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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.

Authors
Qiao-GL; Riviere-JE
Source
Toxicol Appl Pharmacol 2001 Nov 15; 177(1):26-37
NIOSHTIC No.
20021844
Abstract
As a dioxin-like polychlorinated biphenyl (PCB), 3,3',4,4'-tetrachlorobiphenyl (TCB) is receiving increasing research and regulatory interest due to its high toxicity and persistence in the environment. (14)C-TCB was administered at an identical dose of 300 microg via the intravenous (iv) or dermal route to swine to examine the exposure route dependency of the relationship between tissue exposure and blood area under the curve (AUC) and the relationship between dermal absorption and excretion of radiolabel. After iv and dermal exposure, blood, urine, and feces samples were collected during the 11-day in vivo studies. At the end of the experiments, full mass balance studies were conducted to characterize tissue distribution of label. On average, over 70% of the applied dermal and iv doses were recovered. As expected, more than a 10-fold increase in blood AUC (0.49 vs 0.031, h x % dose/ml), plasma AUC (0.40 vs 0.038, h x % dose/ml), urine excretion (29 vs 2.3% of the applied dose), and fecal (30 vs 3.0% of the applied dose) excretion was determined after iv exposure compared to dermal exposure. However, we unexpectedly found that the tissue residue following iv exposure (8.0% of the applied dose) was only half that following dermal exposure (16% of the applied dose). Significantly larger (20- to 30-fold) ratios of blood AUC:tissue residue and excretion:tissue residue were observed after iv exposure compared to dermal exposure. This may indicate a route-related concentration-dependent blood-to-tissue partition process of pooled label, unique skin metabolism, or saturable hepatic metabolism of TCB. Thus, a long-term, low-input exposure pattern similar to this dermal exposure could be more harmful to systemic tissues than a short-term, high-dose exposure similar to this iv exposure. One should be aware that greater absorption, higher blood concentrations, greater blood and plasma AUCs, and greater excretion of label do not necessarily result in a greater overall tissue exposure and that some conventional approaches using label determination in blood and excreta without full mass balance studies may underestimate dermal absorption of chemicals similar to TCB.
Keywords
Tissue-distribution; Tissue-culture; Exposure-levels; Exposure-assessment; Blood-analysis; Blood-samples; Blood-sampling; Biphenyls; Toxic-effects; Absorption-rates; In-vivo-studies; Polychlorinated-biphenyls; Biphenyls; Animal-studies; Laboratory-animals; In-vivo-study
Contact
NIOSH, M/S 3030, 1095 Willowdale Rd., Morgantown, WV 26505-2888
CODEN
TXAPA9
CAS No.
32598-13-3; 11097-69-1
Publication Date
20011115
Document Type
Journal Article
Email Address
gaq1@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0041-008X
NIOSH Division
HELD
Source Name
Toxicology and Applied Pharmacology
State
WV; NC
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