Solvent exposures anesthetics

Most of the alcohol distributes into body water, but like most solvents and anesthetics some distributes into fat. It is excreted in the urine and breath, hence the utility of taking breath samples to evaluate alcohol exposure. The majority of alcohol is metabolized in the liver. Alcohol dehydrogenase (ADH) metabolizes alcohol to acetaldehyde. Acetaldehyde is toxic, with elevated levels causing flushing, headache, nausea, and vomiting. Acetaldehyde is in turn quickly metabolized to the less toxic acetate by acetaldehyde dehydrogenase (ALDH) (Figure 3.1). 

From a health perspective, there are few redeeming features of solvents except when used as anesthetics. Clearly the simple recommendation is to avoid exposure unless administered for some medical reason. In the workplace, appropriate ventilation and personal safety equipment should be in place at all times. There are numerous national and international regulations on solvent exposure in the workplace. Substitution of less-toxic solvents in processes and products can reduce the risk of injury. 

Toxicity. 1,1-Dichloroethane, like all volatile chlorinated solvents, has an anesthetic effect and depresses the central nervous system at high vapor concentrations. The 1991 American Conference of Governmental Industrial Hygienists (ACGIH) recommends a time-weighted average (TWA) solvent vapor concentration of 200 ppm and a permissible short term exposure level (STEL) of 250 ppm for worker exposure. The oral LD q of... 

Jakobson I, Wahlberg JE, Holmberg B, et al. 1982. Uptake via the blood and elimination of 10 organic solvents following epicutaneous exposure of anesthetized guinea pigs. Toxicol Appl Pharmacol 63 181-187. 

Stewart RD, Erley DS, Schaffer AW, Gay HH Accidental vapor exposure to anesthetic concentrations of a solvent containing tetrachloroethylene. Ind Med Surg 30 327-330, 1961... 

The induction of unconsciousness may be the result of exposure to excessive concentrations of toxic solvents such as carbon tetrachloride or vinyl chloride, as occasionally occurs in industrial situations (solvent narcosis). Also, volatile and nonvolatile anesthetic drugs such as halothane and thiopental, respectively, cause the same physiological effect. The mechanism(s) underlying anesthesia is not fully understood, although various theories have been proposed. Many of these have centered on the correlation between certain physicochemical properties and anesthetic potency. Thus, the oil/water partition coefficient, the ability to reduce surface tension, and the ability to induce the formation of clathrate compounds with water are all correlated with anesthetic potency. It seems that each of these characteristics are all connected to hydrophobicity, and so the site of action may be a hydrophobic region in a membrane or protein. Thus, again, physicochemical properties determine biological activity. 

Toxicants may have three effects on pulse rate bradycardia (decreased rate), tachycardia (increased rate), and arrhythmia (irregular pulse). Alcohols may cause either bradycardia or tachycardia. Amphetamines, belladonna alkaloids, cocaine, and tricyclic antidepressants (see imi-primine hydrochloride in Figure 6.12) may cause either tachycardia or arrhythmia. Toxic doses of digitalis may result in bradycardia or arrhythmia. The pulse rate is decreased by toxic exposure to carbamates, organophosphates, local anesthetics, barbiturates, clonidine, muscaric mushroom toxins, and opiates. In addition to the substances mentioned above, those that cause arrhythmia are arsenic, caffeine, belladonna alkaloids, phenothizine, theophylline, and some kinds of solvents. 

Phenoxyethanol produces a local anesthetic effect on the lips, tongue, and other mucous membranes. The pure material is a moderate irritant to the skin and eyes. In animal studies, a 10% v/v solution was not irritant to rabbit skin and a 2% v/v solution was not irritant to the rabbit eye. Long-term exposure to phenoxyethanol may result in CNS toxic effects similar to other organic solvents. 

The precise mechanism of toxicity of cyclohexane has not been identified, but is likely similar to other central nervous system (CNS) depressants and general anesthetics. These compounds are believed to exert their effects through a general interaction with the CNS, and interference with neuronal membrane functions has been postulated as a mechanism of action. Disruption of membrane enzymes and the corresponding alterations in cell functions may account for the behavioral and anesthetic effects observed following exposure to various solvents. 

Stoddard Solvent is a slight to severe skin irritant depending on the exposure condition and duration. This is related to the defatting properties of the solvent. Little is known regarding the specific mechanisms of action for systemic toxicity to Stoddard Solvent. Its effect on the nervous system at high exposure levels may be due to its general solvent properties and anesthetic effect of hydrocarbons in general. 

Although workers are often exposed to a variety of solvents with Stoddard solvent, there are no available studies specifically characterizing the interactions of Stoddard solvent with other chemicals. Since Stoddard solvent may have adverse effects on the nervous system, it may compound the effects of other chemicals that cause central nervous system depression, such as alcohol, barbiturates, benzodiazepines, or medical anesthetics. Guinea pigs with a diet high in vitamin C survived a high exposure to Stoddard solvent vapors better than those with a diet low in vitamin C (Jenkins et al. 1971) however, it is not known how vitamin C levels might affect humans exposed to Stoddard solvent. 

Chloroform (trichloromethane) is a chlorinated hydrocarbon solvent used as a raw material in the production of freon and as an extractant and solvent in the chemical and pharmaceutical industry. Because of its hepatic toxicity, it is no longer used as a general anesthetic or anthelmintic agent. Chronic low-level exposure may occur in some municipal water supplies owing to chlorination of biologic methanes (tri-halomethanes). 

Clinical effects caused by acute tetrachloroethylene exposure include central nervous system depression, liver or kidney injury, and in severe cases even death from anesthetic effects (see Section 2.5). Other effects can include malaise, dizziness, fatigue, headache, and lightheadedness, all of which may disappear soon after the exposure is stopped (HSDB 1996). The mechanism of action for the central nervous system effects has not been clearly established but may be related to solvent effects on lipid and fatty acid compositions of membranes (Kyrklund et al. 1984, 1988, 1990). 

Treatment is nonspecific and should be directed to promote recovery from an anesthetic agent. In treating persons suffering toxic effects caused by exposure to halo-genated solvents, the use of epinephrine (adrenalin) and similar drugs must be avoided because they may produce cardiac arrhythmias, including ventricular fibrillation. 

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