Toxicology of Hazardous Chemicals

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Toxicology of Hazardous Chemicals

• By Jack Hay
• 3/2/06

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Introduction

• 627,000 toxic chemicals/compounds
• More than 600 new added annually
• 1.5 billion tons shipped per year
• 500,000 shipments daily
• 24,359 hazardous chemical accidents 1993-1997

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Epidemiology

• 10-30 of hazardous accidents have victims
• Trauma most common
• Non-traumatic injuries
• Respiratory eye irritation
• Nausea/vomiting
• Headache, dizziness, other neurological effects
• Unknown toxins 25 of cases

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Fatalities

• Trauma (65)
• Burns (22)
• Respiratory compromise (10)
• Common toxins
• Chlorine, ammonia, nitrogen, fertilizer,
  hydrochloric acid

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Nerve Agents (Organophosphates)

• Most toxic chemical threats known
• Liquids with distinct odors
• Tabun (fruity)
• Soman (fruity/camphorous)
• Sarin VX (odorless)
• Powerful AChE inhibitors

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Nerve Agents

• Acetylcholine accumulation
• Initial fasciculations
• Progress to weakness and paralysis
• Tachycardia and hypertension
• Miosis, lacrimation, salivation
• Bronchorrhea, bronchospasm
• Vomiting, diarrhea, excess urination

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Nerve Agents

• Onset type of reaction based on both
  concentration route of exposure
• High risk of secondary contamination
• Wear skin respiratory protection
• Surgical and HEPA masks are inadequate
• Cleanse with soap water

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Nerve Agents

• Oxygenation is next most critical step
• Oxines, ex. 2-PAM (pralidoxine chloride)
• Reactivates AChE
• Atropine
• Blocks muscarinic receptors
• End-point for dosing is drying of pulmonary
  secretions

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Nerve Agents

• Cardiac monitoring for dysrhythmias
• Seizure precautions
• Ventilatory support
• 23 hour observation for
• Symptomatic patients
• Dermal exposure

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Vesicants

• Blistering liquid agents
• Low dose ? vesication
• Erythema progressing to blister formation
• High dose ? systemic toxicity
• Corneal ulcers, ocular edema/irritation
• Cough, hoarseness, bronchospasm
• Hematopoietic, GI, CNS (massive exposure)

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Mustard (H, HS, HD)

• Not the kind that goes on a hot dog
• Oily liquid with odor of mustard, garlic, or
  horseradish
• Alkylating agents attacks peptides, proteins,
  DNA, RNA, cell membranes

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Mustard

• Median lethal dose of 1.5 teaspoon
• ? 25 BSA burn
• Symptoms delayed 4-8 hours
• Urinary thiodiglycol metabolites confirm exposure
• Not available at South Pointe Hospital

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Mustard

• Water irrigation skin, eyes and hot dog
• Supportive care
• Airway, fluids, electrolytes, analgesics
• Send patient to burn center

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Lewisite (L)

• Oily odorless liquid
• Trivalent arsenic inhibits enzymes and interferes
  with glycolysis
• Initial symptoms within 15-30 minutes
• Greater tissue destruction than with mustard
• Rarely pulmonary edema

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Lewisite

• Water irrigation supportive care
• Burn center transfer
• British anti-Lewisite (BAL, dimercaprol)
• Arsenic chelator
• Apply topically within MINUTES of exposure
• Can later be given IM

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Respiratory Agents

• Watch for steam/smoke inhalation injuries
• 100 oxygen
• Humidification for irritative symptoms
• Inhaled bronchodilators for spasm
• Early intubation for upper airway edema
• CXR, lactate level, ECG monitoring ABG with
  carboxyHb, methHb

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Phosgene (CX)

• White gas with odor or newly mown hay
• Instantaneous skin pain/irritation
• Deep necrosis/ eschar formation
• No vesicle formation

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Phosgene

• Initially mild upper airwar irritation
• Later acid burns lower airway
• Pulmonary edema results from alveolar leak
• Usually delayed up to 24 hours
• Onset within 4 hours is very poor prognosis

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Phosgene

• Irrigate with water ONLY
• Supportive care
• Burn center transfer
• A least 24 hour observation even if asymptomatic
• Recovery occurs in 3-4 days

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Chlorine

• Acrid, pungent, yellow-green gas
• Forms acids and oxidants on moist membranes
• Immediate ocular/upper airway irritation
• Nausea/vomiting common in mild exposure

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Chlorine

• Significant exposure
• Cough progresses to pulmonary edema within 24
  hours
• Permanent reactive airway disease
• Treatment is supportive
• Humidified oxygen and bronchodilators
• Nebulized NaHCO3 is controversial

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Nitrogen Oxide

• Result of blasts, obscurants, combustion
• Triphasic illness
• Initially flu-like with dyspnea
• Transient improvement
• Dyspnea worsens with edema 24-72 hours after
  exposure

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Nitrogen Oxide

• Give prophylactic steroids with antibiotics
• Prevents bronchiolitis obliterans
• Supportive treatment
• Humidified oxygen and bronchodilators

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Ammonia

• Colorless, pungent, alkaline corrosive gas
• Immediate induction of symptoms
• Eye, mucous membranes throat irritation
• Anhydrous ammonia penetrates anterior chamber
  within 1 minute of exposure

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Ammonia

• Lower airway involvement
• Bronchospasm ? edema
• Residual reactive airway disease
• Supportive treatment
• Humidified oxygen and bronchodilators
• Ocular irrigation if asymptomatic
• Evaluate for corneal burns

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Metabolic Toxins

• Cyanide
• Well have an exciting and thorough discussion in
  about 10 minutes
• Hydrogen sulfide
• Ricin
• Industrial toxins

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Hydrogen Sulfide

• Colorless flammable
• Disrupts oxidative phosphorylation
• Respiratory ocular irritation
• LOC, seizures death in only a few seconds in
  high concentrations

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Hydrogen Sulfide

• Treat with decontamination, oxygen and hyperbaric
  chamber
• Use Nitrite component of cyanide antidote kit
• Converts sulfide to sulfmethHb

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Ricin

• Ribosome inhibiting protein found in castor bean
  processing
• Mist, powder or pellets dissolve in water or weak
  acids
• Unaffected by heat or cold (extremely stable)
• 500 mcg injection can cause death

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Ricin

• Injected ? multi-organ failure (MOF) and
  coagulopathies lead to death
• Ingested ? MOF GI hemorrhage
• Inhaled ? resp distress pulmonary edema
• No lab test for diagnosis
• Supportive treatment

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Misc. Industrial Toxins

• Aniline or nitrite derivatives
• RBC oxidant stress
• Chlorates, benzene, acetaniid, nitrophenols,
  phenols, sulfonamides, para-toluene
• Supportive treatment

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Hydrocarbons

• Sensitizes myocardium to the dysrhythmic effects
  of catecholamines
• Early mental stimulation followed by confusion,
  coma lethargy, stupor or coma
• Avoid physical activity or sympathomimetics
  except selective for b2 bronchospasm

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Riot Control Agents

• Mace and Capsaicin
• Transient (few hours) but intensely noxious
• Fatalities from pulmonary edema in enclosed space
• Irritation of eyes, skin and respiratory tract
• May have nausea/ vomiting

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Riot Control Agents

• Copiously irrigate eyes with normal saline
• Wash skin with soap and water
• Do not use bleach
• With pre-existing lung disease
• Treat for bronchospasm
• Admit for observation

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Incapacitating Agents

• Not lethal
• Take hours to days to recover completely
• 3-quinuclidinyl benzilate (BZ)
• Anticholinergic deliriant
• Resembles atropine
• Supportive treatment
• Benzodiazepines prevent hyperthermia and
  rhabdomyolysis