Mogelijkheden en beperkingen van Biologische monitoring Gezondheidskundig onderzoek of onderdeel van het blootstellingsonderzoek? Paul T.J. Scheepers, PhD, ERT, RAH, GAGS Toxicoloog, arbeidshygiënist, gezondheidskundig adviseur gevaarlijke stoffen Radboud Institute for Health Sciences CGC-NVAB, Den Bosch, 14 juni 2018
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Mogelijkheden en beperkingen van Biologische monitoring...Beroepen met een risico voor kanker Beroepsgroep aBlootstelling Classificatie Weefsel met tumoren Brandweerman Stoffen die
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Mogelijkheden en beperkingen van Biologische monitoring
Schilder Niet bekend 1 (2012) Long, blaas, leukemie (bij kinderen
van de schilder)
Schoorsteenveger Schoorsteenroet 1 (2012) Long, huid, blaas a 1 = humaan carcinogeen (groep 1), 2 = waarschijnlijk carcinogeen (groep 2A); 2B = mogelijk carcinogeen (groep 2B); b Bij het werk als brandweerman zijn stoffen en weefsels waarin tumoren zijn gevonden niet gespecificeerd; c De onderbouwende volledige rapportage is nog niet verschenen maar een voorpublicatie is beschikbaar (Guha et al., 2017).
Risk assessment and molecular epidemiology
Source: Budnik LT et al. J Occup Med Toxicol. 2018 Feb 5;13:6.
Early indicator of adaptive response According to the meet-in-the-middle principle (Paolo Vineis, Imperial College)
• Biomarker should reflect an ‘early’ non-adverse effect • Biomarker should be a confirmed and causal risk factor of disease • Derived from different routes of uptake (inhalation, dermal, oral)
Like a prognostic clinical biomarker?
Value of DNA adducts and repair products?
Value of urine metabolites vs. protein adducts?
How should these outcomes
be presented to the worker?
Biomarkers
Biomarker of exposure
Reflects (systemic) internal dose of a parent substances or product of metabolism e.g. Ethanol concentration in exhaled air or in blood Biomarker of susceptibility Reflects a person characteristic that interacts with the toxicokinetics and/or
toxicodynamics of the substance of interest e.g. Alcohol dehydrogenase activity
Biomarker of (physiological/biochemical) response Indicates physical change or physiological response to an exposure that is not necessarily adverse
e.g. Heart frequency, cognitive function level, reaction time, et cetera
Zielhuis and Henderson (1986) MOSHE 2015 Pagina 6
Analysis of biomarkers: for what purpose?
1. Detection of aggregated exposure
2. Response to worker’s concerns
3. Testing of a well controlled setting
4. Worker’s performance indicator
Detection of aggregate exposure
The total of all contributions to exposure of a single substance from all sources
- Derived from different routes of uptake (inhalation, dermal, oral) - Exposures at work as well as off-work exposures - Products used at work well as consumer products and dietary contributions - Reflecting recent exposure as well as historic exposure
Biomonitoring as ‘safety net’
Result is often positive for ubitiquous substances
Very specific strategies are required to disentangle
worker’s exposures from ‘background’
Aggregate exposures: contribution of arsenic from diet
Plaice
Reference Salmon
Smart study designs
• Determine a baseline for each individual
• Compare pre-shift and post-shift (or pre-work week and end-of-week) • Compare groups of workers • Make a comparison before and after an intervention • Long-term monitoring to identify workers/situations/trends
tetrachloroethylene
Response to worker’s concerns
Treating the individual outcome as a reflection of uptake to satisfy: • Uncertainty concerning complex procedures or involvement in spill • May satisfy questions related to personal behaviour/hygiene issues • What is the real worker’s incentive? (in need of reassurance?)
Biomonitoring to satisfy concerns?
A low value or non-detect may be reassuring
A high value may lead to questions difficult to answer.
What value to be used as biological guidance value?
What is the health relevance of the lab result?
Worker’s performance indicator
Commissioned by the employer e.g. • Alcohol and drugs testing in demanding tasks • As part of an ALARA strategy • Keep a registry of exposure to CMR substances
Biomonitoring as in a ‘doping test’
What is the worker’s participation incentive?
Are individual results kept confidential from the employer?
How about ethics issues (voluntary participation)?
Testing of good practices
Field test to evaluate the efficacy of an intervention • Gloves to reduce skin absorption (reduce or enhance exposure) • Respiratory protection (technical specs vs. field performance) • Personal hygiene issues
Biomonitoring as tool for evaluation
How does a protective technology perform in practice?
Is the extra effort of wearing PPE worthwhile?
Skin protection in dermatology nurses
Comparison of excretion of 1-hydroxypyrene (1-OHP, total and increase from baseline). Based on
collection of urine during 24 h after application of CTO.