Hazardous Metals Emerging and Long-standing Toxicants Robert - - PDF document

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Hazardous Metals Emerging and Long-standing Toxicants Robert - - PDF document

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Partner Logo Hazardous Metals Emerging and Long-standing Toxicants Robert Goodnough, MD Medical Toxicology Fellow UCSF Department of Emergency Medicine Zuckerberg San Francisco General Hospital California Poison Control System San

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SLIDE 1

Partner Logo

Hazardous Metals

Emerging and Long-standing Toxicants

3/6/2019

Robert Goodnough, MD Medical Toxicology Fellow UCSF Department of Emergency Medicine Zuckerberg San Francisco General Hospital California Poison Control System – San Francisco Division

Financial Disclosures

  • None

3/6/2019 Hazardous Metal 2

Case Introduction

  • A 40 year old man is referred to occupational health clinic.
  • 2-3 months of progressive dyspnea on exertion
  • Normal CBC, chemistry panel.
  • Social History: negative
  • Medical History: none
  • Occupational History: grinding Indium Tin Oxide plates for the last 9

years Presentation:

3/6/2019 Hazardous Metals 3

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SLIDE 2

Objectives

  • Historic
  • Vanadium
  • Germanium
  • Emerging
  • Tellurium
  • Rare Earth Elements
  • Indium Trioxide
  • NOT covering:
  • Cobalt, Arsenic, Lead, Mercury

What we’ll cover:

3/6/2019 Hazardous Metals 4

Historical Hazards

  • Uses:
  • Minor

‒ Pesticides ‒ Dyes ‒ paints

  • Major

‒ Alloying hard steel

  • Nonessential element
  • Vanadium

3/6/2019 Hazardous Metals 5 https://commons.wikimedia.org/wiki/Vanadium#/media/File:Brookite-Quartz-221044.jpg

Historical Hazards

  • Absorption:
  • Mainly Pulmonary
  • GI (2%)
  • Cutaneous (minor)
  • Detection (normal)
  • Serum: 0.12 ug/L
  • Vanadium

3/6/2019 Hazardous Metals 6

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SLIDE 3

Vanadium

  • Pulmonary
  • ILDH 70mg/m3
  • Cough, respiratory distress
  • Lacrimation/rhinorrhea
  • GI
  • Nervous System
  • Headache, tremor
  • Mucosa
  • Green discoloration*
  • Adverse Health Effects in Workers

3/6/2019 Hazardous Metals 7

Vanadium pentoxide V205

  • IARC classification
  • 2B “possible carcinogen
  • Animal inhalation data and lung cancer
  • Cannot be extrapolated to all vanadium compounds
  • Unclear/Possible mechanism

‒ Generation of inflammation ‒ Generation of reactive oxygen species ‒ By acting as phosphate analogues

3/6/2019 Hazardous Metals 8

Assen 2009

Historic Hazards

  • Non-essential Trace Element
  • Occupational use
  • Fiberoptics
  • Semiconductor manufacture
  • Germanium tetrahydride
  • Alternative use
  • Dietary “supplement”
  • Germanium

3/6/2019 Hazardous Metals 9

https://commons.wikimedia.org/wiki/Germanium#/media/File:Diode_germaniu m_OA85.JPG

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SLIDE 4

Germanium

  • Absorption:
  • Pulmonary: rapid
  • Gastrointestinal: rapid
  • Preference for Kidney and

liver

  • Urinary excretion
  • Accumulation in Bone
  • Occupational Exposure

3/6/2019 Hazardous Metals 10 https://commons.wikimedia.org/wiki/Germanium#/media/File:Polycrystalline-germanium.jpg

Germanium

  • Irritant:
  • Lungs
  • Skin
  • Mucosa
  • Kidney:
  • Evidence for proteinuria
  • Glomerular toxin
  • Occupational Toxicity

3/6/2019 Hazardous Metals 11 https://commons.wikimedia.org/wiki/Germanium#/media/File:Polycrystalline-germanium.jpg

Dietary Supplementation

  • Organic
  • Animal studies with some

effect

  • Antitumor
  • Organic compounds
  • No supporting human trials
  • No clear nephrotoxicity
  • Antitumor and anti-inflammatory
  • Inorganic
  • Well described nephrotoxicity
  • Reports since 1980s
  • Dosing: 16-320g
  • Time period: 4-36 months

3/6/2019 Hazardous Metals 12

Schauss 1991

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SLIDE 5

Emerging Hazards

  • Historical Uses
  • Syphilis
  • leprosy
  • Current Uses
  • Vulcanization
  • Alloys*
  • Oxidation (Jewelry)
  • Semiconductors
  • catalytic
  • Tellurium

3/6/2019 Hazardous Metals 13 https://commons.wikimedia.org/w/index.php?search=vulcanized+rubber&title=Special%3ASearch&go=Go#/media/File:In _Touch_by_Joseph_Fahys_%26_co.png

Tellurium dioxide

  • Acute Toxicity
  • CNS Depression
  • Mucosal injury (solvent)
  • GI effects
  • Garlic Odor:
  • Decreased sweat
  • Black Discoloration

‒ Mucosa ‒ skin

  • ingestion

3/6/2019 Hazardous Metals 14 https://commons.wikimedia.org/wiki/Category:Tellurium_dioxide#/media/File:TeO2.jpg

Workplace

  • Exposure:
  • Copper refining
  • vulcanization
  • Absorption:
  • Mainly pulmonary
  • Moderate GI
  • Less cutaneous
  • Tellurium
  • OSHA
  • PEL: 0.1mg/m3 per 8 hrs
  • NIOSH
  • REL: 0.1 mg/m3 per 10 hrs

Normal: Whole Blood: 0.15-0.3 ug/L Urine: 0.1-10 ug/L

3/6/2019 Hazardous Metals 15

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SLIDE 6

Tellurium

  • Case Series
  • 3 lab workers with “classic”

symptoms

  • Tellurium fumes
  • Symptomatic
  • Urine levels: 8-16 ug/L
  • 98 iron foundry workers
  • Urine detectable tellurium
  • Workplace

3/6/2019 Fumigants, Herbicides, and Insecticides 16 https://upload.wikimedia.org/wikipedia/commons/5/54/Hydrogen_telluride.svg 3/6/2019 Hazardous Metals 17 https://commons.wikimedia.org/w/index.php?search=smart+phone&title=Special%3ASearch&go=Go#/media/File:Traditional_cell_phone_vs_Smart_phone.jpg 3/6/2019 Hazardous Metals 18 https://commons.wikimedia.org/w/index.php?search=hybrid&title=Special%3ASearch&go=Go#/media/File:Harrier_hybrid_frontface.jpg

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SLIDE 7

What are Rare Earths Elements

  • Not necessarily rare
  • Minable deposits
  • Value of Import to US $160

million (2018)

  • Mineral sources (US)
  • Bastnaesite
  • Monazite
  • 17 elements
  • ”Critical Mineral”

(USGS 2018)

  • Sources and Uses

3/6/2019 Hazardous Metals 19 https://commons.wikimedia.org/w/index.php?search=rare+earth&title=Special%3ASearch&go=Go#/media/File:RareEarthO reUSGOV.jpg

Rare Earths

  • Sources of US import
  • Mainly China (80%)
  • Present also:

‒ Estonia (6%) ‒ France (3%) ‒ Japan (3%) ‒ Other (8%)

  • Sources and Uses

3/6/2019 Hazardous Metals 20 https://commons.wikimedia.org/w/index.php?search=rare+earth&title=Special%3ASearch&go=Go#/media/File:RareEarthO reUSGOV.jpg

Rare Earths

  • Uses
  • Screens: TVs, Smart Phones
  • Hybrid Vehicles, wind

turbines (magnets)

  • Catalysts (diesel, oil refining)
  • Breakdown
  • Catalysts (60%)
  • Glass/Ceramics (15%)
  • Alloys/Polishing (10%, each)
  • Sources and Uses

3/6/2019 Hazardous Metals 21 https://commons.wikimedia.org/wiki/Cerium#/media/File:Cerium.jpg

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SLIDE 8

Rare Earths

  • Potential Hazards
  • Radioactive Contamination
  • Hypertension*
  • Pneumoconiosis
  • iatrogenic
  • Contamination
  • Airborne
  • Food
  • General Hazards and Population based effects

3/6/2019 Hazardous Metals 22 https://commons.wikimedia.org/w/index.php?search=radioactive&title=Special%3ASearch&go=Go#/media/File:Radioactive_symbol.png

Rim 2013

Pneumoconiosis

  • Case Descriptions

Exposure to carbon arc lamps photoengravers movie projectionists

  • Interstitial Lung disease
  • BAL fluid
  • Presence of Rare Earth Elements
  • Retention of Rare Earth Elements (potential bio-persistence)

3/6/2019 Hazardous Metals 23

Rim 2013

Iatrogenic Harm

  • Lanthanum Carbonate
  • Phosphate binder
  • Case Reports
  • 75F on HD

‒ Encephalopathy ‒ 2.13 ug/L on presentation

  • 70M: ischemic colitis
  • 3rd case: hepatitis
  • Lanthanum

3/6/2019 Hazardous Metals 24 https://commons.wikimedia.org/w/index.php?search=dialysis&title=Special%3ASearch&profile=advanced&fullt ext=1&advancedSearch- current=%7B%22namespaces%22%3A%5B6%2C12%2C14%2C100%2C106%2C0%5D%7D&ns6=1&ns12=1& ns14=1&ns100=1&ns106=1&ns0=1#/media/File:Dialysis_-_arm_-_01.jpg

Muller 2009

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SLIDE 9

Rare Earths

  • Scalp Hair Analysis
  • OEM limits:
  • Yttrium
  • TWA: 1mg/m2
  • IDLH: 500mg/m3
  • General Paucity of data
  • Future work/research required
  • Monitoring

3/6/2019 Hazardous Metals 25 https://commons.wikimedia.org/wiki/Category:Monitoring#/media/File:Acceleromyograp hy_monitoring_with_preload_hand_adapter.jpg

Indium Trioxide

  • Rising importance:
  • Plasma screens
  • Flat panel displays
  • Touch panel displays
  • Poor Enteral Absorption
  • Increasing Pulmonary

Toxicity

  • Emerging Hazards

3/6/2019 Hazardous Metals 26 https://commons.wikimedia.org/w/index.php?search=touch+screen&title=Special%3ASearch&go=Go#/media/File:Touch_screen.jpg

Indium Trioxide

  • “Indium Lung”
  • Production of ITO
  • Start

‒ Pulmonary alveolar proteinosis

  • Progression:

‒ Emphysema and Fibrosis

  • Emerging Hazards

3/6/2019 Hazardous Metals 27 https://commons.wikimedia.org/w/index.php?search=touch+screen&title=Special%3ASearch&go=Go#/media/File:Touch_screen.jpg

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SLIDE 10

Summary Slides

  • Rare Earths:
  • Potentially growing US

industry

  • Pneumoconiosis
  • radiation hazard
  • Some Takeaways and Future Directions
  • Vanadium:
  • Generally Pulmonary

Toxicity

  • Green Discoloration of

mucosa

  • Further Research Needed

Regarding Carcinogenicity

3/6/2019 Hazardous Metals 28

Summary Slides

  • Indium:
  • Semiconductor
  • Pulmonary

Fibrosis/Emphysema

  • Germanium:
  • Industry:

‒ Pulmonary irritant ‒ Possible nephrotoxin

  • Home/Alternative Med:

‒ nephrotoxin

  • Some Takeaways and Future Directions
  • Tellurium:
  • CNS depression
  • Weakness
  • GI symptoms
  • Blue-Black discoloration
  • Garlic Odor

3/6/2019 Hazardous Metals 29 3/6/2019 Fumigants, Herbicides, and Insecticides 30

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SLIDE 11

CME Questions

Robert Goodnough Metals: Past and Emerging

The primary organ (s) of toxicity of Vanadium are:

  • A) Skin/Epithelium
  • B) Pulmonary
  • C) Tongue
  • D) Nail Bed

Clinical Features of Tellurium Toxicity are likely to include

  • A) Microcytic Anemia and wrist drop
  • B) Respiratory Symptoms, garlic odor and blue-black discoloration of skin

and mucosa

  • C) Nail bed alteration and ”Rain Drop on a dusty road” rash
  • D) Pill rolling tremor, shuffling gait, and masked facies
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SLIDE 12

Occupational Exposure To Lanthanum likely places a worker at risk for the following:

  • A) No Documented Toxicity
  • B) Epithelial Malignancy
  • C) Cataract formation
  • D) Respiratory Symptoms/Pneumoconiosis