Tetrakis(2-ethylbutyl) orthosilicate

Endpoint summary

Description of key information

Acute Toxicity - Oral LD50 >2000 mg/kg for rat (OECD TG 425).

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 Aug 2017 - 06 Nov 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Gelest, Inc. OS-140 Lot# 8E-33-134
- Expiration date of the lot/batch: May 2020
- Purity test date: 07 June 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored in a dessicator at room temperature
- Stability under test conditions: stable under conditions of assay
- Solubility and stability of the test substance in the solvent/vehicle: not applicable, test material used as received

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: used as received

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Stone Ridge NY
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 196 - 243 grams
- Fasting period before study: 16 -20 hours prior to dosing
- Housing: The animals were individually housed in suspended wire-bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet No. 5012)
- Water (e.g. ad libitum): Tap water, ad-libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 to 22.38
- Humidity (%): 34.3 to 86.4
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 28 Aug 2017 To: 26 Sep 2017

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.52 mL

Rationale for the selection of the starting dose: The starting dose of 2000 mg/kg was chosen as the test substance was considered likely to have low toxicity.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily thereafter for 14 days for toxicity and pharmacological effects. Body weights were recorded pre-test, weekly, and at termination.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations included, but were not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects including tremors and convulsions, changes in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking backwards). All animals were observed twice daily for mortality on Day 1 to Day 14

Statistics:

Mean and standard deviation of body weight

Preliminary study:

Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All five female rats survived following a single 2000 mg/kg oral dose.

Clinical signs:

Abnormal physical signs including red staining of the nose/mouth area, localized hair loss (abdomen), tips of ears stained red, chromorhinorrhea, wetness of the anogenital area, and piloerection were observed.

Body weight:

All five rats gained body weight by study termination.

Gross pathology:

The gross necropsy revealed no observable abnormalities in four out of five rats. Localized hair loss (abdomen) was observed in one rat.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for Tetrakis(2-ethylbutyl) Orthosilicate following oral intubation was established at >2000 mg/kg for females. This finding does not warrant classification of Tetrakis(2-ethylbutyl) Orthosilicate as an acute oral toxicant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

Tetrakis(2-ethylbutyl) Orthosilicate was administered via oral intubation to 5 female Sprague Dawley rats at 2000mg/kg to assess the acute oral toxicity. Animals were observed daily for 14 days post dosing. No overt signs of toxicity were apparent and mortality was not observed at the dose level tested. All animals were free of abnormalities at postmortem examination except for one female with alopecia of the abdomen. All animals displayed increases in body weight over their day 0 values. The LD50 for Tetrakis(2-ethylbutyl) Orthosilicate based on these data were established at >2000 mg/kg for females. This finding does not warrant classification of Tetrakis(2-ethylbutyl) Orthosilicate as an acute oral toxicant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

It is a reliable study with a klimisch score of 1

Additional information

In the key study (MB Research Laboratories), female rats were given a single oral gavage dose of Tetrakis(2-ethylbutyl) Orthosilicate at 2000 mg/kg bw according to OECD test guideline 425 and observed for 14 days. No mortality was observed in animals treated with 2000 mg/kg. An LD50 value of >2000 mg/kg bw was established.

Justification for classification or non-classification

Tetrakis(2-ethylbutyl) Orthosilicate is minimally toxic via ingestion where the LD50 is >2000 mg/kg in the rat. This finding does not warrant classification of Tetrakis(2-ethylbutyl) Orthosilicate as an acute oral toxicant under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).