2-Propenoic acid, γ-ω-perfluoro-C8-14-alkyl esters

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-05-08 to 2003-07-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The MMAD for the high dose tested achieved only particle sizes of 6.8 µm, which is greater than the targeted MMADs of 1 to 4 µm to allow maximum lung exposure. Histopathologically examination was only performed in the low dose group tested. Although the histopathology is not part of such kind of acute toxicity studies an examination of the high dose group would have been valuable.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Principles of method if other than guideline:

The approximate lethal concentration (ALC) is defined as the lowest dose administered which caused death either on the day of dosing or within 14 days post exposure.

GLP compliance:

yes

Test type:

other: Approximate Lethal Concentration (ALC)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Perfluoroalkylethylacrylate

IUPAC Name:

Perfluoroalkylethylacrylate

Constituent 2

Reference substance name:

2-Propenoic acid, γ-ω-perfluoro-C8-14-alkyl esters

EC Number:

288-003-5

EC Name:

2-Propenoic acid, γ-ω-perfluoro-C8-14-alkyl esters

Cas Number:

85631-54-5

Molecular formula:

C11H7F13O2 - C17H7F25O2

IUPAC Name:

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl prop-2-enoate; 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl prop-2-enoate; 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-henicosafluorododecyl prop-2-enoate; 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,14-pentacosafluorotetradecyl prop-2-enoate

Test material form:

other: solid

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

male

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure chambers were constructed of glass (cylindrical). A baffle indide each chamber promoted uniform distribution of the test atmosphere.
- Exposure chamber volume: Nominal internal volume of 34 L.
- Method of holding animals in test chamber: During exposure animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The resstrainers were insertet into a polymethylmethacrylate faceplate which was attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.
- System of generating particulates/aerosols: Chamber atmospheres were generated by aerolization of the solid test substance in air with a glass, round bottom flask placed in a heating mantle. The flask was heated to approximately 100°C to melt the test substance. Filtered, high pressure air, metered into the flask by a Brooks model 5851E mass flow controller, carried the evolved vapour through heated glass tubing. For the 0.1mg/L exposure, 2 chambers were used. The vapor passed from the heated tubing into the first chamber where a condensation aerosol was formed. The aerosol then passed into the second chamber for animal exposure. For the 1.8 mg/L exposure, the vapor passed from the heated tubing in the exposure chamber where an aerosol was formed.
- Method of particle size determination: A sample to determine particle size distribution (mass median aerodynamic diameter and percent particles less than 1, 3, or 10 µm diameter) was taken during each exposure with a Sierra Series 210 cyclone preseparator/Cascade impactor and Sierra series 110 constant flow air sampler.
- Treatment of exhaust air: Test atmospheres were exhausted through an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.
- Chamber Temperature was targeted at 22 ± 2°C. The temperature was monitored continuesly with a digital traceable thermometer and recorded 3 times during each exposure.
Chamber relative humidity was targeted at 50 ±10%. The relative humidity was measured with a digital psychrometer and recorded 3 times during each exposure.
Chamber oxygen concentration was targeted to be at least 19% and was measured with an oxygen analyser and recorded 3 times during each exposure.
Chamber air flow ranged from 15 to 25 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: The atmopespheric concentration of the test item was determined by gravimetric analysis at approximate 30-minute intervals during each exposure. Known volume of chamber atmosphere were drawn from the sampling port through a 25 mm filter cassette that contained a pre-weighed Gelman glass fiber filter. The filters were weighed on a microbalance. The atmospheric concentration of the test item was calculated from the difference in the pre-and post-sampling filter weights divided by the volume of the chamber atmosphere sampled.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
For the 0.10 mg/L atmosphere : <1 µm 24%; <3 µm 37%; <10 µm 77 %.
For the 1.8 mg/L atmosphere: <1 µm 8 %; <3 µm 13 %; < 10 µm 86 %.
- Measured aerosol concentration 0.10 ±0.058 mg/L and 1.8 ± 0.12 mg/L.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 5.8 ± 2.2 µm for the 0.10 mL/L atmoshpere and 6.8 ± 1.8 µm for the 1.8mg/L atmosphere, respectively.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The atmospheric conc. of the test item was determined by gravimetric analysis at approximately 30-minute intervals during each exposure.

Duration of exposure:

4 h

Remarks on duration:

nose only

Concentrations:

0.10 and 1.8 mg/L (measured aerosol concentration)

No. of animals per sex per dose:

6 males/dose

Control animals:

no

Details on study design:

Two groups of 6 male rats each were exposed to aerosol atmospheres of the test substance in air. Rats were exposed nose only for a single , 4-hour period. Following exposure, 3 rats from the 0.10 mg/L exposure were retained for a 1-day recovery period; the remaining 3 rats were retained for a 14-day recovery period. Rats from the 1.8 mg/L exposure group were retained for a 14-day recovery period.
Rats were approximately 8 weeks old and weighed between 258 and 279 grams at the time of exposure.
Animals were observed for mortality 4 times during each exposure and observed for mortality and clinical signs of toxicity immediately after exposure. During the recovery period, all rats were observed each day for mortality. Rats were weighed and observed for clinical signs of toxicity on the day following exposure and at least twice more during the recovery period. At the end of both recovery periods, all rats from the 1.00 mg/L group were sacrificed for anatomic pathology evaluation. All rats from the 1.8 mg/L exposure were sacrificed by carbon dioxide asphyxiation and discarded.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

other: ALC (approximate lethal concentration)

Effect level:

> 1.8 mg/L air (analytical)

Based on:

act. ingr.

Exp. duration:

4 h

Remarks on result:

other: nose only

Mortality:

No deaths occurred during the study

Clinical signs:

other: Following exposures, when the rats were removed from the restrainers, the clinical signs of toxicity frequently observed included colored dicharge of the nose and eyes. These signs are typically observed in inhalation studies with rats under restraint.

Body weight:

No body weight loss were observed in rats exposed to 0.10 mg/L immediately after exposure or after the 14-day recovery period. Three of the 6 rats exposed to 1.8 mg/L showed slight weight loss (< 10 gramms) on the day following exposure, followed by a normal weight gain rate (approximately 5-10 g/day) for the remainder of the recovery period.

Gross pathology:

Yes.

Other findings:

ANATOMIC PATHOLOGY EVALUATION.
Samples from 3 rats that were sacrified one day after exposure to 0.10 mg/L and from 3 rats that were sacrified 14 days after exposure. Tissues examined: Lung, Trachea, Nose, Larynx, Pharynx. No remarable findings were seen in trachea, nose and pharynx in all 3 rats, whereas in the larynx of one rat sacrifcied one day after exposure infiltration of mononuclear cells were described. In the lung of one rat each (one day and 14 days after exposure) no remarkable findings were described. Alveolar hemorrhage in the lung were described in 2 rats sacrificed one day after exposure to the test item as well as in one rat sacrificed 14 days after exposure. In one rat sacrificed 14 days after exposure perivascular mononuclear cell infiltration was observed. There were no appreciable differences between the two groups. The alveolar hemorrhages were very minimal, and were likely agonal changes occurring at the time of sacrifice. Although no concurrent controls were provided, the changes present in tissues examined were considered to be of the type and severity expected in this strain of rats, and none of them appeared to be the result of treatment.

LUNG WEIGHT
Lung weights in 3 rats sacrificed 1 day after exposure to the test item at 0.10 mg/L did not appear to be different from control rats of similar weights in recent laboratory inhalation studies.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

Under the conditions of this study, the approximate lethal concentration (ALC) for the test item is greater than 1.8 mg/L.

Executive summary:

Two groups of 6 male rats were exposed nose-only, a single 4 -hour period to the test substance in air. Rats were exposed to atmospheres of the test substance in air at concentrations of 0.10 or 1.8 mg/L. The mass median aerodynamic diameters for the aerosol tested were 5.8 and 6.8 µm, respectively. No rats died following exposure to the test substance. Other than slight body weight losses measured in 3 of 6 rats one day after exposure to 1.8 mg/L of the test substance, there were no significant clinical signs observed in the exposed rats at either test concentration, Histological examination of rats exposed to 1.0 mg/L showed no treatment related effects.

Under the conditions of this study, the approximate lethal concentration (ALC) for the test item H-25777 is greater than 1.8 mg/L.

However, the mass median aerodynamic diameter (MMAD) of the tested aerosol at this concentration was 6.8 µm. Targeted MMADs in inhalation studies are from 1 - 4 µm to allow maximum lung exposure. Several attempts were made to produce smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates.