Perspective of Industrial Use of Arsenic

3. Perspective of Industrial Use of Arsenic U.S. industrial usage estimated at 150 tons in 1995 World reserves estimated at 11 million tons

4. Risk of Exposure to Arsenic Species in Ion Implantation Change arsine tank every 3 weeks. house scrubber 1. Replace tungsten filament. 2. Change the slit for the beam. 3. Scrub the implanter weekly. Chimney Replace the catalyst every 2 years. Change pump oil and clean the pump.

5. Chemistry of the Arsenic Species in the Fab Arsenic (As0) • A brittle, crystalline, silvery to black metalloid. Arsenic trioxide (As2O3) • Odorless, tasteless, white or transparent, amorphous or crystalline powder. Accidental generation of AsH3: 6H+ +2Al0 + HAsO2-->AsH3 +2H2O + 2Al 3+ (i.e. aluminum or galvanized buckets to transport arsenical slurry.) • Arsine (AsH3) • Colorless gas with garlic odor. • Highly reactive : risk of explosion upon contact with air or when physically shocked. Removal of arsine in fab by the following chemical reactions Burn Box:2AsH3 + 3O2--> As2O3 + 3H2O 4AsH3 +3O2---> 4As0 + 6H2O Dry Scrubbing: 2AsH3 + 3CuO ---> Cu3As + As0 + 3H2O Cu3As + As0 +3O2 --> 3CuO + As2O3 Wet Scrubbing: 4MnO4- + 2AsH3--> As2O3 + H2O + 4 MnO2 + 4OH- 32MnO4- +12AsH3--> 3As4O10 + 2H2O +32OH- +32MnO2

6. ARSENIC TOXICITY HUMAN Lungs • Target of inhalation exposure • PROVEN LuNG CARCINOGEN Acute Effects • Fatal at 70-180 mg, toxicity at 1-50 mg • Similar to AsH3 except no RBC lysis • Animal models are poor predictors Chronic Effects • Meese’s lines; skin, hair accumlation • Cancer of lungs, skin, kidney, bladder, and liver Kidneys • Toxicity in acute exposure • Suspected kidney carcinogen • RENALFAILURE IS CAUSE OF DEATH in acute exposures Central and Peripheral Nervous System • Neural degradation • Peripheral neuropathy ANIMAL Skin • Suspected skin carcinogen • High accumulation of As in skin • Low overall toxicity • 10-100 times more resistant than humans • Generally non-carcinogenic except as tumor promoters Liver • Suspected liver carcinogen • Enlargement and toxicity

7. AsH3 TOXICITY HUMAN Hemotologic • RBC lysis • (1 - 10 ppm) • Fatal at 50 ppm (30 min) • Around 750 reported exposures, 1/3 resulting in death • Human and animal toxicity is very similar  predictive models Kidneys • Hemoglobinurea • Toxic to nephron • RENAL FAILURE IS CAUSE OF DEATH Central and Peripheral Nervous System • halucinations • headaches • neural degradation • sensory loss ANIMAL • Similar toxic effects seen in mice, rats, and hamsters • RBC lysis at 3-12 ppm exposure • Liver and spleen enlargement with long-term 5 ppm exposure • Kidney toxicity at higher exposure • Fatal at 30-50 ppm Abdominal pain • diarrhea • vomiting • unknown mechanism (GI toxicity?) Liver • Liver toxicity • Altered hepatic function

8. The Main Route of Exposure to AsH3:Inhalation CROSS SECTION of ALVEOLA WALL LUNGS ALVEOLUS Bronchiole Pulmonary arteriole RBC Larynx 50 to 100 nm Trachea Terminal brochiole 7mm Bronchus AsH3 AsH3 AsH3 AsH3 As? Alveolar sac A • Oxidation state of As in RBC is unknown but likely to be As3+. • Toxicity of As species to RBC is oxygen dependent in vitro. H B Arsine diffuses through the alveolar membrane into capillary lumen where it reacts with the Red Blood Cell (RBC). Threshold Limited Value (TLV) for AsH3 is 5ppb.

9. Inhalation of Arsenicals Particulate Arsenic (As2O3, etc.) • Particles deposit in lungs according to size > 6 mm: trapped in nose 1-5 mm: impact on bifurcations 1 mm: reach terminal bronchioles <0.5 mm: suspended in air; diffuse into alveoli • Bronchial airways are coated with mucus that traps particles • Trapped particles are cleared by ciliary action Bronchiole (1mm diameter) Terminal bronchiole Respiratory bronchiole Gaseous Arsenic (AsH3) • Diffuse into alveoli • Some direct toxicity to alveolar cells Alveolar sack (termination of alveolar duct) Alveolar duct

10. The Primary Cytotoxic Target in Acute AsH3 Poisoning: The Red Blood Cell HEMOGLOBIN MOLECULE Chemistry of RBC lysis (cell rupture): • The first target of AsH3 is the RBC. • One site of reaction in the RBC is hemoglobin. • Heme reacts with As species, and it is oxidized from oxyhemoglobin to methemoglobin. • This reduces the O2 carrying capacity of RBC. • Reactions at other sites also result in protein denaturation (e.g. globin) and formation of insoluble precipates called Heinz bodies. • These events lead to rupture of the RBC. Other possible contributions to RBC rupture: • Production of H2O2 and other reactive oxygen species when AsH3 undergoes redox chemistry. • Inhibition of RBC enzymes such as catalase and Na+/K+_ ATP ase. Globin Heme C Red Blood Cell (RBC) consists of millions of hemoglobin molecules, and each hemoglobin is made up of protein called globin, and 4 hemes which carry oxygen.

11. The Most Common Cause for Fatalities in AsH3 Poisoning: Kidney Toxicity glomerulus distal tubule F D G E proximal tubule loop of Henle collecting duct • Renal failure is cause of death at acute exposures of AsH3 and Asin • Direct toxicity of AsH3 to proximal/distal tubule cells • Direct toxicity of AsH3 to glomerulus at high concentration • Indirect toxicity of hemoglobin, Fe to nephron cells • Renal failure induces loss of plasma contents (albumin, glucose, etc.) and electrolyte imbalance

12. Life Cycle of Arsenic Species Outside the Fab Arsenic species in dry scrubbers Waste Handling Company, e.g., Laidlaw in New England • Solid Scrubbers are stabilized in Portland cement. • No leaking of more than 5ppm. • Buried in a land fill (e.g., Model City, N.Y.) Arsenic waste generated by U.S. semiconductor manufacturing: • Laidlaw estimates the amount of As waste in solution generated by New England semiconductor industry is about 275 gallons per month, and it contains less than 5 ppm arsenic waste. Arsenic waste accounts for 1 % of their total chemical waste handling. • Each Novapure solid scrubber may contain up to 4.6 kg of arsenic solid waste. • Wet scrubbers contain permanganate (KMnO4). • Treated in Canadian facility where KMnO4 is • neutralized. • Converted to solid waste to deposit in land fill. Arsenic species in wet scrubbers Arsenic species in slurry • Solution waste is treated in a Dupont Waste • Treatment Plant. Arsenic species in pump oil

13. Chronic Exposure Possible chronic arsenic species exposure routes in ion implantation • Arsenic species such as As2O3 from cleaning and waste handling. • Handling solid As0 source. Toxicity • Chronic exposure to toxic level of inorganic arsenic can have a cumulative damaging effect. • Inorganic arsenic is classified as a human skin and lung carcinogen. • Chronic loss of RBC can lead to anemia. • Increased risk of diabetes and cardiovascular disease. • Peripheral and central nervous system toxicity. • Several studies reported that fab workers do not have increased levels of As in hair, urine, and blood samples.

14. Safety Measures Normal operation • Workers wear smocks and gloves to prevent skin contact with arsenic species (solid and dust). Changing AsH3 gas cylinders • Workers wear self-contained respirators. • The production floor is cleared. Cleaning the ion implanters • Workers clean the chambers and walls with vacuums that contain high efficiency particulate air (HEPA) filters. • Workers wear HEPA filter masks during operation. Trapping and retaining As species (The chemistry slide shows the reactions of these safety devices.) • Burn boxes (AsH3 gas is oxidized to As2O3.) • Dry scrubbers (AsH3 is physically adsorbed onto high surface area catalyst.) • Wet scrubbers (AsH3 reacts with KMnO4 to form As2O3 and As2O5.)

16. PUBLIC HEALTH AND SAFETY Legislative Branch Mandates regulation of food, air, water, and workplace exposure Administrative Branch Implements mandates of congress through different departments -Toxic Substances Control Act -Food, Drug, and Cosmetics Act -Insecticide, Fungicide, Rodenticide Act -Resource Conservation and Recovery Act -Safe Drinking Water Act -Clean Air Act -Consumer Product Safety Act -Comprehensive Environmental Response, Compensation and Liability Act (Superfund)

17. • Department of Health and Human Services - Food and Drug Administration (FDA) Force of law! Sets, regulates and enforces quality of foodstuffs and drugs - Center for Disease Control (CDC) • National Institute for Occupational Safety and Health (NIOSH) Advisory authority only! Research safe workplace practices • Department of Labor - Occupational Health & Safety Administration (OSHA) Force of law! Sets, regulates and enforces workplace exposure limits • Independent Agencies - Environmental Protection Agency (EPA) Force of law! Sets, regulates and enforces waste disposal, Sets U.S. drinking water standards • Independent Scientific Organizations -American Congress of Government Industrial Hygienists (ACGIH) Advisory authority only! Recommends safe workplace exposure limits

18. Regulation of Hazardous Chemicals • Available scientific data is collected • Data is studied by OSHA, NIOSH, EPA, and ACGIH to determine dose-response relationship • Available data is ranked in order of human relevance - Large scale human chronic exposure data - Acute human exposure data - Large scale, long-term, multi-species animal data - Long-term, single species animal data - Acute animal exposure data • Dose information is determined - NOAEL: No Observable Adverse Effects Level - LOEL: Limit of Observable Effects Level (commonly a 10% increase in liver weight) • Dose is then extrapolated and modified for human exposure - Safety factors are introduced for threshold chemicals - Mathematical models are used for non-threshold chemicals

19. REGULATION OF ARSENICAL COMPOUNDS Arsine • 750 documented human exposures • Multi-species (rodent), acute and chronic exposure data available - NOAEL: 0.025 ppm (90 day, 6 hr/day, 5 day/week exposure) - LOEL: 0.5 ppm (RBC lysis and turnover seen) • Scaling factors (used by ACGIH for review of TLV) - Interspecies variability: 3x - Susceptible human populations: 10x - Subchronic exposure data: 10x • Permissible Exposure Level (PEL) set by OSHA: 50 ppb (0.15 mg/m3) • Recommended ExposureLevel (REL) advised by NIOSH: 50 ppb (0.15 mg/m3) • Recommended Threshold Limit Value (TLV) advised by ACGIH: 50 ppb (0.15 mg/m3) • Exposures set as Time Weighted Average (TWA) over an 8 hour workday Ingested Inorganic Arsenic • Extensive human epidemiological studies • Animal experiments are inconclusive and poor models • U.S. EPA regulates drinking water and hazardous waste disposal • Drinking water limit set at 50 mg/L in the U.S. • Majority of U.S. drinking water <5 mg arsenic/L Some areas (AZ) have ~50 mg arsenic/L Airborne Inorganic Arsenic • Proven human lung carcinogen • Extensive human epidemiological data, few animal experiments • Permissible exposure level (PEL) set by OSHA: 15 ppb (0.05 mg/m3) • Recommended exposure level (REL) advised by NIOSH and ACGIH: 3 ppb (0.01 mg/m3)

21. Example of Incorporating ESH into CoO SDS vs. high pressure gaseous AsH3 Regular AsH3 F=fixed costs; P= operation costs; T=throughput, Y=yield, U=utilization SDS estimate • Fixed costs (increase) • Equal to F + the cost of delivery system hardware and software + some other components • Operation costs (similar) • Function of total time of workers , cost of materials, e.g., wafers, cost of arsine, electricity, etc. • Reduction in loss of workers time in changing AsH3 because the lifetime of SDS increased approximately by a factor of 2. • Cost of AsH3 per atom in SDS is 2 to 3 times higher then high pressure tank. • Other functions of operation costs remain unchanged. • Utilization (increase) • More utilization of ion implanters as well as other machines because less time is spent on changing the AsH3 cylinder. • Throughput and yield are estimated to be the same as regular AsH3 Environmentally benign SDS may not impose a significant cost increased as compare to conventional AsH3 sources.

22. Conclusion Strategy for incorporating toxicology into semiconductor manufacturing process design: 1. Investigate a specific chemical in a specific process. 2. Identify routes of exposure. 3. Study the toxicity of that compound and its waste products. 4. Examine the current safety measures and waste handling methods. 5. Recognize alternative environmentally benign processes and resources. 6. Employ CoO to estimate the difference in costs between the conventional technology and environmentally benign technology.