Molecules having a a tetrapyrrole ring (four simple, heterocyclic nitrogen ring compounds bound together to form a ring) that are produced as intermediates during heme synthesis in animals
A group contained in many enzymes.
A heme containing protein that is act as catalysts of oxidation-reduction reactions in processes such as cellular respiration
The damage to biomolecules from free radicals from combining molecular oxygen reduction with energy generation during aerobic metabolism. Free radicals include the superoxide radical (O2) and the hydroxyl radical (OH-).
They damage proteins, plipids, DNA and other biomolecules
A free radical involving an unshared electron of oxygen
hydrophobic chemical stuck in between membrane
hydrophobic chemical interweaving in membrane
A molecule having an unshared electron. (That electron is usually designated by a dot.) Free radicals are extremely reactive. They try and gain stability by capturing an electron. Can lead to a cascade of oxidation/reduction events
Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen. Examples include peroxides,superoxide, hydroxyl radical, and singlet oxygen.
Superoxide dismutase (SOD) reduces oxidative stress by decreasing superoixde radical
An enzyme catalyzing the reaction, 2H2O2 -> 2H20 + O2.
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Involved in reducing oxidative stress
An enzyme catalyzing the reaction, 2 Reduced Glutathione (GSH) + H2O2 -> Oxidized Gluthathione (GSSG) + H20. It is involved in reducing oxidative stress
Redox cycling: The process of reduction of contaminants to free radicals that are then able to participate in redox reactions, producing a superoxide radical.
The oxidation of polyunsaturated lipids in membranes resulting in cell damage during xenobiotic exposures. Lipid peroxidation is known to cause membrane distruption, resulting in the loss of membrane disruption, resulting in the loss of membrane integrity
Malondialdehyde- A breakdown product of lipid peroxidation used as an indicator of oxidative stress
The neutral red retention time (NRRT) assay is useful for detecting decreased lysosomal membrane stability in haemocytes sampled from bivalves, a phenomenon often associated with exposure to environmental pollutants including nanomaterials.
Non-aqueous phase liquids or NAPLs are liquid solution contaminants that do not dissolve in or easily mix with water, like oil, gasoline and petroleum product
Acetylcholine-substrate- Allows ions to go into cell
Acetylcholinesterase- neurotransmitter enzyme
Sends electric signals to brain
Chemical meant to kill pests
Chemical meant to kill insects
Genotoxicity the study of the adverse effects of physical and chemical agents on the genetic material of cells (DNA or chromosomes) and the subsequent expression of these changes. Chemicals that cause genotoxicity are petroleum hydrocarbons (PAH, TPH, etc.), metals, PCBs
Clastogenic agents are those that cause damage to chromosomes
Mutagen-change or damage gene or inhibits or damages the DNA repair mechanism and results in an altered cell
An adduct is defined as the covalent attachment of a chemical compound to DNA (commonly to guanine).
Xenobiotics and their metabolites can damage DNA by covalently binding to a base to form an adduct that could cause cancer. DNA adducts are the best studied genotoxic endpoint. They are thought to play a key role in initiation, early promotion and later stages of tumor progression.
32P Postlabeling facts
Most widely used method for determination of DNA adducts is 32P-postlabeling technique.
For hydrophobic aromatic, aromatic DNA adducts such as PAH-DNA adducts, this method can detect 1 adduct in 10^9-10^10 bases. Autoradiography compares of sampled fish DNA adduct patterns to standard adduct patterns
32P Postlabeling steps
During 32P postlabeling, you isolate DNA, digest DNA, label with 32P, separate via chromatography, autoradiography, determine number of adducts
Hydrogen abstraction (DNA)
HO’ may react with any compound abstracting a hydrogen and yielding a free radical species of the compound and water
HO’ may add to deoxyguanosine (a nucleoside) with formation of the 8-hydroxy-deoxyguanosine oxidized base. This oxidized base can be isolated in vivo, a fingerprint of free radical attack on DNA
A mutation can result in inherited defects when germ cells are mutated (page 41 of Lecture 7). These cells are involved in the production of ova or sperm and can be inherited.
Have a mutant Salmonella bacteria that requires histidine. Expose the bacteria to the toxicant. If it causes a mutation, then the bacteria can grow on the histidine free medium. The Ames test is used to predict potential carcinogens
S9 Mix test
Pro-carcinogens are tested with Ames S9 mix test- Aroclor1254
Take test organism and expose to chemical. Cells are collected lysed to liberate DNA, electrophoresed and stained.
Based on the electrophoretic migration of DNA fragments resulting from strand breakage (broken strands migrate more quickly) Greater migration into the so-called comet during electrophoresis can be used to estimate degree of DNA damage
Mutagen measured during sister chromatid exchange
Sister Chromatid Exchange
Genotoxicity test- The chromatids exchange DNA via crossing over. Proposed biomarker for exposure
Micronuclei- membrane bound masses of chromosome fragments or potentially whole chromosomes (that were not incorporated into a daughter cell during mitrosis or meiosis) Number of micronuclei suggests damage to cell’s ability to divide properly (e.g. clams exposed to PCBs)
Toxicity causing cell death (apotosis)
Cell death from injury or disease
The study of changes in cells and tissues associated with communicable and noncommunicable disease
Pathological alterations of cells, tissues or organs. Can indicate exposure to toxicants and suggest mechanisms of action.
Adverse Outcome Pathway (AOP)
Analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect. The AOP concept was also developed in response to uncertainties in the field regarding usage of the terms mechanism of action and mode of action The AOP concept addresses such terminology problems by requiring an anchor to both a molecular initiating event and an adverse outcome with significance to risk assessment.
Mode of Action
A common set of biochemical physiological or behavioral responses that characterize an adverse biological response where major but not necessarily all linkages between a direct initiating event and an adverse outcome are understood
Mechanism of Action
The mechanism of action describes everything along the way including the specific molecular targets to which the drug binds, such as an enzyme or receptor. Defined as a complete and detailed understanding of each and every step in the sequence of events that leads to a toxic outcome
Occurs primarily when sufficient energy is transferred to molecular oxygen, forming reactive singlet oxygen, a powerful oxidizing agent that can damage a wide variety of biological molecules. This oxidative damage to cellular components is the initiating event for AOP
There are many estrogen receptor (ER) agonists is anchored by the molecular initiating event of binding of an estrogen mimicking chemical to the ER and altered reproduction (embryo production) at the whole-organism level.
Biomarker associated with ER activation. Egg yolk protein. Production of VTG is a specific and sensitive response to ER activation. VTG is critical for oocyte development, reductions in VTG availability can be translated into reductions in fecundity
The actual reproductive rate of an organism or population measured by the number of gametes (eggs), seed set or etc. It is an outcome relevant to population level risk assessments
Molecular Initiating Event (MIE)
The event that happens in the cell that sparks a response from an exposure to a toxicant
Enhanced toxicity of a chemical in the presence of a second chemical that is not itself toxic at its concentration in the mixture
The condtions of additivity exists for two or more toixcants in a mixture if the mixture effect level was simply that expected by summin the expected inidivdual toxicant effects
Toxicant synergism occurs if the joing effect of a mixture was greater than predicted by summing the predicted, separate effects for the individual toxicants in the mixture
Toxicant antagonism occurs if the actual effect level of the mixture was lower than the sum of the predicted effects for the individual toxicants in the mixture
If chemical antagonism is framed in the special context of antidotes, the chemicals whose effect is thought to be reduced is the agonist and the chemical that reduces that effect is the antagonist or antidote
If chemical antagonism is framed in the special context of antidotes, the chemical that reduces that effect is the antagonist or antidote
An approach used to visualize or quantify joint action of chemical mixtures
Antagonism resulting from two chemicals elciting opposite physiological effects and as a consequence, counterbalancing each other’s effect
Anatgonism resulting when two toxicants react with one another to produce a less toxic product
Antagonism involving toxicant mixture effects on the uptake, movement within the organism, deposition at specific sites, and elimination of the toxicants.
The presence of the two toxicants together shifts one or more of these processes to lower the impact of the toxicants at the site(s) of action or target organ(s)
Antagonism that involves the binding of the toxicants to the same receptor and one toxicant blocking the other from fully expressing its toxicity
A rapid, bacterial assay in which a decrease in bioluminescence is thought to refelect toxic action
Similar Joint Action
Toxicants in mixture act by the same mode of action and “one component can be substituted at a constant proportion for the other… toxicity of a mixture is predictable directly from that of the constituents if their relative proportions are known
Independent Joint Action
Independent action of toxicants occurs if each toxicant produces an effect independent of the other and by a different mode of action
Toxic Equivalency Factors
An empricially derived factor that scales the toxicity of a dioxin, dibenzofuran, or dioxin-like polychlorinated biphenyl (i.e., compounds that have toxic modes of action involving binding to the aryl hydrocarbon receptor to that of TCDD
The combiend toxicity of dioxins, dibenzofurans or dioxin like polychlorinated biphenyls (i.e., compounds that have very similar toxic modes of action invovling binding to the aryl hydrocarbon receptor) expressed in units of toxicity of the 2,3,7,8 (TCDD).
This summing to compound effects to generate a TEQ is doen using the Toxic Equivalency Factors defined above
An index for quanitfying the joing action of toxicants in a mixture.
Amount of concentration of a toxicant expressed in units of lethality such as LD50 or LC50. For example, if toxic units are based on the LC50, a chemical with an LC50 of 20 mg/L would be present at 0.5 TU in a 10 mg/L solution
Polychlorinated biphenyls (PCBs) were used as or in lubricants, heat conductors in electrical transformers, plasticizers, printing and many other applciations
A term used to point up the relationship among members of a chemical family such as PCBs. This term is relevant to mixtures of similar compound such as polychlorinated biphenyls (PCBs) This term is relevant to mixtures of similar compounds such as PCBs that differ along a common them.
For example, the PCB congeners in Aroclor 1221 are all the biphenyls in the mixture with different numbers and positions of the substituted chlorine atoms
Ortho position of PCB binds to the receptor which means that it cannot be coplanar
Example of PCB congener in ortho position- They bind to the AhR that works because of additivity
Example of PCB congener in ortho position- They bind to the AhR that works because of additivity
Dioxin that binds to the AhR
Aryl hydrocarbon receptor (AhR) is a gene transcription factor that binds to 2,3,7,8 TCDD and structurally related planar aromatic chemicals. Activation
That it is a solvent with adverse health effects and groundwater contaminant. Carcinogen, metabolism of carbon tetrachloride via CYP2E1 to highly reactive free radical metabolites in postulated mode of action . The free radicals initiate lipid peroxidation by attacking polyunsaturated fatty acids in membranes, setting off a free radical change reaction sequence. It is essentially a toxicant that induces oxidative stress
The most heavily used herbicide in the United States, blocks electron transport in target weed species
Organophosphate insecticide that inhibits the nervous system by forming a stable covalent bond at the active site of acetylcholinesterase
Effects occuring at concentrations/doses below those producing direct somatic death
Ecological death (or mortality)
Can be equivalent to somatic death. E.g. Shrimp example.
The shrimp were going to be eaten by predators when they were immobilized, which is a sublethal effect
Ties into Selyean stress because it plays a central role. The definition is that they are environmental pollutants that interfere with the normal functioning of human and nonhuman animal endocrine systems also known as endocrine disruptors
Often used as the measurement endpoint for sublethal effects, easy to quantify, integrates a suite of biochemical and physiological effects into one effect that is often linked to individual fitness. For example, Cu concentration can be measured with a 96 hour growth inhibition test with Selenastrum (algae)
A biphastic dose-response phenomenon characterized by a low-dose stimulation and high-dose inhibition
Biphasic dose-effect model
Shaped like the threshold model in Figure 7.8. But the curve dips down from the controls before increasing with dose. In this case, the downward dip would reflect enhanced growth of plants exposed to low concentrations but, in other cases, it might reflect decreased mortality or increased fecundity at low concentrations relative to controls
Any physical or chemical agent such as mercury that is capable of causing developmental malformations
The science of fetal or embryonic abnormal development of anatomical structures
Developmental toxicity is the broader term for teratology which is often used to include altered growth, functional deficiences and even death in addition to teratogenic effects
Babies born with limbs having reduced bone lengths
Babies born without limbs
The extreme forward curvature of the spine
The lateral curvature of the spine
Behavioral abnormailites in otherwise normal appearing individuals arising after exposure to an agent as an embryo
Froch embryo teratogensis assay xenopus- Xenopus laevis after clawed frog
Teratogenic index (TI)
Calculated as the LC50 divided by the EC50
Xenobiotic estrogens or xenoestrogens mimic estrogen and can cause changes in the sexual characteristics of individuals.
Tie this back to VTG mechanism. DDT, DDE, dioxin, PCB, alkylphenols (p-nonyl-phenol and alkylphenol polyethoxylate)
Androgen receptor antagonists
DDE is an example.
The imposition of male characteristics on females
Deviation from perfect bilateral symmetry for a population that is thought to reflect developmental instability. A quality is measured from the right and left sides of a bilaterally symmetrical species and the unsigned difference d=|Right-left| is calculated
An ability to produce different or a range of phenotypes under different conditions
The deviation for a population from a mean of zero for the difference between a trait measured from the right and left sides of bilaterally symmetrical individuals from that population. For example, measurement of the difference in weights of left and arms of right0handed humans would display directional asymmetry because most such humans will have larger right arms.
With directional asymmetry, both presence and direction of asymmetry are predetermined.
Antisymmetry occurs when structure is greater on one side than on the other, but it is not predetermined on which side the structure will be larger
Compounds such as many organophosphate and carbamate insecticides that inhibit the normal functioning of the enzyme, acetylcholinesterase, which hydrolyzes the neurotransmitter, acetylcholine
Scope of growth
An index calculated as the amount of energy taken into the organism in its food minus the energy taken into the organism in its food minus the energy used for respiration and excretion. Represents the amount of energy available for growth and/or production of young.
The science of abnormal behaviors produced by exposure to a chemical or a physical agent
Seylean stress is a specific syndrome defined as all nonspecifically induced changes.
The specific effects of growth and developmental changes are not the specific syndrome described by Seylean stress.
Death of an individual
Ability to swim against a current or maintain proper orientation to a current (rheotaxis)
Measured by rheotaxis and the physical capacity to swim against flow
*Frequency and duration of movements *Speed and distance travelled *Frequency and angle of turns *Position in the water column and form and pattern of swimming (surfacing, resting on bottom, head up)
Orientation to water flow
Chlorinated hydrocarbons used extensively in agriculture. Adversely effect electrical impulses in braine. Common ones are DDT, dieldrin
Organic compound produced by flowers of pyrethrums. Prevents closure of the voltage sodium channels
Suppression of maturation of immunity cells (ex: Hematopoietic necrosis virus (HNV) in salmon -> anemia, kidney
Science associated with the detection, quantification and interpretation of direct or indirect alterations to the immune system as a result of exposure to environmental pollutants
Hematopoietic necrosis virus (HNV) is a pathogen of Pacific salmon.
Virus multiplies in skin, gils, and GI tract and moves to kidney or spleen. Juvenile fish die because anemia, kidney failure or electrolyte/fluid imbalances
Population growth rate
r is the rate of increase per individual dependent on survival probabilites, time between reproductive events, reproductive output. L- ginite growth rate
Leslie matrix model
Stage structured population matrix
From all sources water, air and solid phases
Term specific to aquatic toxicology
Within trophic levels
The total mass or amount of contaminant in and in some cases on an individual
The movement of a contaminant into an organism
Cell membrane-associated transport proteins that form channels to allow solute passage through the membrane
Cell membrane-associated proteins that acta as carriers to transfer hydrophilic contaminants across the membrane
The accmulation of a substance at the common boundary of two phases such as that between a liquid solution and solid
Uptake of chemical; the incorporation of solid into liquid
Specific mechanism by which a compound in solution becomes associated with a solid surface that is unknown or poorly defined
The movement of a contaminant down an electrochemical gradient that requires no energy AKA passive diffusion
Diffusion down a gradient not requiring energy, but occuring at rate faster than expected by simple diffusion alone (aq). Carrier molecule needed but no energy from high to low concentration
Movement of a substance up an electrochemical gradient that requires a carrier modlecule and energy (aq) low to high concentration
Uptake of solids (phagocytosis) or liquids (pinocytosis) by cells through a process of engulfing the material and enclosure in a cellular vacuole
Lipophillic chemicals pass through the membrane via the lipid route via lipid bilayer
Hydrophillic chemicals pass through the membrane via the aqueous route
Uptake of liquids
Uptake of solids
Biologically mediated transformation of one chemical compound to another
One possible consequence of biotransformation in which the effect of an active compound is worsened or an inactive compound is converted to one with an adverse bioactivity
A class of polypeptides in plants that are induced by and bind to metals. They may function in the regulation and detoxification of metals by plants. Genes for phytochelatins have now been isolated in several invertebrate species
Fusion of introcellular vesicles with the cell membrane followed by emptying the vesicle contents to the cell exterior
Small compact particle of a substance
The loss of contaminant from an organism that is measured after the organism has been placed into a clean environment and allowed to eliminate the contaminant.
Happens in field
The loss or metabolism of a contaminant resulting in a decrease in the amount of contaminant within an organism
The decrease in contaminant concentration in a growing organism because the amount of tissue in which the contaminant is distributed is increasing. E.g. Grow bigger then concentration decreases because tissue amount is bigger (juvenile to adult) body weight is increasing
Recirculation of toxicant back to the liver after passage into the intestine in bile and then reabsorption in the intestine
The study and predictive modeling of the internal kinetics of toxicants
Bioconcentration factors are determiend from the ratio of chemical concentration in the organism, assuming steady state metabolism and excretion
Biota-sediment accumulation factors are based on the lipid normalized concentration in the organism with respect to organic carbon-normalized concentration in the sediments.
Bioaccumulation Factors based on lipid-normalized concentration of the chemical in the organism with respect to the concentration of the bioavailable fraction of chemical in water
Biologically mediated deposition of minerals
Accumulation factor (AF)
The ratio of nonpolar organic compound concentration in the organism to that of sediments ([organism]/[sediment]) with the organism’s concentation normalized to gram of lipd and sediment concentration normalized to gram of organic carbon
The extent to which a contaminant in a source is free for uptake. In many definitions, especially those associated with pharmacology or mammalian toxicology, bioavaiability implies the degree to which the contaminant is free to be taken up by the organism and to cause an effect at the site of action
The bioavailability of a dose (D) estimated from the area under the curve (AUC) for any route or formulation of the compound divided by the AUC after direct injection of the same dose (D) into the bloodstream
The Bioavailability estimated for a dose administered by any route or formulation relative to a dose administered through a reference (or alternate) route or in a reference formulation
An anion or molecule that forms a coordination compound or complex with metals
Dissolved organic carbon
An anion or molecule that forms a coordination compound or complex with metals- That compete
Free-ion activity model
“The universal importance of free metal ion activities in determining the uptake, nutrition and toxicity of all cationic trace metals.” Free ion is most bioavailable
Biotic Ligand Model
A conceptual model that “focuses on activities on metal-ligand complexes and metal-ligand complexes and the metal-biotic ligand complexes formed at crucial sites on organism surfaces such as gill surfaces.” The BLM is used to imply or predict relationships between dissolved metal concnetration and bioavailability or effect
Metal Species are metals and semi-metals existing as hydroxides, organometallic compounds, biomolecules, and other forms.
Measurement of these molecules is called metals speciation.
Acid Volatile Sulfides (AVS) Sediment associated sulfides extracted with 1 N HCl which are assumed to be primariliy iron sulfides, especially metastable mackinawite and greigite. In some cases, pyrite can also become the dominant component of AVS
Simultaneously extracted metals
Hardness of water
changes chemical and increases competitng cations or makes less toxic
Extracts from soils sequentially. Expose with different extractants and then take extractant and get metals. Keep on mixing then centrifuge and measure
Interstitial or pore water
Collect institutial water- whatever is in there is most bioavailable. Individual particles
A means of esimating bioavailability of contaminants in which contaminant-containing phase is placed into a synthetic digestive juice solution and the amount of contaminant released is measured
A quantitative, often statistical, relationship between a molecular quality or set of qualities and some activity, such as bioavailability or toxicity
The partition coefficient for a compound between n-
It helps you determine the concentration of unionized form of a weak acid, which is important because this form can cross the lipid bilayer route
Acid dissocation content
The study of size and its consequences
Solid phase membrane devices. Generally used for sampling neutral organic chemicals with log kow greater than 3
Polar Organic Chemical Integrative Sampler. Passive sampler that measures less than 3 log kow chemicals
An increase in concentration from one trophic level to the next due to accumulation of contaminant from food
a system of interlocking and interdependent food chains.
Two processes contribute solvent switching and solvent depletion. Solvent switching takes place when a contaminant partitions preferentially into one solvent or phase (e.g. lipids of a prey species) relative to another (e.
g. its surrounding media or food). There is an increase in concentration in the prey but the final media-prey fugacity does not change with solvent switching. When the prey is eaten, solvent depletion occurs with the digestion of the lipids containing the contaminant
Another term for biomagnification
Diminution with increasing trophic level
Concentrations decrease with each exchange e.g. most metals do not biomagnify like organotin or organochlorine
chemical equilibrium is the state in which both reactants and products are present in concentrations which have no further tendency to change with time.
Process of interaction of potentially toxic substances with target sites and the biochemical and physiological consequences laeding to adverse effects
During lactation, accumulated lipophilic chemicals in the adult are redistributed to the milk and adult females pass the cehmicals on to their calves.
Gestation provides another opportunity to transfer chemicals from the mother to fetus
Lactational and gestational process result in a decrease in the maternal body burder and an increase in the calf’s body burden
Organism influence bioavailablity
Size, Sex, Lipid content, life stage/age, species, behavior