Introduction to Hazard Identification, Evaluation and Control

1. Introduction to Hazard Identification, Evaluation and Control EH202 April 1, 2009

2. Overview • Hazard Identification What are the health effects this agent can cause? 2. Exposure Assessment What exposures are currently experienced or anticipated under different conditions? 3. Dose-Response Relationship What is the relationship between dose and occurrence of health effects in humans? 4. Risk Characterization What is the estimated occurrence of the adverse effect in a given population? 5. Risk Management Is the risk acceptable and if not what will you do to control or reduce the risk?

3. Conceptual ModelExposure - Disease Continuum Contaminated Environment (potential exposure) Biological Uptake (exposure) Biologically Effective Dose Target Organ Contact Biologic Change Absorption Distribution Metabolism Excretion Clinical Disease Repair and physiologic adaptation Threshold

4. 1. Hazard identification

5. Combustible Explosive Toxic Corrosive Biological Mechanical Chemical Non-ionizing radiation Ionizing radiation Physical Noise Psychosocial What is a hazard? It is an agent capable of causing an adverse effect

6. What is hazard identification? • Examines the evidence that associates exposure to an agent with its toxicity or potential to cause harm • Collection of data • Various sources • Toxicological and epidemiological studies • Information should answer these questions • Does exposure to the substance produce any adverse effects? • If yes, what are the circumstances associated with the exposure? • Produces a qualitative judgment about the strength of that evidence

7. Process 1. Gather information on the hazard • Toxicity • Concentration • Potential routes of exposure • Acceptable exposure levels

8. Example1. Hazard identification

9. Hazard ID and description What form of mercury? Can the exposure lead to a dose? What are the adverse health effects of the dose? Is there vulnerable sub-populations?

10. What form of mercury?Metallic (Hg0), Inorganic (Hg+1 or +2), Methylmercury (CH3Hg), Dimethylmercury (CH3HgCH3) • Agency for Toxic Substances and Disease Registry • Formally organized in 1985 • Created by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) commonly known as the Superfund law • Lead federal public health agency responsible for determining human health effects associated with toxic exposures • http://www.atsdr.cdc.gov/ • ToxFacts • Highlights • What is mercury? • What happens to mercury when it enters the environment? • How might I be exposed to mercury? • How can mercury affect my health? • How likely is mercury to cause cancer? • How does mercury affect children? • How can families reduce the risk of exposure to mercury? • Is there a medical test to show whether I've been exposed to mercury? • Has the federal government made recommendations to protect human health? • References • Contact Information

11. Elemental: Hg0 • Found in thermometers, barometers, batteries, electrical switches, fluorescent lights, dental fillings, herbal and religious remedies • Not readily absorbed by touch or through the digestive tract • Vaporize at room temperatures • Inhalation of these vapors can be harmful to your health (neurotoxic) • Occupational Standard • 0.05 mg/m3 of metallic mercury vapor for 8-hour shifts and 40-hour work weeks • Minimal Risk Level • Inh. Chr. 0.0002 mg/m3 • Safety factor of 30 • Can you test for Hg0 • Blood or urine

12. Inorganic Mercury Hg1+, Hg2+ • Found in fungicides, antiseptics, skin lightening creams, laxatives, de-worming medicines, and teething powders • MERCURIC CHLORIDE • Oral exposure • Acute 0.007 mg/kg/day • Safety factor of 100 • Intermediate • 0.002 mg/kg/day 100 • Renal health effects 

13. Methylmercury CH3Hg • Two mass poisoning episodes • Basara, Iraq • Minimata Bay, Japan • Paresthesia, severe ataxia, tremor, constriction of visual fields • Cortical and cerebellar atrophy are found at autopsy • Threshold for neurotoxicity in adults: 50-200ug Hg/L in blood, 12-50 ppm in hair

14. Photo by W. Eugene Smith

15. Dimethyl mercury • August of 1996 • Spilled a few drops of dimethyl mercury onto her latex glove • December 1996 • Noticed curious health problems • impaired coordination • Nausea • weight loss • slurred speech • Mercury in her blood was 80 times the threshold of toxicity • Underwent intense chelation therapy • February, 1997 • She fell into a coma • June 1997 • Dr. Karen Wetterhahn died

16. Components of a Hazard Identification • Name of Substance • Physical/Chemical properties of substance • Source of the toxicity information • Epidemiological Studies • Toxicological Studies • Exposure to toxic substances • Route • Duration • Frequency • Other Factors which may affect results • Diet • Lifestyle choices • Occupation What is your qualitative judgment of hazards in tuna?

17. 2. Exposure assessment

18. Exposure Assessment • Identifies opportunities for contact between a human a specific hazard • Identifies affected population • Calculates the amount, frequency, length of time, and route of exposure • The dose and route of exposure depends on • Physical/chemical properties • How it is transported • How it is accumulated in the environment and in tissue • How it is transformed when it is released

19. Exposure Pathways New York Department of Environmental Conservation http://www.dec.ny.gov/images/air_images/mercury.gif

20. Exposure vs Dose • Exposure – refers to the concentration of an agent at the boundary between individual and environment • Dose – the amount of the agent that enters a target in a specified time duration Inhalation AN INTERNAL DOSE AIR Exposure Dermal Dose WATER Intensity Frequency Duration Bioavailability Genetics Susceptibility SOIL Ingestion Environmental Factor

21. Dermal Absorption • Broken or irritated skin increases uptake • Skin thickness • Permeability is dependent upon a toxicant’s molecular size, shape, solubility, ionization (charge) and lipid solubility • Solvents easily absorbed across skin Fitzpatrick Color Atlas McGraw-Hill Companies, 2005

22. Ingestion • Many compounds readily absorbed by GI tract • Carried to the liver where it may undergo metabolism • Can increase toxicity or decrease toxicity of the chemical • Enter venous circulation where it is distributed throughout the body • Depending on the chemical compound • Half-life of chemical is the amount of time it takes for half of the dose to be cleared from the body (or tissue) • Arsenic has ½ life in blood of 3 hrs but ½ life in urine of 3 days • DDT has a ½ life in body of 4+ years

23. Asymptomatic man with elevated Hg blood levels due to daily tuna 54 year old male ate can tuna daily for 5 years Blood Hg = 52ug/LUrine=non-detected Stopped eating tuna Hg decline with t ½~ 80d After 7months blood Hg= 7ug/L

24. Inhalation • Most common route for workplace exposures • ~ 6000 liters of air exchange per day for an adult • Size of the particle important determinant of absorption • Some particles stimulate macrophage inflammatory response From: Sullivan JB, Krieger GR. Clinical Environmental Health and Toxic Exposures, pg. 206

25. Particulate Matter

26. Methods for Exposure Assessment • Indirect Monitoring • Questionnaires – categorically group exposure • Collect data on lifestyle factors, frequency, duration, occupational history • Strengths: Inexpensive and good for historical exposures • Limitations: Subject to recall bias and difficult to verify • Other indirect methods • GIS (Geographical Information Systems) • Fate and transport models • Videotaping

27. Methods for Exposure Assessment • Environmental & Personal Monitoring • Air sampler, duplicate diet, etc. – quantify exposure for large populations and/or individuals • Measurement of a chemical agent or its transformation product in an environmental medium • Strengths: Track movement of pollutants from sources and can evaluate ambient and microenvironments • Limitations: More expensive and doesn’t reflect biological dose

28. Methods for Exposure Assessment • Biomonitoring • Hair, Urine, Blood, Meconium etc.- quantify individual dose • Measurement of a chemical agent or metabolic product within human tissues • Strength: Proof exposure has occurred and takes into consideration physiological processes • Limitation: Expensive and relationship with exposure uncertain

29. Common Problems in Exposure Assessment • Absence of actual data • Lack of personal monitoring • Inaccurate methods • Lack of documentation indicating exposure amount and dose • Lack of published research • Inconsistent data related to exposure and health • Limited use of epidemiological methods • Difficulty in reconstructing historical exposures

30. 3. Dose response

31. Hazard Evaluation orDose-Response Assessment • Determine what dose causes a response • Utilized toxicological data or epidemiological data • Extrapolating from high to low dose • Consider ‘safety factors’ NOAEL = no observed effect level LOAEL = lowest observed effect level Reference Dose = NOAEL Safety Factor

32. Methyl mercury dose responseData from Iraq Adults Offspring Marsh et al., 1987 Bakir et al., 1973

33. Maternal Hair ug/g Geometric mean 4.22 Range 2.55–7.68 Murata et al. 2004

34. Where Do We Set The Limits? • To prevent sub-clinical effects? • To prevent irritant or discomfort effects? • To prevent more serious manifestations of organ illness, even if reversible? • To prevent occurrence of only effects that are not reversible? • To prevent acute effects? • To prevent future effects? • To protect the most vulnerable in the population, like children or the developing fetus?

35. 4. Risk assessment

36. Back to tuna … Is this exposure or dose? Data from FDA

37. NEJM 2002; 347:1735

38. Intake Rate US EPA Exposure Factors Handbook http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12464

39. What is average mercury dose? • One approach… use average fish intake 0.17 ug/gram *3.491 gram/day = 0.6 ug/day Divide by BW (60 kg- average woman) 0.01 ug/kg-day • WHO PTWI of 1.6 µg/kg bw (0.2 ug/kg-day) • EPA RfD (equivalent to ADI) is 0.1 ug/kg-day • What are the strengths/limitations of this approach?

40. Hg Regulations over time

41. Maximize public health Philippe Grandjean

42. Control hazards

43. Hierarch of Controls • Eliminating risk • Substitution • Engineering controls • Administrative controls • Personal Protective Equipment

45. COMPARISON OFPROTECTION OFFERED BY VARIOUS PROTECTIVE CLOTHING ASSEMBLIES Subject SW Conditions: Globe Temperature 190-200ºC Clothing Assembly Exposure Time Reason for Leaving Max. Pulse Rate 1. Standard Task Gear 1 min. 45 secs. Skin pain 114 ppm 2. Standard Task Gear 7 mins. 30 secs. Foot discomfort 165 ppm and Helmut 3. Aluminized Outer 13 mins Equipment 165 ppm Gear and Helmet 4. Aluminized Outer Gear, 20mins. _ 115 - 120 ppm Helmet and Water- cooled Undergarment

46. Haddon’s Matrix • Pre-event phase • Factors that determine whether an accident occurs • Event phase • Factors in an accident that lead to injury • Post-event phase • Everything that determines the consequences of the injuries received

47. Haddon’s Matrix Goal is to reduce the likelihood of the event Reduce the severity of the transfer of energy Reduce the disability due to the injuries

48. Examples of occupational hazards

49. How do we evaluate the workplace environment? The risk management process involves: • identifying work environment hazards; • assessing the risk of injury/illness from these hazards; • implementing appropriate control measures to prevent or minimise the risks; • checking that the control strategies are effectively controlling the risks. To identify environmental hazards in your workplace, you can: • consult with colleagues and supervisors about possible hazards; • walk through the work site and record any hazards; • analyse workplace incident, accident, injury and illness data; • consult with specialist practitioners, industry associations, unions and government bodies. In assessing the risks associated with the work environment, the following two factors should be considered: • the likelihood of an incident, accident, injury or illness occurring because of the risk — a very high likelihood indicates controls may be necessary; • the severity of the consequences if an incident, accident, injury or illness occurred because of the risk — if there were many fatalities, this would constitute extremely severe consequences. If a hazard is determined to be a risk (based on likelihood of occurrence and severity of consequences), it is advisable to provide time, money and personnel resources to help prevent or minimise the risks.