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Toxicological information

Acute Toxicity: inhalation

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
animal weight range exceeds guideline recommendation
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

Constituent 1
Chemical structure
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