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Ernest Hodgson - One of the best experts on this subject based on the ideXlab platform.

  • Biotransformation (Metabolism) of Pesticides
    Pesticide Biotransformation and Disposition, 2012
    Co-Authors: Ernest Hodgson
    Abstract:

    This chapter provides an extensive summary of phase I and phase II Metabolism of Pesticides with particular reference to Metabolism in the liver and extrahepatic tissues of mammals, the latter including lung, nasal tissues, skin, kidney, and the central nervous system. Detailed information is presented on human Metabolism of Pesticides. Information is also included on physiological factors affecting Metabolism such as development, age, and gender, as well as variation between individuals and within strains and species, and on the toxicity of metabolites. Tolerance and resistance to Pesticides are also briefly considered.

  • Metabolism of Pesticides
    Hayes' Handbook of Pesticide Toxicology, 2010
    Co-Authors: Ernest Hodgson
    Abstract:

    Publisher Summary This chapter focuses on biotransformation as it applies to Pesticides. The enzymes involved in biotransformation are frequently referred to as xenobiotic-metabolizing enzymes, XMEs. The word Metabolism may also be used to designate the effect of an organism, through its enzymes, on the chemical structure of foreign compounds now more often referred to as xenobiotics. Knowledge of the Metabolism of Pesticides is essential for several reasons, including the development of more selective insecticides, and provides, in part, the fundamental basis for science-based risk assessments for human and environmental health. Until recently, and as a matter of necessity, this research was carried out almost exclusively on experimental animals and the results, particularly in the case of human health risk assessments, extrapolated to humans. At the same time, studies utilizing surrogate animals will also be revolutionized by such new techniques of molecular biology as the use of knockout and transgenic including “humanized” mice, and the knowledge of the genomes of many species. These same techniques through the study of genetic polymorphisms will enable us to identify human populations at increased risk and enable comparative studies to be carried out at the level of specific isoforms of the XMEs involved.

  • Metabolic Interactions of Pesticides
    Hayes' Handbook of Pesticide Toxicology, 2010
    Co-Authors: Ernest Hodgson
    Abstract:

    Publisher Summary This chapter illustrates the interactions of Pesticides, which act as either enzyme inducers or inhibitors, affecting the Metabolism of other xenobiotics, such as drugs, as well as the Metabolism of endogenous compounds, such as steroid hormones. Knowledge of the Metabolism of Pesticides is essential and further knowledge is still needed for several reasons, including the development of more selective insecticides and for providing, in part, the fundamental basis for science-based risk assessments for human and environmental health. Until relatively recently, and as a matter of necessity, this research was carried out almost exclusively on experimental animals, and the results, particularly in the case of human health risk assessments, were extrapolated to humans. Although the mechanisms of enzyme inhibition and induction are investigated by a variety of biochemical and molecular biological techniques, it is important, for consideration of the implications of these phenomena in human health risk assessment, to demonstrate them in vivo. Molecular techniques also permit the study of genetic polymorphisms that will enable the identification of populations at increased risk and allow studies to be carried out at the level of specific isoforms of the XMEs involved. The interaction of Pesticides and clinical drugs, although long a subject for speculation, has been the subject of little investigation.

  • CHAPTER 23 – Metabolism of Pesticides
    Handbook of Pesticide Toxicology, 2001
    Co-Authors: Ernest Hodgson, E. Levi Patricia
    Abstract:

    This chapter focuses on the Metabolism or biotransformation of xenobiotics, especially Pesticides. The Metabolism of xenobiotics generally occurs in two phases. Phase I involves predominantly oxidations, reductions, and hydrolyses, and serves to introduce a polar group into the molecule. Phase II, consisting primarily of conjugation reactions, involves the combination of the products of phase I reactions with one of several endogenous molecules to form water soluble, and hence excretable, products. In the past, the most emphasis has been placed microsomal cytochrome P450 (P450)-dependent oxidations and reductions of Pesticides, and they are described in detail in this chapter. With the exception of glutathione conjugation, phase II conjugation reactions involving Pesticides are secondary, involving, as substrates, the products of phase I reactions. They include glutathione conjugation, glucoside formation, glucuronic acid formation, sulfate formation, and conjugation with amino acids. This chapter describes various factors affecting the Metabolism of xenobiotics, including species differences due to differences in activity of liver microsomal enzymes, gender of the organism, polymorphisms in the expression of the xenobiotic metabolizing enzymes. The terms resistance and tolerance refer to a relative insusceptibility of a population of organisms to the effects of a toxicant.

  • chapter 23 Metabolism of Pesticides
    Handbook of Pesticide Toxicology (Second Edition), 2001
    Co-Authors: Ernest Hodgson, Levi E Patricia
    Abstract:

    This chapter focuses on the Metabolism or biotransformation of xenobiotics, especially Pesticides. The Metabolism of xenobiotics generally occurs in two phases. Phase I involves predominantly oxidations, reductions, and hydrolyses, and serves to introduce a polar group into the molecule. Phase II, consisting primarily of conjugation reactions, involves the combination of the products of phase I reactions with one of several endogenous molecules to form water soluble, and hence excretable, products. In the past, the most emphasis has been placed microsomal cytochrome P450 (P450)-dependent oxidations and reductions of Pesticides, and they are described in detail in this chapter. With the exception of glutathione conjugation, phase II conjugation reactions involving Pesticides are secondary, involving, as substrates, the products of phase I reactions. They include glutathione conjugation, glucoside formation, glucuronic acid formation, sulfate formation, and conjugation with amino acids. This chapter describes various factors affecting the Metabolism of xenobiotics, including species differences due to differences in activity of liver microsomal enzymes, gender of the organism, polymorphisms in the expression of the xenobiotic metabolizing enzymes. The terms resistance and tolerance refer to a relative insusceptibility of a population of organisms to the effects of a toxicant.

Patricia E. Levi - One of the best experts on this subject based on the ideXlab platform.

  • Pesticides: an important but underused model for the environmental health sciences.
    Environmental Health Perspectives, 1996
    Co-Authors: Ernest Hodgson, Patricia E. Levi
    Abstract:

    Pesticides are high-volume, widely used, environmental chemicals and there is continuous debate concerning their possible role in many chronic human health effects. Because of their known structures, known rates of application, and the presence of a large occupationally exposed population, they are not only important in their own right but are ideal models for the effects of environmental chemicals on the population in general. For reasons that are not always clear, this potential has not been realized. These exposed populations represent an underused asset in the study of the human health effects of environmental contaminants. Chronic effects thought to involve Pesticides include carcinogenesis, neurotoxicity, and reproductive and development effects. In this paper we attempt to summarize this concern and, relying to a large extent on studies in our own laboratory, to indicate the importance and present status of studies of the mammalian Metabolism of Pesticides and indicate the need for further use of this model. Aspects considered include the role of Pesticides as substrates for xenobiotic-metabolizing enzymes such as cytochrome P450 and the flavin-containing monooxygenase and their role as inducers or inhibitors of metabolic enzymes. The interaction of Pesticides with complex multienzyme pathways, the role of biological characteristics, particularly gender, in pesticide Metabolism, and the special role of Pesticides at portals of entry and in target tissues are also considered.

  • Pesticide-metabolizing enzymes.
    Toxicology letters, 1995
    Co-Authors: Ernest Hodgson, Bonnie L. Blake, Randy L. Rose, Doug-young Ryu, G. Falls, Patricia E. Levi
    Abstract:

    Pesticides are known to function as substrates, inhibitors and inducers of drug-metabolizing enzymes, with the same compound frequently acting in more than one of these roles. Current studies of phase I Metabolism of Pesticides include cytochrome P450 (P450) and the flavin-containing monooxygenase (FMO), with particular reference to individual isozymes. In mouse liver, the level of FMO1 is gender dependent, FMO3 is gender specific, while FMO5 appears to be gender independent. The isozyme specificity of methylenedioxyphenyl synergists for induction of P450 in mouse liver involves P450s 1A1, 1A2 and 2B10, including a non-Ah receptor-dependent mechanism for 1A2 induction. The substrate specificity of mouse and human P450 and FMO isozymes is discussed.

  • Enzymatic and immunohistochemical studies on the role of cytochrome P450 and the flavin-containing monooxygenase of mouse skin in the Metabolism of Pesticides and other xenobiotics
    Pesticide Biochemistry and Physiology, 1992
    Co-Authors: Krishnappa Venkatesh, Patricia E. Levi, Alfred O. Inman, Nancy A. Monteiro-riviere, Rama Misra, Ernest Hodgson
    Abstract:

    Abstract The cytochrome P450 (P450) content, the cytochrome c reductase activity, the Metabolism of a variety of P450 substrates, and the presence and role of flavin-containing monooxygenase (FMO) in xenobiotic Metabolism were studied in skin microsomes and compared to those of liver. The cytochrome P450 content of skin as determined by CO-dithionite-reduced minus CO-oxidized spectra was approximately 6.8% of the liver P450 content. By comparison, cytochrome c reductase activity in skin microsomes was high, being equivalent to approximately one-third of the liver microsomal enzyme activity. Skin microsomes metabolized several known P450 substrates and, depending upon the substrate used, the specific activity ranged from 2.5 to 13.4% of the corresponding rates seen in liver microsomes. Skin microsomes exhibited the highest enzymatic activity with benzo[ a ]pyrene and ethoxyresorufin, moderate activity with parathion and aldrin, and low activity with benzphetamine and ethoxycoumarin. Skin microsomes also metabolized the triazine herbicides atrazine, simazine, and terbutryn, with the activity being 2 to 5% of the liver microsomal activity. FMO activity in skin microsomes with thiobenzamide and methimazole as substrates ranged from 10 to 20% of the liver FMO activity. Immunohistochemical studies using antibodies to mouse liver FMO showed localization primarily in the epidermis. Additional studies using pig skin showed a similar distribution pattern. Antibodies developed to mouse liver FMO and the constitutive liver P450 isozyme, 1A2, showed cross-reactivity on Western blots with proteins in skin microsomes that appeared identical to the cross-reacting proteins present in liver microsomes. The relative contribution of P450 and FMO in mouse skin to the sulfoxidation of phorate was investigated and compared to that of liver microsomes. Several procedures were employed to selectively inhibit either P450 or FMO to determine the role of each monooxygenase system in the absence of the other system. In liver microsomes, P450 was responsible for 68 to 85% of the phorate sulfoxidation activity. In contrast, in skin microsomes 66 to 69% of the phorate sulfoxidation activity was due to FMO, while P450 was responsible for the remainder of the activity. Thus, although the overall phorate sulfoxidation rate in mouse skin microsomes was only 3 to 4% of the rate seen in liver, FMO appears to assume a greater relative role to P450 in the metabolic processes in skin.

Patricia Cardoso - One of the best experts on this subject based on the ideXlab platform.

  • Uptake and depuration kinetics of dicofol metabolite 4,4'-dichlorobenzophenone, in the edible Asiatic clam Meretrix meretrix.
    Chemosphere, 2019
    Co-Authors: Lucia Ivorra, Catarina Cruzeiro, Shek Kiu Chan, Karen Arano Tagulao, Patricia Cardoso
    Abstract:

    Abstract Uptake and depuration kinetics of 4,4′-dichlorobenzophenone (main metabolite of dicofol) in the edible clam Meretrix meretrix were evaluated through a mesocosm experiment. M. meretrix was exposed to different dicofol concentrations (environmental concentration, D1 = 50 ng/L; supra-environmental concentration, D2 = 500 ng/L) for 15 days, followed by the same depuration period. To accomplish this goal, an analytical method was successfully optimized for 4,4′-DCBP using QuEChERS as extraction method with a range of concentrations 0.3–76.8 ng/g ww quantified by gas chromatography coupled to tandem mass spectrometry. Our results demonstrated different kinetics of accumulation depending on the two dicofol treatments. For D1, the uptake kinetic was best fitted using a plateau followed by one phase association kinetic model, while for D2 a one phase association kinetic model suited better. Similar bioconcentration factors were obtained for both concentrations but only animals exposed to D2, showed 4,4′-DCBP levels above the limits of quantification after 24 h exposure. These animals also showed lower uptake rate (ku) than organisms exposed to D1. During the depuration period, only organisms exposed to D1 successfully depurated after 24 h. On the other hand, although animals exposed to D2 presented higher elimination factor, they did not reach the original levels after depuration. Moreover, values detected in these clams were higher than the Maximum Residue Level (10 ng/g) established by the European legislation. This indicates that longer periods of depuration time than the ones used in this study, may be needed in order to reach safe levels for human consumption. This work also demonstrated that studies on metabolite kinetics during uptake/depuration experiments, could be a new alternative to understand the impact and Metabolism of Pesticides in the marine environment.

Lucia Ivorra - One of the best experts on this subject based on the ideXlab platform.

  • Uptake and depuration kinetics of dicofol metabolite 4,4'-dichlorobenzophenone, in the edible Asiatic clam Meretrix meretrix.
    Chemosphere, 2019
    Co-Authors: Lucia Ivorra, Catarina Cruzeiro, Shek Kiu Chan, Karen Arano Tagulao, Patricia Cardoso
    Abstract:

    Abstract Uptake and depuration kinetics of 4,4′-dichlorobenzophenone (main metabolite of dicofol) in the edible clam Meretrix meretrix were evaluated through a mesocosm experiment. M. meretrix was exposed to different dicofol concentrations (environmental concentration, D1 = 50 ng/L; supra-environmental concentration, D2 = 500 ng/L) for 15 days, followed by the same depuration period. To accomplish this goal, an analytical method was successfully optimized for 4,4′-DCBP using QuEChERS as extraction method with a range of concentrations 0.3–76.8 ng/g ww quantified by gas chromatography coupled to tandem mass spectrometry. Our results demonstrated different kinetics of accumulation depending on the two dicofol treatments. For D1, the uptake kinetic was best fitted using a plateau followed by one phase association kinetic model, while for D2 a one phase association kinetic model suited better. Similar bioconcentration factors were obtained for both concentrations but only animals exposed to D2, showed 4,4′-DCBP levels above the limits of quantification after 24 h exposure. These animals also showed lower uptake rate (ku) than organisms exposed to D1. During the depuration period, only organisms exposed to D1 successfully depurated after 24 h. On the other hand, although animals exposed to D2 presented higher elimination factor, they did not reach the original levels after depuration. Moreover, values detected in these clams were higher than the Maximum Residue Level (10 ng/g) established by the European legislation. This indicates that longer periods of depuration time than the ones used in this study, may be needed in order to reach safe levels for human consumption. This work also demonstrated that studies on metabolite kinetics during uptake/depuration experiments, could be a new alternative to understand the impact and Metabolism of Pesticides in the marine environment.

Toshiyuki Katagi - One of the best experts on this subject based on the ideXlab platform.

  • Theoretical and organic chemical approaches to environmental behavior and Metabolism of Pesticides.
    Journal of pesticide science, 2020
    Co-Authors: Toshiyuki Katagi
    Abstract:

    Investigation of the dissipation and transformation of pesticide through laboratory experiments, conducted in accordance with standard and newly developed designs, gives us valuable information to understand their environmental behavior. We have also been investigating the mechanisms of partition and transformation reactions of Pesticides, not only through kinetic analyses, but also through theoretical approaches based on their molecular properties estimated using various spectroscopies and molecular orbital calculations. Furthermore, synthetic iron porphyrin with a peroxide was shown to be a good model to simulate the P450-catalyzed oxidation in the Metabolism of Pesticides. Through these investigations, the knowledge of surface water, soil, sediment, and plants, such as their properties and constituents, was found indispensable to a deep understanding of the mechanism in the hydrolysis, photolysis, and Metabolism of Pesticides.

  • In vitro Metabolism of Pesticides and industrial chemicals in fish.
    Journal of pesticide science, 2020
    Co-Authors: Toshiyuki Katagi
    Abstract:

    Metabolism is one of the most important factors in controlling the toxicity and bioaccumulation of Pesticides in fish. In vitro systems using subcellular fractions, cell lines, hepatocytes and tissues of a specific organ, each of which is characterized by usability, enzyme activity and chemical transport via membrane, have been applied to investigate the metabolic profiles of Pesticides. Not only species and organs but also the fishkeeping conditions are known to greatly affect the in vitro Metabolism of Pesticides. A comparison of the metabolic profiles of Pesticides and industrial chemicals taken under similar conditions has shown that in vitro systems using a subcellular S9 fraction and hepatocytes qualitatively reproduce many in vivo metabolic reactions. More investigation of these in vitro systems for Pesticides is necessary to verify their applicability to the estimation of pesticide Metabolism in fish.

  • Bioconcentration and Metabolism of Pesticides and industrial chemicals in the frog
    Journal of Pesticide Science, 2014
    Co-Authors: Toshiyuki Katagi, Keiko Ose
    Abstract:

    Exposure to pesticide residues is claimed to be one of the possible causes of frog decline. Knowledge of basic information on the uptake, Metabolism and depuration processes of Pesticides in the frog is needed to understand the relationship between exposure and toxic effects from their actual body burden, together with their bioconcentration. The hydrophobicity of Pesticides and industrial chemicals was one of the most important factors controlling bioconcentration, similarly to fish, when frogs are exposed to contaminated water. Skin absorption was also a key route in the uptake process especially in the adult frog. The metabolic profiles in the frog, mainly examined by an intraperitoneal injection technique, were common to other aquatic species without any frog-specific transformation reaction. The effects of developmental stage, sex, species and environmental factors such as temperature were observed for bioconcentration and Metabolism. © Pesticide Science Society of Japan

  • bioconcentration bioaccumulation and Metabolism of Pesticides in aquatic organisms
    Reviews of Environmental Contamination and Toxicology, 2010
    Co-Authors: Toshiyuki Katagi
    Abstract:

    From the viewpoint of protecting the natural environment, aquatic ecotoxicological assessment of new Pesticides and many existing ones has increasingly become more important. To assess the impact of Pesticides on aquatic organisms, international authorities (utilizing OECD and USEPA testing guidelines) require completion of many acute and chronic ecotoxicological studies. Among such studies is testing to measure the potential for bioconcentration. In addition, the authorities in these agencies insist that physico-chemical properties and environmental fate be determined for each registered pesticide. The rationale for such testing is based on the concept that, even if used in conformance with good agricultural practices, Pesticides may enter surface waters by several routes such as spray drift, surface runoff, and field drainage, and they may be partitioned to bottom sediments (Katagi 2006). The endpoints of such ecotoxicological testing include mortality and effects on hatching, development, and reproduction. Such endpoints are usually expressed as median-lethal or median-effect concentrations (LC50 and EC50) and no-observed-effect-concentrations (NOEC); such values can be compared with predicted environmental concentrations in exposure media for purposes of risk assessment (Miyamoto et al. 2008). Because aquatic organisms interact with each other in the food web, knowledge of their tendency to bioconcentrate residues in water and from dietary exposure is important when evaluating real environmental pesticide effects. In general, bioconcentration is the most popular term for describing the process by which Pesticides enter organisms directly from water through the gills or through epithelial tissues. In contrast, bioaccumulation includes the effect of dietary uptake through food consumption or intake of bottom sediments (Miyamoto et al. 1990). When the levels of a pesticide, accumulated by organisms, are concentrated through two or more trophic levels in a food web, the process is referred to as biomagnification (Connell 1988).

  • Aerobic aquatic soil Metabolism of Pesticides in water- and sediment-spiked systems
    Journal of Pesticide Science, 2004
    Co-Authors: Rika Kodaka, Toshiyuki Katagi, Terumi Sugano, Manabu Tsuzuki, Yoshiyuki Takimoto
    Abstract:

    The Metabolism of fenitrothion and diethofencarb in aerobic aquatic soil was examined following either water or sediment application. The more hydrophobic fenitrothion rapidly distributed from water to sediment, while a more gradual adsorption of diethofencarb by sediment was observed with insignificant biodegradation. Release of diethofencarb from the spiked sediment was observed but degradation via ester cleavage and reduction of the nitro group with more bound residues resulted in less of a release of fenitrothion into water. The distribution profiles of the Pesticides and their metabolites depended on their adsorption and diffusivity in the sediment phase. The TOXSWA program was useful for evaluating the dissipation profiles of the water-applied Pesticides. © Pesticide Science Society of Japan