Toxicology Exam II

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Rx2013
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71299
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Toxicology Exam II
Updated:
2011-03-07 13:06:42
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Industrial Solvents Continued
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Industrial Solvents Continued
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  1. L-Acetylcysteine used for CCL4 toxicity because
    the sulfhydryl group acts like glutathione to deactivate CCL4
  2. Petroleum and solvent distillates are commonly used in
    • plastic
    • agriculture & chemical industry
  3. Petroleum distilates are commonly used as
    • solvents
    • degreasers
    • fuels
  4. CNS and respiratory depression results from petroleum and solvent distillates because
    cardiac stimulation from sensitization to catacholamines
  5. Peroleum distilates are usually introduced by
    • inhalation
    • skin contact
  6. concentration for a normal 8 hr work day or 40 hour work week to which workers may be repeatedly exposed without adverse effects
    TWA value
  7. maximum concentration that should not be exceeded at any time during a 15 minute exposure period
    STEL value
  8. STEL value is normally ____ than TWA value because
    • higher
    • individual is only allowed to be exposed for 15 min by law.
  9. Aromatic Hydrocarbons
    • Benzene
    • Toluene
    • Xylene
  10. Benzene use
    • solvent properties
    • synthesis of other chemicals
    • not present in house hold products
  11. Benzene mechanism of toxicity
    CNS depression
  12. Exposure to Benzene 7500 ppm for 20 min can cause
    fatality
  13. exposure to benzene at >3000 ppm can cause
    • euphoria
    • nausea
    • locomotor problems
    • coma
  14. Exposure to benzene at 250-500 ppm may cause
    • vertigo
    • drowsiness
    • headache
    • nausea
  15. Chronic exposure to benzene can cause
    • injury to bone marrow
    • plastic anemia
    • leukopenia
    • pancytopenia
    • thrombocytopenia
  16. Bone marrow cells are most sensitive to benzene during
    early stages of development
  17. Benzine is ACGIH category
    • A1
    • human carcinogen
    • causes leukemia
  18. Another mechanism of toxicity to benzene
    sensitization of the myocardium to arrhythmogenic effects of catecholamines
  19. A typical smoker inhales _____ mg of benzene daily.
    1-2 mg
  20. EPA maximum contaminant level (MCL) of benzene in water is
    5 ppb
  21. Antidote for benzene
    no specific antidote
  22. Toluene
    • no myelotoxic properties
    • not associated with leukemia
    • causes CNS depression
  23. Exposure to 800 ppm toluene results in
    severe fatigue and ataxia
  24. Exposure of 10,000 ppm toluene leads to
    rapid loss of consciousness
  25. Chronic effects of long term toluene exposure
    unclear
  26. Xylene
    • three isomers used as components in petroleum hydrocarbon solvents
    • frequent source of lab exposure
  27. commercial xylene
    75-85% p-isomer
  28. toxicity of xylene
    • similar to toluene
    • well absorbed via inhalation and skin contact
    • mild hematopoietic toxicity
    • Lethal dose in 15 mL of gasoline
  29. Xylene metabolism
    • metabolized via oxidation of the methyl group in the O, M, or P position
    • excreted as O, M or P methylhippuric
  30. Treatment of xylene ingestion
    • diazepam to control convulsions
    • supportive therapy
    • monitor hematiopoietic elements
  31. Halogenated unsaturated hydrocarbons
    vinyl chloride
  32. Vinyl chloride uses
    • starting material for plastic
    • polyvinyl chloride (PVC)
    • aerosol propellant
  33. Major routes of exposure to vinyl chloride
    • inhalation
    • skin contact
  34. Acute signs of vinyl chloride exposure
    • CNS depression
    • dizziness, light headedness
    • nausea
    • headache
    • dulling of senses
  35. Chronic exposure to vinyl chloride
    • raynaud's phenomenon (changes of blood supply to periphery by degradation of small vessels)
    • skin changes
    • changes in bones of the hands
    • liver damage or hemangiosarcoma
  36. Metabolism of vinyl chloride
    • undergoes metabolic activation when metabolized by P450 to reactive intermediates which can alkylate DNA and lead to cancer
    • metabolism is saturable
  37. chloroethylene oxide or chloroacetaldehyde
    reactive intermediate formed from vinyl chloride
  38. shows correlation with vinyl chloride exposure
    urinary excretion of cysteine metabolite and thiodiglycolic acid
  39. Tumor incidence with vinyl chloride correlates to
    amount metabolized rather than dose
  40. Household products
    • bleach
    • hydrocarbon solvents (turpentine)
    • antifreeze (ethylene glycol)
    • methanol
    • formaldehyde
  41. Most common substance involved in poison cases by oral ingestion
    bleach
  42. Oral ingestion of bleach
    • burning of mouth, throat and esophagus
    • tissue damage results in edema of pharynx and larynx
  43. Bleach in the stomach
    • generates hypochlorus acid and CL2 gas in the presence of HCL
    • CL2 may be inhaled causing dmg in the lungs
  44. Hydrocarbon solvents
    • turpentine
    • white spirit
    • used for cleaning paint brushes
  45. Aspiration of hydrocarbon solvents leads to
    chemical pneumonitis
  46. toxic constituents of antifreeze
    • ethylene glycol
    • methanol
  47. Ethylene glycol
    • dihydric alcohol
    • sweet tasting
    • similar CNS effects as ethanol
    • sometimes consumed by alcoholics
  48. lethal amount of antifreeze
    1 cup
  49. toxicity of ethylene glycol
    requires metabolism to metabolic products which lead to oxalic acid
  50. oxalic acid
    • toxic metabolite of ethylene glycol
    • can chelate calcium that is important for enzyme fx
    • crystallizes in the brain
    • forms calcium oxalate in kidney tubules (stones) leading to kidney damage
  51. Intermediate acidic metabolites of ethylene glycol cause
    acidosis by increasing NADH levels which increases lactic acid production
  52. First step in metabolism of ehtylene glycol involves
    • alcohol dehydrogenase
    • blocked by the presence of ethanol
  53. Treatment of ethylene glycol poisoning
    • administer ethanol PO or IV
    • Hemoperfusion/dialysis
  54. Methanol found in
    • sometimes in antifreeze
    • methylated spirits
  55. Methanol toxicity comes from
    metabolism to formaldehyde and formic acid
  56. Most likely cause of organ toxicity with methanol poisoning
    • formic acid
    • inhibits cytochrome oxidase activity resulting in tissue hypoxia
    • increased lactic acid formation resulting in metabolic acidosis
  57. Formaldehyde may cause
    • blindness if the dose of MeOH is not rapidly fatal
    • pt will see "snow flakes"
  58. Treatment of methanol poisoning
    • same as ethylene glycol
    • administer ethanol po or iv
    • correct metabolic acidosis
  59. Formaldehyde properties
    • gas at room temp
    • used in lab as 37% solution
    • solution contains 15% methanol
  60. formaldehyde uses
    • manufacture of synthetic resins
    • paper and fabric
    • wood products
    • preservatives
    • disinfectants
  61. exposure to formaldehyde
    • occupational exposure by inhalation or direct skin contact
    • residential exposure from release of formaldehyde fumes from synthetic foam insulation in exterior walls
  62. TLV is ____ in air for formaldehyde
    2 ppm
  63. Odor threshold for formaldehyde is
    1 ppm
  64. Formaldehyde reacts with all cellular proteins but binds 4x as much to
    erythrocytes
  65. Metabolism of formaldehyde
    oxidized to formic acid in erythrocytes and in the liver
  66. Results of exposure to formaldehyde
    • mucous membrane irritation
    • lacrimation
    • cough
    • inflamation of bronchi
    • pulmonary edema
    • death
  67. Direct skin contact with formaldehyde results in
    • dermatitis
    • sensitization occurs with repeated exposure
  68. Ingestion of formaldehyde results in
    • death
    • corrosive dmg to stomach and SI
    • circulatory collapse
    • kidney dmg
  69. biological indicator of formaldehyde exposure
    formic acid in the urine
  70. Major solvent found in glues that causes narcosis
    toluene
  71. Halogenated solvents found in aerosol products (as propellants) are more hazardous and may cause
    • sensitization of myocardium to catecholamines leading to ventricular arrhythmias
    • sudden death from heart attack especially uner certain conditions such as fright
  72. solvents are found in household products such as
    • glues, paint, paint strippers
    • aerosols
    • varnishes
    • cleaning supplies
    • fire extinguishers
  73. Acute toxic effects of toluene abuse
    • narcosis or anesthesia
    • serious myocardial sensitization
  74. chronic effects of toluene abuse
    • personality changes
    • general morbidity
  75. Methanol uses
    • antifreeze
    • paint remover
    • denaturant in denatured alcohol
  76. Metabolism of methanol
    • toxicity of methanol is probably due to conversion to formaldehyde
    • methanol=(alcohol dehydrogenase)=>Formaldehyde
    • Formaldehyde=(aldehyde ")=>formic acid
  77. Formaldehyde causes selective injuries on ____ sx include
    • retinal cells
    • visual disturbances
    • acidosis
    • death (usually due to respiratory suppression)
  78. Treatment of formaldehyde poisoning
    • emesis or lavage
    • 50% ethanol IV
    • treat acidosis with sodium bicarbonate
    • fomepizole
  79. fomepizole (4 mehtylpyrazole) acts by
    inhibiting alcohol dehydrogenase
  80. Ethanol uses
    • beverage
    • solvent antiseptic
    • chemical intermediate
  81. Ethanol is more hazardous as
    a beverage
  82. kinetics of ethanol
    well absorbed and distributed in TBW
  83. 90-95% of ethanol metabolized in the liver by
    • EtOH =(alcohol DHase)=> acetaldehyde
    • Acetaldehyde =(aldehyde DHase)=> acetate
  84. Ethanol is metabolized to aldehyde by three enzymes
    • Alcohol dehydrogenase (major)
    • catalase (10%)
    • CYP2E1 (minor)
  85. catalase uses
    hydrogen peroxide supplied by NADPH oxidase and xanthine oxidase
  86. CYP2E1 is the principal component of
    hepatic microsomal ehtanol oxidizing system
  87. Levels of EtOH obtained through normal "cocktail usage" result in
    stimulating microsomal enzymes
  88. Levels of EtOH obtained in heavy drinking result in
    inhibition of microsomal enzymes
  89. EtOH can influence metabolism of
    drug metabolized by microsomal oxidative enzymes
  90. Alcohol dehydrogenase
    • cytosolic NAD dependant enzyme
    • found mainly in liver and gut
  91. Gut metabolism of EtOH
    • lower in females than in males
    • accounts for metabolism of low to moderate doses
  92. Limited supply of _____ results in ____ order kinetics for metabolism of EtOH
    • coenzyme NAD
    • Zero order kinetics
  93. Fixed capacity of EtOH metabolism is about
    7-10 g/hr
  94. Chronic alcohol use results in
    use of NAD resulting in depletion of the coenzyme for its normal metabolic functions
  95. avg adult can metabolize ___ of whiskey or ___ of beer per hour
    • 1 oz. whiskey
    • 1 can of beer
    • 10ml ethanol/hr
    • zero order kinetics
  96. Aldehyde dehydrogenase
    • acetaldehyde => acetate
    • 50% of asians have inactive ALDH
    • may cause flushing, headache, n/v, tachycardia and hyperventilation with EtOH ingestion
  97. Acute effects of EtOH ingestion
    • CNS depression
    • impaired judgement
    • loss of inhibition
    • slurred speach
    • ataxia
  98. Treatment of EtOH ingestion
    • maintenance of vital signs
    • prevention of aspiration of vomit
    • administration of dextrose to adjust e- balance
  99. Chronic effects of EtOH ingestion
    • tolerance/dependance
    • peripheral neuropathy
    • loss of liver fx with hepatitis/cirrhosis
    • gynecomastia
    • testicular atrophy
  100. Fetal alcohol syndrome
    most common preventable cause of mental retardation and congenital malformation
  101. Diagnostic criteria for fetal alcohol syndrome
    • heavy maternal EtOH consumption during pregnancy
    • pre- & post-natal growth retardation
    • cranifacial malformation (microcephaly)
    • mental retardation
  102. Less complete manifestations of gestational EtOH exposure are referred to as
    • fetal alcohol effects
    • alcohol related neurodevelopmental disorder
  103. Used to treat alcohol dependance
    disulfiram (aldehyde dehydrogenase inhibitor)
  104. Isopropyl alcohol (rubbing alcohol) symptoms
    • cns depression
    • renal damage
  105. Isopropyl alcohol treatment
    • lavage
    • symptomatic
  106. Ethylene glycol is converted to ____ by alcohol dehydrogenase which causes _____
    • oxalic acid
    • acidosis
    • nephrotoxicity
  107. methanol is converted to ____ by alcohol dehydrogenase which causes _____
    • formaldehyde and formic acid
    • severe acidosis
    • retinal damage
  108. ethanol is converted to ____ by alcohol dehydrogenase which causes _____
    • acetaldehyde
    • n/v, headache, hypotension
  109. Competitive substrates for alcohol dehydrogenase
    • ethylene glycol
    • methanol
    • ethanol
  110. inhibitors of aldehyde dehydrogenase
    disulfiram

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