Metabolism toxicity

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

Many pesticides cause endocrine disruption in vertebrate and invertebrate species at concentrations that are not overtly metabolically toxic. The insect growth inhibitor diflubenzuron can affect the reproduction, development and behaviour of estuarine crustaceans at concentrations of just lOmgP (reviewed... 

Mechanistic studies to identify how endocrine disrupting chemicals interact with hormone systems are required. Although population effects coupled with biomarkers of exposure are strongly suggestive of endocrine disruption, the effect could be secondary to metabolic toxicity. Establishing mechanisms may avoid the need to make decisions on a weight of evidence approach alone. 

Tyagi SR, Singh Y, Sriram K, et al. 1985. Quality and quantity of dietary protein and acute endosulfan metabolic toxicity in rat liver microsomes. Indian J Med Res 81 480-487. 

Bruckner JV, Davis BD, Blancato JN. 1989. Metabolism, toxicity, and carcinogenicity of trichloroethylene. CRC Crit Rev Toxicol 20 31-50. 

Daly JW, DM Jerina, B Witkop (1972) Arene oxides and the NIH shift the metabolism, toxicity and carcinogenicity of aromatic compounds. Experientia 28 1129-1149. 

Generation of data on the nutrient content of agricultural products and foods forms the basis for estimating nutrient intakes of populations via dietary surveys, nutritional labelling for consumer protection, nutrition education for consumer food choice, home and institution menu planning and food purchase, and for research in nutrient requirements and metabolism, toxicant chemical composition is used to assess effects of farm management practices, crop culture, and food processing on chemical content and implications for human health. 

Wernsdorfer and Trigg [147] reviewed the pharmacokinetics, metabolism, toxicity, and activity of primaquine. 

Evans WE, Horner M, Chu YQ et al. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. J Pediatr 1991 119 985-989. 

Lake B. 1999. Coumarin metabolism, toxicity and carcinogenicity, relevance for human risk assessment. Food Chem Toxicol 37(4) 423-453. 

Major structural or physiological differences in the alimentary tract (e.g., species differences or surgical effects) can give rise to modifications of toxicity. For example, ruminant animals may metabolize toxicants in the GI tract in a way that is unlikely to occur in nonruminants. 

Primary hepatocytes are a common in vitro system to evaluate metabolism, toxicity and enzyme induction [67-69]. Human hepatocytes are considered the most relevant system to evaluate or predict human metabolism or effects of a new dmg. A significant... 

Commercial interest in CNTs has led to the development of mass production and handling facilities. Risks of exposure by various routes need to be clarified because CNTs may penetrate the body through the skin as well as the lung and gut (Donaldson et al., 2006). Even if our understanding of local, chronic, and metabolic toxicity through the skin penetration is not clear, there is a broad consensus that CNTs can enter through the skin and distribute throughout the body (Nohynek et al., 2007 Tsuji et al., 2006). 

Cheek, P. R. and Kelly, J. D. 1989. Metabolism, Toxicity and Nutritional Implications of Quinolizidine (Lupin) Alkaloids. In Recent Advances of Research in Antinutritional Factors in Legume Seeds Animal Nutrition, Feed Technology, Analytical Methods. Proceedings of the First International Work shop on Antinutritional Factors ANF) in legume seeds. November 23-25, 1988 (Huisman, J., Poel, T. F. van der and Liener, I. E. eds.), pp. 189-201. Agricultural University, Wageningen. 

Eaidoperoxide analogue Number of synthetic steps/Non-racemic (NR), Achiral (A) or Racemic (R) Method of O2 incorporation In Vitro IC50 (nM) //n vivo ED50 (oral) (mg kg- ) Metabolism/Toxicity studies References... 

Lake, B.G (1999) Coumarin metabolism, toxicity and carcinogencity relevance for human risk assessment. Food chem. Toxicol., 37, 423 53 Lake, B.G Evans, J.G (1993) Effect of pretreatment with some mixed-function oxidase enzyme inducers on the acute hepatotoxicity of coumarin in the rat. Food chem. Toxicol., 31, 963-970... 

Local anaesthetics JP Howe andJPH Fee Introduction Chemical structure Mechanism of action Pharmacokinetics Metabolism Toxicity... 

The major advantage of an in vitro system is that it represents a simplified system which allows the experimenter to address questions which cannot be tested in vivo. These systems can allow analysis of activation or metabolism at the single enzyme level. They can test proposed pathways of metabolism or activation. Such studies are not practical with in vivo systems. The major disadvantage is that in vitro systems are a simplified system and the results can be easily over-interpreted. In vitro systems cannot model the pharmacokinetics or toxicokinetics of xenobiotic exposure in vivo. In addition, there may be other, unappreciated enzymes or factors which influence metabolism/toxicity in vivo which are not present in the in vitro system. 

Table 4.5 Formation of Reactive Electrophiles by Metabolic Toxication of Drugs...

Buratti S, Lavine JE. Drags and the liver advances in metabolism, toxicity, and therapeutics. Curr Opin Pedi-atr. 2002 14 601-607. 

Opsoclonus is a disorder of eye movement characterized by multidirectional saccades. Opsoclonus is usually associated with myoclonus, constituting OM, and there are often coexisting signs of cerebellar dysfunction and encephalopathy. The causation of OM is complex, including viral, metabolic, toxic, and structural disorders. Paraneoplastic OM was first described in children. Neuroblastoma is found in 50% of the pediatric OM cases, but on the whole, only 2-3% of all children with neuroblastic tumors have paraneoplastic OM [74, 75]. 

Utility Cytotoxic Agents with Diminished Cellular Metabolic Toxicity... 

Metabolic/toxic encephalopathy hypoglycemia, hepatic failure, alcohol intoxication... 

The resulting cellular structures can be used as models for investigating development, drug metabolism, toxicity, biotransformations, pathogenesis and microorganism replication. 

NTP (2002) NTP Report on the Metabolism, Toxicity, and Predicted Carcinogenicity of Diazoaminobenzene (CAS 136-35-6), TR-073. Research Triangle Park National Toxicology Program. 

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