substantial unexploited opportunities to reduce risks. Information on the fetal and chronic neurological risks of methylmercury further suggests the need to reevaluate the current tolerance in that case.

In the development of advisories for reproductive effects, due weight must be given to the persistence of different toxicants in people. For methylmercury, with an elimination half-life averaging about 70 days, it may well be sufficient to direct advice to couples who intend to have children in the near future. For PCBs on the other hand, with half-lives measured in several years or even decades, reductions in intake only in the months prior to and during pregnancy can be expected to have little impact on effective body burdens and fetal exposure. In that case, cautionary advice may need to extend to the entire population of reproductive and prereproductive ages.



In the methylmercury case, the committee was able to infer the distribution of effective internal dosage and risk to the population by using some fragmentary data on blood levels. Similar blood level population distribution data were also cited in the polychlorinated biphenyl (PCB) case study, although a translation into intake distributions or risks was not possible there because of the incompleteness of information about the pharmacokinetics of different PCB congeners.


A major theme, if not the central organizing principle of traditional physiology and toxicology, is the concept of the "homeostatic system." Biological processes are seen as part of a complex interacting web, exquisitely designed so that modest changes in any parameter will automatically give rise to compensating processes to restore optimal functioning (e.g., too much heat input automatically induces sweating so that temperature is kept within a normal range). In this view, as long as a toxic material or any other disturbing stimulus does not push one or more parameters beyond a specified limit ("threshold"), adaptive processes will repair any damage that may have been temporarily produced and completely restore the system to its normal functional state. This paradigm has enjoyed great success in guiding the design and interpretation of a wide range of experimental findings on acute responses to toxic chemicals, heat, cold, and other agents in which the mechanism of damage, does, in fact, consist of grossly overwhelming a particular set of bodily defenses. Another type of damage mechanism dominates thinking in molecular biology and genetics. At the molecular level, some fundamental life processes are basically fragile, in particular, the integrity of the information coded within the deoxyribonucleic acid (DNA) of each cell. An unrepaired error ("mutation") in copying will usually be passed on to all descendants of the mutated cell, and even if the mistake is confined to a single DNA base, massive adverse consequences may result if important genetic information has been altered in a way that affects its function. For the molecular biologist it is intuitively obvious that even a single molecule of a substance that reacts with DNA has some chance of producing a biologically significant result if it happens to interact with the right DNA site. For the traditional toxicologist, basic intuition leads to the opposite expectation: for any substance there is some level of exposure that will have no significant effect on a given biological system. Clearly, application of either intuition to a particular biological response is appropriate only to the degree

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