L-isoleucine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

L-isoleucine

EC Number:

200-798-2

EC Name:

L-isoleucine

Cas Number:

73-32-5

Molecular formula:

C6H13NO2

IUPAC Name:

L-isoleucine

Test material form:

solid: crystalline

Specific details on test material used for the study:

- Name of test material (as cited in study report): L-isoleucine
- Physical state: white powder
- Analytical purity: 94.2%
- Lot/batch No.: 1
- Storage condition of test material: ambient temperature, dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: Wistar outbred rat; Crl:(WI) WU BR
- Source: Charles River, Germany
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: 164-168 g
- Fasting period before study: overnight and untill 4 hours after exposure
- Housing: max. 6 animals per macrolon cage
- Diet (e.g. ad libitum): standard laboratory diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3°C
- Humidity (%): 30-70%, occasionally up to 74.4% because of meteorological circumstances and/or wet cleaning of the animal room
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

The study was carried out with treatment of two groups of 3 animals each with a dose level of 2000 mg/kg bw. The animals were dosed with a 10 mL/kg bw dose-volume of a 200 mg/mL suspension of the test substance in maize oil in order to obtain the 2000 mg/kg dose level. The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage. Prior to dosing, the animals had fasted overnight. Approx. 4 hours after dosing, they had access to food again. The animals were observed for mortality up to 14 days after treatment.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: clinical signs within 1-4 hours after dosing, and daily afterwards
- Frequency of weighing: on days 0, 3, 7 and 14
- Necropsy of survivors performed: not applicable
- Other examinations performed: at the end of the observation period, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: No clinical signs observed.

Gross pathology:

No treatment-related gross alterations observed.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

L-isoleucine is not harmful if swallowed.

Executive summary:

A sample of L-isoleucine was tested for acute oral toxicity in an experiment with female rats (limit testing) according to OECD 423 and EU B.1tris Guidelines.

No mortality or clinical signs were observed after treatment with 2000 mg/kg bw dose level. Macroscopic examination of the surviving animals at the end of the observation period did not reveal any treatment-related gross alterations.

Since all animals survived the 2000 mg/kg bw dose level, the oral LD50 of L-isoleucine is considered to be higher than 2000 mg/kg bw. According to the EC-standards (Official Journal of the European Communities, L 110A, Volume 36, 4 May 1993), L-isoleucine is considered not harmful if swallowed.