Toxicity intermediates

Hazardous chemicals or mixtures may be replaceable by safer materials. These may be less toxic per se, or less easily dispersed (e.g. less volatile or dusty). Substitution is also applicable to synthesis routes to avoid the use of toxic reactants/solvents or the production, either intentionally or accidentally, of toxic intermediates, by-products or wastes. 

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). 

Developing new chemical engineering design tools to deal with the multiple objectives of minimum cost process resilience to changes in inputs minimization of toxic intermediates and products and safe response to upset conditions, start-up, and shutdown. 

Toxic intermediate products are produced during hydrolysis. Approximate half-life in water at 25°C is 1.3 min. Decomposition comes through slow change into quaternary ammonium salts. Decomposition point is below 94°C. 

Tetrachoroethylene (perchloroethylene, PCE) is the only chlorinated ethene that resists aerobic biodegradation. This compound can be dechlorinated to less- or nonchlorinated ethenes only under anaerobic conditions. This process, known as reductive dehalogenation, was initially thought to be a co-metabolic activity. Recently, however, it was shown that some bacteria species can use PCE as terminal electron acceptor in their basic metabolism i.e., they couple their growth with the reductive dechlorination of PCE.35 Reductive dehalogenation is a promising method for the remediation of PCE-contaminated sites, provided that the process is well controlled to prevent the buildup of even more toxic intermediates, such as the vinyl chloride, a proven carcinogen. 

Direct Black 38 Mixed microbial culture isolated from an aerobic bioreactor treating textile wastewater The dye was transformed into benzidine and 4-aminobiphenyl followed by complete biodegradation of these toxic intermediates [134]... 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

Generate hazardous unstable or toxic intermediates in situ from less hazardous starting materials, avoiding storage and transfer of the hazardous substances. 

At the Sn02 anode only a very small amount of highly toxic intermediates (hydroquinone, catechol, benzoquinone) is formed. These intermediates are formed in large amounts on the Pt anode probably by chemical reaction of adsorbed hydroxyl radicals with phenol. 

The anammox catabolism, an exceptionally slow process generating toxic intermediates (hydroxylamine and hydrazin), takes place in an intracytoplasmic compartment called the anammoxosome. A surrounding impermeable membrane protects the cytoplasm from the toxic molecules produced inside this organelle-like structure. Such a tight barrier against diffusion seems to be realised by four-membered aliphatic cyclobutane rings that have been found... 

CYP1A1. In humans, of the two members, CYP1A2 is the major player while CYP1A1 is a relatively minor extrahepatic isoform associated with the oxidation of polycyclic aromatic hydrocarbons like benzo[a]pyrene. Similarly, in test rodent species it is responsible for the generation of toxic intermediates and carcinogenic metabolites (10). 

Nocerini MR, Carlson JR, Yost GS. Electrophilic metabolites of 3-methylindole as toxic intermediates in pulmonary oedema. Xenobiotica 1984 14(7) 561—564. 

Phenol is catabolized by liver microsomal monooxygenases to hydroxylated products (e.g., 1,4-dihydroxybenzene) that can undergo further conversion to a variety of electrophilic substances (e.g., benzoquinones). Such reactions may be involved in generating reactive toxic intermediates in the liver (Eastmond et al. 1986 Lunte and Kissinger 1983 Subrahmanyam and O Brien 1985). Based on the available data, hepatic effects are unlikely to occur at the exposure levels found in the environment or near hazardous waste sites. 

Schematically, the two major types of reactions undergone by epoxides are rearrangements and addition of nucleophiles. Rearrangements can lead to toxic intermediates, precursors, or metabolites, whereas nucleophilic additions can lead to alkylation of biomacromolecules, i.e., formation of covalent adducts.

A biological difference that could increase susceptibility of fetuses and premature or perinatal infants to 1,2-dibromoethane toxicity is developmental immaturity of the P-450 (microsomal enzyme) system. Biotransformation of xenobiotics occurs predominantly by glutathione conjugation (Benet and Sheiner 1985 Sipes and Gandolfi 1986). This pathway is known to generate a number of toxic intermediate metabolites of 1,2-dibromoethane. In addition, fetal mice have selective binding of... 

The control of the synthesis of polymers is crucial to obtain the final bulk properties of the polymers needed for the end application. The use of enzymes in polymer synthesis has been demonstrated to allow control of polymer properties such as average molecular weight and dispersity, avoid the use of toxic intermediates, enable the selective reaction of functional groups and allow the use of unstable intermediates. 

The metabolism of chloroform is well understood. Approximately 50% of an oral dose of 0.5 grams of chloroform was metabolized to carbon dioxide in humans (Fry et al. 1972). Metabolism was dose-dependent, decreasing with higher exposure. A first-pass effect was observed after oral exposure (Chiou 1975). Approximately 38% of the dose was converted in the liver, and < 17% was exhaled unchanged from the lungs before reaching the systemic circulation. On the basis of pharmacokinetic results obtained in rats and mice exposed to chloroform by inhalation, and of enzymatic studies in human tissues in vitro, in vivo metabolic rate constants (V, 3,C =15.7 mg/hour/kg, = 0.448 mg/L) were defined for humans (Corley et al. 1990). The metabolic activation of chloroform to its toxic intermediate, phosgene, was slower in humans than in rodents. 

These biodegrade via central fission initiation in which the hydrophobe is cleaved from the hydrophile to produce non-surface active, non-toxic intermediates which readily biodegrade to CO2 and H2O. 

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