evaluation of mixture exposures in human health risk...

Evaluation of Mixture Exposures in Human Health Risk Assessments

March 2016

Ruth Custance, MPH

Objectives

• Objectives • Describe each of the major steps of a HHRA

• Data Evaluation • What chemicals and at what levels • Where are they, what media?

• Exposure Assessment • Determine potential for human contact with impacted media

• Toxicity Assessment • Potential for health effects – how much (dose)?

• Risk Characterization • Combine exposure and toxicity assessments to estimate risk

• Examples of mixture HHRA

Overview

• What is a Human Health Risk Assessment (HHRA)? • Used as a tool to identify potential hazards, determine who is

at risk and estimate the probability of adverse health effects • Identify individuals contacting chemicals and the potential for

adverse health outcomes (e.g., cancer) • Intended to be protective of individuals who are at greatest risk;

those more sensitive to health effects (e.g., children, the elderly) • Results tend to be overly protective for most individuals • Not a clinical medical evaluation

• Used to evaluate the need for remediation/corrective action • Use of generic cleanup goals • Develop site-specific cleanup goals

Four Steps of Risk Assessment

Your Logo

Hazard ID Exposure Assessment

Toxicity Assessment

Risk Character-

ization

Risk Characterization

Your Logo

Adverse effect / risk depends on

toxicity and exposure RISK

Data Evaluation

• Initial Step of an HHRA • Develop a data set • Identify media-specific Chemicals of Potential Concern

(COPCs) • Data Evaluation

• Duplicate/split samples • Multiple analytical methods

Data Evaluation

• Selection of COPCs • Comparison to Screening Levels • Frequency of Detection (FOD; 5%) • Other criteria

• Background Evaluation • Metals • Carcinogenic PAHs (cPAHs)

Data Evaluation

• Background Evaluation of Metals • Determine if the data demonstrates more than 1 population; the

lower typically represents local background conditions and the other is considered impacted by site-related activities

• Use a weight of evidence approach where indicators of background consider: • the degree to which the Site data are fit by a normal, lognormal, or

other distribution (Cal-EPA 1997 states that ambient metals data follow a normal or lognormal distribution);

• 2) a graphical assessment (probability, or quantile-quantile plots, against the normal, lognormal, or other distribution) to identify breaks or nonlinearity indicative of more than a single population; and

• 3) the skewness of the data as indicated by the coefficient of variation (CV = standard deviation ÷ average)

Data Evaluation

Data Evaluation

• Evaluating Carcinogenic PAHs (cPAHs) – Current Scheme • Benzo(a)pyrene equivalent concentration derived using toxicity

equivalency factor (TEF) approach. • TEFs based on shared characteristics of the cPAHs • Ranking by using BaP as the reference chemical

• TEFs were multiplied by the individual cPAH concentrations. Adjusted concentrations were then summed to yield a total BaP-equivalent concentration.

• BaP-equivalent compared to southern CA background of 0.9 mg/kg

Proposed Scheme

From EPA 2010

Data Evaluation

• Evaluating Dioxin and Dioxin-like PCB Congeners • Toxicity equivalency factor

(TEF) approach. • TEFs based on shared

characteristics • Ranking by using 2,3,7,8-TCDD

as the reference chemical

Exposure Assessment

• Estimate the magnitude, frequency, duration, and routes of exposure • Identify receptors potentially exposed to COPCs in

environmental media, the exposure pathways and route of potential intake (conceptual site model; CSM);

• Estimate COPC concentrations to which the receptors are potentially exposed (exposure point concentrations, EPCs); • Direct use of monitoring data • Estimating EPCs using Fate and Transport models, which quantify

relationship between COPC concentration in impacted medium (e.g., GW) and the concentration in the exposure medium (e.g., indoor or outdoor air);

• Estimate COPC intake

Presenter

Presentation Notes

Who has the potential for exposure? How can they be exposed? Playing on soil; eating fish When and how often could they be exposed? Every day 5 days a week How much of the COPC could get into someone?

Exposure Assessment

• Conceptual Site Model (CSM) • Identify potential chemical sources

• USTs; ASTs; chemical storage; offsite release; former agricultural area; transformers, former drycleaner; etc.

• Release mechanism – accidental spills/leakage • Impacted exposure media – soil, groundwater • Transport mechanism

• Volatilization; fugitive dust emissions; leaching; direct contact

• Exposure routes • Incidental ingestion, dermal contact; indoor and outdoor inhalation

• Receptors of concern • Depends on current/future land use: residential, commercial, recreational

Exposure Assessment

Conceptual Site Model**

Exposure Assessment

• Exposure Point Concentrations EPCs are the concentrations of chemicals in environmental media to which receptors may be exposed through defined exposure pathways considered complete.

• Identify impacted media • Shallow soil (0 to 10 ft bgs); soil gas; sub-slab; groundwater

• Use of the maximum versus the 95% Upper confidence limit of the average concentration (95UCL) • Site-wide risk assessment (residential vs commercial) • Point-by-point risk assessment

• Derivation of 95UCLs using ProUCL

Exposure Assessment

• Fate and Transport Modeling Quantitative analysis of how chemicals move through the environment and how they are transformed by processes such as chemical reaction and biological degradation

• Transport of particulate-phase COPCs (metals; SVOCs) from soil matrix to outdoor air;

• Transport of vapor-phase COPCs (VOCs) from soil matrix to outdoor air;

• Transport of vapor-phase COPCs (VOCs) from groundwater to outdoor air; and

• Transport of vapor-phase COPCs (VOCs) from the subsurface to indoor air (vapor intrusion pathway).

Exposure Assessment

• Fate and Transport Modeling • Soil to Outdoor Air: Particulate emission factor (PEF)

Where: PEFres = particulate emission factor, cubic meters per kilogram (m3/kg); Q/Cres = inverse of the ratio of the geometric mean air concentration to the emission flux at center of the source (g/m2-s per kg/m3); CF = units conversion factor (3,600 s/hr); 0.036 = empirical constant (g/m2-hr); G = fraction of vegetative or other cover (0.5 unitless; USEPA, 2002); UM = mean annual wind speed (m/sec; NCDC, 2010); UT = equivalent threshold value of wind speed at 7 meters above ground surface (11.32 m/sec; USEPA, 2002); and Fx = function dependent on UM/UT (0.194 unitless; USEPA, 2002).

]F UU G)-(1 [0.036

CF) (Q/C = PEF

x

3

T

M

resres

×

××

×

Exposure Assessment

• Fate and Transport Modeling • Soil to Outdoor Air: Volatilization factors (VFs)

Where: VFsoil = COPC-specific volatilization factor (m3/kg); Q/C = inverse of mean concentration at center of source (g/m2-s per kg/m3); DA = COPC-specific apparent diffusivity (cm2/s); T = exposure interval (seconds; and Pb = soil bulk density (g/cm3).

( )

( )A

1/2A2

24-

soil D Pb 2

T D 3.14 cmm 10 Q/C

= VF××

×××

×

Exposure Assessment

Garage Air

Indoor Air

Indoor Sources

Sub-Slab Soil Vapor

Outdoor Air

AF – attenuation factor

Exposure Assessment

• Fate and Transport Modeling • Vapor Intrusion Pathway

• Soil Gas; Groundwater; Sub-slab Soil Gas • Use of default (Cal-EPA VIG, 2011) versus site-specific attenuation factors

Exposure Assessment

Exposure Assessment

• End product of the Exposure Assessment • COPC Intake = An integration of the exposure parameters for the

receptors of concern with the EPCs for the media of concern • Average daily dose (ADD) for noncarcinogens • Lifetime average daily dose (LADD) for carcinogens • Generic Intake equation:

Where:

EPC = exposure point concentration (e.g., mg of chemical per kilogram of soil);

CR = contact rate with medium (e.g., mg of soil/day);

EF = exposure frequency (days/year);

ED = exposure duration (years);

BW = body weight (kg);

AT = averaging time (days): cancer effects: 70 yrs x 365 days; noncancer effects: ED x 365 days.

• Intake equations for specific exposure routes

ATBW ED EF CR EPCDoseor Intake

××××

=

Exposure Assessment

• Exposure Parameters • HERO Note 1; Cal-EPA DTSC, September 2014 • USEPA* Regional Screening Level (RSL); November 2015

Exposure Assessment

• Other Sources of Exposure Parameters • Standard Default Exposure Factors; USEPA, 1991 • Exposure Factors Handbook; USEPA, 2011 • Child-Specific Exposure Factors Handbook; USEPA, 2008 • Supplemental Guidance for Dermal Risk Assessment; USEPA,

2004 • Risk Assessment Guidance for Superfund (RAGS). Volume I:

Human Health Evaluation Manual, Part A. USEPA, 1989 • Preliminary Endangerment Assessment (PEA) Guidance

Manual. Cal-EPA, 2013

Toxicity Assessment

• Characterizes the relationship between the magnitude of exposure to a COPC and the nature and magnitude of adverse health effects that may result from exposure (dose-response).

• Cancer toxicity criteria: • Carcinogens known to cause cancer • Oral cancer slope factors (CSFs) • Inhalation unit risk factors (URFs or IURs)

• Noncancer toxicity criteria: • Noncarcinogens that may have adverse effects on reproductive,

developmental, other target organs • oral reference doses (RfDs) • inhalation reference concentrations (RfCs) or reference exposure

levels (RELs)

Toxicity Assessment

• Toxicity criteria are selected from the following sources, in order of preference and based on availability:

• Cal-EPA Office of Environmental Health Hazard Assessment (OEHHA) Toxicity Criteria Database, online (Cal-EPA, 2016);

• USEPA Integrated Risk Information System (IRIS) (USEPA, 2016); and

• USEPA Regional Screening Levels (RSL) for Chemical Contaminants at Superfund Sites (USEPA, 2015).

For sites in California, final selection is based on recommendations presented in Cal-EPA DTSC’s HHRA Note 3 (Cal-EPA, 2016).

Toxicity Assessment

• Route-to-route extrapolation • Toxicity criteria based only on oral and inhalation routes of

exposure • Oral toxicity criteria used to evaluate dermal exposures • Sometime route-to-route between ingestion and inhalation

• Surrogate chemical • Toxicity criteria for a structurally similar compound is

assigned to a COPC lacking toxicity criteria

Toxicity Assessment

• Lead evaluated differently • No reference dose available for lead (RfD assumes a threshold; no

adverse effects if concentration below RfD) • Evidence suggests that adverse health effects occur even at very low

exposures to lead (e.g., neurological effects in children)

• Exposure/toxicity evaluated by comparison to blood lead (PbB) levels. Acceptable soil level based on 99% of a population having PbB levels <1 or 10 ug/dL • For sites in California

• Residential soil CHHSL = 80 mg/kg; Commercial soil CHHSL = 320 mg/kg • Cal-EPA LeadSpread

• Calculates cleanup levels for a 2-3 year old child • Adult module being re-evaluated


• Integrates exposure and toxicity assessments to estimate potential cancer risks and noncancer hazards that are then compared to acceptable standards

• Risk Management Criteria (Target risk levels) Various demarcations of acceptable risk have been established. The National Oil and Hazardous Substances Pollution Contingency Plan

(NCP; 40 CFR 300) = an acceptable risk range of 1×10-6 to 1×10-4 for carcinogens and a target noncancer hazard of 1 for noncarcinogens.

DTSC considers the 1×10-6 cancer risk level as the generally accepted point of departure for unrestricted land use (residential).

A 1×10-5 risk level (the “mid-point” of the risk management range) is commonly used for managing commercial/industrial land use sites in California.


• Site-Wide Risk Assessment • Quantify Cancer Risks and Noncancer Hazards

• Individual COPC:

• Multiple COPCs and multiple pathways:

ATBW ED EF CR EPCDoseor Intake

××××

=

( )RELor RfDADD =Quotient Hazard

( )or URF CSF LADD =Risk Cancer ×

( )

++= ∑

=

n

1ioni,inhalatidermali,ni,ingestiototal CRCRCRRiskCancer

( )

++= ∑

=

n

1ioni,inhalatidermali,ni,ingestiototal HQHQHQIndex HazardNoncancer


• Point-by-Point Risk Assessment • Derive Risk-Based Concentrations (RBCs):

• Cumulative Risk at a given sample location:

( )[ ] ( )1inh.sdermaloraloralC-Soil CFECFURFIF IFCSF

TRRBC××++×

=

+

+

=

RfCECF

RfDIF

RfDIF

THQRBCsinh,

oral

dermal

oral

oralNC-Soil

TR

RBCC

RiskCancer n

1i iC,-Soil

iStotal ×

= ∑

=

THI

RBCC

Index Hazardn

1i iNC,-Soil

iStotal ×

= ∑

=


• Point-by-Point Risk Assessment continued • Results for each sample

depth • Risk Exceedance Figures • Lead and Arsenic • Identify Risk Drivers

• COPCs with Cancer Risk >1E-6

• COPCs with Noncancer HQs >1


From EPA 2011

Risk Characterization of Mixtures - Component vs. Whole Mixture Approaches

Component-based methods (Practical) simple models describe complex biological processes-

based method Need good toxicity and exposure data on individual

components Typically additivity is assumed

Whole mixture based assessments (Preferred??) Need good toxicity and exposure data on the whole

mixtures Need to evaluate sufficient similarity Can also assess fractions of the whole mixture Not many assessments done to date Adapted from EPA, 2011

Risk Characterization of Mixtures

Which mixture to test? Actual environmental mixture Similar mixture Lab mixture Key chemicals Complex fractions of whole mixture

Don’t forget Fate & Transport Model needs

Risk Characterization of Mixtures - Component vs. Whole Mixture Examples

Component Carcinogenic PAHS Dioxins Pesticides (Office of Pesticide Programs)

Whole Mixture TPH (Fractions) Aroclors

TPH Risk Assessment

TPH compounds include a wide range of chemicals that are found in crude oils, petroleum products, and other petroleum-related materials.

Chemical properties and environmental behavior vary widely among the many hundreds of compounds present in these mixtures.

TPH mixtures pose a challenge in risk assessment due to difficulty in predicting toxicity as well as environmental fate and transport

TPH Risk Assessment

Traditional approaches to risk assessment evaluate: Indicator compounds (e.g., benzene) – inadequate

coverage Quantify the whole TPH mixture – not relevant to many

sites, as composition is highly variable Massachusetts Dept of Environmental Protection (2002,

2003) VPH/EPH approach VPH & EPH analytical methods differentiate & quantify

aliphatic & aromatic fractions at a site Toxicity values assigned to each fraction, based on

surrogate chemicals Assesses mixture risk, accounts for variations in mixture

composition

TPH Risk Assessment

From EPA, 2009

TPH Risk Assessment

TPH-G =50% of TPH

Aliphatic: C5-C850% of TPH

Aromatic: C9-C16

TPH-D =50% of TPH

Aliphatic: C9-C1850% of TPH

Aromatic: C9-C16

TPH-Mo =50% of TPH

Aliphatic: C18+50% of TPH

Aromatic: C17+

Often assume 50:50 mix if no site-specific fraction data

Comparison of Site-Specific TPH Risks

Compared indicator chemical risks/hazards to TPH hazards

Did the Risk Management Decision Change? Decision Criteria assuming residential land-use Cancer Risk of 1 x 10-6

Hazard Index of 1

Comparison of Site-Specific TPH Risks in Soil

SSCGnc SSCGcNoncancer

HazardCancer

Risk

Benzene µg/kg 336.4 95UCL 6.7E+04 2.2E+02 5E-03 2E-06

Benzo (a) Pyrene mg/kg 0.111 95UCL -- 1.6E-01 -- 7E-07

Naphthalene mg/kg 6.314 95UCL 1.5E+02 4.0E+00 4E-02 2E-06

TPH as Diesel mg/kg 5691 95UCL 1.3E+03 -- 4E+00 --

Constituentof

ConcernUnits EPC EPC

Basis

Onsite Resident

Case #1

Case #2


HazardCancer

Risk





Onsite Resident Constituentof


Basis

Comparison of Site-Specific TPH Risks in Soil

Case #3

Case #4


HazardCancer

Risk

Benzene µg/kg 246 95UCL 6.7E+04 2.2E+02 4E-03 1E-06




Constituentof


Basis

Onsite Resident


HazardCancer

Risk





Constituentof


Basis

Onsite Resident

Comparison of Site-Specific TPH Risks in Sub-Slab Soil Gas

TPH - aliphatic: C5-C8 5.2E-03

TPH - aliphatic: C9-C18 1.3E-01

TPH - aromatic: C9-C16 2.9E+00

1,2,4-Trimethylbenzene 1.4E-01

1,3,5-Trimethylbenzene 1.1E-02

2-Butanone (MEK) 4.1E-05

2-Hexanone 6.3E-04

4-Ethyltoluene 3.1E-03

4-Methyl-2-pentanone (MIBK) 8.1E-06

Acetone 3.1E-05

Benzene 1.2E-02

Carbon disulf ide 1.4E-05

Chloroform 2.8E-04

Chloromethane 1.1E-04

Ethylbenzene 1.0E-04

Napthalene 2.6E-02

Toluene 7.6E-04

Trichloroethene 2.6E-02

Xylene, o- 1.8E-03

Xylenes, m,p- 4.3E-03

Cumulative Risk and Hazard 3E+00

Comparison of Site-Specific TPH Risks

For soil, conclusions are the same in 3 out of 4 cases In one case where the indicator chemicals did not

indicate risk/hazard the TPH hazard was marginally elevated (2 versus Target HI of 1)

This site was dominated by Diesel TPH – other sites may differ

For soil gas VOCs under predicted estimated hazard

Uncertainties in Assessing Chemical Mixtures

Few Mixtures/Chemical Classes Currently Represented Lack of Chemical/Physical Properties for EF&T Modeling Site-specific conditions can change mixtures, e.g. TPH

“weathering” – is the toxicity data really representative of your mixture?

Questions?

evaluation of mixture exposures in human health risk...

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