Biotransformation toxicants

It is known that ruminal bacteria are capable of biotransforming toxic compounds found in plants at very fast rates, as well as other pollutants with chemical similarities to TNT and other munitions. In fact, among nitrated aromatic compounds that are biotransformed by ruminal bacteria are 3-nitropropionic acid, chloramphenicol, and nitrophenols. The authors used the rumen system to obtain a new isolate, which transforms TNT at rates much faster than previously reported and without any detectable... 

It is important to appreciate that the magnitude of the absorbed dose, the relative amounts of bio transformation product, and the distribution and elimination of metaboUtes and parent compound seen with a single exposure, may be modified by repeated exposures. For example, repeated exposure may enhance mechanisms responsible for biotransformation of the absorbed material, and thus modify the relative proportions of the metaboUtes and parent molecule, and thus the retention pattern of these materials. Clearly, this could influence the likelihood for target organ toxicity. Additionally, and particularly when there is a slow excretion rate, repeated exposures may increase the possibiUty for progressive loading of tissues and body fluids, and hence the potential for cumulative toxicity. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

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). 

Covalent binding of chemicals to biological macromolecules can also cause toxicity. During biotransformation and metabolic activation, chemical compounds can be changed to free radicals, which have an unpaired... 

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

Alkylating Agents. Figure 2 Biotransformation of cyclophosphamide - formation of inactive ( ) and toxic ( metabolites. 

Youssef SHA, El-Sayed MGA, Atef M. 1987. Influence of gentamicin and rifamycin on toxicity and biotransformation of methyl parathion in rats. Dtsch Tierarztl Wochenschr 94 203-205. 

Technical-grade endosulfan contains at least 94% a-endosulfan and (3-endosulfan. The a- and (3-isomers are present in the ratio of 7 3, respectively. The majority of the studies discussed below used technical-grade endosulfan. However, a few examined the effects of the pure a- and (3-isomers. Endosulfan sulfate is a reaction product found in technical-grade endosulfan as a result of oxidation, biotransformation, or photolysis. There is very little difference in toxicity between endosulfan and its metabolite, endosulfan sulfate. However, the a-isomer has been shown to be about three times as toxic as the P-isomer of endosulfan. 

Bonse G, Henschler D. 1976. Chemical reactivity, biotransformations and toxicity of polychlorinated aliphatic compounds. CRC Crit Rev Toxicol 10 395-409. 

Cerniglia CE, IP Ereeman, C van Baalen (1981) Biotransformation and toxicity of aniline and aniline derivatives in cyanobacteria. Arch Microbiol 130 272-275. 

In later chapters, considerable weight is given to the environmental significance of biotransformation and the synthesis of toxic metabolites. It is particularly desirable, therefore, to direct effort to the identification of such metabolites. This may present a substantially greater challenge than that of quantifying the original substrate for several reasons ... 

Mere alteration of the strnctnre of the contaminant by biotransformation may not necessarily be acceptable. For example, although anaerobic dechlorination of PCBs is desirable, microbial redaction of 3,3 -dichlorobenzidine, which is an intermediate in the manufacture of dyes, produced benzidine that is both more toxic and more snsceptible to dissemination in the aqnatic phase (Nyman et al. 1997). 

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