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PYRIDINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Pyridine is an alkylpyridine. It is a colorless liquid used as a solvent and in organic syntheses, especially agricultural chemicals.

Specific Substances

    1) Azabenzene
    2) Azine
    3) Pyridin
    4) Pirydyna
    5) Molecular Formula: C5-H5-N
    6) CAS 110-86-1
    1.2.1) MOLECULAR FORMULA
    1) C5-H5-N

Available Forms Sources

    A) FORMS
    1) Pyridine is a colorless or yellow liquid with a sharp, nauseating odor and a definite burning taste (Bingham et al, 2001; HSDB , 2001). Thermal breakdown products include oxides of nitrogen and cyanide. Pyridine is a CNS depressant (Lewis, 2000).
    B) SOURCES
    1) Pyridine was originally discovered in coal tar in the mid 1800's. It is mainly derived from crude coal tar, but is also synthesized from aliphatic compounds. It is also found in tobacco smoke, roasted coffee, creosote oil, wood oil, and in the leaves and roots of Atropa belladonna (Krone et al, 1986; (Reed, 1990; Bingham et al, 2001; HSDB , 2001).
    C) USES
    1) Pyridine is used as a solvent for organic and inorganic compounds. About half of the pyridine in the United States is used in the manufacture of herbicides and insecticides. Pharmaceutical manufacturers use it as an intermediate for the manufacture of steroids, vitamins, and antihistamines, and for general solvent purposes (Clayton & Clayton, 1994; Bingham et al, 2001).
    a) Pyridine was occasionally used as an anticonvulsant before 1950 (Jori et al, 1983).
    2) Less significant amounts of pyridine are used as a dyeing assistant in textiles, denaturant in alcohol and antifreeze, and as a flavoring agent (Reed, 1990).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) ORAL - Acute effects of pyridine involve the CNS, with coma and respiratory depression leading to death. Signs/symptoms may be delayed in onset by several hours.
    1) Signs and symptoms of acute oral exposures may include nausea, headache, insomnia and nervousness, and low back or abdominal discomfort with urinary frequency. Lung congestion may occur.
    B) INHALATION may produce emphysema and chronic bronchitis. High level exposures may cause headache, dizziness, abdominal pain, nausea, insomnia, anorexia, and peripheral weakness.
    C) DERMAL - Skin exposures may cause irritation or systemic intoxication.
    0.2.4) HEENT
    A) Vapors may be irritating to the nose, eyes, and throat.
    0.2.6) RESPIRATORY
    A) Severe acute intoxications may result in respiratory depression and death.
    B) Upper respiratory tract irritation may occur following vapor exposure.
    C) Pulmonary edema and bronchitis developed in a man who drank one-half cup of commercial pyridine.
    0.2.7) NEUROLOGIC
    A) CNS effects range from coma (significant exposure) to nervousness, fatigue, insomnia, headache, faintness, and speech disorders in chronic ingestion or inhalation of the vapors.
    0.2.8) GASTROINTESTINAL
    A) Irritation may result in abdominal pain with vomiting, or diarrhea.
    0.2.9) HEPATIC
    A) Pyridine is hepatotoxic, and may produce hepatic necrosis and cirrhosis, particularly after chronic exposure.
    0.2.10) GENITOURINARY
    A) Kidney damage has been reported. Urinary frequency is seen more often than anuria, which is reported in animals when near death.
    0.2.13) HEMATOLOGIC
    A) Small doses may stimulate the bone marrow to produce more platelets.
    B) Pyridine may theoretically induce methemoglobinemia.
    0.2.14) DERMATOLOGIC
    A) Skin irritation may result from repeated or prolonged exposure or photosensitivity.
    B) Allergic contact dermatitis has been reported.
    0.2.15) MUSCULOSKELETAL
    A) Fatigue and lower back pain have been reported.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) Animal studies on chicks for substituted pyridines have shown teratogenicity. Injected chicken eggs developed leg and skeletal malformations.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies were found on the possible carcinogenic activity of pyridine in humans.

Laboratory Monitoring

    A) Monitor liver and kidney function.
    B) Monitor arterial blood gases and chest xray in patients with respiratory depression or pulmonary edema.
    C) Monitor CNS for depression.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    D) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    E) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    F) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) INHALATION - CNS symptoms have been seen after exposures of 6 to 12 ppm.
    B) Ingestion of 0.5 cup acutely has been fatal in adults.
    C) Ingestion of 1.8 to 2.5 mL per day for 2 months produced liver and kidney damage in adults.

Clinical Effects

Genitourinary

    3.10.1) SUMMARY
    A) Kidney damage has been reported. Urinary frequency is seen more often than anuria, which is reported in animals when near death.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) Kidney damage was noted in patients who ingested 1.8 to 2.5 mL of pyridine daily for up to 2 months (Pollock et al, 1943). Hepatorenal syndrome has been reported following prolonged daily administration of an oral product (HSDB , 2001).
    B) INCREASED FREQUENCY OF URINATION
    1) Inhalation of the vapor has caused increased urinary frequency without obvious kidney damage (Reinhardt & Brittelli, 1981).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) URINE ABNORMAL
    a) Fatty degeneration of the kidney has been seen in animal experiments (Reinhardt & Brittelli, 1981). Animals often had highly colored urine, with bile pigments. Some urine became red, but without blood (Baxter, 1948). Urinary output sometimes increased extensively, but anuria was only seen just before death (Baxter, 1948).

Hematologic

    3.13.1) SUMMARY
    A) Small doses may stimulate the bone marrow to produce more platelets.
    B) Pyridine may theoretically induce methemoglobinemia.
    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOSIS
    1) Small doses may stimulate the bone marrow to produce more platelets (ACGIH, 1991).
    B) METHEMOGLOBINEMIA
    1) It is theoretically possible for methemoglobinemia to result from severe poisonings, however, individual case reports are lacking in the literature to confirm this (Olson (Ed), 1994).

Dermatologic

    3.14.1) SUMMARY
    A) Skin irritation may result from repeated or prolonged exposure or photosensitivity.
    B) Allergic contact dermatitis has been reported.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Skin irritation may occur with prolonged or repeated contact (Hathaway et al, 1996; (Bingham et al, 2001; HSDB , 2001). First-degree skin burns may occur following short exposure; second-degree burns may occur following long exposure (HSDB , 2001).
    B) PHOTOSENSITIVITY
    1) Pyridine may be a photosensitizing agent (Fisher, 1973; Reinhardt & Brittelli, 1981).
    C) CONTACT DERMATITIS
    1) CASE REPORT - Allergic contact dermatitis, an eczema-type reaction, was reported in a laboratory technician after working 6 months with a pyridine mix (Knegt-Junk et al, 1993).

Musculoskeletal

    3.15.1) SUMMARY
    A) Fatigue and lower back pain have been reported.
    3.15.2) CLINICAL EFFECTS
    A) BACKACHE
    1) Lower back pain associated with increased urinary frequency was noted after chronic inhalation (Reed, 1990).
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) MUSCLE WEAKNESS
    a) Animals have experienced limb weakness (Browning, 1965).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) Animal studies on chicks for substituted pyridines have shown teratogenicity. Injected chicken eggs developed leg and skeletal malformations.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) CHICKENS - Leg and skeletal abnormalities were noted when pyridine was injected into eggs (Landauer & Salam, 1974). Various substituted pyridines have shown some teratogenic potential in chicks. The effects were thought to be due to an interference with pyridine nucleotide utilization (Reinhart & Brittelli, 1981).
    2) FROGS - Pyridine was not teratogenic in frogs at sublethal doses (Davis, 1981).
    3) The relevance of these studies to human reproduction is unclear.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS110-86-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Pyridine
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no studies were found on the possible carcinogenic activity of pyridine in humans.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) RATS - Pyridine was injected twice daily into rats at doses of 3 to 100 mg/kg (SC). No incidence of tumors was reported (Mason et al, 1971).

Summary Of Exposure

    A) ORAL - Acute effects of pyridine involve the CNS, with coma and respiratory depression leading to death. Signs/symptoms may be delayed in onset by several hours.
    1) Signs and symptoms of acute oral exposures may include nausea, headache, insomnia and nervousness, and low back or abdominal discomfort with urinary frequency. Lung congestion may occur.
    B) INHALATION may produce emphysema and chronic bronchitis. High level exposures may cause headache, dizziness, abdominal pain, nausea, insomnia, anorexia, and peripheral weakness.
    C) DERMAL - Skin exposures may cause irritation or systemic intoxication.

Vital Signs

    3.3.2) RESPIRATIONS
    A) Acutely poisoned individuals may have depressed respirations (Reed, 1990).
    3.3.3) TEMPERATURE
    A) FEVER has been reported following acute accidental ingestion (Helme, 1893; HSDB , 2001).

Heent

    3.4.1) SUMMARY
    A) Vapors may be irritating to the nose, eyes, and throat.
    3.4.3) EYES
    A) The vapor is irritating to the eyes (Reed, 1990; Grant & Schuman, 1993; Lewis, 2000; Bingham et al, 2001).
    B) Pure pyridine caused moderate injury after 24 hours when applied to rabbit eyes. Commercial pyridine (90%) caused corneal clouding and scarring of the conjunctiva with permanent mild stromal opalescence and subepithelial vascularization (Grant & Schuman, 1993).
    3.4.5) NOSE
    A) The vapor is irritating to the nose (Reed, 1990; Bingham et al, 2001).

Respiratory

    3.6.1) SUMMARY
    A) Severe acute intoxications may result in respiratory depression and death.
    B) Upper respiratory tract irritation may occur following vapor exposure.
    C) Pulmonary edema and bronchitis developed in a man who drank one-half cup of commercial pyridine.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) Respiratory depression, which can lead to death, may result from acute intoxications (Jori et al, 1983).
    a) By all exposure routes, pyridine acutely causes irritation, general CNS depression, and respiratory depression potentially leading to respiratory paralysis (Brunton & Tunnicliffe, 1894-5; Lelsie et al, 1973).
    B) ACUTE LUNG INJURY
    1) Pulmonary edema may occur following severe, acute oral or inhalation exposures (HSDB , 2001).
    2) CASE REPORT - Bronchitis, dyspnea and lung congestion were reported in a 29-year-old male who drank one-half cup of commercial pyridine. The patient died two days later. An autopsy revealed pulmonary edema (Helme, 1893; Pollock et al, 1943).
    C) IRRITATION SYMPTOM
    1) Following acute vapor exposures, pyridine can cause upper respiratory tract irritation (HSDB , 2001).
    D) CHRONIC BRONCHITIS
    1) Chronic inhalation may produce emphysema and chronic bronchitis (Reed, 1990).

Neurologic

    3.7.1) SUMMARY
    A) CNS effects range from coma (significant exposure) to nervousness, fatigue, insomnia, headache, faintness, and speech disorders in chronic ingestion or inhalation of the vapors.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Pyridine is a CNS depressant following acute oral or inhalation exposures. In animal studies, the major toxic effect of pyridine by any route of administration was anesthesia and irritation (Lewis, 2000; Bingham et al, 2001; HSDB , 2001).
    2) CNS depression was noted in patients taking 1.8 to 2.5 mL of pyridine daily for seizure control (Pollock et al, 1943).
    B) HEADACHE
    1) Headache has been noted after chronic oral administration of small amounts (Pollock et al, 1943), and inhalation of the vapor in concentrations of 6 to 13 ppm (Reed, 1990; Bingham et al, 2001).
    C) FATIGUE
    1) Fatigue and faintness were noted in patients taking small oral amounts daily (Pollock et al, 1943) and from inhaling the vapor (Reed, 1990).
    D) INSOMNIA
    1) Insomnia has been reported after chronic exposure to 6 to 13 ppm (Reed, 1990; Bingham et al, 2001).
    E) FEELING NERVOUS
    1) Nervousness has been seen after chronic exposure to the vapors (Reed, 1990; Bingham et al, 2001).
    F) DISTURBANCE IN SPEECH
    1) Speech disorders have been associated with nervous disorders seen after chronic exposure to the vapors (HSDB , 2001; Reinhardt & Brittelli, 1981; Kuzelova et al, 1975).
    G) PARALYSIS
    1) Paralysis of the facial nerves has been noted after pyridine exposure (Ludwig, 1934).
    H) CHRONIC POISONING
    1) Transient symptoms of overexposure are nausea, headache, insomnia and nervousness. These symptoms, without associated evidence of liver or kidney damage, have occurred in individuals exposed to pyridine concentrations averaging 125 ppm, 4 hours a day for 1 to 2 weeks (ACGIH, 1991; HSDB , 2001).
    2) Teisinger (1948) reported 7 cases of chronic occupational exposure resulting in headaches, temporary vertigo, nervousness, and insomnia.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) COMA
    a) Sublethal doses given to animals have caused deep anesthesia which lasted about 2 hours (Brazda & Coulson, 1946).

Gastrointestinal

    3.8.1) SUMMARY
    A) Irritation may result in abdominal pain with vomiting, or diarrhea.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Gastrointestinal upset, with nausea, vomiting and diarrhea may occur following oral or inhalational exposures (Bingham et al, 2001; HSDB , 2001; Lewis, 2000). Chronic inhalation exposures have also resulted in toxic effects related to the GI tract, including nausea and vomiting (HSDB , 2001).
    2) Humans have experienced vomiting, nausea, gastric upset, and anorexia after ingestion of 1.8 to 2.5 mL daily (Pollock et al, 1943; Lublinski, 1885).
    3) Chronic occupational exposures have resulted in nausea and vomiting and non-specific gastrointestinal complaints (Teisinger, 1948; Bingham et al, 2001; HSDB , 2001).
    B) DYSPHAGIA
    1) CASE REPORT - Difficulty in swallowing was noted in one patient who accidentally swallowed one-half cup of commercial pyridine (Pollock et al, 1943).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) VOMITING
    a) Animals have experienced vomiting and diarrhea after administration (Browning, 1965).
    2) SALIVA INCREASED
    a) Animals have experienced excessive salivation (Browning, 1965).

Hepatic

    3.9.1) SUMMARY
    A) Pyridine is hepatotoxic, and may produce hepatic necrosis and cirrhosis, particularly after chronic exposure.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Liver damage has been seen after chronic ingestion in man (Pollock et al, 1943). Doses which are too small to cause overt CNS symptoms may cause cirrhosis if the exposure is chronic (Gehring, 1983). Hepatorenal syndrome has been reported following prolonged daily administration of an oral product (HSDB , 2001).
    B) STEATOSIS OF LIVER
    1) Chronic administration may lead to liver and kidney fatty degeneration (Reinhardt & Brittelli, 1983). Varying degrees of liver damage may occur with centrilobular fatty degeneration, congestion, and cellular infiltration (Bingham et al, 2001).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LIVER FATTY
    a) Fatty changes, liver nodules, vascular engorgement, and hemorrhage have been seen in animal experiments (Baxter & Mason, 1947; Baxter, 1948; Baxter & Mason, 1947) Baxter, 1949; (Jori et al, 1983).
    2) ENZYME ABNORMALITY
    a) DOGS - When injected intravenously into anesthetized dogs at doses of 88 to 880 mg/kg, SGOT and blood urea nitrogen were found to increase, and serum alkaline phosphatase to decrease (Venkatakrishna-Bhatt et al, 1975).
    b) RABBITS - Pyridine, 100 mg/kg IP for 5 days to rabbits, caused an increase in hepatic microsomal cytochrome P-450 content over 2-fold as compared to controls (Kaul & Novak, 1987).

Genotoxicity

    A) Some studies have suggested that pyridine is mutagenic while others have found no mutagenic activiey (Clayton & Clayton, 1994; RTECS , 2001).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor liver and kidney function.
    B) Monitor arterial blood gases and chest xray in patients with respiratory depression or pulmonary edema.
    C) Monitor CNS for depression.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver and kidney function after significant exposure or during chronic exposures. Monitoring should be done even in the absence of CNS symptoms.
    B) ACID/BASE
    1) Follow arterial blood gases in patients with evidence of respiratory depression or pulmonary edema.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Obtain a chest x-ray in patients with evidence of respiratory depression or pulmonary edema.

Methods

    A) CHROMATOGRAPHY
    1) AIR - Absorption on charcoal, desorption with CH2Cl2, and quantitation by gas chromatography with a flame ionization detector (Jori et al, 1983; HSDB , 1999).
    2) WATER - Determination in water may involve gas chromatography and ultraviolet spectroscopy (HSDB , 1999), several colormetric assays (Jori et al, 1983), or infrared analyzers (Reinhardt & Brittelli, 1981).
    3) URINE - Thin layer chromatography, HPLC, and gas liquid chromatography with a flame ionization detector have been used for quantification of pyridine and its metabolites in urine (Damani et al, 1982).
    a) Radiochromatographic analysis has also been used for quantification of pyridine metabolites in urine.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor liver and kidney function.
    B) Monitor arterial blood gases and chest xray in patients with respiratory depression or pulmonary edema.
    C) Monitor CNS for depression.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Emesis is not recommended due to the CNS and respiratory depressant nature of this agent.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Emesis is not recommended due to the CNS and respiratory depressant nature of this agent.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific antidote, treatment is symptomatic and supportive for maintenance of liver, kidney, and respiratory function. Patients should be monitored for liver and kidney function if significant exposure occurs, even if CNS symptoms were not evident.
    2) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    B) EXPERIMENTAL THERAPY
    1) THIAMINE: In one European study, thiamine was used to treat the speech disorder and cortical afflictions seen after an exposure (Kuzelova et al, 1975).
    2) N-ACETYLCYSTEINE: It could not be determined if N-acetylcysteine has ever been tried as treatment for acute, large, overdoses of pyridine. In most cases of mild inhalation exposure liver and kidney function return without additional therapy. Animal studies have indicated a protective effect using methionine, and it is known that pyridine effects the cytochrome P-450 system. IT IS UNKNOWN IF N-ACTEYLCYSTEINE WOULD HAVE ANY PROTECTIVE EFFECT.
    3) METHIONINE/ANIMALS: In animal experiments, methionine provides some protection against the liver and kidney damage of pyridine (Baxter, 1945).
    C) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    D) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) SUPPORT
    1) There is no specific antidote, treatment is symptomatic and supportive for maintenance of liver, kidney, and respiratory function. Patients should be monitored for liver and kidney function if significant exposure occurs, even if CNS symptoms were not evident.
    2) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    B) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) INHALATION - CNS symptoms have been seen after exposures of 6 to 12 ppm.
    B) Ingestion of 0.5 cup acutely has been fatal in adults.
    C) Ingestion of 1.8 to 2.5 mL per day for 2 months produced liver and kidney damage in adults.

Minimum Lethal Exposure

    A) CASE REPORTS
    1) One-half cup of commercial pyridine caused death in an adult (Pollock et al, 1943).
    2) One patient died in an experiment where 1.8 to 2.5 milliliters was ingested daily for up to 2 months (Pollock et al, 1943).
    3) An estimated lethal dose in man is 0.5 to 5 grams per kilogram (HSDB , 2001).
    B) ANIMAL DATA
    1) 170 TO 500 milligrams/kilogram given to rats caused hepatic necrosis and a few hepatic nodules (Reed, 1990).
    2) Daily oral doses of 50 milligrams/kilogram in rats on a low protein diet produced growth cessation almost immediately and, in most cases, death within 2 weeks (Reed, 1990; Jori et al, 1983).
    3) The maximum twice weekly dose (subcutaneous injection) tolerated by rats for a 4 week period was under 180 milligrams/kilogram (Reed, 1990).
    4) Five daily exposures to 3700 parts per million for 40 minutes caused death in rats (Reed, 1990).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Pyridine is detectable at less than 1 ppm and becomes objectionable to unacclimatized individuals at 10 ppm. However, the odor and mild irritant properties of pyridine are not objectionable enough to prevent toxic exposures of the vapors, and skin exposures may cause irritation or systemic intoxication (Clayton & Clayton, 1994).
    2) ORAL - The estimated LDLo in man is 500 milligrams/kilograms orally (Jori et al, 1983; HSDB , 2001). Doses that are too small to create overt clinical symptoms may still cause liver damage if taken chronically (Gehring, 1983).
    a) Small oral doses of 2 to 3 milliliters may cause mild anorexia, nausea, fatigue, and mental depression. Following prolonged daily dosing, hepatorenal damage may occur (HSDB , 2001).
    B) ROUTE OF EXPOSURE
    1) CHRONIC - Exposures to 6 to 13 parts per million chronically have caused headache, vertigo, nervousness, vomiting, and insomnia (Reed, 1990). The maximum long-term exposure is estimated to be in the range of 1 to 5 parts per million (Santodonato, 1985; (Teisinger, 1948).
    2) INHALATION - Mild symptoms may occur with exposure of 10 parts per million (ACGIH, 1991). Concentrations of 6 to 12 parts per million caused central nervous system symptoms (Teisinger, 1948).
    C) ANIMAL DATA
    1) Rabbits given 44 milligrams/kilogram orally for 5 to 7 days showed no toxic effects (Pollock et al, 1943).
    2) Rats given 100 milligrams/kilogram twice weekly, did not show any changes in mortality compared to controls (Mason et al, 1971).
    3) One exposure to 1250 parts per million for 7 hours in rats did not result in a fatality (Reed, 1990).
    4) Daily exposure to 10 or 50 parts per million for 6 months increased liver weight/body weight ratios (HSDB , 2001).

Workplace Standards

    A) ACGIH TLV Values for CAS110-86-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Pyridine
    a) TLV:
    1) TLV-TWA: 1 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: Not Listed
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    c) TLV Basis - Critical Effect(s): Skin irr; liver and kidney dam
    d) Molecular Weight: 79.1
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS110-86-1 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Pyridine
    2) REL:
    a) TWA: 5 ppm (15 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 1000 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS110-86-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Pyridine
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Pyridine
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Pyridine
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Pyridine
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS110-86-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Pyridine
    2) Table Z-1 for Pyridine:
    a) 8-hour TWA:
    1) ppm: 5
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 15
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Reference: RTECS, 2001
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 950 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 1500 mg/kg
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1250 mg/kg
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 866 mg/kg
    5) LD50- (ORAL)RAT:
    a) 891 mg/kg
    6) LD50- (SUBCUTANEOUS)RAT:
    a) 866 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) Pyridine affects aromatic L-amino acid decarboxylase (Juorio & Yu, 1985).
    B) Pyridine inhibits metabolism of benzene (Harper & Legator, 1987; Harper et al, 1984).
    C) Pyridine decreases ammonia excretion and kidney glutamine concentrations (Bolonova, 1972).
    D) Chronic administration will induce cytochrome P-450 forms LM3 and LM4 (shown in the rabbit) and result in an altered substrate specificity and enhanced pyridine N-oxide production (Reed, 1990; Kaul & Novak, 1987; Gorrod & Damani, 1979). Pyridine N-methyltransferase activity appears to be a SAM (S-adenosyl-L-methionine) dependent enzyme located in the cell cytosol, particularly active in rabbit lung (Damani et al, 1986).

Physicochemical

Physical Characteristics

    A) Pyridine is a flammable, slightly yellow or colorless liquid with a characteristic, disagreeable odor (fish-like) and a sharp taste (Budavari, 1996; Lewis, 2000; Bingham et al, 2001).

Ph

    A) 8.5 (for a 0.2 molar aqueous solution) (Budavari, 1996)

Molecular Weight

    A) 79.10 (Budavari, 1996)

Other

    A) ODOR THRESHOLD
    1) 0.17 ppm (Amoore & Hautala, 1983)

References

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