Arsenic toxic effects

Recent studies using cultured cells have shown that MMA(III) and DMA(lll) are at least as toxic as the inorganic arsenic species (97-102). The methylated trivalent arsenic species are also proposed to be the proximate or ultimate genotoxic forms of arsenic (103). Thus, there has been much interest in the determination of these metabolites in humans. The observation of MMA(III) and DMA(III) species in human urine, together with these studies on arsenic toxic effects, indicates that methylation of arsenic may not be entirely a detoxification process for humans, as previously believed (104,105). Toxicological consequences of MMA(lll) and DMA(III) in humans need to be further examined. 

Control of metalloid content in natural objects, foodstuff and pharmaceuticals is an important task for modern analytical chemistry. Determination of elements such as Arsenic is necessary for evaluation of object toxicity, since their content in environment may exceed MCL (maximum contaminant level), posing hazard to human health. Elements such as Selenium in definite doses are healthy, but in greater quantities they produce toxic effect. 

Caution Because tellurium compounds have toxic effects similar to those of arsenic compounds care should be taken not to bring tellurium tetrachloride and its reaction products into contact with the skin. Avoid breathing fumes and dust of tellurium compounds. In addition, hydrogen chloride is evolved in Step A, and pyrophoric Raney nickel is used in Step B. Therefore all manipulations described in this procedure must be carried out in an efficient fume hood. 

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. 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

The evaluation of risk has underlined the possible adverse effects both on human health after the exposure to drinking water contaminated by landfill leachate and on small rodents and aquatic species at the hypothesized condition for humans, the estimated toxic effects of the raw leachate are mainly due to the levels of ammonia and cadmium and carcinogenic effects are induced by arsenic first and then by PCBs and PCDD/Fs while ecological potential risk is mainly attributable to the concentration of inorganic compounds, in particular ammonia for small rodents, cadmium, ammonia, and heavy metals for fishes. 

A case report of acute arsine poisoning in which a 27-y-old man was exposed to arsine during chemical manufacturing was reported by Pinto (1976). The subject was exposed to arsine as a result of arsine production via a reaction between a galvanized bucket and an arsenic-containing sulfuric acid solution. The exposure (duration not specified) produced toxic effects characterized by abdominal cramping, thoracic discomfort, and hematuria. Over the next week, the patient s hematocrit declined from 42.5 to 27.1 and hemoglobin dropped from 14.1 to 9.5 g/dL even with medical intervention (blood transfusions and mannitol diuresis). Nine hours after exposure, blood arsenic was 159 g/dL and urinary arsenic was 1862 ug/L. 

The occupational exposure of five workers to arsine was reported by Phoon et al. (1984). All cases involved hematuria and, except for one patient, abdominal pain and jaundice. One worker was exposed for approximately 1 3/4 h, while the others were exposed for approximately 2 1/4 h. The latency in appearance of toxic effects was unusually short U-3 h). The following day, the arsine level in the workers breathing zone was 0.055 mg/m3 (0.017 ppm), although no processing of arsenic-containing material was taking place at the time of measurement. It was hypothesized by the report authors that the arsine... 

If HL (C03-A010) is involved, then exposure of the skin will produce an immediate burning sensation, which may be quickly followed by reddening of the skin (erythema). In addition to other latent effects, casualties exposed to HL may also develop signs of systemic arsenic toxicity including diarrhea, damage to the liver, kidneys, nervous system, and the brain. 

BAL is the standard treatment for poisoning by arsenic compounds and will alleviate some effects from exposure to arsenic vesicants. It may also decrease the severity of skin and eye lesions if applied topically within minutes after decontamination is complete (i.e., within 2-5 minutes postexposure). Additional chelating agents for the treatment of systemic arsenic toxicity include meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propanesulfonic acid (DMPS). 

Arsenic uptake in rabbit intestine is inhibited by phosphate, casein, and various metal-chelating agents (USEPA 1980). Mice and rabbits are significantly protected against sodium arsenite intoxication by (V-(2,3-dimercaptopropyl)phthalamidic acid (Stine et al. 1984). Conversely, the toxic effects of arsenite are potentiated by excess dithiols, cadmium, and lead, as evidenced by reduced food efficiency and disrupted blood chemistry in rodents (Pershagen and Vahter 1979). 

Rainbow trout (Oncorhynchus mykiss) fed diets containing up to 90 mg As+5/kg were slightly affected, but those given diets containing >120 mg As/kg (as As+3 or As+5) grew poorly, avoided food, and failed to metabolize food efficiently. No toxic effects were reported over 8 weeks of exposure to diets containing 1600 mg/kg, as methylated arsenicals (Table 28.4). Dietary disodium... 

This chapter presents specific information with regard to the effects of environmental and occupational exposure to arsenic on inflammatory processes, the immune system, and host defense. While the focus is on the in vivo and in vitro effects of arsenic on host immune responses (e.g., immunotoxicity and hypersensitivity) and their relationship to clinically observed manifestations of arsenic toxicity (e.g., inflammation and skin cancer), information on the potential mechanisms through which arsenic may exert its biological effects is also provided. 

The term heavy metals is rather broad, relative, and nonspecific. There are many heavy metals. In industrial toxicology, however, the term is used to describe certain heavy metallic substances that can be distinguished from other metals because of their particular toxic effects. Of these, the most common are arsenic, lead, and mercury. These are the ones that will be dealt with here. 

Trace metals (arsenic, cadmium, chromium, copper, nickel, lead, mercury, zinc) Industrial and municipal wastewaters runoff from urban areas and landfill erosion of contaminated soils and sediments atmospheric deposition Toxic effects including birth defects, reproductive failure, cancer, and systemic poisoning. 

Melarsoprol is a divalent arsenical. It reacts with sulfhydryl groups. Melarsoprol is used for the late stage of sleeping sickness. It has to be administered intravenously. Slow i.v. injection is recommended. It is widely distributed and enters the CNS. It has a very short elimination half-life as it is biotransformed to a pentavalent arsenical. Adverse effects include hypersensitivity reactions and gastrointestinal toxicity causing severe vomiting and abdominal pain. CNS reactions are most serious as the encephalopathy may be fatal. Hemolytic anemia may... 

Oberst, F.W., Crook, J.W., Swaim, S.F., Ward, F.P.E., Koon, W.S., Musselman, N.P., Swan, D.J., and Smith, H.A. Toxic effects of high concentrations of bromobenzylnitrlle (CA) vapor in various animal species. U.S. Army Medical Research Laboratory, Edgewood Arsenal, Md. EATR 4078. 1967. 32 p. 

Arsenic compounds are thought to exert their toxic effects by several modes of action. Interference with enzyme function may result from sulfhydryl group binding by trivalent arsenic or by substitution for phosphate. Inorganic arsenic or its metabolites may induce oxidative stress, alter gene expression, and interfere with cell signal transduction. Although on a... 

Concomitants Concomitants can be considered impurities present in naturally occurring, nonsynthesized raw materials. They may either present toxic effects, as with arsenic, or be as harmless as chloride ions. An overview of usual concomitants and their limits cited in pharmacopeial compendia are listed in Table 7. 

---