Enhanced systemic tissue distribution after dermal versus intravenous 3,3 ',4,4 '-tetrachlorobiphenyl exposure: Limited utility of radiolabel blood area under the curve and excretion data in dermal absorption calculations and tissue exposure assessment

As a dioxin-like polychlorinated biphenyl (PCB), 3,3',4,4'-tetrachlorobiphe nyl (TCB) is receiving increasing research and regulatory interest due to i ts high toxicity and persistence in the environment. C-14-TCB was administe red at an identical dose of 300 mug via the intravenous (iv) or dermal rout e to swine to examine the exposure route dependency of the relationship bet ween tissue exposure and blood area under the curve (AUC) and the relations hip between dermal absorption and excretion of radiolabel. After iv and der mal exposure, blood, urine, and feces samples were collected during the 11- day in vivo studies. At the end of the experiments, full mass balance studi es were conducted to characterize tissue distribution of label. On average, over 70% of the applied dermal and iv doses were recovered. As expected, m ore than a 10-fold increase in blood AUC (0.49 vs 0.031, h (.) %. dose/ml), plasma AUC (0.40 vs 0.038, h (.) % dose/ml), urine excretion (29 vs 2.3% o f the applied dose), and fecal (30 vs 3.0% of the applied dose) excretion w as determined after iv exposure compared to dermal exposure. However, we un expectedly found that the tissue residue following iv exposure (8.0% of the applied dose) was only half that following dermal exposure (16% of the app lied dose). Significantly larger (20- to 30-fold) ratios of blood AUC: tiss ue residue and excretion:tissue residue were observed after iv exposure com pared to dermal exposure. This may indicate a route-related concentration-d ependent blood-to-tissue partition process of pooled label, unique skin met abolism, or saturable hepatic metabolism of TCB. Thus, a long-term, low-inp ut exposure pattern similar to this dermal exposure could be more harmful t o systemic tissues than a short-term, high-dose exposure similar to this iv exposure. One should be aware that greater absorption, higher blood concen trations, greater blood and plasma AUCs, and greater excretion of label do not necessarily result in a greater overall tissue exposure and that some c onventional approaches using label determination in blood and excreta witho ut full mass balance studies may underestimate dermal absorption of chemica ls similar to TCB. (C) 2001 Academic Press.