Registration Dossier

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: Guideline study performed under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Batch number: 009141

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl:CD (SD) IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350g
- Housing: solid-floor propylene cages with stainless steels lids, furnished with softwood flakes.
- Diet: Rat and Mouse Expanded Diet No.1, ad libitum
- Water: Mains drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 (both animal holding room and exposure chamber).
- Humidity (%): 55 +/- 15 (both animal holding room and exposure chamber).
- Air changes (per hr): 15 (animal holding room), 20 (exposure chamber)
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark (animal holding room)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cylindrical exposure chamber (dimensions: 28 cm diameter x 50 cm length)
- Exposure chamber volume: approx. 30 litres
- Method of holding animals in test chamber: each test animal was held in a tapered polycarbonate restraining tube and fitted onto a single tier of the exposure chamber and sealed by a rubber 'O' ring. Only the noses of the test animals were exposed to the test atmosphere.
- Rate of air: 10 l/min
- Method of conditioning air: Compressed air was supplied by an oil free compressor and passed through water trap and respiratory quality filters before it was introduced to the test material.
- System of generating particulates/aerosols: Vapourisation of the test material was achieved by directly injecting the test material into the air supply of the exposure chamber. The test material was contained in a glass syringe positioned on an infusion pump and provided a constant supply of test material into the air stream.
- Treatment of exhaust air: Exhaust air from the exposure chamber was passed through a 'scrubber' trap which was connected to a high efficiency filter and metered exhaust system.
- Temperature, humidity in exposure chamber: 21-22 degrees C, 47-55 % humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: During the study, a one litre sample of the chamber atmosphere was pumped through a glass impinger containing 40 ml of acetonitrile. The dreschel head was flushed with a further 10ml of acetonitrile to remove any deposits - this gave a 50ml sample which was analysed by GC using the following parameters:
~ GC system: Agilent Technologies 5890 incorporating autosampler and workstation
~ Column: 2B-624 (60m x 0.32mm x 1.8um)
~ Oven temperature program: initial: 50 degrees C for 1 minute; Rate: 10 degrees C/minute; Final: 200 degrees C for 5 minutes.
~ Injection temperature: 250 degrees C
~ Flame ionisation detector temperature: 250 degrees C
~ Injection volume: 1 ul
~ Retention time: approx. 14 minutes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentration of 20 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 and weighing: Clinical signs were observed at hourly intervals during exposure, once upon removal from restraining tubes and one hour after termination of exposure and subsequently once daily for 14 days. Body weights were measured prior to treatment and on day of exposure and on days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 17.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No treatment related mortality was observed in this study.
Clinical signs:
other: - During exposure: an increase in respiratory rate and wet fur were observed in all animals and an isolated instance of laboured respiration. Upon removal from chamber the following were noted: increased respiratory rate, hunched posture, pilo-erection, w
Body weight:
No significant changes to bodyweight were observed during the study.
Gross pathology:
No macroscopic abnormalities were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of this study, the acute inhalatory toxicity of ethyl methyl carbonate has been evaluated and gave a 4-hour LC50 of >17.6 mg/l (analytical). Given that no treatment-related mortalities and no significant clinical effects were observed (effects that were observed were mainly due to restraint procedures - these were transient and disappeared by day 1), ethyl methyl carbonate is not classified for this endpoint.