Fish acute toxicity syndrome

Last updated
Fish acute toxicity syndrome
Specialty Veterinary medicine

Fish acute toxicity syndrome (FATS) is a set of common chemical and functional responses in fish resulting from a short-term, acute exposure to a lethal concentration of a toxicant, a chemical or material that can produce an unfavorable effect in a living organism. [1] By definition, modes of action are characterized by FATS because the combination of common responses that represent each fish acute toxicity syndrome characterize an adverse biological effect. [1] Therefore, toxicants that have the same mode of action elicit similar sets of responses in the organism and can be classified by the same fish acute toxicity syndrome.

Contents

Background

During the 1970s, large-scale production of chemicals dramatically increased initiating new legislation to appease public concern about potential harmful effects. [2] After implementation of the Toxic Substances Control Act in 1977, the US Environmental Protection Agency (USEPA) required chemicals, new and existing, to be assessed for risks to human health and ecological systems. [3] Since thousands of new chemicals are registered a year, [2] it is important to utilize a screening technique that predicts toxicity of chemicals in a consistent, efficient manner. [3] As a result, researchers in the field of toxicology focused on the development of QSAR models as a means of assessing toxic effects of chemicals in fish. [2]

In toxicology, the quantitative structure-activity relationship (QSAR) approach is a method for predicting toxicity based on the properties and structure of a toxicant. [3] This method has been developed under the assumption that a group of chemicals, with similar structural components, will result in similar toxic effects due to having the same activity, or mode of action. [2] [3] In other words, the toxicity of a chemical is directly related to the chemical's structure. Therefore, QSAR are used to create predictive computer programs and models to correlate structure and activity of chemicals. [4] Overall, the objective is to aid in toxicology by providing databases and predictive models for classifying toxicants by modes of action as well as estimate acute toxicity of a chemical. [5] To utilize the QSAR approach, researchers need to establish a pool of variables to be considered in this modelling process. [2] QSAR models are differentiated by groups of chemicals characterized by a common mode of action. [5] However, limited data is available on defined relationships between toxic responses and chemicals with known modes of action. [4] Consequently, toxicologists have focused on the development of FATS to define these responses to better predict modes of action. [4] This approach focuses on grouping chemical and functional responses in a manner so that individual chemicals with known modes of action can be separated into specific FATS. [3] Overall, FATS aid QSAR models by providing a systematic way of defining and predicting modes of action. [3]

Determination

In 1987, McKim and colleagues began a series of experiments to characterize FATS. These experiments involved whole-fish in vivo analyses. [3] The animals used in these experiments were Rainbow trout (Oncorhynchus mykiss formerly known as Salmo gairdneri). [3] The fish underwent surgery prior to the exposure to implant respiratory and cardiovascular monitoring devices, and immobilize them. [3] During the experiment, the fish were kept in a Plexiglas respiratory-metabolism chamber, which was filled with Lake Superior water. [3] Water temperature was maintained for the duration of the experiments, and other water quality parameters (pH, total hardness, alkalinity, and acidity) were recorded once. [3]

The toxicants used in these experiments were chosen because they had a known mode of action. [3] The only exception to this was the narcotics. McKim et al. and Bradbury et al. used compounds known to be narcotics, and with a discriminant function analysis Bradbury et al. and colleagues identified two separate narcosis syndromes, I and II, which correspond to nonpolar and polar narcotics, respectively. [3] [5] By using compounds with known modes of action, these scientists could develop sets of respiratory-cardiovascular responses unique to a particular mode of action.

In the first experiment, two narcotics, tricaine methanesulfonate and 1-octanol, and two uncouplers of oxidative phosphorylation, pentachlorophenol and 2,4-dinitrophenol, were used. [3] During the second experiment, acetylcholinesterase inhibitors and respiratory irritants were evaluated. The acetylcholinesterase inhibitors were an organophosphate, Malathion and a carbamate, Carbaryl. [4] The respiratory irritants were Acrolein and Benzaldehyde. [4] In part three of the experiment series, polar narcotics phenol, 2,4-dimethylphenol, aniline, 2-chloroaniline and 4-chloroaniline were evaluated. [5] In the last experiment, central nervous system seizure agents were analyzed. These included an acetylcholinesterase inhibitor, Chlorpyrifos; two pyrethroid insecticides, Fenvalerate and Cypermethrin; two cyclodiene insecticides, Endrin and Endosulfan; and a rodenticide, Strychnine. [6] The duration of the exposure depended on the experiment, but the range was from 24 to 48 hours. [3] Therefore, exposure resulted in acute toxicity. [3] The Rainbow trout were exposed to a 24- to 48-hour lethal concentration of the toxicant. The respiratory and cardiovascular responses monitored throughout the exposure were cough rate, ventilation rate, ventilation volume, total oxygen consumption, oxygen utilization, heart rate, arterial blood pressure, arterial blood oxygen, arterial blood carbon dioxide, arterial blood pH, hematocrit, hemoglobin, electrocardiogram, plasma ions (calcium, magnesium, potassium, sodium, and chloride), and osmolality. [3] Pre-dose values were obtained prior to the exposure. [3] The responses were measured at two-hour intervals throughout the exposure, except for blood parameters, which were measured every four to eight hours, and blood ions, which were measured just before death. [3]

Using the results of the experiment, each toxicant was then characterized by a set of respiratory-cardiovascular responses. Statistical analyses were used to determine significant differences in responses between toxicants with different modes of action. [3] Finally, because each toxicant had a known mode of action, the set of responses characterized the mode of action. [3]

Types

Nonspecific

Narcosis

  • Narcosis [5] [7] [8] [9] Narcosis refers to the general depression of biological activity from exposure to a nonspecifically acting toxicant. [1] Toxicants that induce narcosis are known as narcotics or anesthetics. [5] Alcohol is an example of a narcotic and can result in intoxication, a form of narcosis. [1] Using the FATS approach, researchers are able to predict toxicity by assessing responses elicited by narcotics. [5]

Narcotics are a diverse group of chemicals including: inert gases, aliphatic and aromatic hydrocarbons, chlorinated hydrocarbons, alcohols, ethers, ketones, aldehydes, weak acids and bases, and aliphatic nitro compounds. [5] Although narcosis can be induced by a wide range of chemical agents, there are a few chemicals that are not considered narcotics. This includes chemicals that: form irreversible bonds by electrophilic reaction; are metabolically activated by electrophiles; form Schiff bases with amino groups; and any type of a Michael acceptor. [7] In general, narcotics are non-reactive. [7] [9]

Many organic chemicals in high enough concentrations induce narcotic symptoms. [1] [7] Thus, most toxicants can be considered narcotics. Baseline toxicity, or lowest toxicity is often used to refer to narcosis because this mode of action is considered the minimal effect. [1] [7] QSAR models are often used to predict minimum or baseline toxicity of chemicals acting through nonspecific mechanisms. [5] [7]

Mechanisms of action

Narcosis is a reversible state that is considered nonspecific because a single mechanism of action has yet to be established. [5] [7] [8] Although the mechanisms of narcosis remain unclear, current theories suggest that narcosis is associated with altered structure and function of cell membranes. [1] [9] The Critical-Volume Hypothesis theorizes that symptoms of narcosis are due to the toxicant dissolving in the lipid component of a cell membrane. [1] This results in an increased volume of cell membranes and consequently, altered membrane structure and function. [1] The Protein Binding Theory suggests that a narcotic binds to receptors on the hydrophobic region of cellular membrane proteins. [1] [7] In both theories, the cell membranes are targeted by narcotics resulting in decreased functionality, narcosis.

Symptoms

General responses to narcotics include: lethargy, unconsciousness, and overall depression in respiratory-cardiovascular activity. [5] [7] [9] Narcosis can result in death by nonspecific, sustained symptoms. [7] In the final phases of narcosis, McKim and colleagues [3] observed tissue hypoxia, generalized loss of respiratory-cardiovascular function and ultimately, respiratory paralysis. For example, rainbow trout exposed to two narcotics, MS-222 and 1-octanol exhibited a variety of respiratory-cardiovascular responses. [3] The narcotic symptoms included: loss of reaction to external stimuli, loss of equilibrium, decline in respiratory rate and medullary collapse. [3]

Narcosis I and narcosis II

Studies have suggested that two distinct modes of action exist for narcosis: narcosis I and narcosis II. [5] [7] [8] [9] Narcosis I is induced by nonpolar compounds while narcosis II relates to polar compounds. [5] If polar and nonpolar narcotics induced the same effects, baseline-narcosis models should be able to accurately predict toxicity for both groups of chemicals. However, polar compounds have exhibited greater toxicity than predicted by baseline toxicity models. [5] This difference in toxicity between nonpolar and polar narcotics supports the theory that two separate mechanisms of action exist for the different modes of narcosis. [5]

Based on the QSAR approach, differences in the chemical structure can be used to predict the activity of toxicants. [2] The polarity of toxicants can be used to differentiate narcotic modes of action into the two groups: narcosis I and narcosis II. In narcosis I, nonpolar chemicals induced generalized depression of respiratory-cardiovascular responses. [5] I narcosis II, polar chemicals first result in increased activity. [5] The unique response of narcosis II is supported by research conducted on rainbow trout. When exposed to polar narcotics, rainbow trout first exhibited increased muscular activity followed by incoordination and unresponsiveness to external stimuli. [5]

In general, narcosis II is characterized by greater toxicity than narcosis I. [7] Thus, Baseline-narcosis models should be used for predicting the toxicity of nonpolar narcotics. In addition, narcosis I is the generalized depression of biological activity. [5] [7] In contrast, narcosis II symptoms include stimulation of respiratory-cardiovascular responses followed by generalized depression of activity. [5]

Specific

A toxicant which exhibits a specific mode of action binds to a site on a particular biological molecule thereby altering or inhibiting a biological process. [1] In comparison, a toxicant that exhibits non-specific action, also referred to as a narcotic, simply depresses biological activity by unknown means. [1] Scientists are still unsure what site(s) a narcotic binds to, and the biochemical responses that result. [1] Specific action is unique in comparison to non-specific in that relatively lower amounts of toxicant are needed to elicit a response. [1] Because lower concentrations of toxicant are need to elicit a response, specific modes of action are usually seen before non-specific modes of action. Ultimately, with high enough concentrations though, most toxicants are narcotic (demonstrate non-specific modes of action). [1]

There are a variety of specific-action FATS which have been studied and documented. These include acetylcholinesterase (AChE) inhibitors, respiratory irritants, respiratory blockers, dioxin, central nervous system seizure agents, and uncouplers of oxidative phosphorylation. Acetylcholinesterase, an enzyme which degrades acetylcholine an important neurotransmitter, has been demonstrated to be inhibited by particular toxicants like organophosphates and carbamates. [10] Respiratory irritants bind to respiratory tissue membranes, which are the first tissue membranes available for exposure. [6] Respiratory blockers are known to affect the electron transport chain in the mitochondria of cells. [12] Central Nervous System seizure agents are associated with effects such as partial or whole body seizures and coughing. [6] Dioxin is recognized as having a different mode of action than the others, but has not been studied by the FATS method. [1]

Uncouplers of oxidative phosphorylation

Uncouplers of oxidative phosphorylation are specifically acting toxicants. [3] Oxidative phosphorylation is a coupling reaction in which ATP is synthesized from phosphate groups using energy obtained from the oxidation-reduction reactions in the mitochondrial electron transport chain. [11] ATP production is very important because it is essentially the energy currency in biological systems. [11] Under normal circumstances, oxidation-reduction reactions in the mitochondrial electron transport chain produce energy. [11] This energy is used to shuttle protons across the inner mitochondrial membrane, from the mitochondrial matrix into the inner membrane space. [11] This creates a pH gradient where conditions are acidic (i.e. higher concentrations of protons) in the inner membrane space, and more basic (i.e. low concentrations of protons) in the mitochondrial matrix. [11] Due to this gradient, protons pass through ATPase, a protein embedded in the inner mitochondrial membrane, down their concentration gradient, into the mitochondrial matrix driving the production of ATP. [11]

Uncouplers of oxidative phosphorylation disrupt the production of ATP. [11] They do so by binding to the protons in the inner membrane space, and shuttling them into the mitochondrial matrix [11] Therefore, the chemical gradient which drives ATP synthesis is broken down and energy production slows. [11] Oxygen consumption increases to counteract the effects of low ATP production. [3] Also, lactic acid concentrations increase as tissues are switching to anaerobic metabolism which poisons the mitochondria. [3]

Cardiovascular-respiratory responses associated with exposure to uncouplers of oxidative phosphorylation, as determined by the FATS experiment, are the following. Overall, metabolic rate increased so rapid and continuous increases in ventilation volume and oxygen consumption was observed. [3] However, changes in ventilation rate or oxygen utilization were not been observed. [3] This means the fish increased water flow across their gills, but oxygen removal from the water was maintained at a constant rate. However, oxygen consumption increased in the mitochondrial electron transport chain, in an attempt to reproduce the proton gradient and stimulate ATP production. [3] However, the toxicant continued to break down the proton gradient, inevitably leading to mortality.

Applications

As mentioned previously, FATS have been used to establish models that predict toxicity of chemicals. [13] For instance, FATS data is used to develop quantitative structure-activity relationship (QSAR) models. [5] QSAR models developed using FATS data are then used to establish computer based systems that predict toxicity. For example, Russom and colleagues used Fathead Minnow (Pimephales promelas) 96-hour acute toxicity tests data, FATS data and QSARs to create a computer based expert system that predicts chemical toxicity based on chemical structures and properties. [13] These models and systems are useful for screening chemicals to prioritize more toxic substances for further toxicity testing. [6] This is particularly useful for industrial chemicals with unknown toxicity. This due to the quantity of industrial chemicals with unknown toxicity, for which individual toxicity testing is not realistic. [3] In addition, models and computer systems that predict toxicity are also cost-effective in comparison to running toxicity tests on all unknown chemicals. [6] In conclusion, predictive screening techniques derived from FATS data are practical and cost efficient.

Related Research Articles

Oxidative phosphorylation The phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis.

Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.

Toxicity Degree of harmfulness of substances

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.

Chronic toxicity, the development of adverse effects as a result of long term exposure to a contaminant or other stressor, is an important aspect of aquatic toxicology. Adverse effects associated with chronic toxicity can be directly lethal but are more commonly sublethal, including changes in growth, reproduction, or behavior. Chronic toxicity is in contrast to acute toxicity, which occurs over a shorter period of time to higher concentrations. Various toxicity tests can be performed to assess the chronic toxicity of different contaminants, and usually last at least 10% of an organism's lifespan. Results of aquatic chronic toxicity tests can be used to determine water quality guidelines and regulations for protection of aquatic organisms.

2,4-Dinitrophenol Chemical compound

2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula HOC6H3(NO2)2. It is a yellow, crystalline solid that has a sweet, musty odor. It sublimes, is volatile with steam, and is soluble in most organic solvents as well as aqueous alkaline solutions. When in a dry form, it is a high explosive and has an instantaneous explosion hazard. It is a precursor to other chemicals and is biochemically active, uncoupling oxidative phosphorylation from the electron transport chain in cells with mitochondria, by allowing protons to pass from the intermembrane space into the mitochondrial matrix. Oxidative phosphorylation is a highly regulated step in aerobic respiration that is inhibited, among other factors, by normal cellular levels of ATP. Uncoupling it results in chemical energy from diet and energy stores such as triglycerides being wasted as heat with minimal regulation, leading to dangerously high body temperatures that may develop into heatstroke. Its use as a dieting aid has been identified with severe side-effects, including a number of deaths.

Aquatic toxicology

Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from subcellular through individual organisms to communities and ecosystems. Aquatic toxicology is a multidisciplinary field which integrates toxicology, aquatic ecology and aquatic chemistry.

Toxicokinetics is the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compound once it is in the body.

Antimycin A Chemical compound

Antimycin A is a secondary metabolite produced by Streptomyces bacteria and a member of a group of related compounds called antimycins. Antimycin A is classified as an extremely hazardous substance in the United States, as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act, and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.

Oligomycin Group of chemical compounds

Oligomycins are macrolides created by Streptomyces that can be poisonous to other organisms.

Mechanism of action of aspirin

Aspirin causes several different effects in the body, mainly the reduction of inflammation, analgesia, the prevention of clotting, and the reduction of fever. Much of this is believed to be due to decreased production of prostaglandins and TXA2. Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs, which are reversible inhibitors. However, other effects of aspirin, such as uncoupling oxidative phosphorylation in mitochondria, and the modulation of signaling through NF-κB, are also being investigated. Some of its effects are like those of salicylic acid, which is not an acetylating agent.

Dinoseb Chemical compound used as a herbicide

Dinoseb is a common industry name for 6-sec-butyl-2,4-dinitrophenol, a herbicide in the dinitrophenol family. It is a crystalline orange solid which does not readily dissolve in water. Dinoseb is banned as an herbicide in the European Union (EU) and the United States because of its toxicity.

Persistent, bioaccumulative and toxic substances (PBTs) are a class of compounds that have high resistance to degradation from abiotic and biotic factors, high mobility in the environment and high toxicity. Because of these factors PBTs have been observed to have a high order of bioaccumulation and biomagnification, very long retention times in various media, and widespread distribution across the globe. Majority of PBTs in the environment are either created through industry or are unintentional byproducts.

A mode of toxic action is a common set of physiological and behavioral signs that characterize a type of adverse biological response. A mode of action should not be confused with mechanism of action, which refer to the biochemical processes underlying a given mode of action. Modes of toxic action are important, widely used tools in ecotoxicology and aquatic toxicology because they classify toxicants or pollutants according to their type of toxic action. There are two major types of modes of toxic action: non-specific acting toxicants and specific acting toxicants. Non-specific acting toxicants are those that produce narcosis, while specific acting toxicants are those that are non-narcotic and that produce a specific action at a specific target site.

Tissue residue is the concentration of a chemical or compound in an organism's tissue or in a portion of an organism's tissue. Tissue residue is used in aquatic toxicology to help determine the fate of chemicals in aquatic systems, bioaccumulation of a substance, or bioavailability of a substance, account for multiple routes of exposure, and address an organism's exposure to chemical mixtures. A tissue residue approach to toxicity testing is considered a more direct and less variable measure of chemical exposure and is less dependent on external environmental factors than measuring the concentration of a chemical in the exposure media.

Toxicodynamics, termed pharmacodynamics in pharmacology, describes the dynamic interactions of a toxicant with a biological target and its biological effects. A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other receptors. When a toxicant enters an organism, it can interact with these receptors and produce structural or functional alterations. The mechanism of action of the toxicant, as determined by a toxicant’s chemical properties, will determine what receptors are targeted and the overall toxic effect at the cellular level and organismal level.

Pre-spawn mortality is a phenomenon where adult coho salmon, Oncorhynchus kisutch, die before spawning when returning to freshwater streams to spawn. It is also known as Urban Runoff Mortality Syndrome in more recent studies. This occurrence has been observed in much of the Puget Sound region of the Pacific Northwest. During fall migration, salmonids pass through urban watersheds which are contaminated with stormwater runoff. As the coho salmon pass through these waters, many will show symptoms of lethargy, loss of equilibrium and disorientation, and die within a few hours of showing these symptoms. These symptoms and behaviors are prevalent after rain events. Mortality often occurs before salmon have the opportunity to spawn, which is determined by cutting open female carcasses and observing for unfertilized eggs. Rates of pre-spawn mortality could impact the local salmon populations. Based on model projections, if rates continue, populations of coho salmon could become extinct within the next few decades.

The olfactory system is the system related to the sense of smell (olfaction). Many fish activities are dependent on olfaction, such as: mating, discriminating kin, avoiding predators, locating food, contaminant avoidance, imprinting and homing. These activities are referred to as “olfactory-mediated.” Impairment of the olfactory system threatens survival and has been used as an ecologically relevant sub-lethal toxicological endpoint for fish within studies. Olfactory information is received by sensory neurons, like the olfactory nerve, that are in a covered cavity separated from the aquatic environment by mucus. Since they are in almost direct contact with the surrounding environment, these neurons are vulnerable to environmental changes. Fish can detect natural chemical cues in aquatic environments at concentrations as low as parts per billion (ppb) or parts per trillion (ppt).

Fluazinam Chemical compound

Fluazinam is a broad-spectrum fungicide used in agriculture. It is classed as a diarylamine and more specifically an arylaminopyridine. Its chemical name is 3-chloro-N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoromethyl-2-pyridinamine. The mode of action involves the compound being an extremely potent uncoupler of oxidative phosphorylation in mitochondria and also having high reactivity with thiols. It is unique amongst uncouplers in displaying broad-spectrum activity against fungi and also very low toxicity to mammals due to it being rapidly metabolised to a compound without uncoupling activity. It was first described in 1992 and was developed by researchers at the Japanese company Ishihara Sangyo Kaisha.

Occupational toxicology is the application of toxicology to chemical hazards in the workplace. It focuses on substances and conditions that occur in workplaces, where inhalation exposure and dermal exposure are most important, there is often exposure to mixtures of chemicals whose interactions are complex, health effects are influenced or confounded by other environmental and individual factors, and there is a focus on identifying early adverse affects that are more subtle than those presented in clinical medicine.

The acute to chronic ratio (ACR) uses acute toxicity data to gauge the chronic toxicity (MATC) of a chemical of interest to an organism. The science behind determining a safe concentration to the environment is imperfect, statistically limited, and resource intensive. There is an unfilled demand for the rapid assessment of different chemical toxicity to many different organisms. The ACR is a proposed solution to this demand.

Toxic units (TU) are used in the field of toxicology to quantify the interactions of toxicants in binary mixtures of chemicals. A toxic unit for a given compound is based on the concentration at which there is a 50% effect for a certain biological endpoint. One toxic unit is equal to the EC50 for a given endpoint for a specific biological effect over a given amount of time. Toxic units allow for the comparison of the individual toxicities of a binary mixture to the combined toxicity. This allows researchers to categorize mixtures as additive, synergistic or antagonistic. Synergism and antagonism are defined by mixtures that are more or less toxic than predicted by the sum of their toxic units.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Rand GM (1995). Fundamentals of Aquatic Toxicology: Effects, Environmental Fate, and Risk Assessment (2nd ed.). Boca Raton: CRC Press. pp. 50–53. ISBN   1-56032-091-5.
  2. 1 2 3 4 5 6 Kaiser KLE (March 2003). "The use of neural networks in QSARs for acute aquatic toxicological endpoints". Journal of Molecular Structure: THEOCHEM. 622 (1–2): 85–95. doi:10.1016/S0166-1280(02)00620-6.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 McKim JM, Schmieder PK, Carlson RW, Hunt EP (April 1987). "Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1, Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol". Environmental Toxicology and Chemistry. 6 (4): 295–312. doi:10.1002/etc.5620060407.
  4. 1 2 3 4 5 McKim JM, Schmieder PK, Niemi GJ, Carlson RW, Henry TR (April 1987). "Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 2, Malathion, Carbaryl, Acrolein and Benzaldehyde". Environmental Toxicology and Chemistry. 6 (4): 313–328. doi:10.1002/etc.5620060408.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Bradbury SP, Carlson RW, Henry TR (1989). "Polar Narcosis in Aquatic Organisms". In Williams LR, Cowgill UM (eds.). Aquatic toxicology and hazard assessment. Vol. 12. Philadelphia: American Society for Testing and Materials. pp. 59–73. ISBN   0-8031-1253-X.
  6. 1 2 3 4 5 6 7 Bradbury SP, Carlson RW, Niemi GJ, Henry TR (January 1991). "Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Oncorynchus Mykiss) in Identifying Acute Toxicity Syndromes in Fish. 4. Central Nervous System Seizure Agent". Environmental Toxicology and Chemistry. 10 (1): 115–131. doi:10.1002/etc.5620100113.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 Veith GD, Broderius SJ (July 1990). "Rules for distinguishing toxicants that cause type I and type II narcosis syndromes". Environ. Health Perspect. 87: 207–11. doi:10.1289/ehp.9087207. PMC   1567847 . PMID   2269227.
  8. 1 2 3 Netzeva TI, Pavan M, Worth AP (January 2008). "Review of (Quantitative) Structure–Activity Relationships for Acute Aquatic Toxicity". QSAR & Combinatorial Science. 27 (1): 77–90. doi:10.1002/qsar.200710099.
  9. 1 2 3 4 5 Schultz TW (1989). "Nonpolar Narcosis: A review of the mechanism of action for baseline aquatic toxicity.". In Williams LR, Cowgill UM (eds.). Aquatic toxicology and hazard assessment. Vol. 12. Philadelphia: American Society for Testing and Materials. pp. 104–109. ISBN   0-8031-1253-X.
  10. 1 2 3 4 5 6 Fukuto TR (July 1990). "Mechanism of action of organophosphorus and carbamate insecticides". Environ. Health Perspect. 87: 245–54. doi:10.1289/ehp.9087245. PMC   1567830 . PMID   2176588.
  11. 1 2 3 4 5 6 7 8 9 10 Terada H (July 1990). "Uncouplers of oxidative phosphorylation". Environ. Health Perspect. 87: 213–8. doi:10.1289/ehp.9087213. PMC   1567840 . PMID   2176586.
  12. 1 2 Stannard JN, Horecker BL (February 1948). "The in vitro inhibition of cytochrome oxidase by azide and cyanide". J. Biol. Chem. 172 (2): 599–608. PMID   18901179.
  13. 1 2 Russom CL, Bradbury SP, Broderius SJ, Hammermeister DE, Drummond RA (May 1997). "Predicting Modes of Toxic Action From Chemical Structure: Acute Toxicity in the Fathead Minnow (Pimephales Promelas)" (PDF). Environmental Toxicology and Chemistry. 16 (5): 948–967. doi:10.1002/etc.5620160514.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.