Toxic examples

Since feeds contain other substances than those required by the animals of interest, studies have also been conducted on antinutritional factors in feedstuffs and on the use of additives. Certain feed ingredients contain chemicals that retard growth or may actually be toxic. Examples are gossypol in cottonseed meal and trypsin inhibitor in soybean meal. Restriction on the amount of the feedstuffs used is one way to avoid problems. In some cases, as is tme of trypsin inhibitor, proper processing can destroy the antinutritional factor. In this case, heating of soybean meal is effective. 

Some elements found in body tissues have no apparent physiological role, but have not been shown to be toxic. Examples are mbidium, strontium, titanium, niobium, germanium, and lanthanum. Other elements are toxic when found in greater than trace amounts, and sometimes in trace amounts. These latter elements include arsenic, mercury, lead, cadmium, silver, zirconium, beryUium, and thallium. Numerous other elements are used in medicine in nonnutrient roles. These include lithium, bismuth, antimony, bromine, platinum, and gold (Eig. 1). The interactions of mineral nutrients with... 

In addition to ester bonds with P (Section 10.2.1, Figures 10.1 and 10.2), some OPs have other ester bonds not involving P, which are readily broken by esteratic hydrolysis to bring about a loss of toxicity. Examples include the two carboxylester bonds of malathion, and the amido bond of dimethoate (Figure 10.2). The two carboxylester bonds of malathion can be cleaved by B-esterase attack, a conversion that provides the basis for the marked selectivity of this compound. Most insects lack an effective carboxylesterase, and for them malathion is highly toxic. Mammals and certain resistant insects, however, possess forms of carboxylesterase that rapidly hydrolyze these bonds, and are accordingly insensitive to malathion toxicity. 

New substances (hydrolysis products) form when an agent or compound reacts with water. In certain cases hydrolysis does not completely destroy the toxicity of an agent or compound. The resulting hydrolysis products may also be toxic. Examples include lewisite and other agents containing arsenic. 

The PBPK model development for a chemical is preceded by the definition of the problem, which in toxicology may often be related to the apparent complex nature of toxicity. Examples of such apparent complex toxic responses include nonlinearity in dose-response, sex and species differences in tissue response, differential response of tissues to chemical exposure, qualitatively and/or quantitatively difference responses for the same cumulative dose administered by different routes and scenarios, and so on. In these instances, PBPK modeling studies can be utilized to evaluate the pharmacokinetic basis of the apparent complex nature of toxicity induced by the chemical. One of the values of PBPK modeling, in fact, is that accurate description of target tissue dose often resolves behavior that appears complex at the administered dose level. 

The pulmonary system is the site of entry for numerous toxicants. Examples of toxic substances inhaled by human lungs include fly ash and ozone from polluted atmospheres, vapors of volatile chemicals used in the workplace, tobacco smoke, radioactive radon gas, and vapors from paints, varnishes, and synthetic materials used for building construction. 

Other tests can reveal effects indicative of potential reproductive toxicity. Examples include the dominant lethal test, fertility assessment by continuous breeding, repeated-dose toxicity testing, and cancer studies where the gonads are subjected to pathological examination. These tests, however, provide information only on effects after dosing adult animals and are therefore not addressed below. 

There are a number of commercial expert in silico systems available for the prediction of toxicity. Examples of knowledge-based expert systems are DEREK (Lhasa, Leeds, UK), Hazard Expert (ComGenex, San Francisco, CA, USA), Oncologic (San Francisco, CA, USA) and COMPACT (University of Surrey, Guilford, UK). Examples of statistically-based systems are MultiCASE (MultiCase, Beachwood, OH, USA),... 

The most serious adverse effect of simvastatin is myopathy, which rarely may progress to rhabdomyolysis. Abnormalities of liver function may also occur. These effects are dose-dependent, and a number of drugs and foods may inhibit the metabolism of simvastatin, thereby increasing its toxicity. Examples of these are grapefruit juice and erythromycin, both of which should be avoided in patients taking simvastatin. 

Class 2 solvents Solvents to be limited (non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity, solvents suspected of other significant but reversible toxicities). Examples acetonitrile, cyclohexane, and methanol... 

The first is a rule-based system, which makes predictions for untested agents by drawing upon the human interpretation of toxicity data and biological information. That is, it captures, organizes, and applies scientific expertise that relates chemical structures with developmental toxicity. Examples of commercially available rule-based approaches include HazardExpert,23 Deductive Estimation of Risk from Existing Knowledge (DEREK),24... 

The major purpose of biotransformation is to chemically modify (metabolize) poorly excretable lipophilic compounds to more hydrophilic chemicals that are readily excreted in urine and/or bile. Without metabolism, lipophilic xenobiotics accumulate in biota, increasing the potential for toxicity. Examples of such compounds are highly halogenated polychlorinated biphenyls (PCBs) and polychlorinated dibenzofu-rans (TCDD and dioxins) that occur as tissue residues in humans. On the contrary, biotransformation is normally not required for xenobiotics with high water solubility because of rapid excretion in urine. 

Several mechanisms have been identified for the generation of nephrotoxicants following conjugation of halogenated hydrocarbons with glutathione (Table 6). These mechanisms include intramolecular cyclization, activation by cysteine conjugate S-lyase, and facilitated renal accumulation of the toxicant. Examples of each of these bioactivation mechanisms will be discussed in the following sections. 

The chemical composition of soil is complex, naturally containing numerous inorganic and organic compounds. Pollution of soil may be accomplished via the addition of chemical species that are alien to soil, such as organochlorine pesticides, or through the addition of quantities of naturally occurring chemicals that at elevated concentrations are toxic. Examples of the latter are chloride and heavy metals such as copper and selenium. 

In contrast to these chemicals, the newer organic compounds that have come into use within the past two decades are higher cost materials, but they are also much more toxic. Examples are dalapon, which competes with panto-ate and inhibits enzymatic synthesis of pantothenic acid (D,L-N-[2,4—dihydroxy-3,3—dimethylbutyryl]-P-alanine), and the substituted ureas, s-triazines... 

Lipophilic substances with low reactivity may dissolve in the cell membranes and change their physical characteristics. Alcohols, petrol, aromatics, chlorinated hydrocarbons, and many other substances show this kind of toxicity. Other, quite unrelated organic solvents like toluene give very similar toxic effects. Lipophilic substances may have additional mechanisms for their toxicity. Examples are hexane, which is metabolized to 2,5-hexandion, a nerve poison, and methanol, which is very toxic to primates. 

Whereas retinol and its esters (which are the forms of vitamin A in foods) are toxic at higher intake or supplement levels, synthetic analogs may avoid this toxicity, examples being derivatives of retinoic acid. A componnd known as 13-cis-retinoic acid has been noted to reverse premahgnant lesions in the case of certain kinds of... 

V-series nerve agents A class of chemical agents developed in the I950 s that act by inhibiting a key nervous system enzyme. They are generally persistent and have moderate to high toxicity. Examples are VE, VG, VM, VS, and VX. See also nerve ent. 

Many other metal compounds exist including the following often toxic examples barium compounds, eg., barium bromide beryllium compounds, eg., beryllium hydroxide cadmium compounds, e.g., cadmium iodide copper compounds like copper hydroxide, used as a pigment, in paper manufacturing, and as a pesticide lead compounds, like the soluble lead fluorosilicate thallium compounds, e.g., thallium sulphide and vanadium compounds, e.g., vanadium dichloride. 

Elimination (or substitution). In any situation in which an unacceptable risk to health has been identified the preferred course of action is to eliminate the toxic substance from the workplace or substitute it by a less hazardous substance. This is the most certain way of eliminating exposure and therefore removing the risk. However, elimination will in many cases prove impractical, since there may still remain a need for a solvent. Substitution, however, should be seriously considered and there are many situations in which highly toxic solvents have been successfully substituted by those of lower toxicity. Examples are ... 

While a great many different phosphate esters are found in plant and animal life, they are completely harmless (unless deliberately consumed in huge amounts). Some man-made products are on the other hand quite toxic. Examples of the latter are tributyl phosphate (BuO)3PO, and tricresyl phosphate (Me CgH4 P)3PO. These and a few other products are acute local irritants and are moderately toxic by inhalation or ingestion (see Chapter 12.11). 

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