4-ピコリン

log Kow = 1.22

1.2

1.22

0.9548 at 68 °F (NTP, 1992) - Less dense than water; will float

0.9548 g/cu cm at 20 °C

Relative density (water = 1): 0.96

Miscible with water at 20 °C

Soluble in alcohol, ether

Soluble in acetone, carbon tetrachloride

Solubility in water: miscible

134 °F (NTP, 1992)

57 °C

134 °F (57 °C) (Open cup)

39 °C (102 °F) (Closed cup)

57 °C o.c.

292.8 °F at 760 mmHg (NTP, 1992)

145 °C at 760 mm Hg

144-145 °C

38.5 °F (NTP, 1992)

3.68 °C

3.7 °C

Danger

H226: Flammable liquid and vapor [Warning Flammable liquids]

P210, P233, P240, P241, P242, P243, P261, P262, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P316, P317, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P370+P378, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 8.2% (36 of 439) of reports.

Danger

H226 (91.6%): Flammable liquid and vapor [Warning Flammable liquids]

Chemical: Pyridine, 4-methyl-

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Pyridine, 4-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Pyridine, 4-methyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 03-10-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/23905

4-Methylpyridine: Does not have an individual approval but may be used under an appropriate group standard

Excerpt from ERG Guide 129 [Flammable Liquids (Water-Miscible / Noxious)]:

Flammable. Gives off irritating or toxic fumes (or gases) in a fire. Above 57 °C explosive vapour/air mixtures may be formed.

A corrosive substance that can cause injury to the skin, eyes, and respiratory tract; Inhalation of high concentrations can cause unconsciousness; The liquid defats the skin; [ICSC] An irritant; Can be absorbed through skin; [MSDSonline] An irritant that can cause CNS depression; Liver changes occur in rats exposed to chronic high doses; [AIHA] See Pyridine.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 4-Methylpyridine is included on this list. Effective date: 09/10/84; Sunset date: 09/10/94.

4-METHYL PYRIDINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

This compound is not very flammable but any fire involving this compound may produce dangerous vapors. You should evacuate the area. All firefighters should wear full-body protective clothing and use self-contained breathing apparatuses. You should extinguish any fires involving this chemical with a dry chemical, carbon dioxide, foam, or halon extinguisher. (NTP, 1992)

Use water spray, powder, alcohol-resistant foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Rest. Refer for medical attention .

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

To fight fire, use alcohol foam.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Use water spray to cool unopened containers.

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical, or carbon dioxide. /Picolines/

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Waste treatment methods. Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

Personal protection: chemical protection suit including self-contained breathing apparatus. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for 4-METHYLPYRIDINE (6 total), please visit the HSDB record page.

The relationship between the mutagenicity of cobalt (II) heteroaromatic base complex and the strength of their coordinate bonds was examined ... . The mutagenicity of cobalt(II) chloride was studied in Salmonella test strains (TA-1537), (TA-2637), (TA-97a), and (TA-100) in combination with 4-substituted pyridines. The mixtures were divided into three groups based on spectral evidence of lowest relative strength of coordinate bonding (first group), intermediate strength bonding (second group), and highest strength bonding (third group). The first group of pyridine compounds included pyridine ... 4-methylpyridine, 4-ethylpyridine, 4-chloropyridine, and 4-bromopyridine. With these compounds cobalt (II) chloride demonstrated weak to marginal mutagenicity in (TA-1537), and/or (TA-2637), but not in (TA-98) or (TA-100). ... The second group of compounds included 4-aminopyridine and 4-dimethylaminopyridine. Equimolar mixtures of cobalt (II) chloride with these compounds was not mutagenic. The third group included 4-cyanopyridine ... . Equimolar mixtures of cobalt (II) chloride and ... /this/ compound /was/ not mutagenic. The only mixtures of cobalt (II) chloride and pyridines which demonstrated muagenicity in strains (TA-1537) and/or (TA-2637) were those which showed spectral evidence of only a moderate interaction between the metal cation and the pyridine derivatives. The maximum mutagenicity was noted when the mixture was equimolar.

LC50; Species: Pimephales promelas (fathead minnow); Conditions: flow-through bioassay with measured concentrations, 24.7 °C, dissolved oxygen 7.1 mg/L, hardness 45.0 mg/L CaCO3, alkalinity 524 mg/L CaCO3, and pH 7.66; Concentration: 403 mg/L for 96 hr (confidence limit: 351-464 mg/L)

EC50; Species: Pimephales promelas (fathead minnow); Conditions: flow-through bioassay with measured concentrations, 24.7 °C, dissolved oxygen 7.1 mg/L, hardness 45.0 mg/L CaCO3, alkalinity 524 mg/L CaCO3, and pH 7.66; Concentration: <220 mg/L for 96 hr (confidence limit not reliable); Effect: loss of equilibrium

LC50; Species: Cyprinodon variegatus (Sheepshead minnow); Conditions: flow through; Concentration: 400 mg/L for 96 hr

EC50; Species: Tetrahymena pyriformis (Ciliate) GL-C strain; Conditions: freshwater, static, 28 °C; Concentration: 731040 ug/L for 60 hr (95% confidence interval: 583620-959590 ug/L); Effect: population, decreased population growth rate />95% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 115(SRC), determined from a structure estimation method(2), indicates that 4-methylpyridine is expected to have high mobility in soil(SRC). The pKa of 4-methylpyridine is 5.98(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Soil studies with 2-methylpyridine(5), a compound expected to have similar sorption properties as 4-methylpryidine(SRC), demonstrated that Koc can vary with pH with lowest adsorption occurring in the non-ionized form(5). Volatilization of 4-methylpyridine from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 6.0X10-6 atm-cu m/mole(6). 4-Methylpyridine is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 5.77 mm Hg at 25 °C(7). 4-Methylpyridine may biodegrade fairly rapidly in aerobic soil; however, under anaerobic conditions, this compound is expected to be persistent(8,9). 71.7 and 100% of the available nitrogen was released as inorganic nitrogen within 16 and 32 days following the incubation of 4-methylpyridine in aerobic Fincastle silt loam(7). 4-Methylpyridine added to an unpolluted surface soil under denitrifying or sulfidogenic conditions was 40 to 50% degraded in 3 months(8). Acclimation of microbes may be important as demonstrated by complete degradation of 4-methylpyridine in 2 weeks in polluted soil versus 3 months in unpolluted soil(9).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 115(SRC), determined from a structure estimation method(2), indicates that 3-methylpyridine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon a Henry's Law constant of 6.0X10-6 atm-cu m/mole(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 6 and 47 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 1.22(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 4-Methylpyridine may biodegrade fairly rapidly in aerobic waters; however, under anaerobic conditions, this compound is expected to be persistent. Complete biodegradation of 4-methylpyridine was reported in 2 to 4 days following incubation in acclimated natural waters(7). No biodegradation was reported over 200 days when 4-methylpyridine was incubated in sulfidogenic estuarine sediment(8). 4-Methylpyridine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). The UV absorption spectrum of 4-methylpyridine in aqueous solution shows no absorption >290 nm(9); therefore, 4-methylpyridine is not expected to be susceptible to direct photolysis by sunlight(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-methylpyridine, which has a vapor pressure of 5.77 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-methylpyridine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 6 days(SRC), calculated from its rate constant of 2.69X10-12 cu cm/molecule-sec at 25 °C(3). The UV absorption spectrum of 4-methylpyridine in aqueous solution shows no absorption >290 nm(4); therefore, 4-methylpyridine is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 4-Methylpyridine is a colorless liquid with an obnoxious, sweetish odor. It is used as a solvent in synthesis of pharmaceuticals, resins, dyestuffs, rubber accelerators, and pesticides.It is also used in the production of antituberculosis agent, isoniazid; waterproofing agents fo fabrics; as a laboratory reagent, catalyst, and curing agent. HUMAN EXPOSURE AND TOXICITY: Symptoms include occasional diarrhea, weight loss, anemia, and ocular and facial paralysis. 4-Methylpyridine induced a dose-related increased frequency of sister chromatid exchange in human lymphocyte cultures from three individuals. Chromosomal aberrations induced by 4-methylpyridine included: chromatid breaks; centromeric, intermediate and terminal chromosome breaks; terminal and interstitial deletions; translocation; dicentric chromosomes; and isochromosomes. ANIMAL STUDIES: 4-Methylpyridine was severely irritating in rabbit skin tests. It is a potent inhibitor of red cell cholinesterase and an effective miotic inhibitor in mice and rabbits. Adrenal cortisol production also is inhibited by 4-methylpyridine treatment. In neurophysilogical tests in rats 3-methylpyridine and 2-methylpyridine affected electrophysiological parameters more than did 4-methylpyridine. 4-Methylpyridine was not mutagenic in Chinese hamster lung cells, and it was not mutagenic when tested with Salmonella typhimurium strains TA97, TA98, TA100 and TA102.

Burning sensation. Cough. Dizziness. Drowsiness. Headache. Nausea. Sore throat. Unconsciousness. Weakness.

MAY BE ABSORBED! Dry skin. Redness. Burning sensation. Pain. Blisters. Further see Inhalation.

Redness. Pain. Severe deep burns.

Abdominal pain. Burning sensation. Diarrhoea. Vomiting. Further see Inhalation.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of October 22, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=108-89-4]

4-Methylpyridine was detected in 1 of 6 wastewater effluents from energy related processes(1). The process water at a coal gasification facility in Gillette, WY contained 4-methylpyridine in trace quantities(1). Wastewater from coal gasification at the Grand Fork's Energy Technology Center, ND was also reported to contain 4-methylpyridine(2). In addition, wastewater effluent from a shale oil facility in Queensland, Australia was shown to contain 4-methylpyridine(3). Oil shale condensate retort water contained 4-methylpyridine at 6.3 mg/L(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-methylpyridine can be estimated to be 115(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3-methylpyridine is expected to have high mobility in soil. The pKa of 4-methylpyridine is 5.98(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Soil studies with 2-methylpyridine(5), a compound expected to have similar sorption properties as 4-methylpryidine(SRC), demonstrated that Koc can vary with pH with lowest adsorption occurring in the non-ionized form(5). Spectral studies of 4-methylpyridine adsorbed to hydrated and dehydrated silica indicate that hydrogen bonding occurs with silica surface silanols via the nitrogen atom on the pyridine ring and that this interaction is stronger than that between this compound and water(6).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 4-Methylpyridine is included on this list. Effective date: 09/10/84; Sunset date: 09/10/94.

Although the exact mechanism has not been determined, it appears that all methylpyridines are oxidized to their respective aromatic acids. ...Formation of an N-oxide also occurs with 4-methylpyridine.

The biotransformations of gamma-picoline were investigated in the rat. Wistar rats were admin gamma-picoline by stomach tube at a dose of 300 mg/kg body weight. Urine was collected for 24 hours in the presence of acetic acid while expired air was sampled in 5% aqueous sulfuric acid. gamma-Picoline and metabolites were extracted from the samples and characterized by chromatographic analysis and mass spectrometry. Unmetabolized gamma-picoline was identified in both expired air and 24 hour urine; excreted amounts were approx 2.5% in each. The mass spectral characteristics of gamma-picoline-N-oxide, methylisonicotinate and methylisonicotinurate in the urine were examined; excreted amounts were 1.5%, 50% and 5% respectively. The /results suggest/ that two metabolic pathways for gamma-picoline are observed: N-oxidation leads to the formation of N-oxide; and methyloxidation leads to the formation of isonicotinic acid excreted mainly unchanged and partly as the glycine conjugate isonicotinuric acid.

Used as a chemical intermediate, solvent (pharmaceuticals, resins, dyestuffs, rubber accelerators, pesticides, and waterproofing agents), laboratory reagent, catalyst, and curing agent; [HSDB] Picolines are constituents in cigarette smoke, bone oil, coal tar, and coke oven emissions. [AIHA]

Manufacture of isonicotinic acid and derivatives. In waterproofing agents for fabrics. As solvent for resins.

Solvent in synthesis of pharmaceuticals, resins, dyestuffs, rubber accelerators, pesticides, and waterproofing agents, laboratory reagent, making isoniazid, catalyst, curing agent.

The main use of 4-methylpyridine is in the production of the antituberculosis agent, isoniazid; also used to make 4-vinylpyridine, and subsequently polymers.

Production of indolizinium quaternary salts for trimethine dyes

2023: 1,000,000 - <5,000,000 lb

(1989) ca. 1,500 t/a

Pyridine, 4-methyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Pyridine, 4-methyl-. Aggregated National Production Volume: 1 to < 10 million.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Pyridine, 4-methyl-. National Production Volume: Withheld.

... Acetaldehyde and ammonia give 2-methylpyridine and 4-methylpyridine.

From cyclohexylamine plus ammonia and zinc chloride, also from coal tar and bone oil.

Paraldehyde + ammonia (liquid-phase condensation; coproduced with alpha-picoline/2-methyl-5-ethyl-pyridine)

Pyridine bases, crude (fractionation; coproduced with pyridine/alpha-picoline/2,6-lutidine/3,4-lutidine/pyridine bases)

Acetaldehyde + formaldehyde + ammonia (Reilly synthesis; coproduced with pyridine/alpha-picoline/beta-picoline)

All Other Basic Organic Chemical Manufacturing

Pyridine, 4-methyl-: ACTIVE

Pyridine bases are a constituent of tars. They were isolated from coal tar or coal gas before synthetic manufacturing processes became established. The amounts contained in coal tar and coal gas are small, and the pyridine bases isolated from them are a mixture of many components. Thus, with a few exceptions, isolation of pure pyridine bases was expensive. Today, almost all pyridine bases are produced by synthesis. /Pyridine bases/