Methyl tetrahydro-2-furancarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 9 April 1990 to 25 April 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl tetrahydro-2-furancarboxylate

EC Number:

420-670-1

EC Name:

Methyl tetrahydro-2-furancarboxylate

Cas Number:

37443-42-8

Molecular formula:

C6H10O3

IUPAC Name:

methyl oxolane-3-carboxylate

Test material form:

other: liquid

Details on test material:

Identification: Methfat
Source: QO Chemicals, Inc. P.O. Box 2500 West Lafayette, Indiana 47906
Date received: February 23, 1990
Reference number: PP17-9J29
Purity: Assume 100% for acute testing
Physical description: Clear colourless liquid
Storage conditions: sealed container at room temperature

Test material preparation:
A sufficient amount of test material to dose all animals was transferred from the original container to a labeled vial that was covered and transported to the animal room for dosing. The vial contained a stir bar and was amintained on a magnetic stir plate proir to dispensation and throughout the dosing procedure.

Test animals

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Number on study: Fifteen males and fifteen females
- Body weight range: 211 to 244 grams at study initiation
- Age at start of study: young adult
- Method of identification: eartag
- Housing: Individual suspended wire-mesh cages. The animals were maintained by the animal husbandry staff of Wil Research Laboratories, Inc. in accordance with standard operating procedures.
- Quarantine: The animals were acclimated to laboratory conditions for a minimum of 7 days prior to study initiation.
- Food and water: Purina Certified Rodent Chow #5002 and tap water from on-site wells. Analysis of feed is performed and provided by the manufacturer. Water is analyzed twice yearly in accordance with S.O.P. No. A-20.
- Environmental conditions: Animal room with controlled temperature (68-75 °F), humidity (32-68%) and light (12 hours light/12 hours dark). There were approximately 10 fresh air changes per hour.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Method of test material administration
The test material was dosed undiluted as received based on density (specific gravity). The dose volume was determined by dividing the dosage level, expressed in g/kg, by the specific gravity (1.18 g/ml, as provided by the sponsor). Individual doses were calculated based on body weights taken just prior to dosing and the appropriate dose volume.
The test material was administrated orally via gastric intubation with snub-tipped oral dosing needles (16-gauge) which were affixed to one milliliter syringes. the rats were fasted 18-20 hours prior to dosing and returned to feed approximately 3-4 hours after dosing.

Doses:

2893, 3500 and 4235 mg/kg

No. of animals per sex per dose:

5 males and fives females

Details on study design:

Mortality
The rats were observed at 1.0, 3.0 and 4.0 hours post-dose on day 0 and twice daily thereafter for 14 days.

Clinical observations
The rats were observed at 1.0, 3.0 and 4.0 hours post-dose on day 0 and once daily thereafter for 14 days.

Body weights
Study days -1, 0, 7 and 14 and at death.

Necropsy:
Upon study termination surviving rats were sacrificed by carbon dioxide asphyxiation. The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.

Statistics:

The LD50 values and slopes (with 95% confidence limits) were calculated bu the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

3 410 mg/kg bw

Based on:

test mat.

95% CL:

2 855 - 4 073

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 027 mg/kg bw

Based on:

test mat.

95% CL:

2 658 - 3 447

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 217 mg/kg bw

Based on:

test mat.

95% CL:

2 921 - 3 542

Mortality:

Approximately two-thirds of the rats died (19/30); eleven of these were female. All deaths occurred within two days of dosing. There were two deaths on day 0 and ten and seven rats were found dead on days 1 and 2, respectively.

All rats that survived appeared normal by day 6 or earlier and throughout the remainder of the study.

Clinical signs:

other: The majority of clinical observations occurred early in the study period, generally on days 0-2. Bradypnea was present for essentially all animals (28/30). Hypoactivity, impaired equilibrium and clear ocular discharge were observed for two-thirds or more

Gross pathology:

Stomach abnormalities (reddened mucosa, dark red areas or contents, gray mucosa) and clear red fluid contents in the urinary bladder were observed for 11/19 rats that died. Dark red adrenal glands, a typical agonal change, were present in approximately one-half of the rats that died. Dense white regions in one or both eyes were noted for six rats. Four dead rats had hemorrhagic thymus glands. Other findings noted each for two rats were dark red kidneys, a reddened pituitary gland and dark red intestinal contents. In addition, approximately one-half of the rats that died had various external matting.
There were no significant changes observed for all tissues examined for all rats that were terminally sacrificed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD 50 value of Methfat was found herein to be 3217 mg/kg with 95 % confidence limits of 2921-3542 mg/kg when administered orally via gastric intubation to fasted male and female albino rats.