Toxicity to the Central Nervous System

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Inorganic and organic tellurium compounds are highly toxic to the central nervous system of rodents. 

Toxicity to the central nervous system (CNS) is another highly feared illness. Although often not fatal, it is usually long lasting (if not permanent) and debilitating. Fetuses, infants, and even children tend to be more susceptible and sensitive to chemical-induced injury to the CNS. This is because the brain cells and the... 

Ammonia is produced by all tissues during the metabolism of a variety of compounds, and it is disposed of primarily by formation of urea in he liver. However, the level of ammonia in the blood must be kept very fcw, because even slightly elevated concentrations (hyperammonemia) ae toxic to the central nervous system (CNS). There must, therefore, be a metabolic mechanism by which nitrogen is moved from peripheral tissues to the liver for ultimate disposal as urea, while at the same hre low levels of circulating ammonia must be maintained. 

TOXICITY TO THE CENTRAL NERVOUS SYSTEM The Production of Cognitive Deficits... 

SAFETY PROFILE Human poison by an unspecified route. Experimental poison by ingestion, intraperitoneal, intravenous, subcutaneous, and parenteral routes. Moderately toxic by inhalation and skin contact. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic data. Mutation data reported. Lead compounds are particularly toxic to the central nervous system. It is a solvent for fatty materials and has some solvent action on rubber as well. The fact that it is a lipoid solvent makes it an industrial hazard because it can cause intoxication not only by inhalation but also by absorption through the skin. Decomposes when exposed to sunlight or allowed to evaporate forms triethyl lead, which is also a poisonous compound, as one of its decomposition products. May cause elemental lead intoxication by coming in contact with the skin. 

Major target organs are the nervous system, respiratory system, gastrointestinal system, and kidneys. Tetraethyltin is converted to triethyltin, which is a potent skin irritant and neurotoxin. It produces depression with loss of memory and aggressive behavior. It also produces cerebral edema and en cephalopathy. Triphenyltin is an immunodepressant. Some organic tin compounds are unusually toxic to the central nervous system. 

Inorganic salts of mercury do not readily cross the blood-brain barrier or the placenta. They are, therefore, ultimately less toxic to the central nervous system and the developing fetus than either absorbed metallic mercury or organic mercury compounds. Metallic mercury is more readily oxidized to... 

Hazard Ignites in air near its melting point dangerous fire and explosion risk when exposed to water, acids, or oxidizing agents. Extinguish lithium fires only with chemicals designed for this purpose. Lithium in solution is toxic to the central nervous system. 

Halogenated phenols are more powerful disinfectants than simple phenols, as they are more lipophilic. They are also more toxic to the central nervous system. The chlorinated phenols are the most active. Toxicity is specific to each compound. 

The answer is b. (Murray, pp 238-249. Scriver, pp 2165-2194. Sack, pp 121—144. Wilson, pp 287—324.) In treating inborn errors of metabolism that present acutely in the newborn period, aggressive fluid and electrolyte therapy and caloric supplementation are important to correct the imbalances caused by the disorder. Calories spare tissue breakdown that can increase toxic metabolites. Since many of the metabolites that build up in inborn errors ol metabolism are toxic to the central nervous system, hemodialysis is recommended for any patient in stage II coma (poor muscle tone, few spontaneous movements, responsive to painful stimuli) or worse. Dietary therapy should minimize substances that cannot be metabolized—in this case fatty acids, since the oxidation of branched-chain fatty acids results in propionate. Antibiotics are frequently useful because meta-bolically compromised children are more susceptible to infection. 

Nickel is widely used in mining, milling, smelting and refmishing processes and can be extremely toxic to the central nervous system, but nickel-induced OA is very rare. Nickel-specific IgE antibodies have been found in a few individual case reports (Bernstein, IL and Brooks, 1993). 

The low concentration of protein in the interstitial fluid has been suggested as another factor which may reduce the distribution of some substances in the central nervous system. Lipid soluble compounds, such as methyl mercury which is toxic to the central nervous system (see Chapter 7). can enter the brain readily, the facility being reflected by the partition coefficient. Another example which illustrates the importance of the lipophilicity in the tissue distribution and duration of action of a foreign compound is afforded by a comparison of the drugs thiopental and pentobarbital (figure 3,5). These drugs are very similar in structure, only differing by one atom. Their pKa values are similar and consequently the... 

Methanol s toxicity is well-known. Following ingestion, it oxidizes to produce formic aldehyde and formic acid, both toxic to the central nervous system. Formic aldehyde deteriorates the optical nerve, causing blindness. Wines made in the normal way never have methanol concentrations anywhere near dangerous levels (LD50 = 350 mg/kg). 

Among these heat stabilisers, those containing tin (such as tin mercaptides, and tin carboxylates or maleates) are considered to be the most efficient, and can be used in a wide variety of applications. Metallic tin is harmless but there are suspicions that organotin-compounds can be toxic to the central nervous system and the liver. However, tin stabilisers have a low capacity for migrating, and hence they are still considered to be safe. Tin stabilisers such as methyl and octyl tins are used in food contact applications. For PVC, it is believed that tin stabilisers act as HCl scavengers (generating tin chloride) as well as an antioxidant. Thio-tin compounds (preferred for rigid pipe extrusions and profiles (for window frames) of PVC) may develop an odd odour due to sulfur. 

Toxicology Exposure is by inhalation. It is an irritant to eyes, nose and to mucous membranes, and is toxic to the central nervous system. No adverse effects are known for humans, but it causes the kidneys and liver to increase in size. 

In its initial phase acute lead poisoning is associated with anorexia, dyspepsia, and constipation followed by diffuse paroxysmal abdominal pain. The skin is usually pale, the pulse is slow, and blood pressure may increase probably due to spasmodic contraction of smooth muscle. Lead exposure may cause encephalopathy, particularly in children. The Pb-B levels associated with acute encephalopathy onset at 4 xmol/liter with symptoms such as delirium and seizures, in severe cases associated with papilledema [7]. In children the initial symptoms may include vomiting, apathy, stupor, and ataxia. Lead encephalopathy may leave children with persistent neurological and psychological impairment. The alkyl lead species are highly toxic to the central nervous system [2]. 

Most substances absorbed will be carried by the blood stream to the liver where they may be rendered less harmful by a change in their chemical composition. However, some may be made more toxic, e.g. naphthylamine which is responsible for bladder cancer and tetra-ethyl lead which is converted into the tri-ethyl form and is toxic to the central nervous system. 

The chemical transformation of elemental mercury to methylmercury can be performed by bacteria in water and soil. Elemental mercury and methylmercury are both toxic to the central nervous system. Elemental mercury evaporates, aud the toxic vapor is inhaled. The saying mad as a hatter arose from the occupational exposure of hatters to vapors from liquid mercury, which was used for centuries in the manufacture of felt hats. While mercury vapor is very toxic, the liquid metal itself is less so. It does not dissolve well in water, and its poor solubility tends to limit its access to living systems. Methylmercury, on the other hand, dissolves in water and readily enters the body by all exposure routes from the intestinal tract following ingestion, through the skin, and through the lungs. Because exposure to methylmercury can happen quickly and easily, it is considered to be an extremely hazardous chemical. 

---