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The action of most drugs is the result of a series of interactive processes relating to: (a) the physical and chemical properties of the drug, (b) the manner and site of administration, (c) the nature of the drug’s absorption, distribution, and metabolism, and (d) the interaction of the drug with cellular processes. No exploitable unique biochemical processes have been discovered which make neoplastic cells more sensitive to chemotherapeutic agents than dividing normal cells. The selectivity of most antineoplastic agents depends, in part at least, upon particular differences in cell growth kinetics and pharmacologic effects of drug exposure.

Polychlorinated biphenyls (PCBs) have been produced commercially since be fore 1930. They proved to be highly versatile mixtures and their uses continued to expand during the early 1970's even after the unanticipated world-wide en vironmental contamination had been discovered (Jensen et aI., 1969; Koeman et aI., 1969). Over 600,000 metric-tons were produced and/or used in the U. S. during this time and it is estimated that worldwide production totaled about 1,200,000 metric-tons (Table 1). With low acute toxicities (Fishbein, 1974), these mixtures were considered gen erally biologically inactive even though industrial exposure had demonstrated he patic and dermatological effects (Fishbein, 1974; Hansen, 1987). Thus, use and disposal were not carefully monitored and it is estimated that one-third of the world-wide production of PCBs has been released into the global environment (Table 1). Table 1. Estimated production and disposition of PCBs b U. s. a Worldwide 6 6 Production/use 610 X 10 kg 1200 X 10 kg Mobil environmental reservoir 82 400 Static reservoirs In service 340 Dumps 130 Total static 470 800 a NAS, 1979 b Tatsukawa and Tanaba, 1984 2 Environmental Distribution Many countries now impose strict controls on the use and release of PCBs. Re lease into the environment has declined dramatically in the last decade, but con tinued release from reservoirs (Table 1) into burdened ecosystems (Table 2) ap pears inevitable for several more decades (Barros et aI., 1984)."

We have presented data quantifying both the absorption of fluid and solutes from the peritoneal cavity and the effective lymph flow rate of these substances to the blood. Peritoneal loss rate of macromolecules is dependent on IP pressure while the effective lymph flow rate has a much smaller value than the loss rate and is independent of IP pressure. Data has been presented showing the areas of local absorption and accumulation within peritoneal tissue. Macromolecular accumulation in specific peritoneal tissue depends on several factors, the most important of which is the presence or absence of lymphatics. We conclude from our studies that macromolecular agents injected IP will transport to the blood preferentially via the two major lymphatic systems draining the cavity (subdiaphragmatic and mesenteric). We further conclude that significant accumulation of such drugs will occur in the anterior abdominal wall and diaphragm, but that visceral tissues will have concentrations below one-tenth of the value at the peritoneum at positions beyond 1 mm from the peritoneum.