Exam 1 Vocab

Toxciology
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Terms in this set (96)
ChronicAbnormal biological function: low level exposure over time: morbidity/mortality/decreased reproductionAbsorptionhow the chemical enters the organismDistributionhow are the toxicants distributedMetabolismbiotransformation of xenobiotics into potentially less toxic substances/metabolitesExcretionelimination of xenobiotics and metabolitesEffective ConcentrationDose at which toxicity is present in test organisms, interchangeable with the term toxic dose (TD)Lethal ConcentrationDose resulting in the death of the test organismsEC50 and LC50To facilitate the interpretation of data from a single dose response study or when comparing data from two or more dose response studies, it is useful to examine the dose at which a specified cumulative percentage of test organisms exhibit the EC or LDNon-observable Effects Level (NOEL)No responses are observable; sub threshold doses are represented, no responses are seen. Also known as No Observable Adverse Effect Level (NOAELO), Lowest Observable Effect Limit (LOEL), and Threshold Limit Value (TLV)Dose Relationshipmagnitude of response, function of exposure to stimulus/stressorThreshold Doseminimum dose of xenobiotic that triggers minimum detectable biological effect in an animalEcotoxicology Main Areas: 3 "P"sExposure Partitioning Potency3 Ps: Exposure•physical factors: air, soil, water •chemical factors: how the chemical behaves in the physical environment •Biological: •route of exposure - ingest or skin, •Bioavailable: is it available to be taken-in. If it is inside a rock it is hard to be exposed to it. •Chemical form: this is mostly with metals, but some metal salts are more available and/or harmful than others.3 Ps: Partitioning/ToxicokineticWhere it goes in the body Adsorption: how it gets in the organism - ingest, inhale, through the skin Distribution: where it goes in the body. We think of this as hydrophilic (water loving) or hydrophobic (fat loving). Does it stick to fat? Metabolism: how does the body breakdown the compound. Also how fast does it break down the compound Excretion: How does it get rid of the compound.3 Ps: Potency/ToxicodynamicsHow much compound is needed to get an effectPathway from Exposure to Toxic ResponseExposure Tissue Dose Molecular Interactions Early Cellular Interactions Toxic Response3 Questions to Ask1. What is the route of exposure 2. Where does it go in the body 3. What is the dose of the chemical exposure and is it potent enough to cause an effectWhat happens if a fish is exposed to a chemical but no effects are seen?Could be less sensitive to the chemical or it received an extremely low dose that had little to no affect on itDose Response Curve: Comparison of Drug PotenciesIf see effects at lower doses, that means it is more potent/potentially harmful than a similar drug shown at a higher doseDose Response Curve: Comparison of 2 Species with 1 Drugnot all species react the same way to a chemical at the same concentration Species sensivity = some species are more sensitive to a xenobiotic than other species If a species shows a response at a lower dose than the other species, then this species is more susceptibleActive TransportThe movement of ions or molecules across a cell membrane into a region of higher concentration, assisted by enzymes and requiring energyEndogenousgrowing or originating from within an organismEnzymessubstances produced by a living organism which acts as a catalyst to bring about a specific biochemical reactionLipophilichaving an affinity for lipids, such as fatsPassive Transporta type of cellular transport in which substances such as ions and molecules move down their respective concentration gradientsMechanism of DistributionReach site of action by a macromolecule on either the surface or interior of a particular type of cell Porosity of the capillaries of the endothelium Specialized Transport Accumulation in cell organelles Reverse Intracellular bindingSimple diffusionmovement of molecules or ions from high to low concentrationsTarget tissue/organthe site where a toxin produces damage after systematic circulationXenobioticforeign substanceXenosensorreceptors that can sense and bind to foreign substancesPath to Toxicity1. The toxicant is delivered to its target or targets 2a. Interacts with endogenous target molecules OR 2b. Alters the biological environment 3. Triggers perturbations in cell function and/or structure 4. Initiates repair mechanisms at the molecular, cellular, and/or tissue levels Perturbations induced by the toxicant exceed repair capacity or repair malfunctions: toxicity occursAdsorptionTransfer of a chemical from the site of exposure, usually an external or internal body surface, into the systemic circulation is called absorption. A toxicant may pass through a membrane by either: Passive transport: in which the cell expends no energy or Specialized transport, in which the cell provides energy to translocate the toxicant across its membrane.Passive DiffusionFrom the area of high to low concentration; Most toxicants cross membranes by simple diffusionFiltrationwhen water flows in bulk across a porous membrane, any solute is small enough to pass through the pores flows with itSpecial TransportFacilitated Diffusion and Active TransportFacilitated DiffusionCarrier-mediated transport that exhibits the properties of active transport.Active transportCharacterized by: 1.Movement of chemicals against electro-chemical or concentration gradients, 2.Saturability at high substrate concentrations, thus exhibiting a transport maximum 3.Selectivity for certain structural features of chemicals, 4.Competitive inhibition by chemical antagonists or compounds that are carried by the same transporter, 5. Requirement for expenditure of energy (ATP), so that metabolic inhibitors block the transport process.Do all toxins cross the cell membrane?No, some toxicants do not readily cross cell membranes and therefore have restricted distribution, others can pass readily and are distributed throughout the body some selectively accumulate in certain parts of the body as result of protein binding, active transport, or high solubility in fat target organ may not always be the site of accumulationMetabolism/Biotransformation Major Organliver is the main site of biotransformation of toxicants and metabolitesBiotransformationmetabolic conversion of endogenous and xenobiotic compounds to water-soluble compoundsMajor XenosensorsAryl Hydrocarbon receptor (ahR), which induces CYP1 enzymes Constitutive CYP2B,2C, and 3A enzymes Peroxisome proliferator - activated receptor alpha (PPARalpha), which induces CYP4 enzymesMetabolism StepsPhase 1: biotransformation typically results in small increase in hydrophilicity, expose/produce OH, NH2, SH, or COOH Phase 2: biotransformations reactions further increase hydrophilicity and elimination include glucuronidation, sulfonation, acetylation, methylation, and conjugation with glutathione or amino acids Phase 3: further biotransformation and transport out of cellExcretionall body secretions appear to have the ability to excrete chemicals, sweat, saliva, tears, and milk; urinary, fecal, exhalation (toxins that predominantly exist at body temperature or are volatile gases) filtered through the glomerular filtration of the kidneys some chemicals cycle through the body unabsorbed biliary excretion: most important contributing source to the fecal excretionRoutes of entrywater, land, and airHow do Pollutants enter the ecosystem?unintended release (mining operations, waste dam breaking, slurries from waste run off) disposal of waste (sewage and industrial effluents) deliberate applications (pesticides, insecticides, etc) exhuast or dust admissions from cars, factories, etcSource Types: Point Sourcelocalized stationary pollutant source industrial chemical discharge sewage effluent air dischargeSource Types: Non-point sourcewidely distributed or persuasive environmental elements run off: agriculture, residential areas air discharge: car emissions microbial or bacterial influence: leaky sewage pipes, etcPoint Source: Wastewater Treatment PlantsInfluent - primary screen setting (breaks tension between the solids, goes to settling area and joins with hydrophobic compounds, anaerobic system) - Aerate (tons of bacteria that breakdown waste in aerobic digestion) - Cleaning (use of chlorine, kills all bacteria) - Reamination (strip chlorine), Ozonation, UV - Effluent StreamActivated SludgeAnaerobic breakdown; treatment plant drives it and packages it as fertilizerBDLBelow Detection Limit, chemical has been broken/metabolized enough to not accumulate in the environment Metformin is NOT an example of thisHeavy Raincities have channelized waterways so run off quickly moves away from the city, causing increase in pollution further from citiesMovement Storm Sewer Systemsallow water to flow into lower lying areas, like playas opportunity for chemical and nutrients to collect used by insects, amphibians, reptiles, and mammals some are connected and lead to outfall near wastewater treatment plantsRoad saltcontaining chlorine: melts snow and ice, but builds up in water and flows into streams/rivers specific conductance = ions create charge many of these streams exceed the limit for Cl-NutrientsNitrogen and Phosphate enter waterways, causing algal blooms or hypoxic areas also caused by artificial or natural substances like nitrates and phthalatesPathogenic wastebacteria and viruses most of this research focuses on fecal matter anthropogenic causes: leaky sewer pipes, bad septic pipes, legacy systems Animals: areas with high animal concentrations, industrial farms with feed lots, and beaches (caused by galls)Channelized vs dechannelizedChannelized: increase of urbanization and straightened channels, pushed waste downstream and created problems for someone else, more floods Dechannelized: more natural state, saturate more SA, biodegrade pollutants, low cost mechanism to take care of pollutantsMajor Routes of Waste TransmissionWaste dumping (dump, landfill, industrial) Pesticide Application Control of insect vectors flooding rivers and seas Precipitation from air as dust or droplets in rain/snow: soot, dust, acid rain, pesticides gaseous particles can travel long distances (acid rain) or short distances (pesticides) particles/droplets travel short distancesPFAS: Sources and How Interacts with the environmentfirefighting foam, nonstick pans, stain resistant, stoch guard hangs out in water but doesn't dissolve, does not stick to sedimentDomestic/Industrial ChimneysHydrocarbon with incomplete burning: SO2, CO2, and NO2Internal Combustion Enginesvehicles Hydrocarbon with incomplete burning: SO2, NO2, and CO2 metals used in gas, lead and manganese (neurotoxin)What source has to be permitted and by what?Point source, wastewater treatment plants NEPDS permit2 Competing Factors about fate/transport of a pollutantCapable of being transported in an environment/source of chemical physiological chemical properties of chemical and surrounding environmentFateOver time, a chemical settles and breakdowns which environment it is in and physico-chemical properties determines if and how fast a chemical degradesFactors Determining Fate and TransportAir (atmosphere) Surface Water Land Surface (soil or sediment) Living Organisms (biosphere)Movement of pollutants in compartments is determined byproperties of the chemical properties of the environmental compartmentPolaritydictates where the chemical goes into the environment hydrophobic (nonpolar), decreased water solubility hydrophilic (polar), increased water solubilityKowWater Partitioning Coefficient; behavior is between 2 immiscible liquids (octanol and water) Kow = Co/Cw; Co = [inorganic solvent], Cw = [in water phase] greater water solubility, lower log Kow Salts/ions don't have Kow, break apart easily Negative values are almost indefinitely water soluble 2.5 to 4.5 is the line between hydrophilic/hydrophobicKdSoil (sediment) water partitioning, how much pollutant is bound to the soil vs water Kd = Cs/Cw, Cs=[in sediment], Cw=[in water]Kocorganic carbon sorption coefficient how much carbon is in the soil that dictates how much of the pollutant binds to the soil Koc= kd/oc, kd= soil sorption coefficent, oc= proportion of oxygenic carbon increase Koc, increase soil sorption to sediment full of organic matter = increased KocDegradation of Chemicalschemicals degrade or breakdown; metals do not degrade. Chemicals have half life depending on where they exist, influenced by where chemical partitions and degrade examples: - Photodegradation - Hydrolysis - Bacteria (biodegradation)Photodegradationdegradation of chemical through the absorption of sunlight occurs as long as the sediment can absorb sunlight air, soil, water, surfaces of water, plants, and animalsInfluencers of PhotodegradationpH, depth of chemical in soil and water, sorption to soil, sensitizers, effect rate on phototransformation increase half life, longer takes to degrade faster rate, less likelihood of continued exposureHydrolysissoil, water, plants, and animals chemical interaction with contaminant chemical structure & alters transport within the environment environmental factors: hydrolytic degradation: temperature, pH, solubility, sunlight, absorption, and volatilityRate of hydrolysistakes 1/2 of original to be structurally altered to half timeBacteria degradationredox rxns catalyze inorganic N2 to NH4+ in oxygen deficient, lower layers of water body near surface where O2 is available, bacteria convert inorganic to N2 to NO3- redox rxns to gain energy for growth and metabolismToxinPoisonous SubstanceOne Healthapproach calling for the collaborative efforts of multiple disciplines working locally, nationally, and globally, to attain optimal health of people, animals,, and our environmentTarget organismtypically associated with pesticides, organism that chemical is designed to affect a responseOff target organismstypically associated with pesticides, organisms that unintentionally are exposed to chemical/compound which may cause an effectBioaccumulatebecome concentrated inside the bodies of living thingsBiomagnifysubstance that builds up within the organism at each stage of the food chainAcid Rainresults when sulfur dioxide (SO2) and nitrogen oxides (NOn) are emitted into the atmosphere and transported by wind and air currentsSO2 and NOn react with ______ to form ______react with water, oxygen, and other chemicals to form sulfuric and nitric acidMajor sources of SO2 and NOnburning of fossil fuels to generate electricity vehicles and heavy equipment manufacturing, oil refineries, and other industriesTechnologyadvancements in ability to measure chemicals in soil and water even at low concentrationsRachel Carson, James LovelockWrote Silent Spring, created electron capture detector (basis of many analytical techniques such as GC/MS)