Unknown toxicities

Of the approximately 80,000 chemicals that are in commercial use in the United States, even basic toxicity information is missing for nearly 75% of the top 3000 high production volume species. Essentially nothing is known about the toxicities of mixtures of these chemicals. 

The vast majority of the 80,000 chemicals in use have been synthesized since World War II. It is estimated that 3000-5000 new chemicals are introduced each year. Virtually every chemical that is manufactured is ultimately released into the environment. Barely 60 years have transpired since the large-scale release of new chemicals into the environment started. This is a short time span in the evolutionary time frame, meaning that the human species has not had time to adapt to the new chemicals in the environment Further complicating any chance to accurately assess the impact is the fact that new chemicals are constantly being introduced and accordingly, new chemical mixtures are constantly being created. 

Not only new chemicals, but also new, heretofore unknown, classes of chemicals are constantly being introduced. Following are examples of such chemicals  

Polychlorinated biphenyls (PCBs) were introduced for their fire-retardant properties without toxicological evaluation. The health effects that ensued are still being felt today, more than 20 years after they were banned.  

Plasticizers (e.g., phthalate esters and p-nonylphenol) were introduced to impart flexibility to polyvinylchloride (PVC) and other plastics. Their developmental effects on children were subsequently discovered. 

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The Toxic Substances Control Act of 1976 was enacted by Congress to test, regulate, and screen all chemicals produced or imported into the U.S. Many thousands of chemicals and their compounds are developed each year with unknown toxic or dangerous characteristics. To prevent tragic consequences, TSCA requires that any chemical that reaches the consumer market be tested for possible toxic effects prior to commercial manufacture. Any chemical that poses health and... 

Grabo TN. 1997. Unknown toxic exposures. Arts and crafts materials. Aaohn Journal 45(3) 124-130. 

ADRs are believed to be one of the leading causes of death in the United States. Patient exposure from new drugs with unknown toxic effects may be extensive. For instance, nearly 20 million patients in the United States took at least one of the five drugs withdrawn from the market between September 1997 and September 1998. Three of the five drugs were new, having been on the market for less than 2 years. 

Clearly, question 1 is not applicable when the project is a reconnaissance for unknown toxics. In regard to question 2, investigators can sometimes (assuming key parameters such as values are known or can be approximated and that uptake... 

Barlow, S. 2005. Threshold of Toxicological Concern (TTC). A tool for assessing substances of unknown toxicity present at low levels in the diet. ILSI Europe Concise Monograph Series. Europe, Bmssels, Belgium ILSI. http //europe.ilsi.org/publications/Monographs/ThreshoIdToxicoIogicaIConcem.htm Barnes, D., G. Daston, J. Evans, et al. 1995. Benchmark dose workshop Criteria for use of a benchmark dose to estimate a reference dose. Regul. Toxicol. Pharmacol. 21 296-306. 

Ferrostlicons are compds prepd by fusing iron and silica in an electric furnace at high temps. Some of the high silicon varieties, particularly 50/50 compd, are expl and are dangerous to transport and to handle. FeSi is of unknown toxicity. Moisture, steam, or water decompose it and impurities liberate phosphine and arsine with water. Expl and fire hazards are considered moderate and arise from the reaction with water. For shipping purposes FeSi with Sx 30—70% is considered a flammable solid and must carry yellow labels. If the Si is less than 30 or more than 70%, the material is not considered hazardous... 

Genotoxicity. Chronic occupational exposure to multiple insecticides, including diazinon, has been associated with an increased incidence of chromosomal aberration and increased sister chromatid exchange in peripheral blood lymphocytes in these individuals (de Ferrari et al. 1991 Kiraly et al. 1979 See et al. 1990). The results from these studies are confounded by either concurrent or sequential (or both) exposures to other unknown toxic substances, mainly other insecticides, that may be genotoxic. No in vivo genotoxicity studies in laboratory animals were located for diazinon. The results of in vitro tests in... 

Two strategies can be followed to assess the health hazard of organic chemicals occurring as contaminants in an abiotic or a biotic matrix. In the chemical-oriented approach, compounds of known toxicity are monitored and a toxicological examination of identified organics of unknown toxicity is performed. 

For the method to be most useful for the recovery of unknown toxicants in water, certain inherent difficulties of the original parfait method had to be overcome. Also, the method had to be evaluated by using a set of known compounds representative of major chemical groups that could contaminate water. 

Manganese 1 8 2.5-5 mg Enzymes in protein and energy metabolism, superoxide dismutase, mucopolysaccharides synthesis Unknown Toxicity by inhalation... 

It can be converted to a water-soluble, insensitive material, not susceptible to initiation, by treatment for 15 minutes at 87°, with 30 wts of a 15% soln of Na sulfide nonahydrate (Ref 1). Amm sulfide behaves similarly, but reacts much more slowly. These procedures involve reduction of the nitro groups to amino and other groups less energetic than nitro. TNT can be rapidly rendered non-expl by treatment with isopropyl-amine in a good solvent for TNT (eg, acetone or acetonitrile) (Ref 18). This system has been studied for destroying land mines (Refs 11 18). Destruction of the nitro groups in this system apparently occurs by the base-promoted redox reactions discussed under the reaction of TNT with bases. These chemical methods produce products of unknown toxicity, and are therefore suitable only for the treatment of small amounts of material on an occasional basis Other (limited-access) reports on the disposal of TNT are listed in the following Refs (Refs 4, 6,9,19,20 33)... 

The presence of thousands of substances (with well-known or unknown toxic properties), which have not been detected by monitoring. 

In the case of complex mixtures of unknown composition, the application of extrapolation techniques using the approaches described in Sections 5.5 and 5.6 is possible only after the components and other stressors have been identified. Thus, the main issue when starting with an ill-defined mixture, or a mixture of completely unknown toxicants, is to isolate the agents or factors that, cause biological stress. 

However, in tests of chemicals with unknown toxic characteristics, problems often arise because the actual responses of animals differ widely from those anticipated when the study was designed. To address this problem, it is prudent to increase the number of animals to ensure that animals are available at key points of a study to provide adequate information. In acute studies, the requirement for groups and number of animals in groups is related to the reliable determination of acute toxic effects and the estimation of a median lethal dose. In subchronic and chronic testing, the numbers are related to the detection of effects, providing sufficient animals for an acceptable investigation of toxic mechanisms and giving an indication of a no-effect level. ... 

The use of masked methyl isocyanates has been described,32 but this seemed to us merely replacing a known hazardous compound with an isocyanate of unknown toxicity which could well be equally hazardous. In this spirit our Dr. Shen-chun Kuo... 

Directions of Analysis Analytical procedures depends on the type of problem set. Unknown circumstances of an event or an unknown toxic factor require the application of systematic toxicological analysis (STA), so that the analytical procedure encompasses as many toxic substances as possible. In cases where the administered toxic compound is known, first of all a course of analysis targeted at this compound is conducted, and a positive result must be confirmed by another independent method. When working on a case in which only the symptoms of the action of an unknown toxic factor are given, the ability to use complementary techniques as well as knowledge of the fields of medicine, pharmacology and pharmacokinetics are of particular importance [53]. 

During operation of an RVX production or destmction facility, its iimer surfaces might have been treated with various reagents, and it is therefore quite difficult to predict the transformation routes and degradation products of the toxic agent. These products may include previously unknown toxic compounds. We faced such problems in... 

Barlow S, (2005), Threshold of toxicological concern (TTC) a tool for assessing substances of unknown toxicity present in the diet, ILSI Monograph 2005. 

Chemical or toxicological screening tests for possible unknown toxic substances are desirable. However, at present the implementation of chemical... 

In the event that an ingredient without any useable information at all is used in a mixture at a concentration of 1% or greater, it is concluded that the mixture cannot be attributed a definitive acute toxicity estimate. In this situation the mixture should be classified based on the known ingredients only, with the additional statement that x percent of the mixture consists of ingredient(s) of unknown toxicity. 

If the total concentration of the ingredient(s) with unknown acute toxicity is < 10% then the formula presented in 3.1.3.6.1 should be used. If the total concentration of the ingredient(s) with unknown toxicity is >10%, the formula presented in 3.1.3.6.1 should be corrected to adjust for the total percentage of the unknown ingredient(s) as follows ... 

Damage to the basal ganglia may be caused by an environmental factor, such as an unknown toxic chemical. Another supposition is that an early viral infection causes the degeneration. Parkinsonism may follow encephalitis or other forms of brain injury. In 1997, researchers located a specific gene defect which seems to be responsible for some familial cases of Parkinson disease. 

Caution. The germanium compounds encountered in these preparations are of unknown toxicity. Manipulations should be carried out in a vacuum system in a well-ventilated area. 

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