Nonspecific toxicities

Infants maybe sensitive to doses of vitamin A [11103-57-4] in the range of 75,000—200,000 lU (22.5—60 mg), although the toxic dose in adults is probably 2—5 million lU (90.6—1.5 g). Intakes in this range from normal food suppHes without oral supplements are simply beyond imagination (79). Vitamin D [1406-16-2] toxicity is much more difficult to substantiate clinically. Humans can synthesize active forms of the vitamin in the skin upon irradiation of 7-dehydrocholesterol. Toxic symptoms are relatively nonspecific, and dangerous doses seem to He in the range of 1000—3000 lU/kg body wt (25—75 flg/kg body wt) (80). Cases of toxicity of both vitamins E and K have been reported, but under ordinary circumstances these vitamins are considered relatively innocuous (81). 

In several cases, such as shellfish areas and aquatic reserves, the usual water quaUty parameters do not apply because they are nonspecific as to detrimental effects on aquatic life. Eor example, COD is an overall measure of organic content, but it does not differentiate between toxic and nontoxic organics. In these cases, a species diversity index has been employed as related to either free-floating or benthic organisms. The index indicates the overall condition to the aquatic environment. It is related to the number of species in the sample. The higher the species diversity index, the more productive the aquatic system. The species diversity index is computed by the equation K- = (S — 1)/logjg I, where S is the number of species and /the total number of individual organisms counted. 

Applicability/Limitations The process is nonspecific. Solids must be in solution. Reactions can be explosive. Waste composition must be well known to prevent the inadvertent production of a more toxic or more hazardous end product. Oxidation processes are applicable for the following classes of organic contaminants ... 

Liver alcohol dehydrogenase (ADH) is relatively nonspecific and will oxidize ethanol or other alcohols, including methanol. Methanol oxidation yields formaldehyde, which is quite toxic, causing, among other things, blindness. Mistaking it for the cheap... 

The concept of drug development is based on the findings that retinoid receptors (RARs and RXRs) offer a new approach by targeting different genes depending on the activated retinoid receptor complexes. The multiplicity of these retinoid signaling pathways affords potential for therapeutic opportunity as well as retinoid therapy associated undesired side effects. It is possible that the indiscriminate activation of all pathways by nonspecific retinoid ligands could lead to unacceptable side effects so that any enhanced efficacy would be obtained at the cost of enhanced toxicity. 

The development of nucleic acid-based therapeutics is not as straightforward as researchers had initially anticipated. Stability, toxicity, specificity, and delivery of the compounds continue to be challenging issues that need further optimization. In recent years, researchers have come up with intricate solutions that have greatly improved the efficacy of potential antisense, ribozyme, as well as RNAi-based therapeutics. Clinical trials for all these types of nucleic acid-based therapeutics are underway. So far, data from several trials and studies in animal models look promising, in particular, the therapies that trigger the RNAi pathway. However, history has shown that compounds that do well in phase I or phase II clinical trials may still fail in phase III. A striking example is the nonspecific suppression of angiogenesis by siRNA via toII-Iike receptor 3 (Kleinman et al. 2008). It will become clear in the near future which compounds will make it as a new class of antiviral therapeutics. 

Rationale. Microorganisms were isolated from soil and screened for toxin production according to the scheme in Figure 1. Some of the organisms causing strong inhibition on solid medium were tested for toxin production in liquid medium. Liquid culture will be required to obtain large amounts of material for commercial production of herbicides, however, the ability to produce toxins on solid medium does not necessarily imply toxin production in broth (34). Cyclo-heximide, a phytotoxic but relatively nonspecific antibiotic with little value as a herbicide, is produced by many actinomycetes. Liquid cultures were tested for cycloheximide to determine whether it caused the observed toxicity. 

All metals, regardless of whether they are essential or nonessential, can exhibit toxic effects at high concentrations.14-16 Excess concentrations of essential metals can lead to nonspecific binding, which can affect the enzyme structure and function. Because controlling metal concentrations is vital for maintaining homeostatic conditions within bacterial cells, evolution has bestowed upon organisms a number of ways to regulate concentrations of essential metals and to resist the toxicity of nonessential metals.17-20... 

Toxic effects include decreased cardiac output, coma, seizures, vomiting, and respiratory depression. Treatment is nonspecific supportive care. 

Thus the total soil pollution was connected with a respiratory system and a digestive tract. Both systems were also sensitive to such urban pollutants as heavy metals and PAH. For radionuclides the correlation with the given nosologies was not revealed. The asthma morbidity was mostly connected with soil pollution rates. This circumstance, apparently, can be related to nonspecific action of pollutants on a human organism, because the etiology of asthma is connected with the human immune defense system and allergy state (Roite, 1991). The last was shown for pesticides (Nikolaev et al., 1988) and heavy metals (Drouet et al., 1990). The sensitized immune system is, apparently, responsible for chronic toxic effects of other pollutants at low doses (Sidorenko et al., 1991 Novak and Magnussen, 1993). 

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