Methyl carbamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 3, 1982 to June 2, 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to method comparable to OECD Guideline 401, in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

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 material form:

other: Solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Weight at study initiation: 180 - 280 g (after fasting)
- Fasting period before study: 18 h before administration of test substance
- Housing: Rats housed in groups, according to sex, or individually in stainless steel 1/2" wire mesh cages. Size in accordance with the "Guide for the Care and
Use of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council.
- Diet: Wayne Lab Blox, ad libitum
- Water: Fresh tap water, ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C±3°C
- Humidity (%): 30 to 70%
- Photoperiod: 12 h dark and 12 h light

IN-LIFE DATES: From May 03, 1982 to May 17, 1982

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.25% methyl cellulose

Details on oral exposure:

VEHICLE
- Volume administration: 5 mL/kg and 10 mL/kg

- Rationale for the selection of the starting dose: Based on the results of a dose-range-finding study.

Dose preparation
2,000 mg/kg - 6.0 g q.s. to 15 mL of 0.25% methyl cellulose
2,500 mg/kg - 7.5 g q. s. to 15 mL of 0.25% methyl cellulose
3,000 mg/kg - 9.0 g q. s. to 15 mL of 0.25% methyl cellulose
3,500 mg/kg - 10.5 g q. s. to 30 mL of 0.25% methyl cellulose
4,000 mg/kg - 12.0 g q.s. to 30 mL of 0.25% methyl cellulose
4,500 mg/kg - 12.1 g q. s. to 26.9 mL of 0.25% methyl cellulose

Doses:

2,000, 2,500, 3,000, 3,500, 4,000 and 4,500 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations: The rats were observed immediately, 1 h and 4 h after dosing and daily thereafter for pharmacotoxic, CNS effects and mortality.
- Frequency of weighing: Body weights were recorded initially, Day 14 and at time of death.
- Necropsy of survivors performed: Surviving rats were sacrificed by CO2 inhalation and a gross necropsy was performed.

Results and discussion

Preliminary study:

Signs observed in dose ranging finding study were abnormal gait, semiprostration, body drop, loss of equilibrium, decreased activity, prostration, decreased body tone, increased body tone, exophthalmus and yellow-brown discoloration around anus. None of the rats died at 500 mg/kg bw, one rat died at 1,600 mg/kg bw and three rats died at the 5,000 mg/kg bw dose level.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 900 mg/kg bw

Based on:

test mat.

95% CL:

3 514 - 4 329

Mortality:

2 males died at dose level of 3,000 mg/kg bw.
1 male died at dose level of 3,500 mg/kg bw.
2 males and 4 females died at dose level of 4,000 mg/kg bw.
3 males and 4 females died at dose level of 4,500 mg/kg bw.

Clinical signs:

other: Body drop, ptosis, decreased activity, labored respiration, chromodacryorrhea, decreased body tone, abnormal gait, abnormal stance, partial paralysis, loss of equilibrium, dried red exudate around nasal cavity, semiprostration, prostration, ataxia, diarrh

Gross pathology:

Necropsy of animals dying on study revealed distended, air filled stomachs and intestines, discolored adrenals, lungs, thymus, spleen, small ulcers or erosions of glandular mucosa, hemorrhages in cecum and small amounts of fluid in thoracic cavity. No visible lesions were observed in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test substance for male and female rats was determined to be ≥3,900 mg/kg bw, with 95% confidence limits of 3,514 to 4,329 mg/kg bw.

Executive summary:

A study was conducted to assess the acute toxicity of the test substance to rats according to method comparable to OECD Guideline 401, in compliance with GLP. Dose levels were selected on basis of a dose ranging study. In a preliminary dose-range-finding study, three groups of four fasted animals per group, two per sex, were given the test substance at dose levels of 500, 1,600 and 5,000 mg/kg bw orally, by gavage. Signs observed were abnormal gait, semiprostration, body drop, loss of equilibrium, decreased activity, prostration, decreased body tone, increased body tone, exophthalmus and yellow-brown discoloration around the anus. None of the rats died at 500 mg/kg bw, one of four died at 1,600 mg/kg bw and three of the animals died at the 5,000 mg/kg bw dose level. In main study, the test substance was administered to males and females (5 per sex per group) at dose levels of 2,000, 2,500, 3,000, 3,500, 4,000 and 4,500 mg/kg bw. The rats were observed immediately after the administration of the test substance and then 1 h and 4 h after dosing and daily thereafter for 14 d. Body weights were recorded initially, Day 14 and at time of death. The surviving rats were sacrificed by CO₂ inhalation and a gross necropsy was performed. None of the rats died at 2,000 and 2,500 mg/kg bw, two males died at dose level of 3,000 mg/kg bw, one male died at dose level of 3,500 mg/kg bw, two males and four females died at dose level of 4,000 mg/kg bw and three males and four females died at dose level of 4,500 mg/kg bw. Clinical signs observed were body drop, ptosis, decreased activity, labored respiration, chromodacryorrhea, decreased body tone, abnormal gait and stance, partial paralysis, loss of equilibrium, dried red exudate around nasal cavity, semiprostration, prostration, ataxia, diarrhea, hunched body position, poor grooming, shallow respiration, piloerection, clear discharge from eyes and lacrimation. Necropsy of dead animals showed distended, air filled stomachs and intestines, discolored adrenals, lungs, thymus, spleen, small ulcers or erosions of glandular mucosa, hemorrhages in cecum and small amounts of fluid in thoracic cavity. No visible lesions were observed in the remaining animals. Based on the results of the study, the acute oral LD₅₀ of the test substance for male and female rats was determined to be ≥3,900 mg/kg bw, with 95% confidence limits of 3,514 to 4,329 mg/kg bw (Mallory VT, 1982).