Changes in 2,5‐Hexanedione Concentration in the Sciatic Nerve, Serum and Urine of Rats Induced by Combined Administration of 2,5‐Hexanedione with Acetone or Methyl Ethyl Ketone

Abstract

The commonly used organic solvents n-hexane and methyl n-butyl ketone (MBK) are often used together with acetone (AC) and/or methyl ethyl ketone (MEK)1-3). The neurotoxic effects of n hexane and MBK or their metabolite 2,5 hexanedione (2,5-HD) are enhanced by the non neurotoxic hydrocarbons acetone and MEK4-16). Many researchers have investigated the mechanisms of this enhancement.Several metabolic studies 12, 17-21) have shown that the metabolism of n-hexane and the toxicokinetics of 2,5-HD could be influenced by MEK, and previ ous studies 15,[22][23][24] suggested that the toxicokinetic changes in 2,5-HD on coadministration with MEK might be associated with their metabolic interaction in the liver.Wigaeus25) reported that the postexposure elimi nation of acetone via the lung is about 20%, small amounts of acetone (approximately 1%) were elim inated unchanged in urine, and that the metabolized amount excreted in urine exceeded 75%. As it has

Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

“…It is commonly accepted that 2,5-HD concentrations in serum and urine decrease on coexposure to hexane and toluene. Many studies have shown that 2,5-HD levels in serum or urine increase on cotreatment with hexane, MBK or 2.5-HD and with MEK or AC (DiVinceno et al 1978;Perbellini et al 1986;Ahonen and Schimberg 1988;Cardona et al 1993Cardona et al , 1996Yasui et al 1995;Aoki et al 1996), whereas others have found that 2,5-HD concentrations in serum and urine decrease when hexane is given together with MEK (Iwata et al , 1984Shibata et al 1990a, b;Takeuchi et al 1993). …”