Study Set Content:
develop asynchronously. Increased rates of metabolism, urinary excretion, and exhalation by children should hasten elimination and reduce body
P450 isoforms
Age influences the distribution of xenobiotics in the body as well as their metabolism and elimination. • With aging, body fat usually()substantially at the expense of lean mass and body water (decrease lean body mass and body water)
increases
Cardiac output and renal and hepatic blood flows are () in the elderly. • ()()()() diminish with aging, even in the absence of chemical exposure
diminished, Memory, attention, visual perception, and motor skills
The elderly, like infants and children, may be ()() sensitive to the toxicity of solvents than young adults. () organ system toxicity could be due to increased inflammatory damage or to age-related dysregulation of cytokines.
more or less, greater
Other major sources of variability and complexity in () populations include inadequate nutrition, the prevalence of disease states, and the concurrent use of multiple medications.
geriatric
Physiologic and biochemical differences between men and women have the potential to alter tissue dosimetry and health effects of certain solvents.
Gender
occur at different frequencies in different ethnic groups. • Polymorphisms or xenobiotic-metabolizing enzymes may affect the quantity and quality of enzymes and the outcomes of exposures to solvents in different racial groups.
Genetic polymorphisms or biotransformation
Preexposure to chemicals that induce or inhibit biotransformation enzymes can potentiate or reduce the toxicity/carcinogenicity of high doses of solvents that undergo metabolism.
P450 INDUCERS AND INHIBITORS
would generally be anticipated to enhance the toxicity of solvents that are metabolically inactivated and protect from solvents that undergo metabolic activation.
Inhibitors
Exercise () alveolar ventilation and cardiac output/pulmonary blood flow. • Polar solvents with relatively high blood: air PCs (e.g., acetone, ethanol, and ethylene glycol [EG]) are very rapidly absorbed into the pulmonary circulation. () is rate-limiting for these chemicals.
Increases, Alveolar ventilation
()are rate-limiting or uptake of more lipophilic solvents.
Pulmonary blood flow and metabolism
Heavy exercise can increase pulmonary uptake of relatively ()solvents as much as five-fold in human subjects. Light exercise doubles uptake of relatively ()soluble solvents.
polar , lipid
() to the liver and kidneys diminishes with exercise, which may diminish biotransformation of metabolized solvents and urinary elimination.
Blood flow
Presence of food in the stomach and intestines can inhibit systemic absorption of ingested chemicals by preventing contact of the chemical with the GI epithelium. • Food intake results in increased ()()())()
splanchnic blood flow, which favors GI absorption, hepatic blood flow, and biotransformation.
Fasting for 1 to 3 days results in decreased () of electrophilic metabolites (especially since hepatic glutathione levels are decreased) and the formation of cytotoxic, mutagenic, metabolites.
detoxification
Many medications and()and other components of tobacco smoke can induce metabolism of solvents
nicotine
Methyl alcohol or wood alcohol
Methanol
Serious () toxicity is most commonly associated with ingestion.
methanol
Methanol →
alcohol dehydrogenase
→ (alcohol dehydrogenase) →
Formaldehyde
