1. Biologic Monitoring A. H. Mehrparvar, MD
Occupational Medicine department
Yazd University of Medical Sciences

2. Introduction Environmental monitoring vs biologic monitoring
Prediction of biologic levels by environmental monitoring
Sources of variability:
Different sources of exposure RR
Rate of metabolism and excretion
Adipose tissue level
PPD

3. Multiple measurements
Introduction
Assesses the extent of exposure
Indirectly assesses health effects
Probability of illness, never diagnostic
Abnormal biologic monitoring levels:
Multiple measurements
Timing of collection very important:
DS, EOS, EWW, PNS

4. Biologic monitoring program
Necessary conditions:
Determinant
Method of analysis
Sample collection
Interpretation of results
Responding action
Sufficient conditions:
Environmental monitoring
Conducted
Not adequate
Not feasible
Substances
Exposure routes

5. Biomarkers Biologic marker or biomarker:
any substance, structure or process that
can be measured in the human body or human body products, and
may influence or predict disease
Biologic monitoring:
Measuring a chemical, its metabolite or its non-adverse effect in a tissue sample in order to provide a quantitative estimate of its uptake into the body by all routes of exposures

6. Objective of Biological Monitoring as part of Medical Surveillance:
to ensure that current or past exposure of worker is not harmful to his/her health by detecting potential excessive exposure before overt adverse health effects occur

7. Biomarkers (cont.) Classification: Biomarker of exposure
Biomarker of effect
Biomarker of suceptibility

8. Biomarker of internal dose
Blood lead
Urine Mn
Biomarker of effective dose
CoHgb

9. Biomarker of internal dose
Internal dose is dependent on the:
Amount of chemical recently absorbed
Amount of chemicals stored in the whole body
Amount of chemical bound to critical sites of action
Advantage: All routes of exposure assessed and provides a more accurate assessment of health risk than atmospheric monitoring

10. Biological monitoring of occupational exposure to chemicals refers to the concentrations of the chemicals or their metabolites in biological samples:
Blood
Urine
Exhaled air
Faeces
Adipose tissue, hair, nails, saliva, milk
measuring the exposure or body burden

11. Knowledge Required for Biological Monitoring of Exposures
Toxicokinetics of the chemical:
Understanding of absorption, distribution and elimination of chemical
Toxicodynamics of the chemical:
Understand early adverse effects and pathogenic mechanism
Relationship between external exposure, internal dose and adverse health effects

12. Biomarkers of effective dose
Carboxyhemoglobin (exposure to carbon monoxide)
Protein and DNA adducts (exposure to reactive substances in DNA or target tissues)

13. Biomarker of exposure (cont.)
Characteristics:
Correlation with exposure
Correlation with target tissue dose
Reversibility
Appropriate sampling method

14. Biomarker of effect Indicate pathological damage:
Measurement of reversible not adverse biochemical changes after an internal dose
Not pathological effects
inhibition of δ-ALA by lead
Urinary excretion of alpha1 and beta2 microgobulins due to lead, cadmium, mercury
Indicate pathological damage:
liver dysfunction (transaminases), kidney dysfunction (albumin in urine)

15. Biomarker of susceptibility
Biomarker of susceptibility – indicator of inherent or acquired ability of organism to respond to challenge of exposure to specific substance
e.g. ability to acetylate amines – genetically determined and varies with ethnic origin – slow/rapid acetylators
genetically based low level of anti-trypsin – increased risk of emphysema

16. Approaches in Biomonitoring
Specific methods:
Direct measurement of unchanged chemicals or metabolites in biological media e.g. urinary measurement of mercury, mandelic acid (styrene), muconic acid (benzene)
Non-specific methods:
Non-specific indicators of exposure e.g. thioethers in urine (mutagens and carcinogens)

17. Criteria for Selecting Tests for Biological Monitoring
Parameter must be sufficiently specific
Parameter must have adequate sensitivity
Analytical and biological variability of test must be acceptable
Test should provide little discomfort to subject
Selection must take into account ability of tests to evaluate health risks

18. When to Collect Biological Sample?
Prior to work shift
During work shift
End of work shift
Beginning of workweek
End of workweek
Depends on half life of chemical
< 2 hours Not appropriate
2-10 hours End of work shift or Next morning
hours End of shift at end of week
>100 hours Any time

19. Biomonitoring Action Levels
The reference values at or below which the adverse health effects do not appear in most workers who are exposed to the chemicals.
Biological Exposure Indices (BEIs) - ACGIH
Occupational Exposure Limit Based on Biological Monitoring (OEL-B) – Japan

20. BEI represents:
Level of hazardous substance expected in biological material (urine, blood, hair) following exposure to airborne concentration equivalent to time-weighted average exposure standard
Most people will be protected at this level