3-(triethoxysilyl)propanethiol

Endpoint summary

Description of key information

In the key acute oral toxicity study conducted according to OECD Test Guideline 423 and in compliance with GLP (Eurofins / BSL Bioservice Scientific Laboratories, 2019, reliability score 1), the LD50 value for 3-(triethoxysilyl)propanethiol (CAS No. 14814-09-6, EC No. 238-883-1) in the Wistar rat was >2000 mg/kg bw.

 

For dermal toxicity, the key study for 3-(triethoxysilyl)propanethiol pre-dates GLP but was conducted according to a protocol equivalent or similar to OECD Test Guideline 402 (Carnegie-Mellon Institute of Research, 1976, reliability score 2). The LD50 was 2.52 ml/kg bw (approximately 2500 mg/kg bw) in male albino rabbit.

 

The acute inhalation toxicity endpoint is waived since reliable data for the acute oral and dermal endpoints are available.

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:

2019/03/28 - 2019/04/18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001/12/17

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

2008/05/30

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002/12

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, protected from light
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For all animals of the first step, 2.0068 g of the test item was diluted with the vehicle to yield a final volume of 10 ml and to achieve a dose of 2000 mg/kg bw at a dose volume of 10 ml/kg bw. For all animals of the second step, 2.0002 g of the test item was diluted with the vehicle to yield a final volume of 10 ml and to achieve a dose of 2000 mg/kg bw at a dose volume of 10 ml/kg bw.
- Preliminary purification step (if any): none
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 – 10 weeks
- Weight at study initiation: Step 1: 153 – 177 g; Step 2: 189 – 200 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): not specified
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): MKCG3257
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual): For all animals of the first step, 2.0068 g of the test item was diluted with the vehicle to yield a final volume of 10 ml and to achieve a dose of 2000 mg/kg bw at a dose volume of 10 ml/kg bw. For all animals of the second step, 2.0002 g of the test item was diluted with the vehicle to yield a final volume of 10 ml and to achieve a dose of 2000 mg/kg bw at a dose volume of 10 ml/kg bw.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg bw. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.

Doses:

2000 mg/kg bw in step 1 and 2

No. of animals per sex per dose:

3F per step 1 and 2, overall 6 animals used

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Not used

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item showed no mortality and no other acute oral toxicity characteristics after a single dose administration in step 1 and 2.

Clinical signs:

other: No specific sings of systemic toxicity were seen in any of the test animals.

Gross pathology:

No specific findings were seen during pathology examination.

Other findings:

No

Table 1: Absolute Body Weights g and Body Weight Change

Step	Animal No. / Sex	Starting Dose  (mg/kg bw)		BW (g)		Body Weight Change in Comparison to Day 1 (%)
			Day 1	Day 8	Day 15	Day 15
1	1 / Female	2000	177	208	215	21
	2 / Female		158	193	202	28
	3 / Female		153	173	184	20
2	4 / Female	2000	189	217	224	19
	5 / Female		193	195	214	11
	6 / Female		200	221	225	13

Table 2: Findings of the Necropsy - Individual data

Step	Animal No. / Sex	Starting Dose (mg/kg bw)	Organ	Macroscopic Findings
1	1 / Female	2000	-	nsf
	2 / Female		-	nsf
	3 / Female		-	nsf
2	4 / Female		-	nsf
	5 / Female		-	nsf
	6 / Female		-	nsf

nsf = no specific findings

Table 3: LD₅₀Cut-Off

Starting Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths	LD50Cut-Off (mg/kg bw)
2000	6	0	˃ 5000

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

In the key acute oral toxicity study conducted according to OECD Test Guideline 423 and in compliance with GLP (reliability score 1), the LD50 for 3-(triethoxysilyl)propanethiol in the Wistar rat was >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Key reliability score 1 study available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carnegie-Mellon Institute of Research
- Age at study initiation: 3-5 months
- Diet: ad libitum
- Water: ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the trunk
- Type of wrap if used: 'impervious sheeting'

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): maximum dose that can be retained is 16 to 20 ml/kg bw

Duration of exposure:

24 h

Doses:

16, 8, 4, 2, 1 ml/kg bw

No. of animals per sex per dose:

2M (16 ml/kg bw), 4M (8 ml/kg bw), 4M (4 ml/kg bw), 4M (2 ml/kg bw), 4M (1 ml/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Statistics:

Not specified

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2.52 mL/kg bw

Based on:

test mat.

95% CL:

ca. 1 - ca. 6.33

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Based on specific gravity 0.98 g/cm3

Mortality:

2/2 (16 ml/kg bw), 4/4 (8 ml/kg bw), 2/4 (4 ml/kg bw), 2/4 (2 ml/kg bw), 1/4 (1 ml/kg bw)

Clinical signs:

other: Two prostrate at 'one day' (8 and 4 ml/kg bw), one prostrate at 'one day' (2 ml/kg bw). Erythema, ecchymosis, scabs, desquamation at application site, depending on dose.

Gross pathology:

In victims, livers were paled and mottled, spleens dark, kidneys congested. Nothing remarkable in survivors.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Not classified according to Regulation (EC) No. 1272/2008

Conclusions:

In a study pre-dating GLP but conducted according to a protocol equivalent or similar to OECD Test Guideline 402 (reliability score 1), the acute dermal LD50 for 3-(triethoxysilyl)propanethiol in the male albino rabbit was 2.52 ml/kg bw (approximately 2500 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Key reliability score 2 study available

Additional information

In the key acute oral toxicity study conducted according to OECD Test Guideline 423 and in compliance with GLP (Eurofins / BSL Bioservice Scientific Laboratories, 2019, reliability score 1), two groups, each of three female Wistar rats, were treated with 3-(triethoxysilyl)propanethiol by oral gavage administration at a dose of 2000 mg/kg bw. The test item was diluted with the vehicle corn oil at a concentration of 0.2 g/ml and administered at a dose volume of 10 ml/kg bw. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the 14-day observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals gained weight during the study period. All animals survived until the end of the study without showing any sign of toxicity. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. The oral LD50 value for 3-(triethoxysilyl)propanethiol was >2000 mg/kg bw.

 

In a supporting acute oral toxicity study that pre-dates GLP but was conducted according to a protocol equivalent or similar to OECD Test Guideline 401 (Carnegie-Mellon Institute of Research, 1976, reliability score 2), male Wistar rats were exposed to 4, 8, and 16 ml/kg bw of undiluted 3-(triethoxysilyl)propanethiol via oral gavage. In the highest dose group (16 ml/kg bw), the animals were seen to be sluggish, with deep breathing, tremor-like muscular spasms and loss of coordination. The symptoms progressed to salivation and convulsions followed by the death of all three animals. Similar, but milder clinical signs were evident in the lower dose groups. In victims, petechial haemorrhages or congestion was observed in the lungs. This finding was accompanied with mottled livers, slightly speckled and congested kidneys and distended and liquid or gas-filled intestines and stomachs. Nothing remarkable was seen in survivors. The oral LD50 for 3-(triethoxysilyl)propanethiol in the male Wistar rat was 6.17 ml/kg bw (approximately 6050 mg/kg bw).

 

The key acute dermal toxicity study for 3-(triethoxysilyl)propanethiol pre-dates GLP but was conducted according to a protocol equivalent or similar to OECD Test Guideline 402 (Carnegie-Mellon Institute of Research, 1976, reliability score 2). Male albino rabbits (two to four per dose group) were exposed to 1, 2, 4, 8, and 16 ml/kg bw of undiluted 3-(triethoxysilyl)propanethiol applied to clipped intact trunk skin under occlusive conditions for 24 hours. Prostration was seen in one or two animals at 2 to 8 ml/kg bw. Erythema, ecchymosis, scabs and/or desquamation were evident at the application site for 1 to 16 ml/kg bw. In victims, livers were paled and mottled, spleens dark and kidneys congested. No remarkable findings were seen in survivors. The dermal LD50 for 3-(triethoxysilyl)propanethiol in the male albino rabbit was 2.52 ml/kg bw (approximately 2500 mg/kg bw).

 

No reliable data are available for acute inhalation toxicity, however a supporting study (Carnegie-Mellon Institute of Research, 1976, non-guideline / pre-GLP, reliability score 4) reported no deaths or adverse effects in the rat (species / sex not specified) after an 8-hour exposure to substantially saturated vapour of 3-(triethoxysilyl)propanethiol. In accordance with Column 2 of REACH Annex VIII, an acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

Justification for classification or non-classification

Based on the available information, 3-(triethoxysilyl)propanethiol does not require classification for acute toxicity according to Regulation (EC) No. 1272/2008.