Lead: toxic effects

Seregin, 1. V., Ivanov, V. B. Physiological aspects of cadmium and lead toxic effects on higher plants. Russian journal of plant physiology. 2001, V. 48, 523-544. Kabata-Pendias, A., Pendias, El. Trace elements in soil and plants. CRC Press EEC, Boca Raton, FL, 1992, 453 p. 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Workers in the metals treatment industry are exposed to fumes, dusts, and mists containing metals and metal compounds, as well as to various chemicals from sources such as grinding wheels and lubricants. Exposure can be by inhalation, ingestion, or skin contact. Historically, metal toxicology was concerned with overt effects such as abdominal coHc from lead toxicity. Because of the occupational health and safety standards of the 1990s such effects are rare. Subtie, chronic, or long-term effects of metals treatment exposure are under study. An index to safety precautions for various metal treatment processes is available (6). As additional information is gained, standards are adjusted. 

Sodium nitrite is poisonous and prolonged contact with dry sodium nitrite or its solutions can cause irritation to the skin, eyes, and mucous membranes. The LD q (oral, rat) is 85 mg per kg body weight (11). Inhalation or ingestion of significant quantities of dust or mist may result in acute toxic effects such as nausea, cyanosis, and low blood pressure, which can lead to possible coUapse, coma, and even death. 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

Vanadium compounds, including those which may be involved in the production, processing, and use of vanadium and vanadium alloys, are irritants chiefly to the conjuctivae and respiratory tract. Prolonged exposure may lead to pulmonary compHcations. However, responses are acute, never chronic. Toxic effects vary with the vanadium compound involved. For example, LD q (oral) of vanadium pentoxide dust in rats is 23 mg/kg of body weight (24). 

Bismuth subsahcylate [14882-18-9] Pepto-Bismol, is a basic salt of varying composition, corresponding approximately to i9-H0CgH4C02(Bi0). Like a number of other insoluble bismuth preparations, it is not currentiy approved in the United States for the treatment of peptic ulcer disease but is under active investigation for this purpose (180). It does appear to be effective for the rehef of mild diarrhea and for the prevention of travelers diarrhea (181). The ready availabiUty of this dmg, however, may lead to its ovemse and result in toxic effects caused by both the saUcylate and bismuth components. It has been suggested that bismuth subsahcylate is somewhat effective in the symptomatic treatment of isosporiasis, a disease caused by the intracellular parasite Isospora belli (182). 

Drugs and other chemicals such as food additives or insecticides foreign to the body undergo enzymatic transformations that result in loss of pharmacological activity detoxification), or lead to the formation of metabolites with therapeutic or toxic effects bioactivation). 

Histamine is the biological amine, playing an important role in living systems, but it can also cause unnatural or toxic effects when it is consumed in lai ge amounts. It can occur with some diseases and with the intake of histamine-contaminated food, such as spoiled fish or fish products, and can lead to undesirable effects as headache, nausea, hypo- or hypertension, cai diac palpitations, and anaphylactic shock syndrome. So, there is a need to determine histamine in biological fluids and food. 

Heavy metals on or in vegetation and water have been and continue to be toxic to animals and fish. Arsenic and lead from smelters, molybdenum from steel plants, and mercury from chlorine-caustic plants are major offenders. Poisoning of aquatic life by mercury is relatively new, whereas the toxic effects of the other metals have been largely eliminated by proper control of industrial emissions. Gaseous (and particulate) fluorides have caused injury and damage to a wide variety of animals—domestic and wild—as well as to fish. Accidental effects resulting from insecticides and nerve gas have been reported. 

Paracelsus, a Swiss physician of the sixteenth century, stated that everything is toxic, it is just the dose that matters. This statement still holds true 500 years after Paracelsus developed it to defend the use of toxic compounds such as lead and mercury in the treatment of serious diseases such as syphilis. Chemical compounds cause their toxic effects by inducing changes in cell physiology and biochemistry, and an understanding of cellular biology is a prerequisite if one wishes to understand the nature of toxic reactions. 

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

Several toxic effects of inorganic oxides become evident when oxides are inhaled in a finely powdered form. A high concn of powdered oxides can lead to asphyxiation on short exposure or lung cancer at somewhat lower concns if the exposure occurs over a prolonged period. 

For convenience, the processes identified in Figure 2.1 can be separated into two distinct categories toxicokinetics and toxicodynamics. Toxicokinetics covers uptake, distribution, metabolism, and excretion processes that determine how much of the toxic form of the chemical (parent compound or active metabolite) will reach the site of action. Toxicodynamics is concerned with the interaction with the sites of action, leading to the expression of toxic effects. The interplay of the processes of toxicokinetics and toxicodynamics determines toxicity. The more the toxic form of the chemical that reaches the site of action, and the greater the sensitivity of the site of action to the chemical, the more toxic it will be. In the following text, toxicokinetics and toxicodynamics will be dealt with separately. 

Starvation or disease can lead to rapid release of the stored xenobiotic and to delayed toxic effects. In one well-documented case in the Netherlands (see Chapter 5), wild female eider ducks (Somateria mollissima) experienced delayed neurotoxicity caused by dieldrin. The ducks had laid down large reserves of depot fat before breeding, and these reserves were run down during the course of egg laying. Dieldrin concentrations quickly rose to lethal levels in the brain. Male eider ducks did not lay down and mobilize body fat in this way and did not show delayed neurotoxicity due to dieldrin. 

Enterohepatic circulation can lead to toxic effects. For example, the drug chloramphenicol is metabolized to a conjugate that is excreted in bile by the rat. Once in the gut, the conjugate is broken down to release a phase 1 metabolite that undergoes further metabolism to yield toxic products. When these are reabsorbed, they can cause toxicity. The rabbit, by contrast, excretes chloramphenicol conjugates in urine, and there are no toxic effects at the dose rates in question. 

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