D-serine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 January 2005 - 21 April 2005

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:

D-serine

EC Number:

206-229-4

EC Name:

D-serine

Cas Number:

312-84-5

Molecular formula:

C3H7NO3

IUPAC Name:

D-serine

Test material form:

solid

Details on test material:

- Appearance: white solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: K0498003
- Expiration date of the lot/batch: > 31-0CT-2005
- Purity: 100%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.
- Stability under test conditions: Unknown in purified water; is excluded from the statement of compliance.
- Solubility and stability of the test substance in the solvent/vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This trial formulation is excluded from the GLP statement of compliance.

Test animals

Species:

rat

Strain:

other: HanBrl:Wist (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Fasting period before study: approximately 18 hours (access to water was permitted)
- Housing: animals were housed in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwod bedding
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): between 30-70 % (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: Purified water was found to be a suitable vehicle.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability observations were performed 1, 2, 3 and 5 hours after administration and twice daily on days 2 to 15. Body weights were recorded on test days 1 (prior to administration), 8 and 15. Clinical signs were observed 1, 2, 3 and 5 hours after administration and daily thereafter.
- Necropsy of survivors performed: yes. macroscopic examinstaions were performed.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy

Applicant's summary and conclusion

Conclusions:

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted in acordance with the standardised guidelines OECD 423 and EU Method B.1tris under GLP conditions.

During the study, 6 female rats received an oral dose of test material at a concentration of 2000 mg/kg bw, by gavage. Mortality, clinical signs and body weights were observed for a period of 14 days after which time all survivors were necropsied.

Under the conditions of the study none of the animals died and no clinical signs were observed. The body weight of the animals was within the range commonly recorded for this strain and age of rats. No macroscopic findings were recorded at necropsy.

The acute oral LD50 was therefore determined to be in excess of 2000 mg/kg bw.