L-methionine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. The study itself was regarded as reliable without restrictions (Kl.1). However, according to the "Prctical guide 6: How to report read-across and categories" the maximum score for read-across is 2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

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:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

DL-methionine

EC Number:

200-432-1

EC Name:

DL-methionine

Cas Number:

59-51-8

Molecular formula:

C5H11NO2S

IUPAC Name:

methionine

Test animals

Species:

rat

Strain:

other: 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 221-241 g, females 200-217 g
- Housing: individually or X 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

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The study was carried out using a dynamic inhalation chamber (air changes/h ( >= 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The equipment consists of a cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.
The dust of the test item was generated with a rotating brush dust generator.
Concentration (mg/L air): 5.25
Air flow entrance (l/h): 900
Air flow exit (l/h): 800
Air change (changes per hour): 22.5
ln the inhalation chamber, close to the animals' noses, the particlas had a mass median aerodynamic diameter (MMAD) of 2.207 µm as determinedwith a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 3.382. The geometric mean diameter (d50) of the
supplied test substance was 3.2403 µm as determined by the sponsor.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.25 ±0.25 mg D,L-Methionine/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

After completion of exposure, the animals were observed for a period of 14 days.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5.25 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.25 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Body weight:

The animals gained the expected weight throughout the study period.

Gross pathology:

Necropsy of all animals was carried out and all gross pathological changes were recorded. No abnormalities were detected at necropsy.
Histopathology was not carried out as no lesions were observed macroscopically.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the present test conditions, the LC0 and LC50-values for CD® rats following inhalation of D,L-Methionine for 4 hours were determined as
follows (actual concentrations):
LC0 males: > 5.25 mg/L air for 4 hours
females: > 5.25 mg/L air for 4 hours
LC50 males: > 5.25 mg/L air for 4 hours
females: > 5.25 mg/L air for 4 hours