Chemical and biochemical dosimetry of exposure to genotoxic chemicals.

Abstract

Epidemiologic studies designed to evaluate the health significance of environmental chemicals are compromised by the lack of quantitative exposure data for individuals in exposed populations. Monitoring data on levels of compounds in environmental media often represent the only information available, and average population exposure is therefore the only quantitative parameter that can be calculated. Biological monitoring, i.e., measurements on cells, tissues or body fluids of exposed persons, has the objective of defining the so-called "internal dose" or "effective dose" on an individual basis. Such measurements can be used to ensure that current or past exposure does not entail unacceptable health risks, or can detect potentially excessive exposure before the appearance of adverse health effects. Results obtained through this approach can be interpreted on an individual basis and also used to estimate for that individual the amount of chemical absorbed during a specific time interval or the amount bound to critical sites. They may also be useful for characterization of community exposure by analyzing results obtained in groups of individuals within the general population. In this respect, biological monitoring data complement environmental measurements but have certain advantages in estimating health risks. Most importantly, the data obtained are more directly related to adverse effects and thus provide a better estimate of risk than ambient monitoring. Biological monitoring also takes into account absorption by all routes, integrates exposure from all sources, and therefore can be used as a basis for estimate of total risk from multiple chemicals.

A Critical Evaluation of DNA Adducts as Biological Markers for Human Exposure to Polycyclic Aromatic Compounds

“…Nonetheless, the overall data in target organs of animal models seem to point out that the level of DNA adducts is related to cancer risk. In some cases, but not all, the target organs of sensitive animal species had higher adduct levels than the same organs in resistant species (Wogan and Gorelick, 1985).…”

Environmental genotoxicity: probing the underlying mechanisms.

“…Perhaps one of the more serious concerns is the potential for exposure to substances that are genotoxic. This problem arises because some of these pollutants are carcinogens and mutagens with the capacity to affect both the structural integrity of DNA and the fidelity of its biologic expression (1).…”

Aromatische Amine (Anilin, o‐, m‐, p‐Toluidin, 4‐Chlor‐o‐toluidin, 2,4‐ und 2,6‐Toluylendiamin, 4‐Aminodiphenyl, 4,4′‐Diaminodiphenylmethan) [Biomonitoring Methods in German language, 1994]

“…B. die spezifische Onkogen-Aktivierung mit selektiver Induktion spezifischer Kodons im DNA-Strang, kann im allgemeinen aus diesen DNA-bzw. Proteinadduktbildungen molekularbiologisch ein Krebsrisiko durch Aminoaromaten nicht abgeleitet werden [56,57]. Da die N-und Ring-C-Hydroxylierungen von Aminoaromaten keine Phänotypisie-rung bzw.…”