4-Chloropyridine

Slightly soluble in water

Miscible with ethanol

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Cobalt(II) chloride (CoCl2), non-mutagenic by itself, has been tested for mutagenic activity in the presence of 4-substituted pyridines in the test strains of Salmonella typhimurium. CoCl2 was found to be mutagenic in strains TA1537 and TA2637, when combined with pyridine, methyl isonicotinate, 4-methyl-pyridine, 4-ethylpyridine, 4-chloropyridine or 4-bromopyridine. Mixtures of CoCl2 and isonicotinic acid, 4-cyanopyridine, 4-aminopyridine, or 4-dimethylaminopyridine exhibited no mutagenicity. Judging from the spectral observations, such combined mutagenicity may be due to the formation of moderate to weak complexes between these compounds and the Co(II) cation.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a structure estimation method(2), indicates that 4-chloropyridine is expected to have high mobility in soil(SRC). Volatilization of 4-chloropyridine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). 4-Chloropyridine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). 4-Chloropyridine volatilized <1% from soil incubated at 28 °C for 64 days(3). 4-Chloropyridine biodegraded approximately 67%(4) and 85%(3) in 64-day aerobic soil biodegradation studies.

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a structure estimation method(2), indicates that 4-chloropyridine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 5.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 7.8 and 60 days, respectively(SRC). 4-Chloropyridine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 1.28(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. 4-Chloropyridine, incubated for one year anaerobically in an aquifer slurry, biodegraded approximately 73%(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-chloropyridine, which has an estimated vapor pressure of 4.5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-chloropyridine 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 62 days(SRC), calculated from its rate constant of 2.6X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). 4-Chloropyridine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 4-Chloropyridine is a liquid. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: There are no data available. ECOTOXICITY STUDIES: 4-Chloropyridine was administered at 316 mg/kg as single oral dose to adult male Coturnix quail (Coturnix coturnix). It did not reduce the fertility of eggs produced by female mates by more than 50%.

/BIRDS and MAMMALS/ Seventy-one chemicals /(including 4-chloropyridine)/ were administered as single oral doses at about 50% of the estimated LD50 to adult male Coturnix quail (Coturnix coturnix). /The dose used for 4-chloropyridine was 316 mg/kg/. None reduced the fertility of eggs produced by female mates by more than 50%. Of six additional chemicals similarly administered to female quail at 24 to 56% of the estimated LD50, only one, P,P-bis(1-aziridinyl)-N-phenylphosphinic amide, reduced expected egg fertility by more than 50%.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-chloropyridine can be estimated to be 120(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-chloropyridine is expected to have high mobility in soil(SRC).

AEROBIC: 4-Chloropyridine biodegraded approximately 67% in a 64-day aerobic soil biodegradation study. Halogens at the para-position of the pyridine ring are more susceptible to displacement than at other positions and convert readily to hydroxypyridines. Therefore, the biodegradation of 4-chloropyridine was attributed to hydroxylation(1). 4-Chloropyridine was biodegraded 85% in soil incubated at 28 °C for 64 days(2).

ANAEROBIC: 4-Chloropyridine, incubated for one year anaerobically in an aquifer slurry, biodegraded approximately 73%(1).

PURE CULTURE: Complete degradation of 4-chloropyridine was >62 days but <96 days using enrichment cultures isolated from garden soil, incubated aerobically(1). Incubated anaerobically complete degradation of 4-chloropyridine was >96 days(1).

An estimated BCF of 3 was calculated in fish for 4-chloropyridine(SRC), using a log Kow of 1.28(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for 4-chloropyridine is estimated as 5.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-chloropyridine is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 7.8 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 60 days(SRC). 4-Chloropyridine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 4-Chloropyridine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.5 mm Hg(SRC), determined from a fragment constant method(1). 4-Chloropyridine volatilized <1% from soil incubated at 28 °C for 64 days(3).

The rate constant for the vapor-phase reaction of 4-chloropyridine with photochemically-produced hydroxyl radicals has been estimated as 2.6X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 62 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 4-Chloropyridine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 4-Chloropyridine does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). The rate constant for the reaction of hydroxyl radicals in aqueous solutions at pH 9 is 3.1X10+9 L/mol-sec(3); this corresponds to an aquatic half-life of 260 days at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(4).

Occupational exposure to 4-chloropyridine may occur through inhalation and dermal contact with this compound at workplaces where 4-chloropyridine is produced or used. Monitoring and use data indicate that the general population is not likely to be exposed to 4-chloropyridine. (SRC)

4-Chloropyridine's production and use as a laboratory chemical and in the synthesis of other substances may result in its release to the environment through various waste streams. If released to air, a estimated vapor pressure of 4.5 mm Hg at 25 °C indicates 4-chloropyridine will exist solely as a vapor in the atmosphere. Vapor-phase 4-chloropyridine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 62 days. 4-Chloropyridine does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, 4-chloropyridine is expected to have high mobility based upon an estimated Koc of 120. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 5.2X10-6 atm-cu m/mole. 4-Chloropyridine may volatilize from dry soil surfaces based upon its estimated vapor pressure. 4-Chloropyridine volatilized <1% from soil incubated at 28 °C for 64 days. 4-Chloropyridine biodegraded approximately 67 and 85% in 64-day aerobic soil biodegradation studies. If released into water, 4-chloropyridine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. 4-Chloropyridine, incubated for one year anaerobically in an aquifer slurry, was biodegraded approximately 73%. Volatilization from water surfaces is expected based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 7.8 and 60 days, respectively. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to 4-chloropyridine may occur through

Reaction of 4-chloropyridine with mercaptoacetic acid gives pyridylmercaptoacetic acid, which is a precursor for cephalosporin antibiotics (e.g., cephapirin sodium salt).

The 2- and 4-chloropyridines react with various nucleophiles to give alkyl ether, alkyl thioether, and alkylamine derivatives.