HEALTH RISK

ASSESSMENT
PUBH 4101
 COURSE OBJECTIVES
• Understand the fundamentals of risk assessment
• Apply risk assessment principles to real life cases
• Make risk based management decisions
• Communicate risk to various stakeholders
 WHAT IS RISK ASSESSMENT?
• Hazard identification
• Risk estimation/evaluation
• Risk control or remediation
 4 ?’s
• What do we have?
• What does this mean? (RA)
• What should we do about it? (RM)
• Who should we tell and what should we tell them? (RC)
 What is RA?
• Involves hazards and assessments of those hazards
• Physical (includes radiological), psychosocial, biological, ergonomic, chemical
and safety (CCOHS, 2017)
• Looking at vulnerabilities of the population affected
• Could be the whole population
• Could be a section of the population
• Purpose is to eliminate hazards
• Or minimize when the hazard cannot be eliminated
 Common hazards
• Hazards that are common in every day life to which everyone is
affected
• Can you think of such a hazard?
 Specific hazards
• Specific jobs have specific hazards
• Some jobs are more hazardous than others
• Office worker vs. Engineer on an oil rig
What are major hazards associated with cleaning animal cages?
 Major accidents/incidents
• Series of events
• Can result in deaths, environmental damage and property destruction
• Lives, environment, property is always a concern in Risk Assessment
• Exxon valdez
• SARS
• Westray
• Chernobyl
• BP oil
• I’m sure you can think of others – anything recent? Have you ever personally been
affected?
 Risk – 3 questions
1. What can go wrong?
2. How likely is it?
3. What are the consequences?
• Risk Perception
• Can help and hinder
• Vaccination debate (is it even a debate?)
• Propane tanks vs. Hiroshima
CBC News article dated August 24, 2012
• Fertilizers, herbicides and pesticides Sunrise Propane Explosion

• Acceptable vs. unacceptable

 HAZARD IDENTIFICATION
• What is a hazard?
• How can you determine cause and effect?
• Some linkages were discovered prior to understanding the causative
agent, or being able to measure it.
 Hazard
• CCOHS: Canadian Centre for Occupational Health and Safety defines
hazard as: “A hazard is any source of potential damage, harm or
adverse health effects on something or someone.”
• The CSA Z1002 Standard OHS – Hazard identification and elimination
and risk assessment and control
• Harm – physical injury or damage to health
• Hazard – a potential source of harm to a worker
 Severity
• Vocabulary.com Dictionary’s definition is:
“excessive sternness, extreme plainness, something hard to endure,
used of the degree of something undesirable (pair or weather)”
• When it comes to risk assessment, how would you define severity?
 Consequence
• Effect, result or outcome of an occurrence
• Good or bad
 Vulnerability
• Weakness in a system or human that makes them susceptible to harm
 Threat
• Source of danger, can be thought of as a hazard.
Risk Assessment
• Individuals will respond differently depending on how well they feel
they understand the hazard
• Influences
• Environmental
• Biases
• Risk is Measured in
• average annual risk per individual
• average lifetime risk per individual
• average number of individuals affected annually in a given population
Activity Odds
Getting cancer 1 in 2 (lifetime)
Struck by lightning 1 in 10,456
Getting heartburn today 1 in 68
Being murdered in USA 1 in 140 (lifetime)
Serious cut while shaving 1 in 5,044 per year
Dying in car accident 1 in 75 (lifetime)
Having car stolen 1 in 159 yearly
Eating a hotdog today 1 in 7
Seeing Elvis this year 1 in 706,850
Being injured by toilet bowl cleaner 1 in 173,972 yearly
Dying falling out of a chair or bed 1 in 513,142 yearly
Dying while running 1 in 10,000 yearly
Dying while playing football 1 in 57,000 yearly
Dying from heart disease 1 in 6 (lifetime)
Risk Assessment
Models
 Models
• Used for performing risk assessments. Different models are used for different
areas.
• Not an inclusive list
• Models include qualitative and quantitative information

• Human Exposure Model (HEM) – used for performing RA’s on sources that
emit toxins into ambient air (EPA, 2017)
• Breast cancer risk assessment models (Breast Cancer Research)
• Actuarial risk assessment models
• Violence and sex-offender assessments (Journal of American Academic Psychiatry law)
 Risk Assessment Tools – not an inclusive list
• Preliminary hazard analysis (PHA)
• Failure mode and effect analysis (FMEA)
• Event Trees
• Fault tree analysis (FTA)
• Human reliability analysis (HRA)
• Probabilistic risk assessment (PRA)
• The Gail Model (personal medical history, reproductive history, family history)
Canadian Cancer Society
• Breast Cancer Risk Assessment tool (age, age at first period, age at first live birth,
personal history, race/ethnicity) Canadian Cancer Society
• IBIS tool (BRCA1 or BRCA2 mutations) Canadian Cancer Society
 NAS-NRC (National Academy of
Sciences/National Research Council)
Hazard identification

Dose response assessment

Exposure assessment

Risk characterization
Covello Merkhofer Model – microbial food
contamination
Hazard identification

Release assessment

Exposure assessment

Consequence assessment

Risk estimation
Risk Chain Model – supply and demand

Risk source release processes

Exposure processes

consequence processes
 EPA Risk Assessment Model
• Risk analysis
• Hazard identification
Risk • Risk estimation

assessment • Option Evaluation

• Development of options
• Option analysis

• Decision
Risk • Implementation
management • Monitoring and evaluating
• review
 Representatives for RA
• Multidisciplinary team
• Knowledge of work to be assessed
• Who would be the representatives for a RA on an oil Rig?
• Food establishment?
• Office?
• Hospital?
 Goal of RA
• ID hazards or potential hazards
• ID users and/or tasks
• Determine level of risk (low and acceptable vs. high and
unacceptable)
• Evaluate potential controls (elimination, substitution, admin controls,
PPE etc.)
• Develop a report
• Implementation and review
 Risk Perception
• A personal or group assessment of the potential for negative
consequences
• Perceived vs. actual
• Over-react to things that are: intentional, offend our morals, immediate
threats, spectacular and rare, earthquakes, terrorism, risks in situations you
can’t control
• Under-react to things that are: accidents, natural phenomena, long term
threats, things that occur slowly and over time, common risks, slipping on the
floor, street crime and risks you’re willing to take
• Worry more about anthrax than influenza
• Two planes brought down by lightning
 Knowledge
• Emotional
• Cognoscente – scientific apathy
• Experience
• Ideals (principles)
• Ideas
• Rules of thumb
• What are other risk perception influencers?
 Risks and Consequences
• Propane use
• Pest/weed control
• Nuclear power
• “at some point, the benefit of having nuclear electrical power was found to
be greater than the risk of a nuclear reactor meltdown.”
• Driving vs. flying
• Risky driving vs. small chemical plant
 Considerations
• What are all the known hazards
• What are all the possible events involving these hazards
• Have these events occurred before
• How frequently have these events occurred
• What happens when these events occur
• How severe are the consequences of these events
• How hard is it to clean up the mess left by the event
• Who ultimately pays for the cleanup
• What values does the organization consider important
 Important to remember:
• Never dismiss a consequence until it is proven to be not credible
• Consider all credible consequences
• All actions have consequences
• Healthy eating/exercise
• Driving intoxicated
• skydiving
 19th Century Linkages:
• London smog and respiratory disease
• celibacy and breast cancer
• tobacco snuff and nasal cancer
• chimney sweeps and scrotal cancer
• arsenic and cancer
• slum living and illness (generally)
• sunlight and skin cancer
• aromatic amines and bladder cancer
• contaminated water and cholera
 RISK ESTIMATION
• Qualitative
• How will the contaminant or activity adversely affect human health?
• Is it a large risk or small risk?
• size of impact, number of people affected, likelihood of effect
 RISK ESTIMATION
• Quantitative
• How much does the contaminant or activity adversely affect human health?
• shorter life
• illness
• altered quality of life (disabling, etc)
• Measure the contaminant
• Determine dose-response relationship
 RISK CONTROL/REMEDIATION
• Determine which risks can be controlled
• Determine available resources
• Review most effective method of controlling a risk. Consider:
• legal mandate
• cost effectiveness
• public reaction
• sociologic considerations
RISK MANAGEMENT: 10 WAYS TO
MANAGE RISK
• prevent the creation of the hazard
• reduce the amount of hazard
• prevent the release of the hazard
• modify the rate and distribution of the hazard
• separate the hazard from the human
• put up a barrier
• modify the hazard
• make the human more resistant to the hazard
• immediately counter the damage done
• stabilize, repair and rehabilitate
HAZARD IDENTIFICATION

What type of toxicity may occur?

Is this toxicity relevant to humans?
 Site Investigation
• Walk through
• Disease statistics/incidents
• Complaints
• Media coverage
 Walk Through Survey
• Workplace
• access MSDS for site
• determine chemical usage areas
• visually check locations of chemicals
• determine other “hazardous areas”
• is ventilation functioning?
• where are areas of employee concerns?
• etc.
 ILLNESS/INJURY STATISTICS
• Information on the occurrence of disease or injury may be available
• Epidemiological studies
• Statistics Canada
• Local rates of disease
• Hospital reports
 COMPLAINTS
• General public complaints about issues
• Worker complaints
• Media coverage
CHARACTERIZE THE HEALTH HAZARD
• Hazard classification/identification
• Toxicological studies
• Epidemiological studies
 HAZARD IDENTIFICATION
• Toxicity can be characterized by different perspectives
• Systems; nervous, immune, reproductive, endocrine, etc
• Organs; lung, liver, kidney, skin, eye, etc
• Diseases; cancer, birth defects, pneumoconiosis, etc
 HAZARD CLASSIFICATION
• Hazardous agents can be classified as
• carcinogens
• mutagens
• neurotoxins
• developmental/reproductive
• Based upon a “weight of evidence” assessment
• Classifications must be judged with care
 HAZARD IDENTIFICATION
• Chemicals vary greatly in types of toxicity they produce
• No single measure of toxicity can be adequate to characterize all
possible toxic outcomes
 HAZARD IDENTIFICATION
• Substances do not have “all or nothing” toxic properties
• those classified to be one or more of the types of toxic agent do not
necessarily have a proven cause-effect relationship (often cautious)
• those not classified are not judged to be safe
• Hazard classification is a classification of potential
 HAZARD IDENTIFICATION
• Risk assessment judges the hazard potential in relation to exposures
and dose-response relationship to determine likelihood (chance,
probability) of harm
 HAZARD IDENTIFICATION
• Weight of evidence approach considers:
• quality of each relevant study
• quality of data
• specifics of study design
• overall strengths and limitations
• knowledge about principles of each study
• experience and judgment for the interpretation of data
 HAZARD IDENTIFICATION
• Human studies are the best, but
• limited availability for env. exposures
• ethics preclude env. human experiments
• observational nature limits control
• not able to be preventive (predict hazard before human exposure)
• poor quality exposure data (generally)
• encounter unrecognized bias and confounding
• limited statistical power
 HAZARD IDENTIFICATION
• Animal studies offer advantages of:
• lab control
• can be predictive
• existence of some agreement between animal studies and human
• can test exposure patterns (routes, duration, frequency)
• can determine dose response relationships
• can fill gaps in human data
 HAZARD IDENTIFICATION
• Animal studies have disadvantages;
• need to extrapolate results to humans
• need to be on practical scale (high dose to see effect), then have to
extrapolate to low dose human exposure
• In vitro assays and structure activity relationships provide support but
cannot confirm human toxicity
 HAZARD IDENTIFICATION
• Hierarchy of value:
• human>animal>in vitro>theoretical
• Hazard identification should include statements of:
• confidence in conclusions
• alternative conclusions
• evident data gaps
• identification of assumptions
 Hazards
• Well known hazards?
• Carcinogens
• Mutagens
• Neurotoxicants
 CARCINOGENS (CEPA)
• Group I - Carcinogenic to humans
• data from epidem. studies indicate causal relationship
• Group II - Probably carcinogenic to humans
• inadequate epidem. evidence but sufficient animal study info.
• Group III - Possibly carcinogenic to humans
• Group IV - Unlikely to be carcinogenic to humans
• Group V - Probably not carcinogenic to humans
• Group VI - Unclassifiable (not enough info)
 CARCINOGENS
• New US EPA carcinogen guidelines (1996)
• weight of evidence classes for Human Evidence
• Category 1 - conclusive causal
• Category 2 - plausible causal assoc. suggested
• Category 3 - conclusive causal assoc. cannot be judged
• Category 4 - conclusive assoc. does not exist
 CARCINOGENS - US EPA Guidelines
• Weight of evidence for mechanisms of action:
• explained by body of research accepted scientifically
• experimental evidence supports the agent acting by the mechanism
• observed animal effects must be relevant to humans
• agent affects carcinogenesis linearly at low exposure (dose and response)
 Carcinogens
• Chemicals in tobacco
• Arsenic
• What else?
 MUTAGENS
• Agents capable of causing genetic effects by damaging genes or
chromosomes
• links to cancer
• activation of protooncogenes to oncogenes
• inactivation of tumour suppressor genes
 MUTAGENS
• more than 100 bioassay systems for testing mutagenicity
• Ames salmonella assay is most famous
• Used to determine the mutagenic potential of new drugs/chemicals
• Has to do with histidine to show which are mutagens
• no one test can detect full spectrum of genotoxicity
 GENETIC TOXICITY TESTS (in vitro)
• Assessing damage to genetic material:
• mutation is damage to DNA which can be passed on
• DNA organized into chromosomes - damage may also occur at this level
• for genetic damage to occur in future generations, sperm or eggs must be
affected
 GENETIC TOXICITY TEST (in vitro)
• Cells have efficient DNA repair
• many natural errors fixed
• extimated total of 1029 DNA errors in normal lifetime
• suggests that DNA damage only an issue if repair capacity is exceeded
 DEVELOPMENTAL/REPRODUCTIVE
• effects on developing fetus or on reproduction
• traditionally dependent on animal data
• thalidomide wasn’t tested on pregnant animals
• both short and long term bioassays used
 Mutagens
• X-rays
• Gamma rays
• Benzene
• UV
 NEUROTOXICANTS
• agents leading to structural or functional changes in CNS or PNS
• some patterns or types of neurotoxic effect may not be detectable in
animals
• some neurotoxic effects are irreversible
STRUCTURE- ACTIVITY RELATIONSHIP
• Biological effect is dependent on chemical structure of substance
• understand key structural features assoc. with given effects
• relate effects to structures, so that predictions can be made
• quantitative structure-activity relationships QSAR
• QSAR is strictly predictive and cannot confirm toxicity
 Neurotoxicants
• “Only about 200 chemicals out of more than 80,000 registered with
the United States Environmental Protection Agency have undergone
extensive neurotoxicity testing, and many chemicals found in
consumer goods are not required to undergo any
neurodevelopmental testing”
• Miodovnik, A. (2011). Environmental Neurotoxicants and Devloping
Brain. Mt Sinal J Med 78: 58-77.
 Neurotoxicants
• Lead
• Ethanol
• Botulinum toxin
• Tetanus toxin
 TOXICOLOGICAL APPROACHES
• Toxicology is the study of the adverse effects of chemicals on the body
• Science - based on observation and experiment
• Art - based on interpretive and predictive activities
• Health risk assessment relies on the science, but is an application of
the art of toxicology
 DOSE RESPONSE

• Quantitative basis for toxicology is the dose response

• Dose measures are derived from the dose response curve
• generic dose response - change in an indicator
• individual graded response - form or severity of adverse effects as a function of dose
• population quantal response - predict if an effect occurs in response to an agent
 DOSE RESPONSE
• used to assess effects of exposure of chemicals
• vast amount of info on carcinogens
• neither dose nor response is easily quantified
• exposures vary over time
• health effects vary in frequency and severity
• time delay between cause and effect
• type of effect may change with dose
 DOSE RESPONSE - General Rules
• at low exposure, no effects seen regardless of exposure duration
• at slightly higher exp., subtle effects seen in small proportion
• as dose increases, greater proportion of the popn will respond with
subtle effects, small proportion will have severe effects
• as dose further increased, incidence & severity increase
 DOSE RESPONSE - General Rules
• at high dose, nearly whole population will have severe effects, some
with even more severe
• nearly any risk agent at high enough dose will cause death
 Dose Response - General Information
• dose expressed in terms of cumulative exposure or rate per unit time
• response scale depends on the nature of the response
• severity
• probability
• time until occurrence
• estimate “excess risk” (above that of background risk)
 Dose Response Relationship
• can be derived from statistical analysis of observations
• regression analysis of actual events
• adjust for sensitive population
• derive from animal studies
• careful about extrapolations
• estimates only
• use conversion factors
 Dose Response Models
• Simple dose response model
• tolerance distribution models
• mechanistic models
• time to response models
• pharmacokinetic models
 Dose Response
• individual vs. population
• important to understand
• plot dose against response
• shape
• S shaped
• most toxicants
• U shaped
• vitamins
• threshold important
INTERPRETATION
• Statistical inference
• relies on statistical analysis of data
• are responses stat. significant?
• must insure statistical power is adequate for intended purposes
• must distinguish statistical significance from biological significance
 Simple Dose Response Model
• relates single measure of dose to single measure of health response
• eg. exposure to number of deaths
• can be zero threshold or threshold
 ANIMAL TOXICITY TESTING
• Acute toxicity testing objectives
• assess intrinsic toxicity and potency
• identify target organs
• estimate duration of effects
• determine effective dosage ranges for long term studies
 ANIMAL TOXICITY TESTING
• Acute toxicity testing objectives
• assess species susceptibility
• establish reversibility
• determine mechanisms
• determine toxicokinetics
• meet regulatory requirements
 TOXICITY CONSIDERATIONS
• Exposures • Responses
• acute • immediate
• subchronic • delayed
• chronic • Severity
• mild, reversible
• serious, irreversible
• life-threatening
 Probability
• Probability theory
• Important part of risk assessment
• Extent to which something is probable, likelihood of something
happening
• Math – measured by the ratio of favorable cases to the whole number
of cases possible (first class exercise)
• Successful outcomes vs. unsuccessful
• Expressed somewhere between 0 and 1
• 0 means impossible
• 1 means certainty
 Probabilities
• Rolling the number 5 on a die
• Drawing a card 4 or lower in a deck of cards
• Grades of a group of 1000 students in an exam are distributed with a
mean of 70 and a standard deviation of 10
• One student picked randomly
Probability
• Prob that their grade is greater than 80?
• Prob that their grade is less than 50?
• Prob that their grade is between 50 and 80?
• How many students have grades greater than 80?