Dr Shantakumari Rajan

Faculty of Health Sciences

UiTM Puncak Alam
shanta@uitm.edu.my

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 the responsibility for deciding, on the basis of data
provided by descriptive and mechanistic toxicologists,
whether a drug or another chemical poses a sufficiently low
risk to be marketed for a stated purpose

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 Establishing Exposure Guidelines
 Toxicity data from both animal experimentation and
epidemiological studies is used to establish exposure
guidelines.
 The method for deriving a guideline is dependent upon the
type of chemical as well as duration and frequency of
exposure.
 It is also important to make the distinction between an
experimental dose (mg/kg) and an environmental
concentration (mg/m3 or ppm).
 In order to make safety decisions, exposure guidelines are
presented as concentrations so that these values can be
compared to concentrations measured by instrumentation.

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From Data to Decisions: Informing Regulatory Policy

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 Factors Affecting Policy

Economic

Political Policy Cultural

Scientific

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Occupational Safety and Health (Use and Standards of Exposure of
Chemical Hazardous to Health) Regulations 2000

SCHEDULE I [Regulations 6 and 7]

LIST OF PERMISSIBLE EXPOSURE LIMITS

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Food Regulations 1985

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Environmental Quality (Clean Air) Regulations 2014

THIRD SCHEDULE [Regulation 13]

LIMIT VALUES AND TECHNICAL STANDARDS (BY ACTIVITY OR INDUSTRY)

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Malaysia Ambient Air Quality Standards 2013

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 toxicological information from animal experimentation are
used to establish how much of a chemical would cause
illness or death.
 Department of Environment (DOE)

 Department of Occupational Safety and Health (DOSH)

 Ministry of Health (MOH)

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 Exposure Standards - what are they?
 Regulatory agencies set the limits to which workers can be
exposed to particular hazards.
 These are known as "Exposure Standards", "Occupational
Exposure Limits" or "Threshold Limit Values" (TLVs).
 They are numerical values (e.g. parts per million for
chemical fumes; dBA for noise levels, 0C for temperature)
which represent the exposure levels to which workers may
be repeatedly exposed and are regarded as an "acceptable
risk".

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 Exposure standards are legal concentration limits that must
be adhered to.
 A person conducting a business or undertaking must
ensure that a worker is not exposed to contaminants above
the workplace exposure standard.

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 To comply with the Regulations, monitoring of workplace
contaminant levels may need to be carried out if:
 there is an uncertainty whether or not the exposure
standard has been or may be exceeded, or
 it is necessary to determine whether there is a risk to
health.

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 How are they set?
There is a three-stage process to standard setting in
occupational health and safety:
1. Hazard Identification - Identification of anything in the
working environment that may cause harm.
2. Risk Assessment - an assessment of the likelihood of
injury or illness as a result of exposure to that hazard.
Tests in laboratories, or by epidemiological studies may
provide evidence of a link between exposure and dose at
varying levels and any effect or response. The dose
response relationship provides the technical information
on which to base the setting of Standards for "safe"
exposure.

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3. Risk Evaluation - This process is a social one. Reference to
given technical information arrived at in the Risk
Assessment stage is only part of the process of evaluating
risk and determining what is an "acceptable" level of risk
or exposure standard.

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 The process often involves a decision being reached
through consensus amongst representatives of government,
health and safety professionals, unions and employers .
 Generally, the exposure standard is determined by a trade-
off or balancing of the risks and costs of removing those
risks.

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The following criteria is considered by those making decisions
on what is an "acceptable" level of risk:
 The level of knowledge about the hazard
 The extent of knowledge of the risk of exposure
 The costs of "living with" the hazard and associated risk:
- extent of injury/disease;
- extent of social effects on injury/disease;
- extent of demand on and cost of medical and like services;
- costs of compensation premiums and common law claims.

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 The level of knowledge of ways to control the hazard and
reduce exposure levels;
 The availability of ways to control the hazard and reduce
exposure levels;
 The cost to industry of controlling the hazard and reducing
exposure levels;
 The implications of industry meeting that cost.

Therefore the health and safety of workers is not

always paramount in the setting of safe standards.

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Limitations in reliability of the standard-setting process
determining absolute "safe" exposure levels.

 Judgements made in the risk evaluation stage of the process

are often subjective, and not objective;
 The "safe" exposure level is determined by a process based
on a concept of so-called "acceptable risk";
 The technical information illustrated by dose-response
relationships makes predictions for groups of subjects,
showing what is likely to occur "on average" - they cannot
predict for individuals;

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 The dose-response relationships indicate a clear level of
risk for equivalent populations - not all workers' situations
are the same;
 Technical information used to evaluate risk generally
results from tests which only assess short term or acute
effects;

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 Exposure standards are set for individual hazards, and yet
workers are generally exposed to more than one hazard at a
given time - the effects of combined exposure are generally
unknown;
 Exposure standards for chemicals are set for a "normal"
working day of 8 hours - allowing the body 16 hours to
"recover". Working arrangements are changing, however,
and 12 hour shifts have become more common.

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 The process for changing or updating exposure standards
can be very slow, meaning that sometimes exposure
standards may be above those of other countries.

Legal standards should be regarded as the minimum

acceptable standard for any workplace hazard

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Occupational Exposure Limit
 An occupational exposure limit is an upper limit on the
acceptable concentration of a hazardous substance in
workplace air for a particular material or class of materials.
 It is typically set by competent national authorities and
enforced by legislation to protect occupational safety and
health.

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UF

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 The NOAEL (no observable adverse effect level) is the
highest dose or exposure level of a substance or material
that produces no noticeable (observable) toxic effect on
tested animals.
→ some effects may be produced at this level, but they
are not considered adverse effects

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 PEL for methoxychlor

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 In Malaysia, the Occupational Exposure Limits (OELs) are
termed Permissible Exposure Limits (PELs) as quoted in
Occupational Safety & Health Act 1994.
 PEL means a ceiling limit or an 8-hour time-weighted
average airborne concentration or the maximum exposure
limit.

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Time-weighted average - TWA
 A time-weighted average is used to calculate a workers
daily exposure to a hazardous substance (such as
chemicals, dusts, fumes, mists, gases, or vapors) or agent
(such as occupational noise), averaged to an 8-hour
workday, taking into account the average levels of the
substance or agent and the time spent in the area.

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 These limits are intended for use in the practice of
industrial hygiene in the control of potential health hazards
 Not for other use such as:
 in the evaluation or control of community pollution
nuisances
 in estimating the toxic potential of continuous
uninterrupted exposures or other extended work
periods
 as proof or disproof of an existing disease or physical
condition

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 Monitoring, or sampling, is necessary to determine the
identity or type of a substance and the amount of a
substance.
 This information may be used to determine if workers can
enter an area, what PPE they should wear, whether further
cleanup is needed, and if wastes can be mixed.
 Sampling can be classified as personal, area, or
bulk/surface.

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 Personal monitoring is the most
accurate measurement of
exposure because the sampling
device goes where you go and
collects air from your breathing
zone.
 Personal sampling is required
to ensure exposures are below
PELs and provides the most
accurate information on a
worker’s exposure.

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 Area monitoring is not used to determine a specific
worker’s exposure.
 It’s often used to measure background concentrations in
air prior to the start of work, trigger alarms if
concentrations get too high, assess the effectiveness of
controls, and to protect the community.

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 Bulk and surface sampling are used to determine how
much of a hazardous substance is present:
 In water or liquids
 In soil
 In waste
 On surfaces
 In materials

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Acceptable Daily Intake for Total Residues in Food

NOAEL
Toxicological ADI =
Safety Factor

 Safety factor is determined by the type of the study, species

examined and toxicity endpoint (usually 100 to 1000-fold).
 ADI represents the amount of residues that can safely be
consumed per day over a human’s lifetime without adverse
effects
 The more uncertain the data is, the higher will be the total
safety factor applied
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Safety factors

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Safe Concentration (SC)

ADI x Average Human BW (kg)

SC =
Food Consumption (g)

 Provide total residues allowed in each type of food

 Food consumption is the amount of food that is assumed a

persons eats in a day/meal.

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Edible Tissue Food Consumption (g) Calculated SC (mg/kg)
Muscle 300 1.0
Liver 100 3.0
Kidney 50 6.0
Fat 50 6.0

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Biomarkers
 any substance, structure or process that can be measured in
the body or its products and influence or predict the
incidence of outcome or disease
 objective indications of medical state observed from
outside the patient which can be measured accurately and
reproducibly
 measured response may be functional and physiological,
biochemical at the cellular level, or a molecular interaction

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Biomarkers versus Clinical Endpoints

 do not necessarily correlate with a patient's experience and

sense of wellbeing
 clinical endpoints reflect or characterize how a subject
“feels, functions, or survives”

Are biomarkers reliable predictors of disease ?

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Biomarkers in toxicology
 biomarkers of exposure and response

 Specific DNA and protein adducts

 Analysis of urinary metabolite profiles

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 Biomarkers have emerged as an exciting tool in disease
prevention, particularly in the workplace.
 They may be used to document workers' exposure to
toxins, signal the onset of health effects, or identify
individuals with susceptibility to certain environmental
threats.

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Why do we need biomarkers?
 In vivo monitoring

 Serial sampling

 Early detection of metabolic changes

 Detection of organ‐specific effects

 Establishment of “NO EFFECT” level

 Determination of toxic mechanism

 Is required by regulatory agencies

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Biomarkers of exposure, effect, susceptibility
 Biological Standards Analysis of biological samples (e.g.
urine or blood) obtained from exposed workers .
 Body fluids and tissue for lead, arsenic or mercury

 Analysis of metabolite (urine phenol for benzene exposure)

 Analysis of serum to determine the levels of enzyme or

biochemical substance (decreased cholinesterase level due
to exposure to organic phosphate compounds)
 Breath analysis for volatile solvents and ketones.

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 The progress from exposure to disease (and prognosis) is
influenced by various factors from variability in exposure to
genetic factors that condition biological uptake,
distribution, metabolism, excretion, and response.
 genetic factors can influence or modify the transitions.

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 At the individual level, monitoring results can lead to use of
personal protective equipment (PPE), early treatment, and
job placement.
 At the group or population level, monitoring data can be
used to assess the effectiveness of controls, develop risk
communications, and identify failures of prevention and
control.
 There is a need for both levels of analysis to protect
workers.

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