TOPIC 3 : ENVIRONMENTAL

RISK ASSESSMENT

Hazard identification
Dose-response assessment
Human exposure assessment
Risk characterization

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 RISK
• A hazard is something that can cause an
adverse effect/ harm.
• Example of hazard: electricity, chemicals,
working up a ladder, noise, a bully at work,
stress, etc.

• A risk is a measure of the chance or

probability that the hazard will occur under
specific exposure conditions.
• Some risk are well defined (e.g. frequency and
severity of automobile accidents)
• In contrast, other hazardous activities such as
those resulting from the use of alcohol and
tobacco are more difficult to document. Their 5

assessment requires complex epidemiological

 Terminology:
• Exposure
Any condition which provides an opportunity for an
external environmental agent (any chemical,
biological, or physical material capable of eliciting a
biological response) to enter the body

• Dose
The amount of agent actually deposited within the
body.

Exposure and dose are often used interchangeably.

In reality, significantly different doses can result
from the same exposure.

• Threshold 6
 Terminology:

• An acute exposure is one of short duration

whereas a chronic exposure is one that is
repeated or prolonged for an extended period.

• Acute toxicity – a measure of the amount of a

substance that is needed to cause some acute
response, such as organ injury, coma, or even
death. The effect can be within a short period or
after a single exposure

• Chronic toxicity – Adverse effect caused by a

toxic agent after a long period of exposure

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 ACUT E AND CHRONI C T OXI CI T Y

Immediat
e toxic
effect

Prolonged
exposure
before
toxic
effect is
noticed
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ducation/turgeon/lessons/lesson13/l13_23.html
 Terminology:
• Mutagen – an agent that induces a permanent
change in the genetic material of the cell exposed
to it, which can be transmitted to future
generations
• Carcinogen – an agent that causes a cancer
• Cancer – collective noun for 200 different
diseases, all of which are characterized by
unrestrained cell divisions.
• Teratogen – an agent that induces abnormalities in
an embryo/fetus when administered to the
maternal organism
• Benign tumor – A new tumor composed of cells
that, though proliferating in an abnormal manner,
do not spread to surrounding normal tissue
• Malignant tumor – Relatively autonomous growth9
 EXPOSURE TO CHEMICALS:

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lect-wk-7-2-april-2013-id-hazards-and-routes-grp-b
 EXPOSURE TO CHEMICALS:

The permissible exposure
limit (PEL or OSHA PEL) is a legal limit in the
USA set by OSHA for exposure of an employee
to a chemical substance or physical agent
such as loud noise. 
There are three limits:
Time-weighted average (TWA) (should not
be exceeded in 8 work hours)
Short term exposure limit (not exceeding 15
min)
Ceiling limit (should not happen)
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TOXICOLOGY

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The DOSE makes the POISON!

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 RISK
ASSESSMENT
• Risk assessment is the
scientific approaches to
collect data that are
used to relate the
response to a dose of a
pollutant; determination
of the probability that an
adverse effect will result
from a defined exposure.

• Risk management is
the process of deciding
what to do and how to
allocate national
resources to protect
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public health and the
 RISK ASSESSMENT AND RISK
MANAGEMENT

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ps://toxtutor.nlm.nih.gov/06-004.html
 The exposure assessment
process.

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https://prezi.com/dv32gwyakzdn/exposure-pathway-diagram/ 17
• Risk is being expressed as a percentage or as
a decimal fraction, no units.

Example:

In the U.S in 2001, there were about 3.9 million

deaths per year. Of these, about 541,532 were
cancer-related.

The risk of dying from cancer in a lifetime was

about 0.14 or 14%.
The annual risk (assuming a 70-year life
expectancy) is 0.002 or 0.2%

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 1. HAZARD IDENTIFICATION

“What are we considering?”

• Characterize the innate toxic effect of the

agent

• Determine whether or not a particular

chemical is causally link to particular health
effect, such as cancer or birth defects

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Experimental design:

There are a variety of parameters which have to be

considered when testing the toxicity of a
substance, assuming that it is pure.

• Choice of animal model

• Route of administration

• Physical state of toxicant (gas, liquid,

lipophilicity, etc)

• Dose and duration of treatment: acute or chronic

toxicity testing
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Toxicity testing in animal

i. Short-term test, called the Ames mutagenicity

assay, subjects special tester strains of bacteria
to the certain chemical.

ii. Intermediate testing involve relatively short

term (several months duration) carcinogenesis
bioassays in which specific organs in mice and
rats are subjected to known mutagens to
determine whether tumors develop.

iii. The most costly, complex and long-lasting test

– chronic carcinogenesis bioassay.
- Two species of rodents must be tested (mice and rats)
- At least 50 males and 50 females of each species for
each dose 21

- At least two doses must be administered (plus a no-

Human studies

• Epidemiologic is the study of the incidence rate

of disease in real populations.
• Preliminary data analysis involves setting up a
simple 2 x 2 matrix.

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 Limitation of Animal studies and Human studies
Animal studies Human studies
- No species provides an exact - Large populations are required to
duplicate of human response. detect a low frequency of
Certain effects that occur in occurrence of a toxicological
common lab animals generally effect.
occur in people. The exceptions
are toxicities dependent on - A long or highly variable latency
immunogenic mechanisms. Most period may be needed between
sensitization reaction are difficult the exposure to the toxicant and
to induce in lab animals. a measurable effect.

- Inability of a bioassay to detect - Competing causes of the

small risks. Regulatory try to observed toxicological response
restrict human risks due to make it difficult to attribute a
exposure to carcinogens to level direct cause and effect. (cigarette
of about 10-6, yet animal studies smoking, the use of alcohol and
are only capable of detecting drugs, prior disease states)
risks down to 0.01 to 0.1.

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 2. DO SE- RESP ONSE AS SESSMENT

“How bad it is?”

• To obtain a mathematical relationship between

the dose of an agent administrated or
received and the risk that will be an unhealthy
response to that dose.

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Dose-response mortality curves for acute
toxicity.
LD50 = Lethal Dose for 50% of a tested25
Dose-response curve for chronic toxicity

- Organism is subjected to a prolonged exposure

over a considerable fraction of its life

- The abscissa is dose, expressed as the average

milligrams of substance per kilogram of body
weight per day (mg/kg-day). For carcinogen, the
dose is an exposure averaged over an entire
lifetime (for humans, it is assumed to be 70
years).

- The ordinate is the response, which is the risk

that there will be some adverse health effect (e.g.
cancer)

- e.g. if prolonged exposure to some chemical

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Dose-response curve for chronic toxicity
Hypothetical dose-response curves. Dose-
response curves for carcinogens are assumed to
have no threshold; that is, any exposure produces
some chance of causing cancer.

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Potency factor for Carcinogens
At low doses, where the dose-response curve is
assumed to be linear, the slope of the dose-response
curve is called the potency factor (PF)

Incremental lifetime cancer risk = CDI x

PF 28
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Reference dose for Noncarcinogenic effects
RfD is obtained by dividing the NOAEL by an
appropriate uncertainty factor. The uncertainty
factor is typically between 10 and 1 000.

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Noncarcinogens - there is an exposure threshold;
that is, any exposure less than the threshold
would be expected to show no increase in adverse
effect

Lowest-observed-adverse- effect level (LOAEL) :

the lowest dose administered that results in a
response (adverse to health)

No-observed-adverse-effect level (NOAEL) : the

highest dose administered that does not create a
response (adverse to health)

Reference dose (RfD) or acceptable daily

intake (ADI) – an indication of a level of human
exposure that is likely to be without appreciable
risk (unit : mg/kg-day averaged over a lifetime) 32
  𝐴𝑣𝑒𝑟𝑎𝑔𝑒 𝑑𝑎𝑖𝑙𝑦 𝑑𝑜𝑠𝑒 𝑑𝑢𝑟𝑖𝑛𝑔 𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 𝑝𝑒𝑟𝑖𝑜𝑑
𝐻𝑎𝑧𝑎𝑟𝑑 𝑞𝑢𝑜𝑡𝑖𝑒𝑛𝑡 =
𝑅𝑓𝐷

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 3. EXPOSURE ASSESSMENT

“How much of it?”

• Determine the size and nature of the population that has been
exposed to the toxicant
• Estimate the toxicant concentration, frequency and duration
of human exposure to the toxicant
• Route (or pathway) of exposure is one of the factor controlling
how much of a substance gets absorbed into your body. The main
routes of exposure to chemicals in the environment are by
ingestion (gastrointestinal), dermal absorption (through skin),
and by inhalation (through the lungs) 35
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Bioconcentration factor (BCF, L/kg) : Amount of
consumption of a product containing toxicants by a human.
For example: BCF provides the key link measuring the
tendency for a substance to accumulate in fish tissue.

Concentration of toxicant in fish (mg/kg) = concentration in

water (mg/L) x bioconcentration factor (L/kg)

Another way is the estimation of half-life (days) of various

contaminants in water, air, and soil (contaminant degradation
rate).

Half life is the time required for the concentration to be

reduced by 50%.

t1/2 = ln 2 / k C(t) = C0e-kt 37

 4. RISK CHARACTERIZATION

“So, what is the risk?”

• Involves analysis of gathered data to be used in
decision-making process to set regulatory requirements
and control measures.
• It is the final stage in the risk assessment process and
involves the prediction of the frequency and severity of
effects in exposed populations.
• All data collected from exposure and toxicity
assessment are reviewed to corroborate qualitative and
quantitative conclusions about risk.
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 Example # 1
If 70 kg people breath 20 m3/day of air
containing 10-3 mg/m3 of carcinogenic VOC
throughout their entire 70 year lifetime, find the
cancer risk. Given the potency factor = 0.01
(mg/kg-day)-1. Is it less than a goal of 10-6?

2 Incremental lifetime cancer risk = CDI x PF

A:
2.86x10-6
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Example # 2
a. The drinking water standard for tetrachloroethylene
is 0.005 mg/L. Suppose a 70 kg person drinks 2 L of
water every day for 70 years. Find the cancer risk
for this individual. Potency factor of
tetrachloroethylene is 5.1 x 10-2 (mg/kg-day)-1.
b. If a city with 500,000 people in it also drinks the
same amount of this water, how many extra
cancers per year would be expected? Assume the
1
standard 70 year lifetime.

2
Incremental lifetime cancer risk = CDI x PF

3 (RISK / 106) x (5x105 / 70 yr) =

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A: 0.052
Example # 3
Mainstream smoke inhaled by a 70 kg smoker
contains roughly 0.03 mg per cigarette of the class B2
carcinogen, benzo(a)pyrene. From an individual who
smokes 20 cigarettes per day for 40 years, estimate
the lifetime risk of cancer caused by that
benzo(a)pyrene (there are other carcinogens in
cigarettes as well). Given that potency factor
(inhalation route) of benzo(a)pyrene is 6.11 (mg/kg-
day)-1.

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A: 0.03
Example # 4
Suppose a 50 kg individual drinks 1 L/day of water
containing 2 mg/L of 1,1,1-trichloroethane, 0.04 mg/L
of tetrachloroethylene, and 0.1 mg/L of 1,1-
dichloroethylene. Given the oral RfD for 1,1,1-
trichloroethane = 0.035, tetrachloroethylene = 0.010,
1,1-dichloroethylene = 0.009. What is the hazard
index?
Slide # 33

A: 1.45
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Example # 5
Given a daily intake of 54 g of fish for a person, 350
days per year for 30 years eating locally caught fish,
estimate the lifetime cancer risk from fish taken
from waters containing a concentration of
trichloroethylene (TCE) equal to 100 ppb (0.1 mg/L).
The bioconcentration factor for TCE is given as 10.6
L/kg. The cancer potency factor for an oral dose of TCE
is
1.1 x 10-2 (mg/kg-day)-1.

A: 3.6x10- 43

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Example # 6
Suppose an underground storage tank has been
leaking for many years, contaminating the
groundwater and causing a contaminant concentration
directly beneath the site of 0.30mg/L. The
contamination is flowing at the rate of 0.5 ft per day
toward a public drinking water well 1 mile away (1 mile
= 5280 ft). The half-life of the contaminant is 10 years.

a.Estimate the steady-state pollutant concentration

expected at the well.
b.If the potency factor for the contaminant is 0.02
(mg/kg-day)-1, estimate the cancer risk if a 70 kg
person drank 2 L of this water per day for 10 years.

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Example # 6

1. Time to travel = distance / rate

2. Assume exponential degradation of the pollutant,

k = ln2 / duration

3 a. C(t) = Co e-kt =

b. CDI =

4. Risk = CDI x PF =

A: 3.2x10-
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Example # 7

Determine the acceptable groundwater

concentration for the chemical vinyl chloride if a
residential development is placed above a
groundwater aquifer contaminated with vinyl
chloride. Assume that you are determining the risk
for an adult who weighs 70 kg and consumes 2 L
water per day from the contaminated aquifer for 30
years. Given an acceptable risk is 1 cancer
occurrence per 106 people. An oral slope factor for
vinyl chloride of 2.3 per mg/kg-day (assuming the
only route of exposure is from drinking
contaminated water).

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Example # 7

RISK = CDI x PF

Solve for concentration, µg/L

A: 47
3.55x10-3