Methyl ethyl ketone (MEK) is a colorless liquid solvent with an acetone-like odor. It is volatile and potentially explosive. Its main uses are in the manufacture of a number of resins, waxes, and coatings, as well as a general industrial solvent for nitrocellulose coating, vinyl film, and smokeless powder manufacture. Over 500 million pounds of it are produced each year in the United States, and probably more than three million workers are exposed to it yearly(l). MEK has the following structure:
Irritation of the nose and throat has been reported to begin at 100 ppm; eye irritation has been reported to start at 200 ppm (2). Dermatitis of the face, probably due to exposure vapors from the MEK, has been reported at concentrations ranging from 300 ppm to 600 ppm (3). Narcosis can occur at even higher concentrations, although the precise air concentration at which narcosis begins is not known.
There is one report of optic neuritis occurring in a worker using MEK as a solvent during painting (4). Elevated levels of methanol were found in his blood, and it was speculated that the methanol was formed as a metabolite of MEK. There are no other reports of such a metabolic pathway for MEK.
A number of studies have suggested that MEK can increase the neurotoxic effects of the solvents methyl nbutyl ketone and n-hexane (1). The neuropathy in these cases is typically a symmetrical distal sensory and motor neuropathy without loss of deep tendon reflexes initially. The syndrome is often irreversible. It does not appear that MEK alone causes such a neuropathy.
Although there is no evidence to date that MEK is carcinogenic or mutagenic, there is some suggestive evidence that it may be injurious to the fetus at very high maternal doses (5). Further, low level chronic exposure has been shown to cause decreased memory and impairment of the central nervous system (6).
The Threshold Limit Value (that amount for which there are no adverse medical effects expected) for an 8 hour exposure to MEK is 200 ppm, or about 590 mg/cum of air, with a recommended short-term exposure limit (15-minute STEL) of 300 ppm. It should be noted that the TLV is based upon information derived from acute, high-level exposure incidents, not long-term, low-level exposures.
Uptake and Metabolism
MEK is absorbed quickly through the lungs upon inhalation of the vapor. The steady-state concentration in expired air after breathing MEK vapors is about 30% of the environmental concentration, indicating aveolar retention of about 70% (7). MEK is also absorbed quickly through intact skin. Application of MEK to the skin of one forearm leads to levels of MEK in expired air equivalent to breathing at least 10 ppm (8). Contact of the solvent with a larger skin area would be expected to give rise to proportionally more absorption, theoretically exceeding the absorption of the vapor through the lungs.
MEK is almost equally soluble in water and in lipids; and, therefore, its concentrations are about the same in all body tissues after an exposure.
Excretion of MEK is predominantly through exhalation of the unchanged compound. The half-life of MEK in expired air is about 30 to 60 minutes. Measured in blood or tissue, the half-life of MEK is about 4 hours. Humans appear to metabolize MEK differently than rats or guinea pigs. The only urinary metabolite of MEK that has been detected in humans is 3-hydroxy-2-buta-none (also known as acetylmethylcarbinol or AMC). The total urinary excretion of MEK itself and AMC accounts for only about O. 1% of an absorbed dose (7).
Urinary MEK concentrations have been found to correlate fairly well with environmental concentrations. Levels of MEK in urine greater than 0.8 ppm have been associated with airborne concentrations above 100 ug/l, or about 30 ppm (7). Also, airborne concentrations above 50 ppm are associated with urinary MEK concentrations above 1.0 ppm (9). However, there is substantial overlap in these determinations, so that routine use of urinary MEK levels to determine individual exposure is not as useful as it is for group determinations.
The attached graph gives an approximate range of urinary concentrations of MEK obtained after at least two hours of exposure, but before exposure had stopped. No information is available describing the amount of MEK excreted or present in the blood once exposure has stopped.
Lauwerys has proposed a tentative maximum permissible value of 2.6 mg of MEK in urine per gram of creatinine (10). This corresponds to an extrapolation of the urinary excretion curve to an exposure level of about 200 ppm. However, to date, there is no published data on MEK excretion rates for exposures in this range.
For sampling procedures, please see the Pacific Toxicology Laboratories collection and shipping instructions for urine and blood volatiles.
1.) National Institute for Occupational Safety and Health. Criteria for a Recommended Standard: Occupational Exposure to Ketones. DHEW (NIOSH) Publication No. 78-173, 1978.
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