Transcript Toxicology of Hazardous Chemicals

Toxicology of Hazardous
Chemicals
By Jack Hay
3/2/06
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
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
Fatalities
Trauma (65%)
Burns (22%)
Respiratory compromise (10%)
Common toxins
– Chlorine, ammonia, nitrogen, fertilizer,
hydrochloric acid
Nerve Agents
(Organophosphates)
Most toxic chemical threats known
Liquids with distinct odors
– Tabun (fruity)
– Soman (fruity/camphorous)
– Sarin & VX (odorless)
Powerful AChE inhibitors
Nerve Agents
Acetylcholine accumulation
– Initial fasciculations
• Progress to weakness and paralysis
– Tachycardia and hypertension
– Miosis, lacrimation, salivation
– Bronchorrhea, bronchospasm
– Vomiting, diarrhea, excess urination
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
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
Nerve Agents
Cardiac monitoring for dysrhythmias
Seizure precautions
Ventilatory support
23 hour observation for
– Symptomatic patients
– Dermal exposure
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)
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
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
Mustard
Water irrigation – skin, eyes and hot dog
Supportive care
– Airway, fluids, electrolytes, analgesics
Send patient to burn center
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
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
Respiratory Agents
Watch for steam/smoke inhalation injuries
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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
Phosgene (CX)
White gas with odor or newly mown hay
Instantaneous skin pain/irritation
Deep necrosis/ eschar formation
No vesicle formation
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
Phosgene
Irrigate with water ONLY
Supportive care
Burn center transfer
– A least 24 hour observation even if
asymptomatic
Recovery occurs in 3-4 days
Chlorine
Acrid, pungent, yellow-green gas
Forms acids and oxidants on moist
membranes
Immediate ocular/upper airway irritation
Nausea/vomiting common in mild exposure
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
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
Nitrogen Oxide
Give prophylactic steroids with
antibiotics
– Prevents bronchiolitis obliterans
Supportive treatment
– Humidified oxygen and bronchodilators
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
Ammonia
Lower airway involvement
– Bronchospasm  edema
– Residual reactive airway disease
Supportive treatment
– Humidified oxygen and bronchodilators
– Ocular irrigation if asymptomatic
– Evaluate for corneal burns
Metabolic Toxins
Cyanide
– We’ll have an exciting and thorough
discussion in about 10 minutes…
– Hydrogen sulfide
– Ricin
– Industrial toxins
Hydrogen Sulfide
Colorless & flammable
Disrupts oxidative phosphorylation
Respiratory & ocular irritation
LOC, seizures & death in only a few
seconds in high concentrations
Hydrogen Sulfide
Treat with decontamination, oxygen and
hyperbaric chamber
Use Nitrite component of cyanide
antidote kit
– Converts sulfide to sulfmethHb
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
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
Misc. Industrial Toxins
Aniline or nitrite derivatives
RBC oxidant stress
Chlorates, benzene, acetaniid,
nitrophenols, phenols, sulfonamides,
para-toluene
Supportive treatment
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
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
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
Incapacitating Agents
Not lethal
Take hours to days to recover completely
3-quinuclidinyl benzilate (BZ)
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Anticholinergic deliriant
Resembles atropine
Supportive treatment
Benzodiazepines prevent hyperthermia and
rhabdomyolysis