Studies on the respiratory uptake and excretion and the skin absorption of methyl n-butyl ketone in humans and dogs

Methyl n-butyl ketone (MnBK) has produced peripheral neuropathy in experimental animals and is implicated in an occupationally produced neuropathy. Since occupational exposure to MnBK is by inhalation or skin contact, both the absorption and elimination of MnBK vapor and its absorption through skin were investigated. Studies were carried out first with male beagle dogs and subsequently with human volunteers. Humans exposed for 7.5 hours to 10 or 50 ppm or for 4 hr to 100 ppm of MnBK vapor absorbed between 75 and 92% of the inhaled vapor. Unchanged MnBK was not eliminated extensively in the postexposure breath or in urine. 2,5-Hexanedione, a metabolite of MnBK known to be neurotoxic in rats, was found in the serum of humans exposed to either 50 or 100 ppm of MnBK. The absorption and elimination of MnBK in dogs was similar to that observed in humans. The skin absorption of 1-¹⁴C]MnBK or a $\text{9}\text{1}$ ($\text{v}\text{v}$) mixture of methyl ethyl ketone $\text{(MEK)}\text{1-}{}^{14}\text{C]MnBK}$ was determined by excretion analysis. Two volunteers exposed by skin contact to 1-¹⁴C]MnBK absorbed 4.8 μg min^?1 cm^?2 and 8.0 μg min^?1 cm^?2, respectively. Skin exposure to $\text{MEK}\text{1-}{}^{14}\text{C]MnBK}$ resulted in the respective absorption of 4.2 and 5.6 μg min^?1 cm^?2 by two individuals. Two volunteers given an oral dose of 1-¹⁴C]MnBK (2 μCi; 0.1 mg/kg) excreted 49.9 and 29.0% of the dose, respectively, as respiratory ¹⁴CO₂ within 3 to 5 days and 27.6 and 25.0% of the dose, respectively, in urine within 8 days. Both 1-¹⁴C]MnBK and $\text{MEK}\text{1-}{}^{14}\text{C]MnBK}$ were absorbed through the skin of dogs. These findings show that MnBK is readily absorbed by the lungs, the gastrointestinal tract, and through the skin, is not eliminated extensively unchanged in breath or urine, and is metabolized to CO₂ and 2,5-hexanedione. Radioactivity derived from 1-¹⁴C]MnBK was excreted slowly by man, suggesting that repeated daily exposure to high concentrations of MnBK may lead to a prolonged exposure to neurotoxic metabolites.