Biomedical Engineering Reference
In-Depth Information
concentrations of 250 ppm or below, they are grossly inconsistent at
higher airborne methanol concentrations. At 500 ppm, the Battelle
(2006) model predicts a human blood methanol concentration of
41.2mg/l, while the Bouchard et al. (2001) model predicts
15.7mg/l, nearly threefold lower. At 1000 ppm, the Battelle (2006)
model predicts 521mg/l, while the Bouchard et al. (2001) model
predicts 31.3mg/l, nearly 17-fold lower. At 10,000 ppm, the Battelle
(2006) model predicts 12,110mg/l, while the Bouchard et al. (2001)
model predicts only 313mg/l, nearly 39-fold lower. As is discussed in
greater detail below, these gross inconsistencies can be traced to flawed
estimates of key metabolic parameters in the Battelle (2006) human
methanol model.
6.4 ARE THE VALUES OF KEY HUMAN METABOLISM
PARAMETERS CONSISTENT WITH THOSE IN THE
PUBLISHED SCIENTIFIC LITERATURE?
The Battelle (2006) model describes methanol metabolism with satu-
rable Michaelis-Menten kinetics in both mice and humans. However,
while the mouse model has two saturable metabolic pathways, one with
a saturation constant of 12mg/l (K
m
), the other with a saturation
constant of 210mg/l (K
m2
), the human has just one saturable metabolic
pathway with a saturation constant exactly equal, surprisingly, to the
first mouse pathway value, namely, 12mg/l. No rationale was supplied
for why the final human parameter estimate of K
m
is exactly the same as
the final mouse K
m
estimate. Apparently this was just assumed to be the
case. This human value is surprising because it implies that human
methanol metabolism is already halfway to saturation at the compara-
tively low venous blood concentration exiting from the liver of 12mg/l,
a prediction that contradicts considerable evidence in the published
scientific literature.
For example, when Bouchard et al. (2001) calibrated and then
validated their model of methanol disposition in rats, monkeys, and
humans, a saturation constant was required only to describe methanol's
metabolism in rats. In monkeys and humans, the metabolism was
