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Description of key information

In the key acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, the concluded LD50 value was greater than 2000 mg/kg bw (Eurofins, 2019).

A reliable key study for acute dermal toxicity reports an LD50 value of 2.52 ml/kg (estimated to be equivalent to 2494 mg/kg bw) in rat. This study was pre-dating GLP but conducted according to a protocol equivalent to OECD Test Guideline 402 (Carnegie-Mellon 1976).

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

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:
28 March 2019 to 18 April 2019
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:
17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
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 body weight at a dose volume of 10 mL/kg body weight. 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 body weight at a dose volume of 10 mL/kg body weight.
- 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 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

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

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 body weight at a dose volume of 10 mL/kg body weight. 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 body weight at a dose volume of 10 mL/kg body weight.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight. 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/day in step 1 and 2
No. of animals per sex per dose:
3 animals 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
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:
No specific sings of systemic toxicity were seen in any of the test animals.
Body weight:
None of the animals showed weight loss during the observation period.
Gross pathology:
No specific findings were seen during pathology examination.
Other findings:
No

Table 1: Absolute Body Weights in g and Body Weight Change in %

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 - 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 acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, the concluded LD50 value was greater than 2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
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 Research Institute
- 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
Duration of exposure:
24 h
Doses:
16, 8, 4, 2, 1 ml/kg
No. of animals per sex per dose:
2 (16 ml/kg), 4 (8 ml/kg), 4 (4 ml/kg), 4 (2 ml/kg), 4 (1 ml/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Necropsy of survivors performed: yes
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2.52 mL/kg bw
95% CL:
ca. 1 - ca. 6.33
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 470 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Based on specific gravity 0.98g/cm3
Mortality:
2/2 (16 ml/kg), 4/4 (8 ml/kg), 2/4 (4 ml/kg), 2/4 (2 ml/kg), 1/4 (1 ml/kg)
Clinical signs:
Erythema, ecchymosis, scabs, desquamation at application site.
Body weight:
Slight body weight losses were prevalent in test animals.
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 reliable study pre-dating GLP but conducted according to a protocol comparable with the OECD Test Guideline 402, an acute dermal LD50 value of 2.52 ml/kg (estimated to be equivalent to 2470 mg/kg bw) in rats is reported.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 470 mg/kg bw

Additional information

In the key acute oral toxicity study, conducted according to OECD Test Guideline 423 and in compliance with GLP, the concluded LD50 value was greater than 2000 mg/kg bw (Eurofins, 2019).

Two groups, each of three female Wistar rats, were treated with the test item by oral gavage administration at a dose of 2000 mg/kg body weight. The test item, 3-(triethoxysilyl)propanethiol 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. 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 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. All animals gained weight during the study period.

Another supporting acute oral toxicity study reports an LD50 value of 6.17 ml/kg (estimated to be equivalent to 6047 mg/kg bw) in rat. The study was pre-dating GLP but reliable and conducted according to a protocol equivalent to OECD Test Guideline 401 (Carnegie-Mellon 1976). In the highest dose group (16 ml/kg) the animals were seen to be sluggish, deep breathing, with 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 dosage groups. In victims, petechial haemorrhages or congestion was observed in the lungs. This 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 key study for acute dermal toxicity reports and LD50 value of 2.52 ml/kg (estimated to be equivalent to 2470 mg/kg bw) in rat in a study pre-dating GLP but reliable and conducted according to a protocol equivalent to OECD Test Guideline 402 (Carnegie-Mellon 1976). Erythema, ecchymosis, scabs and desquamation were evident at application site with no other reported clinical signs. In victims, livers were paled and mottled, spleens dark and kidneys congested. No remarkable findings were seen in survivors.

No reliable data are available for acute inhalation, however a supporting study (reliability 4) reported no effects after an 8-hour exposure to 'substantially saturated vapour' (Carnegie-Mellon 1976). In accordance with Column 2 of REACH Annex VIII, the 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.