toxicology week 1 (Lecture 1-21)

Ecotoxicology focuses on the effects of pollutants on ecosystems, while environmental toxicology focuses on the effects of pollutants on individual organisms.

Occurrence of chemicals in the environment, pathways of chemicals in the environment, effects of physico-chemical properties on environmental fate of chemicals, deposition and degradation processes, distribution in environmental compartments, intake in organisms.

Biotransformation, distribution of chemicals over organs/tissues, toxicokinetics & toxicodynamics, mode of action, mechanisms of detoxification, mixture toxicity, effects at the individual level.

<p>Ecotoxicology considers the effects of pollutants on ecosystems, whereas traditional toxicology focuses on the effects on individual organisms.</p> Signup and view all the answers

<p>Ecotoxicology</p> Signup and view all the answers

<p>Oral exposure, Dermal exposure, Respiratory exposure</p> Signup and view all the answers

<p>Population dynamics, genetic variability, life cycles, interactions between species, and role of organisms in ecological processes</p> Signup and view all the answers

<p>Absorption, distribution, metabolism, and excretion</p> Signup and view all the answers

<p>Effects on population dynamics, changes in community structure, and disruptions to ecosystem processes</p> Signup and view all the answers

<p>To understand the effects of toxic substances on different life stages and the entire ecosystem</p> Signup and view all the answers

<p>Interactions can enhance or reduce the effects of toxic substances, leading to complex ecosystem responses</p> Signup and view all the answers

<p>Genetic variability can influence the susceptibility of populations to toxic substances</p> Signup and view all the answers

<p>(Bio)degradation ==&gt; Environmental chemistry</p> <p>Fate and exposure model ==&gt; Environmental chemistry</p> <p>Dose ==&gt; Toxicology</p> <p>Toxicodynamics ==&gt; Toxicology</p> <p>Adverse outcome pathway ==&gt; Toxicology</p> <p>Population dynamics ==&gt; Ecology</p> <p>Landscape configuration ==&gt; Ecology</p> Signup and view all the answers

<p>True</p> Signup and view all the answers

<p>DT50 represents the half-life of a chemical, which is the time taken for half of the initial concentration of the chemical to degrade.</p> Signup and view all the answers

<p>Speciation refers to the distribution of a metal among different chemical forms in a particular environment.</p> Signup and view all the answers

<p>The structure of a chemical affects its susceptibility to biodegradation. Chemicals with simpler structures are generally more readily biodegraded.</p> Signup and view all the answers

<p>The Grasshopper Effect refers to the phenomenon where chemicals travel through cycles of evaporation, air transport, and condensation, leading to their long-range transport to remote regions.</p> Signup and view all the answers

<p>The Global Ocean Conveyor System is a system of ocean currents driven by temperature, salinity, and wind that circulate water around the world's oceans, influencing climate patterns.</p> Signup and view all the answers

<p>Hydrophobicity is escaping tendency from water. Two major properties affect hydrophobicity: size and ability to interact with water molecules via for example hydrogen bonding.</p> Signup and view all the answers

<p>Volatility from water is determined by the vapor pressure of the pure chemical and its solubility in water.</p> Signup and view all the answers

<p>Blood-Brain Barrier (BBB) and Placenta.</p> Signup and view all the answers

<p>Endothelial cells, tight junctions, efflux by transporter proteins, and astrocytes (gliacells).</p> Signup and view all the answers

<p>It is not a true barrier, and many lipophilic compounds can diffuse through the placenta.</p> Signup and view all the answers

<p>It enables the BBB to metabolize and detoxify certain xenobiotics.</p> Signup and view all the answers

<p>Methylmercury (MeHg+).</p> Signup and view all the answers

<p>Accelerated excretion and detoxification</p> Signup and view all the answers

<p>To introduce a functional group into the xenobiotic molecule, making it more susceptible to conjugation in Phase II</p> Signup and view all the answers

<p>Activation of compounds into more toxic compounds</p> Signup and view all the answers

<p>Oxygen acts as an electron acceptor, incorporating oxygen from O2 into the substrate</p> Signup and view all the answers

<p>Extracellular mobilization and excretion of the conjugated xenobiotic via bile or renal excretion</p> Signup and view all the answers

<p>They are stored in fat tissue through sequestration</p> Signup and view all the answers

<p>To couple a water-soluble molecule to the compound</p> Signup and view all the answers

<p>To convert toxic compounds into less toxic forms</p> Signup and view all the answers

<p>Phase I reactions introduce functional groups, while Phase II reactions conjugate the xenobiotic to a water-soluble molecule</p> Signup and view all the answers

<p>To facilitate the excretion of toxic compounds</p> Signup and view all the answers

<p>It acts as an electron acceptor, facilitating oxidation reactions</p> Signup and view all the answers

<p>To remove xenobiotics from the body through metabolism and excretion</p> Signup and view all the answers

<p>To enhance the excretion of toxic compounds</p> Signup and view all the answers

<p>Phase III reactions facilitate the final excretion of toxic compounds</p> Signup and view all the answers

<p>Phase 1: activation (oxidation, reduction, hydrolysis). In some cases the compound may be excreted after phase I, but usually it continues to phase II. The main enzyme of phase I is cytochrome P450 (many different iso-enzymes).</p> <p>Phase II: conjugation (binding to an intracellular polar ligand). This will usually detoxify the compound and make it suitable for phase III, however sometimes a compound becomes more toxic in phase II. The conjugation reactions are conducted by a variety of enzymes, some bound to the smooth ER close to P450, some in the cytoplasm. They catalyse conjugations to sulphate, glutathione, glucuronic acid, glucose and water, as well as, more rarely, other compounds.</p> <p>Phase III: excretion. This involves a variety of transporters; the best-known are ABC-transporters, which are highly induced by toxicants and in a medical setting, may make the cell resistant to drugs. Sometimes the product of phase II is still modified in the excretory organ, e.g. glutathione conjugates to mercapturic acids in the kidney.</p> Signup and view all the answers

<p>Aryl hydrocarbon receptor: receptor protein: has a pocket for binding any dioxin-like compound and is then released from its Hsp70 chaperon. Heat shock protein 70: stabilizes Ahr in inactive form, is released when Ahr binds a ligand. Aryl hydrocarbon receptor nuclear translocator: protein that pairs with activated Ahr and allows translocation to the nucleus Xenobiotic-response elements: DNA sequences in the promoter of CYP1A1, binding the Ahr-ARNT-complex which acts as a transcription factor triggering transcription of the downstream coding sequence by RNA polymerase. CYP1A1 gene: DNA sequence with an open reading frame (interrupted by introns) for the CYP mRNA. CYP1A1 mRNA: RNA synthesized by RNA polymerase with nucleotide sequence matching the template strain of the CYP DNA; after splicing out the introns this mRNA is transferred to the cytoplasm. CYP 1A1 protein: peptide synthesized in the ribosome, using tRNAs and CYP mRNA as a template. CYP 1A1 enzymatic activity: after settling in the sER and addition of an iron-porphyrin ring structure the CYP enzyme becomes active</p> Signup and view all the answers

<p>The EROD assay provides a rough measure of biotransformation activity but (1) it is not very specific (many different iso-enzymes of P450 are measured), and (2) activity depends not only on contaminant exposure but also on many other internal and external triggers (hormones, dietary plant compounds, seasonal effects). Also, induction of P450 is not equally strong in different species groups (low among birds of prey and vultures, high among fowl and chicken, low among earthworms, high among crustaceans and insects).</p> Signup and view all the answers

<p>Yc = Ymax * (1 + f * c) / (1 + 2 * f * EC50 + 1/EC50)</p> Signup and view all the answers

<p>To predict the effect caused by toxicant concentrations and estimate the exposure concentration that triggered a certain response.</p> Signup and view all the answers

<p>Forward use predicts the effect caused by toxicant concentrations, while backward use estimates the exposure concentration that triggered a certain response.</p> Signup and view all the answers

<p>Logistic models can handle non-symmetric curves and are more flexible than linear models, allowing for a better fit of the data.</p> Signup and view all the answers

<p>EC50 is the effective concentration of a substance that causes 50% of the maximum response. It is calculated by fitting a dose-response curve to the data and estimating the concentration at which 50% of the maximum response occurs.</p> Signup and view all the answers

<p>Hormesis is a phenomenon where low doses of a toxic substance stimulate biological processes, while high doses inhibit them. This is reflected in the dose-response curve as a biphasic response.</p> Signup and view all the answers

<p>NOAEL is the highest dose of a substance that does not cause adverse effects, while LOAEL is the lowest dose that causes adverse effects.</p> Signup and view all the answers

<p>BMD is the dose that causes a predetermined change in response. It is estimated by fitting a dose-response curve to the data and estimating the dose that corresponds to the predetermined change.</p> Signup and view all the answers

<p>CED is the dose that causes a predetermined adverse effect. It is estimated by fitting a dose-response curve to the data and estimating the dose that corresponds to the predetermined effect.</p> Signup and view all the answers

<p>Alternative models, such as the Weibull model, can provide a better fit to the data and handle non-symmetric curves, allowing for a more accurate estimation of the dose-response relationship.</p> Signup and view all the answers

<p>Understanding dose-response relationships is critical in ecotoxicology as it allows researchers to predict the effects of toxic substances on organisms and ecosystems, and to estimate the exposure concentration that triggered a certain response.</p> Signup and view all the answers

<p>The primary assumption is that the response Yj at concentration cj is normally distributed, with expectation Mj and variance σ2. This assumption can affect the reliability of the results, as it may not always hold true in real-world scenarios.</p> Signup and view all the answers

<p>The limitations of NOEC include inefficient use of test data, level of effect at NOEC regularly &gt; 20%, and poor testing leading to high (unprotective) NOECs. These limitations can affect the interpretation of results by making them less reliable and potentially misleading.</p> Signup and view all the answers

<p>The logistic model is used to describe the dose-response curve, and it is characterized by three parameters: Ymax, b, and EC50. The model describes the relationship between the concentration of a substance and the response, allowing for the estimation of the EC50 value.</p> Signup and view all the answers

<p>Non-symmetric curves can indicate complex dose-response relationships, and they can affect the interpretation of results by making it more difficult to estimate the EC50 value. Non-symmetric curves can also indicate the presence of hormesis or other non-linear effects.</p> Signup and view all the answers

<p>Hormesis is a phenomenon where a substance exhibits a beneficial effect at low concentrations, but a toxic effect at high concentrations. Hormesis can affect the dose-response curve by creating a non-linear or U-shaped response, making it more challenging to estimate the EC50 value.</p> Signup and view all the answers

<p>Such organisms represent a much more homogeneous population regarding age, size, physiology etc. while a field population will show a larger heterogeneity because it will include organisms that vary more in size, age, etc.</p> Signup and view all the answers

<p>EC10 values are derived by curve fitting using all data obtained from a toxicity test, are not affected by the concentration steps taken, are less dependent on number of replicates or variation between replicates and do have a 95% confidence interval indicating their reliability, allowing statistical comparisons of ECx values.</p> Signup and view all the answers

<p>Bioconcentration refers to the process by which a chemical accumulates in an organism from its environment, whereas biomagnification refers to the process by which a chemical accumulates in an organism through the consumption of contaminated food</p> Signup and view all the answers

<p>The BCF is a measure of the ability of a chemical to accumulate in an organism, calculated as the ratio of the concentration of the chemical in the organism to the concentration of the chemical in the surrounding environment</p> Signup and view all the answers

<p>The KOA is a measure of the partitioning of a chemical between the air and octanol phases, which can be used to predict the bioaccumulation potential of a chemical</p> Signup and view all the answers

<p>Bioavailability refers to the fraction of a chemical that is available for uptake by an organism, whereas bioaccumulation refers to the process by which a chemical accumulates in an organism</p> Signup and view all the answers

<p>Biomagnification refers to the process by which a chemical accumulates in an organism through the consumption of contaminated food, whereas trophic magnification refers to the process by which a chemical accumulates in an organism across multiple trophic levels</p> Signup and view all the answers

<p>Partitioning between media, such as water and air, can affect the bioaccumulation of a chemical by influencing its availability for uptake by an organism</p> Signup and view all the answers

<p>The bioconcentration mechanism in air-breathing organisms involves the uptake of chemicals through inhalation, followed by distribution and elimination through various routes, including biotransformation</p> Signup and view all the answers

<p>Biotransformation involves the conversion of a chemical into a more hydrophilic form, which can affect its bioaccumulation potential</p> Signup and view all the answers

<p>Biotransformation</p> Signup and view all the answers

<p>High logKow values are associated with increased bioaccumulation</p> Signup and view all the answers

<p>Bioconcentration occurs within an organism, while biomagnification occurs across trophic levels</p> Signup and view all the answers

<p>KOA is a measure of the partitioning of a chemical between the atmosphere and octanol, which is related to its bioavailability</p> Signup and view all the answers

<p>Trophic transfer is the process by which a chemical is transferred from one trophic level to the next, leading to biomagnification</p> Signup and view all the answers

<p>TMF is a measure of the rate of biomagnification, with higher values indicating greater biomagnification</p> Signup and view all the answers

<p>BCF is the ratio of the concentration of a chemical in an organism to the concentration of the chemical in the surrounding water. It is expressed as mg/kg (on a wet weight or lipid weight basis) or as mg/L (on a volume basis).</p> Signup and view all the answers

<p>Diet composition affects the amount of chemical ingested by an organism, which influences biomagnification</p> Signup and view all the answers

<p>The OECD 305 BCF test protocol is a bioconcentration test that involves exposing fish to two concentrations of a chemical for 28 days. The uptake and depuration phases are monitored to determine the BCF.</p> Signup and view all the answers

<p>Higher lipid content is associated with greater bioaccumulation capacity</p> Signup and view all the answers

<p>The one-compartment model is a mathematical model that describes the uptake and elimination of a chemical in an organism. It is based on the assumption that the chemical is distributed uniformly throughout the organism.</p> Signup and view all the answers

<p>Biotransformation can affect the bioavailability of a chemical by altering its chemical structure and partitioning properties</p> Signup and view all the answers

<p>Kow is a measure of the lipophilicity (hydrophobicity) of a chemical. It measures the partitioning of a chemical between octanol and water.</p> Signup and view all the answers

<p>Higher trophic level organisms tend to have greater bioaccumulation capacity</p> Signup and view all the answers

<p>Bioavailability refers to the fraction of the total concentration of a chemical in a medium that is available for uptake by an organism. It is related to the dissolved water concentration of the chemical.</p> Signup and view all the answers

<p>Biomagnification (BMF) is the process by which the concentration of a chemical increases as it moves up the food chain. It differs from bioconcentration in that it involves the transfer of a chemical from one organism to another.</p> Signup and view all the answers

<p>KOA is a measure of the partitioning of a chemical between octanol and air. It measures the ability of a chemical to pass through the respiratory surface of an organism.</p> Signup and view all the answers

<p>Kow is positively correlated with BCF for lipophilic chemicals. However, for very lipophilic chemicals, the correlation between Kow and BCF breaks down.</p> Signup and view all the answers

<p>Physico-chemical properties such as Kow and KOA are important for predicting the bioaccumulation potential of a chemical as they determine the ability of the chemical to partition into different media.</p> Signup and view all the answers

<p>The partitioning of a chemical between different media affects its bioaccumulation potential by determining the amount of the chemical that is available for uptake by an organism.</p> Signup and view all the answers

<p>BCF = bioconcentration factor, assumes uptake from water only.</p> <p>BSAF = biota-to-soil or sediment bioaccumulation factor; assumes uptake from soil or sediment (and not distinguishing uptake by ingestion of soil/sediment particles or from pore water).</p> Signup and view all the answers

<p>From ingesting sediment particles, from interstitial water (pore water) and from overlaying water.</p> Signup and view all the answers

<p>Fat content, Sex, Biomass/weight, Metabolic activity, Uptake route</p> Signup and view all the answers

<p>(i) Organism is regarded as one compartment – homogeneous concentrationthe whole body and (ii) rates of exchange follow first order kinetics, i.e. rates depends on the concentration.</p> Signup and view all the answers

<p>Looking at a plot of concentration in the organism (on a logarithmic scale) versus time shows two phases: a fast and a slower elimination.</p> Signup and view all the answers

<p>Typical examples of two compartment systems are: blood (I) and liver (II) or liver tissue (I) and fat tissue (II).</p> Signup and view all the answers

<p>A smaller organism has a larger surface to volume ratio and the exchange of chemical between water and an organism via passive diffusion is always via a surface. Because a larger surface is available to “fill” a small volume, kinetics are faster and equilibrium is reached earlier.</p> Signup and view all the answers

<p>Static, as Corg/Caq and kinetic as kw/ke.</p> Signup and view all the answers

<p>Chemical A: Likely in the water: due to the low log Kow uptake in organisms is unlikely. Potentially in algae, some uptake might occur but transfer to other species is unlikely even though the chemical is persistent. Chemical B: algae, chemical will be metabolised in daphnids, resulting in low concentrations in daphnids and absence of transfer to fish. Chemical c: fish: The chemical has a high Log Kow so uptake is to be expected, and the chemical is persistent so transfer to higher trophic level is likely.</p> Signup and view all the answers

<p>Diet composition (you accumulate what you eat) and metabolic capacity</p> Signup and view all the answers

<p>Next to the B of bioaccumulative, and P of persistence, the chemical needs to be Toxic (T-criterium). Hence PBT-chemicals are always treated cautiously.</p> Signup and view all the answers

<p>Time of exposure determines whether or not steady state is reached in the interaction of the organisms with the exposure medium. Whether the CBC is exceeded depends on exposure concentration but also on time of exposure. At high concentrations, the CBC will sooner be reached while at low concentrations it may take longer periods of time, depending on the kinetics of uptake</p> Signup and view all the answers

<p>When total body concentration is not indicative of toxicity, e.g. because (part of) the chemical taken up is stored in an inert form.</p> Signup and view all the answers

<p>It remains uncertain whether equilibrium has been reached, so real BCF or BSAF may be higher.</p> Signup and view all the answers

<p>Expose test organisms for a certain period (e.g. 2-3 weeks, but depending on test species test duration may be shorter or longer) in spiked medium to determine uptake and then transfer them for another period to clean medium to assess elimination. Sample animals at different time intervals during both the uptake and elimination phase, preferably having a higher sampling frequency early in each phase. Take e.g. 3-4 replicate samples at each sampling time. Keep in mind that analysis applying first-order one-compartment modelling is regression based, so it is better to have more sampling times with less replicates rather than having many replicates and few sampling times.</p> Signup and view all the answers

<p>a. Keeping exposure level constant is a problem especially when chemicals are highly lipophilic, but this may also be the case for unstable or volatile chemicals, although such chemicals probably will not require determining bioaccumulation potential.</p> <p>b. In aquatic media this can be solved by applying continuous flow or passive dosing methods.</p> <p>c. In soil, keeping exposure levels is more difficult and in fact can only be realized by transferring animals also during the uptake phase to freshly spiked media. But one may wonder whether it does make sense to determine bioaccumulation potential of chemicals that degrade so fast that concentrations show already strong decline within the duration of relatively short (2-3 week) exposure periods in bioaccumulation kinetics tests.</p> Signup and view all the answers

<p>They provide a more comprehensive understanding of the complex interactions between biological pathways.</p> Signup and view all the answers

<p>To create a fit-for-purpose AOP that can be used to predict adverse outcomes.</p> Signup and view all the answers

<p>To evaluate the strength of evidence supporting an AOP.</p> Signup and view all the answers

<p>MIE is the molecular event that initiates the adverse outcome pathway.</p> Signup and view all the answers

<p>The consideration of biological complexity is crucial in AOP network development, as it acknowledges the complexity of biological systems and the interactions between KEs, and is essential for predictive toxicology, as it enables the development of more accurate and realistic models.</p> Signup and view all the answers

<p>The weight of evidence evaluation is critical in AOP development, as it evaluates the strength and consistency of the evidence supporting the KERs, and is essential for predictive toxicology, as it enables the development of more accurate and reliable models.</p> Signup and view all the answers

<p>It allows for cross-species extrapolation and facilitates the development of Adverse Outcome Pathways (AOPs) that can be applied across different species.</p> Signup and view all the answers

<p>They provide a comprehensive framework for understanding the complex relationships between molecular events, adverse outcomes, and environmental exposures, enabling more accurate risk assessment and prediction of toxic effects.</p> Signup and view all the answers

<p>Biological complexity influences the development of AOPs by introducing variability and uncertainty, which must be considered in the weight of evidence evaluation to ensure accurate risk assessment and prediction of toxic effects.</p> Signup and view all the answers

<p>The key stages include MIE identification, KE identification, and AOP network development, which collectively contribute to the weight of evidence evaluation by providing a comprehensive understanding of the toxicological process.</p> Signup and view all the answers

<p>The weight of evidence evaluation provides a comprehensive assessment of the available evidence, considering factors such as biological plausibility, empirical evidence, and toxicological relevance, to support the development of AOPs and risk assessment.</p> Signup and view all the answers

<p>The AOP framework provides a mechanistic understanding of toxicological processes, enabling the development of novel testing strategies that focus on key toxicity pathways and facilitating predictive toxicology and risk assessment.</p> Signup and view all the answers

<p>An MIE represents the primary interaction of a stressor with a biological receptor (usually a macromolecule) from which all other adverse effects follow.</p> Signup and view all the answers

<p>The AOP concept is particularly suited to integrate in-vitro assay data, because such data support the understanding of intermediate key events, which are biochemical reactions causally linking molecular initiation and adverse outcome.</p> Signup and view all the answers

<p>To support hazard and risk assessment by means of fast assays predictive of apical outcomes.</p> Signup and view all the answers

<p>Three key events are identified: dendritic cell activation and mobilization, keratinocyte activation, and T-cell activation and proliferation.</p> Signup and view all the answers

<p>Individual AOPs are linear, but different AOPs can be connected through shared key events. Within an AOP different key events can be activated simultaneously leading to events propagating in a network, the functional unit of evaluation.</p> Signup and view all the answers

<p>That they have the same mode of action.</p> Signup and view all the answers

<p>A situation where the effect of the mixture is less than the effect of each compound individually.</p> Signup and view all the answers

<p>A situation where the effect of the mixture is greater than the effect of each compound individually.</p> Signup and view all the answers

<p>By looking at the parallelism of their dose-response curves.</p> Signup and view all the answers

<p>To determine if the interaction between two compounds is synergistic, antagonistic, or additive.</p> Signup and view all the answers

<p>Synergism is when the combined effect is greater than the individual effects, while antagonism is when the combined effect is less than the individual effects.</p> Signup and view all the answers

<p>The principle of concentration addition states that one chemical can be replaced totally or in part by an equal fraction of an equi-effective concentration of another, without changing the overall combined effect. This is achieved by summing up the fractions of equi-effective single substance concentrations, also known as toxic units (TU), which add up to an overall toxic unit of the mixture. At the same effect level x, the concentrations of each compound in the mixture are a fraction of the EC50.</p> Signup and view all the answers

<p>The toxic unit sum (TUx) is calculated by summing up the fractions of each compound's concentration relative to its EC50 value. TUx = 1 indicates that the combined effect of the mixture is equal to the effect of one compound at its EC50 value.</p> Signup and view all the answers

<p>Synergism occurs when the combined effect of a mixture is greater than the sum of the individual effects, while antagonism occurs when the combined effect is less than the sum of the individual effects. Synergism increases the combined effect, while antagonism decreases it.</p> Signup and view all the answers

<p>The isobologram method is a graphical representation of the concentration addition principle, where the concentrations of multiple compounds are plotted against each other to visualize the combined effect. It is significant in predicting the combined effects of multiple chemicals by identifying synergistic or antagonistic interactions.</p> Signup and view all the answers

<p>The mode of action of a chemical refers to the way it interacts with biological systems to produce a toxic effect. In concentration addition, chemicals with the same mode of action can be combined using the toxic unit sum, while chemicals with different modes of action may require different approaches to predict the combined effect.</p> Signup and view all the answers

<p>The EC50 value is the concentration of a chemical that produces a 50% effect, and it is used as a reference point for calculating toxic units (TU). The toxic unit is a fraction of the EC50 value, and it represents the relative potency of a chemical.</p> Signup and view all the answers

<p>The concept of concentration addition is based on the idea that different chemicals can have equi-effective concentrations, which are concentrations that produce the same effect. This relationship is significant because it allows for the prediction of combined effects of multiple chemicals using the toxic unit sum.</p> Signup and view all the answers

<p>The equation ∑(c_i / EC50_i) = 1 represents the concentration addition principle, where the sum of the fractions of each compound's concentration relative to its EC50 value is equal to 1. This equation is significant because it allows for the prediction of the combined effect of a mixture of chemicals.</p> Signup and view all the answers

<p>Independent action occurs when the effects of two compounds are additive, whereas dependent action occurs when the effect of one compound is influenced by the presence of another compound.</p> Signup and view all the answers

<p>To predict the combined effect of two compounds with the same mode of action.</p> Signup and view all the answers

<p>Prochloraz induces the P450 system, which activates or detoxifies malathion, leading to a more toxic effect.</p> Signup and view all the answers

<p>A mixture is a combination of two or more compounds, which can interact and produce a different effect than the individual compounds, whereas a single compound has a single mode of action.</p> Signup and view all the answers

<p>Antagonism in relation to Concentration Addition can simply be caused by the compounds behaving according to Response Addition, and not behaving antagonistically. Similarly, deviations from Response Addition could also mean that the chemicals in the mixture do have the same mode of action, so act additively according to Concentration Addition.</p> Signup and view all the answers

<p>The TEF concept is used to express the relative potency of individual dioxin congeners compared to the most potent dioxin, 2,3,7,8-TCDD.</p> Signup and view all the answers

<p>TEQ(total) = Σ{(TEF)(1,n) x <a href="1,n">congener</a>}</p> Signup and view all the answers

<p>The principle is that the total toxicity of a mixture is equal to the sum of the toxicities of the individual congeners, weighted by their TEF values.</p> Signup and view all the answers

<p>The compound must be very persistent against breakdown, bioaccumulative, and have a similar mechanism of action and clinical symptoms as 2,3,7,8-TCDD.</p> Signup and view all the answers

<p>The reporter gene assay is used to measure the toxicity of a sample by detecting the activation of a reporter gene in response to the presence of dioxin-like compounds.</p> Signup and view all the answers

<p>The total dioxin-like activity is calculated by multiplying the concentration of each congener by its TEF value and summing the results.</p> Signup and view all the answers

<p>The WHO-list provides a standardized set of TEF values for different dioxin congeners, allowing for the calculation of the total dioxin-like activity of a mixture.</p> Signup and view all the answers

<p>The TEQ calculation is used to express the total dioxin-like activity of a mixture in terms of a single value, taking into account the relative potency of each congener.</p> Signup and view all the answers

<p>The TEF concept is based on the concentration addition concept, which states that the total toxicity of a mixture is equal to the sum of the toxicities of the individual congeners.</p> Signup and view all the answers

<p>They remain intact for exceptionally long periods, become widely distributed, accumulate in fatty tissue, and are toxic to humans and wildlife.</p> Signup and view all the answers

<p>Natural origin, intentional poisoning, disaster, illegal activities, and background levels.</p> Signup and view all the answers

<p>The movement of persistent organic pollutants (POPs) from hotter regions to colder regions through alternating processes of volatilization and condensation.</p> Signup and view all the answers

<p>Food, particularly fatty fish and dairy products.</p> Signup and view all the answers

<p>Combustion processes, organochlorine production, and leaded fuel.</p> Signup and view all the answers

<p>They accumulate in fatty tissue and are biomagnified up the food chain, resulting in higher concentrations in predators and humans.</p> Signup and view all the answers

<p>A biphenyl structure with chlorine atoms attached to the phenyl rings.</p> Signup and view all the answers

<p>The Ah receptor (AhR) theory, which involves the induction of gene expression and phosphorylation through the binding of dioxin-like compounds to the AhR.</p> Signup and view all the answers

<p>It provides a framework for evaluating the relative toxicity of different congeners and mixtures, allowing for the calculation of TEQ values.</p> Signup and view all the answers

<p>TEF allows for the calculation of the total toxic equivalent of a mixture of dioxin-like compounds, providing a more accurate assessment of their toxicity.</p> Signup and view all the answers

<p>It enables them to persist in the environment and bioaccumulate in fatty tissue, leading to increased toxicity and environmental impact.</p> Signup and view all the answers

<p>Their stability and resistance to electrical, thermal, chemical, or biological breakdown.</p> Signup and view all the answers

<p>It binds to dioxin-like compounds, inducing gene expression and phosphorylation, leading to toxic effects.</p> Signup and view all the answers

<p>PCDDs and PCDFs are unintentional byproducts, while PCBs were produced on purpose and used in various applications.</p> Signup and view all the answers

<p>It demonstrates the biomagnification of PCBs, indicating their potential to accumulate and cause toxic effects in predators and humans.</p> Signup and view all the answers

<p>It allows for the conversion of different dioxin-like compounds to a common unit of toxicity.</p> Signup and view all the answers

<p>They can cause adverse effects on the environment and human health, including toxicity and bioaccumulation.</p> Signup and view all the answers

<p>External exposure refers to the concentration of a toxic substance in the environment (air, water, soil, food), whereas internal exposure refers to the concentration of a toxic substance in the body or a specific body compartment.</p> Signup and view all the answers

<p>The body responds to toxic substances through absorption, distribution, metabolism, and excretion (ADME), which are the four stages of toxicokinetics.</p> Signup and view all the answers

<p>Acute toxicity refers to the effects of a single exposure to a toxic substance over a short period, whereas chronic toxicity refers to the effects of prolonged and repeated exposure to a toxic substance over a longer period.</p> Signup and view all the answers

<p>Dose-response relationships are crucial in ecotoxicology as they describe the relationship between the dose of a toxic substance and the resulting toxic effect.</p> Signup and view all the answers

<p>Toxicodynamics focuses on the effects of toxic substances on the body, including the type and severity of the effects, as well as the dose-response relationship.</p> Signup and view all the answers

<p>The primary route of exposure is through the environment, and it affects the ecosystem by altering population dynamics, community structure, and ecosystem functioning.</p> Signup and view all the answers

<p>The LC50 (Lethal Concentration 50) is the concentration of a toxic substance that causes the death of 50% of the test organisms in an acute toxicity test.</p> Signup and view all the answers

<p>Reversible toxic effects can be repaired by the body, whereas irreversible toxic effects are permanent and cannot be repaired.</p> Signup and view all the answers

<p>Acute toxicity refers to the immediate and severe effects of toxic substances, while chronic toxicity refers to the long-term, low-dose effects. Both are significant in ecotoxicology as they can affect ecosystems in different ways.</p> Signup and view all the answers

<p>Dose-response relationships describe the correlation between the dose of a toxic substance and the resulting effect on an organism. This concept is significant in ecotoxicology, as it enables the prediction of toxic effects on ecosystems.</p> Signup and view all the answers

<p>EC50 (Effective Concentration 50) is the concentration of a toxic substance that causes a 50% effect on a specific endpoint, EC10 (Effective Concentration 10) is the concentration that causes a 10% effect, and NOEC (No Observed Effect Concentration) is the highest concentration that does not cause a significant effect.</p> Signup and view all the answers

<p>Toxicokinetics is the study of the absorption, distribution, metabolism, and elimination of toxic substances in organisms. It is important in ecotoxicology, as it enables the understanding of the fate and effects of toxic substances in ecosystems.</p> Signup and view all the answers

<p>Toxicodynamics is the study of the interactions between toxic substances and biological systems, including the mechanisms of toxicity. It is significant in ecotoxicology, as it enables the understanding of the effects of toxic substances on ecosystems.</p> Signup and view all the answers

<p>Understanding the mechanisms of toxicity is important in ecotoxicology, as it enables the prediction of toxic effects on ecosystems and the development of strategies to mitigate these effects.</p> Signup and view all the answers

<p>Biotransformation is the process by which organisms convert toxic substances into less toxic or more toxic forms. It is significant in ecotoxicology, as it affects the fate and effects of toxic substances in ecosystems.</p> Signup and view all the answers

<p>Understanding the metabolism of xenobiotics is important in ecotoxicology, as it enables the prediction of the fate and effects of toxic substances in ecosystems.</p> Signup and view all the answers

<p>The three primary routes of exposure to toxic substances in animals are: oral via GI track, contact (topical), and respiratory. Examples of each are: oral via food and water, contact via skin (dermal) in vertebrates, and respiratory via lung or gills in vertebrates.</p> Signup and view all the answers

<p>Acute toxicity refers to the short-term effects of a toxic substance on an organism, resulting from a single exposure or a short exposure duration, whereas chronic toxicity refers to the long-term effects resulting from repeated or prolonged exposure to a toxic substance.</p> Signup and view all the answers

<p>Understanding dose-response relationships is crucial in ecotoxicology to determine the toxic effects of a substance on an organism at different exposure levels. An example of its application is in setting safe limits for chemical pollutants in the environment.</p> Signup and view all the answers

<p>Toxicokinetics is the study of the absorption, distribution, metabolism, and excretion of toxic substances in an organism. An example of its relation to the distribution of toxic substances is the role of the blood-brain barrier in restricting the distribution of xenobiotics to the brain.</p> Signup and view all the answers

<p>Toxicokinetics is the study of the absorption, distribution, metabolism, and excretion of toxic substances, while toxicodynamics is the study of the interactions between toxic substances and biological systems. Examples of each are: the absorption of a toxic substance through the skin (toxicokinetics) and the binding of a toxic substance to a receptor, leading to a toxic response (toxicodynamics).</p> Signup and view all the answers

<p>Biotransformation plays a crucial role in the detoxification of xenobiotics by converting them into more water-soluble compounds, making them easier to excrete. An example of a phase I reaction is the oxidation of a xenobiotic by cytochrome P450, resulting in a more hydrophilic compound.</p> Signup and view all the answers

<p>Understanding the phases of toxic response is crucial in ecotoxicology to assess the impact of toxic substances on ecosystems. The phases of toxic response are: exposure, uptake, distribution, metabolism, and response. Examples of each phase are: exposure to a toxic substance through ingestion (exposure), absorption of the substance through the gut (uptake), distribution of the substance to the liver (distribution), metabolism of the substance by cytochrome P450 (metabolism), and the resulting toxic response (response).</p> Signup and view all the answers

<p>Dose-response relationships describe the relationship between the dose or exposure level of a toxic substance and the resulting toxic response. An example of its application in risk assessment is the use of dose-response relationships to determine the safe limits for chemical pollutants in the environment, ensuring that the exposure levels do not exceed the threshold for toxic effects.</p> Signup and view all the answers

<p>Test organisms should be easy to culture and maintain, sensitive, ecologically and economically relevant.</p> Signup and view all the answers

<p>a. Birds are a diverse, abundant order living in areas that have been altered by humans through the use of chemicals (eg agriculture)</p> <p>b. They are physiologically different from many other vertebrate classes and that may alter their sensitivity to chemical exposure.</p> <p>c. They play an essential role in certain ecosystem cycles – for example they aid in seed dispersal and they act as biological control agents of insect pests.</p> Signup and view all the answers

<p>The purpose of a reporter gene assay is to study the effects of toxic substances on gene expression. Fluorescent or luminescent reporter proteins are used because they allow for real-time monitoring of gene expression and provide a sensitive and quantitative measure of the toxic effect.</p> Signup and view all the answers

<p>Totipotent cells can give rise to a complete organism, pluripotent cells can give rise to any cell type in the body, and multipotent cells are limited to differentiating into cell types within a specific germ layer.</p> Signup and view all the answers

<p>Stem cell differentiation is the process by which stem cells become specialized into specific cell types. Human stem cells can be derived from the amniotic fluid, pre-implantation embryos, and adult tissues.</p> Signup and view all the answers

<p>Stem cells can be used to create differentiated cells in vitro for toxicity testing, which allows for the assessment of toxicity in a more relevant and human-relevant model.</p> Signup and view all the answers

<p>Understanding cell potency is crucial in developmental toxicity as it allows for the assessment of the effects of toxic substances on cell differentiation and development.</p> Signup and view all the answers

<p>Stem cells can be used to study the effects of toxic substances on cell differentiation and development, allowing for a better understanding of developmental toxicity.</p> Signup and view all the answers

<p>Metabolism plays a critical role in the biotransformation of toxic compounds, which involves the conversion of xenobiotics into more polar compounds that can be excreted.</p> Signup and view all the answers

<p>Understanding Phase I and Phase II reactions is crucial in understanding biotransformation, which involves the conversion of xenobiotics into more polar compounds that can be excreted.</p> Signup and view all the answers

<p>To measure the response of a specific gene or pathway to a toxic compound.</p> Signup and view all the answers

<p>Primary cells are isolated from an organism and have a limited lifespan, while cell lines are immortalized and can be passaged indefinitely.</p> Signup and view all the answers

<p>Differentiation allows stem cells to be directed toward specific cell types, enabling the study of toxic effects on specific cell types.</p> Signup and view all the answers

<p>The study of the products and intermediates of metabolism, such as changes in metabolic pathways.</p> Signup and view all the answers

<p>The effects of toxic compounds on fetal development and embryogenesis.</p> Signup and view all the answers

<p>To provide a continuous and consistent source of cells for toxicity testing.</p> Signup and view all the answers

<p>Easy read-out and rapid assessment of toxic effects.</p> Signup and view all the answers

<p>Cell viability assays measure the ability of cells to survive, while cell growth assays measure the rate of cell proliferation.</p> Signup and view all the answers

<p>It allows for the direct conversion of fibroblasts into adipocytes, bypassing the need for pluripotency reprogramming.</p> Signup and view all the answers

<p>It determines the ability of stem cells to differentiate into specific cell types and their potential therapeutic applications.</p> Signup and view all the answers

<p>It enables the identification of metabolomic biomarkers that can predict developmental toxicity and inform risk assessments.</p> Signup and view all the answers

<p>They enable the monitoring of gene expression and cell differentiation in real-time.</p> Signup and view all the answers

<p>Ligand binding assays make use of labelled protein ligands. Protein is incubated with the labelled ligand in the presence of different concentrations of the test substance. If protein-binding by the test substance prevents ligand binding to the protein, the free ligand -protein complex, which is isolated after incubation, shows a concentration-dependent decrease in radioactivity.</p> Signup and view all the answers

<p>Enzymatic activity is usually determined as the conversion rate of a substrate into a product. Enzymes are incubated with their substrate in the presence of different concentrations of the test substance. If enzyme activity is inhibited by the test substance, a dose-dependent decrease in product will be measured after the incubation period.</p> Signup and view all the answers

<p>Reporter gene bioassays make use of genetically modified cell lines or bacteria that contain an incorporated gene construct encoding for an easily measurable protein (i.e. the reporter protein). This gene construct is developed in such a way that its expression is triggered by a specific interaction between the toxic compound and a cellular receptor. If the receptor is activated by the toxic compound, transcription and translation of the reporter protein takes place, which can be easily measured as a change in colour, fluorescence, or luminescence.</p> Signup and view all the answers

<p>Primary cell culture:</p> <ul> <li>Cells have similar genotype and phenotype as in vivo</li> <li>Cells remain differentiated</li> <li>Cells can only be cultured for a limited number of passages</li> <li>Cells grow slowly</li> <li>New cell cultures require isolation of fresh tissue from donor organisms</li> <li>Genetic variation between different donors Continuous cell line:</li> <li>New cultures have identical genotypes as previous cultures</li> <li>Cells divide indefinitely</li> <li>Cells grow quickly</li> <li>Cells have a different genotype and phenotype as healthy tissue in vivo</li> <li>Cells have lost differentiation</li> <li>Cells behave like cancer cells</li> </ul> Signup and view all the answers

<p>Embryonic stem cells (ESCs) are isolated from embryonic tissue, thereby raising ethical objections. The earlier the stem cells are obtained during development, the higher is their potency to differentiate into different cell types. Pluripotent stem cells are usually obtained from early embryos, whereas multipotent stem cells may also be obtained from amniotic fluid or umbilical cord blood. Induced pluripotent stem cells are obtained from cells isolated from differentiated (adult) tissue. The cells are reprogrammed into stem cells with pluripotent capacities.</p> Signup and view all the answers

<p>Ca2+ causes vesicles containing acetylcholine to move towards the presynaptic membrane, leading to the release of acetylcholine into the synaptic cleft.</p> Signup and view all the answers

<p>Acetylcholinesterase breaks down acetylcholine into inactive components, terminating the signal.</p> Signup and view all the answers

<p>Organophosphate esters and carbamic esters bind to acetylcholinesterase, blocking its activity and preventing the breakdown of acetylcholine.</p> Signup and view all the answers

<p>Damage to the myelin sheet or neuroglia can disrupt the normal functioning of neurons, leading to neurotoxicity.</p> Signup and view all the answers

<p>Ion channels allow ions to flow into or out of the neuron, changing the membrane potential and transmitting the signal.</p> Signup and view all the answers

<p>AChE inhibitors, such as sarin, prevent the breakdown of acetylcholine, leading to an accumulation of acetylcholine in the synaptic cleft and disrupting normal neurotransmission.</p> Signup and view all the answers

<p>Direct neurotoxicity occurs when a substance directly damages neurons, while indirect neurotoxicity occurs when a substance damages other cells or tissues, leading to indirect damage to neurons.</p> Signup and view all the answers

<p>The goal of biotransformation is to convert toxic compounds into less toxic or more easily excreted forms.</p> Signup and view all the answers

<p>The synapse</p> Signup and view all the answers

<p>Voltage-gated calcium channels</p> Signup and view all the answers

<p>Acetylcholinesterase inhibition</p> Signup and view all the answers

<p>Damage to nervous tissue</p> Signup and view all the answers

<p>Supporting and maintaining the health of neurons</p> Signup and view all the answers

<p>Ca2+ is necessary for the release of neurotransmitters from the presynaptic neuron</p> Signup and view all the answers

<p>Disruption of voltage-gated sodium channels</p> Signup and view all the answers

<p>Accumulation of acetylcholine and disruption of normal neurotransmission</p> Signup and view all the answers

<p>Voltage-gated sodium channels</p> Signup and view all the answers

<p>Type I: Prolonged Na-influx, hyperexcitable state, repetitive firing. Type II: Loss of membrane potential, action potential impossible</p> Signup and view all the answers

<p>Activation of acetylcholine receptor, leading to neural excitation</p> Signup and view all the answers

<p>Interferes with Ca-ATPase, possibly by inhibiting synthesis of prostaglandin E2 (PGE2)</p> Signup and view all the answers

<p>Blocks nicotinic acetylcholine receptors, leading to muscle paralysis</p> Signup and view all the answers

<p>Specifically damages dopaminergic neurons, leading to Parkinsonism</p> Signup and view all the answers

<p>Not directly involved, but calcium channels are important for neuronal function and may be affected indirectly</p> Signup and view all the answers

<p>Type I: Hyperexcitable state, repetitive firing. Type II: Loss of membrane potential, action potential impossible</p> Signup and view all the answers

<p>Through iterative evaporation and condensation, or global distillation, due to low volatility and chemical stability</p> Signup and view all the answers

<p>Very toxic (efficient), degradable in sunlight, and degradable in water</p> Signup and view all the answers

<p>Biotransformation enzymes, biotransformation products, oxidative stress, stress proteins, haematological parameters, immunological parameters, reproductive and endocrine parameters, neuromuscular parameters, genotoxic parameters, and physiological and morphological parameters.</p> Signup and view all the answers

<p>Intersex in roach is an indicator of sexual disruption caused by exposure to endocrine-disrupting chemicals in the environment.</p> Signup and view all the answers

<p>The signal transduction pathway for steroid hormones involves the interaction of steroid hormones with membrane-bound receptors, which triggers a cascade of signaling events leading to changes in gene expression and cellular response.</p> Signup and view all the answers

<p>Biotransformation enzymes play a crucial role in the metabolism of xenobiotics by converting lipophilic compounds into more hydrophilic compounds that can be excreted from the body.</p> Signup and view all the answers

<p>Phase I reactions involve the oxidation, reduction, or hydrolysis of xenobiotics, while Phase II reactions involve the conjugation of activated xenobiotics with endogenous molecules.</p> Signup and view all the answers

<p>The purpose of conjugation in Phase II reactions is to increase the hydrophilicity of xenobiotics, making them more susceptible to excretion from the body.</p> Signup and view all the answers

<p>The Blood-Brain Barrier (BBB) is a critical barrier that restricts the passage of xenobiotics into the brain, protecting it from toxic compounds.</p> Signup and view all the answers

<p>Xenobiotic transport proteins play a crucial role in the defense against toxic compounds by facilitating the efflux of xenobiotics from cells and tissues.</p> Signup and view all the answers

<p>To determine the toxic potential of a substance, typically through the use of bioassays, and to characterize its hazard profile.</p> Signup and view all the answers

<p>Hazard assessment involves identifying the potential adverse effects of a substance, while risk assessment considers the likelihood and potential consequences of exposure.</p> Signup and view all the answers

<p>Biomarkers are used to measure the biological response to exposure to pollutants, providing an early warning of potential adverse effects.</p> Signup and view all the answers

<p>Biotransformation enzymes are proteins that facilitate the breakdown of xenobiotics, and their induction can be used as biomarkers of exposure to pollutants.</p> Signup and view all the answers

<p>EDA is used to identify the causative agents of observed toxic effects, and to prioritize pollutants for further risk assessment.</p> Signup and view all the answers

<p>CYP1A induction is used as a biomarker of exposure to pollutants, such as dioxins and polycyclic aromatic hydrocarbons (PAHs).</p> Signup and view all the answers

<p>Oxidative stress can lead to cellular damage and is an important mechanism of toxicity, particularly at the molecular and cellular levels.</p> Signup and view all the answers

<p>Hazard profiling involves the characterization of the toxic properties of a substance, including its potential to cause adverse effects.</p> Signup and view all the answers

<p>Stress proteins, such as heat shock proteins, are induced in response to cellular stress and can be used as biomarkers of exposure to pollutants.</p> Signup and view all the answers

<p>In vitro bioassays are used to assess the toxicity of substances in a controlled laboratory setting, providing an indication of their potential to cause adverse effects.</p> Signup and view all the answers

<p>VTG is a glyco-lipo-protein that serves as an egg-yolk precursor protein in female fish.</p> Signup and view all the answers

<p>AChE inhibitors work by binding to the enzyme, preventing the breakdown of acetylcholine, and thereby disrupting neurotransmission.</p> Signup and view all the answers

<p>Biotransformation enzymes, such as cytochrome P450, play a crucial role in the detoxification of chemicals by converting them into more hydrophilic and excretable compounds.</p> Signup and view all the answers

<p>In vitro bioassays are used to determine the potency of environmental samples to affect biomarkers, such as EROD, VTG, and AChE, in a controlled laboratory setting.</p> Signup and view all the answers

<p>Biomarkers are used to measure the biological response to a toxic substance, which can be used to assess the hazard of the substance.</p> Signup and view all the answers

<p>EDA is used to identify the causative compounds responsible for the observed effects in a complex environmental mixture.</p> Signup and view all the answers

<p>Hazard assessment is the process of identifying the potential harm of a substance, while risk assessment is the process of evaluating the likelihood of that harm occurring.</p> Signup and view all the answers

<p>Biomarkers can be used to provide a measure of the biological response to a toxic substance, which can be used to assess the risk of the substance.</p> Signup and view all the answers

<p>Toxicity profiling is used to identify the potential hazards of a substance and to assess the risk of that substance to the environment.</p> Signup and view all the answers

<p>Biomarkers are used to measure the biological response to a toxic substance, which is used to identify the potential hazards of the substance in toxicity profiling.</p> Signup and view all the answers

<p>The main purpose of Isotope Cluster Analysis is to identify unknown compounds in a sample by comparing the mass spectra of the unknown compounds to a library of known compounds.</p> Signup and view all the answers

<p>The T4*-TTR binding assay helps to identify compounds that can bind to the thyroid hormone receptor, which is an important step in identifying thyroid hormone disruptors.</p> Signup and view all the answers

<p>Persistent compounds are significant because they can bioaccumulate in the environment and in organisms, leading to increased exposure to thyroid hormone disruptors.</p> Signup and view all the answers

<p>GC-MS analysis helps to identify the chemical structure of compounds in a sample, which is essential for identifying thyroid hormone disruptors.</p> Signup and view all the answers

<p>The Blood-Brain Barrier (BBB) plays a crucial role in protecting the brain from xenobiotics by preventing their entry into the brain.</p> Signup and view all the answers

<p>The primary purpose of Phase I reactions is to convert lipophilic xenobiotics into more hydrophilic compounds, making them more susceptible to Phase II conjugation reactions.</p> Signup and view all the answers

<p>Biotransformation capacity is significant because it determines the rate at which xenobiotics are metabolized and eliminated from the body.</p> Signup and view all the answers

<p>The purpose of conjugation in Phase II reactions is to make xenobiotics more water-soluble, allowing for their excretion from the body.</p> Signup and view all the answers

<p>To identify the toxicants responsible for the observed effects in a complex mixture of compounds</p> Signup and view all the answers

<p>To identify the structure of the compounds and confirm their identity</p> Signup and view all the answers

<p>The effects can be masked by the presence of other compounds, and this can be circumvented by using fractionation and purification techniques to isolate the active chemicals</p> Signup and view all the answers

<p>These databases provide information on the structure, properties, and toxicology of compounds, which is essential for their identification</p> Signup and view all the answers

<p>To determine the toxicity of a sample and identify the responsible toxicants</p> Signup and view all the answers

<p>To direct the identification process by identifying the toxicants responsible for the observed effects</p> Signup and view all the answers

<p>To reduce the complexity of the sample and identify the responsible toxicants</p> Signup and view all the answers

<p>The bioassay response is related to the toxicant, as the bioassay is used to identify the toxicants responsible for the observed effects</p> Signup and view all the answers

<p>To identify the structure and properties of the compounds and confirm their identity</p> Signup and view all the answers

<p>EDA is a powerful tool for identifying the toxicants responsible for the observed effects in a complex mixture of compounds</p> Signup and view all the answers

<p>The primary purpose of Phase I reactions is to introduce a functional group into the xenobiotic, making it more polar and facilitating its conjugation in Phase II. This goal is to convert lipophilic and toxic compounds into more hydrophilic and less toxic compounds, facilitating their excretion from the body.</p> Signup and view all the answers

<p>The Aryl hydrocarbon receptor is involved in the upregulation of cytochrome P450 activity through a complex mechanism that involves binding to xenobiotic-response elements, leading to the enhanced de novo synthesis of enzyme. This process is significant in ecotoxicology as it allows organisms to adapt to xenobiotic exposure and detoxify toxic compounds.</p> Signup and view all the answers

<p>The Blood-Brain Barrier (BBB) is a critical barrier that restricts the distribution of xenobiotics to the brain, protecting it from toxic compounds. The goal of biotransformation is to facilitate the excretion of xenobiotics from the body, and the BBB plays a crucial role in this process by limiting the distribution of xenobiotics to the brain.</p> Signup and view all the answers

<p>Oxygen plays a crucial role in Phase I oxidation reactions, as it is involved in the insertion of oxygen into the xenobiotic, leading to the formation of reactive metabolites. This mechanism is significant in bioactivation, as it allows for the conversion of xenobiotics into more reactive and toxic compounds.</p> Signup and view all the answers

<p>The purpose of conjugation in phase II reactions is to convert the xenobiotic into a more hydrophilic and less toxic compound, facilitating its excretion from the body. This goal is to convert lipophilic and toxic compounds into more hydrophilic and less toxic compounds, facilitating their excretion from the body.</p> Signup and view all the answers

<p>Metabolism is a critical process in the context of toxic compounds, as it allows for the conversion of lipophilic and toxic compounds into more hydrophilic and less toxic compounds. This goal is to facilitate the excretion of xenobiotics from the body, and metabolism plays a crucial role in this process.</p> Signup and view all the answers

<p>The primary difference between Phase I and Phase II reactions is that Phase I reactions introduce a functional group into the xenobiotic, making it more polar, while Phase II reactions involve conjugation of the xenobiotic with a hydrophilic molecule. This difference is significant in biotransformation, as it enables the conversion of lipophilic and toxic compounds into more hydrophilic and less toxic compounds.</p> Signup and view all the answers

<p>Xenobiotic transport proteins play a crucial role in the defense against toxic compounds, as they facilitate the transport of xenobiotics across cellular membranes, enabling their excretion from the body. This goal is to facilitate the excretion of xenobiotics from the body, and xenobiotic transport proteins play a crucial role in this process.</p> Signup and view all the answers

<p>The Placenta is a critical barrier that restricts the distribution of xenobiotics to the fetus, protecting it from toxic compounds. The goal of biotransformation is to facilitate the excretion of xenobiotics from the body, and the Placenta plays a crucial role in this process by limiting the distribution of xenobiotics to the fetus.</p> Signup and view all the answers

<p>Phase III reactions involve the final excretion of toxic compounds from the body, and this is the ultimate goal of biotransformation. The relationship between phase III reactions and the final excretion of toxic compounds is that phase III reactions facilitate the excretion of xenobiotics from the body, achieving the goal of biotransformation.</p> Signup and view all the answers

<p>To monitor the performance of metabolomics workflows and correct for intensity drifts and inter-batch differences.</p> Signup and view all the answers

<p>To correct for intensity drifts and inter-batch differences by using a pooled sample of small amount of each sample.</p> Signup and view all the answers

<p>Quality control (QC) monitors the performance of metabolomics workflows, while quality assurance (QA) is a broader concept that includes QC and aims to ensure the overall quality of the results.</p> Signup and view all the answers

<p>To correct for inter-batch systematic error and ensure the reliability of metabolomics data.</p> Signup and view all the answers

<p>Internal standards are known compounds added to samples to monitor instrument performance and ensure data quality.</p> Signup and view all the answers

<p>Data preprocessing can affect confidence levels by reducing noise, correcting for biases, and improving data quality, leading to more accurate and reliable results.</p> Signup and view all the answers

<p>Quality control helps to detect and correct for errors, ensuring the reliability and accuracy of metabolomics data.</p> Signup and view all the answers

<p>Quality assurance sets standards and procedures, while quality control monitors and corrects for errors, ensuring the overall quality and confidence levels of metabolomics data.</p> Signup and view all the answers

<p>To align the chromatograms from different samples to enable the identification of metabolites.</p> Signup and view all the answers

<p>HRMS allows for the prediction of elemental composition based on exact mass and isotope pattern.</p> Signup and view all the answers

<p>Targeted metabolomics focuses on the detection of specific metabolites, while untargeted metabolomics aims to detect all metabolites in a sample without prior knowledge of their identity.</p> Signup and view all the answers

<p>EI spectrum is used to compare with MS/MS libraries for metabolite identification.</p> Signup and view all the answers

<p>Rt is used to predict the elution order of metabolites and to compare with Rt indices from MS/MS libraries.</p> Signup and view all the answers

<p>To separate overlapping peaks and enable the identification of individual metabolites.</p> Signup and view all the answers

<p>Peak annotation is the process of assigning a metabolite identity to a peak based on its mass, retention time, and other spectral features.</p> Signup and view all the answers

<p>To ensure the accuracy and reproducibility of metabolomics data.</p> Signup and view all the answers

<p>Confidence levels provide a measure of the probability that a metabolite identification is correct.</p> Signup and view all the answers

<p>Data preprocessing is essential to remove noise, correct for instrument variations, and align chromatograms from different samples.</p> Signup and view all the answers

<p>To identify the changes in the abundances of specific metabolites in a biological system after environmental contaminant exposure</p> Signup and view all the answers

<p>Targeted metabolomics focuses on specific metabolites, while untargeted metabolomics provides a complete overview of all detectable metabolites</p> Signup and view all the answers

<p>To ensure the quality and reliability of the data generated</p> Signup and view all the answers

<p>To clean, transform, and prepare the data for statistical analysis</p> Signup and view all the answers

<p>To determine the reliability of the results and the probability of making a type I error</p> Signup and view all the answers

<p>To monitor and control the quality of the data generated during the experiment</p> Signup and view all the answers

<p>To stop enzymatic reactions and preserve the metabolite profile</p> Signup and view all the answers

<p>Internal standard is added to the sample, while external standard is a reference compound</p> Signup and view all the answers

<p>To collect data on the metabolite profile of the biological system</p> Signup and view all the answers

<p>To understand the effects of environmental contaminants on biological systems</p> Signup and view all the answers

<p>EDCs bind to hormone receptors, mimicking or blocking the action of natural hormones, thereby disrupting normal hormone signaling pathways.</p> Signup and view all the answers

<p>Steroid pathways are critical for sex hormone synthesis and regulation. Aromatase enzymes convert androgens to estrogens, and disruption of these pathways by EDCs can lead to altered sex hormone levels and reproductive effects.</p> Signup and view all the answers

<p>Intersex in fish populations refers to the presence of both male and female reproductive characteristics in a single individual. Exposure to EDCs, such as estrogenic chemicals, can induce intersex development in fish, highlighting the risk of EDCs to aquatic species.</p> Signup and view all the answers

<p>TBT was used as a biocide in antifouling paints to prevent fouling of ship hulls. However, it is a potent endocrine disruptor, interfering with steroid hormone regulation and inducing imposex in marine organisms, such as gastropods.</p> Signup and view all the answers

<p>Biomarkers of endocrine disruption include alterations in gene expression, hormone levels, and reproductive morphology. They can be used to detect exposure to EDCs, such as changes in vitellogenin levels in fish or alterations in steroid hormone pathways.</p> Signup and view all the answers

<p>The ER-CALUX bioassay is a cell-based assay that measures the activation of estrogen receptors by EDCs. It is used to detect and quantify (anti-)estrogenic activity of chemicals, providing a sensitive and specific means of assessing their endocrine disrupting potential.</p> Signup and view all the answers

<p>An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.</p> Signup and view all the answers

<p>Agonism (binding and activation of hormone receptors) and antagonism (binding and inactivation of hormone receptors)</p> Signup and view all the answers

<p>Disrupting the synthesis, release, metabolism, and/or excretion of hormones</p> Signup and view all the answers

<p>(Anti-)estrogenic EDCs</p> Signup and view all the answers

<p>Handsoaps and toothpaste</p> Signup and view all the answers

<p>The ability of the estrogen receptor to bind to multiple ligands, including EDCs</p> Signup and view all the answers

<p>Developmental neurotoxicity</p> Signup and view all the answers

<p>The BBB prevents the distribution of xenobiotics to the brain, protecting it from toxic compounds</p> Signup and view all the answers

<p>To convert xenobiotics into more water-soluble compounds that can be excreted</p> Signup and view all the answers

<p>Phase III reactions involve the final excretion of toxic compounds from the body</p> Signup and view all the answers

<p>Steroid hormones bind to specific receptors, triggering a signal transduction pathway that leads to a response, such as gene expression or protein synthesis.</p> Signup and view all the answers

<p>VTG (vitellogenin) is a biomarker for estrogenic exposure, and its presence in male fish is an indicator of intersex, which is a common effect of endocrine disruption caused by estrogenic pollutants.</p> Signup and view all the answers

<p>TBT (tributyltin) in antifouling paints is a potent endocrine disruptor that can cause masculinization of female marine snails and other reproductive abnormalities, leading to impacts on population dynamics and ecosystem health.</p> Signup and view all the answers

<p>The ER-CALUX bioassay is a cell-based assay that measures the estrogenic or anti-estrogenic activity of compounds, using a luciferase reporter gene to detect changes in estrogen receptor activity.</p> Signup and view all the answers

<p>DDT and PCB/DDT metabolites, such as DDE, are known to cause reproductive impairment in wildlife, including birds and seals, by disrupting endocrine function and leading to feminization of males and other reproductive abnormalities.</p> Signup and view all the answers

<p>Biomarkers, such as VTG and sex steroids, are used to detect and monitor endocrine disruption in wildlife, providing insights into the effects of EDCs on reproduction and development, and informing conservation and management efforts.</p> Signup and view all the answers

<p>EDCs, such as natural and synthetic estrogens, can cause feminization of male fish populations, leading to reproductive impairment and altered population dynamics, with implications for ecosystem health and biodiversity.</p> Signup and view all the answers

<p>Intersex in fish populations is a common effect of endocrine disruption, and is characterized by the presence of both male and female reproductive characteristics, leading to reproductive impairment and altered population dynamics.</p> Signup and view all the answers

<p>It involves experts from various disciplines, including molecular techniques, bioinformatics, biostatistics, epidemiology, social sciences, and clinical research, to provide a comprehensive understanding of exposome.</p> Signup and view all the answers

<p>To capture a wide range of environmental pollutants, track physical activity or physiological measures, and monitor location through GPS technology.</p> Signup and view all the answers

<p>To capture psychosocial stress and other relevant information.</p> Signup and view all the answers

<p>Omics sciences, such as genomics, transcriptomics, proteomics, and metabolomics, are used to analyze the biological responses to environmental exposures.</p> Signup and view all the answers

<p>It helps in assessing internal exposure to chemicals and their metabolites, and relates them to health outcomes.</p> Signup and view all the answers

<p>Epidemiological research methods are used to study the relationships between environmental exposures and health outcomes.</p> Signup and view all the answers

<p>To track and assess the levels of environmental pollutants and their impact on human health.</p> Signup and view all the answers

<p>PBDEs (Poly Brominated Diphenyl Ethers), PCBs (Poly Chlorinated Biphenyls), and OCPs (OrganoChlorine Pesticides)</p> Signup and view all the answers

<p>To measure the exposure of chemicals and their effects on human health</p> Signup and view all the answers

<p>It helps in understanding the impact of prenatal and early life exposures on child development and health outcomes.</p> Signup and view all the answers

<p>Not specified in the provided content</p> Signup and view all the answers

<p>To identify the sources and classes of compounds to which humans are exposed</p> Signup and view all the answers

<p>The process by which the body converts chemicals into other forms, and it's important to understand how chemicals are taken up and undergo biotransformation</p> Signup and view all the answers

<p>Not specified in the provided content</p> Signup and view all the answers

<p>To measure the levels of chemicals in human samples accurately</p> Signup and view all the answers

<p>Programmes in NL, Europe, and worldwide</p> Signup and view all the answers

<p>PFOS and PFOA</p> Signup and view all the answers

<p>LINC is a cohort that provides data on perinatal exposure to environmental pollutants and their effects on health outcomes.</p> Signup and view all the answers

<p>The NHANES survey is a continuous program that examines a nationally representative sample of persons to meet emerging health and nutrition needs.</p> Signup and view all the answers

<p>Human biomonitoring is used to measure the exposure of individuals to environmental pollutants and their effects on health outcomes.</p> Signup and view all the answers

<p>Perfluorinated compounds are known to disrupt the endocrine system, leading to various health effects, including obesity and reproductive problems.</p> Signup and view all the answers

<p>The OBELIX project is a research initiative that aims to study the effects of environmental pollutants on human health outcomes.</p> Signup and view all the answers

<p>Breast milk and cord blood are used as biomarkers to measure the exposure of infants to environmental pollutants.</p> Signup and view all the answers

<p>Epidemiological research methods are used to study the correlations between environmental exposures and health outcomes, providing valuable insights for policy-making and public health interventions.</p> Signup and view all the answers

<p>Reactive substances induce carcinogenesis through oxidative stress, leading to DNA damage and mutations, which can ultimately result in cancer.</p> Signup and view all the answers

<p>Intercalating agents, like benzo[a]pyrene, insert themselves between DNA base pairs, causing distortions in the DNA structure and leading to mutations during DNA replication.</p> Signup and view all the answers

<p>Oxidative stress promotes the proliferation of initiated cells, leading to the expansion of mutated cell populations, and ultimately contributing to tumor formation.</p> Signup and view all the answers

<p>Benzo[a]pyrene is metabolized by cytochrome P450 enzymes to form reactive epoxide intermediates, which can bind to DNA and induce mutations.</p> Signup and view all the answers

<p>DNA methylation can silence tumor suppressor genes, leading to the inactivation of cellular defense mechanisms and contributing to tumorigenesis.</p> Signup and view all the answers

<p>A change in the reading frame of the genetic code, leading to a completely different amino acid sequence.</p> Signup and view all the answers

<p>Polycyclic aromatic hydrocarbons, like benzo[a]pyrene, are metabolized to form reactive intermediates that can bind to DNA, leading to mutations and initiating carcinogenesis.</p> Signup and view all the answers

<p>Oxidative stress can promote genetic instability, leading to the accumulation of additional mutations and the progression of tumors.</p> Signup and view all the answers

<p>Acridine causes insertions or deletions of bases in a DNA sequence, leading to frame-shift mutations.</p> Signup and view all the answers

<p>Mutagenic compounds, like benzo[a]pyrene, induce genetic instability by causing DNA damage and mutations, leading to the inactivation of tumor suppressor genes and the activation of oncogenes.</p> Signup and view all the answers