Exposure assessment

Milena Černá

DefinitionExposure is defined as contact over time and

space between a person and one or more biological, chemical or physical agents (contact with the outer part of the human body with a cerrier medium – air, water, food, dust, soil)

Exposure assessment is to identify and define the exposures that occur, occurred or are anticipated to occur in human population

Exposure concentration (mg/L, mg/kg, mg/m3) is defined as the concentration of an environmental agent in the carrier medium at the point of contact with the body.

Aspects important in exposure analysisAspects important in exposure analysis

Agent(s):Agent(s): biological, chemical, physical biological, chemical, physical components, complex mixturescomponents, complex mixtures

Source(s): anthropogenic – natural, area – point, Source(s): anthropogenic – natural, area – point, stationary – mobile, indoor – outdoor…stationary – mobile, indoor – outdoor…

Transport/carrier medium: air, water, soil, dust, Transport/carrier medium: air, water, soil, dust, food, productfood, product

Exposure pathways: eating contaminated food, Exposure pathways: eating contaminated food, breathing polluted air, touching contaminated breathing polluted air, touching contaminated surface etc.surface etc.

Exposure concentration: mg/kg (food) mg/L (water), Exposure concentration: mg/kg (food) mg/L (water), mg/mmg/m33 (air) mg/cm (air) mg/cm22 (contaminated surface) (contaminated surface)

Exposure routes: inhalation, ingestion, dermal Exposure routes: inhalation, ingestion, dermal contact, multiple wayscontact, multiple ways

Aspects important in exposure analysis (cont.)Aspects important in exposure analysis (cont.)

Exposure durationExposure duration: seconds, minutes, hours, : seconds, minutes, hours, days, weeks, months, years, lifetimedays, weeks, months, years, lifetime

Exposure frequencyExposure frequency: continuous, intermitent, : continuous, intermitent, cyclic, random, rarecyclic, random, rare

Exposure settings:Exposure settings: occup., environ., residential, occup., environ., residential, indoors, outdoorsindoors, outdoors

Exposed populationExposed population: general, occupational, : general, occupational, subgroups, individualssubgroups, individuals

Geographic scopeGeographic scope: site/source specific, local, : site/source specific, local, regional, national, international, globalregional, national, international, global

Time frame:Time frame: past, present, future, trends past, present, future, trends

Exposure assessmentExposure assessment - steps - steps

Identifying and evaluation exposure pathwaysIdentifying and evaluation exposure pathways

Determination whether these elements are Determination whether these elements are linked to form an exposure pathwaylinked to form an exposure pathway

Categorization an exposure pathway as a Categorization an exposure pathway as a completed exposure pathway or a potential completed exposure pathway or a potential exposure pathwayexposure pathway

Determination whether the exposure pathway Determination whether the exposure pathway should be eliminated or further discussed in the should be eliminated or further discussed in the health risk assessmenthealth risk assessment

Source of contamination (source of contaminant release into the environment, or the environmental media responsible for causing contamination if the original source is unknown)

Environmental media and transport mechanism (air, groundwater, surface water, surface soil, sediment, biota). Transport mechanisms serve to move contaminants from the source to points where human exposure can occur.

Point of exposure (a location of potential or actual human contact with a contaminated medium

Route of exposure (means by which the contaminant actually enters or contacts the body)

Ingestion, inhalation, dermal contact Remember: Different routes of exposure to a contaminant may result in

different health concerns

Receptor population (persons who are exposed or potentially exposed to the contaminants of concern at a point of exposure)

Remember: an exposure pathway is not simply an environmental medium (e.g. air, soil, water) or a route of exposure. Rather, an exposure pathway includes all the elements that link a contaminant source to a receptor population.

Ad 1 – Identifying of a source of Ad 1 – Identifying of a source of contaminationcontamination

• A contaminant source is the origin of the environmental contamination: e.g. incinerator, pipe, lagoon, landfill..

• It is necessary to describe: location or release point, history of storage, disposal, or release, contaminants and concentrations at the source, emission rates, frequency of release, operating period, and current status.

Ad 2: Identifying of environmental media and transport

• It is necessary to identify all the It is necessary to identify all the environmental media that may serve environmental media that may serve to transport contaminants from the to transport contaminants from the source to possible points of human source to possible points of human exposureexposure

• air - soil, surface water, sediment, air - soil, surface water, sediment, vegetation, fish, cattle....(food chain) vegetation, fish, cattle....(food chain) - waste material, sludge..- waste material, sludge..

• RememberRemember: Contaminants may : Contaminants may move from one medium to anothermove from one medium to another

Once a substance is released to the Once a substance is released to the environment, one or more of the following may environment, one or more of the following may occur:occur:movement - physical transformation (rain, movement - physical transformation (rain, volatilization) - chemical transformation volatilization) - chemical transformation (photolysis, hydrolysis, oxidation/reduction) - (photolysis, hydrolysis, oxidation/reduction) - accumulation in one or more media.accumulation in one or more media.The The bioconcentration factorbioconcentration factor is a measure of is a measure of the extent of chemical partitioning at the extent of chemical partitioning at equilibrium between a biologic medium, such as equilibrium between a biologic medium, such as a fish tissue, and an external medium, such as a fish tissue, and an external medium, such as water. Some contaminants significantly water. Some contaminants significantly bioconcentrate in fish and vertebrate (e.g. PCBs, bioconcentrate in fish and vertebrate (e.g. PCBs, chlorinated pesticides, mercury), some other not chlorinated pesticides, mercury), some other not (e.g. PAHs). (e.g. PAHs). Food chain - Food chain - human exposurehuman exposure

Ad 3: Identifying of a point of exposure

• The point of exposure is the point at which people contact a contaminated medium. It is necessary to recognise also the existed past exposure points and the potential exposure points in the future.

• Air exposure - involve contaminants that are volatile or adsorbed to airborne particulates and may occur indoors or outdoors

• Food chain exposure point occur if people consume plants, animals, or other food products that have contacted contaminated soil, sediment, waste materials, groundwater, surface water, air, or biota

• Soil may serve as an exposure point for on-site workers, for children playing outside, ...

• Groundwater exposure points include wells used for municipal, domestic, industrial, and agricultural purposes. Groundwater may be used as a water supply source for swimming pools and other recreational activities.

• Surface water exposure points include irrigation and public, industrial and livestock water supplies

• Drinking water - chlorination by-products

Ad 4: Identifying of a route of exposure

• Exposure routes are the means by which contaminants enter the human body. They include:

• ingestion of contaminants in food, water, soil

• inhalation of contaminants in air, or via stems and aerosols in water or soil

• dermal contact with contaminants in water, soil, air, food, and other media

Ad 5: Identifying receptor population

• Each exposure pathway should be considered with respect to populations (e.g. workers, residents, children, women, seniors, vegetarians etc.).

• Exposed population should be identified as accurately as possible.

• Location of population• Populations exposed via contact with water (bathing, recreation)• Populations exposed via inhalation• Populations exposed via ingestion of soil• Populations exposed via ingestion of drinking water• Populations exposed via ingestion of food (a survey or other

adequate study of regional dietary habits may be necessary to determine the amount and frequency of contaminated food intake)

Exposed population

Persons should be considered exposed if:

• they ingest, inhale, or contact the contaminant in one or more environmental media

• exposure has been verified by human biologic measurements or medical examination

• Potentially exposed population

• No known exposure

Factors influencing exposure

• Age of populations (children, pregnant women or seniors may be at a higher risk)

• Gender• Climatic conditions• Frequency of outdoor/indoor activities,

recreational activities• Site accessibility• Food sources (agricultural and home fruit and

vegetable production in contaminated soil, irrigated with contaminated water, etc.)

Estimating exposures

The following factors should be considered:

• Exposure duration

• Exposure frequency

• Exposure fluctuation (continuous or intermittent)

Bioavailability

• In order to exert a toxic effect, most chemicals must be absorbed into the body. Absorption of contaminants may vary dramatically depending on the route of exposure.

• Once a contaminant has been absorbed into the body, it is distributed to various organs in accordance with pharmacokinetic principles.

• The dose that reaches the target organ is what ultimately determines the toxic effect.

Calculation of exposure

• Exposure (dose) ( mg/kg bw./d):• = C x IR x EF x ED/BW x AT• Where:• C = concentration of compound in the medium• IR = intake of environmental medium (in cubic meters,

L, g etc. per day)• EF = frequency of exposure (in days) per year• ED = duration of exposure in years• BW = body weight in kg• AT = time (in days), for calculation of exposure (e.g.

70 y for carcinogenic risk)

Limit valuesLimit values

Reference dose Reference dose (RfD) = estimation of daily population (RfD) = estimation of daily population exposure dose (including vulnerable subpopulation exposure dose (including vulnerable subpopulation groups) which does not represent adverse health groups) which does not represent adverse health effect for population during the whole life exposureeffect for population during the whole life exposure

Acceptable daily intakeAcceptable daily intake (ADI) = estimation of peroral (ADI) = estimation of peroral daily intakedaily intake which does not represent adverse health which does not represent adverse health effect for population during the whole life exposureeffect for population during the whole life exposure (WHO - (WHO - used for food additivesused for food additives) )

Tolerable daily intakeTolerable daily intake (TDI) = dt (TDI) = dttto ADI, used for food o ADI, used for food contaminantscontaminants

Tolerable weekly intake (TWI), Tolerable monthly intake Tolerable weekly intake (TWI), Tolerable monthly intake (TMI) = dt(TMI) = dttto, for cumulative compoundso, for cumulative compounds

Human exposure assessment

Environmental monitoring

Personal monitoring

Biological monitoring: Biomarkers of exposure

Biomarkers of effects

Modelling

Advantages of biological markers:

Improved exposure assessment from all sources

Disadvantages:

Lack of specificity, variability of markers, ethical problems

The use of biomarkers in exposure assessment and body burden determination

The use of biomarkers in exposure assessment and body burden determination

BIOMARKERSBIOMARKERS

Environm. Health status

Genetic background

Human exposure

• Absorbed – internal dose

• Biological effective dose

• Early adverse effect

• Disease

Biomarkers

• Biomarkers of exposureBiomarkers of exposure• Biomarkers of effectsBiomarkers of effects• Biomarkers of susceptibilityBiomarkers of susceptibility

Internal (absorbed) dose

Tissue dose

Cell dose

Macromolecular dose

Target dose

Biologically active dose

Exposure

Effect Molecular dosimetry

Human biomonitoring

Analysis of contaminants, their metabolites Analysis of contaminants, their metabolites or other changes related to the exposure or other changes related to the exposure in human body fluids and tissues.in human body fluids and tissues.

Blood, urine, saliva, hair, nails, teeth etcBlood, urine, saliva, hair, nails, teeth etc

Different population groupsDifferent population groups

StandardizedStandardized sampling and analysissampling and analysisStatistical evaluationStatistical evaluation

Interpretation of resultsInterpretation of results Long-term time trendsLong-term time trends

NHANESNHANES

• ““Third National Report on Human Third National Report on Human Exposure to Environmental Chemicals”Exposure to Environmental Chemicals”

• Department of Health and Human Department of Health and Human ServicesServices

• Centers for Disease Control and Centers for Disease Control and PreventionPrevention

• July 2005July 2005• http://www.cdc.gov/exposurereport/http://www.cdc.gov/exposurereport/

3rd/pdf/thirdreport.pdf3rd/pdf/thirdreport.pdf

SCALE SCALE

• “SCALE Baseline Report on ”Biomonitoring of Children” in the framework of the European Environment and Health Strategy (COM(2003)338 final)”

• Technical Working Group on Integrated Monitoring subgroup Biomonitoring of children

• January 2004• http://www.brussels-conference.org/

Download/baseline_report/BR_Biomonitoring_final.pdf

European Commission, European Commission, BrusselsBrussels

Human Biomonitoring: • Support to the European Environment &

Health Action Plan 2004-2010• Under Action 3 of the European Environment

and Health Action Plan 2004-2010, the European Commission announced to develop a coherent approach to human biomonitoring in Europe and to launch an EU Pilot Project on human biomonitoring by the end of 2006.

• www.eu-biomonitoring.org

IG Human biomonitoringIG Human biomonitoringLisabon, June 2005Lisabon, June 2005

Environmental Health Environmental Health Monitoring SystemMonitoring System in in the Czech the Czech

RepublicRepublic

Resolution No. 369/1991 of Resolution No. 369/1991 of the Government of the the Government of the Czech RepublicCzech Republic.

Routinely operated since Routinely operated since 1994.1994.

One of the priorities of the One of the priorities of the National Environmental National Environmental Health Action Plan Health Action Plan (Government Resolution No. (Government Resolution No. 810/199).810/199).

Relied upon the Act No. Relied upon the Act No. 258/2000 on Public Health258/2000 on Public Health.

www.szu.czwww.szu.cz

Structure of the Czech Environmental Health Monitoring System

• Subsystem 1 - AirSubsystem 1 - Air• Subsystem 2 – Drinking waterSubsystem 2 – Drinking water• Subsystem 3 - Subsystem 3 - NNoiseoise• Subsystem 4 – Dietary exposureSubsystem 4 – Dietary exposure• Subsystem 5 – Biological monitoringSubsystem 5 – Biological monitoring• Sobsystem 6 – Health status Sobsystem 6 – Health status • Subsystem 7 – Occupational environmentSubsystem 7 – Occupational environment• Subsystem 8 - SoilSubsystem 8 - Soil

Human Biological Monitoring in CR

• Adult population – blood donors• Children 8 – 10 y• Women after delivery (human milk)

• Body fluids and tissues:Blood/serum, urine, human milk, hair, teeth

M uži

4944 44 45

49

4034 35

4944 44 45

49

4034 35

1996 1997 1998 1999 2000 2001 2002 2003

Ro ky

0

20

40

60

80

100

120

µg

/l

M e d iá n 25% -75% kv a n t il 5% -95% kv a n t il

Blood lead levels in menBlood lead levels in men

Že ny

3027 27 29

3228

2225

3027 27 29

3228

2225

1996 1997 1998 1999 2000 2001 2002 2003

R o ky

0

20

40

60

80

100

120

µg

/l

M e d iá n 25% -75% kv a n t il 5% -95% kv a n t il

Blood lead levels in women

31

36

41

2124

29

0

10

20

30

40

50

Men <25yrs*

Men 25 -35 yrs*

Men >35yrs*

Women<25 yrs•

Women 25- 35 yrs•

Women>35 yrs•

µg/l

Blood lead levels related to ageBlood lead levels related to age

1 .2 0

0 .4 00 .5 0

1 .2 0

0 .4 00 .5 0

K u řáci N ek u řáci P as iv n í k u řáci0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

3 .0

3 .5

4 .0

µg/

l * p < 0 .0 5K u ř á ci v s . N ek u ř á ciK u ř á ci v s . P a s iv n í k u ř á ci

*M ed ián 2 5 % -7 5 % k v an t il 5 % -9 5 % k v an t il

Blood cadmium levels according to smoking Blood cadmium levels according to smoking habithabit

0 .6 00 .5 0 0 .5 0 0 .5 0

0 .4 0 0 .4 5 0 .4 00 .3 0

0 .6 00 .5 0 0 .5 0 0 .5 0

0 .4 0 0 .4 5 0 .4 00 .3 0

1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 0 0 0 2 0 0 1 2 0 0 2 2 0 0 3

R o k y

0

1

2

3

4

µg/

l

M ed ián 2 5 % -7 5 % k v an t il 5 % -9 5 % k v an t il

Blood cadmium levels in Blood cadmium levels in nonsmokersnonsmokers

0.30

0.42

0.30

0.42

M u ži Ž e n y0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

µg

/g k

reat

inin

u

N =768

N =279

M e d iá n 25% -75% kv a n t il 10% -90% kv a n t il

Urine cadmium level according to Urine cadmium level according to gendergender

Cadmium in blood of the Czech population - gender, smoking - 1996-1998 (medians, mg/l)

0,7 0,7

1,2

0,5

0,7

1

0,6

0,15

0

0,2

0,4

0,6

0,8

1

1,2

1,4

Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston

2000/01 – 32000/01 – 3rdrd round of the WHO international round of the WHO international study WHO– sum of indicator PCBs in human study WHO– sum of indicator PCBs in human

milk, ng/g fatmilk, ng/g fat

0

100

200

300

400

500

600

Cze

ch R

ep.

Slova

kia

Italy

Spa

in

Ger

man

y

Luxe

mb. NL

Belgium

Rom

ania

Swed

en

Ukr

aine

Cro

atia

Rus

sia

Nor

way

Egy

pt

Finlan

d

Irelan

d

USA

China

Bulga

ria

New

Zea

land

Hun

gary

Aus

tralia

Phillipp

ines Fidji

Bra

zilia

Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston

33rdrd round of WHO study; PCDDs and PCDFs in round of WHO study; PCDDs and PCDFs in human milk expressed as WHO-TEQ values, human milk expressed as WHO-TEQ values,

pg/g fatpg/g fat

0

5

10

15

20

25

30

35

TEQ-PCDD/DF TEQ/PCB

3000

1355 1273

831709 717 740 653

539799 756

0

500

1000

1500

2000

2500

3000

3500

1985 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

ng/g

fat

Levels of indicator PCBs in human milk Levels of indicator PCBs in human milk (sum of congeners (138+153+180) x 1.7(sum of congeners (138+153+180) x 1.7 – –

comparison with the results in 1985 comparison with the results in 1985 (prohibition of PCBs in CR)(prohibition of PCBs in CR)

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Years

0

100

200

300

400

500

600

700

µg

/kg

fat

Median 25% -75% 10% -90%

Levels of indicator congener PCB 153 in Levels of indicator congener PCB 153 in human milkhuman milk

BIOMARKERs of early adverse biological effects (genotoxins)

BIOMARKERs of early adverse biological effects (genotoxins)

FISH

Sister chromatid exchange

Micronuclei

Mutation in hypoxantin-guanin

fosforibosyltransferase gen (HPRT)

Activation of oncogens coding synthesis of

proteins p53 a p21

Chromosomal aberration

In the Czech Rep. the cytogenetic analysis of human peripheral lymphocytes is used

as relevant biomarker for monitoring exposure and early effect of

persons occupationally exposed to genotoxic carcinogens

sincesince 1974 1974

Group exposure test:

Till 2% of aberrant cells in group = background value

2 – 4% of aberrant cells in group = increased exposure

Over 4 % of aberrant cells in group = high exposure

CONVENTIONAL TECHNIQUE

SCE

Micronuclei

FISH

COMET

6.52

2.6 2.7

2.2

0

1

2

3

4

5

6

7

Brno 1985 NL 1994 Praha 1994 Brno 1999

% A

B.C

.Frequency of chromosomal Frequency of chromosomal

aberrations in nurses handling aberrations in nurses handling CYTOSTATICSCYTOSTATICS

Frequency of chromosomal Frequency of chromosomal aberrations in nurses handling aberrations in nurses handling

CYTOSTATICSCYTOSTATICS

2,63 2,7 2,76 2,87 3,053,3 3,44 3,64 3,73

4,65 4,68 4,715,07

0

1

2

3

4

5

6

% A

B.B

.

Spontaneous level - 1.77

OCCUPATIONAL EXPOSUREOCCUPATIONAL EXPOSURE

S pontaneous frequency of aberrant ce lls (AB.C.) in Czech adult popula tion (19 93 - 2005 )

2 .05

1 .40

1 .03 1 .06

1 .26

1 .651 .81

1993 1994 1996 1999 2001 2003 20050 .0

0 .5

1 .0

1 .5

2 .0

2 .5

3 .0

3 .5

4 .0

% A

B.C

.

M ean 0 .95 *SD

*

N = 179 N = 626 N = 381N = 381N = 392N = 366N = 330

Spontaneous frequency of chromosomal Spontaneous frequency of chromosomal aberrations in the Czech general populationaberrations in the Czech general population

Conclusion

• Data on exposure/dose are crucial in health risk Data on exposure/dose are crucial in health risk assessment process (no risk without exposure)assessment process (no risk without exposure)

• Combination of calculation of exposure with Combination of calculation of exposure with human biological monitoring approach are human biological monitoring approach are necessary in the problem of environment and necessary in the problem of environment and health relationshiphealth relationship

• Human biological monitoring streams to molecular Human biological monitoring streams to molecular dosimetry and molecular epidemiologydosimetry and molecular epidemiology

• In the framework of EU environmental – health In the framework of EU environmental – health activities the activities the EuropeanEuropean Human biological Human biological monitoringmonitoring is going on– pilot study is going on– pilot study startsstarts in 2006 in 2006