DL-serine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 March 2003 - 9 April 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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:

DL-serine

EC Number:

206-130-6

EC Name:

DL-serine

Cas Number:

302-84-1

Molecular formula:

C3H7NO3

IUPAC Name:

DL-serine

Test material form:

other: powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 20017
- Expiration date of the lot/batch: 5 July 2003
- Purity: 98.5%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: five to seven weeks.
- Weight at study initiation: 88.4 - 113.5g
- Fasting period before study: overnight prior and approximately 4 hours after dosing
- Housing: animals were housed in groups of 3 in metal cages with mesh floors
- Diet: ad libitum (stardard laboratory rodent diet)
- Water: provided ad libitum
- Acclimation period: mnimum period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24-hour period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality observation were performed at least twice daily. Clinical signs were observed soon after dosing and at frequent intervals for the remainder of day 1 and twice daily thereafter. Body weights were recorded on days 1 (prior to dosing), 8 and 15
- Necropsy of survivors performed: yes. All animals were subected to gross macroscopic examination.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: Clinical signs of reaction to treatment were confined to piloerection in two females, salivation, abnormal gait and hunched posture, seen in one female on Day 1 resolving completely by Day 3. In addition a protruding left eye and opaque left eye was noted

Gross pathology:

Abnormalities revealed at the macroscopic examination at study termination on Day 15 comprised of pallor of the kidneys in all males and liver in one male. No macroscopic abnormalities were noted in any of the females at stdy termination on Day 15.

Applicant's summary and conclusion

Conclusions:

The acute lethal oral dose (LD50) to rats of the test substance was demonstrated to be greater than 2000 mg/kg bodyweight.

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. Clinical signs of reaction to treatment were confined to piloerection in two females, salivation, abnormal gait and hunched posture, seen in one female on Day 1 resolving completely by Day 3. In addition a protruding left eye and opaque left eye was noted in one female from Day 8 with the sign persisting through to study termination on Day 15. No signs of reaction to treatment were observed in the remaining female or any males throughout the duration of the study. All animals were considered to have achieved satisfactory bodyweight gains throughout the study. Abnormalities revealed at the macroscopic examination at study termination on Day 15 comprised of pallor of the kidneys in all males and liver in one male. No macroscopic abnormalities were noted in any of the females at stdy termination on Day 15.

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