Methyl 2-ethylhexanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 2-ethylhexanoate

EC Number:

212-429-2

EC Name:

Methyl 2-ethylhexanoate

Cas Number:

816-19-3

Molecular formula:

C9H18O2

IUPAC Name:

methyl 2-ethylhexanoate

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

- Physical state: Clear colourless liquid
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: Stored at room temperature.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 9 weeks
- Weight at study initiation: Females 164 - 185g
- Fasting period before study: Fasted overnight
- Housing: Individually housed suspended stainless steel caging with mesh floors consistent with Guide for the Care and Use of Laboratory Animals DHEW (NIH).
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): flitered tap water ad libitum
- Acclimation period: 6 - 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod: 12 hours light/12 hours dark

IN-LIFE DATES: 08/10/2003 To: 28/10/2003

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: Individual doses were calculated based on the initial body weights, taking into account the specific
gravity of the test substance (0.866 g/ml) determined by the laboratory. The maximum dose volume applied was 0.43 ml test substance.

Doses:

2000 mg/kg; dosed sequentially in a limit test based on absence of mortality at the limit dose.

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: The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the
first several hours post-dosing and at least once daily thereafter for 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: Individual body weights of the animals were recorded prior to test substance administration (initial)
and again on Days 7 and 14 (termination) after dosing.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

Clinical observations noted for two animals included hypoactivity, piloerection, and reduced fecal volume. However, the affected animals recovered by Day 2 and, along with the other animals, appeared active and healthy for the remainder of the study.

Body weight:

All animals gained body weight during the course of the study.

Gross pathology:

No gross abnormalities were noted on necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) in the female rat was greater than 2000 mg/kg body weight.

Executive summary:

The study was performed to OECD 425 and US EPA OPPTS 870.1100 in accordance with GLP to assess the acute oral toxicity of the test material in the female Sprague-Dawley rat. The test material was administered orally, after fasting overnight. An initial dose of 2,000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females received the same dose level. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) after dosing. There was no mortalities and body weights increased following administration, clinical observations noted for two animals included hypoactivity, piloerection, and reduced fecal volume. However, the affected animals recovered by Day 2 and, along with the other animals, appeared active and healthy for the remainder of the study. No gross abnormalities were noted at necropsy. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 2,000 milligrams of the test substance per kilogram of body weight in female rats.