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
TEN LEADING SOURCES OF FATAL OCCUPATIONAL INHALATION, UNITED STATES, 1992-1998 NUMBER
Carbon monoxide 175 33.5
Sulfur and sulfur compounds 51 9.7
Sewer gas, mine gas, methane 40 7.6
Nitrogen oxides 26 5.0
Coal, natural gas, petroleum fuels and compounds 24 4.6
Smoke, fire gases 21 4.0
Halogens and halogen compounds 20 3.8
Ammonia and ammonium compounds 15 2.9
Acids and alkalis 14 2.7
Aromatics and hydrocarbon derivatives, except halogens 13 2.5
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

19
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
22
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
23
Hydrogen cyanide
24
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
29
Phosgene
30
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
33
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