acrylic acid, 3-(trimethoxysilyl)propyl ester

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

no

Test material

Test material information

1

Reference substance name:

-

EC Number:

419-560-6

EC Name:

-

Cas Number:

4369-14-6

Molecular formula:

C9H18O5Si

IUPAC Name:

3-(trimethoxysilyl)propyl prop-2-enoate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent
- Females nulliparous and non-pregnant: Not specified
- Age at study initiation: Young adult
- Weight at study initiation: males 244-317 g; females 210-241 g
- Fasting period before study: Not specified
- Housing: In groups of 5 per sex
- Diet (e.g. ad libitum): Rat and Mouse Expanded diet No. 1, ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 49-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 2.2 - <= 2.4 µm

Geometric standard deviation (GSD):

>= 0.43 - <= 0.49

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION:
- Exposure apparatus: Exposure chamber
- Exposure chamber volume: 30 litres
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single ties of the exposure chamber and sealed by means of a rubber "O" ring. Only the noses of the animals were exposed to the test atmosphere.
- Source and rate of air: Compressed air was supplied by means of a Gast oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.0005 µm before it was introduced to the nebuliser.
- Method of conditioning air: See source and rate of air.
- System of generating particulates/aerosols: The test material was aerosolised using a glass concentric jet nebuliser located at the top of the exposure chamber. The nebuliser was connected to a syringe attached to a modified infusion pump, which provided a continuous supply of test material under pressure, and a metered compressed air supply.
- Method of particle size determination: Particle size determination was performed at least three times during each exposure period using a Cascade Impactor. This device consisted of 6 impactor stages with stainless steel collection substrates and a back up glass fibre filter housed in an aluminium sampler. The sampler was temporality sealed in a sampling port near the animals' breathing zone. Exposure chamber air was drawn through the cascade impactor using a vacuum pump for a suitable time period. The collection substrates were weighed before and after sampling and the weight of test material, collected at each stage, calculated by the difference in weight. From the results obtained, the weight distribution of particles in the size range > 10 µm, 10-6 µm, 6-3.5 µm, 3.5-1.6 µm, 1.6-0.9 µm and 0.9-<0.5 µm was calculated.
- Treatment of exhaust air: Not specified
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout each 4-hour exposure period.

TEST ATMOSPHERE:
- Brief description of analytical method used: The chamber concentration was estimated at regular intervals during each exposure period. The gravimetric method used employed glass fibre filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period. Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights divided by the volume of air sampled was the chamber concentration.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated):
- Particle size distribution: See attachment
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): See attachment

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: 5 mg/L (nominal, 5.06 mg/L measured) was used for the first exposure. Further concentrations (0, 1.96, and 3.22 mg/L measured) were selected after consideration of the results of the previous exposure.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.96, 3,22, and 5.06 mg/L

No. of animals per sex per dose:

5M, 5F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during the exposure, immediately on removal from the restraining tubes at the end of the exposure, one hour after termination of the exposure, and subsequently once daily for the 14 days. Individual body weights were recorded on the day of exposure and on days 7 and 14 or at death.
- Necropsy of survivors performed: Yes
- Other examinations performed: The respiratory tract was subject to a detailed macroscopic examination for signs of irritancy or local toxicity.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.79 mg/L air (analytical)

Based on:

test mat.

95% CL:

>= 3.2 - <= 4.48

Exp. duration:

4 h

Mortality:

At 5.06 mg/L: On day one following exposure, two males were found dead and three males and four females were killed in extremis. One female survived.

At 3.22 mg/L: One male and one female were killed in extremis on day 1.

At 1.96 mg/L: No deaths occurred.

Clinical signs:

other: Clinical signs: Wet fur, hunched posture, lethargy, pilo-erection, decreased respiratory rate, ptosis, pallor of the extremities, and abnormal reddening of the eyes, snout and forefeet. Dose-related incidents: Gasping / noisy respiration and ataxia.

Body weight:

Body weight loss or decreased body weight gain were noted during the first week of the observation period. Normal body weight gain was observed in the surviving animals during the second weeks of the 14-day observation period.

Gross pathology:

The animals that died or that were killed in extremis at 3.22 and 5.06 mg/L showed pale and swollen lungs, and two showed abnormal darkening of the lungs. Incidents of pallor and/or accentuated lobular patterning of the liver, pale kidneys and congestion, gaseous distension and reddening of the small intestine were noted. One animal exposed to 5.06 mg/L showed a small left kidney. There were two incidents of dark patches or dark foci on the lungs of surviving animals exposed to 3.22 mg/L but otherwise no abnormalities were detected in surviving animals at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

This classification is consistent with Annex VI of Regulation (EC) No. 1272/2008.

Conclusions:

In the acute inhalation toxicity study, conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value was 3.79 mg/L for male and female rats following a 4-hour inhalation exposure to 3-(trimethoxysilyl)propyl acrylate aerosol.