3-(methylthio)propionaldehyde

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-11-02 to 1987-11-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 07 Sep 2009

Deviations:

yes

Remarks:

no information on particle size distribution

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(methylthio)propionaldehyde

EC Number:

221-882-5

EC Name:

3-(methylthio)propionaldehyde

Cas Number:

3268-49-3

Molecular formula:

C4H8OS

IUPAC Name:

3-(methylthio)propionaldehyde

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: 9 weeks (males) and 11 weeks (females)
- Weight at study initiation: 262.4 - 289.1 g (males) and 207.0 - 234.8 g (females)
- Housing: in groups of 5 in Makrolon type 4 cages with standard softwood bedding
- Diet: pelleted standard Kliba 343 (Batch 83/87, from Kliba Klingentalmuehle, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

The aerosol generation system was chosen to achieve the intended aerosol concentration with a mass median aerodynamic diameter (MMAD) of 3 µm or less. The particle size distribution is not shown in this study report. The MMAD itself and corresponding geometric standard deviation (GSD) were not determined.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Flow past nose-only design.
- Method of holding animals in test chamber: The animals are confined separately in tubes which are positioned radially around the exposure chamber
- System of generating particulates/aerosols: The test article atmosphere was generated by a constant volume reservoir feeding a Hospitak No. 950 nebuliser following dissolution with water. Following the nebuliser, a dilution system was used to dilute the test article output of the nebuliser with clean air to concentration required for the study. Following aerolisation, the test article was discharged into the exposure chamber. The exposure aerosol enters the inlet at the top under a slight positive pressure and is distributed to the entrance of each of the feed tubes. The aerosol is then delivered through these tubes to the animal's nose and is then extracted away through a second concentric tube which is maintained under a negative pressure through aspiration at the outlet.
- Temperature, humidity and oxygen content were measured at the start of the exposure period: 22.5 °C, 16% humidity, 20.9% oxygen

TEST ATMOSPHERE
- Brief description of analytical method used: The test article was sampled from the exposure unit and passed through three bottles, each filled with 80 mL of ethyl acetate and cooled with dry ice. The ethyl acetate solutions were transferred into a 100 mL volumetric flask, the bottle was rinsed with ethyl acetate and the volume made up. The solutions were analysed by gas chromatography using a Carlo Erba HRGC 5300 apparatus.
- Samples taken from breathing zone: yes

VEHICLE
- Concentration of test material in air: Mean exposure concentration: 4.84 mg/L air. For details please refer to “Any other information on materials and methods incl. tables”.

TEST ATMOSPHERE
- Particle size distribution: The aerosol generation system was chosen to achieve the intended aerosol concentration with a mass median aerodynamic diameter of 3 µm or less, if technically possible.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

4.84 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were inspected for mortalility/viability once per hour during exposure, once after exposure on test Day 1 and twice daily thereafter. Symptoms were recorded once per hour during exposure (only grossly abnormal signs, due to the animals being in restraint tubes) and once daily thereafter.
- Frequency of weighing: At Day 1 (day of exposure), 8 and 15 of the test.
- Necropsy of survivors performed: yes
- Other examinations performed: The lungs from all animals were collected and kept in a neutral 4% formaldehyde solution.

Statistics:

Logit model could not be applied to the data, estimation without statistical analysis.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 4.8 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 2/5 males died

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 4.8 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality observed in females.

Mortality:

4.84 mg/L: 2/5 males and 0/5 females died (8 and 11 days after exposure)

Clinical signs:

other: Somnolence, hunched posture, piloerection and/or epistaxis in males and females after exposure, fully reversible within 24 h. In addition, rales were observed, which were fully reversible in males by Day 12 and fully reversible in females by Day 4.

Body weight:

The mean body weight gain shown over the study period was within the range expected for rats of this strain and age used in this type of study.

Gross pathology:

Necropsy of surviving animals revealed no abnormal findings. Reddening of the lung or spots on the lung lobes were observed in 2/2 dead males.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute Inhal. 4, H332 according to Regulation (EC) No. 1272/2008 based on mortality observed in males (2/5) at 4.8 mg/L air