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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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)

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

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

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

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