1. 1
Biomonitoring after chemical incidents
and during maintenance works
A versatile tool for exposure analysis and assessment in the chemical industry
Michael Bader, Stefan Lang, Christoph Oberlinner
BASF SE, Occupational Medicine & Health Protection, 67056 Ludwigshafen, Germany
Occupational Medicine & Health Protection
Chief Medical Officer: Dr. med. Stefan Lang

2. 2
Human Biomonitoring (HBM) of Benzene
exposure
Steam Cracking & Products Synthesis of Aromatics Transport & Storage
normal working conditions
maintenance & revisions
accidental contact
regular surveillance
targeted HBM programs
individual biomonitoring

3. 3
Targeted HBM - Maintenance and Revisions
Naphtha (80 – 200 °C)  Ethylene & Propylene
 Methane, Hydrogen
 C4/C5 cuts
 (pyrolysis products)
regular maintenance and revision
complete shutdown, partial dismantling
cleaning and re-assembling
Steamcracker, BASF Antwerp, Belgium
safety instructions
emergency medical care
biomonitoring surveillance  benzene
BASF SE (Ludwigshafen)
2 Steamcrackers (1965 & 1980)
2 Mio. tons of Naphtha per year
supply by pipeline or cargo ships

4. 4
trans,trans-Muconic Acid Reference Remarks
1.6 mg/L DFG – EKA equivalent to 0.6 ppm
0.5 mg/g creatinine ACGIH – BEI equivalent to 0.5 ppm
0.5 mg/g creatinine BASF internal action value = BEI value
S-Phenylmercapturic Acid Reference Remarks
25 µg/g creatinine DFG – EKA equivalent to 0.6 ppm
25 µg/g creatinine ACGIH – BEI equivalent to 0.5 ppm
25 µg/g creatinine BASF internal action value = BAT/BEI value
unmetabolized Benzene Reference remarks
5 µg/L BASF internal action value Bader et al., ICOH 2012
Targeted HBM - Assessment Values for Benzene

5. 5
Aromatics Plant
2006
(n = 183)
Steamcracker
2008
(n = 148)
Aromatics Plant
2011
(n = 182)
Steamcracker
2011
(n = 490)
ttMA (mg/g crea.)
median
95%
range
0.08
0.46
0.01 – 4.14
0.21
2.21
0.01 – 4.86
0.12
0.44
0.01 – 0.69
0.10
0.50
0.01 – 5.46
SPMA (mg/g crea.)
median
95%
range
--- --- 1.7
21.5
0.5 – 32.7
1.7
15.9
0.2 – 142.5
Benzene (mg/L)
median
95%
range
--- --- 0.6
13.1
0.01 – 24.2
0.6
6.5
0.01 – 135.4
Targeted HBM - Aggregated results from recent turnarounds

6. 66
0%
20%
40%
60%
80%
100%
30.04.
01.05.
02.05.
03.05.
04.05.
05.05.
06.05.
07.05.
08.05.
09.05.
10.05.
11.05.
12.05.
13.05.
14.05.
15.05.
16.05.
17.05.
18.05.
19.05.
20.05.
21.05.
22.05.
23.05.
24.05.
25.05.
26.05.
27.05.
percentageofsamples
day of maintenance
> 0.5 mg/g crea. 0.25 - 0.50 mg/g crea. < 0.25 mg/g crea.
- plant is shut down
- installations are dismantled
- emptying & flushing
of pipes and vessels
residual works
sludge-contaminated material
- work on pipes and
heat exchangers
- sludge-contaminated material
Targeted HBM - Steamcracker Shutdown 2011
ttMA in urine

7. 7
Targeted HBM - Ethylbenzene/Styrene Plant Turnarounds
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
1993 1994 1995 1996 1998 2001 2003 2006 2012
33 17 46 32 58 34 60 55 49
43 54 386 68 243 57 125 196 223
employees
no. of samples
samples
< 0.25
0.25 – 0.49
0.50 – 1.69
1.70 – 10.0
> 10.0
ttMA
(mg/g creatinine)
action value =
1.7 mg/g crea. (2 mg/L)
action value =
0.5 mg/g crea.

8. 8
n = 372 postshift samples
0.3 ≤ creatinine ≤ 3.0 g/L
biomarkers > LOD
25 µg SPMA/g crea.
 3.8 µg Benzene/g crea.
log Benzene = 0.797 (0.049)  log SPMA – 0.531 (0.035)
R2 = 0.414, p < 0.001
with 1.4 g crea./L urine
 5.3 µg Benzene/L
Targeted HBM - Generation of „Added Value“

9. 9
October 13, 2005 (05:30 h)
pyraclostrobin smoldering and release from a heated barrel
carbonization of pyraclostrobin yields, e.g., p-chloroaniline (p-CA)
p-CA detected in fire extinguishing water
p-CA biomonitoring was offered to all persons involved (15:30 h)
 T
Were firefighters and other emergency responders exposed to p-CA?
Incident HBM - p-Chloroaniline Accident
©iStockphoto.com/mevans

10. 10
Incident HBM - p-Chloroaniline Study Group and HBM
subgroup persons (n) samples (n)
fire brigade 1 (local) 25 46
fire brigade 2 (BASF) 7 11
fire brigade 3 (local) 6 11
fire brigade 4 (local) 1 1
paramedics 4 4
BASF employees 76 87
contractor workers 8 12
remediation service 11 11
site security 7 7
total 145 190

11. 0
10
20
30
40
50
60
11
< 5 µg/g crea.
5 – 20 µg/g crea.
20 – 100 µg/g crea.
100 – 1000 µg/g crea.
> 1000 µg/g crea.
Incident HBM - p-Chloroaniline Results
Oct 13 Oct 14 Oct 15 Oct 17-19 Oct 24 Nov 2
p-CA
(µg/g creatinine)

12. 12
Published Concepts for Incident HBM
Scheepers et al. (2011)
J Expo Sci Environ Epidemiol 21:247-261
Decker et al. (2013)
Military Medicine 178:68-75
Müller & Schmiechen (2012)
German Federal Office of Civil Protection
and Disaster Assistance, www.bbk.bund.de
stepwise decision process
- toxicokinetic data
- significant health effects
- analytical methods
selected compounds
- toxicokinetics known
- methods available
- medical assessment possible
- sampling time interval
based on t1/2 and LOD
- AEGL-2-derived
assessment values
- cost/benefit relation
- full substance profiles
- list of HBM laboratories
- if in doubt, collect samples
- focused on emergency
responders
- formal decision process
- risk communication required
decision based on
- appropriateness
- feasibility

13. 13
Factor Rationale Criterion
CMR chemicals
- considerable systemic toxicity
- low dose effects or no NO(A)EL
- susceptible groups
GHS classification
skin absorption
- additional uptake
- air monitoring not representative
- depot effect, delayed response
skin notation
bioaccumulation
- additive effects of repeated exposure
- background exposure
- long clearance time
long t1/2
health concerns
- objective evidence of exposure
- inclusion of medical/toxicological expertise
- responsible care
situational
Important Triggers for Human Biomonitoring

14. 14
Medical and Toxicological Risk Assessment
Occupational Exposure Limits
DFG MAK
ACGIH TLV
SCOEL OEL
HSE WEL …
Limit Values in Air
EPA AEGL 1 - 3
AIHA ERPG 1 - 3
EU AETL 1 - 3
NIOSH IDLH …
HBM Assessment Values
DFG BAT, BLW, EKA
ACGIH BEI
SCOEL BLV
HSE BMGV …
chronic exposure
ooops…
acute exposure
basis ?
rationale ?

15. 15
Incident HBM - Response and Communication
Attribute translates as
based on facts
details on incident
exposure data and/or medical/toxicological experience
co-ordinated
involvement of concerned parties (representatives)
round tables and public information
timely
selection of biomarkers
sample collection, analysis and data evaluation
tiered
step-by-step process of monitoring/measures
focus on assumedly higher exposed persons
transparent
timely internal and external communication
audience oriented information

16. 16
Incident HBM - The p-Chloroaniline Experience
- exposure confirmed (or ruled out)
- comparison with available exposure data
- occupational medical assessment
- no acute toxic effects observed
- low risk of cancer from single exposure
positive response from employees and authorities
rapid and professional reaction to incident
transparent process
timely and adequate communication
credible committment to responsible care
©iStockphoto.com/mevans

17. 17
Summary and Conclusions
After incidents, HBM allows for a distinction between exposed and non-exposed persons.
HBM is a useful tool for the analysis of infrequent or short-term exposures.
In case of targeted programs, HBM shows the efficiency of safety measures.
Current concepts for HBM after incidents should include transnational networking
(laboratories, methods, capacities, quality assessment, toxicological assessment).
The toxicological assessment of incident HBM needs further discussion.
Adequate communication is a key factor for the success of HBM programs.