4-methylpyridine

Endpoint summary

Description of key information

Acute oral toxicity: Weight of evidence: Experimental results from studies performed with the analogue substances piperidine and pyridine. Results of both studies showed that the LD50 in rats is between 300 and 2000 mg/kg bw which leads to a classification of category 4 according to CLP Regulation EC No. 1272/2008. Based on these results, the read-across approach was applied and 4-methylpyridine can be also considered classified as acute oral toxicity category 4 according to CLP Regulation EC No. 1272/2008.

Acute inhalation toxicity: Weight of evidence: Experimental results from studies performed with the analogue substances piperidine, pyridine and 2-methylpyridine. Most of results from these studies showed that the 4-hour LC50 in rats was over 2000 ppm and less than or around 4000 ppm which leads to a classification that straddles the border between category 3 and category 4 according to CLP Regulation EC No. 1272/2008. Based on these results, the read-across approach was applied and 4-methylpyridine could be also considered between category 3 and category 4. However, 4-methylpyridine is considered classified as acute inhalation toxicity category 4 according to the harmonized classification (Annex VI of CLP Regulation (EC) No 1272/2008).

Acute dermal toxicity: Key study. Test method similar to EPA OPPTS 870.1200. The dermal LD50 of 4-methylpyridine in rabbits was 0.27 ml/kg or 260 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance piperidine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Control animals:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

487 mg/kg bw

Based on:

test mat.

Remarks on result:

other: read-across from an analogue for which LD50 = 445 mg/kg bw

Mortality:

No data.

Clinical signs:

other:

Gross pathology:

Acute standard method: Congestion of stomach blood vessels.

Interpretation of results:

other: Category IV (CLP Regulation EC no. 1272/2008)

Conclusions:

LD50 for substance piperidine is:
- For males: 405 mg/kg bw
- For females: 488 mg/kg bw
- For males/females: 445 mg/kg bw
Based on read across from the analogue piperidine, the LD50 of the substance in rats (males and females) can be considered to be 487 mg/kg bw.

Executive summary:

The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 401 (Acute Oral Toxicity). 5 animals per sex dose from strain Sprague-Dawley rats were administered by oral gavage using the Standard acute method.  The study was performed at the doses of: 5, 50, 500 and 2000 mg/kg bw.

The LD50 of the test item is determined to be: 

- For males: 405 mg/kg bw
- For females: 488 mg/kg bw
- For males/females: 445 mg/kg bw

Based on these results, the read-across approach was applied and the LD50 of the substance in rats (males and females) can be considered to be 487 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance pyridine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 860 mg/kg bw

Based on:

test mat.

Interpretation of results:

other: Category IV (CLP Regulation EC no. 1272/2008)

Conclusions:

The oral LD50 of pyridine in rats is 1580 mg/kg bw. Based on read across from the analogue pyridine, the oral LD50 of the substance in rats is considered to be 1860 mg/kg bw.

Executive summary:

The acute oral toxicity of the test item has been tested in accordance with procedure that precedes establishment of guideline and GLP in rats administered by oral.

The LD50 of the test item is determined to be 1580 mg/kg bw.

Based on these results, the read-across approach was applied and the oral LD50 of the substance in rats is considered to be 1860 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

487 mg/kg bw

Quality of whole database:

Weight of evidence of two studies with Klimisch score = 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance pyridine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

10 608 ppm

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: read-across from an analogue for which LC50 = 9010 ppm.

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

10 620 ppm

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: read-across from an analogue for which LC50 = 9020 ppm.

Mortality:

LC50 was established for a 1 hour exposure.

Interpretation of results:

other: Category 4 (CLP Regulation EC no. 1272/2008)

Conclusions:

Pyridine vapour is acutely toxic to rats at concentration levels of over 9000 ppm for a 1 hour period. Based on read across from the analogue pyridine, the test substance vapour should be acutely toxic to rats at concentration levels of over 10600 ppm for a 1 hour period.

Executive summary:

Pyridine was investigated in an inhalation test. Five rats per group, weighing 200 to 300 g, were exposed to the test substance for a one-hour period. The test was performed using bell jars or large desiccators. Concentrations of test item were measured in the chamber. Results showed that pyridine vapour is acutely toxic to rats at concentration levels of over 9000 ppm for a 1 hour period. Based on these results, the read-across approach was applied and the test substance vapour should be acutely toxic to rats at concentration levels of over 10600 ppm for a 1 hour period.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance 2-methylpyridine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 2 000 - < 4 000 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: read-across from an analogue for which LC50 >2000 ppm and <4000 ppm

Mortality:

2,000 ppm - 0/6
4,000 ppm - 6/6

Interpretation of results:

other: Straddles border of Category 3 and Category 4 (CLP Regulation EC no. 1272/2008)

Conclusions:

The 4 hour LC50 of 2-methylpyridine in rats was over 2000 ppm and less than 4000 ppm. Based on read across from the analogue 2-methylpyridine, the 4 hour LC50 of the test substance in rats was over 2000 ppm and less than 4000 ppm.

Executive summary:

2-methylpyridine was investigated in an inhalation test at concentrations of 2000 and 4000 ppm during 4 h exposure. No deaths ocurrred at 2000 ppm while 6/6 deaths ocurred at 4000 ppm. Thus, the 4 hour LC50 of 2-methylpyridine in rats was over 2000 ppm and less than 4000 ppm. Based on these results, the read-across approach was applied and the 4 hour LC50 of the test substance in rats was over 2000 ppm and less than 4000 ppm.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance pyridine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

< 4 709 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: read-across from an analogue for which LC50 <4000 ppm (5/6 deaths).

Mortality:

5/6 deaths after 4 hours. Time of exposure for no deaths: 30 min.

Interpretation of results:

other: Category 4 (CLP Regulation EC no. 1272/2008)

Conclusions:

The inhalation toxicity of pyridine in rats is less than 4000 ppm after a 4 hour exposure. Based on read across from the analogue pyridine, the inhalation toxicity of the test substance in rats is less than 4709 ppm after a 4 hour exposure.

Executive summary:

Pyridine was investigated in an inhalation test up to a concentration of 4000 ppm during 4 h exposure. 5/6 deaths ocurrred after 4 hours. Time of exposure for no deaths was assessed to be 30 min. Thus, the 4h-LC50 is less than 4000 ppm. Based on these results, the read-across approach was applied and the 4h-LC50 for the test substance is less than 4709 ppm.

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance piperidine which shares the same functional groups with the substance 4-methylpyridine also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 2 187 - < 4 375 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: read-across from an analogue for which LC50 >2000 ppm and <4000 ppm

Mortality:

2187 ppm 0/6 animals died;
4375 ppm 6/6 animals died.

No mortality was observed after 4 h exposure in a vapour atmosphere enriched with 8.47 mg/l (2187 ppm) of the test substance. Mortality of 6/6 rats was observed after 4 h exposure in a vapour atmosphere enriched with 16.95 mg/l (4375 ppm).

Interpretation of results:

other: Category 3 (CLP Regulation EC no. 1272/2008)

Conclusions:

The 4 hour LC50 of piperidine in rats was over 2000 ppm and less than 4000 ppm. Based on read across from the analogue piperidine, the 4 hour LC50 of the test substance in rats was over 2187 ppm and less than 4375 ppm.

Executive summary:

Piperidine was investigated in an inhalation test at concentrations up to 4000 ppm during 4 h exposure. No deaths ocurrred at 2000 ppm while 6/6 deaths ocurred at 4000 ppm. Thus, the 4 hour LC50 of piperidine in rats was over 7.07 mg/l (200 ppm) and less than 14.14 mg/l (4000 ppm). Based on these results, the read-across approach was applied and the 4 hour LC50 of the test substance in rats was over 8.47 mg/L (2187 ppm) and less than 16.95 mg/l (4375 ppm).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

> 2 000 - < 4 000 ppm air

Physical form:

inhalation: vapour

Quality of whole database:

Weight of evidence of several studies with Klimisch score = 2

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Well conducted study. The study was done prior to implementation of GLPs.

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Trunk
- Type of wrap if used: Impervious plastic film

Duration of exposure:

24 hours

Doses:

No data

No. of animals per sex per dose:

Four animals used in study

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.27 mL/kg bw

Based on:

test mat.

Remarks on result:

other: With a density of 0.96, 0.27 ml/kg is equivalent to 0.26 g/kg or 260 mg/kg.

Interpretation of results:

other: Category 3 (CLP Regulation EC no. 1272/2008)

Conclusions:

The dermal LD50 of 4-methylpyridine in rabbits was 0.27 ml/kg or 260 mg/kg.

Executive summary:

4-methylpyridine was investigated for acute dermal toxicity in rabbits by standard acute method. Four New Zealand White rabbits were dermally administered occlusive for 24 hours with substance applied as such. Based on results, the dermal LD50 was determined to be 0.27 ml/kg or 260 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

260 mg/kg bw

Quality of whole database:

Key study with Klimisch score = 2

Justification for classification or non-classification

4-methylpyridine is classified as Category 4 for acute oral and inhalation and category 3 for acute dermal, according to Regulation EC No. 1272/2008. This conclusion is based on the following:

The acute oral LD50 of 487 mg/kg bw is between 300 and 2000 mg/kg for Category 4.

The acute dermal LD50 of 260 mg/kg bw is between 200 and 1000 mg/kg for Category 3.

The acute inhalation LC50 over 2000 ppm and less than or around 4000 ppm straddles the border between category 3 (between 500 and 2500 ppm) and category 4 (between 2500 and 20000 ppm). However, the substance is considered classified as category 4 according to the harmonized classification (Annex VI of CLP Regulation (EC) No 1272/2008).