%
- Photoperiod: 12 hrs dark / 12 hrs light (7 a.m. - 7 p.m.)

IN-LIFE DATES: From 07-JAN-2000 or 14-JAN-2000 to 27-JAN-2000 (females) and 03-FEB-2000 (males)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
Not applicable

MAXIMUM DOSE VOLUME APPLIED: 1.22 mL/kg
Doses:
2000 mg/kg
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: observation of 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; body weight 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-hour fasting period.
- Necropsy of survivors performed: yes, on all animals (fasted overnight) killed by excision of the femoral arteries, after intraperitoneal overdosage anaesthesia with 5% sodium pentobarbital, at the end of the 14-day observation period. Gross pathology performed.
Statistics:
LD50 was not calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study period. The LD50 was not calculated; it was considered to be higher than 2000 mg/kg.
Clinical signs:
Diarrhea and piloerection were observed between 4 and 24 hours after dosing. No clinical abnormalities were seen afterwards.
Body weight:
Body weights of both males and females were found to be unaffected by the test article administration.
Gross pathology:
At the necroscopy carried out at the end of the observation period, no appreciable macroscopic findings were evident in the rats.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was higher than 2000 mg/kg. At this dose, the test substance induced transient diarrhoea in the treated rats.
Executive summary:

The purpose of the study was to evaluate the acute oral toxicity of the test article. The test method was in accordance with EU method B.1 and OECD guideline 401 and in compliance with good laboratory practices (GLP).

 

Male and female Sprague Dawley Crl:CD(SD) BR rats (5 per sex and group) received a single oral administration of the test article at the dosage of 2000 mg/kg. The test article was administered undiluted as supplied by the Sponsor. The volume of administration was 1.22 mL/kg (the density of the test article is 1.64 g/mL).

All rats were treated after a 16-hour fasting period. The day of treatment was considered as day 1 of the study. Animals were weighed twice before treatment (at randomization and on day 1 just before treatment) and on days 3, 8 and 14. They were clinically observed for 14 days following the treatment. On day 15, rats were killed (fasted overnight) by excision of the femoral arteries after intraperitoneal overdosage anaesthesia with 5% sodium pentobarbital; then, animals were subjected to a thorough necroscopy.

 

No deaths occurred in any animal. Transient diarrhoea was seen in animals. No effects on body weight growth were seen in rats during the study. At the autopsy carried out at the end of the observation period, no appreciable macroscopic findings were evident in rats.

 

In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was higher than 2000 mg/kg. At this dose, the test substance induced transient diarrhoea in the treated rats.