Lecture 20Lecture 20ToxicologyToxicology

HRhHRh

ToxicologyToxicology

Environmental HazardsEnvironmental Hazards are the pollutants that are potentially are the pollutants that are potentially harmful and may pose long-term health risks to people who live harmful and may pose long-term health risks to people who live and work around the area or facilities that produce or use themand work around the area or facilities that produce or use them

Hazardous materialsHazardous materials includeinclude::

Infectious AgentsInfectious Agents► Environmentally transmitted infectious diseases Environmentally transmitted infectious diseases spread from spread from

interactionsinteractions of individuals with food, water, air, or soil of individuals with food, water, air, or soil ► Environmentally transmitted diseases include Environmentally transmitted diseases include Salmonella, Salmonella,

malaria, etc.malaria, etc.

ToxicologyToxicology

Toxic Heavy MetalsToxic Heavy Metals► Among the heavy metals, Among the heavy metals,

mercury, lead, arsenic, mercury, lead, arsenic, cadmium, copper, zinc, cadmium, copper, zinc, seleniumselenium are of most concern are of most concern

► Have direct Have direct physiological physiological toxictoxic effects effects

► Some are stored or Some are stored or incorporated in incorporated in living tissueliving tissue, , sometimes permanently sometimes permanently

Organic CompoundsOrganic Compounds ► Difficult to generalize about Difficult to generalize about

the environmental and health the environmental and health effects effects

► There are There are so manyso many of them, of them, so many usesso many uses, and they can , and they can produce produce so manyso many different different kindskinds of effectsof effects

► Pest control, Pest control, pharmaceuticals, food pharmaceuticals, food additives, and other additives, and other consumer productsconsumer products

ToxicologyToxicology

RadiationRadiation► Nuclear radiation is Nuclear radiation is

considered as a category of considered as a category of pollution because exposure pollution because exposure to nuclear radiation is linked to nuclear radiation is linked to serious health problems, to serious health problems, including including cancercancer Thermal PollutionThermal Pollution

► Changes the average water Changes the average water temperature and temperature and concentration of dissolved concentration of dissolved oxygen, changing the rivers oxygen, changing the rivers speciesspecies compositioncomposition

ParticulatesParticulates► Released into the atmosphere by many Released into the atmosphere by many

natural processes and human activities natural processes and human activities ► Chemical toxins, such as heavy metals, Chemical toxins, such as heavy metals,

enter the biosphere as particulatesenter the biosphere as particulates

AsbestosAsbestos► Asbestos refers to a group of Asbestos refers to a group of fibrous fibrous

silicate mineralssilicate minerals ► Used Used as insulation materialas insulation material around around

pipes and for brake linings of pipes and for brake linings of automobilesautomobiles

► When When inhaledinhaled it may cause it may cause asbestosisasbestosis (a pneumonia condition), (a pneumonia condition), bronchogenicbronchogenic carcinomacarcinoma (lung (lung cancer)cancer)

ToxicologyToxicology

Electromagnetic Fields Electromagnetic Fields (EMFs)(EMFs)

► Electromagnetic fields are Electromagnetic fields are part of our everyday urban part of our everyday urban life life

► Children exposed to EMFs Children exposed to EMFs from power lines have an from power lines have an increasedincreased risk of risk of contracting leukemia, contracting leukemia, lymphomas, and nervous lymphomas, and nervous system cancerssystem cancers

Noise PollutionNoise Pollution

Personal pollutantsPersonal pollutants► Most common of these are Most common of these are tobacco, tobacco,

alcohol, and other drugsalcohol, and other drugs► Use and abuse lead to a variety of Use and abuse lead to a variety of

human illshuman ills ranging from suffering ranging from suffering and/or dying from chronic disease, and/or dying from chronic disease, criminal activity such as reckless criminal activity such as reckless driving or manslaughter, street driving or manslaughter, street crime, loss of careerscrime, loss of careers

► 30% of all cancers30% of all cancers in the US are in the US are tied to smoking-related disorderstied to smoking-related disorders

Fundamentals of ToxicologyFundamentals of Toxicology

A A poison or toxicantpoison or toxicant is a substance that is harmful to living is a substance that is harmful to living organisms organisms

ToxicologyToxicology is the science that studies is the science that studies poisons (or toxinspoisons (or toxins))► A A basic concept ofbasic concept of toxicology istoxicology is that that any synthetic or natural any synthetic or natural

chemical (even water) can be harmful if ingested in a large enough chemical (even water) can be harmful if ingested in a large enough quantityquantity

• Environmental toxicologyEnvironmental toxicology concerned with concerned with how environmental how environmental toxicantstoxicants, through their interaction with humans, animals, and , through their interaction with humans, animals, and plants, plants, influence the health and welfareinfluence the health and welfare of humans, animals, and of humans, animals, and plants, as well as plants, as well as ways to prevent or minimizeways to prevent or minimize adverse effects adverse effects

ToxicologyToxicology

ToxicityToxicity measures how harmful a substance ismeasures how harmful a substance isToxicityToxicity depends on depends on severalseveral factors:factors:

► DoseDose► Frequency ofFrequency of exposureexposure► Who is exposedWho is exposed► How wellHow well the body’sthe body’s detoxification systemsdetoxification systems ( (liver, lungs, and liver, lungs, and

kidneys) kidneys) workwork► Genetic makeupGenetic makeup that determines an individual’s that determines an individual’s sensitivitysensitivity to a to a

particular toxin particular toxin Several Several other factorsother factors can can affectaffect the the harm causedharm caused by a substance, by a substance, such assuch as

ToxicologyToxicology

Whether a toxicant is Whether a toxicant is solid, liquidsolid, liquid, or , or gasgas, , organic organic or or inorganicinorganic, , ionizedionized or or nonionizednonionized; ; solubilitysolubility (whether in water or fat); (whether in water or fat); persistencepersistence; ; bioaccumulation, biomagnification, chemical bioaccumulation, biomagnification, chemical interactionsinteractions

The The effect effect of toxicants following exposure can be immediate (of toxicants following exposure can be immediate (acute acute toxicitytoxicity) or prolonged () or prolonged (chronic toxicitychronic toxicity))

Acute toxicityAcute toxicity, which ranges from , which ranges from dizziness and nausea to deathdizziness and nausea to death, , occurs immediately to within several days following a occurs immediately to within several days following a single single exposureexposure

Chronic toxicityChronic toxicity generally produces damage to vital organs, such as generally produces damage to vital organs, such as the kidneys or liver, following a the kidneys or liver, following a long-term, low-level exposurelong-term, low-level exposure to to toxicantstoxicants

ToxicologyToxicology

Concept of Dose and ResponseConcept of Dose and Response► Dose is the most important factorDose is the most important factor affecting the toxicity affecting the toxicity► DoseDose or concentrationor concentration is the amount of a harmful substance a is the amount of a harmful substance a

person person ingests, inhales, or absorbsingests, inhales, or absorbs► The effect of a certain chemical on an individual depends on the The effect of a certain chemical on an individual depends on the

dose or concentrationdose or concentration of the toxic factor— of the toxic factor—dose-responsedose-response

Concept of Dose and ResponseConcept of Dose and Response

► Usually when we think of dose, we think in terms of taking one Usually when we think of dose, we think in terms of taking one vitamin capsule a day or two aspirin every four hours, or vitamin capsule a day or two aspirin every four hours, or something like thatsomething like that

► Contamination of food or water with chemicals can also Contamination of food or water with chemicals can also provide doses of chemicals each time we eat or drinkprovide doses of chemicals each time we eat or drink

► Some commonly used measures for expressing levels of Some commonly used measures for expressing levels of contaminants are listed in contaminants are listed in Table 1Table 1

► These measures tell us how much of the chemical is in food, These measures tell us how much of the chemical is in food, water or airwater or air

► The amount we eat, drink, or breathe determines the actual The amount we eat, drink, or breathe determines the actual dose we receivedose we receive

Table 1. Measurements for Expressing Levels of Contaminants in Food and Water

DoseAbbre

vMetric

equivalentAbbre

vApprox. amt. in water

parts per million ppm

milligrams per kilogram

mg/kg

1 teaspoon per 1,000 gallons

parts per billion ppb

micrograms per kilogram ug/kg

1 teaspoon per 1,000,000 gallons

ToxicologyToxicology

ResponseResponse is the effect upon an organism resulting from is the effect upon an organism resulting from exposure to a toxicantexposure to a toxicant

► ResponseResponse variesvaries greatly greatly with duration of exposurewith duration of exposure► The The modemode of exposureof exposure, whether , whether continuous or intermittentcontinuous or intermittent► Activity level of an exposed organismActivity level of an exposed organism► Normally, Normally, continuous exposurecontinuous exposure is is more injurious than more injurious than

intermittentintermittent exposure exposure► Individuals differIndividuals differ in their in their response response to environmental toxins, to environmental toxins,

just as they do in response to all environmental conditionsjust as they do in response to all environmental conditions

Dose-Response CurveDose-Response Curve► The relationship of dose The relationship of dose

to response can be to response can be illustrated as a graph illustrated as a graph called a called a dose-response dose-response curvecurve

► The dose is represented The dose is represented on the on the xx-axis-axis and and response is represented response is represented on the on the yy-axis-axis

► The following graph The following graph shows a simple example shows a simple example of a dose-response curve of a dose-response curve for an individual with a for an individual with a single exposure to the single exposure to the chemical ethanol chemical ethanol (alcohol), with graded (alcohol), with graded responses between no responses between no effect and deatheffect and death

Individual Dose-Response Curve

Dose-Response CurveDose-Response Curve► An important aspect of dose-response An important aspect of dose-response

relationships is the concept ofrelationships is the concept of thresholdthreshold, below which there are no , below which there are no adverse effects from exposure to the adverse effects from exposure to the chemicalchemical

► The human body has defenses against The human body has defenses against many toxic agentsmany toxic agents

► Cells in human organs, especially in Cells in human organs, especially in the liver and kidneys, break down the liver and kidneys, break down chemicals into nontoxic substances chemicals into nontoxic substances that can be eliminated from the body that can be eliminated from the body in urine and fecesin urine and feces

► In this way, the human body can take In this way, the human body can take some toxic insult (at a dose that is some toxic insult (at a dose that is below the threshold) and still remain below the threshold) and still remain healthyhealthy

► It is important for toxicologists to It is important for toxicologists to identify a level exposure to a chemical identify a level exposure to a chemical at which there is no effect and to at which there is no effect and to determine thresholds when possibledetermine thresholds when possible

► The most commonly used measure, linked to the dose-The most commonly used measure, linked to the dose-response curve, is the response curve, is the amount of exposure require for amount of exposure require for 50%50% of a population or observed subjects to show a of a population or observed subjects to show a responseresponse

► The dose at which 50% of the population dies is called the The dose at which 50% of the population dies is called the median lethal dose 50median lethal dose 50, or , or LDLD5050 (lethal dose) (lethal dose)

► TheThe EDED5050 ( (effective dose 50%effective dose 50%) is the dose that causes an ) is the dose that causes an effect in 50% of the population or observed subjectseffect in 50% of the population or observed subjects

► For example, the For example, the EDED5050 of aspirin would be the dose that of aspirin would be the dose that relieves headaches in 50% of the peoplerelieves headaches in 50% of the people

► The The TDTD5050 ( (toxic dose 50%toxic dose 50%) is defined as the dose that is ) is defined as the dose that is toxic to 50% of the populationtoxic to 50% of the population

ToxicologyToxicology

Health Risk AssessmentHealth Risk Assessment

The The four steps involvedfour steps involved in risk assessment in risk assessment

are: are:

(1) Hazard Identification (1) Hazard Identification

(2) Dose-response assessment(2) Dose-response assessment

(3) Exposure assessment(3) Exposure assessment

(4) Risk characterization(4) Risk characterization

Step What It Answers

1.Hazard Identification

Does exposure to a substance cause an increased likelihood of an adverse health effect such as cancer or birth defects?

2. Dose-response assessment

What is the relationship between amount of exposure (dose) and the seriousness of the adverse health effects?

3.Exposure assessment

How much, how often, and how long are humans exposed to the substance in question? For hazardous air pollutants, emissions are measured and analyzed to determine the relationship between emissions and concentrations in the environment. Where humans live relative to the emissions is also considered.

4.Risk characterization

What is the probability of an individual or population having an adverse health effect? Risk characterization combines and evaluates data from dose-response assessment and exposure assessment (step 2 & 3).

Health Risk AssessmentHealth Risk Assessment

► Once a risk assessment has been performed, its results are Once a risk assessment has been performed, its results are evaluatedevaluated

► Evaluation, which includes the development and implementation Evaluation, which includes the development and implementation of laws to regulate hazardous substances, is known as of laws to regulate hazardous substances, is known as risk risk managementmanagement

Risk assessment helps us to estimate the probability that an event Risk assessment helps us to estimate the probability that an event will occur and enables us to set priorities and manage risks in an will occur and enables us to set priorities and manage risks in an appropriate wayappropriate way

Conceptual Framework

Hazard AssessmentToxicity Assessment

Acute & Chronic Toxicity

ExposureChemical and physical

transformation

Risk Characterization

Risk Management

End of SlidesEnd of Slides