By 202380261
Discussion
V. MOVEMENT OF TOXICANTS IN THE ENVIRONMENT
Categories of Toxic effects
➤ When reversible interactions are responsible for toxic effects, the concentration of the chemical present at the site of action is the only determinant of toxic outcome.
➤ When the concentration of the xenobiotic is decreased by excretion or biotransformation, a parallel decrease of toxic effects is observed.
After complete excretion of the toxic agent, toxic effects are reduced to zero.
➤ For example, carbon monoxide binds to hemoglobin and, due to the formation of the stable hemoglobin-carbon monoxide complex, binding of oxygen is blocked. As a result of the impaired oxygen transport in blood from the lung, tissue oxygen concentrations are reduced and cells sensitive to oxygen deprivation will die. The toxic effects of carbon monoxide are directly correlated with the extent of carboxyhemoglobin in blood, the concentration of which is dependent on the inhaled concentration of carbon monoxide. After exhalation of carbon monoxide and survival of the acute intoxication, no toxic effect remains.
Irreversible toxic effects
➤ often caused by the covalent binding of toxic chemicals to biological macromolecules.
➤ Under extreme conditions, the modified macromolecule is not repaired; after excretion of the toxic agent, the effect persists.
➤ Further exposure to the toxic agent will produce additive effects.
➤ many chemicals carcinogens are believed to act through irreversible changes.
Table 3. Reversible and irreversible interactions of chemicals with cellular macromolecules as a basis for toxic response
Toxic response neurotoxicity cancer oxygen deprivation in tissues neurotoxicity
Example tri-o-cresylphosphate dimethylnitrosamine carbon monoxide carbamate pesticides