[Factors contributing to interindividual variability to chemical toxicity].
Recognising toxicokinetic and toxicodynamic variability is important in the risk assessment of chemicals and may help to explain individual differences in susceptibility in exposed populations. This presentation discusses the influence of age, gender, disease and genetics on toxicokinetic and toxicodynamic processes. Neonates have a reduced capacity for metabolism and elimination of xenobiotics that may enhance chemical toxicity caused by a parent chemical. Furthermore, the brain, reproductive organs and immune system have critical postnatal periods of maturation where they appear highly sensitive to toxic effects that interfere with the maturation process and may lead to permanent structural or functional organ changes. In the elderly, a combination of reduced organ function, disease and use of pharmaceuticals contributes to enhanced chemical sensitivity reflected in an increased incidence of adverse drug reactions in this population. There is a high degree of functional polymorphism in biotransforming enzymes. Such polymorphisms have been shown to contribute to interindividual variability in chemical response. During the last few years, accounts have been given of several polymorphisms in genes with importance for toxicodynamic processes, such as DNA repair genes and receptor genes. However, further information is needed in order to evaluate the functional contribution of these polymorphisms to chemical sensitivity and health risk.
Lindeman
Birgitte
B
Divisjon for miljømedisin Nasjonalt folkehelseinstitutt Postboks 4404 Nydalen 0403 Oslo.
Søderlund
Erik J
EJ
Dybing
Erik
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002648:Child; D004351:Drug Resistance / Q000502:physiology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005767:Gastrointestinal Diseases / Q000378:metabolism; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic / Q000502:physiology; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors