Exposure assessment Milena Černá

Definition Exposure 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 analysis Agent(s): biological, chemical, physical components, complex mixtures Source(s): anthropogenic – natural, area – point, stationary – mobile, indoor – outdoor… Transport/carrier medium: air, water, soil, dust, food, product Exposure pathways: eating contaminated food, breathing polluted air, touching contaminated surface etc. Exposure concentration: mg/kg (food) mg/L (water), mg/m3 (air) mg/cm2 (contaminated surface) Exposure routes: inhalation, ingestion, dermal contact, multiple ways

Aspects important in exposure analysis (cont.) Exposure duration: seconds, minutes, hours, days, weeks, months, years, lifetime Exposure frequency: continuous, intermitent, cyclic, random, rare Exposure settings: occup., environ., residential, indoors, outdoors Exposed population: general, occupational, subgroups, individuals Geographic scope: site/source specific, local, regional, national, international, global Time frame: past, present, future, trends

Exposure assessment - steps Identifying and evaluation exposure pathways Determination whether these elements are linked to form an exposure pathway Categorization an exposure pathway as a completed exposure pathway or a potential exposure pathway Determination whether the exposure pathway should be eliminated or further discussed in the health risk assessment

Ingestion, inhalation, dermal contact 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 contamination 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 environmental media that may serve to transport contaminants from the source to possible points of human exposure air - soil, surface water, sediment, vegetation, fish, cattle....(food chain) - waste material, sludge.. Remember: Contaminants may move from one medium to another

Once a substance is released to the environment, one or more of the following may occur: movement - physical transformation (rain, volatilization) - chemical transformation (photolysis, hydrolysis, oxidation/reduction) - accumulation in one or more media. The bioconcentration factor is a measure of the extent of chemical partitioning at equilibrium between a biologic medium, such as a fish tissue, and an external medium, such as water. Some contaminants significantly bioconcentrate in fish and vertebrate (e.g. PCBs, chlorinated pesticides, mercury), some other not (e.g. PAHs). Food chain - human 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 values Reference dose (RfD) = estimation of daily population exposure dose (including vulnerable subpopulation groups) which does not represent adverse health effect for population during the whole life exposure Acceptable daily intake (ADI) = estimation of peroral daily intake which does not represent adverse health effect for population during the whole life exposure (WHO - used for food additives) Tolerable daily intake (TDI) = dtto ADI, used for food contaminants Tolerable weekly intake (TWI), Tolerable monthly intake (TMI) = dtto, 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 Environm. Health status BIOMARKERS Genetic background

Human exposure Absorbed – internal dose Biological effective dose Early adverse effect Disease

Biomarkers Biomarkers of exposure Biomarkers of effects Biomarkers of susceptibility

Internal (absorbed) dose Biologically active dose Exposure Internal (absorbed) dose Tissue dose Cell dose Macromolecular dose Target dose Biologically active dose Effect Molecular dosimetry

Human biomonitoring Analysis of contaminants, their metabolites or other changes related to the exposure in human body fluids and tissues. Blood, urine, saliva, hair, nails, teeth etc Different population groups Standardized sampling and analysis Statistical evaluation Interpretation of results Long-term time trends

NHANES “Third National Report on Human Exposure to Environmental Chemicals” Department of Health and Human Services Centers for Disease Control and Prevention July 2005 http://www.cdc.gov/exposurereport/3rd/pdf/thirdreport.pdf

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, Brussels 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 biomonitoring Lisabon, June 2005

Environmental Health Monitoring System in the Czech Republic Resolution No. 369/1991 of the Government of the Czech Republic. Routinely operated since 1994. One of the priorities of the National Environmental Health Action Plan (Government Resolution No. 810/199). Relied upon the Act No. 258/2000 on Public Health. www.szu.cz

Structure of the Czech Environmental Health Monitoring System Subsystem 1 - Air Subsystem 2 – Drinking water Subsystem 3 - Noise Subsystem 4 – Dietary exposure Subsystem 5 – Biological monitoring Sobsystem 6 – Health status Subsystem 7 – Occupational environment Subsystem 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

Blood lead levels in men

Blood lead levels in women

Blood lead levels related to age

Blood cadmium levels according to smoking habit

Blood cadmium levels in nonsmokers

Urine cadmium level according to gender

Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston 2000/01 – 3rd round of the WHO international study WHO– sum of indicator PCBs in human milk, ng/g fat Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston

Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston 3rd round of WHO study; PCDDs and PCDFs in human milk expressed as WHO-TEQ values, pg/g fat Malisch and van Leeuwen, Vol. 60-65, Dioxin 2003 Boston

Levels of indicator PCBs in human milk (sum of congeners (138+153+180) x 1.7 – comparison with the results in 1985 (prohibition of PCBs in CR)

Levels of indicator congener PCB 153 in human milk

BIOMARKERs of early adverse biological effects (genotoxins) Chromosomal aberration FISH Sister chromatid exchange Micronuclei Mutation in hypoxantin-guanin fosforibosyltransferase gen (HPRT) Activation of oncogens coding synthesis of proteins p53 a p21

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 since 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

Frequency of chromosomal aberrations in nurses handling CYTOSTATICS

OCCUPATIONAL EXPOSURE % AB.B. Spontaneous level - 1.77

Spontaneous frequency of chromosomal aberrations in the Czech general population

Conclusion Data on exposure/dose are crucial in health risk assessment process (no risk without exposure) Combination of calculation of exposure with human biological monitoring approach are necessary in the problem of environment and health relationship Human biological monitoring streams to molecular dosimetry and molecular epidemiology In the framework of EU environmental – health activities the European Human biological monitoring is going on– pilot study starts in 2006