BIOLOGICAL, BIOLOGICAL AND HEALTH BIOLOGICAL, BIOLOGICAL AND HEALTH EFFECTS MONITORINGEFFECTS MONITORING

Name: Dr Abu Hasan SamadOrganisation: Academy of Occupational & Environmental

Medicine, Malaysia;Prince Court Medical Centre, K. Lumpur

Venue: Kuala Lumpur Convention CenterDate: 17th September 2012

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.

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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.

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Types of Biological Monitoring

• Biological Monitoring of Exposure • Biological Monitoring of Effective Dose • Biological Effects Monitoring• Biological Monitoring of Susceptibility

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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

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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).

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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

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Biological Monitoring of Effective Dose

• Carboxyhemoglobin (exposure to carbon monoxide)

• Protein and DNA addicts (exposure to reactive substances in DNA or target tissues)

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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

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• 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)

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Biological Effects Monitoring

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

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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)

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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

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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

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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

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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

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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.

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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

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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.

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