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EC number: 203-636-9 | CAS number: 108-99-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Corrosive to the skin and causing severe damage to the eye
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: US. 52 FR 42964, 49 CFR 173.136(a)
- Principles of method if other than guideline:
- Test material is applied to the shaved skin of rabbits for 3 min, 60 min and 4 hr, and then removed and the site is rinsed. Evaluations of the site are made at 30-60 min and 48 h after exposure. Skin erythema, edema and corrosion are assessed.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Type of coverage:
- occlusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- 0.5 ml/site, undiluted
- Duration of treatment / exposure:
- 3 min, 60 min and 4 h.
- Observation period:
- 30-60 min, and 48 h.
- Number of animals:
- 6 rabbits per group
- Details on study design:
- Corrosion is defined as irreversible alteration or destruction to the tissue in at least 3 of the animals. Necrosis is defined as ulceration or necrosis of the skin.
- Irritation parameter:
- other: necrosis
- Basis:
- mean
- Time point:
- other: 3 min
- Score:
- 0
- Max. score:
- 6
- Reversibility:
- other: not applicable
- Remarks on result:
- other: no indication of corrosion
- Remarks:
- Corrosion study at 3 min, 60 min, 4 h
- Irritation parameter:
- other: necrosis
- Basis:
- mean
- Time point:
- other: 60 min
- Score:
- 1
- Max. score:
- 6
- Reversibility:
- not reversible
- Remarks on result:
- other: in 1 of 6 animals in this group
- Remarks:
- Qualitative scoring: presence/absence of ulceration/necrosis. Corrosion study at 3 m, 60 min and 4 h
- Irritation parameter:
- other: necrosis
- Basis:
- mean
- Time point:
- other: 4 h
- Score:
- 4
- Max. score:
- 6
- Reversibility:
- not reversible
- Remarks on result:
- other: in 3 of 6 animals
- Remarks:
- Qualitative scoring: presence/absence of ulceration/necrosis. Corrosion study at 3 m, 60 m and 4 h
- Interpretation of results:
- corrosive
- Remarks:
- Migrated information Criteria used for interpretation of results: other: U.S. Department of Transportation
- Conclusions:
- 3-Methylpyridine was tested for skin corrosion using U.S. Department of Transportation guidelines. The substance was corrosive to the skin of rabbits after a 4 h occlusive exposure.
Reference
No effects after a 3 minute exposure.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
Eye irritation
Link to relevant study records
- Endpoint:
- eye 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: Guideline study, where conduct according to GLP is not noted.
- Qualifier:
- according to guideline
- Guideline:
- other: Primary Eye Irritation, 16 CFR 1500.42
- Principles of method if other than guideline:
- One eye of each of 6 rabbits was tested for eye irritation according to the Draize scale.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- 0.1 ml
- Duration of treatment / exposure:
- 1 second duration in the eye
- Observation period (in vivo):
- 24, 48 and 72 h
- Number of animals or in vitro replicates:
- 6
- Irritation parameter:
- maximum mean total score (MMTS)
- Basis:
- mean
- Time point:
- 24 h
- Score:
- 65
- Max. score:
- 110
- Reversibility:
- not reversible
- Remarks on result:
- other: interpreted as Extremely irritating
- Irritant / corrosive response data:
- Corneal damage was observed in all 6 animals. The condition persisted throughout the entire observation period. Hyperemia, chemosis and conjunctival discharge were observed in all rabbits.
- Other effects:
- Iridial damage was observed in 3 of 6 animals.
- Interpretation of results:
- Category 1 (irreversible effects on the eye)
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- 3-Methylpyridine is severely irritating to the eye, according to a guideline study (U.S. Department of Transportation) on eye irritation. The Maximal Mean Test Score was 65/110, with one animal exibiting scores of over 80.
Reference
The average test scores of the six animals were: 74, 52, 56, 63, 57 and 88. Two of the animals had at least 1 test score over 80.1 (out of a maximum of 110. The average score of 65 falls between 50.1 and 80 (severely irritating), but is raised to the next highest score based on the severity of reaction of individual animals.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
3 -Methyl pyridine and pyridine compounds exhibit skin and eye irritation properties. Classification according to the requirements of the CLP Regulation is not straightforward, as not all studies follow the recommended test guidelines currently in effect. The current guideline for skin irritation is compared with older methods, with a conclusion that the current method is less stringent. The OECD 404 Guideline for skin irritation and corrosion, also Regulation EC No. 440/2008, uses a semi-occlusive exposure of intact skin occurs for 4 hours, with evaluation at 1, 24, 48 and 72 hours after patch removal and extended evaluation of observation-based reversibility up to 14 days), whereas older methods commonly used occlusive patches and had limited follow-up assessment for reversibility. Similarly for eye irritation studies, the current OECD 405 method recommends a 21-day recovery period during which reversibility is assessed, whereas older studies rarely include a recovery period of this length. Furthermore, studies which do not provide the individual and/or group data cannot allow evaluation of any excessive reactions by individual animals.
A weight of evidence approach is used for evaluation of irritation and corrosion. The highest-weighted dermal study for 3-methylpyridine is by Fitzgerald, 1991 (Klimisch 1), using a U.S.-compliant GLP corrosion protocol with occlusive exposure 6 rabbits. Data on the individual animals is summarized, with necrosis observed in 1 animal after 60 minutes, and in 3 animals after 4 hours, irreversible at 48 hours after patching. The substance is evaluated as corrosive.
The published study of Duterte-Catella, et al. (1989, Klimisch 2) provides summary data on skin and eye irritation in a study based on the French guidelines of 1982 and 1984 (used for evaluation of cosmetic products and similar to standard Draize irritation protocols, employing occlusive patching of intact and abraded skin). It is possible that eye and skin testing was performed in the same 6 animals, which could contribute to artificially enhanced reactions due to excessive stress. In addition, information was used from histopathology investigations which occurred at 7 and 14 days after dosing. No individual animal data is provided. The authors use terminology which is inconsistent with the guideline, when assigning irritation classes. 3-Methylpyridine was concluded to be severely irritating to skin with a score of 6.8 (of 8, total) in 6 rabbits (Primary Irritation Index between 5 and 8. This corresponds to an expression of irritation per the guideline as “highly irritating”. In an eye irritation protocol, the substance was initially evaluated to be an irritant (using a group score of 45 at one hour/one day (of 110, total)), but was upgraded to “severely irritating” (“very irritating” according to the guideline’s recommended expression of results) based on histopathology findings at day 7 (abrasion of the cornea and fibrillary edema in the lamellae with thickness and cellular inflammatory infiltrate). Note that macroscopic assessment of recovery was not carried out to day 21, according to current guidelines.
In another test for skin corrosion according to United States Department of Transportation (U.S. DOT) guidelines, (Spear, 1984), 3-methylpyridine was found at 48 hours to be corrosive to the skin of all six rabbits tested. In an eye irritation study according to U.S. DOT requirements (based on the Draize method), all six animals showed scores between 50 and 80 (of 110), initially corresponding to “severely irritating”. But with individual animals showing scores over 80, the next highest category of corrosion was selected.
Handbooks, textbooks and reviews of toxicology (Trochimowitz, 1994; WEEL, 1988) classify 3-methylpyridine as a skin corrosive “with necrosis and burns”, and either moderately to severely irritating to the eye, or causing irreversible “corneal cloudiness”.
In other components of a weight of evidence approach, 3-methylpyridine does not have physico-chemical attributes which are informative in evaluation of skin and eye irritation. 2-Methylpyridine, a structural analogue of 3-methylpyridine, has a harmonized classification of eye irritation Category 2, according to Annex VI, Regulation EC No. 1272/2008, Index 613-036-00-2. Another analogue, 4-methylpyridine is harmonized as both an eye and skin irritant, category 2, in Index 613-037-00-8.
In consulting 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. As 3-methylpyridine is a skin corrosive, serious damage to eye is expected.
The criteria for subcategorization of skin corrosive Category 1 into A, B, and C refer to the potency or strength of the effect, with variable durations of exposure. Occlusive dermal exposure to 3-Methylpyridine for 60 minutes resulted in 1 of 6 animals showing necrosis; three animals showed necrosis after 4 hours. Considering that now only 3 animals are used, and a semi-occlusive patch and a 14 day recovery period are used in tests to address this endpoint, the most appropriate subcategory is “C”.
For substances whose mechanism of action is corrosion, the CLP regulation requires classification of the substance as EUH071, “Corrosive to the respiratory tract”. While there is no specific data on respiratory corrosion, this default classification is accepted.
In conclusion, the weight of evidence shows that 3-methylpyridine displays severe skin with necrosis and significant eye irritation, in all studies.
Irritation with necrosis qualifies as “corrosion, Category 1C, with
associated precautionary phrases. For the eye, a
classification of Category 1, “Causes serious eye damage”. These
are combined in the H314 phrase, “Category 1, Causes severe skin burns
and eye damage.” The substance also requires EUH071, “Corrosive to the
respiratory tract”.
Justification for selection of skin irritation / corrosion endpoint:
experimental result according to a guideline method
Justification for selection of eye irritation endpoint:
experimental result according to a guideline method
Effects on skin irritation/corrosion: corrosive
Effects on eye irritation: highly irritating
Justification for classification or non-classification
The weight of evidence shows that 3-methylpyridine displays severe skin and eye irritation with necrosis. This qualifies as “corrosion, Category 1C, with associated precautionary phrases. For the eye, a classification of Category 1, “Causes serious eye damage”. These are combined in the H314 phrase, “Category 1, Causes severe skin burns and eye damage.” It also requires EUH071, “Corrosive to the respiratory tract”
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