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

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 Francisco Division 3/6/2019 Financial Disclosures  None 2 Hazardous Metal 3/6/2019 Case Introduction Presentation:  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 3 Hazardous Metals 3/6/2019

Objectives What we’ll cover:  Historic • Vanadium • Germanium  Emerging • Tellurium • Rare Earth Elements • Indium Trioxide  NOT covering: • Cobalt, Arsenic, Lead, Mercury 4 Hazardous Metals 3/6/2019 Historical Hazards  Vanadium  Uses: • Minor ‒ Pesticides ‒ Dyes ‒ paints • Major ‒ Alloying hard steel • Nonessential element https://commons.wikimedia.org/wiki/Vanadium#/media/File:Brookite-Quartz-221044.jpg 5 Hazardous Metals 3/6/2019 Historical Hazards  Vanadium  Absorption: • Mainly Pulmonary • GI (2%) • Cutaneous (minor)  Detection (normal) • Serum: 0.12 ug/L 6 Hazardous Metals 3/6/2019

Vanadium  Adverse Health Effects in Workers  Pulmonary • ILDH 70mg/m 3 • Cough, respiratory distress • Lacrimation/rhinorrhea  GI  Nervous System • Headache, tremor  Mucosa • Green discoloration* 7 Hazardous Metals 3/6/2019 Vanadium pentoxide V 2 0 5  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 Assen 2009 8 Hazardous Metals 3/6/2019 Historic Hazards  Germanium  Non-essential Trace Element  Occupational use • Fiberoptics • Semiconductor manufacture • Germanium tetrahydride  Alternative use • Dietary “supplement” https://commons.wikimedia.org/wiki/Germanium#/media/File:Diode_germaniu m_OA85.JPG 9 Hazardous Metals 3/6/2019

Germanium  Occupational Exposure  Absorption: • Pulmonary: rapid • Gastrointestinal: rapid  Preference for Kidney and liver  Urinary excretion  Accumulation in Bone https://commons.wikimedia.org/wiki/Germanium#/media/File:Polycrystalline-germanium.jpg 10 Hazardous Metals 3/6/2019 Germanium  Occupational Toxicity  Irritant: • Lungs • Skin • Mucosa  Kidney: • Evidence for proteinuria • Glomerular toxin https://commons.wikimedia.org/wiki/Germanium#/media/File:Polycrystalline-germanium.jpg 11 Hazardous Metals 3/6/2019 Dietary Supplementation  Antitumor and anti-inflammatory • Organic  Inorganic  Well described nephrotoxicity  Animal studies with some effect  Reports since 1980s • Antitumor • Organic compounds  Dosing: 16-320g  No supporting human trials  Time period: 4-36 months  No clear nephrotoxicity Schauss 1991 12 Hazardous Metals 3/6/2019

Emerging Hazards  Tellurium  Historical Uses • Syphilis • leprosy  Current Uses • Vulcanization • Alloys* • Oxidation (Jewelry) • Semiconductors • catalytic 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 13 Hazardous Metals 3/6/2019 Tellurium dioxide  ingestion  Acute Toxicity • CNS Depression • Mucosal injury (solvent) • GI effects • Garlic Odor: • Decreased sweat • Black Discoloration ‒ Mucosa ‒ skin https://commons.wikimedia.org/wiki/Category:Tellurium_dioxide#/media/File:TeO2.jpg 14 Hazardous Metals 3/6/2019 Workplace  Tellurium  OSHA  Exposure: • PEL: 0.1mg/m 3 per 8 hrs  NIOSH • Copper refining • vulcanization • REL: 0.1 mg/m3 per 10 hrs  Absorption: • Mainly pulmonary Normal: • Moderate GI Whole Blood: 0.15-0.3 ug/L • Less cutaneous Urine: 0.1-10 ug/L 15 Hazardous Metals 3/6/2019

Tellurium  Workplace  Case Series • 3 lab workers with “classic” symptoms • Tellurium fumes • Symptomatic • Urine levels: 8-16 ug/L • 98 iron foundry workers • Urine detectable tellurium https://upload.wikimedia.org/wikipedia/commons/5/54/Hydrogen_telluride.svg 16 Fumigants, Herbicides, and Insecticides 3/6/2019 https://commons.wikimedia.org/w/index.php?search=smart+phone&title=Special%3ASearch&go=Go#/media/File:Traditional_cell_phone_vs_Smart_phone.jpg 17 Hazardous Metals 3/6/2019 https://commons.wikimedia.org/w/index.php?search=hybrid&title=Special%3ASearch&go=Go#/media/File:Harrier_hybrid_frontface.jpg 18 Hazardous Metals 3/6/2019

What are Rare Earths Elements  Sources and Uses  Not necessarily rare • Minable deposits  Value of Import to US $160 million (2018)  Mineral sources (US) • Bastnaesite • Monazite  17 elements  ”Critical Mineral” https://commons.wikimedia.org/w/index.php?search=rare+earth&title=Special%3ASearch&go=Go#/media/File:RareEarthO (USGS 2018) reUSGOV.jpg 19 Hazardous Metals 3/6/2019 Rare Earths  Sources and Uses  Sources of US import • Mainly China (80%) • Present also: ‒ Estonia (6%) ‒ France (3%) ‒ Japan (3%) ‒ Other (8%) https://commons.wikimedia.org/w/index.php?search=rare+earth&title=Special%3ASearch&go=Go#/media/File:RareEarthO reUSGOV.jpg 20 Hazardous Metals 3/6/2019 Rare Earths  Sources and Uses  Uses • Screens: TVs, Smart Phones • Hybrid Vehicles, wind turbines (magnets) • Catalysts (diesel, oil refining)  Breakdown • Catalysts (60%) • Glass/Ceramics (15%) • Alloys/Polishing (10%, each) https://commons.wikimedia.org/wiki/Cerium#/media/File:Cerium.jpg 21 Hazardous Metals 3/6/2019

Rare Earths  General Hazards and Population based effects  Potential Hazards • Radioactive Contamination • Hypertension* • Pneumoconiosis • iatrogenic  Contamination • Airborne • Food https://commons.wikimedia.org/w/index.php?search=radioactive&title=Special%3ASearch&go=Go#/media/File:Radioactive_symbol.png Rim 2013 22 Hazardous Metals 3/6/2019 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) Rim 2013 23 Hazardous Metals 3/6/2019 Iatrogenic Harm  Lanthanum  Lanthanum Carbonate • Phosphate binder  Case Reports • 75F on HD ‒ Encephalopathy ‒ 2.13 ug/L on presentation • 70M: ischemic colitis • 3 rd case: hepatitis https://commons.wikimedia.org/w/index.php?search=dialysis&title=Special%3ASearch&profile=advanced&fullt ext=1&advancedSearch- Muller 2009 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 24 Hazardous Metals 3/6/2019

Rare Earths  Monitoring  Scalp Hair Analysis  OEM limits: • Yttrium • TWA: 1mg/m 2 • IDLH: 500mg/m 3  General Paucity of data https://commons.wikimedia.org/wiki/Category:Monitoring#/media/File:Acceleromyograp hy_monitoring_with_preload_hand_adapter.jpg  Future work/research required 25 Hazardous Metals 3/6/2019 Indium Trioxide  Emerging Hazards  Rising importance: • Plasma screens • Flat panel displays • Touch panel displays • Poor Enteral Absorption • Increasing Pulmonary Toxicity https://commons.wikimedia.org/w/index.php?search=touch+screen&title=Special%3ASearch&go=Go#/media/File:Touch_screen.jpg 26 Hazardous Metals 3/6/2019 Indium Trioxide  Emerging Hazards  “Indium Lung”  Production of ITO • Start ‒ Pulmonary alveolar proteinosis • Progression: ‒ Emphysema and Fibrosis https://commons.wikimedia.org/w/index.php?search=touch+screen&title=Special%3ASearch&go=Go#/media/File:Touch_screen.jpg 27 Hazardous Metals 3/6/2019

Summary Slides  Some Takeaways and Future Directions  Rare Earths:  Vanadium: • Potentially growing US • Generally Pulmonary industry Toxicity • Pneumoconiosis • Green Discoloration of mucosa • radiation hazard • Further Research Needed Regarding Carcinogenicity 28 Hazardous Metals 3/6/2019 Summary Slides  Some Takeaways and Future Directions  Indium:  Tellurium: • Semiconductor • CNS depression • Pulmonary • Weakness Fibrosis/Emphysema • GI symptoms • Blue-Black discoloration  Germanium: • Garlic Odor • Industry: ‒ Pulmonary irritant ‒ Possible nephrotoxin • Home/Alternative Med: ‒ nephrotoxin 29 Hazardous Metals 3/6/2019 30 Fumigants, Herbicides, and Insecticides 3/6/2019

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