acrylic acid, 3-(trimethoxysilyl)propyl ester

Endpoint summary

Description of key information

The key acute oral toxicity study with 3-(trimethoxysilyl)propyl acrylate (CAS No. 4369-14-6, EC No. 419-560-6) was conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP (reliability score 1, Hita Research Laboratories, 1994a). The LD50 value in this study was >2000 mg/kg bw in male and female rats.

 

The key acute inhalation toxicity study with 3-(trimethoxysilyl)propyl acrylate aerosol was conducted according to OECD Test Guideline 403 and in compliance with GLP (reliability score 1, SafePharm Laboratories Limited, 1995c). The LC50 value in this study was 3.79 mg/L aerosol for male and female rats following a 4-hour inhalation exposure.

 

A dermal study does not need to be conducted because the registered substance is classified as corrosive to the skin.

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:

7th April 1994 - 28th July 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 5 weeks old
- Weight at study initiation: Males 104-113.7 g; females: 93.9 - 101.9 g
- Fasting period before study: Yes, overnight
- Housing: Individually
- Diet (e.g. ad libitum): MF pelleted diet, ad libitum
- Water (e.g. ad libitum): Municipal water, ad libitum
- Acclimation period: Yes, but duration not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE:
- Concentration in vehicle: 0, 10 and 20 w/v % in olive oil
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Not specified

DOSAGE PREPARATION (if unusual): The test substance was weighed and dissolved in olive oil. The dose formulations were prepared daily before dosing. Stability of the test substance in dose formulations were confirmed for 3 days before dosing. Test concentrations were confirmed.

Doses:

0, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5M, 5F

Control animals:

yes

Remarks:

vehicle (olive oil) control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for general condition were carried out continuously up to 6 hours post-dosing, and once a day until 14 days post-dosing. Body weights were recorded at days 1, 3, 7, 10 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: In each animal surface, orifices, organs in skull, thoracic cavity and abdominal cavity were examined macroscopically.

Statistics:

Mean values and standard deviations for body weights in each group were calculated.

Preliminary study:

Doses: 0, 20, 100, 500, and 2000 mg/kg bw
Mortality data: No animals died at any of the tested dose levels.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No males died during the study.

One female at 2000 mg/kg bw died 1 day after dosing. Decreased spontaneous locomotion, respiratory rate, ptosis and salivation, mucous stool, and soft stool were observed from 30 minutes after dosing in this female.

Clinical signs:

other: Males: Decreased spontaneous locomotion, respiratory rate, ptosis and salivation were observed from 15 minutes after dosing at 2000 and 1000 mg/kg bw. These effects resolved by day 1 post-dosing. Mucous stool was seen in males at 0, 1000, and 2000 mg/kg b

Gross pathology:

Dead female at 2000 mg/kg bw: Reddish spots in the mucosa of the glandular stomach were observed.

Surviving females: No abnormalities were seen at any dose.

Males (all survived): Adhesion to the diaphragm and liver (1/5) in the forestomach was seen at 2000 mg/kg bw, with no abnormalities noted at 1000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute oral toxicity study with 3-(trimethoxysilyl)propyl acrylate in olive oil, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 value was >=2000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 2 000 mg/kg bw

Quality of whole database:

Reliability 1, OECD Test Guideline 401 study

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 790 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

Reliability 1, OECD Test Guideline 403 study

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key acute oral toxicity study with 3-(trimethoxysilyl)propyl acrylate, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP (reliability score 1, Hita Research Laboratories, 1994a), 5 male and 5 female rats were given a single oral gavage dose (in olive oil) of 0, 1000 or 2000 mg/kg bw. Following administration, the animals were observed for 14 days. Observations for general condition were carried out continuously up to 6 hours post-dosing, and once a day until 14 days post-dosing. Body weights were recorded at days 1, 3, 7, 10 and 14. At the end of the observation period, necropsy was performed and, in each animal, the surface, orifices, organs in skull, thoracic cavity and abdominal cavity were examined macroscopically.

 

No males died in the study. One female from 2000 mg/kg bw group died on observation day 1. The animal exhibited decreased spontaneous locomotion, respiratory rate, ptosis, salivation, mucous stool, and soft stool from 30 minutes after dosing. In males, decreased spontaneous locomotion, respiratory rate, ptosis and salivation were observed from 15 minutes after dosing in the 1000 and 2000 mg/kg bw groups, with these effects resolved by day 1 post-dosing. Mucous stool was seen for males in the control, 1000, and 2000 mg/kg bw group males, as well as soft stool for the control group. In females, decreased spontaneous locomotion, respiratory rate and ptosis seen in the 1000 and 2000 mg/kg bw groups and salivation in the 2000 mg/kg bw group. These effects in females were observed from 15 minutes for the 1000 mg/kg bw group and 30 minutes after dosing for the 2000 mg/kg bw group, with recovery by day 1. Mucous stool was seen for the control, 1000, and 2000 mg/kg bw group females. For body weight gain, a tendency to decrease this parameter was observed for males in the 2000 mg/kg bw group at day 1, with recovery thereafter. No effect on body weight gain was seen in the surviving females. Locally in the stomach, reddish spots in the mucosa of the glandular stomach were seen in the single dead female at 2000 mg/kg bw. Adhesion to the diaphragm and liver (1/1) in the forestomach was observed during necropsy in 1 out of 5 males at 2000 mg/kg bw. There were no abnormalities seen in either sex at 1000 mg/kg bw, or for surviving females at 2000 mg/kg bw.

The oral LD50 value was >2000 mg/kg bw in male and female rats.

 

In the key acute inhalation toxicity study, conducted according to OECD Test Guideline 403 and in compliance with GLP (reliability score 1, SafePharm Laboratories Limited, 1995c), 5 male and 5 female rats were subjects to a single 4-hour nose only inhalation exposure to 3-(trimethoxysilyl)propyl acrylate aerosol at concentrations of 1.96, 3.22 and 5.06 mg/L. The 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 14 days. Individual body weights were recorded on the day of exposure and on days 7 and 14 or at death. At the end of the 14-day exposure period, the surviving animals were killed and subject to macroscopic examination. The respiratory tract was subject to a detailed macroscopic examination for signs of irritancy or local toxicity.

 

Following exposure to 5.06 mg/L, two males were found dead, and three males and four females were killed in extremis on day 1. At this concentration, no males were alive past day 1, with the one female surviving until day 14. Following exposure to 3.22 mg/L, one male and one female were killed in extremis on day 1. No deaths occurred at 1.96 mg/L.

 

Clinical signs observed during the study included wet fur, hunched posture, lethargy, pilo-erection, decreased respiratory rate, ptosis, pallor of the extremities and abnormal reddening of the eyes, snout and forefeet. There were incidents of laboured gasping and noisy respiration and ataxia which were dose-related in incidence and there were occasional or isolated incidents of red/brown staining around the snout, swelling of the tongue, dehydration, distended abdomen, increased salivation, and occasional sneezing. Surviving animals recovered to appear normal 1 to 8 days after exposure.

 

Incidents of 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 week of the 14-day observation period.

 

The animals that died or were killed in extremis at 3.22 and/or 5.06 mg/L showed pale and swollen lungs, 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.

 

The LD50 value determined to be 3.79 mg/L for male and female rats following a 4-hour inhalation exposure to 3-(trimethoxysilyl)propyl acrylate aerosol.

Justification for classification or non-classification

3-(Trimethoxysilyl)propyl acrylate is classified for acute inhalation toxicity Cat. 4, H332: "Harmful if inhaled" according to Annex VI of Regulation (EC) No. 1272/2008, as supported by the acute inhalation toxicity data for this substance. 3-(Trimethoxysilyl)propyl acrylate does not require classification for acute oral toxicity according to Regulation (EC) No. 1272/2008.