1. Exposure assessment
Milena Černá

2. 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.

3. 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

4. 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

5. 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

6. 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.

7. 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.

8. 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

9. 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

10. 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

11. 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

12. 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)

13. 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

14. 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.)

15. Estimating exposures The following factors should be considered:
Exposure duration
Exposure frequency
Exposure fluctuation (continuous or intermittent)

16. 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.

17. 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)

18. 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

19. 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

20. The use of biomarkers in exposure assessment and body burden determination
Environm.
Health status
BIOMARKERS
Genetic background

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

22. Biomarkers Biomarkers of exposure Biomarkers of effects
Biomarkers of susceptibility

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

24. 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

25. NHANES
“Third National Report on Human Exposure to Environmental Chemicals”
Department of Health and Human Services
Centers for Disease Control and Prevention
July 2005

26. 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

27. European Commission, Brussels
Human Biomonitoring:
Support to the European Environment & Health Action Plan
Under Action 3 of the European Environment and Health Action Plan , 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.

28. IG Human biomonitoring Lisabon, June 2005

29. 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.

30. 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

31. 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

32. Blood lead levels in men

33. Blood lead levels in women

34. Blood lead levels related to age

35. Blood cadmium levels according to smoking habit

36. Blood cadmium levels in nonsmokers

37. Urine cadmium level according to gender

39. 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 , Dioxin 2003 Boston

40. 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 , Dioxin 2003 Boston

41. Levels of indicator PCBs in human milk (sum of congeners ( ) x 1.7 – comparison with the results in 1985 (prohibition of PCBs in CR)

42. Levels of indicator congener PCB 153 in human milk

43. 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

44. 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

45. CONVENTIONAL TECHNIQUE

46. SCE

47. Micronuclei

48. FISH

49. COMET

50. Frequency of chromosomal aberrations in nurses handling CYTOSTATICS

51. OCCUPATIONAL EXPOSURE
% AB.B.
Spontaneous level
- 1.77

52. Spontaneous frequency of chromosomal aberrations in the Czech general population

53. 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