L-threonine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

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-threonine

EC Number:

200-774-1

EC Name:

L-threonine

Cas Number:

72-19-5

Molecular formula:

C4H9NO3

IUPAC Name:

L-threonine

Test animals

Species:

rat

Strain:

other: rat/CD/Crl:CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males 45 days, females 56 days
- Weight at study initiation: males 204-228 g, females 194-220 g
- Fasting period before study: 16 hours before exposure
- Housing: caged by sex in groups of 2-3 animals/cage
- Diet: feeding was discontinued approx. 16 hours before exposure
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17.11.2003 To: 02.12.2003

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation chamber (Rotameter, ROTA Apparate- und Maschinenbau, 0-79664 Wehr/Baden)
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: in pyrex tubes at the edge of the chamber in a radial position.
- Flow rate of air: 900 L/h
- Method of conditioning air: air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-li ne disposable
gas filter
- System of generating particulates/aerosols: rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, 0-76229
Karlsruhe)
- Method of particle size determination: cascade impactor (MAY, K.R. Aerosol impaetion jets, J.Aerosol Sei..§, 403 (1975), RESEARCH ENGINEERS Ltd, London N1 5RO, UK
- Treatment of exhaust air: passage through appropriate filter
- Temperature, humidity, oxygen content in air chamber: temperature 22°C +/- 3°C, humidity based on the guidelines, recordings of humidity in
the chamber are not made where dust examinations are carried out, oxygen content 21%

TEST ATMOSPHERE
- Brief description of analytical method used: Dust sampies were taken once every hour during the exposure. For that purpose, a SARTORIUS filter
(Minisart SM 17598 0.45 µm) was placed in the purpose-made inlet of the inhalation chamber in such a way that the opening of the filter was close
to the animals' noses. By means of a piece of silicon tubing, the filter was connected to an air-flow meter attached to a pump. The filter was
weighed before and after sampling (accuracy: 10 µg)
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle: clean air
- Concentration of test material in vehicle:
- Purity: filtered using an in-line disposable gas filter)

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 2.383 µm
- Geometric mean diameter: 3.3575 µm
- GSD (Geometric st. dev.): 3.629 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.15 +/- 0.10 mg/l

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations for mortality and clinical signs: during and after exposure, daily thereafter
- Frequency of weighing: day 0 (prior to dosing), day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy, organ weights,

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5.15 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.15 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality occurred

Clinical signs:

other: Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma

Body weight:

Individual weights of animals were determined before the exposure and weekly after exposure. Changes in weight were calculated and recorded when survival exceeds one day.

Gross pathology:

Macroscopic post mortem findings: no pathological findings

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the present test conditions, no signs of toxicity were observed at 5.15 ± 0.1 0 mg L-threonine/L air. No mortality occurred. No abnormalities were detected at necropsy. The animals gained the expected weight throughout the study period.