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

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

sodium 1,5-dioxo-1,5-bis({[1-(2,2,3,3,3-pentafluoropropoxy)butan-2-yl]oxy})-3-({[1-(2,2,3,3,3-pentafluoropropoxy)butan-2-yl]oxy}carbonyl)pentane-2-sulfonate

EC Number:

700-541-9

Cas Number:

1472634-24-4

Molecular formula:

C27H34F15NaO12S

IUPAC Name:

sodium 1,5-dioxo-1,5-bis({[1-(2,2,3,3,3-pentafluoropropoxy)butan-2-yl]oxy})-3-({[1-(2,2,3,3,3-pentafluoropropoxy)butan-2-yl]oxy}carbonyl)pentane-2-sulfonate

Test material form:

liquid

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.