2-methylpyridine

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non guideline study. Published in peer reviewed literature. Minor restrictions in design and reporting but adequate for assessment.

Principles of method if other than guideline:

Male Wistar albino rats were orally exposed to the test substance by gavage followed by a 14 day observation period. Besides mortality, animal weight was recorded. Necropsy was performed on all animals that died and on sacrificed survivors to examine for gross pathology.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3-4 wk
- Weight at study initiation: 90-120 g
- Fasting period before study: No fasting took place
- Diet: Commercial rodent feed, ad libitum
- Water: Municipal water, ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of dosing, and 14 d post dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross pathology

Statistics:

LD50 values and their 95% confidence limits were calculated by the moving average method of Thompson (1947) and the tables of Weil (1983).

Sex:

male

Dose descriptor:

LD50

Effect level:

885 mg/kg bw

95% CL:

600 - 1 314

Remarks on result:

other: Value reported 0.93 (0.63-1.38) mL/kg

Mortality:

Animals died within 4 hours after dosing.

Clinical signs:

other: - Rapid progression of lethargy, laboured breathing, ataxia, and prostration, all occurring within a few minutes. - Convulsions at day 1.

Gross pathology:

- Animals that died: lung haemorrhage, congested kidneys, and hyperaemic stomachs and/or intestines.
- Animals that survived: most survivors showed no gross pathology, a few had lung haemorrhages.

Interpretation of results:

harmful

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

885 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non guideline study. Published in peer reviewed literature. Minor restrictions in design and reporting but adequate for assessment.

Principles of method if other than guideline:

A constant exposure time of 4 hours was used and the concentration of test material in the chamber air was varied until mortality data were sufficient to allow the calculation of an LC50. Rats were examined frequently during exposure and daily for 14 post-exposure days. All rats that died and sacrificed survivors were subjected to necropsy.

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3 - 4 wk
- Weight at study initiation: 90 - 120 g
- Fasting period before study: No fasting took place
- Diet: Commercial rodent feed ad libitum
- Water: Municipal water, ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: dried air

Details on inhalation exposure:

- The test material was pumped into the top of a vertical glass evaporator tube, which was heated sufficiently to cause vaporization (Snelling & Dodd, 1990). Dried air was introduced through the bottom of the tube (counter-current to the sample flow) and the resultant vapor-containing atmosphere passed to a 9-L exposure chamber.
- Chamber concentrations were determined by adjustment of sample and/or air flow rates.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were measured just before exposure and at sacrifice.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology

Statistics:

LC50 were calculated along with 95% confidence limits using the method of moving averages (Thompson, 1947; Weil, 1983)

Sex:

female

Dose descriptor:

LC50

Effect level:

2 100 ppm

95% CL:

1 700 - 2 600

Exp. duration:

4 h

Remarks on result:

other: 7993.9 mg/m3

Mortality:

Times to death: 1.7 hour - 1 day

Interpretation of results:

toxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

7 994 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

Acute toxicity: oral

In a publication from Myers and Ballantyne (1997), 5 male Wistar albino rats per dose were orally exposed to the test substance by gavage followed by a 14-day observation period. Besides mortality, animal weight was recorded. Necropsy was performed on all animals that died and on sacrificed survivors to examine for gross pathology. No detailed mortality data was published. Clinical signs included rapid progression of lethargy, labored breathing, ataxia, and prostration, all occurring within a few minutes. At day 1 convulsions were observed. Gross pathology revealed lung haemorrhage, congested kidneys, and hyperaemic stomachs and/or intestines in the animals that died. The LD50 was determined to be 885 mg/kg bw.

In an acute oral toxicty study (TSCATOTS42014_1976) single oral doses of 950, 790 and 550 mg/kg of the test substance were administered to Sprague-Dawley rats (10 per dose) and the animals were held for a 28 day observation period prior to sacrifice and histopathalogical examination. At 950 mg/kg bw, 4 out of 10 rats died. At 790 and 550 mg/kg bw no mortality was occurred. The remaining 6 animals showed decreased body weight throughout the study period and 2/6 showed functional impairment observed as muscular incoordination and loss of equilibrium. These findings are assessed as indication of CNS damage. During gross pathology these rats showed signs of encephalomalacia (areas devoid of neuronal elements, neurons and supportive cells normally found in brain tissue). The LD50 was determined to be slightly greater than 950 mg/kg bw.

In a study by Smyth (1951), Carworth-Wistar rats were exposed to the test substance by oral gavage and observed for 14 days. The oral LD50 has been determined to be 1410 mg/kg bw.

In a another study (TSCATOTS0206650_1964) two groups of 2 rats each were orally exposed to an aqueous solution of the test substance at 500 and 1000 mg/kg bw. Besides mortality, clinical signs were recorded and autopsy performed. At 500 mg/kg bw no mortality occurred. The animals looked okay during and after feeding. At 1000 mg/kg bw one animal died overnight. The other three days after feeding. Kidney injury was observed upon autopsy (1000 mg/kg bw). An LD50 was not determined but based on these results the acute oral LD50 is in between 500 and 1000 mg/kg bw.

In a summary document from Eastman Kodak (TSCATOTS0206640_1980) the results of a rat and a mice oral toxicity study is presented. For both rats and mice the oral LD50 was determined to be between 400 and 800 mg/kg bw.

Besides these studies of which the report were available, in a document by EFSA an additional LD50 of 810 mg/kg bw has been reported and in the NTP database (1991) an acute oral LD50 of 790 mg/kg bw has been published.

Acute toxicity: inhalation

In a publication from Myers and Ballantyne (1997), the test substance was evaluated for its acute inhalation toxicity. A constant exposure time was used (4 h) and the concentration of test material in the chamber air was varied until mortality data were sufficient to allow the calculation of an LC50. Rats were examined frequently during exposure and then daily for 14 post-exposure days (or until death). All rats that died and sacrificed survivors were subjected to necropsy. The LC50 was determined to be 2100 ppm or 8.0 mg/L.

In a study by Smyth (1951), six rats were exposed to 2-picoline at concentrations of 2000 and 4000 ppm (approximately 7.6 and 15.2 mg/L, respectively) for 4 hours and observed for 14 days post exposure. The rats exposed to 2000 ppm (7.6 mg/L) for 4 hours all survived. The rats exposed to 4000 ppm (15.2 mg/L) for 4 hours all died. Therefore, the LC50 was determined to be in between 7.6 and 15.2 mg/L.

In a study by Birch (summarized in the EPA 2009 report), Sprague-Dawley rats (6 males) were exposed to the test substance at an average chamber concentration of 13.2 g/m3 (approximately 13.2 mg/L) for 4 hours. All animals died at this concentration.

 

Acute toxicity: dermal

In a publication from Myers and Ballantyne (1997), the test substance was evaluated for its acute percutaneous toxicity. The test substance was applied to the skin of New Zealand White rabbits and covered with plastic sheeting for 24 hours. After exposure, the site was cleaned follwed by a 24 hour observation period. In addition, necropsy of survivors performed on decedents and sacrificed survivors. Times till death of rabbits was: 1-8 d (middle dosage 0.40 mL/kg) animals given the test substance died up to 8 d after dosing. Clinical sign included local skin lesions with necrosis. No systemic effects were noted. Weight gain was observed. Congested and mottled lungs, liver, kidneys, and spleen were found at necropsy of animals that died. The dermal LD50 was determined to be 267 mg/kg bw.

In another study (TSCATOTS02065560_1984), two groups of 2 rabbits were exposed (Cuff Technique) to 0.252 and 0.50 g/kg for 24 hours. At 252 mg/kg bw no mortality occurred. At 500 mg/kg bw all animals died. One animal died overnight, the other nine days later. Clinical signs included moderate necrosis with slight edema after removal of the cuff, but animals recovered normally (252 mg/kg bw). Severe necrosis and slight edema upon removal of the cuff was observed and one animal lost control over his hind quarters to a certain extent (500 mg/kg bw). The dermal LD50 was determined to be in between 252 and 500 mg/kg bw

In a study by Smyth (1951), four rabbits per dose were exposed to the test substance under occlusive conditions to the skin and observed for 14 days.The oral LD50 has been determined to be ca 390 mg/kg bw.

In a study by Birch (summarized in the EPA 2009 report), New Zealand White rabbits (1/sex/dose) were administered the test substance dermally on to clipped hair at 79.4 (female), 200 (male), 316 (female), 501 (male), 1000 (female), or 2000 (male) mg/kg bw under occluded conditions and observed for 14 days post exposure. All rabbits exposed to 316 mg/kg -bw or above died within one day of exposure. The dermal LD50 value was determined to be in between 200 and 316 mg/kg bw.

In a summary document from Eastman Kodak ( TSCATOTS0206640_1980) the results of a skin absorption study are presented. The dermal LD50 was determined to be between ca. 950 and ca. 1900 mg/kg bw.

Justification for classification or non-classification

The test substance has to be classified for Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn: R22: Harmful if swallowed in accordance with Directive 67/548/EEC (DSD).

The test substance has to be classified for acute toxicity Cat 3: H331: Toxic if inhaled in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and T R23: Toxic by inhalation in accordance with EU Directive 67/548/EEC (DSD).

The test substance has to be classified for acute toxicity Cat 3: H311: Toxic in contact with skin in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn R21: Harmful in contact with skin in accordance with EU Directive 67/548/EEC (DSD).