2-methylpyridine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976-08-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well conducted study similar to OECD 401 protocol. The study was done prior to implementation of GLPs.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

includes 28-day observation period

Principles of method if other than guideline:

28 day observation period

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpyridine

EC Number:

203-643-7

EC Name:

2-methylpyridine

Cas Number:

109-06-8

Molecular formula:

C6H7N

IUPAC Name:

2-methylpyridine

Details on test material:

- Physical state:Liquid
- Analytical purity:99.5%
- Impurities (identity and concentrations): Pyridine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spartan Laboratories
- Age at study initiation: Adult
- Weight at study initiation: 178 g
- Fasting period before study: 16-18 h
- Housing: Individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%

Doses:

550, 790, 950 mg/kg

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: daily observations/once per week weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

Body weight - analysis of variance and Dunnett's Test (p<0.05)

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 950 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 950 mg/kg- highest dose tested

Mortality:

550 mg/kg - 0/10
790 mg/kg - 0/10
950 mg/kg - 4/10 (by day 2)

Clinical signs:

other: 550 mg/kg - lethargy 790 mg/kg - lethargy 950 mg/kg - lethargy, loss of muscle coordination (1/10)

Gross pathology:

550 mg/kg - no treatment related effects
790 mg/kg - no treatment related effects
950 mg/kg (animals that died during study) - accumulation of exudate around mouth and eyes, decreased content of fluid in gastrointestinal tract, darkened liver, gastric hemorrhage, moist edematous appearance of tissues
950 mg/kg (surviving animals) - decreased content of adipose tissue (4/6), decreased size of carcass (1/6)

Other findings:

- Organ weights:
- Histopathology: 950 mg/kg (animals that died during study) - focal gastric hemorrhage (1/4); 950 mg/kg (surviving animals) - encephalomalacia
(2/6) including animal with loss of muscle coordination
- Potential target organs: CNS
- Other observations:

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of alpha-picoline was greater than 950 mg/kg (highest dose tested). The incidence of mortality was 40% at 950 mg/kg. The histopathological examination of surviving animals showed encephalomalacia in two rats suggesting that the CNS was a target organ.