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PDC 809: Risk Assessment Boot Camp – Environmental and Occupational Health Applications

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AIHA must ensure balance, independence, objectivity, and scientific rigor in its individual and co-sponsored educational events. Instructors are expected to disclose any significant financial interests or other relationships with:

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Since standards and codes vary from one place to another, consult with your local Occupational or Environmental Health and Safety professional to determine the current state of the art before applying what you learn from this course.

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PDC 809

Risk Assessment Boot Camp – Environmental and Occupational Health Applications Intermediate | Competent, Experienced, Expert Thursday, May 24 | 8:00 AM – 5:00 PM Credits: 7 CM Credit Hours Topics

Emerging Issues, Exposure Banding/Occupational Exposure Limits, Risk Assessment and Management Description IH professionals have to be aware of the most up-to-date risk assessment methods and techniques. This PDC will take participants for an intensive ride! We will begin by reviewing the basics and methodology of risk assessment related to typical hazards industrial hygienists face. Structural components of the risk assessment paradigm (hazard identification, exposure assessment, dose-response assessment, and risk characterization) will be reviewed from a practical point of view. The methodology of risk characterization will be discussed, and risk calculation tools will be provided, along with practical exercises proposed to test the models in real-life applications. Participants will learn how to apply risk calculation methods and models to evaluate probabilities of disease in exposed cohorts and populations. Prerequisites Laptop computer with Excel spreadsheet software. Value Added Participants will receive Excel spreadsheets for health risk calculations. Outcomes Upon completion, participants will be able to:

Perform occupational and environmental health risk assessments. Define major metrics of risk assessment. Use Excel spreadsheets for risk calculations. Calculate internal occupational standards based on risk assessments. Evaluate existing occupational exposure limits (OELs). Apply four steps of risk assessment in IH practice. Utilize statistical methods in risk assessment procedure. Recognize uncertainties and limitations in risk assessments. Distinguish between acceptable and unacceptable risk levels.

Outline

Risk Assessment and its Role in IH practice National Research Council (NRC) Paradigm of Risk Assessment

Risk Assessment Methodology, Metrics and Tools Four Steps of a Risk Assessment Procedure Risk-based Occupational Exposure limit (OEL) Derivation Class Discussion

Transfer of Knowledge Instructors will evaluate participants’ understanding of the materials presented based on:

Group activities Hands-on demonstrations and practicum

Instructors Andrey Korchevskiy, PhD, DABT, CIH, Chemistry & Industrial Hygiene, Inc., Wheat Ridge, CO. Eric Rasmuson, MS, CIH, Chemistry & Industrial Hygiene, Inc., Wheat Ridge, CO. Robert Strode, MS, CIH, FAIHA, Chemistry & Industrial Hygiene, Inc., Wheat Ridge, CO.

© American Industrial Hygiene Association 3141 Fairview Park Drive, Suite 777, Falls Church, VA 22042 ● phone +1 703-849-8888 ● fax +1 703-207-3561

Risk Assessment Boot Camp -Environmental and

Occupational Health Applications

• President of Chemistry & Industrial Hygiene, Inc.•Diplomate of American Board of Toxicology

(DABT)• Certified Industrial Hygienist (CIH) • Certified Risk Assessor – Bloomberg, Johns

Hopkins School of Public Health, Summer 2016•Multiple published works, presentations,

and classes in exposure and risk assessment, industrial hygiene, retrospective exposure assessment, simulation testing, regulatory compliance, and quality assurance

Eric Rasmuson

AIHce EXP 2018 PDC 809

Page 1

Robert Strode

• Technical Director of Industrial Hygiene Services at Chemistry & Industrial Hygiene, Inc.

• Certified Industrial Hygienist (CIH)• Master of Science in microbiology• Authored and/or provided publications and

presentations in the fields of chemistry, industrial hygiene, exposure assessment, and microbiology

• 2009 AIHA Fellow Award winner

•Director of Research and Development at Chemistry & Industrial Hygiene, Inc.•Diplomate of American Board of Toxicology

(DABT)• Certified Industrial Hygienist (CIH)•Distinguished lecturer of AIHA• PhD in applied mathematics and biology• Former advisory expert and vice-chairman

of the Environmental Action Plan for Eastern Europe, Caucasus and Central Asia (OECD, Paris)• Chairman of the International Task Force for

Children’s Environmental Health • Chairman of the AIHA Standards Advisory

Panel (SAP)

Dr. Andrey Korchevskiy


Page 2

Learning Outcomes

• Perform occupational and environmental health risk assessments.

• Define major metrics of risk assessment.• Use Excel spreadsheets for risk calculations.• Calculate internal occupational standards based on risk

assessments.• Evaluate existing occupational exposure limits (OELs).• Apply four steps of risk assessment in IH practice.• Utilize statistical methods in risk assessment procedure.• Recognize uncertainties and limitations in risk assessments.• Distinguish between acceptable and unacceptable risk levels.

AgendaTopic Teacher TimeCourse introduction. Introduction of the teaching crew. Course outline, learning outcomes.

Andrey Korchevskiy 8:00 – 8:15

General Principles of Risk Assessment. Eric Rasmuson 8:15 – 10:00

COFFEE BREAK 10:00 -10:30

Occupational Health Risk Assessment Case Study: Heavy Metals on the Surfaces.

Rob Strode 10:30 – 12:00

LUNCH BREAK 12:00 – 1:00

Occupational Health Risk Assessment Case Study (continued). Rob Strode 1:00 – 1:30

Environmental Health Risk Assessment Case Study: Naturally Occurring Asbestos (NOA) and Erionite.

Andrey Korchevskiy 1:30 – 3:00

COFFEE BREAK 3:00 – 3:30

Environmental Health Risk Assessment Case Study (continued) Andrey Korchevskiy 3:30 – 4:00

Discussion and questions Eric Rasmuson 4:00 – 4:45

Review of the learning outcomes Andrey Korchevskiy 4:45 – 5:00

THE CLASS AGENDA


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Risk AssessmentGeneral principles

Eric Rasmuson, MS, DABT, CIH

Various Definitions of Risk1. Probability or possibility that harm will occur (Kemshall,

Pritchard, 1997).2. Combination of the likelihood of occurrence of a work-

related hazardous event or exposure(s) and the severity of injury and ill health that can be caused by the event or exposures (ISO 45001).

3. The likelihood that the potential for harm will be attained under the condition of use and/or exposure, and the possible extent of the harm (European Commission, 1996).

4. The chance of harmful effects to human health or to ecological systems resulting from exposure to an environmental stressor (EPA).


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Risk

Risk is the probability of an adverse outcome based on the exposure and potency of the hazardous agents.

Risk is measured as a fraction of 1 (or recalculated to

cases per population, like, per

1,000,000 ), ,

Casarett & Doull's Toxicology: The Basic Science of Poisons, 8th Edition

Risk Assessment

Risk Assessment is the systematic scientific evaluation of potential adverse health effects resulting from human exposures to hazardous agents or situations.

NRC, 1983


Page 5

Why we use risk assessment in industrial hygiene and toxicology?

• It is a well-developed and structured procedure of analysis • It allows predicting health effects of toxicants in certain

circumstances• Risk assessment is a more useful instrument than just comparison

of exposures with “safe levels” Often, there are no defined “safe levels”Exposure limits are not established for the majority of toxic substancesEstablished exposure limits are not strictly health-basedIn the ideal, exposure limits should be risk-based

• Risk assessment can factor uncertainty into consideration • We can compare risks across various types of hazards etc.

Scientific Care Daubert Standard: Essential for Risk Assessment!

“Standard used by a trial judge to make a preliminary assessment of whether an expert’s scientific testimony is based on reasoning or methodology that is scientifically valid and can properly be applied to the facts at issue.”

(1) whether the theory or technique in question can be and has been tested; (2) whether it has been subjected to peer review and publication; (3) its known or potential error rate; (4) the existence and maintenance of standards controlling its operation; and (5) whether it has attracted widespread acceptance within a relevant scientific community.

See Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993).

https://www.law.cornell.edu/wex/daubert_standard


Page 6

NRC (NAS) Paradigm on Risk Assessment (2009)

NAS Risk Assessment Methodology: Use Four Steps!

I. Hazard IdentificationII. Exposure assessmentIII.Dose-Response AssessmentIV.Risk Characterization


Page 7

National Academy of Sciences, 2009, Paradigm

What is the compound?

Where does it come from?

What are the target health effects?

Hazard Identification in Toxicology

In order to assess the toxicity of chemicals, information from four types of studies is used:1. structure-activity relationships (SAR)2. in-vitro or short-term studies3. in vivo animal bioassays4. epidemiology

Casarett & Doull's Toxicology: The Basic Science of Poisons, 8th Edition


Page 8

Advice for Hazard Identification

• Define the compound of interest

• Take notes about chemical and physical characteristics

• Search ToxNet and IRIS online databases

• Select important health effects from literature

• Check for causality criteria (Bradford Hill!)

• Try to identify “mode of action”

What is important? Bradford Hill Criteria

Bradford Hill Criteria for Causality

1) The strength of the association2) The consistency of findings across studies3) Specificity (uniqueness in quality or

quantity)4) The temporal sequence5) Dose-Responsiveness6) Biological Plausibility7) Coherence: logical and consistent


Page 9

What is important? Mode of ActionThe term “mode of action” is defined as a sequence of key events and processes, starting with interaction of an agent with a cell, proceeding through operational and anatomical changes, and resulting in cancer formation. A “key event” is an empirically observable precursor step that is itself a necessary element of the mode of action or is a biologically based marker for such an element…

In the absence of sufficiently, scientifically justifiable mode of action information, EPA generally takes public health protective, default positions regarding the interpretation of toxicologic and epidemiologic data:

animal tumor findings are judged to be relevant to humans, and cancer risks are assumed to conform with low dose linearity.

U.S. EPA, 2005

National Academy of Sciences2009


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Exposure» Concentration of substance in air, water, soil, or food that

contacts the human body

Cumulative Exposure» Average exposure per unit time X duration» Approximately proportional to cumulative dose

Some Important Concepts and Definitions

Frequency: How often is a task performed during a shift?

Duration: How much time does the task take when performed?

Proximity: Exposure resulting from primary work activities or other?

Intensity: What is the exposure level during the activity?

Core Elements of Workplace Exposure Assessment


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Guidelines for its use in exposure assessment published by USEPA

Available as an add-on to an Excel Spreadsheet

» Crystal Ball» Monte Carlo programs can be written

from software in SAS and other statistical programs

We can use Monte Carlo simulation (MCS) in Risk Assessment

National Academy of SciencesDose Response, 2009


Page 12

Typical (“Stylized”) Cumulative Exposure-Response Curve

Constant Exposure Intensity (f/cc)

Canc

er ri

sk (e

xces

s cas

es p

er 1

,000

,000

)

Threshold (?)

B

C

D

E

α

β

γ

A

δ

Data points:

A – lowest level of biologically (epidemiologically)observes exposureB – highest non-statistically significant response point (NOAEL)C – lowest observed adverse response level (LOAEL)D, E – other significant response levels

Models extrapolating data to low exposure levels:

α – supralinearβ – linearγ - sublinearδ - threshold

Metrics of Risk

• Absolute risk increase• Relative risk• Attributable risk fraction• Ratio of concentration to RfC or

RfD• Other


Page 13

Absolute Risk Increase: Example

Smith-Bindman, et al. estimate that 1 in 270 women who undergo CT coronary angiography at age 40 years will develop cancer from that scan, compared with 1 in 600 men…

Lin, E. (2010).

[Usually, risks are measured in units of incidence (cases per 1,000,000 (or other power of 10, like 10,000)].

In this case, absolute lifetime risk increase (or predicted incidence) for women is 3,703 per 1,000,000.]

Absolute Risk Increase: Example (continues)

“Another useful way to express radiation risk is to compare it to common activities of daily life. For example, radiation doses from 0.1 to 1.0 mSv carry an additional risk of death from cancer comparable to the risk of death associated with a flight of 4500 miles, whereas doses in the range of 1 to 10 mSv have a higher risk, comparable to driving 2000 miles.”


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Why we should be careful comparing risks…

It is very useful to have comparable risk metrics (like, cases per 1,000,0000).

For example, it is possible to compare toxicants by their risk levels.

However, risks of toxic substances are often “involuntary” vs. “voluntary” risks from flying or driving (limitation for comparison!).

Linear Model

Increased Risk = Average Lifetime Daily Dose (mg/kg/day) X Slope Factor (mg/kg/day)-1

» Slope factor typically calibrated in units of cases per million per year or cases per million per lifetime (usual), etc.

» USEPA typically utilizes the upper bound 95% confidence limit when animal data is the basis, but sometimes utilizes the best estimate based on human epidemiology

Generally used for the low-dose portion of the dose-response curve

Same form of equation for dermal, oral, or inhalation uptake of carcinogens

Simple Cancer Slope Factor or Potency Factor (Applied to Most Carcinogens)


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Increased Lifetime Cancer Risk =

Average continuous lifetime exposure (e.g., mg/m3 of air contaminant) X Unit Risk (fractional risk/mg/m3, for example)

Unit Risk: Another Term for Slope Factor, but Usually Applied to Exposure, not Dose!

The upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 μg/m³ in air.

The interpretation of inhalation unit risk would be as follows: if unit risk = 2 × 10⁻⁶ per μg/m³, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 μg of the chemical per m³ of air.

U.S. EPA, IRIS

Inhalation Unit Risk


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For non-carcinogenic effects: comparison with RfC and RfD

For example: Benzene

RfD (oral+dermal) = 4.0 x 10-3 mg/kg/day (decreased lymphocyte count)

RfC (inhalation) = 3.0 x 10-2 mg/m3 (decreased lymphocyte count)

U.S. EPA IRIS, “Benzene”

Estimation of risks: ratio of actual uptake to RfD or concentration to RfC.

RfC (reference concentration). An estimate (with uncertainty spanning perhaps an order of magnitude or higher) of a chronic inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of non-cancerous deleterious effects during a lifetime.

RfD (reference dose). An estimate (with uncertainty spanning perhaps an order of magnitude or higher) of a chronic daily uptake to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of non-cancerousdeleterious effects during a lifetime.

Hazard Quotient

Hazard quotient (HQ): ratio of the potential exposure and the level at which no adverse effects are expected.

For example, ratio of a concentration a RfC

Or, ratio of a daily intake and RfD.


Page 17

Relative Risk

The relative risk (RR) of the event is the likelihood of its occurrence after exposure as compared with the likelihood of its occurrence in a control or reference group.

Relative Risk =

Relative Risk: Example

Methods: We conducted meta-analyses of studies examining the relationship of exposure to PM2.5 and PM10 with lung cancer incidence and mortality. In total, 18 studies met our inclusion criteria and provided the information necessary to estimate the change in lung cancer risk per 10 μg/m3 increase in exposure to PM. We used random-effects analysis to allow between-study variability to contribute to meta-estimates.Results: Relative risk for lung cancer with PM2.5 1.09 (95% CI: 1.04, 1.14). Relative risk of lung cancer with PM10 1.08 (95% CI: 1.00, 1.17).

Relative risk of adenocarcinoma:PM2.5 1.40 (95% CI: 1.07, 1.83) PM10 1.29 (95% CI: 1.02, 1.63) (Hamra et al, 2014)


Page 18

Rule of Thumb for Relative Risk

If confidence interval for relative risk includes 1, the risk elevation is not statistically significant.

Attributable Risk Fraction

The fraction of disease in a population that will be removed if the exposure is eliminated:

ARF =

(for example, for RR=2, ARF=50 %).


Page 19

National Academy of Sciences, 2009

How low is low?


Page 20

Acceptable Risk in the Workplace (OSHA)

In the Benzene Decision, the Supreme Court stated:

“…if the odds are one in a thousand that regular inhalation of gasoline vapors that are 2% benzene will be fatal, a reasonable person might well consider the risk significant and take the appropriate steps to decrease or eliminate it.”

56 FR 64004, Dec. 6, 1991; 57 FR 29206, July 1, 1992

Negligible Risk In Radiation Protection

Negligible individual dose corresponds to cancer mortality of 0.03 cases per 1,000 (30 cases per 1,000,000)

NCRP (1993). National Council on Radiation Protection and Measurements. Limitation of Exposure to Ionizing Radiation, NCRP Report No. 116 (National Council on Radiation Protection and Measurements, Bethesda, Maryland).

Data from ICRP (1991). International Commission on Radiological Protection. 1990Recommendations of the International Commission on Radiological Protection,ICRP Publication 60, Annals of the ICRP 21 (1-3) (Pergamon Press, Elmsford,New York).


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European Union (REACH)

Tolerable lifetime cancer risk levels:

• 1 case per 100,000 for workers

• 1 case per 1,000,000 for general population

Position of Regulators: UKRisk of death per year:

• 1 in 1000 as the ‘just about tolerable risk’ for any substantialcategory of workers for any large part of a working life.• 1 in 10,000 as the ‘maximum tolerable risk’ for members of thepublic from any single non-nuclear plant.• 1 in 100,000 as the ‘maximum tolerable risk’ for members of thepublic from any new nuclear power station.• 1 in 1,000,000 as the level of ‘acceptable risk’ at which no further improvements in safety need to be made.

Health and Safety Executive, U.K.


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Acceptable Environmental Risk (U.S. EPA)

• One-in-a-million lifetime risk: “So small as to be negligible.”

• Between one-in-a million and one-in-ten thousand lifetime risk: “Generally considered to be acceptable.”

http://www.epa.gov/region8/r8risk/hh_risk.html

New Chemical Carcinogen Policy of NIOSH(National Institute of Occupational Safety and Health,

CDC, USA)Main ideas:

NIOSH plans to introduce its own classification of carcinogens;

NIOSH will perform quantitative risk assessment for different chemicals and publish exposure levels for corresponding cancer risks from 1 in 100 to 1 to 1000000;

NIOSH will establish “risk management limit for a carcinogen” (RML-CA) corresponding to the 95% lower confidence limit of the 1 in 10,000 risk estimate.


Page 23

Enhanced risk assessment approach: U.S. EPA guidelines for carcinogen risk assessment (2005)

Major features:

• Critical Analysis of Available Information as the Starting Point for Evaluation

• Mode of Action • Weight of Evidence Narrative • Dose-response Assessment • Susceptible Populations and Lifestages• Evaluating Risks from Childhood

Exposures • Emphasis on Characterization

Individual vs. Population Risk Assessment: Differences and Synergism

Questions for individual risk assessment

• Are individuals at [excess] risk from exposure to the substances under study?

• To what risk levels are the persons at the highest risk subjected? Who are these people, what are they doing, where do they live, etc., and what might be putting them at this higher risk?

• Can people with a high degree of susceptibility be identified?

• What is the average individual risk?

Questions for population risk assessment

• How many cases of a particular health effect might be probabilistically estimated for a population of interest during a specified time period?

• For noncarcinogens, what portion of the population exceeds the reference dose (RfD), the reference concentration (RfC), or other health concern level?

• For carcinogens, how many persons are above a certain risk level such as 10-6 or a series of risk levels such as 10-5, 10-4, etc? How do various subgroups fall within the distributions of exposure, dose, and risk? What is the risk for a particular population segment?

• Do any particular subgroups experience a high exposure, dose, or risk?

U.S. EPA, “Guidelines for Exposure Assessment,” EPA/600/Z-92/001 (1992).


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Risk Assessment

Occupational Health Case Study

Rob Strode, MS, CIH, FAIHA

Occupational Health Risk Dermal Exposure Scenario

What we will cover in this session:• An examples of a remedial design and cleanup of a cadmium-

contaminated facility based on Risk Assessment methods• Goal is protection against risks to future workers and other

building occupants assuming a facility change of use• Options for determining an acceptable cleanup level including

OELs, published guidelines, and classic risk assessment procedures

• Emphasize the NAS paradigm and introduce standard US EPA risk assessment methods to calculate risk for various routes of exposure and back calculate a site-specific cleanup standard for cadmium


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Occupational Health Risk Dermal Exposure Scenario

Goals for this session:• Understand why risk assessment (RA) is useful for IH problems• Understand how to use available US EPA and other risk-based

cleanup levels and terminology • Apply the NAS paradigm to surface metal cleanup levels• Gain knowledge of various sources for surface cleanup guidance• Class Excercises:

• Identify source and application of appropriate parameter inputs• Utilize available data to calculate dose and determine risk• Assess difference input variables and their impact

• Compare the RA-based cleanup level to the available OELs and surface cleanup guidance criteria

• Discuss the usefulness and implications of the various RA methods

NAS PARADIGM

Hazard IdentificationExposure assessment

Dose-Response AssessmentRisk Characterization

This paradigm has been adopted by most agencies including OSHA and US EPA


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Our Case Study

What are we trying to do:Assess whether and to what extent facility needs to be decontaminated to allow "safe” use

HARM = Physical injury or damage to healthHAZARD = Potential to harm

RISK = Probability of harmSAFETY = Acceptable risk of harm

Our Case StudySite Background:• Prior manufacturing operations using metallic

deposition for solar collection• Abrupt and unexpected termination of operations• Contingency plan for re-purposing not

implemented• Nature and extent of contamination • Contaminated areas and general levels

o Airo Surfaceo Waste


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Our Case Study

Why use risk assessment (RA) for our problem?• Allows us to consider various outcomes based

on risk estimation • Provides a means to address problems that may

not fit into the IH box• Provides a standardized approach to assessing

exposure problems based on health risk characterization as opposed to other approaches

Our Case Study

Other reasons for performing a risk assessment to determine cleanup levels:

• Lack of regulatory surface standards or specific health-based guidance from OSHA and other regulatory agencies

• Available cleanup guidance may not be appropriate for expected future uses (not site specific)

• Need to consider other types of occupants• Meets regulator requirements for no further action

(NFA)


Page 28

Metals Background Information

Metals of concern:• More common situations include lead,

cadmium, chromium, and other “heavy” metals historically used in manufacturing industries

• Less common situations (but growing) are more exotic metals used in equipment and parts manufacturing such as plating, coatings, thin films and other electronic and electrochemical manufacturing (beryllium, rare earths, arsenicals, etc.)


Concerns associated with metals surface contamination:

• Health risks (our focus)o Current occupantso Future occupants

• Other concerns with metals contamination???


Page 29


OHSA Compliance and other OELs:• Assessment of potential exposures to surface

contamination – how do we assess the following:o Inhalation: aerosolization of settled materialso Oral: Hand to mouth exposure and skin

contacto Dermal: skin contact

We will focus on skin contact routes


OHSA Compliance and other OELs:• No surface standards under OSHA

From the CDC regarding metals toxicity: “OSHA, NIOSH, AIHA, and ACGIH have not recommended criteria for

use in evaluating wipe samples”

• OSHA Technical Manual, Section II, Chapter 2, Part II:“One of the simplest ways of determining this amount is to estimate the amount of a chemical which can be absorbed into the body based upon an air exposure limit.”*

*Assumes 10m3 breathing X PEL (mg/m3) = allowable mg on skin. For liquids uses flux rate and US EPA permeability factors to estimate total dose at a known liquid organic concentration. Unclear whether or how this should be applied to metallic solids.


Page 30


OHSA Compliance and other OELs:• Typical OSHA language for surface dust = “free as

practicable”• Applicable standards with free as practicable

language: Arsenic: 1910.1018(k); Cadmium: 1910.1027(k); Chromium: 1910.1026(j); Lead: 1910.1025(h); Acrylonitrile: 1910.1045(k) DBCP: 1910.1044(k); MDA: 1910.1050(l)

• Sampling is not required by OSHA to verify freedom from surface contamination


Metals Health Risks:• Non-carcinogenic - primarily• Carcinogenic – far fewer

o Arsenico Berylliumo Cadmiumo Chromiumo Nickel


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Metals Background InformationMethods for metals surface sampling:

• Wipe (dust and surface-bound material)ASTM E1728 – designed for leadASTM D6966 – designed for metals in generalASTM E1792 – wipe materials specificationNIOSH 9100 - designed for leadBNL – IH75190 - designed for metals in general

• Vacuum (mostly bulk dust)ASTM D7144 – designed for metals in generalASTM D5438 – floor dust – metals and other

• Others???


Examples of Locations and Situations of Concern in Occupational and Environmental Settings:

• Electronics/Semiconductor industries• Battery manufacturing/recycling• Anti-corrosion/plastic stabilizers• Areas with high historical metals emissions

(e.g., mining operations, smelters)• Cigarettes


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Working Through the Risk Assessment General Process

RA process will follow basic principles of US EPA Risk Assessment Guidelines for Superfund (RAGS)

• Hazard Identification• Exposure assessment• Toxicity/Dose-Response Assessment• Risk Characterization

Working Through the Risk AssessmentHazard Identification





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Identify Potential Contaminant (s) of Concern (US EPA) • Data review and identification of known chemicals at

site• PCOCs = chemical(s) that are potentially site-related

and whose data are of sufficient quality for use in a quantitative risk assessment

• Identification of chemicals at levels that potentially place individuals at risk – Basis???


PCOCs COC? Basis of COC DeterminationArsenic Yes Present in sewer sediment above applicable RSL

Barium No Below applicable RSLs and other ARAR criteria

Cadmium Yes Present above applicable RSL and other ARAR criteria

Chromium No Below Applicable RSLs and other ARAR criteria

Lead Yes Present in sewer sediment above applicable RSL

Mercury No Below applicable RSLs

Nickel No Below applicable RSL and other ARAR criteria

Selenium No Below applicable RSL

Silver No Below applicable RSL

Tellurium Yes Detected in air and wipe samples – no RSLs/ ARARs


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• What do we know about the types of site hazards?o Metals present - cadmium, tellurium, lead, arsenico Other potential hazards - high voltage, fluids and

solids in process and waste lines, etc.• What data do we have regarding nature and extent?• What kinds of hazards do these metals present?

Our focus will be on cadmium due to site characteristics but other metal(s) could be chosen


Cadmium Non-carcinogenic Health Effects/Toxicity• Well known in OEH&S for what disease???• Most important high exposure health effects

Kidney dysfunction (nephrotoxicant)Bone loss/fragility

• Other known/potential non-carcinogenic health effects

Airway diseases (COPD/asthma)Immunosuppression


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Cadmium Carcinogenic Health Effects/Toxicity• Cancers

Lung/other respiratory?Prostate?Testes?

• Bad news: causes cancer(s)• Good news: does not generate reactive oxygen

species (ROS) and DNA damage must be due to indirect effects – however, may reduce antioxidant defenses


Cadmium Health Effects/Toxicity• Health effects influenced exposure route• Not required by body as trace element• “Critical” effect is proteinuria

What route is driver for this???Other possible routes?

• CD present as Cd2+ mimics other 2+ metals • Acts as Trojan horse for Ca2+ and other

divalents (e.g., Fe2+) – bone effects


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National Academy of Sciences, 2009Exposure Assessment

Working Through the Risk AssessmentExposure Assessment

Basis for Determining Acceptable Levels of Potential Concern for Surface Contamination (Screening Level):• Simple calculations based on potential for

aerosolizationconvert units to mg/m2

convert mg/m2 to mg/m3

(mg/m2/height (m) = mg/m3

(problems???)• Historical data (comparison to known priors)• Established guidelines from various agencies• Quantitative risk assessment


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Working Through the Risk Assessment Exposure Assessment

Available Guidelines for Benchmarking Surface Concentrations (Compare to RA output):

• DOE – Brookhaven National Laboratory• U.S. Army CHPPM Technical Guide 312 (offices)• US EPA – WTC cleanup levels (residential/worker)• May, et al., 2009• Others - (SEMI.org)

Links to websites or pdfs for above provided in resource materials

Working Through the Risk Assessment Exposure Assessment

Class exerciseFind Cd cleanup information for each of the following:

• DOE – Brookhaven National Laboratory (surface wipe criteria for Non-Operational Areas: Floors & accessible surfaces)

• U.S. Army CHPPM Technical Guide 312 (surface wipe screening level)

• US EPA - Regional RSLs (soil, composite worker, Carcinogenic SL, TR=1E-06)


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CFD Model Nature and Extent for Surface Samples

= max greater than 300 ug/100 cm2




Summary of Site-specific Nature and Extent:• Spatial differences related to process location and

proximity to coating area• Outside coating area minimum surface wipe Cd

> 3 ug/100cm2, maximum Cd ~80 μg/100cm2

• Inside coating area surface wipe Cd >> 5 ug/100cm2, maximum ~100,000 μg/100cm2

• Air concentrations generally < 2 ug/m3 in coating areas, << 2 ug/m3 outside coating area (<DL) -

• No significant bulk dust outside coating area, coating area bulk dust samples > 150,000 mg/kg


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Class Exercise

Determining a daily dose based on aknown surface concentration

(sum of ingestion and dermal contact)


CALCULATOR VIEW – ADULT WORKER INPUT


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Do = (C x SAh x CFh x FTSH x FTHM x ABSo)/BW Do =Oral dose (mg/kg/day) C = Concentration of chemical on contaminated surface (mg/cm2) SAh =Exposed hand surface area (cm2) CFh =Contact frequency of hand against surface (times/day) FTSH= Fraction transferred from surface to hand FTHM= Fraction transferred from hand to mouth ABSo= Oral absorption fraction BW =Body weight (kilograms)

Equation to determine ingestion exposure based on surface concentration


Dd = (C x SAs x CFs x FTSS x ABSd)/BW Dd =Dermal dose (mg/kg/day) C = Concentration of chemical on contaminated surface (mg/cm2) SAs =Exposed skin surface area (cm2) CFs =Contact frequency of skin against surface (times/day) FTSS= Fraction transferred from surface to skin ABSd= Dermal absorption fraction BW =Body weight (kilograms)

Equation to determine dermal exposure based on surface concentration


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Example Child and Adult Exposure Factors for Calculator Input

Exposure Parameters Abbrev. Units Infant Child Adult SourceAbsorption Fraction, Oral ABSo unitless 0.025 0.025 0.025 USEPA (2013)Body Weight BW kg 11.2 21.7 70.0 CDPHE (2005)Contact Frequency of Hand to Surface CFh times/day 74 52 35 CDPHE (2005)Dermal Absorption Fraction ABSd unitless 0.001 0.001 0.001 USEPA (2013)Events per day CFs event/day 2 2 2 CDPHE (2005)Surface Area - Soil or Bulk Dust Contact SAs cm2 4290 2800 5700 CDPHE (2005)Exposed Hand Surface Area SAh cm2 135 193 410 CDPHE (2005)Fraction Transferring from Surface to Hand FTSH unitless 0.50 0.50 0.50 CDPHE (2005)Fraction Transferring from Hand to Mouth FTHM unitless 0.10 0.10 0.10 CDPHE (2005)Fraction Transferring from Surface to Skin FTSS unitless 0.50 0.50 0.50 CDPHE (2005)Cadmium Reference Dose (Diet) RfD mg/kg-d 1.00E-03 1.00E-03 1.00E-03 USEPA (2013)


CALCULATOR VIEW – ADULT WORKER INPUT


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Child and Adult Dose Output @ 60 ug/100cm2

Dose [DO](mg/kg-d)

Infant Child AdultIngestion 7E-04 3E-04 2E-04Dermal 2E-04 8E-05 5E-05

Exposure PathwayAdult2E-045E-05

National Academy of SciencesDose-Response, 2009


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Working Through the Risk Assessment Dose-Response

US EPA Dose-Response Terms:• Cancer

Expressed as case per million or ratios (e.g., 100 cases per million or 1:10,000 risk)

• Non-CancerExpressed in ratios of dose (actual divided by acceptable)Greater than or less than unity (or 0.1 for conservatism)


Example US EPA Equations Based on Dose-Response:• Cancer risk (cases per million) =

UR * Concentration * 1,000,000(ug/m3, ug/L)

• Non-cancer risk (compared to unity or 0.1) = Ingestion/Dermal HQ = RfD/Oral Dose

(both in mg/kg-day)

Inhalation HQ = RfC/Oral Dose (both in mg/kg-day)

HI = HQ1 + HQ2 + HQX


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Cancer risk:• Human epidemiology studies indicate inhalation

route only cancer route• Human lung cancer

2-fold excess risk of LC in cadmium smelter workers

• Conflicting epi data on prostate cancer risk for workers exposed to cadmium dust or fumes

• Animal cancer data similar to human – LC by inhalation and injection, none by oral


Non-cancer risk:• Human nephrotoxicity

RfD is based on human renal cortex Cd concentration (i.e., the critical level) not associated with significant proteinuria (i.e., the critical effect)200 ug cadmium (Cd)/gm wet human renal cortex is the highest renal level not associated with significant proteinuria (NOAEL)


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Non-cancer risk (cont.):• Toxicokinetic model available to equate to 200

ug cadmium (Cd)/gm wet human renal cortexNOAEL for chronic Cd exposure is 0.005 mg Cd/kg/day (water) and 0.01 mg Cd/kg/day (food)Assuming UF of 10 yields oral RfDs of 5E-4 (water) and 1E-3 (food)

• UF of 10 (low UF) based on large quantity of both human and animal toxicity data are available

National Academy of Sciences, 2009Risk Characterization


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Working Through the Risk Assessment Risk Characterization

Risks we could assess for our case study:• Inhalation of entrained air contaminants

Ingestion of breathed materials generally not assessed (<< inhaled or other ingestion)

• Ingestion, inhalation, and dermal contact with bulk dust

• Dermal contact and ingestion of surface-bound materials (versus bulk dust)

(Note: All risk equations included in calculator)


Surface materials risk focus (spreadsheet allows calculation of other risks) :

• Possible exposure for surface contamination???Dermal?Inhalation?Ingestion?Injection?


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Working Through the Risk Assessment Risk Assessment Terminology

US EPA Exposure Risks:• Non-Cancer Risks

HQ = hazard quotient (unitless)HI = hazard index (sum of HQs for similar toxic effects)RfD = reference dose oral/dermal (mg/kg-day)RfC = reference dose inhalation (mg/kg-day)

Working Through the Risk Assessment Risk Assessment Terminology

US EPA Risk Factors and Units :• Cancer Risks (linear mode of action)

UR = inhalation or drinking water unit risk (ug/m3 or ug/L [from mg/kg-day])OSF = oral slope factor (mg/kg-day)

• Cancer Risks (non-linear mode of action)RfD = reference dose oral (mg/kg-day)RfC = reference dose inhalation (mg/kg-day)


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Standardized Guidance for Risk Screening:• US EPA “Regional SLs” (RSLs)

Based on conservative assumptionsCombined Regional EPA effort to consolidate PRGs, RBCs, and HHMSSL tablesLookup tables by chemical both non-cancer and cancer risksConsiders various scenarios by media (e.g., residential inhalation risk vs commercial)Simple guide to cleanup levels accepted without additional justification


Risks by media and route of entry:

• Surface materials in ug/100cm2 (no aerosol)IngestionDermal

• Bulk dust in mg/kg (including aerosol)IngestionDermalInhalation

• Inhalation (aerosol only)


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Practical example considering surface materials:

• Do we need to assess bulk dust risks???

Bulk dust not prevalentAny bulk dust standard will be met by surface material removal

Pre-established RSLs attainable

• Do we need to assess inhalation risks???

Pre-established RSLs attainable


Class Exercises• Using the calculator 1 – inhalation risk

calculation at various OELs

• Using the calculator 2 – risk calculation from dermal dose estimates

• Using the calculator 3 – back calculation of acceptable clearance (Als) at various surface dust concentrations

• Using the US EPA online RSL calculator for inhalation risk (if time and internet allow)


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Resources and Reference Materials

US EPA Risk Assessment Guidance for Superfund (RAGS): https://www.epa.gov/risk/risk-assessment-guidance-superfund-rags-part

US EPA RAGS Part E (dermal exposures): https://www.epa.gov/risk/risk-assessment-guidance-superfund-rags-part-e#docs

US EPA Human Health Evaluation Manual, Supplemental Guidance: Update of Standard Default Exposure Factors, Feb 6, 2014: https://semspub.epa.gov/work/HQ/190670.pdf

US EPA Guidelines for Carcinogenic Risk Assessment: https://www3.epa.gov/airtoxics/cancer_guidelines_final_3-25-05.pdf

US EPA Dermal Exposure Assessment: A Summary of EPA Approaches, 600/R-07/040F, 2007:https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=183584&keyword=jpg+AND+4&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50&CFID=68458488&CFTOKEN=21602405


US EPA Risk Screening Tables Generic: https://www.epa.gov/risk/regional-screening-levels-rsls-generic-tables

US EPA RSL website: https://www.epa.gov/risk/regional-screening-levels-rsls-users-guide-november-2017

US EPA RSL calculator: https://epa-prgs.ornl.gov/cgi-bin/chemicals/csl_search

US EPA vapor intrusion SL (VISL) calculator: https://epa-visl.ornl.gov/cgi-bin/visl_search

US EPA Glossary: https://www.epa.gov/national-air-toxics-assessment/nata-glossary-terms#hi

US EPA ARARs Guidance: https://www.epa.gov/superfund/applicable-or-relevant-and-appropriate-requirements-arars

US EPA Basic information on IRIS: https://www.epa.gov/iris/basic-information-about-integrated-risk-information-system

US EPA IRIS Cadmium chemical assessment summary: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0141_summary.pdf#nameddest=canceroral


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Cal DTSC Homepage: http://www.dtsc.ca.gov/

Cal DTSC Metal Contaminated Structural Surfaces HHR Evaluation Guidance: http://www.dtsc.ca.gov/AssessingRisk/upload/Eval-Metal-Contaminated-Surfaces.pdf

Cal DTSC Preliminary Endangerment Assessment (PEA) Guidance Manual, Rev. 2015: http://www.dtsc.ca.gov/PublicationsForms/prog_pubs_keyword.cfm?prog=Site%20Cleanup&keyword=Preliminary%20Endangerment%20Assessment

California DTSC SLs - HERO HHRA NOTE NUMBER: 3 , DTSC- modified Screening Levels (DTSC -SLs) RELEASE DATE: January 2018: https://www.dtsc.ca.gov/AssessingRisk/upload/HHRA-Note-3-January-2018.pdf

Colorado Department of Public Health and Environment (CDPHE) Support for Selection of a Cleanup Level for Methamphetamine at Clandestine Drug Laboratories. February 2005: https://environmentalrecords.colorado.gov/HPRMWebDrawerHM/Recordview/403424

U.S. Department of Health and Human Services (HHS), CDC Exposure Assessment-Recycling Operations-326-12a: https://www.cdc.gov/niosh/surveyreports/pdfs/326-12a.pdf


Technical Basis and Background for the 2013 Maine Remedial Action Guidelines for Soil Contaminated with Hazardous Substances: https://docslide.net/documents/1b1-rags-soil-technical-basis-pr-draft-03-11-2013docx.html

U.S. Army CHPPM TG 312: http://foundationforworkerhealth.wikischolars.columbia.edu/file/view/Reference+3_TG+312+%28Health+Risk+Assessment+Methods+and+Screening+Levels+for+Evaluating+Office+Worker+Exposures.pdf

Brookhaven National Laboroatories IH75190: https://www.bnl.gov/esh/shsd/sop/pdf/ih_sops/ih75190.pdf

May, L.M. B. Gaborek, T. Pitrat, and L. Peters. 2002. Derivation Of Risk Based Wipe Surface Screening Levels For Industrial Scenarios. The Science of the Total Environment 288. 65-80.


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Risk Assessment

Environmental Health Case Study

Andrey Korchevskiy, PhD, DABT, CIH

Case Study

Mr. Galetsky lived in a county where naturally-occurring asbestos (NOA) is found on a local trail. He arrived to the county in the age of 12 with his parents, and stayed for 4 years. During not-rainy period of the year (36 weeks), he was involved in moderate-intensity activity pattern, including jogging/biking on the trail (2 hours per day in average). Activity-based air samples were taken on the trail for jogging/biking, determining average level of fibers concentration at 0.03 f/cc (maximum 0.08 f/cc). The fibers were determined to be 50 % chrysotile, 40 % tremolite, 10 % erionite. Evaluate risk level for this scenario and assess for acceptability.


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Riding through unknown risks…

NAS Risk Assessment Methodology: Use Four Steps!

I. Hazard IdentificationII. Exposure assessmentIII.Dose-Response AssessmentIV.Risk Characterization


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Hazard Identification






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What our case study is about?

Chrysotile 50 %

Tremolite40 %

Erionite 10 %

Asbestos: Regulatory DefinitionAsbestos includes chrysotile, amosite, crocidolite, tremolite asbestos, anthophyllite asbestos, actinolite asbestos, and any of these minerals that have been chemically treated and/or altered.

OSHA 1910.1001

“Asbestos” means the fibrous form of mineral silicates belonging to rock-forming minerals of the serpentine group, namely chrysotile, and the amphibole group, namely actinolite, amosite, anthophyllite, crocidolite, tremolite or any mixture containing one or more of these minerals.

An Act respecting occupational health and safety, Quebec, Canada (chapter S-2.1, s. 223)


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“Fibers” and “asbestiform fibers”

Mineral fibers are fragments of a mineral with a length to diameter (aspect) ratio of 3:1.

“Asbestiform” describes a special type of fibrosity. Asbestiform fibers are separable, strong and flexible.

Cleavage fragments are shorter and thicker fragments of minerals, as a rule not expressing strength and flexibility of asbestiform fibers.

NRC, 1984

Fibers as a Category of Particulates

Fiber means a particulate form of asbestos 5 micrometers or longer, with a length-to-diameter [aspect] ratio of at least 3 to 1.

OSHA 1910.1001


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Asbestos Fiber Types

Chrysotile Crocidolite

Tremolite Amosite

Anthophyllite Actinolite

Pictures courtesy of USGS

Two distinct mineral groups of asbestos

Serpentine fibers (represented by chrysotile):• low in iron concentration, • have distinct fiber morphology, • typically comprised of clumps in the air, • have magnesium hydroxyl groups on the surface, which allow decomposition in

acid, generally cleared easily in the human lung (half-life on the order of weeks in the lung).

Amphibole asbestos fibers (such as amosite and crocidolite):• higher in iron, • more chemically resistant, • more difficult for the body to clear (with half-lives in the human lung of decades).

Pictures courtesy to USGS


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Amphibole minerals can produce two types of particulates:

“asbestiform fibers” and “cleavage fragments”

Asbestiform tremolite Tremolite cleavage fragments

The term “asbestos” tends to expand

Libby amphibole is mostly comprised of the unregulated amphiboles, winchite (84%) and richterite (11%), and regulated asbestiform fibers, tremolite (6%).

Naik et al. (2017)


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Other Important Determinants of Asbestos Hazard

• Commercial asbestos product or naturally-occurring asbestos

• Friability of the material• How well bound to the product (like, asbestos

cement)• Potential contamination of other minerals in mining

or construction operations• Contaminated media characteristics

Exposure to asbestos (or similar) fibers is measured as…

(1) Fibers per cubic centimeter (f/cc) as exposure intensity (air concentration).

(2) Fibers per cubic centimeter -years (f/cc-years) as cumulative exposure.


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Brief Review of Asbestos Health Effects

Hazard Identification of Asbestos: Numerous Sources of Toxicological Information

PubMed:

13,732 sources for “asbestos”2,230 sources for “chrysotile”818 sources for “amphibole”

113,737 sources for “tobacco”

ToxLine:

26,395 sources for “asbestos”4,837 sources for “chrysotile”1,335 sources for “amphibole”

61,412 sources for “tobacco”


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Asbestos health effects

Cancer:

• Mesothelioma• Lung Cancer• Other Cancers

Non-Cancer:

• Pleural Plaque• Pleural

Changes• Asbestosis

Cancers are primary targets for asbestos risk assessment

• Most dangerous and fatal effects.• Significant economy losses. • Stochastic character (appears

randomly in exposed cohort).• Mesothelioma has been considered a

signature asbestos-related cancer for long time.

• Difficult to prevent.


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Pleura is the most sensitive to asbestos fibers impact

The lung is surrounded by the visceral and parietal pleura, giving rise to the fluid-filled intrapleuralcavity.

Mesothelioma

• Estimated ~14,000+ cases of mesothelioma are diagnosed worldwide annually•Approximately 3,000 in the U.S. and 2,500 in the U.K.•Multiple cancer sites, although most diagnosed cases are pleural•Diagnosis at other sites less prevalent: 10 to 20% in the peritoneum, ~1% in the tunica vaginalis testis, ovary, and pericardium• Latency with asbestos exposure 10-60 years


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Mesothelioma •Mesothelioma is not always asbestos-related.•Other agents associated with increased risk of mesothelioma include erionite, fluoro-edenite, radiation, certain chronic inflammatory processes, etc.• Spontaneous (aka idiopathic) mesothelioma apparently occur at a rate of 1-3 cases per 1,000,000 (population) per year (this estimation needs more robust scientific basis!).• Threshold for asbestos exposure is nor well defined, but most probably it is at least 7-25 f/cc-years for chrysotile, and 0.05-0.25 f/cc-years for amphiboles.

Mesothelioma

Background rate:•One “background” case of mesothelioma per million per year means at least 75 cases per million per lifetime


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Lung Cancer •Most common cancer in both males and females.• Approximately 221,000 new cases of lung cancer were

projected in the U.S. in 2015 (~225,000 in 2013).• Estimated that smoking accounts for about 90% of lung

cancer cases in men and 80% in women.•Other risk factors for lung cancer include radon,

radiation, asbestos, arsenic, beryllium, hydrocarbons, nickel, social, behavior, infection, etc.• Respiratory disease predisposes.• Genetic predisposition likely.• Latency with asbestos exposure> 10 years

New information on cancer background: new developments are expected!

Dr. Cristian Tomasetti(The Bloomberg School of Public Health)

…we calculate that 35% (95%CI: 30 to 40%) of total driver gene mutations [in lung adenocarcinomas] aredue to factors unrelated to E [environmental] or H [hereditary] and presumablyare due to R [gene replication errors].

Tomasetti, Vogelstein (2017)


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Asbestos: mechanisms and modes of toxicity

1.A complete theory of fibers toxicity has not yet been developed.

2.Most important hypotheses are:• Macrophages being stuck when trying to consume fibers• Inflammation• Iron content of fibers causing forming of free radicals• Silanol groups interacting with iron in cells (Ghio, 1994)• Radioactive “hot spots” around asbestos bodies

(Nakamura, 2009)• Other

3. Fiber size and fiber types implicated in carcinogenic potential of mineral fibers.

Fiber Types and Health-Based Endpoints

There are distinct differences in the propensity of the different asbestos fibre types to cause mesothelioma. Amphibole (amosite and crocidolite) asbestos is considerably more potent than chrysotile, and crocidolite is more dangerous than amosite.International Agency for Research on Cancer, “Pathology and Genetics of Tumors of the Lung, Pleura, Thymus and Heart” Lyon, IARC (2004).

Some believe that there are not major differences in potency between fiber types.


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Fiber Sizes and Health-Based Endpoints

Berg, G., Maillie, H., “Measurement of Risks,” Plenum Press, New York and London, 1980.

Half-Life of Different Mineral Types of Asbestos in Human Lungs…

Asbestos Mineral Type Half Life (months)Chrysotile, Quebec 2 1,2

Amosite 240 3

Crocidolite, South Africa 72 4

Crocidolite, Australia 92 5

Libby amphibole (as tremolite)

480 6

1. Hesterberg, T., Chase, G., Axten, C., Miiller, W., Musselman, R., Kamstrup, O., Hadley, J., Morscheidt, C., Bernstein, D., Thevenaz, P., “Biopersistence of Synthetic Vitreous Fibers and Amosite Asbestos in the Rat Lung Following Inhalation, “ Toxicol. Appl. Pharmacol. 151 (2), 262–275 (1998).

2. Churg, A., “Influence of Fiber Type, Size, and Number in Human Disease: Conclusions from Fiber Burden Analysis ,”http://www.epa.gov/oswer/asbestos_ws/abstract.htm#churg (2003).

3. Churg, A., Vedal, S., “Fiber Burden and Patterns of Asbestos-Related Disease in Workers with Heavy Mixed Amositeand Chrysotile Exposure,” Am J Resp Crit Care Med 150, 663-669 (1994).

4. Du Toit, R., “An Estimate of the Rate at Which Crocidolte Asbestos Fibres are Cleared from the Lungs,” Ann Occup Hyg 35(4), 433-438 (1991).

5. de Klerk, N., Musk, W., Williams, V., Filion, P., Whitaker, D., Shilkin, K., “Comparison of Measures of Exposure to Asbestos in Former Crocidolite Workers From Wittenoom Gorge, W. Australia,” American Journal of Industrial Medicine 30, 579-587 (1996).

6. Churg, A., “Deposition and Clearance of Chrysotile Asbestos,” Ann Occup Hyg. 38(4),625-633 (1994).


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Reminder: Case Study

Mr. Galetsky lived in a county where naturally-occurring asbestos (NOA) is found on a local trail. He arrived to the county in the age of 12 with his parents, and stayed for 4 years. During not-rainy period of the year (36 weeks), he was involved in moderate-intensity activity pattern, including jogging/biking on the trail (2 hours per day in average). Activity-based air samples were taken on the trail for jogging/biking, determining average level of fibers concentration at 0.03 f/cc (maximum 0.08 f/cc). The fibers were determined to be 50 % chrysotile, 40 % tremolite, 10 % erionite. Evaluate risk level for this scenario and assess for acceptability.

Erionite: The most toxic mineral on earth?

Erionite, a naturally occurring fibrous mineral, is found in volcanic ash that has been altered by weathering and ground water, and it forms brittle, wool-like fibrous masses in the hollows of rock formations.

It is the most commonly occurring of the approximately 40 zeolite group of minerals and has been demonstrated in animal studies to have greater carcinogenic potential than crocidolite and chrysotile asbestos fibers (Carbone et al 2002, Maltoni et al 1982,Wagner et al 1985).

Radiographic Changes Associated with Exposure to Erionite in Road Gravel in North Dakota. Report EP-R8-06-02/TO #0803, prepared for U.S. EPA, Region 8 (2010).


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Mesothelioma epidemics in Turkey villages

At the end of the 1970s, a very high incidenceof pleural mesothelioma was observed inone of the regions of Turkey, in three villages inCappadocia where erionite was present (Sarihidir, Tuzkoy, and Karain). During 1970–87, 108 cases of pleural mesothelioma were recorded in the small village of Karain (604 inhabitants in 1974) – equivalent to an annual incidence of more than 800 cases/100000, that is, about 1000 times the rate observed in the general population of industrializedcountries. These cases were responsiblefor nearly half the deaths reported in this village.

IACR, “Erionite,” in 100C Monograph (2012)

Karain

Fibrous erionite deposits in the United States

Carbone, M., et al., “Erionite Exposure in North Dakota and Turkish Villages with Mesothelioma,” PNAS108(33), 13618-13623 (2011).


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Erionite in Mexico

High rates of lung cancer and mesothelioma mortality in the village of Tierra Blanca, Mexico, most probably caused by erionite exposure.

Ortega-Guerrero, M. et al., “High Incidence of Lung Cancer and Malignant Mesothelioma Linked to Erionite Fiber Exposure in a Rural Community in Central Mexico,” Occup Environ Med 10.1136/oemed-2013-101957 (2014).

Fibrous Erionite in Italy


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Mesothelioma in Rats from Erionite Exposure

Wagner, J., Skidmore, J., Hill, R., Griffiths, D., “Erionite Exposure and Mesothelioma in Rats,” Br. J. Cancer 51, 727-730 (1985).

Our risk assessment study shows…

For total cancer, erionite is approximately 10 times more potent than crocidolite, 2500 time more dangerous that chrysotile.


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How erionite is regulated in the United States?

• There are no regulatory or consensus standards or occupational exposure limits for airborne erionite fibers.

• Significant new use reporting is mandatory for erionite fibers under EPA regulations (40 CFR 721.2800).

• Listed as cancer-causing substance under California Proposition 65.

Summary of Hazard Identification

• Asbestos remains a significant occupational and environmental health problem worldwide

• The term “asbestos” tends to be expanded to cover more of the emerging fibrous hazards

• Erionite is a fibrous zeolite having asbestiform habit and characteristics

• Among the numerous health effects of asbestos and erionite, mesothelioma and lung cancers are especially important

• Various characteristics of asbestos fibers should be taken into account when health effects are discussed (fiber type, size, biopersistence etc.)


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Exposure Assessment



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Reminder: Exposure to asbestos (or similar) fibers is measured as…

(1) Fibers per cubic centimeter (f/cc) as exposure intensity (air concentration).

(2) Fibers per cubic centimeter -years (f/cc-years) as cumulative exposure.

Total Exposure = C * t (good metric for chronic exposures)

Cumulative (or Total) Exposure – Haber’s Rule

Haber, F., “”Zur Geschichte des Gaskriegas,” in Fuenf Vortraege aus den Jahren 1920-1923, pp. 76-92. Julius Springer, Berlin (1924).


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Cumulative exposure problem

Mr. Johnson worked in construction industry for 15 years.His average TWA asbestos exposure was 0.1 f/cc.

What was Mr. Johnson’s cumulative asbestos exposure (in f/cc-years)?

Cumulative exposure problem - 2

Mr. Johnson worked in construction industry for 15 years.One hour per day, in average, he was involved in working with asbestos-containing materials. His average TWA asbestos exposure during that time was 0.1 f/cc.

What was Mr. Johnson’s average cumulative asbestos exposure?


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Cumulative exposure calculation

1 hour/8 hours x 15 years x 0.1 f/cc = 0.18 f/cc - years

Cumulative exposure problem - 3

Mr. Johnson lived 70 years in a neighborhood where average asbestos exposure was 0.00006 f/cc.

What was Mr. Johnson’s average cumulative asbestos exposure (in occupational equivalent)?


Page 76

Cumulative exposure calculations

70 years x 0.00006 f/cc x 2.8 = 0.012 f/cc-years

Coefficient recommended by EPA to account for difference in

working week vs. calendar week, and for difference in

breathing rate during work and residentially

06 f/cc x 2.8

How to find average exposure if I know cumulative exposure?

Cumulative exposure of Mr. Jones during 30 years was 0.02 f/cc-years.

What was his average exposure intensity (f/cc)?


Page 77

Asbestos PEL for workers

• 0.1 f/cc as TWA

• Applied for all types of asbestos

• Note. Can be too strict for chrysotile, too weak for amphiboles and zeolites.

How asbestos concentrations in air are measured

Method PCM NIOSH 7400

Phase-Contrast Microscopy

1.Allows to get high-contrast image of fibers on the filter.

2.Criteria: Aspect ratio > 3:1, length > 5 μm, width >0.25 μm

3.Doesn’t distinguish between asbestos and other fibers.

4.Depends on the qualification of analyst.5.Number of fibers recalculated to

concentration.

400x


Page 78

How asbestos concentrations in air are measured (continued)

Method TEM NIOSH 7402

Transmission Electron Microscopy

1.Electron ray is used to increase the object; electron microprobe utilized to get spectrum of the fibers.

2.Criteria: Aspect ratio > 3:1, length > 5 μm, width >0.25 μm

3.Distinguish asbestos and its types.4.Depends on the qualification of analyst.5.Number of fibers recalculated to

concentration.

Other important methods

1. PLM (Polarized-Light Microscopy) – for bulk samples.

2. SEM – other type of electronic microscopy.

3. XRD – analysis of crystal structure .


Page 79

PCME Concept

Fiber concentrations are measured by TEM, but criteria of PCM method are applied (aspect ratio > 3:1, length > 5 μm, width >0.25 μm)

Shipyard Insulator» 1960s, ~7 f/cc» Earlier, 10 to 30 f/cc» Up to 40 or 50% amphibole exposure

Insulator in Commercial and Industrial Applications

» 1960s, ~3 f/cc» Earlier, 5 to 20 f/cc» Up to 40 or 50% amphibole exposure

Steamfitters, pipefitters, and plumbers» New construction, 0.01 to 0.1 f/cc» Renovation and maintenance, 0.01 to

1 f/cc or higher» Amphibole exposure from thermal

insulation and A/C pipe

Ballpark Examples of Past Occupational Asbestos Exposure TWA Estimates (Depends on Actual Work History!)

Drywall taper and sander» 1 to 5 f/cc» Chrysotile

Electrician» Not far from 0.01 f/cc, electrical

products» Potential disturbance of fireproofing

and insulation materials, depending on work history, 0.01 to 1 f/cc

Vinyl asbestos floor tile and linoleum installer» 0.0 to 0.1 f/cc» Chrysotile


Page 80

Asbestos Exposure from Soil Contamination

• Asbestos can become airborne if soil contains asbestos fibers

• Airborne asbestos concentrations can be approximately predicted if asbestos content in soil (%) is measured

• Airborne concentrations will significantly depend of soil type, asbestos fiber type and dimensions, asbestos conditions (loose fibers vs. asbestos cement) and other factors.

Screening method to determine airborne asbestos concentrations (f/cc) based on asbestos soil content (%)

Asbestos in air (PCME, f/cc) ≈ Respirable dust concentration (mg/m3) x Asbestos in soil (%)/100 x Weight-to-count-factor (f/cc per 1 mg/m3),

Weight-to-count-factor ≈ 33 (95 % CI 5, 200).


Page 81

Hands on Exercise

Calculate lifetime cumulative exposure (occupational equivalent) for the residential population living in the area with average respirable dust concentration 300 μg/m3, asbestos content in soil 0.001 %.

Reminder: Case Study

Mr. Galetsy lived in a county where naturally-occurring asbestos (NOA) is found on a local trail. He arrived to the county in the age of 12 with his parents, and stayed for 4 years. During not-rainy period of the year (36 weeks), he was involved in moderate-intensity activity pattern, including jogging/biking on the trail (2 hours per day in average). Activity-based air samples were taken on the trail for jogging/biking, determining average level of fibers concentration at 0.03 f/cc (maximum 0.08 f/cc). The fibers were determined to be 50 % chrysotile, 40 % tremolite, 10 % erionite. Evaluate risk level for this scenario and assess for acceptability.


Page 82

Let’s Assess Exposure for our Case Study…EXPOSURE ASSESSMENTDuration (years)Onset age (years)Hours per day (hours)Weeks per year (weeks)Cumulative exposure, Chrysotile (occupational equivalent, f/cc-years, PCME)Cumulative exposure, Tremolite (occupational equivalent, f/cc-years, PCME)Cumulative exposure, Erionite (occupational equivalent, f/cc-years, PCME) Average exposure, Chrysotile (f/cc, PCME)Average exposure, Tremolite (f/cc, PCME)Average exposure, Erionite (f/cc, PCME)

Using Monte Carlo Method for Exposure Assessment

Fibers concentrations: 0.03 f/cc in average, 0.08 f/cc maximum

Hours per day on the trail: 2 hours in average (assume 3 hours maximum)


Page 83

Exposure simulation results

Dose-Response Assessment


Page 84

National Academy of SciencesDose Response, 2009

Case StudyMr. Galetsy lived in a county where naturally-occurring asbestos (NOA) is found on a local trail. He arrived to the county in the age of 12 with his parents, and stayed for 4 years. During not-rainy period of the year (36 weeks), he was involved in moderate-intensity activity pattern, including jogging/biking on the trail (2 hours per day in average). Activity-based air samples were taken on the trail for jogging/biking, determining average level of fibers concentration at 0.03 f/cc (maximum 0.08 f/cc). The fibers were determined to be 50 % chrysotile, 40 % tremolite, 10 % erionite. Evaluate risk level for this scenario and assess for acceptability.


Page 85

Dose-Response Assessment

Assume that we know

exposure (for example, in f/cc-

years).

We want to predict the effect (number of cancer

cases):• To evaluate the

outcomes;• To establish safety

standards;• To compare with other

risks etc.?

Dose-Response Assessment for Asbestos is Complex, Because of:

• Usually dose-response relationships are explored in animals, but for asbestos there is no good correlation between animals and human responses;

• Human epidemiological data for asbestos is difficult to derive, because of limited number of studies;

• Exposure metrics and methods changed with time;• Mesothelioma is an extremely rare disease etc.


Page 86

Epidemiology to the rescue: How we can establish a dose-response relationship

Wittenoom, Australia Quebec, Canada

Predominant crocidolite exposure.

Predominant chrysotile exposure.

Average cumulative exposure 23 f/cc-years


Cohort of 5173 men Cohort of 9780 men

165 cases of mesothelioma 38 cases of mesothelioma

De Klerk, N., Musk, A., Armstrong, B., Hobbs, M., “Diseases in Miners and Millers of Crocidolite from Wittenoom, Western Australia: A Further Follow-Up to December 1986,” Ann. Occup. Hyg. 38(1), 647-655 (1994). Liddell, F., McDonald, A., McDonald, J., “The 1891-1920 Birth Cohort of Quebec Chrysotile Miners and Millers: Development from 1904 and Mortality to 1992,” Ann. Occup. Hyg. 41 (1), 13-36 (1997).

Approximate (Ballpark) Valuesfor Slope Factors

Wittenoom, Australia Quebec, CanadaPredominant crocidolite exposure.

Predominant chrysotile exposure.



Cohort of 5173 men Cohort of 9780 men165 cases of mesothelioma

38 cases of mesothelioma

1.39 cases of mesothelioma per 1,000 per 1 f/cc-years of exposure to crocidolite

0.006 cases of mesothelioma per 1,000 per 1 f/cc-years of exposure to chrysotile


Page 87

Why in Reality it is More Complex Than That Simple Calculation

• Difference in age structure of cohorts causes various level of mortality;

• Mesothelioma and lung cancer risks vary with time since the exposure;

• Lung cancer excess risk depends on the background incidence;

• To determine risk slope factors, we may need to reconcile data from different cohorts (“meta-analysis”) etc.

Dose-Response Models for Asbestos

U.S. EPA/Nicholson (1986/2008)

Hodgson/Darnton(2000, 2010)

Berman/Crump (2003, 2008a,b,

2011)

Other


Page 88

Dose-Response Models for Asbestos

U.S. EPA/Nicholson (1986/2008)

Hodgson/Darnton(2000, 2010)

Berman/Crump (2003, 2008a,b,

2011)

Other

Original model of

Julian Peto

Prof. Julian Peto

Dr. Wayne Berman


Page 89

Andrew Darnton John

Hodgson

What Peto model is about?

Exposure to crocidolite,1 f/cc, during 17 years starting at the age of 25

Peto’s rule:Number of mesothelioma cases grows as the 3rd power of age


Page 90

Age-Related Model for Lung Cancer Risk

Exposure

11.0021.0041.0061.0081.011.0121.0141.0161.0181.02

0100020003000400050006000700080009000

10000

35 40 45 50 55 60 65 70 75Age (years)

Lung Cancer Absolute and Relative Risks Changing with Age

Absolute Risk (per 1,000,000) Relative Risk

What is “potency factor” for carcinogens?

Higher the potency factor, greater the carcinogenic effect per unit of exposure

Different “potency factors”: inhalation unit risk, slope factor, and other


Page 91

Inhalation Unit Risk (IUR) for several carcinogens

Carcinogen Inhalation Unit Risk per 1,000,000 per 1 μg/m3

Benzene 7.8Benzo(a)pyrene 600Chromium (VI) 12,000Arsenic, inorganic 4,300Cadmium 1,800Asbestos (mixed fibers) 230,000 per 1 f/cc, or 7,666

per 1 μg/m3

Question: What type of potency factors we use for asbestos?

Answer: Different methods may use various types of factors.


Page 92

Both IRIS (Nicholson) and Berman, Crump Models Use Slope Factors KL and KM for Cancer Potency of Asbestos

KL – potency factor for lung cancer

KM – potency factor for mesothelioma

U.S. EPA IRIS


Page 93

U.S. EPA IRIS is a Great Source for Risk Assessment Information

Use https://www.epa.gov/iris for various chemicals.

Example of Dose-Response Relationship: U.S. EPA IRIS

RISK = UR * Exposure * 1,000,000,

RISK – excess cancer risk (per 1,000,000),

UR – inhalation unit risk (by IRIS, UR= 0.23),

Exposure - asbestos exposure assumed to be constant continuous (24/7) lifetime exposure (f/cc) (PCM equivalent)

U.S. EPA, “Integrated Risk Assessment System (IRIS). Asbestos (CASRN 1332-21-4),” [Online] Available at http://www.epa.gov/iris/subst/0371.htm.


Page 94

Hands-On Exercise

Calculate IRIS cancer risk (per 1,000,000)

for continuous lifetime asbestos exposure (24/7) to 0.01 f/cc


Page 95

Potency Factors Used by Nicholson, 1986 (PCME fibers)

Mesothelioma (KM*108

, 95 % CI)Lung cancer

(KL*102, 95 % CI)

Amphiboles Chrysotile Amphiboles Chrysotile1 1 1 1

If calculated with life tables, it yields 0.23 coefficient for total cancer, mixed fiber types

Problems with the Asbestos U.S. EPA IRIS Model

• The slope factor (UR=0.23) was calculated using Peto’s model, but on a very limited set of data (almost no information for mesothelioma cohorts);

• Doesn’t distinguish between fiber types or sizes;• Doesn’t allow to evaluate separately mesothelioma

and lung cancer risks; • In its initial version, allows only lifetime exposure

calculations.


Page 96

Berman, Crump Model

Berman, Crump Model (2003, 2008, 2011)

• Was initially developed for the U.S. EPA; • Used original Peto model for age-related

mesothelioma and lung cancer calculations (compatible to the IRIS model);

• Linear by exposure intensity (f/cc)• Allowed to account for fiber type and

size;• Separate calculations for mesothelioma

and lung cancer, if needed;• Considered the problem of tremolite

contamination of chrysotile.


Page 97

Berman/ Crump Updated Potency Factors for Mesothelioma

Berm

an, C

rum

p, 2

003,

200

8a

Berman/ Crump Updated Potency Factors for Lung Cancer

Berm

an, C

rum

p, 2

003,

200

8a


Page 98

Pooled PCME Potency Factors for Chrysotile and Amphiboles: Difference Between Berman, Crump

and the original U.S. EPA Model

Mesothelioma(KM*108

, 95 % CI)Lung cancer

(KL*102, 95 % CI)

Amphiboles Chrysotile Amphiboles Chrysotile

Berman, Crump (2008b)

8.5(3.5, 19)

0.009 (0, 0.16)

1.4 (0.23, 5.9)

0.20 (0, 0.55)

Nicholson, 1986 1 1 1 1

Comparison Between Berman, Crump and IRIS Risk Calculations

Exposure (occupational, PCME, f/cc)

Berman, Crump Total Cancer Excess Risk (Cases per 1,000,000)

U.S. EPA IRIS Total Cancer Excess Risk (Cases per 1,000,000)

0.005 15 670.05 146 6740.1 293 13480.5 1,493 6,7401 2,926 13,47910 29,257 134,79550 146,285 673,974

Chrysotile exposure starting at the age of 25 years, 17 years duration


Page 99

Hodgson, Darnton Model

Hodgson, Darnton (2000, 2010)

• Developed by HSE (England);• Contains two parts, considered linear

and non-linear model by cumulative exposure (f/cc-years);

• Used modified Peto model for age-related mesothelioma and lung cancer calculations;

• Allowed to account for fiber type and size;

• Separate calculations for pleural, peritoneal mesothelioma and lung cancer, if needed.


Page 100

Hodgson, Darnton Model Uses Slope Factors RL and RM for Cancer Potency of Asbestos

RL – potency factor for lung cancer

RM – potency factor for mesothelioma

Hodgson/Darnton Linear Mesothelioma Risk Metric

RM = 100 OM/(EAdj * X),

where RM – risk metric,OM – observed number of mesothelioma deaths,EAdj – the total expected deaths from all causes adjusted to an age of first exposure of 30,X – cohort mean cumulative exposure (f-cc/years)


Page 101

Hodgson/Darnton Linear Lung Cancer Risk Metric

RL = 100 (OL –EL)/(EL *X),

where RL – risk metric,OL – observed lung cancers,EL - expected lung cancer,X – cohort mean cumulative exposure (f-cc/years)

Mesothelioma potency assessment based on epidemiological information

Mineral type, location Mesothelioma potency factor, RM

Chrysotile, Quebec 0.0009Amosite, South Africa

0.06

Crocidolite, South Africa 0.59Crocidolite, Australia 0.49Libby amphibole 0.03Anthophyllite, Russia 0.056

Erionite, Turkey 4.67


Page 102

Lung cancer potency factors based on epidemiological information (with erionite)

Mineral type, location

Lung cancer potency factor, RL

Chrysotile, Quebec 0.06Amosite, South Africa

1.9

Crocidolite, South Africa 5.2Crocidolite, Australia 4.6Libby amphibole 0.8Erionite, Turkey 82

Hodgson, Darnton: Non-Linear Assumptions

Cumulative Exposure (f/cc-years)

Risk

(Exc

ess C

ance

r Cas

es pe

r 1,0

00,0

00)

Superlinear

Sublinear

Linear


Page 103

Hodgson, Darnton Explanation of a Power Function Shape for Pleural Mesothelioma Dose-Response

Fibers createspherical

“inflammation foci”; their volume is proportional to

cumulative exposure:= CE,

CE = cumulative exposure (f/cc-years)

Pleura is thin compared to inflammation volume. Risk is

proportional to “cut” area:

RISK = βπR2

RISK = γCE0.67

Risk estimates for different levels of exposure (assuming 18 years old onset time, 45 years duration)

Total Excess Cancer Risk per 1,000,000Chrysotile Crocidolite Amosite

Exposure intensity (f/cc)

Berman, Crump method

Hodgson, Darntonmethod (NL/L)


Hodgson, Darnton method


Hodgson, Darnton method

0.001 7 4(2) 220 608 (207) 220 91 (89)0.01 72 26 (16) 2202 3535

(2070)2202 628 (895)

0.1 719 189 (157) 22,020 22,306 (20.702)

22,020 5869 (8946)

1 7189 1868 (1572)

220,204 186743 (207018)

220,204 83184 (89457)

NL – non-linear, L - linear

*Erionite will yield approximately an order of magnitude higher than crocidolite


Page 104

The Risk Calculator

The Fibrous Minerals Risk Calculator: The unique tool to apply and compare risk assessment approaches

1. Developed by C&IH in collaboration with Wayne Berman, John Hodgson and Andrew Darnton.

2. Includes various models.

3. Utilizes life-tables for risk calculations.

4. Calculations are based on exposure intensity, duration, onset age, fiber type and dimensionality.


Page 105

Three “Scenarios” – Three Exposure Metrics

Scenario 1. Only PCM concentrations of asbestos are known.

Scenario 2. PCME (TEM) concentrations of asbestos are known; mineral type is determined; but no information about fiber-size distribution.

Scenario 3. TEM concentrations of asbestos are known, the information includes mineral type and is fiber-size specific.

Scenario 1Only PCM concentrations of asbestos are known.

That means:

• I know something about the elongated mineral particles present/absent in the air.

• I don’t know mineral type of the fibers.• Generally speaking, I even don’t even know if it is asbestos.

How can I estimate risk?

• Use the U.S. EPA IRIS method.• Use compatible “Nicholson” method with original 1977 life-tables and smoking data.• Use “Nicholson” method with updated 2009 life-tables and smoking data.


Page 106

Scenario 2PCME (TEM) concentrations of asbestos or erionite are known; mineral type is

determined; but no information about fiber-size distribution.

That means:

• I know that asbestos is present/absent in the air.• I know the mineral type of the fibers (chrysotile, crocidolite, amosite, or other

amphiboles).How can I estimate risk?• Use Berman, Crump method (with 2009 life-

tables and smoking information).• Use linear and non-linear Hodgson-Darnton

method for comparison.

Scenario 3TEM concentrations of asbestos are known, the information

includes mineral type and is fiber-size specific.

That means:

• I know that asbestos is present/absent in the air.• I know the mineral type of the fibers (chrysotile, crocidolite, amosite, or

other amphiboles).• I know the fractions of the fibers for different size groups.

How can I estimate risk?

• Use Berman, Crump method for different groups of fiber sizes, with 2009 life-tables and smoking information.

• For comparison, use tools in scenarios 1 or 2, also.


Page 107

Risk Characterization

National Academy of Sciences, 2009Risk Characterization


Page 108

Let’s Characterize Risks for our Case Study using linear Hodgson, Darnton Method

Chrysotile Tremolite Erionite TotalMesothelioma excess risk, per 1,000,000Lung cancer excess risk, per 1,000,000Total cancer excess risk, per 1,000,000

Exercise: Assume background lung cancer risk as 40,000 cases per

1,000,000 per lifetime.

What is a relative risk of lung cancer for Mr. Galetsky?

What is the attributable risk fraction?


Page 109

Reminder: Relative Risk

The relative risk (RR) of the event is the likelihood of its occurrence after exposure as compared with the likelihood of its occurrence in a control or reference group.

Relative Risk =

Reminder: Attributable Risk Fraction

The fraction of disease in a population that will be removed if the exposure is eliminated:

ARF =

(for example, for RR=2, ARF=50 %).


Page 110

Hands-On Exercise: Evaluation of the Existing Occupational Exposure Limits

Calculate linear Hodgson, Darntoncancer risk (per 1,000,000)

for occupational exposure (8/5), starting at the age of 20, duration of

45 years, to 0.1 f/cc to chrysotile, and

separately to crocidolite


Page 111

Hands-On Exercise: Calculation of the Internal Occupational Exposure Limits

Using linear Hodgson, Darnton cancer risk model, calculate occupational

exposure to erionite, starting at the age of 20, duration of 45 years, that can be accepted as internal

occupational exposure limit.


Page 112

Let’s discuss typical uncertainties and limitations of the risk

assessment…

Other Emerging Hazardous Minerals


Page 113

LIBBY AMPHIBOLES

Recent Publication of the U.S. EPA

IRIS: Risk Assessmentfor Libby Amphiboles

Libby, Montana: Amphibole Fibers Exposure of Vermiculate Mine Workers and the Community


Page 114

Libby Amphibole Asbestos (LAA)

LAA refers to various mineral forms of amphibole asbestos found in the rocks and ore of Zonolite Mountain, 6 miles northeast of Libby, MT.

Zonolite Mountain contains a large vermiculite deposit that has been mined since the early 1920s for various commercial uses.

Vermiculite miners, mill workers, and thoseworking in the processing plants were exposed to these amphibole fibers, which remain within the vermiculite ore and product.

U.S. EPA, “Toxicological Review of Libby Amphibole Asbestos,” (2014).

BLUESCHIST AND OTHER NOAsIN CALIFORNIA


Page 115

Calaveras Dam Asbestos Contamination

Na Amphiboles

Chrysotile

Chrysotile Actinolite

Electron MicrographBlueschist


Page 116

Is it Possible to Model the Potency Factor for a Fibrous Material

if no Epidemiology Data Available?

Forward Stepwise Regression: Empirical Search of the Best Model Parameters to Estimate Fibers Potency

SiO2

Total Fe

Fe2O3

Al2O3 MgO

CaO

MnO

Na2O

K2O

MES

OTHE

LIO

MA

AND

LUNG

CA

NCER

POT

ENCY

FACT

ORS

Aspect ratio


Page 117

The model for mesothelioma selected by computerized (in silico) “blind” process

Empirically-generated model :

log10(RM) = -4.71+2.09log10(SiO2)++1.32log10(AR-3)+0.35log10(Fe2O3)--1.51log10(MgO),

R=0.997, F=120.99, p=0.0082,where RM – average mesothelioma potency, Fe2O3 – ferric iron oxide content (%), MgO – average magnesium oxide content (%), SiO2 – average silicon dioxide content (%), AR – median aspect ratio. (Korchevskiy, Rasmuson, Rasmuson, in print)

(+)SiO2

(+)Fe2O3, or total

iron

(-)MgO

(+)Median Aspect Ratio of

the Fibers

Modeled and Published Average Mesothelioma Potency (Fe3+)

Red – average potency,blue – LCL 95 % potency,green – UCL 95 % potency,red line – modeling to published levels regression,dotted line – prediction interval.

R=0.997,P=0.0082,F=120.99

Erionite

Crocidolite

Amosite

Anthophyllite

Libby amphiboles

Tremolite

Chrysotile


Page 118

Published and Modeled Mesothelioma Potency Factors for Mineral Fiber Types (Mining and Natural

Environments)Mineral Type Location

Average RMPublished or

EstimatedModeled (Fe3+) Modeled (total

iron)Chrysotile Quebec 0.0009 0.0008 0.0009

Zimbabwe - 0.0010 0.0012Russia - 0.0018 0.0015

Amosite South Africa 0.06 0.065 0.093Tremolite Pakistan - 0.014 0.023Crocidolite Cape Province 0.59 0.72 0.61

Transvaal - 0.48 0.41Bolivia - 0.09 0.06Australia 0.49 0.36 0.28

Libby amphibole Montana 0.03 0.03 0.03Erionite Turkey 4.66 4.53 4.78Balangeroite Italy - 0.004 0.004Anthophyllite Russia 0.056 0.05 0.06

Finland - 0.04 0.03Actinolite Susa Valley - 0.024 0.024

How the model estimates mesothelioma potency (RM) for various fibers with limited epidemiological data?

Fluoro-Edenite

0.20

Glaucophane

0.04

Bolivian crocidolite

0.09

Tremolite,Fibers0.02

Tremolite, Cleavage fragments0.007

Balangeroite

0.004

Erionite, Turkey 4.5


Page 119

Lung cancer model

log10(RL) = -10.237+6.45log10(SiO2)--0.26log10(AEROD)+0.158log10(FeO)--0.99log10(MgO),

R=0.99999, F=21,398, p=0.00512,where RL – average lung cancer potency, FeO – ferric iron oxide content (%), MgO – average magnesium oxide content (%), SiO2 – average silicon dioxide content (%), AEROD – aerodynamic diameter. (Korchevskiy, Rasmuson, Rasmuson, in print)

(+)SiO2

(+)total iron

(-)MgO

(-)Median aerodynamic diameter of

fibers

Modeled and Published Average Lung Cancer Potency (Total Fe)

R=0.99999,P=0.00512,F=21398

0.03 0.1 0 31 1.0 3.1 10 31.6 100

0.03

0

.1

0.31

1

.0

3.1

10

31.

6

100

Erionite

Crocidolite, South AfricaCrocidolite, Australia

Amosite, South Africa

Libby amphiboles

Chrysotile

Modeled potency, RL

Publ

ished

(es

timat

ed) p

oten

cy, R

L


Page 120

What is a physical meaning of the model’s parameters?

SiO2 Aspect Ratio Iron oxides MgOSilanol groups (Si(OH)x) are implicated with increased biological activity of fibrous minerals (Aust, Cook, Dodson, 2011, Fubini et al., 1990, National Academy of Sciences, 2006,Ghio, Pavlisko, Roggli, 2015)

Long, thin fibers are associated with higher mesothelioma risks in animals and humans (Stanton, 1972, Berman, 2008, 2011, Lippmann, 2009)

Iron is implicated as one of the main drivers of asbestos toxicity (Kamp, Weitzman, 1999, Toyokuni, 2009). According to some sources, surface Fe3+ of fibers are a determinant of free radical damage (Ghio, 1992, 1994, Toyokuni, 1996).

Some authors suggested that presence of magnesium changesvarious characteristics of amphiboles (Addison, White , 1968, Ilgren et al, 2012). (Other sources suggest that magnesium depletion reduce toxicity of chrysotile).

In reality, it is possible that hidden or unknown factors influence each of the parameters and the dependent variable

Another model to fit the data


log10(RM) = -32.37+17.21log10(SiO2)--1.93log10(WIDTH)+0.66log10(Fe)--0.52log10(MgO),

R=0.999, F=981, p<0.00102,where RM – average mesothelioma potency, Fe – ferric and ferrous iron oxides content (%), MgO – average magnesium oxide content (%), SiO2 – average silicon dioxide content (%), WIDTH – median airborne fiber width (μm).

(+)SiO2, %

(+) Total iron

oxides, %

(-)MgO, %

(-)Median Width of

the Fibers


Page 121

… and another one


log10(RM) = -33.16+18.11log10(SiO2)--2.00log10(AEROD)+0.68log10(Fe)--0.46log10(MgO),

R=0.999, F=610, p<0.0016,where RM – average mesothelioma potency, Fe – ferric and ferrous iron oxides content (%), MgO – average magnesium oxide content (%), SiO2 – average silicon dioxide content (%), AEROD – aerodynamical diameter of fibers (μm).

(+)SiO2, %

(+) Total iron oxides, %

(-)MgO, %

(-)Aerodynamical

diameter of fibers

Strategy on assessing risks for unknown fibrous minerals

1.Test the material by TEM to determine mineralogical type and dimensionality.

2.Perform exposure assessment for affected groups/population.3.Use asbestos risk assessment calculator to preliminary assess risk.4.Evaluate “logical tree” of possible potency factors involved.Amphiboles can be assessed using scenario 2 or 3.If the material is similar to Libby amphiboles (so called : tremolite-actinolite solid solution series), the potency can be lower than for crocidolite.If there are reasons to believe in erionite typology, use higher potency estimations (higher than for crocidolite by at least a factor of 10).5. Initiate systematical analysis of the material involved.


Page 122

Learning Outcomes (Revisiting)

• Perform occupational and environmental health risk assessments.

• Define major metrics of risk assessment.• Use Excel spreadsheets for risk calculations.• Calculate internal occupational standards based on risk

assessments.• Evaluate existing occupational exposure limits (OELs).• Apply four steps of risk assessment in IH practice.• Utilize statistical methods in risk assessment procedure.• Recognize uncertainties and limitations in risk assessments.• Distinguish between acceptable and unacceptable risk levels.


Page 123

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To register, visit www.aiha.org/education/FacetoFace

Fundamentals of Industrial Hygiene› 32 Contact Hours› Westerville, OH / March 19 - 22 / September 17 - 20This four-day course is a great refresher for those re-entering the field or needing a brush-up, as well as OEHS professionals new to IH responsibilities.

Exposure and Chemical Monitoring: Beyond IH Fundamentals› 24 Contact Hours › Westerville, OH / October 15 - 17This intermediate course is perfect for professionals and senior managers, designed to provide additional training on occupa-tional exposure, qualitative exposure assessment, equipment calibration, and sampling.

Make meaningful connections with a wide range of events for professionals of all levels: • Personal Mock Interviewing Sessions • Résumé Critiquing and Improvement • Seminars • Speed Networking

Questions?Contact Wanda Barbour, Senior Manager of Member and Customer Relations, at [email protected] or 703-846-0782.

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Find your perfect match at theCareerAdvantage “Building Careers for Life”

Development Fair

Join us! Pennsylvania Convention Center, Hall B – The Hub, Section CADF Monday, May 21 – Wednesday, May 23, 20189:00 a.m. – 4:00 p.m. daily

Visit our website for the full schedule of events: www.aihce2018.org

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http://www.aihce2018.org

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The 11th International Occupational Hygiene Association (IOHA)International Scientific Conference

September 24-26, 2018 | Washington, DC, USA | #IOHA2018USA

What is IOHA 2018 and Why should you attend?The 11th IOHA International Scientific Conference (IOHA 2018) is a special event, whose mission is to create a global appeal to an interna-tional audience of multi-dis-ciplined professionals with a focus on worker health pro-tection and exposure control. The conference will provide a unique integrated platform of workplace health and well-being in a professional and scientific arena ideal for hearing the latest science and viewpoints, as well as networking and professional development opportunities.

WWW.IOHA2018.ORG

ANNOUNCING Keynote SpeakerNancy Leppink - Branch ChiefInternational Labour Organization, (LABADMIN/OSH)Genève, Switzerland

Ms. Leppink will present worker health issues in a global economy dominated by large multinational corporations with access to labor in lesser developed countries, the impacts of such dependencies on worker well-being and rights, and the occupa-tional health infrastructure needs in developing countries to ad-dress these new challenges.

Where will IOHA 2018 be located?The IOHA conference will be held in Washington, DC, USA at the Marriott Marquis Hotel, 901 Massachusetts Avenue, NW.

Important Dates• Professional Development Course (PDC)

Presentations - September 22-23 & 27, 2018• Conference - September 24-26, 2018

For more information, visit www.ioha2018.org.

SAVE

THE DATE

MAY 20-22MINNEAPOLIS, MNAdvancing Worker Health & Safety

PDC 809 Handout 2018 PDC...2018-05-14 · PDC Evaluations . We sincerely appreciate your feedback!...

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Transcript of PDC 809 Handout 2018 PDC...2018-05-14 · PDC Evaluations . We sincerely appreciate your feedback!...