Neurotoxicity of Volatile Organic Compounds

Volatile organic compounds (VOCs), such as solvents, esters, hydrocarbons, aromatic compounds, and other organic chemicals, are characterized by low boiling temperature and higher volatility (Table 23.2). They are ubiquitous in agriculture, providing power for vehicles and used in every technological process. Volatile organic compound toxicity is divided into clinical syndromes based on the organ system: the lungs are affected most commonly, but instances of neurological, cardiac, gastrointestinal, renal, hematological, and skin pathology are also well documented. Three factors affect the selectivity and severity of toxic effects: the identity of the VOC, the dose, and the route of exposure (Table 23.2) (32-34).

Almost all VOCs are strongly lipophilic and attracted to neural tissue. Demyelinating peripheral polyneuropathy is associated with exposure to 6-carbon aliphatic hydrocarbons (n-hexane, methyl-n-butyl-ketone) that are metabolized into a compound that interferes with axonal transport. Long-term workplace exposure or inhalant abuse (solvent sniffing) may result in chronic headaches, cerebellar ataxia, and encephalopathic findings of cognitive and psychopathic impairment (34).

Butane, benzene, toluene, and xylene are CNS depressants, have a disin-hibiting euphoric effect, and are used as agents of abuse. Patients present with symptoms of CNS disinhibition, such as dizziness, slurred speech, ataxia, and obtundation. Ventilatory drive may be compromised. The initial

Table 23.2. Chemicals found in specific products.

Product

Solvents

Balsa wood cement

Ethyl acetate

Contact adhesives

Toluene, hexane, esters

Tire adhesive

Toluene, xylenes

PVC cement

Trichloroethylene

Air freshener, deodorants, fly spray,

Halons (chloro-fluoro-organic compounds),

hair lacquer, spray paints,

butane, dimethyl ether, methylbutyl ketone

aerosol packages

Anesthetics/analgesics

Nitrous oxide, ether, chloroform

Commercial dry cleaning, domestic

1,1,1-Trichloroethane, tetrachloroethylene,

spot remover

trichloroethylene

Fire extinguishers

Bromochlorodifluoromethane, halons 11 and 12

Cigarette lighters

n-Butane, isobutane, propane

Nail/varnish remover

Acetone and esters

Paints/paint thinners

Butanone, esters, hexane, toluene, xylene

Paint stripper

Dichloromethane, toluene

Surgical plaster/chewing gum removers

Trichloroethylene

Paint thinners

1,1,1-Trichloroethane, toluene, hexane,

methyl n-butyl ketone

PVC, polyvinyl chloride.

Source: Data from Feldman (1), Ford (3), and LaDou (4).

PVC, polyvinyl chloride.

Source: Data from Feldman (1), Ford (3), and LaDou (4).

Table 23.3. Toxic effects of various volatile organic compounds.

Specific compound

Signs and symptoms

Aliphatic hydrocarbons n-Butyl, isobutyl, and amyl nitrite Naphtha, kerosene

Gasoline n-Hexane

Benzene

Naphthalene

Styrene Toluene

Dizziness, syncope, giddiness, hypotension, cerebral ischemia, headache, tachycardia Increased intraocular pressure, confusion, sudden death, convulsion, coma Irritation of mucous membranes, nausea, ataxia, dizziness, hallucinations Respiratory arrest, syncope, death, myoclonia, chorea, encephalopathy, tremor, pulmonary hemorrhage and edema, pneumonitis, plumbism, anemia, lead encephalopathy, confusion, dementia, cerebral edema, peripheral and cranial neuropathies, paresthesias, proteinuria, hematuria Eye and nasopharynx irritation, dizziness, giddiness, nausea, headache, CNS depression, peripheral neuropathy, anemia, basophilic stippling, bone marrow depression, fatal overdose Irritation of conjunctivae and visual blurring; irritation of mucous membranes; dizziness; headache; unconsciousness; convulsions; tremors; ataxia; delirium; tightness in chest; irreversible brain damage with cerebral atrophy; fatigue; vertigo; dyspnea; respiratory arrest; cardiac failure and ventricular arrhythmias; leukopenia; anemia; thrombocytopenia; petechiae; blood dyscrasia; leukemia; bone marrow aplasia; fatty degeneration and necrosis of liver, heart, adrenal glands; fatal overdose Irritation and injury of conjunctivae and corneas, perspiration, nausea, vomiting, headache, cataracts, hemolytic anemia (greater in G-6-PD deficiency), hepatic necrosis, hematuria, jaundice, proteinuria, oliguria, anemia, excitement, confusion, convulsions, coma, dermatitis, fatal overdose Irritation of mucous membranes, CNS depression and narcosis, fatal overdose CNS depression, syncope, coma, cardiac arrhythmias and sudden death, ataxia, convulsions, rhabdomyolysis, increased creatine phosphokinase, abdominal pain, nausea, vomiting, hematemesis, peripheral neuropathy, paresthesias, encephalopathy, optic neuropathy, cerebral ataxia, distal renal tubular acidosis, hyperchloremia, hypokalemia, azotemia, hypophosphatemia, hematuria, proteinuria, pyuria, hepatosplenomegaly, lymphocytosis, macrocytosis, basophilic stippling, hypochromia, eosinophilia, EEG abnormalities, decreased cognitive function, fatal overdose presentation may mimic alcohol intoxication. In some patients, an initial component of CNS stimulation may present as agitation, tremor, or seizure (Table 23.3) (35-37).

A physician dealing with the predominantly rural population may expect to see intermediate and long-term, low-level exposures that can lead to reversible and nonreversible neurological abnormalities. In some cases exposures that caused long-term neurotoxic effects have been estimated

Table 23.3. Toxic effects of various volatile organic compounds. (continued)

Specific compound

Signs and symptoms

Xylene

Esters Glycols

Irritation to eye and mucosa; CNS depression and narcoses; reversible corneal damage; death; pulmonary edema and hemorrhage; fatty degeneration of heart, liver, and/or adrenal glands; abnormal liver function tests Irritation of eyes, skin, and mucous membranes; CNS depression; liver and kidney necrosis; fatal overdose Oxalosis, impaired renal and liver function, stupor, coma, convulsions, irreversible brain damage, pulmonary edema, respiratory failure, nausea, vomiting, headache, tachycardia, hypotension, hypoglycemia, hypocalcemia, intravascular hemolysis, lymphocytosis, proteinuria, hematuria, fatal overdose

Decreased myocardial contractility, arrhythmias, cardiac arrest and failure, myocarditis, renal failure, paresthesias, tinnitus, ataxia, headache, narcosis, CNS damage, sudden death Nausea; vomiting; confusion; unconsciousness; coma;

respiratory slowing; color blindness; blurred vision; memory loss; paresthesias; tremors; dermatitis; CNS edema, congestion, and hemorrhage; edema and inflammation of the lungs, kidneys, spleen, and pancreas; fatty degeneration of liver; cardiac arrhythmias; sudden death Liver and kidney abnormalities, fatal overdose Abdominal discomfort, dizziness, fatigue, headache, nausea, vertigo, CNS depression, coma, vomiting, acidosis, mydriasis, retinal edema and ganglion cell destruction, philophobia, mydriasis, areflexia, hemorrhagic infiltration of basal ganglia, decreased vision and blindness, fatal overdose Irritation of eyes and mucous membranes, nausea, vomiting, abdominal pain, hematemesis, narcosis, coma, areflexia, depressed respiration, oliguria, diuresis, fatal overdose Coma, areflexia, depressed respiration, oliguria and diuresis, fatal overdose, irritation of eyes and mucous membranes, CNS depression, kidney and liver damage, fatal overdose

CNS, central nervous system; G-6-PD, glucose-6-phosphate dehydrogenase. Source: Data from Feldman (1), Ford (3), LaDou (4), and So (5).

Trichloroethane, trichloroethylene, methylchloroform Carbon tetrachloride, ethylene dichloride

Methylene chloride Methyl alcohol

Isopropyl alcohol Butyl alcohol to be below levels designated in regulations as acceptable for workers (Table 23.4) (37).

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