Toxicokinetics, biotransformation

From their high n-octanol/water partition coefficient (K, ) (see Table 15) it can be assumed that PBDEs could be bio concentrated to a high extent in fish and other aquatic organisms. Recently the analysis, environmental fate, toxicokinetics, biotransformation, bio accumulation, toxicity, and environmental occurrence was reviewed by Pijnenburg et al. [249]. In the following part the bioconcentration of PBDEs in aquatic organisms, especially fish, is critically reviewed. Some information on endocrine disrupting properties of PBDEs is also presented. 

The kinetic properties of chemical compounds include their absorption and distribution in the body, theit biotransformation to more soluble forms through metabolic processes in the liver and other metabolic organs, and the excretion of the metabolites in the urine, the bile, the exhaled air, and in the saliva. An important issue in toxicokinetics deals with the formation of reactive toxic intermediates during phase I metabolic reactions (see. Section 5.3.3). 

Absorption, distribution, biotransformation, and excretion of chemical compounds have been discussed as separate phenomena. In reality all these processes occur simultaneously, and are integrated processes, i.e., they all affect each other. In order to understand the movements of chemicals in the body, and for the delineation of the duration of action of a chemical m the organism, it is important to be able to quantify these toxicokinetic phases. For this purpose various models are used, of which the most widely utilized are the one-compartment, two-compartment, and various physiologically based pharmacokinetic models. These models resemble models used in ventilation engineering to characterize air exchange. 

No information is available on the toxicokinetics of -hexane in children or in young animals compared to adult animals. No information is available as to whether metabolism of M-hcxanc in children differs from that of adults. No studies were located comparing metabolism in young and adult animals. The toxicity of -hexane results from biotransformations yielding the active metabolite 2,5-hexanedione. The initial step is an oxidation to 2-hexanol catalyzed by a cytochrome P-450 enzyme. Some P-450 enzymes are developmentally regulated (Leeder and Kearns 1997) however, it is not completely clear which P-450 enzymes are involved in -hexane metabolism. 

To date, very little quantitative data exist regarding the toxicokinetics of endrin and its metabolites. Limited data were found regarding the absorption, distribution, metabolism, and excretion of endrin in humans and animals after inhalation, oral, or dermal exposure, which is especially relevant to occupational exposure scenarios. Endrin appears to be well absorbed orally, and distribution is primarily to fat and skin. Endrin is excreted in urine and feces, and the major biotransformation product is anti-12-hydroxy-... 

Although there is no reason to suspect that the pharmacokinetics of 1,4-dichlorobenzene differs in children and adults, scant data are available to support or disprove this statement. Studies of absorption, distribution, metabolism, and excretion in children would aid in determining if children are at an increased risk, particularly if conducted in an area where a high-dose acute or low-dose chronic exposure to an environmental source were to occur. With regard to exposure during development, additional research on maternal and fetal/neonatal toxicokinetics, placental biotransformation, the mechanism of... 

Pharmacokinetics The study of the movement of xenobiotics within an organism. Such a study must consider absorption, distribution biotransformation, storage and excretion. Synonym toxicokinetics. 

Castagnoli, N. and Castagnoli, K.P. (1993) Biotransformation of xenobiotics to chemically reactive metabolites, in Drug Toxicokinetics. Drug and Chemical Toxicology Series vol. 9 (eds P.G. 

Perkins Jr, E.J. and Schlenk, D. (2000) In vivo acetylcholinesterase inhibition, metabolism, and toxicokinetics of aldicarb in channel catfish role of biotransformation in acute toxicity, Toxicological Sciences 53 (2), 308-315. 

Toxicokinetics Quantitative uptake of xenobiotics by the body, its biotransformation, distribution, metabolism, and elimination from the body. 

Toxicokinetics. The process of the uptake of potentially toxic substances by the body, the biotransformation they undergo, the distribution of the substances and their metabolites in the tissues, and the elimination of the substances and their metabolites from the body. Both the amounts and the concentrations of the substances and their metabolites are studied. (Pharmacokinetics is the term used to study pharmaceutical substances.)... 

The pharmacokinetic evaluation of biopharmaceuticals is generally simplified by the usual metabolism of products to small peptides and to amino acids, and thus classical biotransformation and metabolism studies are rarely necessary. Routine studies to assess mass balance are not useful. However, both single- and multiple-dose toxicokinetic data are essential in safety pharmacology asessments, and these can be complicated by two factors (1) biphasic clearance with a saturable, initial, receptor-dependent clearance phase, which may cause nonlinearity in dose-exposure relationships and doseresponses [14] and (2) antibody production against an antigenic biopharmaceutical that can alter clearance or activity in more chronic repeat-dose safety studies in the preclinical model. 

Stereoselective toxicokinetics of pyrethroids was observed in rodents. Rats injected with a racemic dose of 0-cypermethrin had much lower amounts of the (+)-enantiomer compared to the (—)-enantiomer in plasma, heart, liver, kidney, and fat tissues. The authors suggested rapid interconversion of (+)-a5, l/f,35 -cypermethrin to its antipode ( )-a/f,15, 3R-cyper-methrin in plasma, but no reverse conversion of the ( )-enantiomer back to the (+)-enantiomer. This hypothesis was criticized [285] as implausible, as three separate epimer-ization reactions would be necessary for conversion of (+)-a5, l/f,35 -cypermethrin to (—)-a R, 15,3R-cypermethrin. However, the results do indicate significant enantioselectivity in the in vivo processing of cypermethrin by rats, but is not clear to what extent this enantioselectivity was from biotransformation or from tissue-specific redistribution. The latter was suggested by the data [84] consistent with the highly enantioselective screening of a-HCH by the rat blood-brain barrier [259]. 

See also Biotransformation Distribution Excretion Exposure Gastrointestinai System Modifying Factors of Toxicity Pharmacokinetics/Toxicokinetics Respiratory Tract Skin Toxicity Testing, Dermai Toxicity Testing, Inhaiation. 

Toxicokinetics The pattern of distribution and elimination of DBCM was very similar to that observed with BDCM, but it is the least studied THM. Presumably, metabolism proceeds via the same routes of biotransformation as described for BDCM. Oxidative metabolism of DBCM would be expected to yield a bromochlorocarbonyl rather than phosgene, and reductive dehalogenation would produce a bromochloromethyl radical. Half-lives of DBCM in rats and mice were estimated to be 1.2 and 2.5 h, respectively. 

Cyfluthrin is excreted mainly as urinary metabolites but a portion of it is also excreted unchanged in feces. Toxicokinetic studies with " C-cyfluthrin in rats have shown that the initial step of biotransformation includes ester hydrolysis resulting in 3-phenoxy-4-fluorobenzyl alcohol intermediate and permethric... 

See also Absorption Biotransformation Distribution Kidney Liver Metais Pharmacokinetics/Toxicokinetics. 

See also Absorption Analytical Toxicology Biotransformation Distribution Exposure Mechanisms of Toxicity Mixtures, Toxicology and Risk Assessment Pharmacoki-netics/Toxicokinetics Resistance to Toxicants. 

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