3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanesulphonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Jun 2017 to 04 Aug 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17 December 2001.

Deviations:

yes

Remarks:

Between the administration of the second female and sacrifice of the first animal, these animals of different dose groups were co-housed

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2004/73/EC of 29 April 2004

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanesulphonate

EC Number:

261-818-3

EC Name:

Potassium 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanesulphonate

Cas Number:

59587-38-1

Molecular formula:

C8H5F13O3S.K

IUPAC Name:

potassium 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctane-1-sulfonate

Test material form:

solid

Details on test material:

Purity: 97.1%

Specific details on test material used for the study:

Purity: 97.1%

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan®:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks at treatment
- Weight at study initiation: 152 to 182 g at treatment
- Fasting period before study: overnight before dosing
- Housing:
Sighting Study: In groups of four/three during acclimatization, and two during the study (For animal welfare reasons, a spare animal was used in order not to house the animal individually.) in Makrolon type-4 cages with Lignocel S8-15 sawdust bedding.
Main Study: In groups of four/three during acclimatization and in groups of four during the study (unless number is reduced by mortality) in Makrolon type-4 cages with Lignocel S8-15 sawdust bedding.
- Diet: Pelleted standard Teklad Global Diet 2014C rat/mouse maintenance diet ad libitum (supplied by Envigo RMS, S.A., batch no. 021517MA and 011017MA, expiry dates: 12 November 2017 and 7 October 2017, respectively).
- Water: Tap water in bottles ad libitum.
- Acclimation period: 7 to 23 days between arrival and treatment start

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24
- Humidity (%): 30 to 70
- Air changes (per hr): 15 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL for the 300 mg/kg bw dose group, 200 mg/mL for the 2000 mg/kg dose group.
- Amount of vehicle: 10 mL/kg bw
- Lot/batch no: MKBW9504V

Doses:

300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

SIGHTING TEST
1 female was dosed at 300 mg/kg bw. If no signs of toxicity occured another female was dosed at 2000 mg/kg bw. If no mortality occured within 5 days, the main test was conducted.
MAIN TEST 1
4 additional females were dosed at 2000 mg/kg bw.
MAIN TEST 2
-Another four animals were dosed at 300 mg/kg bw.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Viability and mortality were recorded daily during the acclimatization period and were checked together with clinical signs. Body weights were recorded on study days 1 (pre-administration), 8 and 15. Clinical signs were recorded daily during the acclimatization period and once during the first 30 minutes and at 1, 2, 3 and 5 hours after administration on test day 1 and during days 2 to 15. All abnormalities were recorded.
- Necropsy of survivors performed: All surviving animals were sacrificed at the end of the observation period (day 15), by intraperitoneal injection of sodium pentobarbital at the dose of 200 mg/kg and at 4 mL/kg. The animals were then examined macroscopically and all abnormalities recorded. Thereafter, the carcasses were discarded. The females found dead on study days 7 and 5 (female no. 2 and 4, respectively) and those euthanized for welfare reasons on day 8 (females no. 3, 5 and 6) were necropsied.
Organs showing evidence of macroscopic pathology were preserved for possible future examination.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The animal administered at 300 mg/kg in the sighting study did not die or show any clinical signs.
Another animal was administered at 2000 mg/kg and it showed no signs of toxicity nor did it die either before the administration of the four additional females at this dose level in order to complete the Main Study.
After the start of the main study, the first animal dosed at 2000 mg/kg bw and one female of the main study were found dead on study days 7 and 5, respectively. As a consequence, and seeing that the rest of the animals were showing the same clinical signs and a body weight loss between days 1 and 8, it was considered necessary to sacrifice them for welfare reasons.Therefore, it was necessary to administer another four animals at 300 mg/kg in order to complete the main study at this dose level. No deaths occurred in this dose-group.

Clinical signs:

- 300 mg/kg bw: there were no clinical signs during the study.
- 2000 mg/kg bw: Piloerection and/or hunched posture were observed in all animals between day 4 and their sacrifice. The initially dosed female also showed decreased activity, hypothermia, abnormal gait, reduced body tone and pallor on day 7, just before the animal was found dead.

Body weight:

- 300 mg/kg bw: No effects in body weight were observed as body weights were within the range commonly recorded for this strain and age.
- 2000 mg/kg bw: A body weight loss of 13-23% was observed in all the animals that survived until day 8 of study.

Gross pathology:

- 300 mg/kg bw: No macroscopic findings were recorded at necropsy.
- 2000 mg/kg bw: Enlarged kidneys were observed in all animals. Additionally, one of them showed stomach with reddish area in mucosa. No other macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral toxicity test showed an LD50 between 300 and 2000 mg/kg bw

Executive summary:

The acute oral toxicity of the test substance was assessed according to the Fixed dose Method (OECD guideline 420) and GLP principles. In this study one female Wistar (RccHan®:WIST) rat was dosed with 300 mg/kg bw test substance by gavage. Since no toxicity was observed, an additional female was treated with 2000 mg/kg bw and subsequently, since no mortality occurred within 5 days, 4 additional females were treated at this dose. However, the first animal dosed at 2000 mg/kg bw and one female of the main study were found dead on study days 7 and 5, respectively. As a consequence, and seeing that the rest of the animals were showing the same clinical signs and a body weight loss between days 1 and 8, it was considered necessary to sacrifice them for welfare reasons. Therefore, it was necessary to administer another four animals at 300 mg/kg in order to complete de main study at this dose level. No deaths occurred in this dose group during the 14 -day observation period. In the animals treated at 2000 mg/kg bw piloerection and/or hunched posture were observed in all animals between day 4 and their sacrifice. The initially dosed female also showed decreased activity, hypothermia, abnormal gait, reduced body tone and pallor on day 7, just before the animal was found dead. In addition, a body weight loss of 13-23% was observed in all the animals in this dose group that survived until day 8 of study. Gross pathology revealed enlarged kidneys in all animals. Additionally, one of them showed stomach with reddish area in mucosa. No other macroscopic findings were recorded at necropsy. In the animals treated at 300 mg/kg bw, no clinical signs, effects on body weight or gross pathology observations were found. Therefore, under the conditions of the test, the acute oral LD50 for the test substance in rat was determined to be between 300 and 2000 mg/kg bw. Based on these results, the test substance is considered to be acutely harmful (category 4).