9.3 Cocker

An Agency of the Health and Safety Executivewww.hsl.gov.ukAn Agency of the Health and Safety Executive

A perspective on biological monitoring guidance values

John Cocker

An Agency of the Health and Safety Executive

From Hazard to Disease

EXPOSURE UPTAKE EFFECT DISEASE

HAZARD

Biological EffectMonitoring

Environmental Monitoring

DiagnosisWell-being

E.g.Air samplesSurface wipes

E.g.CholinesteraseAsthma/allergy

E.g. Urine: PAHsCarcinogensMetalsIsocyanates

BiologicalMonitoring

Occupational

Environmental

Exposure Assessment Health Surveillance

© Crown Copyright 2013

Increasing exposure/dose


Who uses BM & why ?

• Occupational health providers

• Occupational hygienists

• Employers & managers• Researchers• Epidemiologists• Regulators

• Compliance with regulation (e.g.lead)

• Are the exposure controls working?

• Do I have a problem?• Publications• Links to disease• ‘Safe’ levels

All motivated by a desire to prevent ill-health but all with different requirements



Requirements for BM

• Ethics – informed consent– Why, what, when, how, meaning of results

• Matrix– Blood, urine, saliva, breath etc

• Analyte– Specific, metabolite, related to toxicity,

stability, kinetics, dose-response• Analytical Method

– Specific, accurate, precise, • Quality assurance



Requirements for BM guidance values

• Data to establish a relationship between – BM value & (absence of) ill-health– BM value & exposure– BM value & good occupational hygiene practice– BM value & ‘normal’ levels

• Peer reviewed publications– Workplace studies– Volunteer studies– Population studies



Biological Guidance Values

• Health-based– HBM 1 & 2 (HBM Commission)

– BEIs 44 (ACGIH)

– BATs 66 (MAK/DFG)

– BLVs ?? (SCOEL)

– BMGVs 10 (HSE)

• Non-health-based– Reference values– BARs 30 (MAK/DFG)

– BLWs 8 (MAK/DFG)

– EKAs 26 (MAK/DFG)

– Good OH practice BMGVs (90% values) 7(HSE)


Confusing?• Differing types/basis• Differing values for the same substances

• E.g. HSE’s BMGV for Mercury ~35μg/g, BEI 10 μg/g• HSE’s BMGV for TDI ~1μg/g, proposed BEI 5μg/g

• Some might impossible to achieve – e.g. BLVs at background levels e.g BAR for Cd 0.8 μg/l cf BEI 5 μg/l


BM Guidance values

• Health-based • Non-health-based

Exposure or absence of ill-health

BM value

BMGV

Health-based exposure limit e.g TLV or MAK

BM value

BMGV

Non-health-based exposure limit e.g. TRK

e.g BAT,Or BEI

e.g EKA



Good-practice-based BMGVs• UK good occupational hygiene practice (or ‘benchmark’)

values are based on the 90th percentile of data fromworkplaces with good control of exposure.

• Not health-based

• Easy to set up, require fewer data

• Suitable for:

• Carcinogens & mutagens

• Data-poor substances

• ‘In-house’ use

• Examples include: Chromium VI, Glycerol trinitrate, Isocyanates, MbOCA,

4,4’-Methylenedianiline (MDA),Polycyclic aromatic hydrocarbons



90% BMGV helps to reduce exposure

Cl

NH2 CH2

Cl

NH2

Each bar is the 90th percentile of results from 79 – 400 urine samples from 20 – 35 companies each year


0

5

10

15

20

25

30

35

1986

1987

1988

1989

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1991

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MbOCA S

tudy

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2nd s

tudy2

008

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1996 Biological Monitoring Guidance value

1987 Biological Monitoring Guidance value

90%

val

ue M

bOC

A µ

mol

/mol

cre

atin

ine

Firmer guidance improves control and reduces exposure

Do 90% BMGVs need regular updating to maintain effect?


90% Guidance value for PAHs

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 600

20

40

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Frequency distribution of urinary 1-hydroxypyrene

90% all workplaces < 7 μ mol/mol creatinine

μmol/mol creatinine

Freq

uenc

y

90% value from workplaces with good control < 4μmol/mol creatinine

1 µmol/mol ~ 2 µg/g


Survey of 25 workplaces


Urinary 1-hydroxypyrene: perspective

m edian va lues in 12 bac kground s tud ies& 207 s am ples from the HS E s urvey

smokers non-smokers HSE0 .0

2 .5

4

1 0

2 0

3 0

1-O

H-P

um

ol/m

ol

90% value from places with good occupational hygiene practice (UK)

Upper limit of non-occupational exposure (USA, BEI)

BM Equivalent to airborne limit (DFG - EKA)



• Examples:– Mercury, MEK, MIBK, xylene, CO, chlorobenzene (UK)– ACGIH BEIs, (USA)– DFG BATs (Germany)

• If value exceeded unlikely to see health effects• Regularly exceeding the BEI/BAT suggests

exposure controls could be improved• Good occupational hygiene practice should be to

reduce exposure

Deutsche Forschngsgemeinschaft List of MAK and BAT values 2012 Wiley VCH ISBN 978-3-527—33470-4ACGIH 2012 TLVs and BEIs published by ACGIH Worldwide ISBN 978-1-607260-48-6

Action for Health-Based BMGVs



• Examples:– DFG EKAs, BLWs

• acrylonitrile, benzene, cobalt, hydrazine, nickel, etc

• UK ‘Benchmark’ (90%) values

• If BMGV is exceeded it indicates control ofexposure may not be adequate

• Good occupational hygiene practice should be toreduce exposure ALARP

Deutsche Forschngsgemeinschaft List of MAK and BAT values 2012 Wiley VCH ISBN 978-3-527—33470-4

Action for Non Health-based BMGVs:



Summary

• BM is a tool for exposure assessment• Guidance values available (not ‘limits’)

– Set by different organisations– Set in different ways– Same substance can have different BMGVs– If BMGV exceeded the action is the same –

examine controls and reduce exposure – For long half-life substances action is

needed before BMGV reached• Should we provide simpler guidance?



Would a traffic light system help?

Levels << 90% value or in the background range - regular monitoring

Levels > a 90% value or half the BMGV

Look for a reason – Check controls

Levels > BMGV

Collect another sample, Check controls urgently



Pleas• On behalf of organisations setting BMGVs:

– Please publish your studies– Please include details of exposure controls

• PPE, exposure levels, process & task details– Please visit as many workplaces as possible

• To referees & editors– Please ask for these details– Please recognise that the ‘real world’ rarely

lends itself to ‘ideal’ studies or academic perfection

• Most of all – do more biological monitoring!


• BM is a tool for exposure assessment • Guidance values are available• Guidance values are not ‘limits’

• If BMGV exceeded - reduce exposure• For long half-life substances act before BMGV

reached• 90% value BMGVs need updating

• We need guidance values for more substances• 90%value BMGVs are easier to develop• Do more research – and publish!

• We need to help our ‘customers’ understandBMGVs

Conclusions



Conclusions• BM for isocyanate exposures recommended

and increasingly used.

• Guidance values available as well as adviceon interpretation.

• Potential confounding by amine exposuresbut BM still reflects body burden tohazardous chemicals.

• Further research on-going to find anisocyanate-specific metabolite.

Thank you for [email protected]

9.3 Cocker

Health & Medicine

Transcript of 9.3 Cocker