Carbonic acid, ethyl methyl ester

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-12-06 - 2001-11-01

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

433-480-9

EC Name:

-

Cas Number:

623-53-0

Molecular formula:

C4H8O3

IUPAC Name:

ethyl methyl carbonate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 d

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 15, 150, 1000 mg/kg/d
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Clinical observations: one and five hours after dosing during working weeks, one hour after dosing at weekends.
Functional observations: day 7, 14, 18, 25.
Body weight: day 0, 7, 14, 18, 25.
Food consumption: weekly.
Haematological and blood chemistry: at the end of the study

Sacrifice and pathology:

Organ weights, histopathology

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical signs were confined to 1000 mg/kg/day females who showed an isolated instance of increased salivation.

Mortality:

mortality observed, treatment-related

Description (incidence):

Clinical signs were confined to 1000 mg/kg/day females who showed an isolated instance of increased salivation.

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

Detailed open-field observations confirmed the clinical signs of hunched posture detected in 1000 mg/kg/day females. No effects were detected in 1000 mg/kg/day males or animals of either sex treated with 150 or 15 mg/kg/day.

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

2

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Oral administration of the test material, MEC to rats for a period of twenty-eight consecutive days at dose levels of up to 1000 mg/kg/day produced minor treatment-related changes confined to 1000 mg/kg/day females. No such effects were demonstrated in males treated with 1000 mg/kg/day or animals of either sex treated with 150 mg/kg/day or 15 mg/kg/day the "No Observed Effect Level" was, therefore, considered to be 1000 mg/kg/day in males and 150 mg/kg/day in females.

The treatment-related changes detected were confined to clinical observations of hunched posture. This effect was considered not to represent serious damage to health, as defined by the criteria given in the EC labelling guide of Commission Directive 93/21/EEC.

Executive summary:

Oral administration of the test material, MEC to rats for a period of twenty-eight consecutive days at dose levels of up to 1000 mg/kg/day produced minor treatment-related changes confined to 1000 mg/kg/day females. No such effects were demonstrated in males treated with 1000 mg/kg/day or animals of either sex treated with 150 mg/kg/day or 15 mg/kg/day the "No Observed Effect Level" was, therefore, considered to be 1000 mg/kg/day in males and 150 mg/kg/day in females. The treatment-related changes detected were confined to clinical observations of hunched posture. This effect was considered not to represent serious damage to health, as defined by the criteria given in the EC labelling guide of Commission Directive 93/21/EEC.