Phosphoric acid, mixed esters with 3,3,4,4,5,5,6,6,7,7,8,8,8 –tridecafluorooctan-1-ol and polysubstituted alkane, mono- and diammonium salts

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was selected as a key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Only males were studied; 4 concentrations were used; 5 animals/group were used.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

- Purity: not reported as such

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: Not reported
- Fasting period before study: No
- Housing: Except during exposure, animals were housed individually in solid bottom caging with bedding with bedding and nestlets as enrichment.
- Diet (e.g. ad libitum): Ad libitum, except during exposure
- Water (e.g. ad libitum): Ad libitum, except during exposure
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26ºC
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Approximate 12-hour light/dark cycle. On October 25, 2009 and November 1, 2009, the animals in the 50, 86, and 150 mg/m³ groups received a 11/13-hour light/dark cycle because of the time change during Daylight Saving time.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure chamber was constructed of glass (cylindrical). A polycarbonate baffle at the chamber inlet promoted uniform chamber distribution of the test atmosphere.
- Exposure chamber volume: 34L
- Method of holding animals in test chamber: During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethylmethacrylate faceplate attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.
- Source and rate of air: Chamber airflow was 14 L/min which provided 25 air changes per hour
- Method of conditioning air: Chamber oxygen concentration was 21%.
- System of generating particulates/aerosols: Chamber atmospheres were generated by aerosolisation of the test substance in air with a nebulizer. The test substance was metered into the nebulizer with a syringe infusion pump. High-pressure air, metered into the nebulizer by a flow controller, carried the resulting atmosphere into the exposure chamber. The syringe infusion pump was controlled and monitored by an automated data system. Chamber concentrations of test substance were controlled by varying the test substance feed rate to the nebulizer.
- Method of particle size determination: A sample to determine particle size distribution (mass median aerodynamic diameter, geometric standard deviation, and percent particles less than 10 μm diameter) was taken during each exposure with a cyclone preseparator/cascade impactor and a constant flow air sampler.
- Treatment of exhaust air: Test atmospheres were exhausted through a dry-ice cold trap prior to discharge into the fume hood.
- Temperature, humidity, pressure in air chamber: 19 - 21°C, 50 - 66%, pressure not reported.

TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheric concentration of the test substance in the test chamber was determined by gravimetric analysis at approximately 30-minute intervals. Known volumes of chamber atmosphere were drawn from the sampling port through a 25 mm filter cassette containing a pre-weighed glass fibre (Type A/E) filter. The filters were weighed on a microbalance. The filter weights were automatically transferred to an automated data system, which calculated the chamber concentrations based on the difference between pre- and post-sampling filter weights divided by the volume of chamber atmosphere sampled. Gravimetric sample start- and stop-times for each sample were controlled and recorded by an automated data system. Because of the chemical composition of the test substance, it was decided to sample for ammonia in the exposure chamber during the 500 and 50 mg/m³ exposures. Using a Drager-Tube apparatus specific for ammonia, concentrations of 50 and 20 ppm of ammonia were measured during the 500 and 50 mg/m³ exposures, respectively. Ammonia chamber concentrations were not measured in the subsequent intermediate level exposures.
- Samples taken from breathing zone: yes
- Aerosol size: See Table 1

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

50 ± 3.4 mg/m³, 86 ± 4.0 mg/m³, 150 ± 7.2 mg/m³, 500 ± 28 mg/m³ (mean atmospheric aerosol concentrations)

No. of animals per sex per dose:

5 male rats per dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for mortality and response to alerting stimuli 3 times during each exposure and observed for mortality and clinical signs of toxicity immediately after they were removed from the restrainers following exposure. During the recovery period, all rats were observed each day for mortality. Rats were observed for clinical signs of toxicity on the day following exposure and at least twice more during the recovery period.
- Frequency of weighing: Rats were weighed on the day following exposure and at least twice more during the recovery period.
- Necropsy of survivors performed: No

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

other: approximate lethal concentration (ALC)

Effect level:

86 mg/m³ air

Exp. duration:

4 h

Mortality:

One day post-exposure all five rats of the 500 mg/m³ and 150 mg/m³ exposure groups were found dead. One day post-exposure, one rat of the 86 mg/m³ exposure group was found dead. All other animals survived.

Clinical signs:

other: Four of the 5 rats exposed to 500 mg/m³ exhibited laboured breathing after the exposure. All 5 rats had nasal discharge. Two of the 5 rats exposed to 150 mg/m³ exhibited laboured breathing after the exposure. All 5 rats had nasal discharge. Two of the 5 r

Body weight:

One day post-exposure following the 86 mg/m³ exposure the 4 surviving rats lost 7-30 grams. Two days post-exposure, 2 of 4 rats lost 5-9 grams. Beginning at 3 days post-exposure, the 4 surviving rats gained weight at a normal rate for the remainder of the recovery period.
One day post-exposure following the 50 mg/m³ exposure, 4 of 5 rats lost 1-29 grams. Beginning at 2 days post-exposure, all rats gained weight at a normal rate for the remainder of the recovery period.

Applicant's summary and conclusion

Conclusions:

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
ALC (male rats) = 86 mg/m³

Executive summary:

Four groups of 5 male Crl:CD(SD) rats each were exposed nose only for a single 4-hour period to the test substance in air. The test atmosphere was generated by aerosolisation and the aerosol concentration was determined by gravimetric analysis.

Rats were exposed to mean atmospheric aerosol concentrations of 500 ± 28 mg/m³, 150 ± 7.2 mg/m³, 86 ± 4.0 mg/m³, and 50 ± 3.4 mg/m³. The fractional mortality (number dead/ number exposed) for these exposures were 5/5, 5/5, 1/5, and 0/5, respectively. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) measured for the test atmospheres ranged from 2.0- 2.2 μm and 1.9-2.0, respectively and 99% of the aerosol was less than 10 μm for all the exposures.

Following the 500 mg/m³ exposure, 4 of 5 rats exhibited laboured breathing and 5 of 5 rats had nasal discharge. One day post-exposure, all 5 rats were found dead. Following the 150 mg/m³ exposure, 2 of 5 rats exhibited laboured breathing and 5 of 5 rats had nasal discharge. One day post-exposure, all 5 rats were found dead. Following the 86 mg/m³ exposure, 2 of 5 rats had nasal discharge. One day post-exposure, one rat was found dead. The 4 surviving rats lost 7-30 grams. Two days post-exposure, 2 of 4 rats lost 5-9 grams. Beginning at 3 days post-exposure, the 4 surviving rats gained weight at a normal rate for the remainder of the recovery period. No rats at this dose level exhibited any adverse clinical signs beginning at 1 day post-exposure and for the remainder of the recovery period. Following the 50 mg/m³ exposure, 2 of 5 rats had nasal discharge. One day post-exposure, 4 of 5 rats lost 1-29 grams. Beginning at 2 days post-exposure, all rats gained weight at a normal rate for the remainder of the recovery period. No rats at this dose level exhibited any adverse clinical signs beginning at 1 day post-exposure and for the remainder of the recovery period.

Under the conditions of this study, the approximate lethal concentration (ALC) was 86 mg/m³.