Registration Dossier

Administrative data

Description of key information

LD50 oral, rat > 2000 mg/kg bw
LD50 dermal, rat > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
Reference:
Composition 0
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 information:
Composition 1
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
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)
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
One study on the test item was available. This study was considered sufficient for the assessment of acute toxicity via oral route, therefore the overall quality of the dataset is considered to be good.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 402 and EU method B.3.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
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: 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
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: 236-347 g for males and 209-226 g for females
- Fasting period before study: no data available
- Housing: animals were housed individually during the 24-hour treatment period and then 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: more than 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 and 14-JAN-2000 to 28-JAN-2000 (females) and 04-FEB-2000 (males)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approximately 24 hours before the test, fur was clipped from the dorsal and ventral area of the trunk of the test. An area of about 6x5 cmq of the body dorsal surface was cleared for the application of the test article.
- % coverage: about 10% of the total body surface
- Type of wrap if used: the treated area was covered with the 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
- Washing (if done): the residual test article was wiped off with water.
- Time after start of exposure: at the end of the exposure period, i.e. 24 h

TEST MATERIAL
- Amount(s) applied: 1.22 mL/kg or 2000 mg/kg
- Concentration: not applicable
- Constant volume or concentration used: yes

VEHICLE
Not applicable
Duration of exposure:
ca. 24 hours
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 8 and 15. Volume of administration was based on day 1 body weight.
- 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.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the study. The LD50 was not calculated; it was considered to be higher than 2000 mg/kg.
Clinical signs:
No general or local clinical abnormalities were seen in any animal.
Body weight:
No changes in body weight growth were found in both males and females.
Gross pathology:
No appreciable changes were evident in the treated animals of either sex at the autopsy carried out at the end of the observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, the test article, when administered by dermal route to the rat, did not cause mortality or show appreciable toxic effects at the limit dose of 2000 mg/kg. The LD50 by dermal route was considered to be higher than 2000 mg/kg.
Executive summary:

The purpose of the study was to evaluate the acute dermal toxicity of the test article. The test method was in accordance with EU method B.3 and OECD guideline 402 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 dermal administration of the test article at the dosage of 2000 mg/kg. The test article was applied uniformly onto the cleared dorsal and ventral area of rat trunk (fur was clipped 24 hours previously). A porous gauze was fixed to the area and remained there for about 24 hours. The individual dosages were based on body weight taken just before treatment.

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 8 and 15. They were clinically observed for 14 days after the 24-hour exposure period. On day 16 all rats were killed (fasted overnight) by excision of the femoral arteries after intraperitoneal overdosage anaesthesia with 5% sodium pentobarbital; animals were then submitted to a thorough autopsy.

 

No animals died and no general or local clinical signs or body weight abnormalities were observed in any treated rat during the observation period. No macroscopic findings were evident at the final autopsy.

 

In conclusion, the test article, when administered by dermal route to the rat, did not cause mortality or show appreciable toxic effects at the limit dose of 2000 mg/kg. The LD50 by dermal route was considered to be higher than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
One study on the test item was available. This study was considered sufficient for the assessment of acute toxicity via dermal route, therefore the overall quality of the dataset is considered to be good.

Additional information

The acute toxicity of the test item was tested in rats using two usual routes of administration: oral and dermal. One study of reliability 1 according to Klimisch criteria was available for each route of administration and both were selected as key studies.

 

The potential acute toxicity of the test substance was first investigated following a single oral administration (gavage) to rats according to OECD guideline 401 and EU method B.1, and in compliance with GLP (Yu P., 2000).

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

In conclusion, the oral LD50 of the test article, when administered to rats as a single dose by oral route, was higher than 2000 mg/kg, therefore warranting no classification according to the classification criteria of Regulation (EC) No. 1272/2008.

 

An acute dermal study was conducted to assess the toxicity potential of the test item, in accordance with the standardised OECD guideline 402 and EU method B.3, and in compliance with GLP (Yu P., 2000).

Male and female Sprague Dawley Crl:CD(SD) BR rats (5 per sex and group) received a single dermal administration of the test article at the dosage of 2000 mg/kg. The test article was applied uniformly onto the cleared dorsal and ventral area of trunk of the rats (fur was clipped 24 hours previously). A porous gauze was fixed to the area and remained there for about 24 hours.

No animal died and no general or local clinical signs or body weight abnormalities were observed in any treated rat during the observation period. No macroscopic findings were evident at the final autopsy.

In conclusion, the test article, when administered by dermal route to the rat, did not cause mortality or show appreciable toxic effects at the limit dose of 2000 mg/kg. The LD50 by dermal route was considered to be higher than 2000 mg/kg, therefore warranting no classification of the test item according to the classification criteria of Regulation (EC) No. 1272/2008.

 

By inhalation route, no study was available on the test item. According to column 2 adaptation of REACH Annex VII (section 8.5), an acute inhalation toxicity study was not considered scientifically justified as acute toxicity studies using the oral and dermal exposure routes were available, both studies showing no effect of the substance.

 

Regarding the specific target organ toxicity - single exposure (STOT SE), no sign of impairment was observed in any organ investigated in the studies cited above, and this regardless of the route of administration (i.e., oral and dermal).

Justification for classification or non-classification

The available data on the test item showed that no mortality occurred in rodents after exposure at the tested limit dose of 2000 mg/kg bw, regardless of the exposure route (oral and dermal). Thus, the test substance is not classified according to the classification criteria of Regulation (EC) No. 1272/2008.

 

Moreover, no sign of impairment was observed in any organ investigated regardless of the administration route (i.e., oral and dermal), thus requiring no STOT SE classification for the test item according to Regulation (EC) No. 1272/2008.