An Update on Selected Toxic Gases in Industry

1
An Update on Selected Toxic Gases in Industry

• Stephen W. Borron, MD, MS, FACEP, FACMT
• Juan C. Arias, MD
• South Texas Poison Center
• San Antonio, TX

2
Acknowledgments and Conflicts of Interest

• Some material in this presentation was kindly
  supplied by Dr. Patrick Conner and the American
  Chemistry Council (Diller Registry on Phosgene
  Effects)
• The presenter has received research funding and
  consulting fees from the manufacturer and
  distributers of hydroxocobalamin, a cyanide
  antidote

3
Overview

• Overview of occupational gas exposures and
  injuries
• Epidemiology
• Sources and use
• Clinical case presentations
• Update on treatments

• Carbon monoxide
• Hydrogen sulfide
• Hydrogen cyanide
• Phosgene
• Arsine

4
Occupational deaths injuries

• Fatal

• Nonfatal

• Work injuries 5,703 3.9/100,000 workers
• Deaths from exposure to harmful substances or
  environments 525 (9)
• Deaths from inhalation of substances 58 (11 of
  exposure deaths, 1 of deaths)

• Nonfatal exposures to chemicals 18,230
• Inhalation 5, 180
• Confined spaces 920

U.S. 2006 Bureau of Labor Statistics
5
Top 10 reasons it may not pay to show up for work
Valent 2002 Chest 121969-975
6
Carbon monoxide
7
Carbon monoxide

• General epidemiology
• 15,000 ED visits/yr for unintentional,
  non-fire-related CO
• 500 deaths
• Mostly men (3/4)
• 15 yrs and above
• Attributed to working with fuel-powered tools /
  appliances

U.S. Centers for Disease Control
8
Carbon monoxide

• Occupational epidemiology
• Study of 1992-1996
• 148 occupational CO unintentional deaths
• Services industries (25)
• Manufacturing (14)
• Construction (14)
• Agriculture (14)
• Majority involved motor vehicle exhaust

Janicak 1998 Compens Work Condition Fall26-28
9
Carbon monoxide

• Epidemiology
• AAPCC 2006
• 48 fatal CO exposures (alone/combination)
• 14 fatal occupational CO exposures
• 29 of all CO deaths
• 58 of 24 total occupational fatalities
• Occupational exposures comprise 1.5 of NPDS

Bronstein 2007 Clin Toxicol 45815-917
10
Carbon monoxide

• Epidemiology
• 1989-2004 68 incidents of CO poisoning in hotels
• 772 accidentally poisoned 711 guests, 41
  employees or owners, and 20 rescue personnel (8
  occupational).
• 27 died, 66 had confirmed sequelae, 6 had
  sequelae resulting in a jury verdict
• Faulty room heating caused 45 incidents, pool/spa
  boilers 16, CO entrained from outdoors 5
• Public verdicts averaged 4.8 million per
  incident
• Poisonings occurred at hotels of all classes

YOU CAN CHECK OUT ANY TIME YOU LIKE, BUT YOU CAN
NEVER LEAVE
Weaver 2007 Am J Prev Med 3323-27
11
Carbon monoxide

• Epidemiology
• 167 patients treated for CO poisoning during
  hurricanes of 2004 in Florida
• Portable gas-powered generators responsible in
  nearly all non-fatal and all fatal poisonings
• 48 of generators were outside the home
• 33 in the garage
• 15 inside the home
• 3 occurred at businesses

US Consumer Product Safety Commission estimates
a typical 5-kilowatt generator generates a
concentration of CO equivalent to the tailpipe
emissions of between 252 and 572 idling vehicles
Van Sickle 2007 Am J Prev Med 32340-346
12
Carbon monoxide

• Case scenario
• 23 y/o commercial coffee roaster entered a 2 x
  2.7 meter storage tank to retrieve a tool
• He lost consciousness, retrieved 40 mins later,
  dead
• 5 coworkers sent to hospital
• 3 had lost consciousness, 2 were presyncopal
• All rescuers recovered, but 1 hospitalized
• Maximum CO concentrations up to 100,000 ppm

Nishimura 2003 JAMA 290334
13
Carbon monoxide

• What is and what isnt

• 150 children with CO poisoning
• Categorized according to source of CO
• Dramatic differences in signs / symptoms and
  outcomes with almost no difference in COHb

Chou 2000 Pediatr Emerg Care 16151-155
14
Carbon monoxide

• Treatment HBO The intergalactic battle rages
  on

• Buckley 2005
• Conflicting evidence regarding efficacy
• Evidence of bias in studies
• Firm guidelines cannot be established
• More research is needed to define the roleif
  anyof HBO

• Bentur 2005
• This review cannot dispel the current
  disagreement
• Brent 2005
• HBOT best reserved for selected patients
• Seger 2005
• I dont know

Buckley 2005 Toxicol Rev 2475-92
15
Carbon monoxide

• Treatment failuresor not
• CO poisoned patients may be successfully used as
  donors
• Bentley 2001 Ann Thorac Surg 711194-1197
• Two hearts
• Luckraz 2001 Ann Thorac Surg 72709 13
• Six hearts, one lung
• One organ failure at 12h ? death

16
Hydrogen sulfide
HSH
17
Hydrogen sulfide

• Product of decomposition
• Petroleum (sour gas)
• Paper pulp industry (Kraft process)
• Decomposing food waste
• Offal
• Fish scrap
• Manure
• Sewers
• Compost pits

18
Hydrogen sulfide

• Sources and uses
• Intermediate in production
• Elemental sulfur
• Sodium sulfide
• Other inorganic sulfides
• Sulfuric acid
• Extreme pressure lubricants and cutting oils

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Hydrogen sulfide

• Epidemiology
• AAPCC 2006
• 5 occupational deaths due to H2S alone or in
  combination out of 8 total deaths (62.5)
• 344 (all causes) treated in HCF with 10 moderate
  and 1 lethal outcome as single agent
• Valent 2002
• 2 cause of fatal inhalational occupational
  injuries
• Responsible for 9.7 of these deaths

Bronstein 2007 Clin Toxicol 45815-917
Valent 2002 Chest 121969-975
20
Hydrogen sulfide

• Epidemiology
• Review of 77 deaths related to manure storage
  over a 30 year period 1975-2004
• 34 died while doing repair or maintenance of
  manure handling equipment
• 22 died while trying to effect a rescue
• 21 involved persons lt16 years of age
• Confined space entry identified as a particular
  risk

Beaver 2007 J Agromedicine 123-23
21
Hydrogen sulfide

• Case scenario
• 16 y/o male sent to clean a reoxygenation tank in
  a fish hatchery known to be contaminated with H2S
  after it is drained and the smell dissipates
• As he begins to clean out the sludge in the 5 m
  deep tank he collapses. His adult co-worker
  attempts to rescue him and dies
• EMS administers oxygen and the youth awakens
• He survives intact after prolonged
  hospitalization and rehabilitation

Nikkanen 2004 Pediatrics 113927-929
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Hydrogen sulfide

• Treatment
• Not much new
• Nitrite treatment (induction of
  methemoglobinemia?) remains controversial
• HBO therapywell, you can guess
• Hydroxocobalamin?
• Shown to form sulfitocobalamin with H2S
• Clinical significance remains unknown

Farquharson 1977 Am J Clin Nutr 301617-1622
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Hydrogen cyanide
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Hydrogen cyanide

• Epidemiology
• AAPCC 2006
• 0 pure HCN gas fatalities
• 7 non-gas (cyanide salts) fatalities, all
  ingestions, none occupational
• 118 unintentional exposures, 5 major outcomes
• Valent 2002
• Fire smoke is the 6th most common cause of
  occupational inhalational fatal injuries
  accounting for 4 of those deaths

Bronstein 2007 Clin Toxicol 45815-917
Valent 2002 Chest 121969-975
25
Hydrogen cyanide

• Sources and uses
• 1.5 million tonnes / yr used worldwide
• Vast majority used for manufacture of methyl
  methacrylate (?plexiglas) and adiponitrile (?
  nylon)
• Other nitrile manufacture (acrylonitrile)
• Gold and silver extraction, electroplating
• Jewelry cleaning
• Vermin extermination
• Fire smoke

Cummings 2004 Occup Med 5482-85
26
Hydrogen cyanide

• Case scenario
• 25-year-old male electroplater entered a metal
  plating holding tank for excess zinc cyanide to
  clean it
• Holding tank had been emptied by a waste disposal
  company, but had 2 zinc cyanide sludge
• The victim manually pumped in between 1 and 2
  gallons of 1 muriatic acid, then climbed into
  tank without respiratory protection
• 4 minutes later, he collapsed

http//www.cdc.gov/niosh/face/In-house/full8833.ht
ml
27
Hydrogen cyanide

• Case scenario, contd.
• 4 coworkers entered the tank to attempt to rescue
  the victim, none had respiratory protection all
  collapsed
• Additional workers tried to attempt rescue one
  was able to rescue one of the 4 coworkers and
  administer CPR
• 5 workers died
• 17 police officers and firefighters received
  toxic exposures 30 total victims were treated

http//www.cdc.gov/niosh/face/In-house/full8833.ht
ml
28
Hydrogen cyanide

• Treatment
• ECETOC is currently studying cyanide antidotes to
  determine the most appropriate one(s) for
  industry, several EAPCCT members on Task Force
• Hydroxocobalamin has recently been approved by
  the EMEA and US FDA
• Cobinamide and various prodrugs of
  3-mercaptopyruvate are undergoing advanced
  studies in the US

Broderick 2006 Exp Biol Med 231641-651
Nagasawa 2007 J Med Chem 506462-6464
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Phosgene
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Phosgene

• Sources and uses
• A high production volume chemical (OECD)
• Phosgene is used in manufacture of
• Polymeric isocyanates (polyurethane, resins)
• Polycarbonates (plastics)
• Carbamates and related pesticides
• Aniline dyes
• Perfumes
• Pharmaceuticals
• Heating of chlorinated hydrocarbons

31
Phosgene

• Epidemiology
• AAPCC 2006
• No phosgene exposures reported
• Diller registry (American Chemistry Council)
• Deleted from Wikitox slide set
• Permission not requested or obtained for web
  publication
• See ACC website for more information

Bronstein 2007 Clin Toxicol 45815-917
32
Phosgene

• Case scenario
• 43 y/o male helping demolish a refrigeration
  plant
• Cut through a pipe containing chlorodifluoromethan
  e, noted a musty smell
• Immediate lacrimation, cough, burning in throat
• Later, dyspnea and chest pain
• Admitted to hospital x 24h
• Slow recovery, with lethargy, exertional dyspnea
• Return to work at 2 weeks

Wyatt 1995 J Accid Emerg Med 12212-213
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Phosgene

• Pathophysiology
• Acylation
• Reaction with amino, hydroxyl, and sulfhydryl
  groups
• Denaturation of proteins and lipoids
• Irreversible alterations of membrane structures
• Disruption of enzyme and other cell functions
• Hydrolysis
• Less important formation of HCl

Borak 2000 J Occup Environ Med 43110-119
34
Phosgene

• Treatment
• Steroid
• Inhalers
• Prednisolone 250 mg IV
• Ibuprofen
• 25-50 mg/kg
• N-acetylcysteine
• 20 mL of a 20 NAC solution administered by
  nebulizer
• Positive airway pressure ventilation
• Rest and observation

Borak 2000 J Occup Environ Med 43110-119
35
Arsine
H
As
H
H
36
Arsine

• Sources and uses
• Production of gallium arsenide
• Dopant in solid-state electronics
• Manufacture of LEDs
• Product of chemical reaction of arsenic salts
  with strong mineral acids
• Metal smelting and refining
• Arsenical pesticide use
• Battery manufacture
• Art restoration

37
Arsine

• Epidemiology
• AAPCC 2006
• No arsine exposures reported
• 1 arsenic death due to ingestion
• Pullen-James 2006
• Approximately 750 reported exposures
• 1/3 lethal

Bronstein 2007 Clin Toxicol 45815-917
Pullen-James 2006 J Natl Med Assoc 981998-2001
38
Arsine

• Case scenario
• 55 y/o male c/o flank pain radiating into groin
  for two hours, with weakness, followed by gross
  hematuria
• PMH of testicular cancer
• Developed hypotension during CT to rule out
  stone, required vasopressors
• WBC 36k, CPK 546, UA with WBC, 6-8 rbc/hpf, Cr
  1.0
• Admitted to ICU with dx of sepsis

Pullen-James 2006 J Natl Med Assoc 981998-2001
39
Arsine

• Case scenario, contd
• Deteriorated overnight, developed ARDS
• Skin became beet red, urine black, WBC increased
  to 43,000, Hb dropped from 11.2 to 8.8 mg/dl,
  Creatinine increased to 2.6 (229.8 µmol/l)
• Occupational history taken on day 2
• Water detoxification plant
• Removing As from water using an acid preparation
• Recalled smelling garlicky odor above water
• 2 coworkers presented shortly after with hematuria

Pullen-James 2006 J Natl Med Assoc 981998-2001
40
Arsine

• Signs and symptoms of poisoning
• Concentration-dependent symptom delay
• Headache, vomiting, chills, dyspnea
• Pain in chest, lumbar area, abdomen
• Fever, tachypnea
• Oliguria ? anuria
• Dark urine, skin tone ? jaundice at 24-48h
• Leukocytosis, Heinz bodies, basophilic stippling
  , anemia
• Hyperkalemia
• Ur As gt 200 mcg/l

41
Arsine

• Pathophysiology
• Uncertain definitely involves O2Hb
• COHb is protected
• Oxidation of red blood cells resulting in massive
  hemolysis
• Sodium-potassium pump poisoning
• Swelling of RBC
• Renal injury due to hemolysis, direct toxicity

42
Arsine

• Treatment
• Supportive care
• Plasma exchange
• Antidotes for As not indicated
• Exchange transfusion
• Hemodialysis
• Bicarbonate for hemolysis
• Glutathione (?)
• Dexamethasone (?)

Pullen-James 2006 N Natl Med Assoc 981998-2001
Song 2007 Clin Toxicol 45721-727
43
Arsine

• Treatment by plasma exchange

Song 2007 Clin Toxicol 45721-727
44
Summary

• Toxic gases continue to cause lethal and injuries
  in industry
• These exposures account for a small percentage of
  fatal occupational injuries
• Confined space exposures and unprotected rescue
  attempts result in many injuries and deaths
• Treatments continue to slowly evolve and improve