Route dependence

The piefeiied route depends upon the avajlabihty of a hydrogen atom in the beta-position to the thiol group. In other words, a-toluenethiol (in toluene) decomposes to give 1,2-diphenylethane and hydrogen sulfide, via the homolytic route, whereas 2-methyl-2-propanethiol decomposes to give 2-methyl-1-propene and hydrogen sulfide. 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

Isoprene itself is not the true biological precursor of terpenoids. As we ll see in Chapter 27, nature instead uses two "isoprene equivalents"—isopentenvl diphosphate and dimethylallyl diphosphate—which are themselves made by two different routes depending on the organism. Lanosterol, in particular, is biosynthesized from acetic acid by a complex pathway that has been worked out in great detail. 

Immunotoxicity. Only a single case report of skin allergy to methyl parathion has been reported in humans (Lisi et al. 1987). No studies are available in humans exposed to methyl parathion via the inhalation or oral route. Based on limited animal studies, immunotoxicity may be a sensitive end point of methyl parathion-induced toxicity (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). Thus, humans may be at risk for adverse immunological effects following exposure to methyl parathion. The limited information available on the effects of combined exposure to methyl parathion suggest the its toxicity is not route-dependent. Therefore, there is no reason to suspect that the immunotoxic effects observed following oral exposure of animals are route-specific. 

The catalyst life-time for the four types of catalysts, prepared by different preparation routes, depends on the catalyst loading which is related to the preparation route [20]. The larger the loading, the longer the catalysts could be used before reactivation. The four catalysts had the following sequence of life-time and activity ... 

Route Dependent Toxicity. The toxicity of trichloroethylene does not seem to be heavily dependent upon its route of entry. Inhalation and ingestion are the primary exposure routes, and the liver, heart, and central nervous system are the primary targets for both routes (Candura and Faustman 1991). Renal toxicity results principally from oral exposure, and dermal exposure generally confines its toxic effects to the skin, although broad systemic effects can be induced imder conditions of high exposure (Bauer and Rabens 1974). Attributing such effects solely to dermal exposure, however, is difficult because inhalation exposure is often a factor in these cases as well. 

Much of the pulmonary NEP activity is believed to reside in the epithelium, as has been demonstrated in the ferret (Borson et al., 1986), and thus it is likely that inhaled ozone would preferentially destroy luminal NEP before affecting any enzymes in the vasculature, which may degrade peptides delivered by the intravenous route. This may explain the route-dependency of BHR after ozone in guinea pigs. Further evidence that the oxidant effects of inhaled ozone are selective is provided by the findings that pressor responses to angiotensin I (which requires conversion by ACE to angiotensin II) were not altered by ozone exposure (Yeadon et eU., 1992). 

A list of the mines where different processing of gold ores is carried out is shown in Table 5.12. Although the pressure oxidation process appears to be the current leading technology, selection of the optimum route depends on several factors. 

Route Dependent Toxicity. The toxicity of lead does not appear to be dependent on the route of exposure, but the time course may be affected. 

The nitrosophenol (10), which may be isolated, is oxidised very rapidly by nitric acid to yield the p-nitrophenol (11) and nitrous acid more nitrous acid is produced thereby and the process is progressively speeded up. No nitrous acid need be present initially in the nitric acid for a little of the latter attacks phenol oxidatively to yield HN02. The rate-determining step is again believed to be the formation of the intermediate (9). Some direct nitration of such reactive aromatic compounds by N02 also takes place simultaneously, the relative amount by the two routes depending on the conditions. 

K. S., A new physiologically based, segregated-flow model to explain route-dependent intestinal metabolism, Drug. Metab. Dispos. 2000, 28, 224-235. 

Crofton KM, Kehn LS, Gilbert ME (1995) Vehicle and route dependent effects of a pyrethroid insecticide, deltamethrin, on motor activity in the rat. Neurotoxicol Teratol 17 489 195... 

CHEC-II(8)421>. Reaction of 94 with water can proceed by two different routes depending on the substitution pattern in the case of the bromo-substituted derivative the unsaturated ketone 97 was formed in high yield, whereas the derivative being unsubstituted at the pyrimidine moiety gave the methyl ester 98, also in very good yield. 

Route-dependent Toxicity. w-Hexane toxicity does not appear to be route-dependent. Peripheral neuropathy can be produced in rats by the oral route (Krasavage et al. 1980) at high doses (4,000 mg/kg/day). The clinical and histopathological signs were similar to those seen after inhalation exposure. No reports of neurotoxicity after dermal exposure were located. 

Disilanes and cyclic silanes can be polymerized via a number of routes, depending on their substituents, and are described in Section 3.11.4. 

One aspect to be addressed in order to obtain a realistic vision of the toxicity of these kinds of compounds is their environmental behaviour. Surfactants tend to be adsorbed on particulate matter and thus subsequently to sediment. Consequently, the highest surfactant concentrations are found in sediments, although their distribution is dependent on the partitioning equilibrium between the substrate and interstitial water. This results in two possible routes for uptake (bioaccumulation) and effect. The relative importance of each of these routes depends on the special habits of each benthic organism. 

Wang P-Y, Kaneko T, Sato A, et al. 1995. Dose and route dependent alteration of metabolism and toxicity of chloroform in fed and fasting rats. Toxicol Appl Pharm 135(1) 119-126. 

Drug deliveiy to the colon by the oral route depends on gastric emptying and the small-bowel transit time. Drugs taken before meals usually pass out of the stomach within 1 hr, but can take up to 10 hr if taken after a meal. The transit time in the small intestine is relatively constant, ranging between 3 and 4 hr, regardless of various conditions such as physical state, size of dosage form, or presence of food in the stomach [9]. 

Toxicokinetic studies are designed to obtain species-, dose-, and route-dependent data on the concentration-time course of the parent compound and its metabolites, e.g., in blood, urine, feces, and exhaled air. From these data toxicokinetic parameters can be derived by appropriate techniques. The information, which can be taken from in vivojex vivo toxicokinetic studies is (EC 2003) ... 

Cancer does not exist. There exist actually 104 different types of cancers — or more precisely of human tumors — which may attack any part of the body and which nearly always enter by furtive and mysterious routes, depending on so many intangible factors, that mankind has up to now been completely powerless to prevent cancerisation in humans. 

Hexachlorobutadiene may enter your body through the lungs when you breathe air contaminated with it. It also may enter your body if you drink water or eat food contaminated with hexachlorobutadiene. With the exception offish and shellfish, however, hexachlorobutadiene has not been found in food. The amount of hexachlorobutadiene that enters your body by these routes depends on how much of the chemical you eat or drink. 

Theoretically, many of the above discrepancies could be settled by experiments with carboxyl-labeled shikimic acid because this functional group would be lost in the formation of phenylalanine, but retained in the case of a direct conversion to gallic acid. Only ambiguous evidence was obtained, however, from such efforts (10), and it was concluded that at least two pathways for gallic acid biosynthesis must exist (14), with the preferential route depending on leaf age and plant species investigated (15,16). 

Figure 8 gathers the various schemes that can be involved in these solution-mediated synthesis routes depending on solution parameters (pH, fluorine, calcium and phosphate concentrations). 

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