Solvent metabolism

Dietary habits can influence the TK and toxicity of solvents in several ways. The mere bulk of food in the stomach and intestine can inhibit systemic absorption of VOCs. Solvents in the GI tract partition into dietary lipids, largely remaining there until the lipids are emulsified and digested. This substantially delays the absorption of VOCs such as CCI4 and its hepatotoxicity. Increased incidences of cancer have been observed in obese humans possibly due to increase in liver CYP2E1 by ketone body formation. Caloric restriction has clearly been shown to reduce the incidence of cancer. Fasting results in increased P450 activities and reduced GSH, which affect the TK and toxicity of VOCs. Food may contain certain natural constituents, pesticides, and other chemicals, which may enhance or reduce the solvent metabolism. 

Carbon monoxide (CO). One of the most important agents involved in poisoning cases with many sources (fires, car exhausts, solvent metabolism) and difficult to detect. Binds avidly to iron atoms in haemoglobin forming carboxyhaemoglobin (COHb) which may be determined in the blood 20% COHb may lead to impairment of normal function, 60% to death. The main target organs are the brain... 

Mineral oil and paraffins should not be used, because these are not metabolized and may irritate tissue. Various other additives are needed for stabiUty, stefihty, and isotonicity antimicrobial preservatives, antioxidants (qv), chelating agents (qv), and buffers. No parenteral container material is completely inert to parenteral solvent systems. 

E. Biowning, Toxicity and Metabolism of Industrial Solvents, Elseviei, Amsteidam, The Nethedands, 1965, p. 326. 

Button, L.G. (2000) Avoiding Static Ignition Hazards in Chemical Processes, American Institute of Chemical Engineers. Browning, E. (1965J Toxicity and Metabolism of Industrial Solvents, Elsevier, Amsterdam. 

Inhalant intoxication dehrium can occur as a consequence of disturbances in dopaminergic, glutamatergic, and GABAergic neu to transmission secondary to acute, high-level exposure to psychoactive ingredients in solvents such as toluene, trichloroethane, and trichloroethylene. Systemic effects of solvent inhalation such as cerebral hypoxia and/or metabolic acidosis may also be involved (Rosenberg 1982). Under these circumstances, inhalant intoxication dehrium develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. Usually, the delirium resolves as the intoxication ends or within a few hours after cessation of use. 

Differences among individuals can partially explain the differences in the before workshift and end of workshift levels of trichloroethylene and its metabolites. Increased respiration rate during a workday, induced by physical workload, has been shown to affect levels of unchanged trichloroethylene more than its metabolites, while the amount of body fat influences the levels of the solvent and its metabolites in breath, blood, and urine samples before workshift exposure (Sato 1993). Additionally, liver function affects measurements of exhaled solvent at the end of workshift increased metabolism of trichloroethylene will tend to decrease the amount exhaled after a workshift. Increased renal function would affect levels of TCA and trichloroethanol in blood before a workshift in the same way, but it probably would not affect urine values between the begiiming and the end of the workshift because of the slow excretion rate of TCA. 

Often solvents do not extract 100% of the total radioactive residue. In this case, knowledge about the concentration of the target analyte(s) in the extract and the filter cake is necessary. Even if large amounts of radioactivity remain in the solid residual materials, the extraction efficiency may be sufficient if this unextracted radioactivity is permanently bound to the matrix or if it is associated with compounds which are not included in the residue definition. Finally, in all cases a well performed metabolism study can provide the answers needed, even where residues in the edible parts of treated crops or animals do not occur. If incurred residues do not occur, clearly the determination of extraction efficiency is not required. 

Consequently, separate experiments for the determination of extraction efficiency are often not required. An expert statement based on the results of metabolism studies is sufficient in most cases. These statements should also refer to the extraction solvent used for the analysis of samples of supervised trials. Residue levels found in these trials are the criterion for GAP and the basis for the setting of MRLs. Even if a solvent with insufficient extraction efficiency is used for samples from supervised trials, the later choice of better solvents would not result in lower safety for the consumer. 

Several extraction techniques have also been described that use enzymatic or chemical reactions to improve extraction efficiency. A technique that has been used to increase the overall recovery of the marker residue is enzymatic hydrolysis to convert specific phase II metabolites (glucuronides or sulfates) back into the parent residue. Cooper etal used a glucuronidase to increase 10-fold the concentration of chloramphenicol residues in incurred tissue. As an example of a chemical reaction, Moghaddam et al. used Raney nickel to reduce thioether bonds between benomyl and polar cellular components, and as a result achieved a substantially improved recovery over conventional solvent extraction. In choosing to use either of these approaches, thorough characterization of the metabolism in the tissue sample must be available. 

In some cases, microorganisms can transform a contaminant, but they are not able to use this compound as a source of energy or carbon. This biotransformation is often called co-metabolism. In co-metabolism, the transformation of the compound is an incidental reaction catalyzed by enzymes, which are involved in the normal microbial metabolism.33 A well-known example of co-metabolism is the degradation of (TCE) by methanotrophic bacteria, a group of bacteria that use methane as their source of carbon and energy. When metabolizing methane, methanotrophs produce the enzyme methane monooxygenase, which catalyzes the oxidation of TCE and other chlorinated aliphatics under aerobic conditions.34 In addition to methane, toluene and phenol have been used as primary substrates to stimulate the aerobic co-metabolism of chlorinated solvents. 

Organic contaminants such as petroleum hydrocarbons or chlorinated solvents can be directly metabolized by proteins and enzymes, leading to the degradation, metabolism, or mineralization of the contaminants. Furthermore, many of these contaminants can be broken down into harmless products or converted into a source of food and energy for the plants or soil organisms.50... 

Chauret, N., Gauthier, A. and Nicoll-Griffth, D.A. (1998) Effect of common solvents on in vitro cytochrome P450 mediated metabolic activities in human liver microsomes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 26, 1-4. 

Easterbrook, J., Liu, C., Sakai, Y. and Li, A.P. (2001) Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 29, 141-144. 

Although the exact mechanism of degradation at metabolic level for each compound or group of compounds is not well known, the involvement of extracellular oxidative enzymes such as LAC, MnP, LiP, and versatile peroxidase (VP) (see Tables 1 and 2 of Chap. 6) and intracellular monooxygenases as cytochrome P-450 is well documented for pollutants such as hydrocarbons, dyes, and halogenated solvents [25]. To determine the actual role of the extracellular enzymes, many studies are performed in vitro experiments with purified enzymes. In the case of cytochrome P-450, usually inhibitors are used. 

In summary, we may add that bacterial utilization of quinoline and its derivatives as a rule depends on the availability of traces of molybdate in the culture medium [363], In contrast, growth of the bacterial strains on the first intermediate of each catabolic pathway, namely, the lH-2-oxo or 1 II-4-oxo derivatives of the quinoline compound was not affected by the availability of molybdate. This observation indicated a possible role of the trace element molybdenum in the initial hydroxylation at C2. In enzymes, Mo occurs as part of the redox-active co-factor, and all the Mo-enzymes involved in N-heteroatomic compound metabolism, contain a pterin Mo co-factor. The catalyzed reaction involves the transfer of an oxygen atom to or from a substrate molecule in a two-electron redox reaction. The oxygen is supplied by the aqueous solvent. Certainly, the Mo-enzymes play an important role in the initial steps of N-containing heterocycles degradation. 

Further work at EniTecnologies was conducted with Rhodococcus strains. Rhodococ-cus was selected for its metabolical versatility, easy availability in soils and water, and remarkable solvent tolerance. Its capabilities for catalyzing diverse transformation reactions of crude oils, such as sulfur removal, alkanes and aromatics oxidation and catabolism caught their attention. Hence, genetic tools for the engineering of Rhodococcus strains have been applied to improve its biotransformation performance and its tolerance to certain common contaminants of the crude oil, such as cadmium. The development of active biomolecules led to the isolation and characterization of plasmid vectors and promoters. Strains have been constructed in which the careful over-expression of selected components of the desulfurization pathway leads to the enhancement of the sulfur removal activity in model systems. Rhodococcus, Gordona, and Nocardia were transformed in this way trying to improve their catalytic performance in BDS. In a... 

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