HUMAN BIOLOGICAL MONITORING FOLLOWING CHEMICAL INCIDENTS

Implementation of a guidance

Paul T.J. Scheepers, Rob Anzion, Gwendolyn Beckmann, Janine Oosting, Radboud University Nijmegen Medical Centre

Train accident in Wetteren, Belgium, May 4th 2013

• Train carrying 300 tons of acrylonitrile derailed from a track between Brussels and Gent (too high speed)

• 6 tanker wagons derailed and 3 tanker wagons set on fire

• Thermal decomposition products (hydrogen cyanide, nitrogen oxides and acetylene)

Source: http://nl.wikipedia.org/wiki/Trein-_en_giframp_bij_Wetteren;

Train accident in Wetteren, Belgium, May 4th 2013

• 2,000 inhabitants were evacuated (3 days - 3 weeks)

• Toxic substances reached Wetteren via water (not via air)

• One inhabitant was killed and many have been exposed

• 1,300 blood and urine samples were collected

• Initial results of HBM campaign: 83 out of 243 blood samples contained ‘elevated levels’ of N-Cyanoethylvaline

Source: De Tijd 31.08.2013

Introduction

• Persons can be involved in chemical incidents in many ways; chemical exposure is one of many reasons for concern

• Many individuals are victims but not many victims may actually be exposed to toxic substances

• Questions need answers to support reliable exposure classification in the interest of an appropriate follow-up

• HBM should complement other methods for exposure classification (health complaints, air monitoring, modeling)

In June 2012 a guidance for use of biological monitoring for small-scale chemical incidents was established by the regional health services and the Natl. Inst. Public Health Environ (RIVM).

Potential added value of human HBM in an incident setting

• Confirm identity of the chemical substance• Support the classification of an individual as (un)exposed

and in the interest of (avoiding) treatment.• Integrate exposure from:• Multiple sources and exposure events (peak exposures)• Different routes of uptake

• Traces of the parent substance or its metabolites may be available for a long time depending on the choice of the biomarker (days-weeks-months).

• Reconstruct the exposure level at the time of the incident if there is an opportunity to collect biological materials repeatedly over time.

Concerns from the end-user

User: Public Health Advisor Hazmat (N = 25) hired by one out of 20 safety regions (availability 24/7).End-user: public authorities local/regional/national level

Who will provide the …• information and knowledge to support a decision?• expertise to conduct the study in the field?• materials for sample collection?• services pretreatment, storage, transportation and

analysis?

Service to support HBM following chemical incidents

Mission statementUse available knowledge and experience to support a HBM campaign in response to an emergency situation in an effective and efficient manner.

• Service desk• Standard list of biomarkers• Standard set of sample collection materials• Arrangement with experienced laboratories

Service desk

Front office: senior technician at clinical laboratory of Radboud University Nijmegen Medical Centre (RUNMC)• Intake using numbers from a list of biomarkers (by phone)• Send materials for sample collection as soon as possible• Arrange required pretreatment, storage and transport

Back office: toxicologists and technicians at Research Laboratory Molecular Epidemiology of RUNMC• Information to support decision making• Technical support for performance of campaign• Interpretation of reported lab results

List of biomarkers for HBM following chemical incidents

• Biomarkers for which biological limit values were established• Biomarkers identified by unique number • Biomarkers: 224 (for 132 chemical substances)• Principle of chemical analysis and LOQ • Information on half life in humans (for 105 biomarkers)• Involvement of 10 laboratories with EQUAS certificates for 115 analyses

No Substance CAS no. Biomarker MediumMaterials sample

collection

Sample pre-

treatment

Conditions for storage/ transport

Dectectionmethod LOQ

Elimination half life in humans

EQUAS certificate

(year)

0010-1 Acetone 67-64-1 Acetone urine URM CT GC-MS 0.6 mg/L - 2011

0020-1 Acetylcholinesterase inhibitors (organophosphates. carbamates) - Acetylcholinesterase ery’s EDT CT/AT Colorimetric 10 hU/L 32d UKNEQAS

0030-1

Acrylamide 79-06-1

N-(Carbonamidethyl) valine from HB adduct blood EDT RHB FT GC-MS/MS 4 pmol/g

Globin 60 d 2013

0030-2 Acrylamide mercapturic acid urine URM AT LC-MS/MS 1 µg/L - 2012

0040-1Acrylonitrile 107-13-1

N-Cyanoethylvaline from HB adduct blood EDT RHB FT GC-MS/MS 0.2 ng/g Globin 60 d 2013

0040-2 Cyanoethylmercapturic acid1-cyano-2-hydroxyethylmercapturic acid urine URM FT LC-MS/MS 1 µg/L 8 h Not avail.

0050-1 Aluminium (Al) and its inorganic compounds 7429-90-5 Aluminium

urine URM AT ICP-MS 0.03 µg/L ~8h 2012

0050-2 serum EDT PL AT AAS 0.5 µg/L - 2012

Standard set of materials for collection of biological samples

One box for transportation to the incident location (same or next day) with instructions for sample collection and pre-treatment (only if needed).• Blood: 9 mL-vacutainers for organic

substances (EDTA/ Hep/serum) + needles (for metals low-metal vacutainers and needles) + Tubes for head-space analysis of volatile organic compounds.

• Urine: beakers and 9 mL-vacutainers• Exhaled air: 140 mL Bio-VOC with

standard adsorbent tube for industrial chemicals

Arrangements with laboratories

• Principle: efficient flow in procedures normally used to be able to provide long-term high quality services.• Keep sampling materials in stock at RUNMC• Treat requests same (work)day before 15:00 h• Use standard 24 h delivery service for transport• Use cool packs or dry ice only when required

• Follow preference of lab-of-final-analysis for sample collection, pretreatment, storage and transportation.

• Urgent requests will receive a priority treatment in terms of planning (within usual constraints of the provided services which are laboratory dependent).

Logistics and time-flow

Case report: inhalation of mercury vapor from barometer

Setting: two young children and a nanny involved in a residential exposure event involving a broken barometer

Motivation to apply biological monitoring• Exposure was complex due to contamination of clothes and

dispersion throughout the residence• Potential high exposure due to vacuum cleaning • Children have a potential higher uptake and increased

susceptibility• Provide accurate information concerning the uptake and

systemic availability of mercury for the medical staff and to the parents

Case report: mercury blood level in nM

Person Gender Age (year)

Dec‐03‐2012 Dec‐07‐2012 Jan‐11‐2013Day 1 Day 5 Day 40

Child A Male < 1  156 44 5.5Child B Female 2.5 128 26 4.0Nanny Female 52 99 53 ‐

• Uptake by skin absorption is likely• Uptake from ingestion is probably negligible• Level on day-1 corresponding to 1-2 x ACGIH BEI• Moutinho et al (1981) reported on a boy (7 months) with a

blood level of 175 nM 4 days after inhalation of mercury vapour who died in the hospital within 1 week

• Elimination in the children appeared somewhat more rapidly than in the adult (initial half-life is 1-3 days and terminal half-life is 1-3 weeks (Barregard et al., 1992; Sandborgh-Englund et al., 1998)

• Level on day-41 was just below the 90-percentile for children of 6-11 y in NHANES 2003-2004 survey (5.7 nM)

Discussion

For the moment there many questions:• When will HBM be considered?• What will be the added value for individual and society?• What will be the success and fail factors?• How will emergency professionals evaluate HBM?

Perspective

• Standardization of ad hoc practice• Increase level of experience• Collaboration with physicians responsible for treatment in

emergency and follow-up• Revision of HBM guidance Would you collect a

urine sample, please?

Acknowledgements

• Marieke van Ballegooij-Gevers and Henk Jans of the Office for Health, Environment & Safety, Public Health Services Brabant/Zeeland for sharing the case-report on mercury

• Members of the Dutch HBM Working Group• Rob van den Berg, Stan Verweij, Ingrid Beckmann-Beumer, Arnoud

Loof of the Clinical Laboratory, RUNMC

This study was supported by the National Institute of Public Health and the Environment, Bilthoven, The Netherlands