Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYRIDINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed2006

Formation and decay of the triplet excited state of pyridine.

A pulse radiolysis study of the formation and decay of the triplet excited state of liquid pyridine has been performed using quenching techniques. The pyridine triplet excited state is observed with an absorption band at lambda = 310 nm and has a first-order decay with a lifetime of 72 ns. Stern-Volmer plots of the quenching of the pyridine triplet excited state with anthracene, naphthalene, and biphenyl give its yield to be 1.3 molecules/100 eV. This value is very similar to the previously determined yield of 1.25 molecules/100 eV for dipyridyl, the predominant condensed-phase product in the gamma-radiolysis of liquid pyridine. The rate coefficient for pyridine triplet excited-state scavenging by oxygen is estimated to be 6.6 x 10(9) M(-1) s(-1). Oxygen may also scavenge the electron precursor to the pyridine triplet excited state, whereas nitrous oxide is observed to have little effect. A pyridyl radical-pyridine (dimer) complex produced in the pulse radiolysis of neat liquid pyridine is detected at lambda = 390 nm and is consistent with iodine scavenging effects. Formation of the pyridiniumyl radical cation-pyridine charge-transfer complex is proposed to be insignificant in liquid pyridine.

Journal Article↗
PubMed1984

A high-performance liquid chromatographic method for the simultaneous determination of nicardipine and its pyridine metabolite II in plasma.

A rapid and specific method in which reverse-phase high-performance liquid chromatography (HPLC) with UV detection was used for the simultaneous determination of nicardipine and its pyridine metabolite II in human plasma is described. Nicardipine, its pyridine metabolite II, and the internal standard were extracted from plasma and partially purified by acid-base partitioning. Final purification and quantitation were achieved by HPLC by using a reverse-phase column and a UV detector (254 nm). The extraction efficiencies for nicardipine and its pyridine metabolite II from 1 mL of plasma were 77.4 and 81.1%, respectively. The sensitivity of the assay was 5 ng/mL for both nicardipine and its pyridine metabolite II, and the linear concentration range of the assay was 5-150 ng/mL for both compounds. The low coefficients of variation (less than or equal to 5%) for samples spiked with nicardipine and its pyridine metabolite II in this concentration range demonstrate good reliability and reproducibility of the assay. The HPLC procedure has been validated by comparison with a GC-electron-capture detection (ECD) procedure, which gives the combined concentration of nicardipine-its pyridine metabolite II (total) and with an HPLC/GC-ECD procedure, which gives the concentration of its pyridine metabolite II. All three methods, which were developed in our laboratory, were used to analyze nicardipine and its pyridine metabolite II in specimens of plasma from subjects treated with nicardipine hydrochloride. Good correlations were found for concentrations of nicardipine, its pyridine metabolite II, and nicardipine plus the metabolite determined by these three procedures. The HPLC procedure is suitable for use in pharmacokinetic studies following administration of nicardipine hydrochloride to humans.

Biotransformation↗
PubMed1994

Olfactory mucosal lesions in F344 rats following inhalation exposure to pyridine at threshold limit value concentrations.

Pyridine is a volatile solvent used as an intermediate in the production of insecticides, herbicides, pharmaceuticals, and dyes. Pyridine is also found in tobacco smoke. Because inhalation is a primary route of exposure to pyridine, we examined the effect of inhaled pyridine on morphology at the portal of entry, the nose. Nasal tissues from F344/N rats exposed using a nose-only mode 6 hr/day for 4 days to either filtered air (controls) or one of two concentrations of pyridine vapor were examined histologically. The rats had been killed 18 hr after the last exposure. The two pyridine concentrations were the current threshold limit value (TLV, 5 ppm) and a high concentration (444 ppm). Olfactory epithelial lesions in rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of neurons; and the presence of intraepithelial luminal structures. The lesions were only slightly more severe in the rats exposed to 444 ppm compared to those rats exposed to 5 ppm pyridine. The results show that inhalation of pyridine at the current TLV concentration of 5 or 444 ppm causes lesions in the olfactory epithelium of rats.

Administration, Inhalation↗
PubMed1987

Pyridine prevents the clastogenicity of benzene but not of benzo[a]pyrene or cyclophosphamide.

Pyridine has been shown to be a much more potent inhibitor than other solvents of the metabolism and therefore the clastogenicity of benzene. In this report, pyridine prevented benzene-derived micronucleus formation in the bone marrow of ICR Swiss mice at much lower levels than xylene did. Time-course experiments did not indicate any delay in the peak micronucleus response to benzene caused by either pyridine or xylene. Similar experiments using pyridine with benzo[a]pyrene and pyridine with cyclophosphamide indicated that the effect of pyridine was specific for benzene. Benzo[a]pyrene (150 mg/kg) was inhibited by pyridine only at levels of 100 mg/kg or more, compared to inhibition of benzene (440 or 880 mg/kg) by pyridine at levels of 5 mg/kg. Cyclophosphamide was not inhibited at any level, and micronucleus formation was increased at lower ratios of pyridine to cyclophosphamide. These results provide indirect conformation of the work by others indicating that benzene is activated in part by a cytochrome P450 isozyme different from those activating benzo[a] pyrene or cyclophosphamide. Since DBA/2 mice (AHH-non-inducible) are more sensitive to benzene than C57Bl/6 mice (AHH-inducible), single and multiple treatments with benzene were compared by micronucleus response in these two strains. DBA mice were more responsive in all cases. Pretreatment with methylcholanthrene caused a greater response to benzene in DBA/2 mice, suggesting that the cytochrome P450 isozyme involved is one of the forms induced by methylcholanthrene independent of the high-affinity Ah receptor. It is hypothesized that more efficient activation of benzene by the unique cytochrome P450 isozyme, perhaps combined with relatively less conjugation, may result in a greater sensitivity of the bone marrow versus the liver, and of DBA/2 versus C57Bl/6 mice.

Animals↗
PubMed1991

Drug metabolizing enzyme induction by simple diaryl pyridines; 2-substituted isomers selectively increase only conjugation enzyme activities, 4-substituted isomers also induce cytochrome P450.

Pyridine derivatives bearing aryl containing substitutions at the 2- and 4-position were administered to male rats, daily, for 3 days at 75 mg/kg. All five 2-substituted pyridines investigated increased rat hepatic UDP-glucuronosyltransferase activities toward three aglycones (morphine, p-nitrophenol, and 1-naphthol) without inducing cytochrome P450. Two of the 4-substituted pyridines investigated (4,4'-dipyridyl, 4-benzylpyridine) significantly induced cytochrome P450. UDP-glucuronosyl-transferase activity by the 4-substituted pyridines was increased to a much lesser extent than seen for the equivalent 2-isomers. The two 4-substituted pyridines eliciting induction of cytochrome P450 were also the only 4-isomers which increased cytosolic glutathione-S-transferase activity, but three 2-substituted pyridines (2-benzoylpyridine, 2-benzylpyridine, and trans-1,2-bis(2-pyridyl)ethylene) increased this activity in the absence of cytochrome P450 induction. No compound investigated induced cytosolic sulfotransferase activity. Diaryl compounds lacking a heterocyclic ring did not increase any of the investigated drug metabolizing enzyme activities. For simple diarylpyridines, the position of substitution on the pyridine ring rather than the nature of the substituent appears to be a major determinant for selective induction of UDP-glucuronosyltransferases without concurrent increases in cytochrome P450. The 2-substituted pyridines were consistently selective inducers of only Phase II or conjugation enzymes. The 4-substituted pyridines included derivatives that could selectively induce Phase II and nonselectively induce both Phase I and Phase II and one derivative that induced neither.

Animals↗
PubMed2005

Biodegradation of pyridine in a completely mixed activated sludge process.

A potential bacterial culture (P1), isolated from garden soil and identified as Pseudomonas pseudoalcaligenes-KPN, was used as a starter seed to develop the biomass in a completely mixed activated sludge (CMAS) reactor and the system was evaluated for treatment of wastewater containing pyridine. The results of this study indicate that pyridine could be degraded efficiently at a loading of 0.251 kg pyridine kg MLSS(-1) d(-1) (0.156 kg TOC kg MLSS(-1) d(-1)) and at an optimal hydraulic retention time (HRT) of 24 h. Pyridine was used as the sole source of carbon and nitrogen by the biomass. Ammonia-nitrogen (NH3-N) was formed due to the metabolism of the pyridine ring. In the present investigation, the performance of CMAS with reference to pyridine biodegradation and the bio-kinetic constants for the biodegradation of pyridine, in a continuous system, were computed. The results indicate that a CMAS system inoculated with P. pseudoalcaligenes-KPN, under optimum conditions of HRT and pyridine loading, gives a yield coefficient of (Y) 0.29, decay coefficient (Kd) 0.0011 d(-1), maximum growth rate constant (mumax) 0.108 d(-1) and saturation rate constant (Ks) 5.37 mg L(-1) for pyridine.

Biodegradation, Environmental↗
PubMed2006

Biotreatment of waste gas containing pyridine in a biofilter.

Industrial waste gas emissions containing pyridine are generated from pyridine manufacturing industries, and in industrial operations where pyridine is used as a solvent, as an intermediate for synthesis and as a catalyst for a variety of applications. Pyridine has unpleasant fishy odor with an odor index of 2390 and waste gaseous emissions containing pyridine require proper treatment prior to discharge. A biofilter, packed with compost and wood chips and inoculated with Pseudomonas pseudoalcaligenes-KPN for enrichment of pyridine-degrading microorganisms, was operated on a continuous feed basis for a period of more than 2 years. The results indicate that the biofilter medium with optimal moisture content of 68% and an effective bed retention time (EBRT) of 28.50s could degrade pyridine effectively (>99%) at a loading of 434 g pyridine m(-3)h(-1). The treated waste gas was also found to be free from pyridine odor.

Air Pollutants↗
PubMed1999

Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60.

Antineoplastic Agents↗
PubMed2001

Regulation of cyclosporin A sensitive mitochondrial permeability transition by the redox state of pyridine nucleotides.

The mechanisms involved in the induction of cyclosporine A sensitive mitochondrial swelling by oxidative stress were investigated in isolated guinea pig liver mitochondria. The aim of our study was to investigate, if swelling is inevitably associated with the oxidation of pyridine nucleotides, and if the oxidized pyridine nucleotides have to be hydrolysed for the induction of mitochondrial swelling. Quantitative measurement of oxidized pyridine nucleotides was performed with HPLC. Mitochondrial swelling was recorded by monitoring the decrease in light scattering of the mitochondrial suspension. Reduction and oxidation of pyridine nucleotides were followed by monitoring the changes of the autofluorescence signal of reduced pyridine nucleotides. Qualitative measurement of mitochondrial membrane potential was performed with the fluorescence indicator rhodamine 123. Neither t-butyl hydroperoxide nor the dissipation of the mitochondrial inner membrane potential with FCCP (carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone) induced the opening of the membrane permeability transition pore, unless an extensive oxidation of mitochondrial pyridine nucleotides took place. Mitochondrial swelling induced by our experimental conditions was always sensitive to cyclosporine A and accompanied by a cyclosporine A sensitive release of inner mitochondrial pyridine nucleotides without pyridine nucleotide hydrolysis. Not the cycling of calcium across the mitochondrial inner membrane but the accumulation of calcium inside the mitochondria was a prerequisite for mitochondrial swelling. The mitochondrial membrane permeability transition is neither caused nor accompanied by the hydrolysis of mitochondrial pyridine nucleotides.

Animals↗
PubMed1997

Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat: interactions and effects of route of exposure.

1. Male Sprague-Dawley rats were exposed to either pyridine, acetone or a combination of both compounds by either intraperitoneal administration (100 mg/kg pyridine or 400 mg/kg acetone) or whole-body inhalation (200 ppm pyridine or 1000 ppm acetone). Plasma and tissue levels of both compounds were determined by gas chromatography/mass spectrometry. 2. Both chemicals were well distributed in the tissues examined following either route of exposure, with concentrations in the order kidney > liver > plasma > lung. 3. Plasma half-life of pyridine was 7 h following a single 100 mg/kg dose of the compound, and 8 h following the last dose of a 3-day, 8 h/day exposure to a 200 ppm inhalation dose of the compound. 4. Plasma half-life of acetone was 4 h and was independent of the route of exposure. 5. The pharmacokinetics of pyridine was not affected by co-exposure to acetone. Similarly, the pharmacokinetics of acetone was not affected by co-exposure to pyridine. 6. Ethoxyresorufin O-deethylase activity in lung and liver and methoxyresorufin O-demethylase activities in liver were induced by pyridine but not by acetone at the doses examined. Pyridine-induced ethoxyresorufin O-deethylase activity was higher following inhalation exposure than following i.p. administration of pyridine but did not parallel tissue levels of the compound.

Acetone↗
PubMed1997

Anaerobic and aerobic degradation of pyridine by a newly isolated denitrifying bacterium.

New denitrifying bacteria that could degrade pyridine under both aerobic and anaerobic conditions were isolated from industrial wastewater. The successful enrichment and isolation of these strains required selenite as a trace element. These isolates appeared to be closely related to Azoarcus species according to the results of 16S rRNA sequence analysis. An isolated strain, pF6, metabolized pyridine through the same pathway under both aerobic and anaerobic conditions. Since pyridine induced NAD-linked glutarate-dialdehyde dehydrogenase and isocitratase activities, it is likely that the mechanism of pyridine degradation in strain pF6 involves N-C-2 ring cleavage. Strain pF6 could degrade pyridine in the presence of nitrate, nitrite, and nitrous oxide as electron acceptors. In a batch culture with 6 mM nitrate, degradation of pyridine and denitrification were not sensitively affected by the redox potential, which gradually decreased from 150 to -200 mV. In a batch culture with the nitrate concentration higher than 6 mM, nitrite transiently accumulated during denitrification significantly inhibited cell growth and pyridine degradation. Growth yield on pyridine decreased slightly under denitrifying conditions from that under aerobic conditions. Furthermore, when the pyridine concentration used was above 12 mM, the specific growth rate under denitrifying conditions was higher than that under aerobic conditions. Considering these characteristics, a newly isolated denitrifying bacterium, strain pF6, has advantages over strictly aerobic bacteria in field applications.

Aerobiosis↗
PubMed2005

Electrochemistry and spectroelectrochemistry of heterobimetallic porphyrin-corrole dyads. Influence of the spacer, metal ion, and oxidation state on the pyridine binding ability.

Combined electrochemical and UV-visible spectroelectrochemical methods were utilized to elucidate the prevailing mechanisms for electroreduction of previously synthesized porphyrin-corrole dyads of the form (PCY)H2Co and (PCY)MClCoCl where M = Fe(III) or Mn(III), PC = porphyrin-corrole, and Y is a bridging group, either biphenylenyl (B), 9,9-dimethylxanthenyl (X), anthracenyl (A), or dibenzofuranyl (O). These studies were carried out in pyridine, conditions under which the cobalt(IV) corrole in (PCY)MClCoCl is immediately reduced to its Co(III) form, thus enabling direct comparisons with the free-base porphyrin dyad, (PCY)H2Co(III) under the same solution conditions. The compounds are all reduced in multiple one-electron-transfer steps, the first of which involves the M(III)/M(II) process of the porphyrin in the case of (PCY)MClCoCl and the Co(III)/Co(II) process of the corrole in the case of (PCY)H2Co. Each metal-centered redox reaction may be accompanied by the gain or loss of pyridine axial ligands, with the exact stoichiometry of the exchange process depending upon the specific combination of metal ions in the dyad, their oxidation states, and the particular spacer in the complex. Before this study was started, it was expected that the porphyrin-corrole dyads with the largest spacers, namely, O and A, would readily accommodate the formation of cobalt(III) bis-pyridine adducts because of the larger size of the cavity while dyads with the smallest B spacer would seem to have insufficient room to add even a single pyridine within the cavity, as was structurally seen in the case of (PCB)H2Co(py). This is clearly not the case, as shown in the present study. A reversible Co(III)/Co(II) reaction is seen for (PCB)MnClCoCl at -0.62 V, which when combined with spectroscopic data, leads to the assignment of (PCB)Mn(III)(py)2Co(III)(py) as the species in pyridine. The reduction of (PCB)Mn(III)(py)2Co(III)(py) to (PCB)Mn(II)(py)Co(III)(py) is accompanied on the slower spectroelectrochemical time scale by the appearance of a 603 nm band in the UV-vis spectra and is consistent with the addition of a second pyridine ligand to the Co(III)(py) unit of the dyad as one ligand is lost from the electrogenerated manganese(II) porphyrin, thus maintaining one pyridine ligand within the cavity. A different change in the coordination number is observed in the case of (PCB)FeClCoCl. Here the initial Fe(III) complex can be assigned as (PCB)Fe(III)ClCo(III)(py), which has no pyridine molecule within the cavity and the singly reduced form is characterized as (PCB)Fe(II)(py)2Co(III)(py)2, which contains two pyridine ligands inside the cavity. A following one-electron reduction of the Fe(II)/Co(III) complex then gives [(PCB)Fe(II)(py)2Co(II)]-.

Journal Article↗
PubMed1997

Synthesis and Magnetic Properties of Six New Trinuclear Oxo-Centered Manganese Complexes of General Formula [Mn(3)O(X-benzoato)(6)L(3)] (X = 2-F, 2-Cl, 2-Br, 3-F, 3-Cl, 3-Br; L = Pyridine or Water) and Crystal Structures of the 2-F, 3-Cl, and 3-Br Complexes.

The reaction of N-n-Bu(4)MnO(4) or NaMnO(4) with appropriate reagents in ethanol-pyridine leads to the high-yield formation of new mixed-valence trinuclear oxo-centered Mn(III,III,II) complexes of general formulation [Mn(3)O(X-benzoato)(6)L(3)] (1, X = 2-fluoro, L = pyridine; 2, X = 2-chloro, L = pyridine; 3, X = 2-bromo, L = pyridine; 4, X = 3-fluoro, L = 2 pyridine + 1 H(2)O; 5, X = 3-chloro, L = 2 pyridine + 1 H(2)O; 6, X = 3-bromo, L = 2 pyridine + 1 H(2)O). The crystal structures of 1, 5, and 6 were determined. Complex 1 crystallizes in the monoclinic system, space group C2/c with a = 15.774(2) Å, b = 17.269(2) Å, c = 21.411(2) Å, beta = 91.11(1) degrees, and Z = 4. Complex 5 crystallizes in the monoclinic system, space group P2(1)/n with a = 15.172(2) Å, b = 17.603(2) Å, c = 21.996(3) Å, beta = 106.300(10), and Z = 4. Complex 6 crystallizes in the monoclinic system, space group P2(1)/n with a = 15.533(3) Å, b = 17.884(2) Å, c = 21.997(4) Å, beta = 106.95(1) degrees, and Z = 4. The three complexes are neutral and possess an oxo-centered Mn(3)O unit with peripheral ligands provided by bridging carboxylate and terminal pyridine or H(2)O groups. Each manganese ion is distorted octahedral, and consideration of overall charge necessitates a mixed-valence Mn(II)Mn(III)(2) description. In 1, the presence of a C(2) axis through the central O atom and one of the manganese atoms (Mn(II)) and the absence of imposed symmetry elements in 5 and 6 (they have the two Mn(III) with a terminal pyridine group and the Mn(II) with a H(2)O terminal molecule) suggest a trapped-valence situation in all three cases. The Mn(II) is assigned on the basis of its longer metal-ligand distances. Variable-temperature magnetic susceptibility studies were performed on 1-6 in the temperature range 2-300 K. Satisfactory fits to the observed susceptibility data were obtained by assuming isotropic magnetic exchange interactions and using the appropriate spin Hamiltonian and susceptibility equation. The derived J and J exchange parameters are all relatively small in magnitude, |J| < 10 cm(-)(1). J characterizes the Mn(II).Mn(III) interactions and J the Mn(III).Mn(III) interaction. Magnetization measurements at 2 K up to 50 kG indicate the variability of the ground state: S = (3)/(2) for 2 and 3; S = (1)/(2) for 1, 4, and 5; and S = (3)/(2), (1)/(2) for 6. X-band EPR spectra measured from 4 K to room temperature on polycrystalline samples of 1-6 show highly significant differences when the ground state is (3)/(2) or (1)/(2). For S = (3)/(2) complexes (2 and 3), there is a transition centered at g approximately 4, which decreases in intensity with increasing temperature. For S = (1)/(2) complexes, this g approximately 4 band does not appear but instead there are broad bands centered at g approximately 2. These results are discussed in terms of spin frustration within the Mn(3)O core, which produces different spin ground states and susceptibility values.

Journal Article↗
PubMed2005

Control of adhesion and surface forces via potential-dependent adsorption of pyridine.

The orientation and extent of adsorption of pyridine on a gold electrode is known to depend on applied potential and is well characterized. By use of the electrochemical surface forces apparatus, we measured the potential dependence of the double-layer interactions and adhesive forces between a gold electrode and a mica surface for different pyridine concentrations. We observed that, unlike mica-mica interactions, the gold-mica interactions were strongly affected by the presence of small concentrations of pyridine. We are able to reach high negative surface potentials (as determined by applying Derjaguin-Landau-Verway-Overbeek theory to our force measurements), which is similar to what is observed in the absence of pyridine. This demonstrates the electronic nature of the forces measured and shows that pyridine does not displace potential-determining ions on the surface. At positive potentials, where the interaction between gold and mica is attractive, pull-off measurements are a strong function of applied potential. The major effect of the presence of pyridine is on the observed shift in the potential of zero force (PZF), moving it to more negative potentials. This effect is caused by the strong dipole of the pyridine molecule. When the applied potential is cast as a deviation from the PZF, the effect of pyridine is to reduce adhesion between gold and mica. We modeled the potential-dependent adhesion of this system using an electrocapillary framework developed previously, and in doing so, we establish the relationship between the gold-liquid and gold-mica surface energies. In addition, we show that pyridine adsorption affects the capacitance of the gold-mica interface.

Journal Article↗
PubMed1979

Bioassay of 2-(Chloromethyl)Pyridine Hydrochloride for Possible Carcinogenicity (CAS No. 6959-47-3).

2-(Chloromethyl)pyridine hydrochloride, an aromatic heterocycle used in a variety of syntheses, was selected for bioassay by the National Cancer Institute because of the structural similarity of this compound to 2-(a,b-dichloroethyl)-pyridine hydrochloride, a carcinogen in rats, mice, Syrian hamsters, and Mongolian gerbils. A bioassay for the possible carcinogenicity of 2-(chloromethyl)pyridine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. 2-(Chloromethyl)pyridine hydrochloride was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, with the exception of 49 male rats in the high dose group. Twenty animals of each sex and species were placed on test as vehicle controls. The high and low dosages of 2-(chloromethyl)pyridine hydrochloride administered were, respectively, 150 and 75 mg/kg for rats and 250 and 125 mg/kg for mice. The compound was administered for 99 weeks to rats and mice. The period of compound administration was followed by an observation period of 6 weeks for rats and 5 weeks for mice. There were no significant positive associations between the dosages of 2-(chloromethyl)pyridine hydrochloride administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed in mice of both sexes, indicating that the dosages of 2-(chloromethyl)pyridine hydrochloride administered tothese animals in this bioassay may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression relative to vehicle controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of 2-(chloromethyl)pyridine hydrochloride to rats, it is possible that these animals may have been able to tolerate a higher dosage. None of the statistical tests for any site in female rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. There was a significant positive trend between the dosages administered and the incidences of subcutaneous fibromas in male rats. The Fisher exact comparisons, however, were not significant. Under the conditions of this bioassay, administration of 2-(chloromethyl)pyridine hydrochloride was not carcinogenic to Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonyms: 2-(Cl-methyl)pyridineHCl; 2-pyridylmethyl chloride hydrochloride; 2-picolylchloride hydrochloride

Journal Article↗
PubMedDate not supplied

Pyridine does not induce unscheduled DNA synthesis (UDS) in hepatocytes of male B6C3F1 mice treated in vivo.

Pyridine was evaluated in an in vivo/in vitro mouse DNA repair assay. Unscheduled DNA synthesis (UDS) was used as an indicator of DNA damage to hepatocytes from male B6C3F1 mice. Test animals were exposed by oral gavage to pyridine or to the vehicle or positive control articles, and hepatocytes were collected and labeled by incubation in media supplemented with [3H]thymidine. Following labeling, the cultures were processed for autoradiographic analysis. Doses were selected based on a pilot study in which 0, 250, 500, 750, 1000 or 2000 mg kg(-1) pyridine in water was administered by gavage. Mice in the 1000 and 2000 mg kg(-1) dose groups were comatose following dosing and died within 24 h of dose administration. Pyridine dose levels for the UDS determination were set at 175, 350 and 700 mg kg(-1). Pyridine solutions in water were administered to mice 2 or 16 h prior to the scheduled sacrifice. The vehicle control group received water 16 h before sacrifice and the positive control group received 10 mg kg(-1) dimethylnitrosamine (DMN) 2 h before sacrifice. Pyridine did not significantly increase the UDS response in hepatocytes isolated from the treated animals, as measured by the incorporation of [3H]thymidine, using standard criteria for a negative response: less than zero mean net grains in repair (NG) and <20% of cells in repair (% IR; cells in repair have at least 5 NG). The vehicle control group and the low, mid- and high pyridine dose groups yielded less than -8.3 NG and < or =1% IR. The positive control group yielded a positive UDS response, with 10.8 NG and 62% IR. These results indicate that pyridine is non-genotoxic in B6C3F1 mouse liver using the UDS endpoint.

Animals↗
PubMed1995

Relaxation of rat thoracic aorta induced by pyridine.

The pharmacological and toxicological activity of pyridine was determined in rat thoracic aorta. Pyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of pyridine and this relaxing effect was not affected by indomethacin (20 microM), NG-monomethyl-L-arginine acetate (50 microM) or methylene blue (50 microM). In high-K+ medium (80 mM), pyridine inhibited the Ca2+ concentration-dependent vasocontraction. Moreover, in Ca(2+)-free medium, the norepinephrine (3 microM)-induced phasic contraction was also suppressed by pyridine, while the caffeine (10 mM)-induced contraction remained unaffected. The cAMP and cGMP levels of rat aorta were not changed by pyridine. The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by pyridine in a concentration-dependent manner. All of these findings indicated that pyridine relaxes rat thoracic aorta by virtue of its Ca2+ channel-blocking properties in vascular smooth muscle.

Animals↗
PubMed2007

Isomerization dynamics and control of the eta2/N equilibrium for pyridine complexes.

A series of pyridine complexes are prepared of the general form TpW(NO)(PMe3)(pyr) where pyr is either pyridine or a substituted pyridine. Depending on substitution pattern, the pyridine can be either N- or eta2-coordinated, and the role of the pyridine substituents and metal oxidation state in determining this equilibrium is explored. For eta2-pyridine complexes, the substituent pattern and solubility characteristics also determine the ratio of coordination diastereomers. Rates of both intra- and interfacial linkage isomerizations are explored along with the pyridine rotational barrier. This study is supported by DFT calculations and X-ray data and includes characterization of both eta2-pyridine and eta2-pyridinium complexes.

Crystallography, X-Ray↗