3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene

Endpoint summary

Description of key information

Acute oral toxicity (OECD 420, GLP): LD50 (rat, female) > 2000 mg/kg bw

Acute dermal toxicity (OECD 402, GLP): LD50 (rat, female/male) > 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:

06 Feb - 21 Mar 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted Feb 2002

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan (Hino Breeding Center)
- Age at study initiation: 8 weeks
- Weight at study initiation: 176.5 g (sighting study); 174.1 - 181.6 g (main study) (ranges)
- Fasting period before study: Yes, the animals were fasted for 17 - 19 h before dosing.
- Housing: The animals were housed in the barrier-system animal rooms in stainless steel cages with mesh-floor (W 260 x D 380 x H 180 mm) before the group allocation and in stainless steel cages with mesh-floor (W 165 x D 300 x H 150 mm) after the group allocation.
- Diet: Pelleted diet (MF, lot number 160915 and 161118, Oriental Yeast), ad libitum
- Water: Chlorinated water (chloric level maintained at 3 - 5 ppm by adding sodium hypochlorite), ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Sighting study: From: 21 Feb 2017 To: 07 Mar 2017; Main study: From: 23 Feb 2017 To: 09 Mar 2017

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

including 3% (w/v) Tween80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 3% (w/v) Tween80
- Amount of vehicle (if gavage): 20 mL
- Justification for choice of vehicle: The test substance was homogenously suspended to olive oil including 3% (w/v) of Tween80. Additionally, the condition of the formulation such as colour did not change at room temperature 4 h after the preparation. Therefore, olive oil including 3% (w/v) Tween80 was selected as vehicle.
- Lot/batch no.: 605027 (olive oil) and ECE6558 (Tween80)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

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: The animals were observed continuously for 10 min, and 30 min and 3 h after dosing on the administration day, and thereafter once in the morning during the observation period. Body weights of all animals were recorded before dosing, and on Day 1, 7 and 14 after dosing with an electric balance.
- Necropsy of survivors performed: Yes, the animals were euthanized by bleeding from the abdominal aorta under isoflurane anesthesia. External surface of the body, all orifices, subcutis, cranial, thoraic, abdomial and pelvic cavities with their contents were observed.

Preliminary study:

In the sighting study one female was dosed at 2000 mg/kg bw. No clinical signs was observed after dosing. Based on this result, additional 4 females were dosed at 2000 mg/kg bw in the main study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

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:

20 Feb - 12 Apr 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted Feb 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan (Hino Breeding Center)
- Age at study initiation: 7 weeks (males); 9 weeks (females)
- Weight at study initiation: 232.2 - 255.7 g (males); 207.4 - 226.7 g (females) (ranges)
- Housing: The animals were housed individually in the barrier-system animal room in stainless steel cages with mesh floor (W 260 x D 380 x H 180 mm).
- Diet: Pelleted diet (MF, lot number 161118, Oriental Yeast), ad libitum
- Water: Chlorinated water (chloric level maintained at 3 - 5 ppm by adding sodium hypochlorite), ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Sighting study: From: 07 Mar 2017 To: 21 Mar 2017

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 5 x 10 cm clipped skin of the dorsal area of trunk.
- Type of wrap: The dosing formulation on a non-woven gauze was applied over the clipped dorsal area and fixed by elastic adhesive bandage (Silkytex5, lot # 51113254, Alcare).

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with purified water (lot # PC160915, Takasugi Pharmaceutical) and absorbent cotton.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1.28 mL/kg bw
- Concentration: 100%

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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: The animals were observed continuously for 10 min, and once 30 min and 3 h after dosing on the administration day, and thereafter once in the morning during the observation period. Body weights of all animals were recorded before dosing, and on Day 1, 7 and 14 after dosing with an electric balance.
- Necropsy of survivors performed: Yes, the animals were euthanized by bleeding from the abdominal aorta under isoflurane anesthesia. Application site, external surface of the body, all orifices, subcutis, cranial, thoraic, abdomial and pelvic cavities with their contents were observed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Slight decreased spontaneous locomotion was sporadically observed in all animals of both sexes from 5 min to 3 h after dosing. The latter mentioned clinical sign of toxicity disappeared in all animals after removal of the non-woven gauze and elastic adhes

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

There are data available regarding acute oral toxicity and acute dermal toxicity for 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene (CAS 25291-17-2) in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

Acute oral toxicity

An acute oral toxicity study (limit test) was performed with the registered substance according to OECD guideline 420 and GLP conditions (Daikin Industries, AOT, 2017). In the sighting study 1 female Crl:CD(SD) rat received a single oral gavage dose of 2000 mg/kg bw of the test substance suspended in olive oil including 3% (w/v) of Tween 80. The animal was observed for 14 days after administration. No mortality and no evidence for toxicity occurred. Based on this result, in the main study additional 4 female Crl:CD(SD) rats received single oral gavage doses of 2000 mg/kg bw and were observed for 14 days after dosing. No clinical signs and no mortality were observed in any of the animals. Necropsy revealed no substance-related findings and no effect on body weight was noted. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

Acute inhalation toxicity

Data waiving

 

Acute dermal toxicity

An acute dermal toxicity study (limit test) was performed with the registered substance according to OECD guideline 402 and GLP conditions (Daikin Industries, ADT, 2017). 5 male and 5 female CRl:CD(SD) rats were exposed to 2000 mg test substance /kg bw for 24 h on the dorsal area of trunk under occlusive conditions. The observation period was 14 days. No mortality was observed. Slight decreased spontaneous locomotion was sporadically observed in all animals of both sexes from 5 min to 3 h after dosing. The latter mentioned clinical sign of toxicity disappeared in all animals after removal of the non-woven gauze and elastic adhesive bandage on the next day of the application. Thereafter, no clinical signs were noted in any animal throughout the study. Body weight gains and necropsy at study termination revealed no abnormalities of toxicity. The application site did not display any signs of skin irritation. Thus, the acute dermal LD50 in rats was found to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral and acute dermal toxicity with 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene (CAS 25291-17-2) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.