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Acute Toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(triethoxysilyl)propanethiol
EC Number:
238-883-1
EC Name:
3-(triethoxysilyl)propanethiol
Cas Number:
14814-09-6
Molecular formula:
C9H22O3SSi
IUPAC Name:
3-(triethoxysilyl)propanethiol
Test material form:
liquid
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

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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

Any other information on results incl. tables

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

 

 

Applicant's summary and conclusion

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.