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

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

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

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

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 6

0%

20%

40%

60%

80%

100%

30.0

4.

01.0

5.

02.0

5.

03.0

5.

04.0

5.

05.0

5.

06.0

5.

07.0

5.

08.0

5.

09.0

5.

10.0

5.

11.0

5.

12.0

5.

13.0

5.

14.0

5.

15.0

5.

16.0

5.

17.0

5.

18.0

5.

19.0

5.

20.0

5.

21.0

5.

22.0

5.

23.0

5.

24.0

5.

25.0

5.

26.0

5.

27.0

5.

pe

rcen

tage

of sa

mp

les

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

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

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

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

© iS

tockp

ho

to.c

om

/me

va

ns

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

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

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

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

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

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

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

© iS

tockp

ho

to.c

om

/me

va

ns

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.