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Risk Assessment

Introduction to Environmental Health

Fall 2011

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Risk Assessment in Environmental Health A process employed to estimate the potential for selected

health effects that may be caused by exposure to toxicants in the environment.

May be used assess the risk of health effects from actual, potential, or theoretical exposure.

Risk assessment is a modeling process that relies on a number of assumptions and

Model output cannot be more precise or accurate than the input data. Thus, understanding the assumptions and input data is essential to interpret and explain the results.

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What is Risk? Risk = the likelihood or probability of an adverse event or

outcome

The concept of risk is utilized in many fields including finance, insurance engineering etc.

Health Risk – likelihood of an adverse health effect or illness

Risk may be expressed either quantitatively or qualitatively. The expressions used vary by application.

Qualitative – “Little or no risk”

Quantitative – Compare dose or exposure concentration with appropriate reference value.

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Risk Assessment: Basic Paradigm

Risk is proportional to Hazard x Exposure

Hazard is a property of the substance being studied. Is it toxic? How toxic?

Is it in a form & location that we come in contact with? i.e. A lead fishing sinker is less hazardous than lead dust or fume in

most circumstances.

Exposure is the extent to which we are in contact with the hazard. What environmental media? (Air, Water, Soil, Food etc)

Concentration of the substance in that media

Route of exposure

Duration of exposure

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“All Things Considered” Why is it being conducted?

What questions need to be answered?

Who is affected?

What is known about the health effects and dose-response relationship of the substance?

What are the important exposure pathways and what is the expected contaminant concentration in these media?

How will the result be used?

How much uncertainty is acceptable?

Source: ATSDR- Public Health Assessment Guidance Manual

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Hazard Identification

Dose-Response Assessment*

Exposure Assessment

Risk Characterization

The 4-Step Risk Assessment Process

* a.k.a Toxicity Assessment

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Hazard Identification Characteristics of the Hazardous Substance A description of the potential health effects attributable to a

specific chemical or physical agent.

Consider physical properties and “transformation” of the substance

Physical state, Solubility, Vapor Pressure, Binding capacity

Consider fate, transport and transformation in the environment

Mobility – SoilWaterAir etc. Bioaccumulation Transformation i.e. Hgmethylmercury

What are the adverse effects? Most relevant and sensitive? Irritation, Organ-specific Toxicity, Cancer etc.

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The determination of the relationship between the magnitude of administered, applied, or internal dose and a specific biological response. Response can be expressed as measured or observed incidence, percent response in groups of subjects (or populations), or the probability of occurrence of a response in a population.

If there are multiple health effects (toxicologic endpoints), determine which “non-trivial” effect occurs at the lowest dose.

Sufficient data to support a dose-response relationship is not always present for human exposure, especially for non-occupational exposure to “low-level” environmental contaminants.

Comparison values developed by various agency are a product of the dose-response assessment. They may be appropriate to specific assessments and are typically intended to ensure that risk is not underestimated.

Dose-Response Assessment

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Source: USEPA

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Use of Comparison Values in Dose-Response Assessment For carcinogenic effect:

Cancer Slope Factor Inhalation Unit Risk Factor

Non-carcinogenic effects: Minimal Risk Level or MRL Reference Dose or RfD Reference Concentration or RfC Many others

Media specific “screening levels” or standards Brief or emergency exposures (ERPG, AEGL)

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Derivation of comparison values Benchmark A dose associated with a specified

low level of risk (e.g. 5%, 10% etc.)

NOAEL (No Observed Adverse Effect Level) Highest dose level (below the LOAEL) at which no adverse or toxic effect has been observed.

LOAEL (Lowest Observed Adverse Effect Level) The lowest dose level at which an adverse or toxic effect has been observed.

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Uncertainty factors used in determining comparison values Uncertainty Factors (UF)

are applied to assure the comparison value is protective.

Default UFs vary within and among agencies.

Adjustments are multiplied.

If a UF of 10 were applied for each of three reasons to a LOAEL, the resultant comparison value would be 1/1000th of the LOAEL.

Basis for adjustment

UF

Variation in human sensitivity

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Extrapolating data from animal studies to humans

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Extrapolation of data from subchronic studies to chronic exposure

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Use of LOAEL instead of NOAEL

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Other (severe or irreversible

effects )

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Understanding the assumptions The RfD and RfC are intended to provide an estimate of a daily

exposure to the human population including sensitive subgroups that is likely to be without an appreciable risk of deleterious effects during a lifetime (70 yrs).

Cancer slope factors and inhalation unit risk factors are intended too provide a means to estimate a theoretical risk of one excess cancer in a population of 1 million over a lifetime of exposure.

AEGLs (Acute Exposure Guideline Levels) are intended to estimate the risk of acute health effects resulting from exposures ranging from 10 minutes to 8 hours.

NJ Soil Cleanup Criteria assumptions for non-carcinogens Residential: EF 350 days, ED 6 yrs; BW 15 kg; IR 200

mg/day Non-residential:EF 225 days, ED 25 yrs; BW 70 kg; IR 100 g/day

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“Comparing comparison values” Comparison values for a substance are derived based upon a specific

health effect and are sometimes specific to a route of exposure.

Comparison values may differ among and sometimes within agencies for the same substance, health effect and route of exposure. Variation in uncertainty factors. Different studies form the basis of the dose-response

determination Assumptions regarding exposure differ

Assure a comparison value is appropriate to your assessment and evaluation. More than one value may be used.

There is no single source of “the correct” comparison values. All are estimates based on assumptions and research, both of which are subject to change.

Selecting the “right” comparison values requires an understanding of the assumptions an data.

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Multiple Comparison ValuesExample: Mercury Vapor (ug/m3)Workers OSHA PEL 100.0 NIOSH REL 50.0 ACGIH TWA 25.0

Acute population exposure EPA 1hr-AEGL3* 2,200.0 EPA 1hr-AEGL2* 333.0 Cal-OEHHA REL 1.8

* see below

Chronic population exposure EPA RfC 0.3 ATSDR MRL 0.2 Cal-OEHHA REL 0.09

Other advisory values** Isolate persons from exposure 10.0 Post-remediation re-occupancy

1.0

**ATSDR and others

AEGL3 - the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.

AEGL2 - … irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.

Source: http://epa.gov/oppt/aegl/pubs/define.htm

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Exposure Assessment Exposure - contact between a human and a contaminant.

It is influenced by many factors including:

Concentration of a contaminant in environmental media How much? What media?

The manner and extent of an individual’s contact with that media. What route? How often? How long? How much?

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Exposure Measurement

Measure the concentration of a contaminant in an environmental media and estimate or measure the an individual’s contact with that media and integrate these to develop the exposure estimate or dose.

Measure substances (biomarkers) that are indicative of exposure or effect in human biological media (tissues, hair, blood, urine, feces, breath etc.) the toxicant itself its metabolite substances formed by the body in response to the toxicant

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Direct Exposure Measurement - Biomarkers Exogenous chemicals, their metabolites, or products of

interactions between a xenobiotic chemical and some target molecule or cell that is measured in a compartment within an organism.

Typically reflect internal exposure from all pathways and sources.

Provide individualized exposure measurements. Considerations:

Validity of the marker for its intended use Invasiveness of the sampling method Practicality of the sampling method (e.g. 24-hr urine specimen) Legal requirements

Informed consent Privacy rules

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Biomonitoring: Population “norms” It may not be “normal” to have

toxicants in our body however most of us do.

CDC and others are conducting ongoing assessments human exposure through biomonitorng.

http://www.cdc.gov/exposurereport/

0

2

4

6

8

10

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0 25 50 75 100

Percentile

Blo

od

Hg

(u

g/L

) No fish meal

fishmeals 1-2

fishmeals +3

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Indirect Exposure Measurement Concentration of the contaminant in environmental media

Sample collection (air, water, soil, food) How? Where? When? How Many?

Sample analysis Where? What methods?

Extent of contact of individuals with environmental media Dependant on individual characteristics and activity patterns

How much air does a person breathe? How long is the person in the “contaminated” environment? What is the person doing when they are in that environment?

Exposure factors are available to aid in these determinations

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Exposure Factors Physical characteristics

Body mass and surface area by age and gender

Contact rates Inhalation rates by age, gender and activity level Water consumption by age, gender, activity level and climate Food ingestion by type, locale, etc.

Activity patterns Hours spent at home, in car, etc. by age and gender Activity level by age, gender, etc. Shower and bath frequency and duration

Many others Soil ingestion Soil adherence to skin

“MUST SEE” ReferencesExposure Factors Handbook, U.S. EPA.Child-Specific Exposure Factors Handbook,, U.S.EPAAvailable: http://cfpub.epa.gov/ncea/cfm/efprog.cfm

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Exposure Factors – Default Assumptions All factors are estimates. Using factors more specific to the population

or circumstances will help refine the estimate. For example, use gender or age specific factors if you have the data to support it.

Default assumptions are used where insufficient data exists and also for purposes of screening.

Adults Children Bodyweight 70 kg 16 kg (1-6 y.o)

Inhalation male 15.2 m3/day 8.7 m3/day (1-12 y.o.)

female 11.3 m3/day

Drinking water 2 L/day 1 L/day

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Estimating Daily Intake DI = (C x IR) / BW

Where: DI = Daily intake (mg/kg)

C = Concentration in environmental medium (mg/kg, mg/L, mg/m3)

IR = Intake rate of the environmental medium (kg/day, L/day, m3/day)

BW = Body weight (kilograms)

For multimedia exposure: [(C x IR )air + (C x IR)…] / BW

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Integrate environmental and individual data

Personal measurement

Measurement in media proximal to the points of exposure

Extrapolation of measurements media elsewhere to the point of exposure

Extrapolation based on little or no site specific information

Measure or direct observation

Self-reports, activity logs, records

Use “refined” reference values incorporating some specific information

Use “default” reference values

The exposure estimate integrates information regarding environmental contamination and individual factors that determine their contact with the contaminant.

A: Contaminant B: Individual

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Risk Characterization The results of the Exposure Assessment and Dose-Response

Assessment are summarized and integrated into quantitative and qualitative expressions of risk.

For non-carcinogenic effects, comparisons are made between projected intakes of substances and comparison values. The numeric expression of this comparison is often called the Hazard Quotient.

Carcinogenic effects are typically expressed as a probability of developing cancer assuming a lifetime of exposure.

Risk characterization includes qualitative and quantitative expressions of risk and must also include explanation and interpretation of the risk in light of the assumptions, judgments, and uncertainty inherent in the process.

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Output Hazard Index (HI). The sum of more than one hazard quotient

for multiple substances and/or multiple exposure pathways. The HI is calculated separately for chronic, subchronic, and shorter-duration exposures.

Hazard Quotient. The ratio of a single substance exposure level over a specified time period (e.g., subchronic) to a reference dose for that substance derived from a similar exposure period.

Slope Factor. A plausible upper-bound estimate of the probability of a response per unit intake of a chemical over a lifetime. The slope factor is used to estimate an upper-bound probability of an individual developing cancer as a result of a lifetime of exposure to a particular level of a potential carcinogen.

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Numeric estimates of risk Non-carcinogens – Hazard Index (HI), Hazard

Quotient (HQ) Divide daily intake by comparison value (RfD, RfC, MRL)

Value < 1 = no appreciable risk

Carcinogens – Excess risk of developing cancer Multiply DI by cancer slope factor (CSF) or unit risk

factor (URF) Value = additional cancers per number of

individuals exposed (e.g. 0.00001 = a risk of 1 additional person per among 100,000 population developing cancer over a lifetime)

What is the daily intake of arsenic from this exposure? (DI) = (C x IR) ÷ BW DI = (0.05 mg/L x 2 L/d) ÷ 70 kg = 0.0014 mg/kg-d

What is the non-cancer risk estimate of this exposure? Comparison value (e.g. EPA Oral RfD = 0.0003 mg/kg-d) Hazard Index = DI ÷ RfD Hazard index = 0.0014 mg/kg-day ÷ 0.0003 mg/kg-d = 4.7

What is the cancer risk estimate for this exposure? Comparison value (e.g. EPA Oral CSF = 1.5 (for DI in mg/kg-d) Excess cancer risk = DI X CSF Excess cancer risk = 0.0014 mg/kg-day x 1.5 = 0.002

(e.g. 2 excess cancers per 1,000 people consuming this water over a lifetime)

Example: Quick screening scenario

Assume persons weighing 70 kg consume 2 L/day of drinking water containing 50 ug/l arsenic. Ignore other routes or sources of exposure.

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IMPORTANT Simply being exposed to a hazardous substance

does not make it a health risk. The magnitude, frequency, timing, and duration of exposure and the toxicity characteristics of individual substances affect the degree of risk, if any.

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How much risk is acceptable? Depends on the context and who you ask.

Hazard quotient - A comparison of an estimated chemical intake (dose) with a reference dose level below which adverse health effects are unlikely. Conservatively < 1 is good.

“De minimis risk" refers to a level of risk which is too small to be concerned with -- some refer to this as a "virtually safe" level. For cancer risk, an increase of 1 in 1,000,000 or lower is considered de minimis.