chloromethane; methyl chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 - 26 Nov 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

animal weight range exceeds guideline recommendation

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

animal weight range exceeds guideline recommendation

GLP compliance:

yes (incl. QA statement)

Remarks:

The department of health of the government of the United Kingdom

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chloromethane

EC Number:

200-817-4

EC Name:

Chloromethane

Cas Number:

74-87-3

Molecular formula:

CH3Cl

IUPAC Name:

chloromethane

Details on test material:

- Name of test material (as cited in study report): methyl chloride
- Physical state: gaseous
- Analytical purity: 99.9981%
- Purity test date: 2008-10-07
- Lot/batch No.: R7030

Test animals

Species:

rat

Strain:

other: HsdRccHan (TM):WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratries Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: randomly allocated to cages and ear tagged, 5 per sex in solid floor polypropylene cages furnished with soft wood flakes
- Diet: ad libitum Harlan 2014 Rodent Diet, Harlan Laboratories Ltd, Oxon, UK
- Water: ad libitum mains drinking water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the test material was ducted directly from the gas canister into a 25 L SKC Tedlar Gas Bag (SKC Ltd Dorset, UK). The gas was then transferred from the gas bag to the exposure chamber by means of a Watson Marlow 505S peristaltic pump.
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: compressed air
- Method of conditioning air: supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the exposure chamber.
- Treatment of exhaust air: exhaust air passed through a scrubber tarp and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: 19-21 °C, 52-63%, negative air pressure


TEST ATMOSPHERE
- Brief description of analytical method used: samples were removed using a gas-tight syringe and were transferred to 20 mL head space vials for GC-FID analysis
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC-FID

Duration of exposure:

4 h

Concentrations:

4020 mg/m³, 8420 mg/m³ and 21800 mg/m³

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 and weighing: once per hour during exposure, at the end of exposure, 1 h post-exposure from then on once daily for up to 14 d
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, mortality

Statistics:

Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 21 800 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality occured

Clinical signs:

other: 4.02 mg/L: Increased respiratory rate was noted in all animals during exposure, on removal from chamber and one hour post-exposure. The animals appeared normal thereafter. 8.42 mg/L: Increased respiratory rate was noted in all animals during exposure, on

Body weight:

4.02 mg/L: no effect on body weight gain compared to controls
8.42 mg/L: 2 females and one male exhibited slight body weight losses or a reduced body weight gain during week 1
21.80 mg/L: 2 females exhibited slight body weight losses or a reduced body weight gain during week 1 and one of them also in week 2

Normal body weight development was noted for all other animals during the course of the study.

Gross pathology:

Following macroscopic abnormalities were detected amongst several animals at necropsy:
lungs: dark patches
kidneys: speckled appearance

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DSD: not classified
CLP: not classified