BIOLOGICAL MONITORING ON

BENZENE EXPOSED WORKER

SHO’IM HIDAYAT, dr.,MS

 Introduction
Petroleum
Composition :
 Mixture of hydrocarbone (– H – C– )
 Alkane / parrafine (straight, branched)

 Cycloalkane / naphtene

 Aromatics : benzene, toluene, xylene

 Asphaltics

 Other organic compounds contain N, O, S

 Trace amount of metal : Fe, Ni, Co, Vn

Physical form of alkanes:

 Gaseous : C1 – C4

 Liquid : C5 – C35

 Solid : C36 - more

Benzene :
Source : petroleum, cigarette
Uses : solvent, gasoline additive, intermediate chemical
Colorless, highly flammable, non polar liquid
Volatile organic compound (VOC)
Carcinogenic to human (group 1)(IARC), hematotoxic
Potentially exposure :
 Occupational : petrochemical, petrol station, industries used
benzene as solvent, etc
 Non occupational : smoking

Route of entry : inhalation, skin, ingestion

Properties of benzene :

Chemical structure
Chemical formula C6H6
Molecular mass 78.11 g/mol
Flash point -11.1oC
Flammable limit 1.3 – 7.1 %
Melting point 5.5oC
Boiling point 80.1oC (at 760 mmHg)
Solubility in water 1.8 g/L; miscible with acetic acid,
acetone, chloroform, diethyl ether,
ethanol
Relative vapour density 2.7
Odour threshold 4.8 – 15 mg/m3
Monitoring :
Environmental monitoring
Biological monitoring
Environmental monitoring : external dose effect
Biological monitoring : determination of the
concentration of the chemical or its metabolites or the
metabolic effect they produce from analysis of
biological specimen (blood, urine, exhaled air, etc)
Biological monitoring is complementary to env monit.
It is represent overall exposure from inhalation, skin
or ingestion  internal doses
The primary objective of biomonitoring is to ensure
that the current or past exposure of the worker is not
harmful to his/her health by detecting potential
excessive exposure before overt adverse health effects
occur.
In practical domain, biomonitoring is usefulness as a
guidelines in industrial hygiene practice.
To understanding about biomonitoring, it is needed
the information about toxicokinetics and
toxicodynamics of the substances.
TOXICOKINETICS
Absorption & distribution
Inhalation : 17% exhaled
Skin (fat solubility)
Ingestion
Absorbed benzene  circulation  accumulated in fat /
fatty tissue .
Biotransformation :
The biotransformation of benzene can be explained as
below
TOXIC EFFECTS
Systemic
Acute, high dose (> 800 ppm) death
Acute, low - moderate dose : dizziness, rapid heart rate,
headache, tremor, confusion, unconcioussness
Haematotoxic effect
Chronic exposure
Leucopenia, thrombocytopenia, anemia
May be reversible or irreversible
Carcinogenic effect
Acute myelocitic leukemia (after 5 – 15 yrs exposure)
IARC : group 1 (human carcinogen)
 MONITORING
Monitoring :
An Industrial hygiene practice  control measurement of toxic
substance
Monitoring :
Exposure (environmental and biological monitoring)
Effects  health surveillance
Environmental monitoring :
External dose : ambient air concentration
Reference : TLV (TWA, STEL)
Biological monitoring
Internal dose : parent compound or its metabolites
Reference : biological exposure indices (BEI) TWA
Complementary of environmental monitoring
Study on relation of exposure and effects 
epidemiological study (cross-sectional, cohort, case-
control) :
Traditional epidemiology
Molecular epidemiology
Molecular epidemiology :
Potentially explain state of the art of the disease
Recent scientific mainstream  study on cancer
pathogenesis
Study about biomarkers  the good predictor value of
exposure, effect and susceptibility
Framework of continuum of events in molecular epidemiology

Exposure (external dose)

TRADITIONAL EPIDEMIOLOGY
Exposure markers
Internal dose

Susceptibility markers
Effective dose

Early biological effect

Effect markers

Altered structure / function

Clinical disease

Prognostic significance
External dose : the amount of xenobiotic in ambient air
Internal dose : the amount of a xenobiotic or its metabolites
found in a biological medium (blood, urine, etc)
Effective dose : the amount of a xenobiotic or its metabolites
that interacts with a critical subcellular, cellular or tissue
target
Early biological effect : representing an event correlated with,
and possibly predictive of health impairment
Altered function / structure : altered which are considered as
precursor biological changes that are closely related to
disease development
Clinical disease : the presence of current clinical disease
Prognostic significance : possibly of future development of
the disease
ENVIRONMENTAL MONITORING
Exposure in ambient air  airborne toxicant
Standard reference : TLV
TLV-TWA : airborne concentration (average) of
chemical substances and represent condition under
which it is believed that near all workers may be
repeatedly exposed, day after day, over a working
lifetime, without adverse health effects (ACGIH, 2005)
Time weighted : 8 h/day
Benzene : TLV-TWA = 0.5 ppm; STEL = 2.5 ppm
BIOLOGICAL MONITORING OF BENZENE
EXPOSURE WORKERS
Biological medium : urine
Timing of urine collection : end of shift
Biomarkers (based on ACGIH):
S-phenyl mercapturic acid (SPMA) and or
Tt-muconic acid (tt-MA)
BEI :
SPMA = 25 µg/g creatinine
tt-MA = 500 µg/g creatinine
Timing urine collection : within 1 h after cessation of
work, 50 – 100 ml.
Storage of sample : around 4oC
Volume of sample : 2 ml for one analysis
Type of container : acid prerinsed plastic
Principles of analysis : GC-MS-MS
Limited of determination : < 1 µg/L
Background exposure : smoking habit (piece-day)
BTX