Central nervous system, effect of lead

Govoni S, Battaini F, Rius RA, et al. 1988. Central nervous system effects of lead A study model in neurotoxicology. NATO ASI Ser 100(A) 259-275. 

Murata K, Araki S, Yokoyama K, et al. 1995. Autonomic and central nervous system effects of lead in female glass workers in China. Am J Ind Med 28(2) 233-244. 

Bornschein R, Pearson D, Reiter L Behavioral effects of moderate lead exposure in children and animal models, part 1 clinical studies. Grit Rev Toxicol 8 43-99, 1980 Brady M, Torzillo P Petrol sniffing down the track. Med J Aust 160 176-177, 1994 Burchfiel JL, Duffy FH, Bartels PH, et al The combined discriminating power of quantitative electroencephalography and neuropsychologic measures in evaluating central nervous system effects of lead at low levels, in Low Level Lead Exposure The Clinical Implications of Current Research. Edited by Needleman HL. New York, Raven, 1980, pp 75-89... 

Anhalonodine leads to sedation at levels of 100-250 mg. in man—a slightly quieted state, but absolutely no central [nervous system] effects of any type whatsoever. 

Air-poUutant effects on neural and sensory functions in humans vary widely. Odorous pollutants cause only minor annoyance yet, if persistent, they can lead to irritation, emotional upset, anorexia, and mental depression. Carbon monoxide can cause death secondary to the depression of the respiratory centers of the central nervous system. Short of death, repeated and prolonged exposure to carbon monoxide can alter sensory protection, temporal perception, and higher mental functions. Lipid-soluble aerosols can enter the body and be absorbed in the lipids of the central nervous system. Once there, their effects may persist long after the initial contact has been removed. Examples of agents of long-term chronic effects are organic phosphate pesticides and aerosols carrying the metals lead, mercury, and cadmium. 

Like many volatile halocarbons and other hydrocarbons, inhalation exposure to carbon tetrachloride leads to rapid depression of the central nervous system. Because of its narcotic properties, carbon tetrachloride was used briefly as an anesthetic in humans, but its use was discontinued because it was less efficacious and more toxic than other anesthetics available (Hardin 1954 Stevens and Forster 1953). Depending on exposure levels, common signs of central nervous system effects include headache, giddiness, weakness, lethargy, and stupor (Cohen 1957 Stevens and Forster 1953 Stewart and Witts 1944). Effects on vision (restricted peripheral vision, amblyopia) have been observed in some cases (e.g., Johnstone 1948 Smyth et al. 1936 Wrtschafter 1933), but not in others (e.g., Stewart and Wtts 1944). In several fatal cases, microscopic examination of brain tissue taken at autopsy revealed focal areas of fatty degeneration and necrosis, usually associated with congestion of cerebral blood vessels (Ashe and Sailer 1942 Cohen 1957 Stevens and Forster 1953). 

Exposure levels leading to effects on the central nervous systems of humans are not precisely defined. No symptoms of lightheadedness or nausea were experienced by humans exposed to 50 ppm for 70 minutes or 10 ppm for 3 hours (Stewart et al. 1961), but nausea, headache, and giddiness were found to be common symptoms in workers exposed to carbon tetrachloride for 8 hours a day at concentrations of 20-125 ppm (Elkins 1942 Heimann and Ford 1941 Kazantzis and Bomford 1960). Dizziness has also been reported in humans following short-term exposure (15 minutes) at a higher concentration (250 ppm) (Norwood et al. 1950). This suggests that the threshold for central nervous system effects in humans is probably in the range of 20-50 ppm for an 8-hour workday. 

As discussed in Section 2.2, the effects that are most often observed in humans exposed to carbon tetrachloride are liver and kidney injury and central nervous system depression. Exposure levels leading to these effects in humans are not well-defined. The threshold for central nervous system effects following exposures of 8 hours or more is probably in the range of 20-50 ppm (Elkin 1942 Heimann and Ford 1941 Kazantzis and Bomford 1960). On the other hand, kidney and liver effects can occur following exposure (15 minutes to 3 hours) to vapor concentrations of 200 and 250 ppm, respectively (Barnes and Jones 1967 Norwood et al. 1950). These doses correspond to an absorbed dose of approximately 100-200 mg/kg. 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

As previously noted, opioids have significant constipating effects (see Chapter 31). They increase colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption. They also decrease mass colonic movements and the gastrocolic reflex. Although all opioids have antidiarrheal effects, central nervous system effects and potential for addiction limit the usefulness of most. 

Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system. Inhibition of acetylcholinesterase results in accumulation of acetylcholine at muscarinic and nicotinic receptors leading to peripheral and central nervous system effects. These effects... 

These high solvent exposures lead to concern about the possibility of chronic central nervous system effects in professional painters. 

The most probable cause of a submarine sinking is flooding caused by an event that breaches the outer hull. The force required would have to be substantial. Potential causes include surface collision, grounding, external explosion, and catastrophic failure of a hull valve. It is likely that such an event also would start a fire within the submarine. The immediate concern for the crew is the release of toxic gases that are produced as the combustion products of on-board fires (U.S. Navy 1998). Human exposure to these gases can lead to adverse health effects, particularly respiratory and central nervous system effects, and even... 

These exposures may sometimes have long-term effects, not least on children. For instance, reduced birth weights or birth lengths have been associated with environmental levels of bisphenol A (NTP-CERHR 2008), PFOA (Fei et al. 2008), phthalates (Latini et al. 2003) and others (IFCS 2003a), and effects on the central nervous system that may lead to effects on intelligence or behaviour (IFCS 2003a) have been associated with environmental levels of lead, mercury and PCBs. 

Benzene also affects the central nervous system. Effects noted include drowsiness, dizziness, headache, vertigo, tremor, delirium, and loss of consciousness (Flury 1928 Greenburg 1926 Kraut et al. 1988 Yin et al. 1987b). Since benzene may induce an increase in brain catecholamines, it may also have a secondary effect on the immune system via the hypothalamus-pituitary-adrenal axis (Hsieh et al. 1988b). Increased metabolism of catecholamines can result in increased adrenal corticosteroid levels, which are immunosuppressive (Hsieh et al. 1988b). Further studies to determine the molecular mechanism of these effects could lead to additional approaches for reducing the toxic effects of benzene. 

SAFETY PROFILE Poison by ingestion, intraperitoneal, parenteral, and intravenous routes. Moderately toxic by skin contact. An experimental teratogen. Experimental reproductive effects. Lead and its compounds have dangerous central nervous system effects. A flammable liquid and very dangerous fire hazard when exposed to heat, flame, or oxidizers. Moderate explosion hazard in the form of vapor when exposed to flame. May explode when heated above 90°C. Explosive reacdon with tetrachlorotrifluoromethyl phosphorane. 

Inhalation Inhalation of high concentrations may cause central nervous system effects characterized by nausea, headache, dizziness, unconsciousness, and coma. Causes respiratory tract irritation. May cause liver and kidney damage. Aspiration may lead to pulmonary edema. Vapors may cause dizziness or suffocation. Can produce delayed pulmonary edema. Exposure to high concentrations may produce narcosis, nausea, and loss of consciousness. May cause burning sensation in the chest. 

Ethylene glycol and glycoaldehyde have an intoxicating effect on the central nervous system that can lead to ataxia, sedation, coma, and respiratory arrest. The metabolic acidosis reported in toxicity is due to the acidic metabolites, especially glycolic acid. Ethylene glycol itself may result in a large osmolar gap. Oxalic acid may combine with calcium to form calcium oxylate crystals. The precipitation of these crystals in tissue may result in renal failure and hypocalcemia. 

Terfenadine binds to peripheral H-1 receptors. Receptor affinity for muscarinic, a, and /i-adrenergic receptors is low. Poor penetration of terfenadine across the blood-brain barrier limits central nervous system effects. Therefore, terfenadine is classified as nonsedating and lacks anticholinergic side effects. However, accumulation of the parent drug, terfenadine, results in prolongation of the QT interval by blocking the delayed rectifier potassium current in the heart. Prolongation of the QT interval can lead to torsade de pointes and death. 

Researchers have discovered that there are two types of monoamine oxidase enzyme MAO-A and MAO-B, each located in different regions of the body. Older MAOIs, such as Nardil, inhibit both versions of monoamine oxidase, resulting in increased serotonin and norepinephrine inside the cell (and also leakage into the synapse, thus activating receptors). Increases in serotonin and noreinephrine receptor activation can lead to several over-stimulating side effects. These central nervous system effects include tremors, insomnia, agitation, and occasionally, precipitation of a mania in patients with bipolar depression. 

Toxic compounds which interfere with major pathways in intermediary metabolism can lead to depletion of energy-rich intermediates. For example, fluoroacetate blocks the tricarboxylic acid cycle, giving rise to cardiac and central nervous system effects which may be fatal (see Chapter 7). Another example is cyanide (see Chapter 7). 

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