1. A perspective on biological
monitoring guidance values
John Cocker
www.hsl.gov.uk
AnAn Agency of the Health and Safety
Agency of the Health and Safety Executive
Executive

2. From Hazard to Disease
Environmental
Monitoring
Occupational
H
A
Z
A
R
D
Biological
Monitoring
Biological Effect
Monitoring
Exposure Assessment
Diagnosis
Well-being
Health Surveillance
Increasing exposure/dose
EXPOSURE
UPTAKE
EFFECT
DISEASE
Environmental
E.g.
Air samples
Surface wipes
An Agency of the Health and Safety Executive
E.g. Urine:
PAHs
Carcinogens
Metals
Isocyanates
E.g.
Cholinesterase
Asthma/allergy
© Crown Copyright 2013

3. 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
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4. 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
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5. 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
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6. 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
Confusing?
(HSE)
• 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
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7. BM Guidance values
•
•
Health-based
BM value
Non-health-based
BM value
BMGV
BMGV
e.g BAT,
Or BEI
e.g EKA
Exposure or
absence of
ill-health
Health-based
exposure limit
e.g TLV or MAK
An Agency of the Health and Safety Executive
Non-health-based
exposure limit
e.g. TRK
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8. Good-practice-based BMGVs
• UK good occupational hygiene practice (or ‘benchmark’)
values are based on the 90th percentile of data from
workplaces 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
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9. 90% BMGV helps to reduce exposure
Each bar is the 90th percentile of results from 79 – 400 urine
Cl
samples from 20 – 35 companies each year
H2N
Cl
CH2
NH2
35
1987 Biological Monitoring Guidance value
25
Do 90% BMGVs need regular updating
to maintain effect?
20
1996 Biological Monitoring Guidance value
15
Firmer
guidance
improves
control and
reduces
exposure
10
5
05
St
ud
y
20
06
2n
d
20
st
ud 07
y2
00
8
20
09
20
10
04
M
bO
C
A
20
20
03
02
20
01
20
00
20
99
20
98
19
97
19
19
96
95
19
94
19
93
19
92
19
91
19
90
19
89
19
19
88
19
19
19
87
0
86
90% value MbOCA µmol/mol creatinine
30
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10. 90% Guidance value for PAHs
Frequency distribution of urinary 1-hydroxypyrene
140
Survey of 25 workplaces
120
Frequency
100
80
90% value from w orkplaces w ith good control < 4μ mol/mol creatinine
90% all w orkplaces < 7 μ mol/mol creatinine
60
40
20
0
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 60
μ mol/mol creatinine
An Agency of the Health and Safety Executive
1 µmol/mol ~ 2 µg/g
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11. Urinary 1-hydroxypyrene: perspective
m e d ia n va lu e s in 1 2 b a c kg ro u n d s tu d ie s
& 2 0 7 s a m p le s fro m th e H S E s u rve y
1-OH-P umol/mol
30
BM Equivalent to airborne limit (DFG - EKA)
20
10
4
90% value from places with good
occupational hygiene practice (UK)
2 .5
Upper limit of non-occupational
exposure (USA, BEI)
0 .0
smokers
An Agency of the Health and Safety Executive
non-smokers
HSE
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12. Action for Health-Based BMGVs
•
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—33470-4
ACGIH 2012 TLVs and BEIs published by ACGIH Worldwide ISBN 978-1-607260-48-6
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13. Action for Non Health-based BMGVs:
•
Examples:
– DFG EKAs, BLWs
• acrylonitrile, benzene, cobalt, hydrazine, nickel, etc
• UK ‘Benchmark’ (90%) values
•
If BMGV is exceeded it indicates control of
exposure may not be adequate
•
Good occupational hygiene practice should be to
reduce exposure ALARP
Deutsche Forschngsgemeinschaft List of MAK and BAT values 2012 Wiley VCH ISBN 978-3-527—33470-4
An Agency of the Health and Safety Executive
© Crown Copyright 2013

14. 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?
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15. Would a traffic light system help?
Levels > BMGV
Collect another sample, Check controls urgently
Levels > a 90% value or half the BMGV
Look for a reason – Check controls
Levels << 90% value or in the
background range - regular monitoring
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16. 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!
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17. Conclusions
•
•
•
•
•
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’ understand
BMGVs
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© Crown Copyright 2013

18. Conclusions
• BM for isocyanate exposures recommended
and increasingly used.
• Guidance values available as well as advice
on interpretation.
• Potential
confounding by amine exposures
but BM still reflects body burden to
hazardous chemicals.
• Further research on-going to find
Thank you for listening
isocyanate-specific metabolite.
John.cocker@hsl.gsi.gov.uk
An Agency of the Health and Safety Executive
an