BIOLOGICAL, BIOLOGICAL AND HEALTH EFFECTS MONITORING

1. BIOLOGICAL, BIOLOGICAL AND HEALTH EFFECTS MONITORING Name: Dr Abu Hasan Samad Organisation: Academy of Occupational & Environmental Medicine, Malaysia; Prince Court Medical Centre, K. Lumpur Venue: Kuala Lumpur Convention Center Date: 17th September 2012

2. What is Biological Monitoring? Biological monitoring is the measurement of a substance or its metabolite in biological material in order to provide a quantitative estimate of its uptake into the body by all routes of exposures.

3. 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.

4. Types of Biological Monitoring • Biological Monitoring of Exposure • Biological Monitoring of Effective Dose • Biological Effects Monitoring • Biological Monitoring of Susceptibility

5. Biological Monitoring of Exposures • Biological monitoring attempts to estimate the internal dose of a chemical exposure. • 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

6. Biological Monitoring of Exposures • Biological monitoring of occupational exposure to chemicals refers to the concentrations of the chemicals or their metabolites in biological samples e.g. blood, urine, exhaled air, faeces, adipose tissue, hair, nails, saliva, milk (measuring the exposure or body burden).

7. 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

8. Biological Monitoring of Effective Dose • Carboxyhemoglobin(exposure to carbon monoxide) • Protein and DNA addicts (exposure to reactive substances in DNA or target tissues)

9. Biological Effects Monitoring Biological monitoring of non-adverse reversible effects - early biochemical changes which are reversible and non-adverse biomarkers of exposure: • Inhibition of delta-amino laevulinic acid dehydratase by lead • Inhibition of pseudocholinesterase by organophosphates

10. Biological Effects Monitoring • Reversible non adverse effects or early detection of health impairment: • Urinary excretion of alpha1 and beta2 microgobulins due to lead, cadmium, mercury • Indicate pathological damage: • liver dysfunction (transaminases), kidney dysfunction (albumin in urine)

11. Biological Monitoring 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

12. 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. diazopositive metabolites in urine (aromatic amines), thioethers in urine (mutagens and carcinogens)

13. Development of Valid Test for Exposure Monitoring • Fate of pollutant and compound to be determined • Biological material to be analyzed • Time of sampling and duration urine sample to be collected • Storage and preservation of specimens • Methods of analysis and units of measurement • Frequency of testing • Use in establishing biological limits

14. 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

15. 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 • 10-100 hours End of shift at end of week • >100 hours Any time

16. 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

17. Roadblocks for Application/Commercialization of Biomarkers (Steven Rosen) • Analytical, diagnostic and etiological validity of new markers need to be established. • Recognized disease end points need to be more clearly associated with the biomarkers. • Standardized criteria for quantitative measurement of markers must be established. • Predictive values of biomarkers must be determined by population studies.

18. Health Effects Monitoring • Asbestos, Silica • Medical, occupational and smoking history • Physical examination • Chest X-Ray PA view • Pulmonary Function Testing • Noise Exposure) Regulations 1989 • Audiometric testing: 0.5,1,2,3,4 and 6 kHz

19. CONCLUSION • Biological, biological effects and health effects monitoring are the various components of a good medical surveillance program. • How effects of exposures to hazards are assessed and monitored depends on the type of the hazard and its effects.