((BIOBIOMARKERMARKER))

.... .(1) .. ().

(Hazard surveillance)

(Health surveillance)

(surveillance)

(Diagnosis)

(Disability evaluation)

- - -

- - - - - -

- - - -

1) (parameter)

2) (non-occupational exposure) (individual variability)

3) (multiple exposures)

4)

1) 2) (

zinc protoporphyrin

3) half-life dimethylformamide 24 48 N-methylformamide (NMF) dimethylformamide

4) (surface acting agent)

5)

biological monitoring

- - asbestos thalidomide- -

biological monitoring

Exposure - - pack-year- / -

Internal dose DDT

Biological effective dose DNA/ protein adduct

Early biological effect

Alternative morphology & structure SGOT/SGPT

Disease cancer Prognosis lymph node +ve

Exposure InternaldoseBiologically

Effectivedose

Earlybiological &

geneticeffect

Alternation in morphology.structure &

function

PrognosisD

N

A

a

d

d

u

c

t

s

:

I

n

s

i

t

u

W

B

C

U

r

i

n

e

C

h

r

o

m

o

s

o

m

e

a

b

e

r

r

a

t

i

o

n

s

,

S

i

s

t

e

r

c

h

r

o

m

a

t

i

d

e

x

c

h

a

n

g

e

s

,

M

i

c

r

o

n

u

c

l

e

i

,

D

N

A

b

r

e

a

k

s

Clinicaldisease

E

n

v

i

r

o

n

m

e

n

t

a

l

m

o

n

i

t

o

r

i

n

g

C

h

e

m

i

c

a

l

s

u

b

s

t

a

n

c

e

s

a

n

d

m

e

t

a

b

o

l

i

t

e

s

i

n

b

i

o

l

o

g

i

c

a

l

f

l

u

i

d

s

T

u

m

o

u

r

m

a

r

k

e

r

s

E

x

f

o

l

i

a

t

i

v

e

c

y

t

o

l

o

g

y

C

A

T

s

c

a

n

M

e

t

a

s

t

a

t

i

c

s

p

r

e

a

d

Exposure Effect

Biomarkers of exposure and effect

Biomarker US National Academy of Science(1989):

Hulka, et al(1991):

Biological monitoring

biological monitoring biomarker

Biological Exposure Index (BEIs)

TLVs

Biological monitoring

(metabolite)

Biological monitoring

Biological monitoring PPE

Biological Exposure Index BEI BEI

susceptibility

8/ 5 /

biomarker

exposure dose

(t1/2)- < 5 = peak of exposure phenol- > 5 = -> workweek TCA

(prior to shift) 16 (during shift) 2 (end of shift) (end of the workweek)

4 5 5

(discretionary) 2-3

biomarker

preclinical

outcome

biomarker

1. 2.

- - -

3.

biomarker

Biomarker of exposure Biomarker of effect Biomarker of susceptibility

Biomarker Biomarker of exposure

Biomarker of exposure

methylmercury

Biomarker Biomarker of effect

/

Biomarker of effect

carboxyhaemoglobinZinc-protoporphylin

cholinesteraseMicroglobulinsDNA damage

CO

organophosphatel

Biomarker Biomarker of susceptibility

HIV + ve CD4 , sickle cell trait diisocynate RADS

Studies on genetic variants, occupational carcinogens & cancer

Author YearOccupational

exposure Gene Cancer Sample

size Location Study design Interaction

Sak 2005 General XPC Bladder 547/579 UK Case-control Assessed Vineis 2001 General NAT2 Bladder 1530/731 Multicenter Pooled Assessed Shen 2003 PAH XRCC1, XRCC3, XPD Bladder 201/214 Italy Case-control Assessed Lin 2005 Benzidine UGT2B7 Bladder 36/251 China Nested CC Not assessed Ma 2003 Benzidine GSTP1 Bladder 101/109 China Case-control Not assessed Ma 2002 Benzidine GSTM1, T1, P1 Bladder 101/110 China Case-control Not assessed Zhang 2002 Benzidine AHR Bladder 61/183 China Case-control Not assessed Shinka 1998 Dyes - AA GSTM1 Bladder 36/101 Japan Workers-only Not assessed Schroeder 2003 General p53, GSTM1, NAT1 Bladder 245/215 US Case-control Not assessed Hung 2004 PAH, AA MPO, COMT, MnSOD, NQO1 Bladder 201/214 Italy Case-control Assessed Dialyna 2004 Pesticide CYP19 Breast 202/284 Greece Case-control Not assessed Saito 2000 Vinyl-chloride Connexin37 Hemangiosarcoma 22 Multicenter Case-only Not assessed Buzio 2003 Metal, pesticide GSTM1, GSTT1 Kidney 100/200 Italy Case-control Assessed Bruning 1997 Trichloroethene GSTM1, T1 Kidney 45/48 Germany Case-control Not assessed Sun 2001 Aflatoxin GSTM1, T1 Liver 79/149 Taiwan Case-control Assessed Butkiewicz 2004 General XPA Lung 416/460 Germany Case-control Assessed Schabath 2002 Asbestos MPO Lung 375/378 US Case-control Assessed Stucker 2001 Asbestos GSTM1, T1 Lung 651/983 Multicenter Pooled Assessed Wang 2004 Asbestos MnSOD Lung 811/957 US Case-control Assessed Malats 2000 General GSTM1, T1 Lung 122/121 Multicenter Case-control Assessed Hirvonen 2002 Asbestos MnSOD Mesothelioma 63/61 Finland Workers-only Not assessed Hirvonen 1996 Asbestos GSTM1, T1, NAT2 Mesothelioma 76/69 Finland Nested CC Not assessed

biomarker

Limit of detection ;LOD / dose-response

- - - - -

pre-analytical phase level EDTA K sorbic acid t,t muconic acid 4

Analytical phase lab LOD lab lab GC/MS Lab ISO 17025

Post-analytical phase

WHO Cr >0.3g/L Sp.gr. 1.010-1.030

- , , - - , -

, ,

1. 2. 3. 4.

(Anticoagulants)

1. EDTA (Ethylene diamine tetra-acetic acid) Ca++ clot

2. Heparin enzyme thrombin

3. Sodium citrate Ca++ clot 3.8%

2

1. Random Specimen (Single Voiding)

2. Time Specimen 24 .

Toluene, HCl

,

Spectrophotometer

; (absorb)

(absorbance)

Atomic Absorption Spectrophotometer

Flame AAS

Gas Chromatogaphy (GC)

2

Gas Chromatogaphy (GC)

mass spectrometer GC-MS

High Pressure Chromatography (HPLC)

GC (Mobile phase)

GC

Automate -> ->

-> -> ->

Biomarker disease monitoring biomarker

Biological monitoring

Acetone, Alcohol, Organophosphate, Inorganic arsenic, Benzene, Cadmium, Carbon disulfide, Carbon monoxide, Chromium,n-Hexane, Lead, Methyl ethyl ketone(MEK), Parathion, Phenol, Polycyclic aromatic hydrocarbon (PAHs), Styrene,Toluene, Trichloroethylene (TCE), Xylene, Cyclophosphamide

(BioMARKER) biological monitoring biological monitoringBiomarkerBiological monitoringBiological monitoringBiological monitoringBiological monitoringBiological Exposure Index biomarker biomarker biomarker biomarkerBiomarkerBiomarker of exposureBiomarkerBiomarker of effectBiomarkerStudies on genetic variants, occupational carcinogens & cancer biomarker (Anticoagulants) 2 SpectrophotometerAtomic Absorption SpectrophotometerFlame AASGas Chromatogaphy (GC)Gas Chromatogaphy (GC)High Pressure Chromatography (HPLC) Automate