Toxicological Review of n-Hexane (CAS No. 110-54-3) (PDF)

Tissues
Time after exposure (hours) a
0 1 2 4 8
2-Hexanone 0.69 ± 0.13 0.29 ± 0.02 0.11 ± 0.01 0.03 ± 0.01 0.01 ± 0.00 ND ND
2,5-HD 2.41 ± 0.30 1.79 ± 0.10 3.10 ± 0.34 3.61 ± 0.40 2.07 ± 0.09 0.29 ± 0.01 0.16 ± 0.01
Blood
n-Hexane 0.45 ± 0.11 0.30 ± 0.05 0.13 ± 0.02 0.04 ± 0.01 ND ND ND
2-Hexanone 0.70 ± 0.10 0.30 ± 0.05 0.10 ± 0.01 0.04 ± 0.01 0.01 ± 0.00 ND ND
2,5-HD 1.06 ± 0.27 0.93 ± 0.12 1.51 ± 0.21 1.73 ± 0.30 0.74 ± 0.09 0.33 ± 0.03 0.14 ± 0.04
Fetus
n-Hexane 0.61 ± 0.14 0.31 ± 0.12 ND ND ND ND ND
2-Hexanone 0.51 ± 0.08 0.18 ± 0.00 0.10 ± 0.01 0.03 ± 0.00 0.01 ± 0.00 ND ND
2,5-HD 1.17 ± 0.15 0.97 ± 0.16 1.24 ± 0.09 1.67 ± 0.16 0.80 ± 0.05 0.29 ± 0.07 0.07 ± 0.01
a Values are µg/mL or µg/g wet weight ± SEM.
ND = Not detected.
Source: Bus et al., 1979.
The kinetics of the metabolism of n-hexane has also been investigated in vitro using
microsomal preparations from the liver and lung of male Sprague-Dawley rats (Toftgard et al.,
1986). The concentrations of the metabolic products formed and the reaction velocities were
determined. The kinetic data were plotted using an Eadie-Scatchard transformation. An Eadie-
Scatchard transformation is a plot of velocity/substrate concentration on the y-axis against
velocity on the x-axis. It is used to estimate the K m and V max for an enzyme. The estimated
parameters for n-hexane hydroxylation in the liver and lung are presented in Table 3-5.
The values for 1- and 2-hexanol suggested that a two-enzyme system is responsible for
the metabolism of n-hexane to these metabolites in liver tissue. The lower a K m value, the higher
the affinity of an enzyme for a substrate. The data indicate that one of the metabolic enzymes
has a high affinity for n-hexane as a substrate, while the other has a lower affinity. The
metabolite of greatest interest in the liver is 2-hexanol because of its conversion to
2,5-hexanedione, a toxicologically active metabolite. The enzyme represented by K m1 in Table
3-5 with a K m of 6.0 µM is primarily responsible for the production of 2-hexanol. The second
enzyme system (K m2) involved in the production of 2-hexanol has a K m of 1,100 µM and thus a
far lower affinity for n-hexane than the first system. This suggests that the first system is likely
to play the major role in the production of 2-hexanol in the liver. The production of 1-hexanol in
the liver also appears to involve two enzymes with considerably different affinities for the
substrate. The enzyme represented by K m1 with a K m of 0.4 µM has a greater affinity for hexane
12
12
18