Registration Dossier

Administrative data

Description of key information

This substance is corrosive to the skin and causes serious damage to the eye.  The harmonized classification of the substance in Regulation (EC) No. 1272/2008 is "Category 2 irritant" for both skin and eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, but no mention of GLP.
Qualifier:
according to guideline
Guideline:
other: U.S. Department of Transportation, 49 CFR 173.240
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: stainless teel with elevated wire mesh flooring, 1 rabbit/cage.
- Diet (e.g. ad libitum): Wayne 15% rabbit ration
- Water (e.g. ad libitum): tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-75 degrees F
- Humidity (%): 40-45%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1983-06-09 To: 1983-06-11
Type of coverage:
occlusive
Preparation of test site:
shaved
Controls:
no
Amount / concentration applied:
0.5 ml portion of test substance was applied to the skin covering 1 square inch. Surgical gauze patches measuring not less than 1" x 1" and two single layers thick were placed over the treated area and an impervious material was wrapped snugly around the trunk of the animal to hold the patch in place.
Duration of treatment / exposure:
4 hour contact period. At this time, the site was examined, then washed off with water to avoid continued exposure.
Observation period:
Readings were made at 4, 24 and 48 hours after application.
Number of animals:
6
Details on study design:
Corrosion was considered to have resulted if the material in contact with skin had caused destruction or irreversible alteration of the tissue. Tissue destruction was considered to have occurred if, at any of the readings, tere was ulceration or necrosis. Thissue destruction was not considered to have occurred if merely sloughingof the epidermis, erythema, edema or fissuring was evident.
Irritation parameter:
other: objective evaluation of irritation/corrosion
Basis:
animal #1
Time point:
other: 24
Remarks on result:
other: moderate erythema, slight edema, no corrosion
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #1
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, no corrosion
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #2
Time point:
other: 24
Remarks on result:
other: severe erythema, slight edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #2
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #3
Time point:
other: 24
Remarks on result:
other: severe erythema, slight edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #3
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #4
Time point:
other: 24
Remarks on result:
other: severe erythema, slight edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #4
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #5
Time point:
other: 24
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #5
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #6
Time point:
other: 24
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritation parameter:
other: objective assessment of irritation/corrosion
Basis:
animal #6
Time point:
other: 48
Remarks on result:
other: severe erythema, no edema, Corrosive
Irritant / corrosive response data:
5 of 6 animals displayed evidence of corrosion
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: other: U.S. Department of Transportation
Conclusions:
4-Methylpyridine was corrosive to the skin of rabbits after a 4 hour exposure, according to a U.S. Department of Transportation protocol.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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: Similar to guideline study but taking place prior to establishment of guideline and GLP.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
; treated eyes were washed at 15 minutes and 1 hour, rather than at 24 hours.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml undiluted, placed in conjunctival sac of right eye
Duration of treatment / exposure:
15 min and 24 h
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
The treated eye of the rabbits was washed with physiological saline at 15 minutes and at 1 hour after exposure . Evaluations were made according to the Draize scale. Animals were evaluated for 14 days after treatment
Irritation parameter:
maximum mean total score (MMTS)
Remarks:
according to Draize, Woodard and Calvery, 1944
Basis:
mean
Time point:
other: 24 h
Score:
71.6
Max. score:
80
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Observations at 1 and 24 h after exposure: corneal cloudiness, moderate to severe erythema and edema, iris unresponsive to light, copious discharge.
Other effects:
Improvement throughout the observation period, with no abnormalities noted at 14 days post treatment.
Interpretation of results:
highly irritating
Remarks:
Migrated information severe irritant according to the Draize criteria Criteria used for interpretation of results: EU
Conclusions:
4-Methylpyridine was tested in the Draize eye irritation protocol in rabbits, with the conclusion that the substance is a severe eye irritant. Corneal cloudiness observed after the exposure resolved in 14 days.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Based on in vivo studies in rabbits, exposure to this substance results in skin corrosion (Costello, 1983 and Duterte-Catella et al., 1989). Another study of skin irritation showed severe irritation with a score of 7/8. Testing also indicates that in vivo exposure in the eye demonstrated corneal opacity and severe irritation. There is no known data on respiratory irritation. These data indicate that the hazard of skin and eye exposure to 4 -methylpydine is higher than that reflected in the harmonized classification as irritants.


Justification for selection of skin irritation / corrosion endpoint:
experimental data

Justification for selection of eye irritation endpoint:
experimental data

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

4 -Methylpyridine is harmonized for classification for the endpoints of skin irritation, Category 2 and Eye Irritation, Category 2. The substance has been shown to cause destruction of skin tissue, ulceration and necrosis in all animals exposed for 4 hours using a protocol for Department of Transportation skin corrosion. The substance is classified as a Category 1 (C) skin corrosive. The substance also causes severe damage to the eyes. According to the 2013 Guidance on the Application of the CLP Criteria, version 4.0, Section 3.3, if a substance is classified as skin corrosive category 1, then serious damage to eye is implicit and there is no need to proceed with classification for eye effects. The substance is therefore considered as corrosive to the skin and causing serious eye damage. This is a change from the harmonized classification of "Eye Irritant, Category 2".Based on a corrosive mechanism of action, Regulation (EC) No. 1272/2008 Table 3.1.3 Note 1 requires classification of this substance as EUH071, corrosive to the respiratory tract.