Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: official guideline method, GLP with certificate, good documentation, identity of substance clear but no details on its purity.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test material as stated in study report ("Sponsor's identification"): EMC
Description: Clear colourless liquid
Batch number: 009141
Date received: 11.27.2000
Storage conditions: Room temperature, in the dark until 01.16.2001, thereafter stored at approximately 4 °C in the dark.

Remark of the author of this IUCLID dossier concerning the substance identity:
Every page of the copy of the study report contains an annotation referring to the data sharing agreement in place between the licensee that uses this study report and the data owner. In this data sharing agreement the identity of the chemical substance is specified with "Ethyl Methyl Carbonate - EC No. 433-480-9, CAS Nr. 623-53-0".

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl:CD (registered trademark) (SD) IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Sprague-Dawley Crl:CD(R) (SD) IGS BR strain rats were supplied by Charles River (UK) Ltd, Margate, Kent.
Animal age before study: approximately eight to twelve weeks
Animal weight: 200 - 350 g (one female rat below weight range with 186 g)
Females, specification: nulliparous, non-pregnant
Acclimatisation: minimum 5 d
Animal identification: individually numbered by ear punching and a number written on a colour-coded cage card

Husbandry: groups of five, sex-separated, solid-floor polypropylene cages with stainless steel lids floored with softwood flakes (Datesand Ltd., Cheshire, UK), enriched with wooden chew blocks (B & K Universal Ltd, Grimston, Hull, UK) and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK). Diet, drinking water, bedding and chew blocks routinely analysed and considered free of any contaminants that could affect the study results. Drinking water and food ad libitum except during exposure period (food: Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK). Temperature 21 +/- 2 °C, relative humidity 55 +/- 15 % (occasional deviations of rel. humidity at beginning of study), air exchange rate minimum 15 times/h, light-darkness times 12h/12h (electric lighting); except during actual exposure to the test substance these conditions were maintained throughout the study.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Details on inhalation exposure:
Test material was vaporised by injecting it directly into the air supply to the exposure chamber (30 L). The material was contained in a glass syringe located on an infusion pump thus providing a constant supply of test material into the air stream. Immediately after the injection site, the air supply was ducted, via suitable tubing and a conical flask, through a water bath, maintained at approximately 60 °C, to ensure complete vaporisation.

Concentration equilibration prior to beginning of exposures. Homogeneity of the test substance in the chamber was assumed as for chambers of the same design this has been validated (reference to publication).

The rats were held in a restraining tube and only the nose was exposed to the test atmosphere. The oxygen concentration in test atmosphere was at least 19 %, the temperature 21-22°C and the relative humidity 47-55 %.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
20.0 mg/L (target); 20.8 mg/L (nominal); 17.6 mg/L (mean achieved, determined by analytical verification via GC) with standard deviation of 0.42. Concentrations were measured ca. every 1 h during the exposure period.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
A group of ten rats (five males, five females) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 20.0 mg/L was used for exposure.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 17.6 mg/L air
Exp. duration:
4 h
Remarks on result:
other: SD 0.42
Mortality:
no mortality at a mean achieved atmospheric concentration of 17.6 mg/L of test material.
Clinical signs:
other: During exposure, increased respiratory rate and wet fur were noted in all animals and there was an isolated instance of laboured respiration. On removal from the chamber, animals showed increased respiratory rate, hunched posture, pilo-erection and wet fu
Body weight:
Normal bodyweight development was noted during the study (measured prior to treatment on day of exposure, on days 7 and 14).

Any other information on results incl. tables

No macroscopic abnormalities were detected at necroscopy.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
No deaths occured in a group of ten rats exposed to a mean achieved atmosphere concentration of 17.6 mg/L. The acute inhalation median lethal concentration (LC50) of MEC, in the Sprague-Dawley Crl:CD(R) (SD) IGS BR strain rat, was therefore greater than 17.6 mg/L.

In REGULATION (EC) No 1272/2008 (16 Dec 2008), 3.1.2. Criteria for classification of substances as acutely toxic, the lowest acute toxicity hazard category falls in the range of LC50 = 10-20 mg/L. As no mortalities occurred at 17.6 mg/L and the substance did not lead to other major signs of toxicity the substance is regarded as not to be classified in any acute toxicity hazard category.