Handbook of Solvents - George Wypych - ChemTech - Ventech!

1386 Nachman Brautbar
tors, concluded that the capacity of xylene and xylene isomers to induce hepatic cytochrome
P450 suggests the possibility of synergistic toxic effects from simultaneous exposure to
xylene and substances metabolically activated by these cytochromes P450. Therefore, exposure
to a mixture of solvents which also include xylene will increase the toxicity and
xylene is a synergistic liver toxicant. For instance, the formation of 2-hexanoyl a metabolic
precursor of 2,5-hexanedione, which is the main metabolite found in urine of workers exposed
to n-hexane, is increased following xylene treatment. 27
20.7.4 SOLVENT MIXTURES
Various solvent mixtures have been reported as hepatotoxic, Fishbien et al. 28,29 reported abnormal
liver functions in chemical workers exposed to a mixture of solvents. It was suggested
that bile acids as indicators of hepatic function will be utilized as markers of injury.
Franco et al. 30 examined a group of workers exposed to organic solvents, and used the criteria
addressing exposure to solvent mixtures for over two years, daily ethanol consumption
less than 50 grams, no history of hepatic disease, no drug intake in the previous three
months. Workers were exposed to between 6 and 9 solvents, mostly toluene, xylene, acetone,
methyl acetate, and butanol ethyl acetate. The mean levels of liver enzyme activities in
the exposed and the control group were similar. The mean serum bile acid contents was statistically
and significantly increased in the exposed group compared to the controlled group.
The authors concluded that the observation of higher serum bile acid levels in the group of
workers currently exposed to organic solvents might be explained by a change in hepatocyte
function, and that the commonly followed parameters of liver enzymes may be insensitive
to these preliminary initial changes in liver function. Conventional liver function tests seem
to be rather insensitive to early detect liver damage from solvents exposure. Early detection
is crucial, but is probably missed since the standard liver functions tests are not sensitive
enough to detect early liver damage from solvents. What that means is that by the time the
patient is seen by the doctor with liver fibrosis or necrosis and solvent toxicity, it is already
in advanced stages. Joung-Dar-Chen et al. 31 evaluated the effects of solvents exposure on
liver functions, specifically looking at gamma glutamyl transferase activity. They have
studied the effects of xylene and toluene. The median air concentration was evaluated in the
exposed workers who used mixed solvents in the process of spray booth car painting. These
investigators showed that gamma glutamyl transferase activities increased independently
with both an increased consumption of alcohol and exposure to a mixture of solvents. They
have concluded that an increase in GGT activity may be a form of enzyme induction rather
than a marker for cellular damage. Kurpper et al. 32 examined the effect of mixed organic solvents
on liver enzymes activity in car painters, and found that at the exposure level of that
study (at that time was 1/2 the level recommended by the regulatory agencies) the liver enzyme
activities of car painters were not effected by exposure to mixed solvents. The continuation
of the previous study by Franco et al. 33 examined serum bile acid concentrations as a
marker of liver functions in a group of workers exposed to organic solvents. They have
shown a significantly increased concentration of serum bile acids with normal liver enzymes,
and concluded that this indicated a very sensitive and early marker of liver function
abnormality in patients exposed to mixed solvents, and might be explained as an early sign
of liver dysfunction. While it was not possible to state which solvent caused what type of abnormality,
the authors concluded that conventional liver function tests seem to be rather insensitive
for early liver disease detection, and normal measurement does not rule out the
existence of subclinical disease, and therefore, an elevation of serum bile acid indicates