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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From December 27, 1980 to January 31, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is well documented and meets generally accepted scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl carbamate
EC Number:
209-939-2
EC Name:
Methyl carbamate
Cas Number:
598-55-0
Molecular formula:
C2H5NO2
IUPAC Name:
methyl carbamate

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Portage, Michigan
- Date of birth of test animals: November 21, 1979 to November 28, 1979
- Date of arrival: December 27, 1979
- Housing: Polycarbonate cages with snow filtration filter sheets and placed in stainless steel racks
- Water: City, untreated; ad libitum.
- Quarantine Period: December 27, 1979 to January 14, 1980

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 12.8- 26.7°C (55-80°F)
- Humidity (%): 55-80%
- Air: Air filtered through a Flanders air filter, AC45L

IN-LIFE DATES: From January 15, 1980 to January 31, 1980

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
The appropriate weight of test substance for each dose was weighed out in a 100 mL volumetric flask. Water was added to the 100 mL mark, the flask was stoppered and the contents were shaken until the solution was thoroughly mixed. Test substance doses were prepared in sufficient quantities for one week's dosing. Doses were prepared on the Friday prior to expected usage. All test substance doses were stored at room temperature and used within 8 d of initial preparation.
Duration of treatment / exposure:
17 d
Frequency of treatment:
Once daily (doses were not given on weekends) and at least two consecutive doses administered prior to the day of the scheduled terminal sacrifice.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500, 1,000, 2,000 and 4,000 mg/kg bw/day
Basis:
actual ingested
Control animals:
yes
Details on study design:
Method of dosing: Stainless steel animal feeding tube (gavage needle with ball tip - 3 inch, 18 gauge) in 2.5 mL glass syringes (needles: Popper and Sons, Inc., New Hyde, N.Y.; syringes: B-D, Inc.)
Volume: 5 mL/kg bw
Length of compound administration: 12 individual doses for each surviving animal given on consecutive week days (doses were not given on weekends)
Method of sacrifice: CO2 asphyxiation

Examinations

Observations and examinations performed and frequency:
Observation Period: Twice daily observations

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: At start and termination of study
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
CLINICAL SIGNS AND MORTALITY
The two highest doses (2,000 and 4,000 mg/kg bw/day) were lethal to all male and female rats. 3 male rats died in the 1,000 mg/kg bw/day dosage group. Clinical signs of toxicity were observed in male and female rats receiving 1,000 mg/kg bw/day or higher doses.

BODY WEIGHT AND WEIGHT GAIN
Relative weight gains were suppressed in all dosage groups.

GROSS PATHOLOGY
Gross observations at necropsy indicate hemorrhaging in the GI tract, subcutaneous vascular bed and brain in some rats receiving 1,000 mg/kg bw/day or higher doses. Some female rats receiving 250, 500 and 1,000 mg/kg bw/day demonstrated reproductive tract lesions.

HISTOPATHOLOGY
No toxicity related microscopic lesions were observed in rats receiving 500 mg/kg bw/day.

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The no observed adverse effect level (NOAEL) for the test substance can be established at 500 mg/kg bw/day.
Executive summary:

A study was conducted to assess the toxicity of the test substance following repeated administration. On basis of acute dose toxicity test, test substance was given to males and females rats at dose levels of 0, 250, 500, 1,000, 2,000 and 4,000 mg/kg bw/day for 17 d on consecutive week days (doses were not given on weekends). All dose levels were prepared with water as vehicle and in sufficient quantities for one week's dosing. All dosing solutions were stored at room temperature and used within 8 d of preparation. Parameters measured during the study included mortality, observation of clinical signs, body weight and gross pathology evaluation. Animals were sacrificed by CO2 asphyxiation and gross necropsy was performed for all surviving animals. All male and female rats in the two highest doses (2,000 and 4,000 mg/kg bw/day) died by Day 4. Three male rats died in the 1,000 mg/kg bw/day dose level. There was reduction in relative weight gains at all dose levels. Clinical signs of toxicity were observed in male and female rats dosed with 1,000 mg/kg/day or higher doses. Gross observations at necropsy revealed hemorrhaging in the GI tract, subcutaneous vascular bed and brain in some rats receiving 1,000 mg/kg bw/day or higher doses. Reproductive tract lesions were also observed in some female rats receiving 250, 500 and 1,000 mg/kg bw/day dose. No toxicity related microscopic lesions were observed in rats receiving 500 mg/kg bw/day. Under the conditions of this study, the no observed adverse effect level (NOAEL) for the test substance can be established at 500 mg/kg bw/day (Dinowitz M, 1980).