Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February - March 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethanol, 2,​2'-​[1,​2-​ethanediylbis(oxy)​]​bis-​, reaction products with 3-​(triethoxysilyl)​-​1-​propanamine

EC Number:

813-152-5

Cas Number:

152261-44-4

Molecular formula:

Unspecified

IUPAC Name:

Ethanol, 2,​2'-​[1,​2-​ethanediylbis(oxy)​]​bis-​, reaction products with 3-​(triethoxysilyl)​-​1-​propanamine

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: WISTAR Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

ANIMALS
- Species/strain: WISTAR rats Crl: WI(Han)
- Source: Charles River, Sulzfeld, Germany
- Sex: Female (non-pregnant and nulliparous)
- Number of animals: 3 per step
- Age at the beginning of the study: 10–12 weeks
- Body weight on the day of administration:Step 1: 182–209 g; Step 2: 204–232 g; Step 3: 210–233 g

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare the animals were bred for experimental
purposes. This study was performed in an AAALAC-accredited laboratory. According to German animal protection law, the study type has been reviewed and accepted by local authorities. Furthermore, the study has been subjected to Ethical Review Process and was authorised by the Bavarian animal welfare administration.

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 3 to 4 hours post (last) dosing.

HOUSING
- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x 1 hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test item was administered at a dose volume of 10 mL/kg body weight.
At dose level of 300 mg/kg body weight (step 1) the test item was administered at a single dose by gavage using a feeding tube.
At a dose level of 2000 mg/kg body weight the test item was administered in smaller fractions over a period of maximum 24 hours according to OECD Guideline 423.
The test item was administered by gavage using a feeding tube. Two separate administrations (1000 mg/kg body weight each time) were performed for steps 2 and 3, both at an interval of 3 hours.

Doses:

300 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

Step 1: 3
Step 2: 3
Step 3: 3

Control animals:

no

Details on study design:

One group, of three female WISTAR Crl: WI(Han) rats, was treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was emulsified with the vehicle corn oil at a concentration of 0.1039 g/mL and administered at a dose volume of 10 mL/kg.

A second and third group, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight The test item was emulsified with the vehicle corn oil at a concentration of 0.6896 g/mL and administered in two doses of 1000 mg/kg bw at dose volume of 10 mL/kg in an interval of 3 hours.

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item showed no mortality and but other acute oral toxicity characteristics after a single dose administration.

Clinical signs:

The test item showed acute oral toxicity characteristics after a single dose administration.

Body weight:

None of the animals showed weight loss during the observation period.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Any other information on results incl. tables

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity but not with mortality.

Under the conditions of the present study, a double oral application of the test item to rats at a dose of 1000 mg/kg body weight (i.e. 2000 mg/kg body weight in total) at an interval of 3 hours was associated with signs of toxicity but not with mortality.

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture, ataxia and half eyelid-closure. All animals recovered within up to 2 days post-dose.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The median lethal dose of Ethanol, 2,2’-[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine after a single or double oral administration to female rats, observed over a period of 14 days is: LD50cut-off (rat): 5000mg/ kg bw.
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture, ataxia and half eyelid-closure. All animals recovered within up to 2 days post-dose.

Executive summary:

One group, of three female WISTAR Crl: WI(Han) rats, was treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was emulsified with the vehicle corn oil at a concentration of 0.1039 g/mL and administered at a dose volume of 10 mL/kg.

A second and third group, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight The test item was emulsified with the vehicle corn oil at a concentration of 0.6896 g/mL and administered in two doses of 1000 mg/kg bw at dose volume of 10 mL/kg in an interval of 3 hours.

All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the 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 showing signs of toxicity.

The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg bw were reduced spontaneous activity, piloerection, and hunched posture. All animals recovered within up to 2 days post-dose.

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture, ataxia and half eyelid-closure. All animals recovered within up to 2 days post-dose.

Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain.

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

LD₅₀cut-off (rat): 5000mg/kg bw

Species/strain: WISTAR Crl: WI(Han) rats

Vehicle: Corn oil

Number of animals: 3 per step / 2 steps performed

Conclusion

Under the conditions of the present study, a single oral application of the test item Ethanol, 2,2’-[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity but not with mortality.

Under the conditions of the present study, a double oral application of the test item Ethanol, 2,2’-[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine to rats at a dose of 1000 mg/kg body weight (i.e. 2000 mg/kg body weight in total) at an interval of 3 hours was associated with signs of toxicity but not with mortality.

The median lethal dose of Ethanol, 2,2’-[1,2-ethanediylbis(oxy)] bis-, reaction products with 3-(triethoxysilyl)-1-propanamine after a single or double oral administration to female rats, observed over a period of 14 days is:

LD₅₀cut-off (rat):5000mg/ kg bw