Organic Solvent Neurotoxicity

The acute neurotoxic effects of organic solvent exposure in workers and laboratory animals are narcosis, anesthesia, central nervous system (CNS) depression, respiratory arrest, unconsciousness, and death. Acute experimental exposures of human volunteers to one or several organic solvents have impaired psychomotor function as measured by reaction time, manual dexterity, coordination, or body balance. Chronic animal studies with a limited number of organic solvents support the evidence for peripheral neuropathy and mild toxic encephalopathy in solvent-exposed workers. Epidemiologic studies of various groups of solvent-exposed workers have demonstrated statistically significant chronic changes in peripheral nerve function (sensory and motor nerve conduction velocities and electromyographic abnormalities) that persisted for months to years following cessation of exposure. Epidemiologic studies have also shown statistically significant increases in neurobehavioral effects in workers chronically exposed to organic solvents. These effects include disorders is characterized by reversible subjective symptoms (fatigability, irritability, and memory impairment), sustained changes in personality or mood (emotional instability and diminished impulse control and motivation), and impaired intellectual function (decreased concentration ability, memory, and learning ability). Among organic solvent abusers, the most severe disorders reported are characterized by irreversible deterioration in intellect and memory (dementia) accompanied by structural CNS damage.

Physical and Chemical Properties

The term "organic solvents" refers to a group of volatile compounds or mixtures that are relatively stable chemically and that exist in the liquid state at temperatures of approximately 0° to 250°C (32° to 482°F). Common organic solvents are classified as aliphatic hydrocarbons, cyclic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ketones, amines, esters, alcohols, aldehydes, and ethers. Many common solvents often exist as mixtures or blends of chemical compounds (e.g., Stoddard solvent and thinners) (WHO 1985; Parrish 1983).

The second level of disorder is described as mild chronic toxic encephalopathy (WHO Workshop), or the Type 2 disorder (International Solvent Workshop). This level involves both symptoms of neurotoxicity and abnormalities of performance on formal neuropsychological testing. The Type 2 disorder has been divided into Type 2A (sustained personality or mood changes such as emotional instability and diminished impulse control and motivation) and Type 2B (impairment in intellectual function manifested by diminished concentration, memory, and learning capacity).

Conclusions

In man, the acute reversible effects of exposure to organic solvents appear to result from properties of the parent compound. However, the chronic effects may be caused by metabolic activation of the parent compound, which results in more reactive intermediate metabolites (e.g., 2,5-hexanedione, a metabolite of n-hexane and methyl n-butyl ketone) that may alter nervous tissue structure. Chronic effects are often correlated with changes in nervous tissue structure and function that may be irreversible.

Chronic neurotoxicity in workers exposed to organic solvents over a period of months to years includes (1) peripheral neuropathies such as axonal degeneration seen in workers exposed to hexacarbon solvents (e.g., n-hexane, methyl n-butyl ketone), (2) Type 1 CNS symptoms such as fatigability irritability, and memory impairment, and (3) Type 2 mild toxic encephalopathy, including sustained personality or mood changes such as emotional instability, diminished impulse control and motivation, and impairment in intellectual function manifested by diminished concentration, memory, and learning capacity. Epidemiologic studies have demonstrated correlations of workplace solvent exposures with the types of solvent-related CNS dysfunctions noted above and changes in neurophysiologic parameters such as nerve conduction velocities. Studies have demonstrated that these effects can persist for months to years after removal of workers from solvent exposure. The extent to which chronic neurotoxicity is reversible remains to be established; peripheral nerves have the capacity to regenerate, but damage to the CNS is more often permanent.

J. Donald Millar, M.D., D.T.P.H. (Lond.)
Assistant Surgeon General
Director, National Institute for
Occupational Safety and Health
Centers for Disease Control

ORGANIC SOLVENT NEUROTOXICITY

Extract from http://www.cdc.gov/niosh/87104_48.html

Abstract

Physical and Chemical Properties

Conclusions