Handbook of Solvents - George Wypych - ChemTech - Ventech!

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the skin, whether the skin is healthy or not (there is increased absorption if the skin has reduced
cellular membrane), and the lipid solubility of the solvent.
As far as the gastrointestinal tract, commonly this is not a significant route of absorption.
Solvents absorbed via the gastrointestinal tract are removed immediately by the liver
through the first-pass metabolism. If the amount of solvents and quantity of solvents ingested
is increased significantly and exceeds the capacity of the liver to metabolize the solvents,
then the gastrointestinal tract route will become significant. 4,5,6
The distribution of an organic solvent in the human body depends upon its partial pressure
in the arterial blood and the solubility of the solvent in the tissue, as well as the blood
flow rate through the tissue. 7 Data on tissue distribution of various solvents are limited at
best.
The metabolism of solvents depend on the solvent. Alcohols are metabolized via alcohol
dehydrogenase, whereas other organic solvents are mainly metabolized by the
cytochrome P-450-dependent enzymes. These enzymes may be found in the liver, kidneys,
lungs, gastrointestinal tract, gonads, adrenal cortex, and other body organ tissues. The metabolism
of solvents has been described extensively, 8,9 and the reader is referred to those
writings.
The metabolites of the organic solvents are eliminated via the kidneys through urine
excretion and to some extent, by exhalation of the unchanged original solvent. Commonly
the parent solvent is eliminated by the kidneys and this amounts to less than 1%. The metabolites
are the main source of excretion of the metabolized parent solvent.
In the last several decades, there have been several studies in experimental animals,
case reports in humans, case studies in humans, and epidemiological studies in humans on
the effects of solvents on the kidney, both acutely and chronically. The scope of this chapter
is the clinical chronic effects of solvents on the kidney (chronic nephrotoxicology).
20.4.2 EXPERIMENTAL ANIMAL STUDIES
The toxic effects of organic solvents on the kidneys has been studied in several experimental
species, especially mice and rats. Damage to the kidney has been shown in these experimental
animals in the form of acute damage to various parts of the nephron, especially the
tubules. This has usually been described as tubular degeneration with regenerative epithelium,
deposits of mineral crystals and of intralobular proteins, and interstitial inflammation.
8,10-15 Several studies have shown glomerular damage in experimental animal 16,17 and
have suggested that long-term solvent exposure alters the immune system and leads to the
glomerulopathy with mesangial IgA deposits.
While the exact mechanism is not known and various mechanisms have been postulated,
it is reasonable to accept a mechanistic approach which takes into account genetic, environmental,
susceptibility (such as pre-existing diseases including hypertensive kidney
disease and diabetes), direct tubular toxicity, permeability changes and immunosuppression.
20.4.3 CASE REPORTS
The earlier documentation of chronic renal disease and hydrocarbon exposure consists of
case reports, and this data was summarized by Churchill et al. 18 describing Goodpasture’s
syndrome in 15 adults, epimembranous glomerulonephritis in 5 adults, and subacute
proliferative glomerulonephritis in one adult. The hydrocarbon exposures were for solvents
in 12 patients, gasoline in 4, gasoline-based paint in 3, jet fuel, mineral turpentine and un-