2,2-bis(methylthio)propane

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:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

EC directive 92/69/EEC, Part B.2 "Acute Toxicity (Inhalation)" OECD, No. 403

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-900-1

EC Name:

-

Cas Number:

6156-18-9

Molecular formula:

C5 H12 S2

IUPAC Name:

2,2-bis(methylthio)propane

Details on test material:

- Name of test material (as cited in study report): Bismethylthiopropane
- Physical state: Liquid
- Analytical purity: 97.22%
- Purity test date: 2007-11-19
- Lot/batch No.: 2KS149
- Expiration date of the lot/batch: 2008-11-28
- Storage condition of test material: At room temperature (20 ± 5°C) protected from direct sun light.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation:
Males: 8 weeks
Females: 9 weeks
- Weight at study initiation:
Males: 244.7 to 258.7 g
Females: 191.8 to 207.9 g
- Fasting period before study:
- Housing: In groups of up to five of the same sex in Makrolon® type-4 cages with wire mesh tops and standard softwood bedding
- Diet: ad libitum access to a pelleted standard Kliba-Nafag 3433 rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland)
- Water: Tap-water ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 29-Apr-2008 To 14-May-2008

Administration / exposure

Route of administration:

other: inhalation: vapor and aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation by nose-only, flow-past exposure
- Method of holding animals in test chamber: The animals were confined separately in restrained tubes which were positioned radially around the flow-past, nose-only exposure chamber.
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols: The test aerosol was generated using a plastic nebulizer, Hospital model 950, New-York, U.S.A. connected to a syringe pump. The polyethylene injector inside model 950 of the Hospitak nebulizer was replaced by a stainless steel injector.
- Method of particle size determination: Particle size determination was not performed. Due to high level of evaporation of the test item such determinations were proved not to be feasible.
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber: The relative humidity and temperature in the chamber was measured continuously during exposure using Rotaric Hygrometer I-20. The results are reported at 30 minute intervals from the start of exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: Chemical determinations of aerosol concentration were performed by drawing the test aerosol through a HVLP-filter type loaded in a 47 mm in-line stainless steel filter sampling device connected to two wash-bottles placed in series each containing 80 mL of acetone, cooled in water ice. The determinations were performed four times during exposure. Each filter was put into appropriately labelled vials and covered with 5 mL acetone. The content of each wash-bottle was transferred into appropriate glass flasks, the wash-bottles were rinsed with acetone and the flasks made up to 100 mL with the rinsing and tightly closed. The filters and the content of the wash-bottles were forwarded at 2-8 °C in a cool box to the study scientist for the analytical laboratory and stored at 2-8 °C until analysis. Analysis of the samples was performed using a GC method coupled to a FID detector and quantified with the area under the peak..
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Approximately half of the test item was in the vapour phase because it passed the filter and was trapped in the first wash bottle. Therefore, the determination of a MMAD was considered not to be feasible. Accordingly, the test item was considered to be respirable to rats since approximately half of the total amount was in the vapour phase.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above

Duration of exposure:

4 h

Concentrations:

20.2 mg/L (analytical)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations
- Viability /Mortality
Observations for viability were recorded once before exposure on the day of exposure, once per hour during exposure, once after exposure on test day 1 and twice daily during the remainder of the observation period.

- Clinical Signs
Each animal was examined once per hour during exposure, once after exposure on test day 1 and once daily during the observation period.

- Body Weights
The body weight of each animal was recorded on test days 1 (before exposure), 4, 8 and 15 (before necropsy).

Pathology
- Necropsy
All animals were necropsied and descriptions of all macroscopic abnormalities were recorded. The lungs, trachea, larynx and the head containing the nasopharyngeal tissue and gross findings were collected from all animals and fixed in neutral phosphate-buffered 4% formaldehyde solution. The lungs were instilled with the fixative at a hydrostatic pressure of 30 cm.

Statistics:

Not appropriate

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 20.2 mg/L air

Exp. duration:

4 h

Remarks on result:

other: No mortality was observed

Mortality:

All animals survived the scheduled observation period of 15 days.

Clinical signs:

other: During exposure, salivation, bradypnea and decreased spontaneous activity were noted in all animals. Additionally, after the end of exposure, lateral recumbency was noted. From test day 2 onwards, all animals were free from clinical signs until their sche

Body weight:

From test day 1 to test day 4, marginal to slight body weight loss was noted in two males and two females. In addition, reduced body weight gain was observed for the remaining males and 1 female. From test day 4 onwards, all animals showed a normal body weight development.

Gross pathology:

No treatment-related macroscopical findings were recorded.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LC0 of Bismethylthiopropane was estimated to be greater than 20.2 mg/L air (analytically determined mean aerosol concentration).

Executive summary:

The acute inhalation toxicity of Bismethylthiopropane was evaluated in a study performed following the OECD guideline 403. A group of five male and five female Wistar was exposed by nose-only, flow-past inhalation to the test item at an analytically determined mean concentration ofv 20.2 mg/L air. All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. On day 15, all animals were sacrificed and necropsied. The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. All animals survived the scheduled observation period. Salivation, decreased activity, lateral recumbency and bradypnea were observed in all animals on the day of exposure. No symptoms were recorded during the observation period from test day 2 onwards. Transient effects on the body weight were noted in most animals between test days 1 and 4. No treatment-related macroscopical findings were recorded. The LC0 of Bismethylthiopropane was estimated to be greater than 20.2 mg/L air. There was no indication of relevant sex-related differences in toxicity of the test item.