The Role of Metabolism in Establishing Chemical-Specific Adjustment Factors for n-Hexane and Methyl n-Butyl Ketone

ABSTRACT

This paper focuses on the derivation of chemical-specific adjustment factors (CSAFs) for two neurotoxic solvents, n-hexane and methyl n-butyl ketone (MBK). Workers are exposed to the chemicals mainly via inhalation when they are used, for example, as solvents in adhesives. In order to derive CSAFs for n-hexane and MBK, research data were used from animal studies conducted in our laboratory. Also, MEDLINE and TOXLINE databases were searched for references containing animal and human toxicokinetic and toxicodynamic data. International Programme on Chemical Safety (IPCS) guidelines were followed. From the available data, the composite factor (CF) for n-hexane was calculated to be 18.2. Because n-hexane and MBK are most often used in combination with other solvents, e.g., methyl ethyl ketone (MEK), the metabolic induction of the toxicity of n-hexane or MBK by MEK should be considered in the derivation of CSAFs. However, in the presence of MEK the calculated CF for both n-hexane and MBK is 13. As more human data become available, the CFs for the mixtures may be reduced compared to the individual chemicals.

Keywords:

• CSAFs
• n-hexane
• methyl n-butyl ketone
• metabolism.

Notes

^a Mean ± SD

^b Interspecies kinetic adjustment factor = mean_human/mean_animal; References: Shibata et al. 1990, 2002.

^a Maximal motor nerve conduction velocity

^b Residual latency of motor nerve conduction

^c Mean ± SD

^d Significantly different from controls (p < 0.05)

^e Intraspecies dynamic + kinetic adjustment; factor = mean + 2 SD/mean for exposed group; Reference: Sanagi et al. 1980.

^a Exposure: 12 h/d; 6 d/wk; 20 wk; n = 8/group

^b Mean ± SEM

^c HX = hexane; MEK = methyl ethyl ketone

^d Significantly different from HX and HX + MEK (2000 + 200) (p < 0.01)

^e Adjustment factor for the mixture = mean_HX+MEK/mean_HX; Reference: Ichihara et al. 1998.

^a HX = hexane; MEK = methyl ethyl ketone

^b Mean ± SD

^c Significantly different from controls (p < 0.01)

^d Adjustment factor for the mixture (includes both kinetics and dynamics) = mean + 2 SD/mean for exposed group; Reference: Mutti et al. 1982.