3-Chloropyridine

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a structure estimation method(2), indicates that 3-chloropyridine is expected to have high mobility in soil(SRC). Volatilization of 3-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). 3-Chloropyridine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). 3-Chloropyridine volatilized 54% from soil incubated at 28 °C for 64 days(3). 3-Chloropyridine did not biodegrade in a 64-day aerobic soil biodegradation study(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a structure estimation method(2), indicates that 3-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). 3-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 4(SRC), from its log Kow of 1.33(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. 3-Chloropyridine, incubated for one year anaerobically in an aquifer slurry, was not biodegraded(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3-chloropyridine, which has an estimated vapor pressure of 4.4 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 3-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). 3-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: 3-Chloropyridine is a clear liquid. It is used as a laboratory chemical. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: 3-Chloropyridine showed a dose-dependent cytotoxicity and clastogenicity towards V3 cells. The L5178Y mouse lymphoma assay was used to examine the potential mutagenicity of 3-chloropyridine. Without activation, 3-chloropyridine produced a small increase in mutant frequency. It was also clastogenic as demonstrated by increases in chromosome aberrations and micronuclei.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3-chloropyridine can be estimated to be 120(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3-chloropyridine is expected to have high mobility in soil(SRC).

AEROBIC: 3-Chloropyridine did not biodegrade in a 64-day aerobic soil biodegradation study(1).

ANAEROBIC: 3-Chloropyridine, incubated for one year anaerobically in an aquifer slurry, was not biodegraded(1).

PURE CULTURE: Complete degradation of 3-chloropyridine was >32 days but <65 days using enrichment cultures isolated from garden soil, incubated aerobically(1). Incubated anaerobically resulted in complete degradation of 3-chloropyridine in >278 days(1).

An estimated BCF of 4 was calculated in fish for 3-chloropyridine(SRC), using a log Kow of 1.33(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 3-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 3-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). 3-Chloropyridine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 3-Chloropyridine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.4 mm Hg(SRC), determined from a fragment constant method(1). 3-Chloropyridine volatilized 54% from soil incubated at 28 °C for 64 days(3).

/GENOTOXICITY/ The Salmonella/microsome assay with strains TA97, TA98, TA100 and TA102 was used to examine the potential mutagenicity and structure-activity of 16 mono- and di-halogenated pyridines. The chemical reactivity of the halopyridines suggests that nucleophilic displacement of halogens can occur with halogens at positions 2, 4 and 6 being displaced in addition-elimination reactions. 2-Chloropyridine gave a positive result with rat-liver metabolic activation, and 2-fluoropyridine gave equivocal results under these conditions. Mutagenic responses were also obtained with 2-chloromethyl pyridine and 3-chloromethyl pyridine, in both the presence and absence of rat-liver S9. These results suggest that the halogenated pyridines, especially with halogens at the 2-position, and singly on a methyl substituent, have mutagenic activity in the Salmonella assay. ... No mutagenic activity was observed with /3-chloropyridine in/ any of the assay conditions used ... . Toxicity, as evidenced by thinning of background lawn and/or decrease in his+ colonies, was seen ... with 3-chloropyridine (at 1000 ug/plate with S9) ... .

/GENOTOXICITY/ During metabolic processes, substituted pyridines may undergo N-oxidation and decomposition. It is a matter of discussion whether these processes influence the reactivity of this class of compounds. To elucidate this problem, the cytotoxicity and clastogenicity of two selected chloropyridines on cultured V3 cells was assessed in the absence and in the presence of pyridine N-oxide. For this purpose two cytotoxicity assays in parallel with chromosomal analysis were performed. In the dose range from 400 to 3200 ug/mL, 3-chloropyridine showed a dose-dependent cytotoxicity and clastogenicity towards V3 cells, whereas in the same dose range 2-chloropyridine was found to be non-cytotoxic and non-clastogenic. Pyridine N-oxide (200 ug/mL) showed protective effects against 3-chloropyridine-induced cytotoxicity and clastogenicity. Under analogous experimental conditions cytotoxic and clastogenic effects were induced by 2-chloropyridine. ...

/GENOTOXICITY/ The L5178Y mouse lymphoma assay was used to examine the potential mutagenicity of three halogenated pyridine compounds. Position effects of the halogen moiety and the role of metabolic activation were analyzed based on induced mutant frequency, gross chromosome aberrations, and micronuclei. Without activation, 2-chloropyridine, 3-chloropyridine, and 2-chloro-5-trifluoromethylpyridine produced a small increase in mutant frequency; only the 2-chloropyridine activity was significantly increased with activation. All three compounds were also clastogenic as demonstrated by increases in chromosome aberrations and micronuclei (except for 2-chloro-5-trifluoromethylpyridine which did not induce micronuclei either with or without activation).

The rate constant for the vapor-phase reaction of 3-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). 3-Chloropyridine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 3-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).

Occupational exposure to 3-chloropyridine may occur through inhalation and dermal contact with this compound at workplaces where 3-chloropyridine is produced or used. Monitoring and use data indicate that the general population is not likely to be exposed to 3-chloropyridine. (SRC)