1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Endpoint summary

Description of key information

In the acute oral toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 401, without information on GLP compliance, the reported LD50 value for female rats was 1713 mg/kg bw (BRRC, 1990).

In the acute inhalation toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 403, without information on GLP compliance, no mortality was observed in rats after 6 hours of exposure to substantially saturated vapour of the test item (BRRC, 1990).

In the acute dermal toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 402, without information on GLP compliance, the reported LD50 value is > 19200 mg/kg bw (16.0 mL/kg bw) in rabbits (BRRC, 1990).

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute 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: no data
- Age at study initiation: no data
- Weight at study initiation: 200-300 g
- Fasting period before study: the rats were fasted overnight prior to dosing
- Housing: no data
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

other: stomach intubation

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg

Doses:

Male rats: 8.0, 4.0, 2.83, 2.0, 1.0 mL/kg bw (9384, 4692, 3320, 2346, 1173 mg/kg bw based on density of 1.173)
Female rats: 4.0, 2.0, 1.41, 1.0 mL/kg bw (4692, 2346, 1654, 1173 mg/kg bw based on density of 1.173)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on days 0, 7 and 14. The frequency of observations for clinical signs of toxicity is not clarified in the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and histopathology was performed to kidneys and bladders of animals treated with 1.0 to 4.0 mL/kg bw test substance.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2.55 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 2988 mg/kg bw

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1.46 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 1713 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2.01 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 2358 mg/kg bw

Mortality:

Death occurred between 1 to 6 days post-administration. the survivors recovered between 3 and 8 days from the 14-day study period. 5 out of 5 males treated with 8.0 or 4.0 mL/kg bw died, as well as 4 out of 5 males treated with 2.83 mL/kg bw. Male rats treated with lower doses survived the 14-day study period. 5 out of 5 females treated with 4.0 or 2.0 mL/kg bw died, as well as 2 out of 5 females treated with 1.41 mL/kg bw. The females treated with lower doses survived until the end of the study.

Clinical signs:

other: Signs of toxicity included sluggishness, lacrimation in two animals, salivation in one animal, prostration in two animals, red crust on the perinasal and periocular fur, red stain on the periurogenital fur and blood in the urine.

Gross pathology:

Necropsy of the animals that died during the study revealed pink to red lungs, discoloured livers, discoloured stomach or intestines, stomach distended with white material and/or gas, haemorrhaged stomachs, discoloured kidneys, one enlarged kidney, kidneys filled with white or brown material, bladders filled with red liquid and numerous instances of blood in the urine. Gross pathologic evaluation of survivors revealed one dark red liver, red to yellow intestines in one animal, and a trace amount of blood in the urine in one animal.

Other findings:

- Histopathology: The kidney lesions included hyaline droplet accumulation, tubular proteinosis and tubular epithelial cell degeneration, haemorrhage, tubular cell hyperplasia or hypertrophy, tubular basofilia, mineralization, pyelonephritis and microthrombi. In the bladder haemorrhage, hyperplasia, cellular debris, hyaline droplet accumulation and thrombi were observed. These lesions were notable at higher dose levels.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In the acute oral toxicity study for tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 401, without information on compliance with GLP, the reported LD50 value for female rats was 1713 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 713 mg/kg bw

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 200-300 g
- Fasting period before study: the rats were fasted overnight prior to dosing
- Housing: no data
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: animal chamber
- Exposure chamber volume: 100 to 151 L
- Method of holding animals in test chamber: no data
- Source and rate of air: The vapour is produced by enclosing approximately 100 g of the test material in a sealed chamber.
- Method of conditioning air: A mixing fan periodically agitates the chamber atmosphere to aid in distribution of the vapour. Oxygen is added for static exposures to maintain oxygen content of 20 % in the chamber.
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: no data


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Concentrations:

substantially saturated vapour

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights were recorded on days 0, 7 and 14. Frequencies of observations for clinical signs of toxicity were not clarified.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight.

Key result

Sex:

male/female

Dose descriptor:

other: substantially saturated vapour

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: No deaths occurred

Mortality:

No deaths occurred during the 14-day observation period following 6-hour exposure.

Clinical signs:

other: No clinical signs of toxicity were observed after 6-hour exposure to substantially saturated vapour of the test item.

Body weight:

Expected body weight gain was observed in all test animals.

Gross pathology:

No macroscopic abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute inhalation toxicity study for tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD test guideline, but without information about GLP compliance, no mortality was observed in rats after 6-hour exposure to substantially saturated vapour of the test item.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2000-3000 g
- Housing: no data
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: no data
- Type of wrap if used: gauze patch was wrapped around the trunk and bandaging tape was wrapped around the impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data, but excess fluid was removed to diminish ingestion
- Time after start of exposure:

Duration of exposure:

24 hours

Doses:

16, 8 and 4 mL/kg bw

No. of animals per sex per dose:

5 male and 5 female treated with 16 mL/kg bw
1 male and 1 female treated with 8 or 4 mL/kg bw

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for skin reactions were made at 1 hour, then on days 7 and 14 post-application. Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 19200 mg/kg bw

Mortality:

No deaths occurred during the 14-day observation period.

Clinical signs:

other: Diarrhoea was observed in one male treated with 16 mL/kg bw on day 14. No clinical signs of toxicity were observed in the rest of the test animals.

Gross pathology:

Mottled dark red lungs were observed in one male treated with 16 mL/kg bw. Haemorrhaged, liquid and gas-filled intestines were evident in another male treated with 16 mL/kg bw. Dark red lung was observed in one female treated with 8 mL/kg bw. No other macroscopic abnormalities were noted in the rest of the animals.

Other findings:

Erythema and oedema were noted in males and females treated with 16 mL/kg bw. Desquamation was evident in female group treated with 16 mL/kg on days 7 and 14.

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute dermal toxicity study for tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 404 without information about GLP compliance, the reported LD50 value is > 16.0 mL/kg bw in rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

19 200 mg/kg bw

Additional information

In the acute oral toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 401, without information on GLP compliance, the reported LD50 value female rats was 1713 mg/kg bw (BRRC, 1990).

Following oral administration of a single dose of 8.0, 4.0, 2.83, 2.0, 1.0 mL/kg bw (equivalent to 9384, 4692, 3320, 2346, 1173 mg/kg bw based on density of 1.173) to 5 male rats per dose and 4.0, 2.0, 1.41, 1.0 mL/kg bw (equivalent to 4692, 2346, 1654, 1173 mg/kg bw based on density of 1.173) to 5 female rats per dose, male and female rats treated with 8.0, 4.0, 2.83, 2.0 and 1.41 mL/kg bw (equivalent to 9384, 4692, 3320, 2346, 1654 mg/kg bw based on density of 1.173) test substance died between 1 to 6 days post-administration with one male survival at a dose level of 2.83 mL/kg bw (equivalent to 3320 mg/kg bw based on density of 1.173) and 2 female survivals at a dose level of 1.41 mL/kg bw (equivalent to 1654 mg/kg bw based on density of 1.173). The rest of the animals survived during the 14-day study period.

The observed signs of toxicity included sluggishness, lacrimation in two animals, salivation in one animal, prostration in two animals, red crust on the perinasal and periocular fur, red stain on the periurogenital fur and blood in the urine. Body weight gain was observed in all the survivals.

Necropsy of the animals that died during the study revealed pink to red lungs, discoloured livers, discoloured stomach or intestines, stomach distended with white material and/or gas, haemorrhaged stomachs, discoloured kidneys, one enlarged kidney, kidneys filled with white or brown material, bladders filled with red liquid and numerous instances of blood in the urine. Similar lesions were observed in males treated with 8.0, 4.0 and 2.83 mL/kg bw (equivalent to 9384, 4692, 3320 mg/kg bw based on density of 1.173) that died during the study period. Gross pathologic evaluation of survivors revealed one dark red liver, red to yellow intestines in one animal, and a trace amount of blood in the urine in one animal.

In the acute inhalation toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 403, without information on GLP compliance, no mortality was observed in rats after 6-hour exposure to substantially saturated vapour of the test item (BRRC, 1990).

Following 6-hour exposure of 5 male and 5 female rats to substantially saturated vapour of test substance, no mortality was observed during the 14 -day study period. The expected body weight gain was noted in all the animals. No macroscopic abnormalities were evident at necropsy in any of the test animals.

In the acute dermal toxicity study for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, conducted according to a protocol similar to OECD 402, without information on GLP compliance, the reported LD50 value is > 19200 mg/kg bw (16.0 mL/kg) in rabbits (BRRC, 1990).

Following 24-hour dermal application of 16 mL/kg bw test material onto the skin of 5 male and 5 female rats, kept in contact with the skin under occlusive dressing, no deaths occurred during the 14-day observation period. Mottled dark red lungs were observed in one male treated with 16 mL/kg, as well as haemorrhaged, liquid and gas-filled intestines in another male from the same test group at necropsy. Lower doses of 8 and 4 mL/kg bw test material were also applied to 1 male and 1 female rats per dose. No mortality occurred in any of the test animals, however dark red lung was observed in one female treated with 8 mL/kg bw.

No other macroscopic abnormalities were noted in the rest of the animals from all test groups. Erythema and oedema were noted in males and females treated with 16 mL/kg bw. Desquamation was evident in females treated with 16 mL/kg bw test material on days 7 and 14. The expected body weight gain was observed in all the animals.

Justification for classification or non-classification

Based on the available data for 1,3,5-tris[3-(trimethoxysilyl)propyl]-1,3,5-triazinane-2,4,6-trione, Category 4 classification is required for acute oral toxicity, " H302: Harmful if swallowed " according to Regulation (EC) No. 1272/2008.