Study Set Content:
also can vary from quite water soluble (e.g., glycols and alcohols) to quite lipid soluble (e.g., halocarbons and aromatic hydrocarbons).
Lipophilicity
Many solvents have a relatively low molecular weight and are uncharged, enabling () through membranes from areas of high to low concentration.
passive diffusion
Most systemic absorption of inhaled VOCs occurs in the (), with some absorption occurring in the upper respiratory tract.
alveoli
Gases in the alveoli equilibrate almost () with blood in the pulmonary capillaries
instantaneously
air partition coefficients (PCs) of VOCs
Blood
o May be defined as the ratio of concentration of VOC achieved between two different media at equilibrium
air partition coefficients (PCs) of VOCs
More hydrophilic solvents have relatively () blood: air PCs, which favor extensive uptake. o Because VOCs diffuse from areas of concentration, increases in respiration (to maintain a high alveolar concentration) and in cardiac output/pulmonary blood flow (to maintain a large concentration gradient by removing capillary blood containing the VOC) enhance ()
high, high to low, pulmonary absorption
() are well absorbed from the GI tract. Peak blood levels are observed within minutes of dosing, although the presence of food in the GI tract can delay absorption.
Solvents
Absorption of solvents through the skin can result in both local and systemic effects. Lipophilic solvents penetrate the () by passive diffusion.
stratum corneum
Solvents absorbed into () blood from the GI tract are subject to uptake/elimination by the liver and exhalation by the lungs during their first pass through the pulmonary circulation . • Solvents that are well () and quite () are most efficiently eliminated before they enter the arterial blood blood
Portal venous,metabolized, volatile
• Hepatic first-pass elimination depends on the chemical and the rate at which it arrives in the liver. • Pulmonary first-pass elimination, in contrast, is believed to be a() process as a fixed percentage of the chemical is thought to exit the pulmonary blood at each pass through the pulmonary circulation.
zero-order
Many solvents are poorly soluble in water and must be enzymatically () to relatively water-soluble derivatives, which may be more readily eliminated in the largely aqueous urine and/or bile.
converted
Some solvents can undergo bioactivation to produce reactive metabolites that are cytotoxic and/or mutagenic. • ()()()()() are examples of solvents that are metabolized to toxic products
Toluene, benzene, 1,1,1-trichloroethylene, hexane, and carbon tetrachloride
In particular,() catalyzes the oxidation of halogenated and aromatic hydrocarbons, including benzene, styrene, chloroform, and vinyl chloride to electrophilic metabolites capable of causing cytotoxicity and/or mutagenicity.
CYP2E1
Most age-dependent differences are less than an order of magnitude, usually varying no more than ()()fold. • The () and more immature the subject, the more different is his or her response from that of adults.
two- to three, younger
GI absorption of solvents varies little with age, because most solvents are absorbed by
passive diffusion
Systemic absorption of inhaled VOCs may be greater in() and ()than in adults owing to the relatively high cardiac output and respiratory rates despite their lower alveolar surface area
infants and children
, expressed as percentage of body weight, is highest in newborns and gradually diminishes through childhood.
Extracellular water
is high from ~1/2 to 3 years of age, and then steadily decreases until adolescence, when it increases again in females
Body fat content
during maturation may impact susceptibility to solvent toxicity.
Changes in xenobiotic metabolism
