dimethyl 5-methylpyridine-2,3-dicarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl 5-methylpyridine-2,3-dicarboxylate

EC Number:

601-161-5

Cas Number:

112110-16-4

Molecular formula:

C10 H11 N O4

IUPAC Name:

Dimethyl 5-methylpyridine-2,3-dicarboxylate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc., Stoneridge, NY
- Age at study initiation: approximately 9-10 weeks
- Weight at study initiation: 192 g to 318 g
- Fasting period before study: overnight prior to administration of the test material
- Housing: individually, in suspended wire stainless-steel cages with automatic watering
- Diet (e.g. ad libitum): PMI Certified Rodent Chow #5002 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C ± 4°C
- Humidity (%): 50% ± 20%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: nominal concentration: 50% w/v
The test article/carrier mixture was not assayed to determine concentration, homogeneity, or stability in conjunction with this study.

MAXIMUM DOSE VOLUME APPLIED: a constant volume of 10 ml/kg was applied.

DOSAGE PREPARATION (if unusual): The test material was ground to a fine powder with a mortar and pestle and then mixed with Scientific Products (S/P) High Purity Water® to achieve a uniform dispersion.

Doses:

5,000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical Signs:
The test animals were observed for clinical signs and mortality at one, two, four, and eight hours following dosing and daily for the remainder of the 14-day test period.
Body Weights:
Individual body weights were recorded prior to dosing (Day 0), at 7 days postdosing and terminally (Day 14) prior to sacrifice and necropsy.

- Necropsy of survivors performed: yes; on all survivors at the end of the study. The following organs were examined grossly: liver, kidney, spleen, stomach, intestinal tract, lung, urinary bladder and external surfaces

Statistics:

There was no statistical analysis done in conjunction with this study.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

All animals survived the study period.

Clinical signs:

Clinical signs were limited to salivation (6/10), decreased activity (7/10), and prostration (1/10) during the first hour postdosing. By two hours postdosing all animals returned to normal.

Body weight:

All animals gained weight during the study

Gross pathology:

There were no gross pathological changes noted in animals which were sacrificed at the termination of the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the mortality data, the oral LD50 of 2,3-Pyridinedicarboxylic acid, 5-methyl-, 2,3-dimethyl ester was determined to be greater than 5,000 mg/kg for both male and female rats.

Executive summary:

Five male and 5 female rats were dosed orally with 2,3-Pyridinedicarboxylic acid, 5-methyl-, 2,3-dimethyl ester at a dose level of 5,000 mg/kg of body weight. The test material was ground to a fine powder and then mixed with High Purity Water to achieve a uniform dispersion at a nominal concentration of 50% weight by volume (w/v). The test material was administered by oral gavage using a 15 gauge gavage needle at a constant volume of 10 ml/kg. The animals were observed daily for clinical signs during the 14-day test period. Body weights were recorded on the day of dosing (Day 0), Day 7 and at study termination (Day 14). Necropsies were performed on all survivors at the end of the 14-day observation period.

Clinical signs were limited to salivation, decreased activity, and prostration during the first hour postdosing. By two hours postdosing all animals returned to normal. All test animals survived the 14-day test period. All animals gained weight during the study. There were no gross pathological changes noted in animals which were sacrificed at the termination of the study.