4-methylpyridine

Endpoint summary

Description of key information

Skin irritation/corrosion (in vivo): Weight of evidence: 4-Methylpyridine was tested in vivo for skin irritation/corrosion but it was not able to be evaluated because the test item resulted to be lethal to the animals. Experimental results from studies performed with the analogue substances pyridine, 2-methylpyridine and 3-methylpyridine. Results from these studies showed that test items should be considered as skin irritant (cat 2) 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 skin irritant (cat 2) according to CLP Regulation EC No. 1272/2008.

Eye irritation (in vivo): Key study. Test method according to French official protocol (Draize JH, Woodard G and Calvery HO, 1944). Based on the results of this study, 4-methylpyridine can be considered classified as eye irritant (cat 2) according to CLP Regulation EC No. 1272/2008.

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

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

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

4.8

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: evaluated as irritating

Irritant / corrosive response data:

Pyridine is evaluated as "irritating", as the PII falls within the range of 2 and 5. Pyridine demonstrated necrosis on the abraded skin of all animals. On the 7th day after exposure, ulceration, necrosis and leucocyte infiltration were important and impairment of hair follicles was severe. On intact skin, individual differences were important: very slight to severe erythema with rare necrosis, no or slight oedema. In all cases, no regeneration occured after 72 hours.

Interpretation of results:

other: Category 2 (CLP Regulation EC no. 1272/2008)

Conclusions:

The dermal irriation of pyridine was tested in rabbits according to standard Draize protocol and was found to be a skin irritant. Based on read across from the analogue pyridine, the substance is considered as a skin irritant.

Executive summary:

The skin irritation/corrosion of the test item has been tested in accordance of French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944.

6 rabbits from New Zealand White strain were used for this test in a period duration of 24 hours.

The score obtained was 4.8 and the max. score 8.

Based on these results, the read-across approach was applied and the substance 4-methypyridine can be considered as a skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

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 3-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

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48 h

Score:

6.8

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: Evaluated as "highly or severely irritating", the maximum rating.

Irritant / corrosive response data:

3-Methylpyridine is evaluated as "highly or severely irritating", as the PII falls within the range of 5 and 8. With 3-methylpyridine, erythema and oedema were severe, with frequent necrosis. Oedema generally decreased after 72 hours. Histopathological examinations showed both lesions of necrosis and regeneration.

Interpretation of results:

other: Category 2 (CLP Regulation EC no. 1272/2008)

Conclusions:

The dermal irriation of 3-methylpyridine was tested in rabbits according to French guidelines, similar to a standard Draize protocol (occlusive exposure to intact and abraded skin), and was found to be highly irritating to the skin. Based on read across from the analogue 3-methylpyridine, the substance is considered as highly irritating to the skin.

Executive summary:

The skin irritation/corrosion of the test item has been tested in accordance of French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944.

6 rabbits from New Zealand White strain were used for this test in a period duration of 24 hours.

The score obtained was 6.8 and the max. score 8.

Based on these results, the read-across approach was applied and the substance 4-methypyridine can be considered as highly irritating to the skin.

Reference 3

Endpoint:

skin irritation: in vivo

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

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

5.8

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: Evaluated as "highly or severely irritating", the maximum rating

Irritant / corrosive response data:

2-Methylpyridine is evaluated as "highly or severely irritating", as the PII falls within the range of 5 and 8. With 2-methylpyridine, erythema and oedema were moderate to severe, with necrosis observed in 2 of 5 animals. Histopathological examinations showed both lesions of necrosis and regeneration.

Interpretation of results:

other: Category 2 (CLP Regulation EC no. 1272/2008)

Conclusions:

The dermal irriation of 2-methylpyridine was tested in rabbits according to French guidelines, similar to a standard Draize protocol (occlusive exposure to intact and abraded skin), and was found to be highly irritating to the skin, consistent with necrosis. Based on read across from the analogue 2-methylpyridine, the substance is considered as highly irritating to the skin.

Executive summary:

The skin irritation/corrosion of the test item has been tested in accordance of French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944.

6 rabbits from New Zealand White strain were used for this test in a period duration of 24 hours.

The score obtained was 5.8 and the max. score 8.

Based on these results, the read-across approach was applied and the substance 4-methypyridine can be considered as highly irritating to the skin.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer-reviewed publication using a cosmetics guideline method. No mention of GLP

Qualifier:

equivalent or similar to guideline

Guideline:

other: French Journal Officiel 1982

Principles of method if other than guideline:

French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944. Methods for the study of irritation and toxicity of stubstances applied topically to the skin and mucous membranes. J. Pharmacol Exp Therap 82:377-390.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male New Zealand albino rabbits were obtained from CEGAV, 61350 Saint-Mars-d'Egrenne and weight 2.5 kg at the beginning of the study. They were housed inidvidually in wire mesh cages and fed on a commercial diet with tap water ad libitum. They were kept at least one week for acclimatization prior to testing. Animals were sacrificed after 7 or 14 days.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

Not specifically stated. The method quoted requires 0.5 ml or 0.5 g of material.

Duration of treatment / exposure:

24 hours

Observation period:

72 hours according to the method quoted. However, the study was extended to 14 days with histopathology review at 7 and 14 days.

Number of animals:

6

Details on study design:

The skin of albino rabbits was clipped of hair on the back and flanks 1 day prior to exposure. An area of 14 cm x 14 cm was prepared. On the right side of the vertebral axis, three parallel abrasions were made with a lancet over a length of about 2.5 cm, spaced approximately 5.0 cm apart. These are restricted to the epidermis without reaching the dermis and without bleeding. The test material (0.5 gm or 0.5 ml) was introduced to the 2.5 x 2.5 cm gauze patches and applied immediately to the skin. One face of the gauze was covered with adhesive film, hypoallergenic and waterproof. The gauze was kept in place with tape, a fixing band and a protective pad. The animals were placed in a holding device during the 24-hour patch exposure. Upon removal of patches the resulting reactions were evaluated, and again at 72 hours. A Primary Irritation Index was calculated as an average.

In this study, histopathological examination of the exposure sites took place on the 7th and 14th days. In this study, treatment of the eyes and skin occured in the same animals. Eyes were fixed in 10% neutral buffered formalin and skin in Bouin's solution. Sections of tissues were stained with hematoxilin-eosin-saffron.

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

other: qualitative

Basis:

mean

Time point:

24 h

Reversibility:

not reversible

Remarks on result:

other: Lethal in all animals at 24 h

Irritant / corrosive response data:

4-Methylpyridine is not able to be evaluated for corrosion, due to lethality.

Interpretation of results:

other: Lethal

Conclusions:

The dermal irriation of 4-methylpyridine was tested in rabbits according to French guidelines, similar to a standard Draize protocol (occlusive exposure to intact and abraded skin). When animals were exposured this way, the test material was lethal.

Executive summary:

The skin irritation/corrosion of the test item has been tested in accordance of French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944.

4-Methylpyridine is not able to be evaluated for corrosion, due to lethality.

6 rabbits from New Zealand White strain were used for this test in a period duration of 24 hours.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Cosmetic guideline study with no information on GLP

Qualifier:

according to guideline

Guideline:

other: French Journal Officiel 1984

Principles of method if other than guideline:

French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944. Methods for the study of irritation and toxicity of stubstances applied topically to the skin and mucous membranes. J. Pharmacol Exp Therap 82:377-390.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Amount / concentration applied:

6 male New Zealand albino rabbits were obtained from CEGAV, 61350 Saint-Mars-d'Egrenne and weight 2.5 kg at the beginning of the study. They were housed inidvidually in wire mesh cages and fed on a commercial diet with tap water ad libitum. They were kept at least one week for acclimatization prior to testing. Animals were sacrificed after 7 or 14 days.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

Test material (0.1 ml) is instilled into the conjunctival sac and the eye is held closed for 10 seconds. The animals are held in a holding device for 1 hour, and then returned to their cages. Readings are made at 1 hour and also at 1, 2, 3, 4 and 7 days after instillation. Aqueous fluorescein 2%, preferably freshly prepared, is used to inspect the eye, together with a flashlight and ophthalmology UV lamp lens

In this study, histopathological examination of the exposure sites took place on the 7th day. In this study, treatment of the eyes and skin occured in the same animals. Eyes were fixed in 10% neutral buffered formalin and skin in Bouin's solution. Sections of tissues were stained with hematoxilin-eosin-saffron.

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

cornea opacity score

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

58

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: severe irritation

Irritant / corrosive response data:

Data on individual animals is not available, nor is the IOI (the sum of the scores for each animal at the various time points, which provides an indication of individual variation.
For pyridine, the maximum irritation occured at one hour with a score of 43, which is evaluated as an "irritant". It is noted that there was individual variation, with a few rabbits recovering completely while the lesions of others got worse between the first and last reading. Because overall recover is poor, the category of irritation is increased to "severely" in the text. However, this is not defined in the 1982 grading system

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

4-Methylpyridine was tested for eye irritation in the official French protocol (based on a Draize scale) in rabbit, and found to be "very irritating or severely irritating".

Executive summary:

The eye irritation of the test item has been tested in accordance with French official protocol after the method of: Draize JH, Woodard G and Calvery HO, 1944.

Test material was instilled into the conjunctival sac of 6 males from New Zealand albino rabbits and was found  to be "very irritating or severely irritating".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation/corrision: Based on the available data, the substance is classified as skin irritant (Cat 2) according to CLP Regulation no. 1272/2008.

Eye irritation: Based on the available data, the substance is classified as eye irritant (Cat 2) according to CLP Regulation no. 1272/2008.