bisc 312 environmental toxicology i
Post on 20-Jul-2022
2 Views
Preview:
TRANSCRIPT
1
BISC 312BISC 312Environmental Toxicology IEnvironmental Toxicology I
Instructor: Instructor: OnkarOnkar BainsBainsINTRODUCTIONINTRODUCTION
Mark BreakdownMark Breakdown
Midterm 1 Midterm 1 (Monday, October 4(Monday, October 4thth) ) –– 20%20%
Midterm 2 Midterm 2 (Monday, November 8(Monday, November 8thth ) ) –– 20%20%
Final Exam Final Exam (December 14(December 14thth) ) –– 45%45% Cumulative with emphasis on material following Midterm 2Cumulative with emphasis on material following Midterm 2
Group Presentation Group Presentation –– 15%15% Around 10 people per groupAround 10 people per group 15 - 20 minutes to present15 - 20 minutes to present Q&AQ&A Taking place mid November and onTaking place mid November and on Material discussed will be on final !!Material discussed will be on final !! 9% based on presentation; 6% based on your group mark9% based on presentation; 6% based on your group mark
2
Instructor InfoInstructor Info
Email addressEmail address –– obains@sfu.caobains@sfu.ca
OfficeOffice –– SSB 6125 SSB 6125
Office HoursOffice Hours –– Mondays from 1:00pm to Mondays from 1:00pm to2:00pm or by appointment (not Tuesdays or2:00pm or by appointment (not Tuesdays orThursdays)Thursdays)
Topics to be coveredTopics to be covered What is Environmental Toxicology?What is Environmental Toxicology?
Dose, Dose ResponseDose, Dose Response
Toxicity and Toxicity TestingToxicity and Toxicity Testing
Uptake, Distribution, Biotransformation, EliminationUptake, Distribution, Biotransformation, Elimination
TeratogenesisTeratogenesis, Mutagenesis, Carcinogenesis, Mutagenesis, Carcinogenesis
3
Topics to be coveredTopics to be covered
Environmental Pollutants:Environmental Pollutants:
PAHsPAHs
PCBsPCBs
Dioxins/furansDioxins/furans
PesticidesPesticides
Heavy metalsHeavy metals
Endocrine disruptorsEndocrine disruptors
Biological toxinsBiological toxins
Topics to be coveredTopics to be covered
Multixenobiotic/MultidrugMultixenobiotic/Multidrug resistance resistance
Oil spills and bioremediationOil spills and bioremediation
Atmospheric pollution and Greenhouse effectAtmospheric pollution and Greenhouse effect
Acid rainAcid rain
Biomarkers and Biomarkers and BioindicatorsBioindicators
Group presentation topicsGroup presentation topics
4
Group Presentation TopicsGroup Presentation Topics
Waste water treatmentWaste water treatment
AsbestosAsbestos
Pulp and paper mill effluentPulp and paper mill effluent
ArsenicArsenic
Free radical toxicityFree radical toxicity
PhthalatesPhthalates
EutrophicationEutrophication
TributyltinTributyltin
CFCCFC’’s (maybe)s (maybe)
Guest SpeakersGuest Speakers
Mr. Rick LeeMr. Rick Lee Cancer and CarcinogenesisCancer and Carcinogenesis
Ms. Vicki FlemingMs. Vicki Fleming M.E.T. project based on oral cancer and smokingM.E.T. project based on oral cancer and smoking
Mr. Mr. JasenJasen Nelson Nelson Endocrine disruptorsEndocrine disruptors
5
Guest SpeakersGuest Speakers
Mr. Keith Tierney and Ms. Amber TaylorMr. Keith Tierney and Ms. Amber Taylor Pesticides and olfactionPesticides and olfaction
Ms. Michelle Ms. Michelle StockwellStockwell Pesticides and fish farmingPesticides and fish farming
Mrs. Helena Mrs. Helena DaudtDaudt CadmiumCadmium
BISC 312BISC 312Environmental Toxicology IEnvironmental Toxicology I
ENVIRONMENTALENVIRONMENTALTOXICOLOGY, DOSE, DOSE-TOXICOLOGY, DOSE, DOSE-
RESPONSERESPONSE
6
What is Environmental Toxicology?What is Environmental Toxicology?
traditional definition oftraditional definition of toxicology istoxicology is““________________________________________________________________________________”” Poison = Poison = a substance that can cause damage or disturbancea substance that can cause damage or disturbance
to the function of organisms or ecosystemsto the function of organisms or ecosystems
"the study of the _________ effects of chemicals or"the study of the _________ effects of chemicals or______________ on living organisms______________ on living organisms““
TerminologyTerminology
ToxicToxic substances are not usually referred to as poisons substances are not usually referred to as poisons
XenobioticXenobiotic::
Toxicant:Toxicant:
Toxin:Toxin:
7
TerminologyTerminology
Pollutant:Pollutant:
Contaminant:Contaminant:
Environmental ToxicologyEnvironmental Toxicologyincorporatesincorporates……
BiologyBiology ChemistryChemistry
and more !and more !
8
Ultimate Goals of EnvironmentalUltimate Goals of EnvironmentalToxicologyToxicology
Investigate and quantify effects of toxicants onInvestigate and quantify effects of toxicants onindividual organismsindividual organisms
Identify ecological consequences, i.e. make linkIdentify ecological consequences, i.e. make linkbetween _____________________ andbetween _____________________ and__________________ in organisms__________________ in organisms
Predict _______________________________Predict _______________________________
ParacelsusParacelsus
From http://www2.bren.ucsb.edu/~keller/courses/esm202/ESM202Lecture11_2004.pdf.pdf
9
DoseDose
By definition is the amount of a substance administered at oneBy definition is the amount of a substance administered at onetimetime
However, other parameters are needed to characterize theHowever, other parameters are needed to characterize theexposure to exposure to xenobioticsxenobiotics.. The most important are the number of The most important are the number ofdoses, frequency, and total time period of the treatment.doses, frequency, and total time period of the treatment.
For example:For example:
Usual dosage unit is __________________Usual dosage unit is __________________
10
DoseDose
Numerous types of doses, for example:Numerous types of doses, for example:
Dose-Response CurveDose-Response Curve
X axisX axis——DOSEDOSE
Y axisY axis——RESPONSERESPONSE
A higher dose or concentration causes a more intense effect (response)
11
Significance of Dose-ResponseSignificance of Dose-Response
Knowledge of the dose-response relationship:Knowledge of the dose-response relationship:
establishes causality that the chemical has in fact induced theestablishes causality that the chemical has in fact induced theobserved effectsobserved effects
establishes the lowest dose where an induced effect occurs -establishes the lowest dose where an induced effect occurs -the threshold effectthe threshold effect
determines the rate at which injury builds up - the slope fordetermines the rate at which injury builds up - the slope forthe dose responsethe dose response
INTERPRETING DOSE-INTERPRETING DOSE-RESPONSE CURVESRESPONSE CURVES
12
ThresholdThreshold Point at which toxicity first appears is known as thePoint at which toxicity first appears is known as the
______________________________________________ A thresholdA threshold for toxic effects occurs at pointfor toxic effects occurs at point
where______________________________________where____________________________________________________________________________________________________________________________
From http://www.sis.nlm.nih.gov/ToxTutor/Tox1/a22.htm
NOAEL and LOAELNOAEL and LOAEL
NOAELNOAEL ““no observed adverseno observed adverse
effect leveleffect level””
LOAELLOAEL ““lowest observed adverselowest observed adverse
effect leveleffect level”” From http://www.sis.nlm.nih.gov/ToxTutor/Tox1/a25.htm
13
What does the slope of a doseWhat does the slope of a doseresponse curve tell us?response curve tell us?
A steep slope indicates that a small change inA steep slope indicates that a small change indose will result indose will result in____________________________________________________________________________________________________________________________________________________
A flat slope indicates a large change in dose isA flat slope indicates a large change in dose isrequired before a significant change in responserequired before a significant change in responsewill be observedwill be observed
STEEPSLOPE
FLATTERSLOPE
14
Effective, Toxic and Lethal DosesEffective, Toxic and Lethal Doses
EffectiveEffective represented represented ““EE””
ToxicToxic represented represented ““TT””
LethalityLethality represented represented ““LL””
Dose versus ConcentrationDose versus Concentration
LDLD represents the_____________ represents the_____________
LCLC represents the ______________________ represents the ______________________
ConcentrationConcentration is used when working with is used when working with__________________ or when the toxicant is__________________ or when the toxicant isin the _________in the _________
15
Definitions of PercentagesDefinitions of Percentages
ECEC1100::
LDLD1100::
ECEC2525::
PotencyPotency
When comparing 2 or more toxicants, the one with theWhen comparing 2 or more toxicants, the one with thesmallersmaller ED, LD or TD (EC, LC or TC) is considered ED, LD or TD (EC, LC or TC) is consideredto be __________________to be __________________
Valid comparisons between dose response data areValid comparisons between dose response data arethose with same _______________________those with same _______________________ Example:Example:
Comparing Comparing LDLD5050 of Toxicant A with an of Toxicant A with an LDLD5050 of Toxicant B of Toxicant B NotNot comparing comparing LDLD5050 of Toxicant A with an of Toxicant A with an LDLD1010 of Toxicant B of Toxicant B
16
PotencyPotency
Example:Example: Toxicant A LDToxicant A LD5050 = 23 mg/kg = 23 mg/kg Toxicant B LDToxicant B LD5050 = 38 mg/kg = 38 mg/kg Toxicant C LDToxicant C LD5050 = 67 mg/kg = 67 mg/kg
EfficacyEfficacy
Toxicant is said to have high efficacy whenToxicant is said to have high efficacy whendose-response relationshipdose-response relationship____________________________________________________________________________________________________________________________________________________
17
Therapeutic IndexTherapeutic Index Used to compare the therapeutically ___________ toUsed to compare the therapeutically ___________ to
the _______________the _______________
Statement of relative safety of a drugStatement of relative safety of a drug
Ratio of dose producing toxicity to dose needed toRatio of dose producing toxicity to dose needed toproduce desired therapeutic responseproduce desired therapeutic response
__________________________________________________________
Common method used to derive TI is to use ____Common method used to derive TI is to use ____%%dose-response pointsdose-response points
Therapeutic IndexTherapeutic Index
For example, if LD50 is 200 and ED50 is 20 mg,For example, if LD50 is 200 and ED50 is 20 mg,the TI would be ____ the TI would be ____ (____/____)(____/____)
The larger the therapeutic index, the _______The larger the therapeutic index, the _______the drug.the drug. Some drugs have a low therapeutic index, e.g.,Some drugs have a low therapeutic index, e.g.,
DigoxinDigoxin Others have a high therapeutic index, e.g., Others have a high therapeutic index, e.g., NaloxoneNaloxone
18
Therapeutic Index & Margin ofTherapeutic Index & Margin ofSafetySafety
Use of the EDUse of the ED5050 and LD and LD5050 doses to derive the doses to derive the TI TI may bemay bemisleading as to safety, depending on slope of dose-responsemisleading as to safety, depending on slope of dose-responsecurves for therapeutic and lethal effectscurves for therapeutic and lethal effects
To overcome this deficiency, toxicologists often use anotherTo overcome this deficiency, toxicologists often use anotherterm to denote safety of drugterm to denote safety of drug——MarginMargin of Safetyof Safety (MOS)(MOS)
MOSMOS = ratio of dose that is just within the lethal range (LD= ratio of dose that is just within the lethal range (LD0101) to) tothe dose that is 99% effective (EDthe dose that is 99% effective (ED9999)) MOS =MOS = LD LD0101/ED/ED9999
Physician must use caution in prescribing a drug in which MOSPhysician must use caution in prescribing a drug in which MOSis < 1is < 1
19
BISC 312BISC 312Environmental Toxicology IEnvironmental Toxicology I
TOXICITY AND TOXICITYTOXICITY AND TOXICITYTESTINGTESTING
Toxic EffectsToxic Effects
Toxicity can result from adverse cellular, biochemical, orToxicity can result from adverse cellular, biochemical, ormacromolecular changes.macromolecular changes. Examples are: Examples are:
cell replacement, such as fibrosiscell replacement, such as fibrosis
damage to an enzyme systemdamage to an enzyme system
disruption of protein synthesisdisruption of protein synthesis
production of reactive chemicals in cellsproduction of reactive chemicals in cells
DNA damageDNA damage
interference with nutritioninterference with nutrition
20
Toxicity Depends UponToxicity Depends Upon…… The toxicity of a substance depends on the following:The toxicity of a substance depends on the following:
form and innate chemical activityform and innate chemical activity
dosage, especially dose-time relationshipdosage, especially dose-time relationship
exposure routeexposure route
speciesspecies
ageage
sexsex
metabolismmetabolism
ability to be absorbedability to be absorbed
excretionexcretion
distribution within the bodydistribution within the body
presence of other chemicalspresence of other chemicals
FormForm The formThe form of a substance may have a profoundof a substance may have a profound
impact on its toxicity especially for metallicimpact on its toxicity especially for metallicelements.elements. For example: For example:
21
Innate Chemical ActivityInnate Chemical Activity
Innate chemical activityInnate chemical activity of substances also variesof substances also variesgreatly.greatly. Some can quickly damage cells causing Some can quickly damage cells causingimmediate cell death.immediate cell death. Others slowly interfere only with Others slowly interfere only witha cell's function.a cell's function. For example: For example:
nicotine binds to cholinergic receptors in the CNS alteringnicotine binds to cholinergic receptors in the CNS alteringnerve conduction and inducing gradual onset of paralysisnerve conduction and inducing gradual onset of paralysis
AgeAge
Age Age may be important in determining the response tomay be important in determining the response totoxicants.toxicants. Some chemicals are more toxic to infants or Some chemicals are more toxic to infants orolder organisms than to young adults.older organisms than to young adults. For example: For example:
22
SexSex
Although uncommon, toxic responses can varyAlthough uncommon, toxic responses can varydepending on sex.depending on sex. Examples are: Examples are:
MetabolismMetabolism
Metabolism, also known as biotransformation, is a major factorMetabolism, also known as biotransformation, is a major factorin determining toxicityin determining toxicity
The products of metabolism are known as ______________The products of metabolism are known as ______________
There are two types of metabolism - detoxification andThere are two types of metabolism - detoxification andbioactivationbioactivation:: DetoxificationDetoxification——process by which process by which xenobioticxenobiotic is converted to is converted to
__________________.__________________. This is a natural defense mechanism of the This is a natural defense mechanism of theorganism.organism. Generally the detoxification process converts lipid-soluble Generally the detoxification process converts lipid-solublecompounds to polar compounds.compounds to polar compounds.
BioactivationBioactivation——process by which a process by which a xenobioticxenobiotic may be converted to may be converted to____________________________________.____________________________________.
23
ExcretionExcretion Site and rate of excretionSite and rate of excretion is another major factor affecting theis another major factor affecting the
toxicity of a toxicity of a xenobioticxenobiotic
Kidney is the primary excretory organ, followed by theKidney is the primary excretory organ, followed by thegastrointestinal tract, and the lungs gastrointestinal tract, and the lungs (for gases)(for gases)
XenobioticsXenobiotics may also be excreted in sweat, tears and milk may also be excreted in sweat, tears and milk
Lipid-soluble toxicants are reabsorbed and concentrated inLipid-soluble toxicants are reabsorbed and concentrated inkidney cellskidney cells
Impaired kidney function causes slower elimination of toxicantsImpaired kidney function causes slower elimination of toxicantsand increases their toxic potentialand increases their toxic potential
Presence of other ChemicalsPresence of other Chemicals
Presence of other chemicals may decrease, addPresence of other chemicals may decrease, addto or increase toxicityto or increase toxicity of some of some xenobioticsxenobiotics
There are four basic types of interactions:There are four basic types of interactions:
24
AdditivityAdditivity
Toxicity of the mixture will be approximatelyToxicity of the mixture will be approximatelythe summation of the toxicity of the individualthe summation of the toxicity of the individualtoxicantstoxicants
Toxicants that share a common mechanismToxicants that share a common mechanism 1+1=21+1=2 Example:Example:
AntagonismAntagonism
Occurs when one chemical inhibits the action ofOccurs when one chemical inhibits the action ofanotheranother
2+2=12+2=1 AntidotesAntidotes Example:Example:
NaNONaNO22 used to treat used to treat NaCNNaCN poisoning poisoning DimercaprolDimercaprol (BAL) (BAL) chelateschelates metal ions (e.g., metal ions (e.g.,
mercury, arsenic, lead)mercury, arsenic, lead)
25
PotentiationPotentiation
Occurs when one substance does have a toxicOccurs when one substance does have a toxiceffect but when mixed with another chemicaleffect but when mixed with another chemicalmakes that chemical much more toxicmakes that chemical much more toxic
0+2=200+2=20 Example:Example:
SynergismSynergism
Occurs when the combined effect of 2Occurs when the combined effect of 2chemicals is much greater than the sum ofchemicals is much greater than the sum ofeffects of each chemical aloneeffects of each chemical alone
2+2=202+2=20 Example:Example:
26
Presence of other ChemicalsPresence of other Chemicals
This table quantitatively illustrates the percent of the population affected byThis table quantitatively illustrates the percent of the population affected byindividual exposure to chemical A and chemical B as well as exposure to theindividual exposure to chemical A and chemical B as well as exposure to thecombination of chemical A and chemical B.combination of chemical A and chemical B. It also gives the specific type of It also gives the specific type ofinteraction:interaction:
top related