EXPOSURE ASSESSMENT ibiomarkers

An exposure scenario is a set of conditions or assumptions about sources, exposure pathways, amount or concentrations of agent(s) involved, and exposed organism, system or (sub)population (i.e. Numbers, characteristics, habits) and used to aid in the evaluation and quantification of exposure(s) in a given situation. GENERAL PRINCIPLES EXPOSURE EVALUATION  The purpose of exposure assessment is to identify the routes by which humans are exposed and the magnitudes of that exposure, including the frequency and duration. Identify the number of exposed people along with either characteristics  Exposure may be measured as the amount of the contaminant in various media and an estimate of human intake of these media under different activity patterns  Some people may be exposed to more than one media. Total intake must be evaluated.

 Generel introduction to exposure science

 Biomarkers pro and con

 Exposure asessment – use of biomarkers

 Biomarkers for air pollution

 Conclusion

OUTLINE

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RISK = HAZARD X EXPOSURE

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WHAT IS EXPOSURE ASSESSMENT?

• EXPOSURE is the contact of a chemical,

physical, or biological substance with the

outer boundary of an organism

• EXPOSURE ASSESSMENT is the

determination or estimation of the

magnitude, frequency, duration, and route of exposure

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An exposure scenario is a set of

conditions or assumptions about

sources, exposure pathways, amount

or concentrations of agent(s) involved,

and exposed organism, system or

(sub)population (i.e Numbers,

characteristics, habits) and used to aid

in the evaluation and quantification of

exposure(s) in a given situation.

IPCS

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GENERAL PRINCIPLES EXPOSURE EVALUATION

 The purpose of exposure assessment is to identify

the routes by which humans are exposed and the

magnitudes of that exposure, including the frequency and duration Identify the number of exposed people along with either characteristics

 Exposure may be measured as the amount of the

contaminant in various media and an estimate of

human intake of these media under different activity patterns

 Some people may be exposed to more than one

media Total intake must be evaluated.

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biochemical effects

biological effects

in blood, urine

protein adducts DNA adducts

cytogenetic parameters

enzymes, enzyme levels

importance for estimating the risk

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ADVANTAGE - BIOMARKERS

Demonstrate that exposure has occurred

Integrate dose across all routes of exposure

Reflect activity pattern

Validation of exposure models

Relates exposure to dose

Do not depend on memory/records

Characterization of individual exposure-dose

Cohort studies relating exposure to early

•Lack of normative values for comparison

• Exposure – effect relationship

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VALIDATION OF BIOMARKERS

• Transport and storage

• Degradation, evaporation and interaction

Analytical method

• Accuracy and reproducibility

• Sensitivity Sensitivity and specificity of marker

• Temporal relevance

• Background variability

• Confounding factors

FATE AND ELIMINATION

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BIOMARKERS -TIME

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NATIONAL REPORT ON HUMAN EXPOSURE

TO ENVIRONMENTAL CHEMICALS

What it is:

An ongoing (every 2 years) biomonitoring assessment of the exposure of the U.S population to selected environmental chemicals

Matrices monitored: Urine; blood and its

components

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Percentage of children 1-5 years old in the US

with elevated blood lead levels ( ≥ 10 µg/dl)

lead soldered cans, phase-out begins 1978

lead &

copper rule 1991

lead soldered cans, phase-out ends 1992

leaded gas removal complete 1991

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a concentration of a substance in human biological

material which is statistically derived from a defined

group (representative) of the general population

(e.g 95 th percentile)

Reference value

• not health based

HUMAN BIOMONITORING GERMANY

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below which there is no risk for adverse health effects

above which adverse health effects cannot completely ruled out

above which there is an increased risk for adverse health

Mercury in urine

(exposure to inorganic mercury)

increased risk of adverse health effects

a rule out neurotoxic and nephrotoxic effects

b for children and adults without amalgam fillings

Hg (u) [µg/l]MERCURY (1999)

exposure general population

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DEDUCTION HBM I-VALUE

5OH-MEHP+5oxo-MEHP

Molar conversion

x 0.75 Excretion factor 5OH-MEHP+5oxo-MEHP (40%):

x 0.4

50 µg/kg/day general population

20 µg/kg/day women of reproductive age

Reference values for urinary excretion:

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Parameter Matrix Population group reference value

[µg/l]

HBM I [µg/l]

HBM II [µg/l]

5OH-MEHP urine Children and adults 220 - 5oxo-MEHP urine Children and adults 150 - -

-Σ 5OH-MEHP,

5oxo-MEHP

urine Children

Female adults Male adults

- -

-500 300 750

- -

-REFERENCE AND HBM VALUES

Phthalates - DEHP

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BIOMARKERS - LEAD

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BLOOD LEAD LEVEL IN CHILDREN

BIOLOGICAL MONITORING

PESTICIDES

Cytogenetic analysis: SCE in lymphocytes and MN in buccal cells

Metabolites: Atrazine in saliva (ELISA) (herbicide applicators

Malathione in urine (date dusters and harvesters) Captan fungicides in urine (strawberry harvesters) Alachlor in urine (ELISA) (pesticides applicators)

Effect markers: Inhibition of cholinesterase activity – serum

Inhibition of anticholinesterase activity - erythrocytes

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AIR POLLUTION EXPOSURE

BENZENE

Benzene in exhaled air

Metabolites in urine

muconic acids

S-phenylmercapturic acid (S-PMA)

Reaction products with proteins

Early biological effects

Comet assay,

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Taxidrivers Cityroad

Suburban Rural

PMA as BIOMARKER FOR BENZENE

Avogbe PH et al, Carcinogenesis 26: 613-620, 2005

Cotonou, Benin

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PAH EXPOSURE – BANGKOK

1-hydroxypyrene

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GENE EXPRESSION AS BIOMARKER

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PUBLIC HEALTH USE OF DATA

• Identifies environmental chemicals

• Provides reference range for selected chemicals in

population

• Identifies prevalence of persons with elevated levels

• Identifies population groups with elevated levels

• Monitors changes in exposure over time

• Assesses effectiveness of public health efforts to

reduce exposures

• Provides exposure data for risk assessment

• Helps set priorities for human health effects

research

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BIOMARKERS - WILDLIFE

 To assess environmental burden of toxic

compounds

 To provide an ”early warning” or indication of

possible effects on humans

 To provide an economically effective way of

ranking human health questions by indicating the type of responses

 To assess whether exposure was from chemical passing through food chains or by other routes –

e.g inhalation

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