Sodium 6,14-diethyl-1,1,1,2,2,18,18,19,19,19-decafluoro-8,12-dioxo-10-({[1-(2,2,3,3,3-pentafluoropropoxy)butan-2-yl]oxy}carbonyl)-4,7,13,16-tetraoxanonadecane-9-sulfonate

Endpoint summary

Description of key information

Key, acute toxicity, limit test, rat, oral (gavage), OECD 423, GLP: LD₅₀ > 2000 mg/kg bw

Key, acute toxicity, limit test, rat, inhalation, aerosol, OECD 436, GLP: LD₅₀ > 5500 mg/m³ air

Key, acute toxicity, limit test, rat, dermal, OECD 402, GLP: LD₅₀ > 2000 mg/kg

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 APR - 28 JUN 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 DEC 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: 8 weeks (males) and 9 weeks (females)
- Weight at study initiation: 180 g (range from 191 - 200 g (males), 164-172 g (females))
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 23 °C
- Humidity (%): 52 to 75 %
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15

Route of administration:

oral: gavage

Vehicle:

other: Methocel K4M Premium solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: excellent vehicle performance in long range historical data
- Lot/batch no. (if required): DTl70406

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 (m) / 3 (f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, gross pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All rats survived the observation period.

Clinical signs:

other: No signs of toxicity were seen in the 3 male and 3 female rats after treatment with 2000 mg/kg.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Other findings:

None

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Executive summary:

Study design

This GLP study was performed according to the OECD Guideline for Testing of Chemicals, No. 423: Acute Oral Toxicity - Acute Toxic Class Method (adopted on 17 December 2001) and according to Council Regulation (EC) No. 440/2008. The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight.

Results

No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg of the test item.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD₅₀ value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

This GLP study was performed according to the OECD Guideline for Testing of Chemicals, No. 423: Acute Oral Toxicity - Acute Toxic Class Method (adopted on 17 December 2001) and according to Council Regulation (EC) No. 440/2008. Therefore, the quality of the database is high.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 AUG 2012 - 13 FEB 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

7 SEP 2009

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: 9 weeks
- Weight at study initiation: Males: 262.5 to 268.5 g; Females: 184.4 to 195.1 g
- Fasting period before study: no
- Housing: in groups of 3 of the same sex in Makrolon type IV cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C,
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

IN-LIFE DATES: From: day 1 To: day 14

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Remarks:

flow past

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.37 - <= 1.97 µm

Geometric standard deviation (GSD):

>= 2.43 - <= 2.89

Remark on MMAD/GSD:

The particle size distribution of the generated aerosol was stable during the whole exposure period. The MMADs were at the lower limit of the target range of 1 to 4 μm. Therefore deposition of the particles can be assumed to have occurred mainly in the lower but also in the upper respiratory tract. The GSDs were within the target range of 1.5 to 3. Hence, the particle size distributions obtained were considered to be respirable to rats and appropriate for acute inhalation toxicity testing.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose only, flow past exposure chamber
- Method of holding animals in test chamber: animals were confined separately in restraint tubes
- Source and rate of air: 1.0 L/min
- System of generating particulates/aerosols: Hudson nebulizer connected to a Lomir syringe pump.
- Method of particle size determination: Gravimetric analysis of the test item deposited on each stage of the cascade impactor.

TEST ATMOSPHERE
Brief description of analytical method used: Gravimetric and chemical determinations of aerosol concentrations.
- Gravimetric determinations were performed twelve times during exposure. The samples were collected on GF/C filters, which were weighed before and after sampling. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Chemical determinations were performed twelve times during exposure. The samples were collected on GF/C filters and analyzed using a LC-MS method.

- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
The particle size distribution of the test aerosol was determined three times during exposure using a Mercer 7 stage cascade Impactor. The particle size distribution was measured by gravimetrically analyzing the test item deposited on each stage of the cascade impactor. Mass Median Aerodynamic Diameters (MMAD) and Geometric Standard Deviations (GSD) were calculated on the basis of the results from the impactor. The target range was 1 to 4 μm for the MMAD and between 1.5 and 3 for the GSD.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The target concentration of 5 mg/L air for 4 hours is the recommended concentration for a limit test (OECD 436, “Acute Inhalation Toxicity - Acute Toxic Class Method”).

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric and chemical determination

Duration of exposure:

4 h

Remarks on duration:

The exposure was interrupted twice for a total of 10 minutes for cleaning purposes.

Concentrations:

5.5 mg/L (chemically determined)

No. of animals per sex per dose:

6 (3m / 3f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 1 (before exposure), 2, 4, 8 and 15 (before necropsy). For single animals body weight was determined additionally on test day 6.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic abnormalities

Statistics:

No statistical analysis was performed as only one group was allocated to the study.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All animals survived the scheduled observation period.

Clinical signs:

other:

Body weight:

From test day 1 to test day 4, moderate to marked body weight loss was noted in two males (no. 1 and 2) and one female (no. 6). The remaining animals showed moderate to marked body weight loss from test day 1 to test day 2. Normal body weight development was recorded in all animals from test day 6 onwards.

Gross pathology:

No macroscopic findings were present at necropsy.

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The LC50 for 4-hour exposure of the test material obtained in this study was greater than 5.5 mg/L air (chemically determined mean aerosol concentration of the active ingredient). There was no indication of relevant sex-related differences in toxicity of the test item.

Executive summary:

Study design

This GLP study was performed according to OECD Guidelines for Testing of Chemicals, Section 4, No. 436: “Acute Inhalation Toxicity – Acute Toxic Class Method" (adopted September 7, 2009). In the study a group of three male and three female albino rats was exposed by nose-only, flow-past inhalation for four hours to the test material at a chemically determined mean concentration of 5.5 mg/L air. All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy and additionally on test day 6 as moderate to marked body weight loss was observed in single animals. On test day 15 all animals were sacrificed and necropsied.

The aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

Results

All animals survived the scheduled observation period. Clinical signs observed in this study consisted of decreased activity, ruffled fur and salivation in all animals, of labored breathing in all males and in two females, of breathing noises in single animals of both sexes, of hunched posture in all males and of excitement or tachypnea in one male and female, respectively. Clinical signs were of a slight to moderate severity and persisted mainly from test day 1 to test day 5. No clinical signs were recorded from test day 6 onwards. Moderate to marked body weight loss was noted in two males and one female from test day 1 to test day 4 and from test day 1 to test day 2 in the remaining animals. No macroscopic findings were recorded during necropsy.

Conclusion

In conclusion, the LC₅₀ for 4 -hour exposure of the test material obtained in this study was greater than 5.5 mg/L air (chemically determined mean aerosol concentration of the active ingredient). There was no indication of relevant sex-related differences in toxicity of the test item.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 500 mg/m³ air

Quality of whole database:

This GLP study was performed according to OECD Guidelines for Testing of Chemicals, Section 4, No. 436: “Acute Inhalation Toxicity – Acute Toxic Class Method" (adopted 7 September 2009). Therefore, the quality of the database is high.

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:

9 OCT 2015 - 8 FEB 2016

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:

24 FEB 1987

Deviations:

yes

Remarks:

The room temperature during the study was transiently outside the anticipated range (measured temperature 18.9 - 24.1°C). This minor transient deviation did not influence the integrity or outcome of the study.

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Energie, Landwirtschaft und Verbraucherschutz (18 NOV 2014)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany
- Age at study initiation: 9 weeks (males), 12 weeks (females)
- Weight at study initiation: 267 - 271g (males), 210 - 221g (females)
- Housing: The rats were kept individually in type III Makrolon cages, with a shelter and a play tunnel, on softwood bedding material.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 24.1°C
- Humidity (%): 47.2 - 67.3%.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: day 1 To: day 15

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 36 cm²
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residue of the test item was wiped off with a dry cloth.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): single dermal administration of 2000 mg/kg
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 (5f / 5m)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, 15
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

other: No clinical signs of toxicity were observed. The application site was brownish stained in all rats after removal of the gauze patch and test item.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

Under the conditions of the present study, the test item revealed no acute toxic potential after single dermal administration in rats. The LD50 value is considered to be higher than 2000 mg/kg.

Executive summary:

Study design

This GLP study was performed according to the OECD Guideline for Testing of Chemicals 402: "Acute dermal toxicity" (adopted on February 24, 1987) and the Council Regulation (EC) No. 440/2008. The test item was applied to the skin of 5 female and 5 male rats at 2000 mg/kg (limit test) by single dermal administration for 24 hours followed by a 2 -week observation period. Mortality and clinical signs were monitored for at least 6 hours after start of exposure and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

 

Results

No mortality occurred during the course of this study.

No clinical signs of toxicity were observed.

The body weight development was inconspicuous throughout the study.

The gross pathological examination revealed no organ alterations.

 

Conclusion

Under the conditions of the present study, the test item revealed no acute toxic potential after single dermal administration in rats. The LD₅₀ value is considered to be higher than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

This GLP study was performed according to the OECD Guideline for Testing of Chemicals 402: "Acute dermal toxicity" (adopted on 24 February 1987) and the Council Regulation (EC) No. 440/2008. Therefore, the quality of the database is high.

Additional information

Acute toxicity - Oral

Acute oral toxicity, OECD 423

The acute oral toxicity of the test item was determined in a limit test, following GLP and according to the OECD Guideline for Testing of Chemicals, No. 423: Acute Oral Toxicity - Acute Toxic Class Method (adopted on 17 December 2001) and according to Council Regulation (EC) No. 440/2008.

Study design

In the study test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight.

Results

No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg of the test item.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD₅₀ value is higher than 2000 mg/kg after single oral administration in rats.

Acute toxicity - inhalation

Acute inhalation toxicity, OECD 436

The acute inhalation toxicity of the test item was determined in a limit test, follwing GLP and according to OECD Guidelines for Testing of Chemicals, Section 4, No. 436: “Acute Inhalation Toxicity – Acute Toxic Class Method" (adopted on 7September 2009).

Study design

In the study a group of three male and three female albino rats was exposed by nose-only, flow-past inhalation for four hours to the test material at a chemically determined mean concentration of 5.5 mg/L air. All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy and additionally on test day 6 as moderate to marked body weight loss was observed in single animals. On test day 15 all animals were sacrificed and necropsied.

The aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

Results

All animals survived the scheduled observation period. Clinical signs observed in this study consisted of decreased activity, ruffled fur and salivation in all animals, of labored breathing in all males and in two females, of breathing noises in single animals of both sexes, of hunched posture in all males and of excitement or tachypnea in one male and female, respectively. Clinical signs were of a slight to moderate severity and persisted mainly from test day 1 to test day 5. No clinical signs were recorded from test day 6 onwards. Moderate to marked body weight loss was noted in two males and one female from test day 1 to test day 4 and from test day 1 to test day 2 in the remaining animals. No macroscopic findings were recorded during necropsy.

Conclusion

In conclusion, the LC₅₀ for 4 -hour exposure of the test material obtained in this study was greater than 5.5 mg/L air (chemically determined mean aerosol concentration of the active ingredient). There was no indication of relevant sex-related differences in toxicity of the test item.

Acute toxicity - dermal

Acute dermal toxicity, OECD 402

The acute oral toxicity of the test item was determined in a limit test, following GLP and according to the OECD Guideline for Testing of Chemicals 402: "Acute dermal toxicity" (adopted on 24 February 1987) and the Council Regulation (EC) No. 440/2008.

Study design

In the study the test item was applied to the skin of 5 female and 5 male rats at 2000 mg/kg (limit test) by single dermal administration for 24 hours followed by a 2 -week observation period. Mortality and clinical signs were monitored for at least 6 hours after start of exposure and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

 

Results

No mortality occurred during the course of this study.

No clinical signs of toxicity were observed.

The body weight development was inconspicuous throughout the study.

The gross pathological examination revealed no organ alterations.

 

Conclusion

Under the conditions of the present study, the test item revealed no acute toxic potential after single dermal administration in rats. The LD₅₀ value is considered to be higher than 2000 mg/kg.

Justification for classification or non-classification

Based on the results of the key study (LD₅₀ in rats > 2000 mg/kg bw), no classification for acute oral toxicity is triggered in accordance with Regulation (EC) No 1272/2008.

Based on the results of the key study (LD₅₀ in rats > 5500 mg/m³ air) no classification for acute inhalation toxicity is triggered in accordance with Regulation (EC) No 1272/2008.

Based on the results of the key study (LD₅₀ in rats > 2000 mg/kg), no classification for acute dermal toxicity is triggered in accordance with Regulation (EC) No 1272/2008.