Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.1 Toxicokinetics, toxicodynamics, and toxicology 1317
Dermal absorption of solvents is shown in Table 20.1.1.
Table 20.1.1. Dermal uptake of solvents according to the German MAK-list. 2,64
Benzene
Bromomethane
2-Butanone
2-Butoxyethanol
Carbon disulfide
2-Chloroethanol
Chloromethane
Cresol(s)
Cycolhexanol
Cyclohexanone
Dimethylformamide
Dimethylsulfoxide
1,4-Dioxane
2-Ethoxyethanol
Ethylbenzene
Ethyl formate
Ethylene glycol
n-Hexane
2-Hexanone
Methanol
2-Methoxyethanol
Methyl formate
Nitrobenzene
Nitrotoluene(s)
Phenol
iso-Propyl benzene
n-Propanol (from ACGIH 1 )
1,1,2,2-Tetrachloroethane
Tetrachloroethene
Tetrachloromethane
Toluene
Toluidine(s)
1,1,2-Trichloroethane
Trichloromethane
Xylene(s)
20.1.1.2 Metabolism, distribution, excretion
Specific toxicity of solvents is directly related to their metabolism which is predominantly
catalyzed by cytochrome P-450 mixed-function oxidases in the liver or other tissues.
Relevant examples of specific metabolism are toxic epoxides of benzene
(hemopoietic toxicity), n-hexane 2,5-hexanedione (peripheral neurotoxic effects), metabolites
of ethylene glycol ethers (reproductive toxicity), and unidentified metabolites from trichloroethylene
(renal-toxic effects). 13 It should be emphasized that only the metabolites of
these solvents are associated with toxic effects.
Other relevant metabolic pathways result in detoxified substances, such as
biotransformation processes in the liver − conjugation with glycine, glucuronic acid and
sulphuric acid (e.g., via hydroxylation of toluene) or biotransformation by hydrolysis, oxidation
and conjugation (e.g., glycol ethers).
It should be noted that metabolism processes vary according to the following conditions:
14
• Species, sex, age, genetics, e.g., variability in enzymatic factors such as
polymorphisms (cytochrome systems) or tissue repair mechanisms 15
• Life style − diet, smoking, drug consumption, physical activity
• Saturation. Massive concentrations of solvents result in saturation of metabolic
pathways. This is important with regard to detoxification
• Induction of enzymes. Specific induction of enzyme systems by chemicals (solvents
as well as other chemicals such as drugs) may consequently provoke an increase or
decrease of solvent toxicity
• Interactions may be involved in enhancing or reducing toxicity of solvents. For
example Bloch et al. 16 showed that in cases of alcohol abuse an increase in the toxic
effects of benzene and other lipophilic petroleum derivatives occurs. Also, it has
been shown that benzene inhibits the metabolism of toluene. 17
Solvents can be excreted via various pathways:
• Exhalation (unchanged)
• Urine tract and biliary tract (unchanged or metabolites, e.g. water-soluble
conjugates)
20.1.1.3 Modeling of toxicokinetics and modifying factors
The complexity of toxicokinetic processes of solvents can be described in models, e.g., predicting
exposure situations and distribution phenomena in the human body and quantifying
these processes (e.g. dose-effect response relationships). This applies especially to simula-