Kukor Lect 1_What is Enviro Toxicol

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  • 7/31/2019 Kukor Lect 1_What is Enviro Toxicol

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    What is environmental toxicology ?

    ecotoxicology

    Definition: study of impacts of pollutants on the

    structure and function of ecosystems

    manmade poisonous chemicals and their effect on theenvironment

    does not include the study of naturally occurring toxins, forexample cholera toxin, or brevitoxin

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    Environmental toxicology is a new discipline that grew out ofstudies on the environmental fate and transport of pesticides inthe 1940s and 1950s

    The discipline toxicology is as old as medicine many toxic

    plant chemicals are used as therapeutic agents in medicine.

    The term ecotoxicology appeared in the literature in 1969

    Field was pioneered by Rachel Carson

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    Environmental toxicology is highly interdisciplinary field

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    Rachel Carson

    1907-1964 Marine Biologist from Pennsylvania

    MA from Johns Hopkins U.

    Author of Silent Spring

    Received much attention, because she wrote

    and presented scientific facts well

    She was disturbed by the widespread and indiscriminate use ofpesticides

    Many of these pesticides were known to affect wildlife e.g. kill birds

    She lobbied very hard to control and ban certain highly toxicchemicals

    Testified before congress in 1963 and called for new policies withrespect to human health and the environment

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    Environmental toxicology is driven by legislation

    National Environmental Policy Act

    Clean Air Act

    Federal Environmental Pesticide Control Act

    Federal Water Pollution Control Act

    Safe Drinking Water Act

    Toxic Substances Control Act

    Resource Conservation and Recovery Act

    Comprehensive Environmental Response, Compensation and Liabilities Act

    Clean Water Act

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    First piece of environmental legislation was the NationalEnvironmental Policy Act 1970

    Created the EPA Initially 5000 employees (1970)

    Budget of 1.3 B

    In 1995 there were >18,000 employees, budget of 7.2 B

    USA is divided into 10 management regions

    Clean Air Act Also in 1970

    Required the EPA to set standards

    EPA in charge of controlling mobile and stationary emissionssources

    EPA controls hazardous pollutants

    Amended in 1977 to set compliance standards

    Amended again in 1990 to regulate acid rain and CFC emissions

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    Federal Environmental Pesticide Control Act 1972

    amended to FIFRA Federal Insecticide, Fungicide, and

    Rodendicide Act Required manufactures to provide PMNs (Pre Manufacture

    Notice) with toxicological information to register a pesticide

    Sets up system of tiered toxicity testing mechanism, mesocosmexperiment, field test

    Federal Water Pollution and Control Act 1972

    Provided sewage treatment plant grants for many municipalities

    Set effluent limits based on technology standards

    Toxicity testing is used to set maximum allowable concentrationsof toxicants in discharges and receiving waters

    Goal was to have all water fishable and swimable by 1983

    Established goal to eliminate pollution discharges by 1985

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    Safe Drinking Water Act 1974

    Set mandatory drinking water standards

    Controlled underground injection of wastes (aquifer protection) Amended in 1984 to set a schedule for establishing drinking

    water standards for 80 chemicals (provides notice to consumers)

    Toxic Substances Control Act 1976

    Regulated the use of chemicals in manufacturing and production

    Goal was to characterize the human health and environmentalimpact of EVERY chemical manufactured in the USA

    EPA has only 90 days to review the PMN to evaluate data

    Because there are thousands of chemicals produced in the USAevery year, QSAR models or rapid throughput assays are usuallyused

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    Resource Conservation and Recovery Act 1976

    Controlled the disposal of solid waste

    Set new hazardous waste regulations

    Comprehensive Environmental Response, Compensationand Liabilities Act

    Also known as SUPERFUND 1980

    Provided funding mechanisms to clean up abandoned wastesites

    Amended in 1984 to ban land disposal of hazardous waste

    Amended in 1986 to include requirements for communityemergency plans and publication of corporate Toxic ReleaseInventories

    Established the SBRP program to develop innovative approachesfor cleanup and assessment of hazards

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    Clean Water Act

    1987

    sets national water quality standards

    Toxicological (animal) testing of xenobiotics is federallymandated by

    Federal Insecticide, Fungicide, and Rodendicide Act (FIFRA)

    Federal Environmental Pesticide Control Act

    Federal Water Pollution Control Act

    Safe Drinking water act

    Toxic Substances control Act

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    Definition : XENOBIOTIC

    a chemical that is foreign to the biosphere i.e. is not produced by anatural biological or abiotic source

    Also called anthropogenic, man-made, synthetic, pollutant,contaminant, recalcitrant, persistent, and toxicant

    Distinguishes between quantity and scale Gordon Gribble e.g.studied the natural occurrence of organohallogens (chlorbenzoatesin fungi) this is different from large scale chemical processes forthe production of PCBs

    BTEX is an acronym for benzene, toluene, ethylbenzene, andxzylene natural ??

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    Environmental toxicology depends on

    Lab work Effects of toxicants on biochemistry and physiology

    Field work Field observations of reproduction and survival in polluted vs.

    non-polluted sites

    Modeling of fate and transport of toxicants in theenvironment i.e. exposure and risk assessment

    Static models : short term modeling of ecosystems

    Strategic models : model of a specific aspect of a

    system

    Testable models : model makes predictions that can

    be tested in the field or laboratory

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    Purpose/function of environmental toxicology is to

    Identify the mode / site of action of a xenobiotic

    FATE and TRANSPORT / interaction of a xenobiotic with thebiosphere (including specific organisms) after it is released /pollution occurs

    identify the effect the xenoboitic has on an ecosystems / higherlevel organisation e.g. loss of fertility of Alligators in Lake Apopca

    Introduction ofxenobiotic

    Ecosystemeffect

    site ofaction

    biotransformation

    physiologybehavior

    communityparameters

    biochemistry population

    dynamics

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    Introduction ofxenobiotic

    Ecosystemeffect

    DNARNA

    ReceptorsKey enzymes

    Biochemical integrity

    enzyme inductionGlutathione S TransferaseMixed Functional Oxidases

    HydrolasesDNA repair mechanisms

    Physiology, BehaviorChromosome damage

    Lesions, NecrosisTumors

    Teratogenic effectsBehavior, Mortality

    Community structure

    DiversityEnergy transfer

    StabilitySuccession

    Chemical parameters

    Stress proteins

    Metabolic indicatorsAcetylcholinesterase inhibition

    Adenyl energy chargeMetallothionen production

    Immuno suppression

    Population densityProductivityMating success

    FecundityGenetic alterations

    Competitive alterations

    Parameters of xenobiotic interaction with the ecosystem

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    How do we measure these effect ?

    Physio-chemical characteristics:

    QSAR (quantitative structure activity relationship)

    CH2

    NH

    CH

    O

    CH

    N

    O

    S

    CH3

    CH3

    COOH

    CH2

    O

    HN

    CH CH

    N

    O

    S

    HC

    N

    S

    CH3

    CH3

    COOH

    CH3

    CH3

    COOH

    Estimate the contribution of portions of the molecule to physio-chemical characteristics

    Ionic interactions

    Hydrophobic interactions

    Van der Vaals forces

    Hydrogen bonding

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    Abiotic environmental fate

    Partitioning

    Adsorption Transport/advection

    PCB vs. Benzene

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    Biotic environmental fate

    The interaction of a xenobiotic at the site of action in an organism is oftenmolecular happenstance i.e. xenobiotic mimic compounds which are naturally

    found in species that they affect hormone mimics

    Bioaccumulation

    The storage of a compound in fatty tissue of an animal

    Result of food chain / trophic levels

    Biotransformation

    Metabolic processes, mainly by environmental bacteria, that alter the

    structure and toxicity of a compound

    Biodegradation

    Breakdown of a xenobiotic to CO2 and water

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    Biotic mode of action (Receptors)

    Chemicals that interfere with biochemical receptor sites

    Signaling

    proteins in membranes

    Replication

    Protein synthesis

    Chemicals that damage biochemical or molecular targets

    DNA damage

    Strange breakage

    Chromosome abnormalities

    Cancer

    Non-genotoxic effects such as immunosuppression

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    Physiological and behavioral effects

    Standard tool for assessing toxicological effects on populations Tissue lesions

    Tumors

    Reproductive success

    Population success

    Population age structure xenobiotics often exert a strongereffect on juveniles => a shift in age structure might indicate that apopulation is not doing well, because it is affected by a

    xenobiotic Shift in bacterial communities contamination reduces bacterial

    diversity; bacterial numbers often increase because thecontaminant is food for some while it is toxic for others

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    Community effects

    Species diversity

    Abundance Distribution

    Ecosystem effects

    Productivity Trophic level structure Stability