12/8/2023

Toxicity Assessment Basics

• Toxicity assessment is a major component of risk assessment.

• It provides an estimate of how much of a substance causes what

kind of harm.

Evaluation of Toxicity

V.Vijitha
Lectrurer (Prob.)
Dept. of Biosystems Technology
FoT, UoJ

Toxic Effects • Chronic effects happen only after repeated long-term

exposure
• Toxic effects are classified as either acute or chronic o Cigarette smoking

o Eating foods with low levels of contaminants

• Acute effects happen very rapidly after a single exposure
o Breathing polluted air

has occurred
• Examples of chronic effects
• Food poisoning
o Cancer

• Breathing fumes from a chlorine spill o Organ damage

o Reproductive difficulties
• Death
o Nervous system impairment

• All quantitative toxicity assessments are based on the dose-

• Chronic effects fall into two categories
response concept.
• Carcinogenic effects - Cancer
• Increase the dose (exposure), the response (toxicity) also
• Non-carcinogenic effects
increases.
• Organ damage:
• Acute toxic effects are estimated by:
• Damage in liver from long-term alcohol consumption
• LD50 studies or
• Reproductive difficulty:
• Observation of accidental exposures
• Decreased fertility from the pesticide dibromochloropropane
• Chronic toxic effects are estimated by dose-response studies
• Nervous system impairment:
on animals.
• Mental retardation in people exposed to high levels of lead during
• Especially, the carcinogenic effects are estimated by study
early childhood
called carcinogenesis bioassay.

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Dose - Response Relationship Dose - Response curve

• Dose : Amount that enters the body
• Response : Type and amount of damage cause by
a specific dose

• Dose - response relationship used to estimate

the health hazards of different exposure.
Eg: To identify critical value

• Dose - response curve

Illustrate the effect of different doses on a population
Allow us to predict effects of higher doses
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ED, TD & LD
Note: Threshold is a level,
ED: Effective Dose - Below: no effect occurs
TD: Toxic Dose - Above: effects being to occur
LD: Lethal Dose
If there is a Threshold exists, then the
concentration below the threshold is safe

If there is no Threshold Dose, then even

the smallest amount has some negative
toxic effect

Note: The smallest LD50, the more

ED50: Dose at which 50% of population therapeutically responds lethal the chemical
LD50: Dose at which 50% of population dies
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TD50: Dose at which 50% of population experiences toxicity

Assessing Acute Toxicity

• Acute toxicity of chemicals to humans comes from
accidental poisonings or exposures.
• Eg: Drug overdoses, Chemical spills
• Scientists also use animal tests called LD50 (Lethal Dose)
studies to assess acute toxicity.
• These studies determine the amount of a substance
that will kill half the test animals in 14 days.
• Ex: A reported "rat oral LD50 of 50 mg/kg" means that half
of the rats that ingested a dose of 50 mg of the substance
per kg of body weight died within 14 days
• LD50 values are unknown for humans, since LD50
experiments are not conducted on humans.
• If the LD50 is 50 mg/kg:
• The lethal amount for a child would be 50 mg/kg times 10 kg,
which equals 500 mg (about 1/8 tsp.)

• LD50 is stated in mg of chemical per kg of body weight. • The lethal amount for an adult would be 50 mg/kg times 70 kg,
which is 3,500 mg (about 3/4 tsp.)

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Assessing Chronic Toxicity • Example of a carcinogenesis bioassay

• Carcinogenic Assessment • A carcinogenesis bioassay was performed for benzene on both

• Test animals are administered different large doses of a rats and mice.

substance daily over a lifetime (24-30 months in rats) • Both sexes of each species got leukemia at the high doses

• At the end of the study, the animals are examined to see if administered.

cancer can be found. • Result of extrapolating the cancer incidence at high dose to

• If cancer is found, scientists use: low dose and from rodents to humans in the risk estimation is

• available data and given below:

• Benzene dose of 1 mg/kg/day will result in 3 cancers per 100 people
• mathematical models
exposed daily for a lifetime to that dose
to estimate the cancer incidence at the lower doses more likely
to occur in the environment.

• Non-Carcinogenic Assessment Role of Toxicity Assessment

• Non-carcinogenic chronic toxicity is assessed by administering
varying amounts of a substance (dose) to laboratory animals and • Toxicity assessment provides information on how much
noting the effects (responses). of a chemical causes what kind of harm.
• Essentially, the scientists look for the smallest dose that causes any
• As the toxicity assessment is based on an animal study,
detectable effect.
the degree of harm to humans must be extrapolated
• This smallest dose is called the Lowest Observable Effect Level
(LOEL). using mathematical models.
• Scientists also determine the highest dose at which no effects occur • It is done based on a variety of assumptions.
which is termed as NOEL.
• The NOEL is considered the "safe level" for that chemical in the
• Thus the toxicity assessment provides only an estimate
species of the harm to humans.

• HHRA is a screening tool that helps individuals to,

Identify and understand their health risks
Monitor health status over time
Human Health Risk • It includes a questionnaire, an assessment of health
Assessment status, and personalized feedback about actions that can
be taken to:
Reduce risks
Maintain health

Prevent disease

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• A health risk assessment usually includes questions in Planning and Scoping

the following areas: • Human health risk assessment starts with a good plan

Demographic characteristics: age, gender regarding the,

• Purpose, scope, and technical approaches that will be
Lifestyle behaviours: exercise, eating habits,
used
alcohol and tobacco use
• Risk assessors will typically ask the following questions
Emotional health: mood, stress, life events
1. Who/What/Where is at risk?
Physical health: weight, blood pressure,
 Individual
cholesterol levels  General population

 Life stages
Current and previous health conditions

3. Where do these environmental hazards come from?

2. What is the environmental hazard of concern?  Point sources (smoke or water discharge from a factory)
 Non-point sources (automobile exhaust, agricultural runoff)
Chemicals (single or multiple/cumulative risk)  Natural sources

Radiation 4. How does exposure occur?

 Air
Physical (dust, heat)
 Surface Water
Microbiological or biological  Groundwater
 Soil
Nutritional (for example, diet, fitness, or metabolic
 Solid Waste
state)  Food
 Non-food consumer products, pharmaceuticals

6. What are the health effects?

5. What does the body do with the environmental
 Some health effects include cancer, heart disease, liver disease and nerve
hazard and how is this impacted by factors such as disease

age, race, sex, genetics, etc.?
 Absorption - does the body take up the environmental hazard
 Distribution - does the environmental hazard travel throughout
the body or does it stay in one place?
 Metabolism - does the body break down the environmental
hazard?
7. How long does it take for an environmental hazard to cause a
toxic effect? Does it matter when in a lifetime exposure occurs?
How long?
 Acute - right away or within a few hours to a day
 Subchronic - weeks or months
 Chronic - a significant part of a lifetime or a lifetime

 Excretion - how does the body get rid of it? Timing

 Is there a critical time during a lifetime when a chemical is most toxic (fetal
development, childhood and during aging)?

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Steps-HHRA

• Step 1: Hazard Identification

• Step 2: Dose Response

• Step 3: Exposure Assessment

• Step 4: Risk Characterization

Step 1: Hazard Identification Step 2: Dose Response

• Objective: • Objective:
Identify the types of adverse health effects that can be Document the relationship between dose and toxic effect
caused by exposure to some agent
• A dose-response relationship describes how the
 Eg: Cancer and Birth defects
likelihood and severity of adverse health effects are
• Key Components of Hazard Identification
related to the amount and condition of exposure to an
• Toxicokinetic:
agent
• Considers how the body absorbs, distributes, metabolizes, and
eliminates specific chemicals. • Typically, as the dose , the measured response
• Toxicodynamic: • At low doses there may be no response.
• Focus on the effects that chemicals have on the human body

• Dose-response relationships observed from animal Step 3: Exposure Assessment

studies. • Objective:
• Animal studies must also be extrapolated from that Calculate a numerical estimate of exposure or dose.
animal species to humans.
• Exposure assessment is the process of measuring or
• It is done only to predict the relationship for humans. estimating the,
• It helps to find the NOAEL. Magnitude
Frequency
• Therefore the critical region where the dose level Duration
begins to cause the adverse effect in the human of human exposure to an agent in the environment.
population can be identified.

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• An exposure assessment includes some discussion of the,
Size
Nature
Types
of human populations exposed to the agent.
• Exposure can be measured directly.
• But more commonly is estimated indirectly through:
• Consideration of measured concentrations in the
environment
• Consideration of models of chemical transport and fate
in the environment
• Estimates of human intake over time
Range of Exposure
• There is a range of exposures actually experienced by
individuals for any
specific agent or site.
• Some individuals may have a high degree of contact for an
extended period.
Clarity
• The products from the risk assessment should be
readily understood by readers inside and outside
of the risk assessment process.
Consistency
• The risk assessment should be conducted and
presented in a manner which is consistent with
EPA policy.
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Exposure assessment considers 3 facts
Exposure pathway (the course an agent takes from its
source to the person(s) being contacted)
Exposure route (means of entry of the agent into the
body)
• It is described as
intake (taken in through a body opening) or
uptake (absorption through tissues)
Step 4: Risk Characterization
• Objective :
• Summarize and integrate information from the
proceeding steps of the risk assessment
to synthesize an overall conclusion about risk.
• Principles of conducting risk characterizations
Transparency
• The characterization should fully and explicitly
disclose the risk assessment
Reasonableness
• The risk assessment should be based on sound
judgment, with methods and assumptions
consistent with the current state-of-the-science.
• It should be conveyed in a manner that
complete
balanced and
informative
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Risk Management
• Develop and implement solutions for high priority
problems for protecting public health and the
environment
• Examples of risk management actions:
 deciding how much of a substance a company may discharge
Risk Management and into a river
Communication  deciding which substances may be stored at a hazardous
waste disposal facility

 deciding to what extent a hazardous waste site must be

cleaned up

 setting permit levels for waste discharge, storage, or transport

 establishing national ambient air quality standards

 determining allowable levels of contamination in drinking

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Agencies of risk management Risk Communication

• These are real-time exchange of
• Food and Drug Administration (FDA)
Foods, additives, cosmetics, drug, medical devices information, advice and opinions
between experts or officials and people
• Environmental Protection Agency (EPA) who face a hazard or threat to their
Pesticides, industrial chemicals, and any synthetic - survival
chemicals not covered by other agencies - health or
- economic or
• Occupational Health and Safety Administration (OHSA) - social wellbeing
Workplace hazards

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Thank You