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EXECUTIVE SUMMARY
Pages 1-14

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From page 1...
... Previous subcommittees of the Committee on Biological Marlcers have published separate volumes on reproductive and clevelopmental toxicology, pulmonary toxicology, ~ ~ The Subcomm~ttee on u~O~OglC Variers in Urinary Toxicology, which prepared this report, comprised scientists with diverse baclcgrouncls in and icnowleclge of nephrology, urology, pathology, renal toxicology and metabolism, pharmacolcinetics, immunology, risk assessment, pharmacology, renal physiology, and other disciplines. In response to the charge to the subcommittee, this report discusses current and immunotoxicology.
From page 2...
... Several characteristics of the normal genitourinary tract increase the risk of damage by toxic chemicals. For example, the total amount of noxious substances clelivered to the kidneys can be high, owing to the large amount of blood flowing to them.
From page 3...
... EFFECTS OF Toxic EXPOSURE OF THE URINARY TRACT Advances in understanding and using biologic markers should assist in identifying xenobiotics that are toxic to the urinary tract. The functional role of the urinary tract, including clearance of toxic substances from the blood, predisposes it to xenobiotic exposure and toxicity.
From page 4...
... The possible link between a family history of renal disease and the development of renal failure might be an inherited susceptibility or a common geographic exposure. Alterecl nutrition and some coexisting diseases, including addictive behavior, are aclditional characteristics that in(licate increased risk associated with nephrotoxicants.
From page 5...
... Identifying these mariners is lilcely to require a more complete understanding of the biochemical and physiologic properties of the Icic3ney ant! lower urinary tract, as well as better insight into factors that control the linkages between cell growth, clifferentiation, proliferation, and malignant transformation.
From page 6...
... Itis reasonable to use animal models for extrapolation to humans unless specific information on specific chemicals indicates otherwise. Identification of chemical hazards should inclucle assimilation and evaluation of all relevant information including appraisal of physical and chemical properties and structure-activity relationships which often can provide important inclications of potential toxicity.
From page 7...
... Improved understanding of the mechanisms of cell growth and metabolism will enable further definition of the steps in the initiation and progression of various urinary tract cancers. It is anticipated that parallels will emerge that will yield insight into the progression of parenchymal renal disease.
From page 8...
... Extrapolation'; and New Technologies. The Kidney · For patients entering programs for treatment of en~i-stage renal disease (ESRD)
From page 9...
... These effects should be correlated with biochemical and anatomic changes. The Bladder · Human bladder cancer induced by xenobiotic exposure in worker cohorts should be investigates!
From page 10...
... Among them are tests of urinary excretion of various growth factors, such as epidermal growth factor (EGF) , and other tubular enzymes, such as intestinal alkaline phosphatase (IAP)
From page 11...
... proliferation. Insight into the factors that control the cell cycle, regulate various growth factors, influence gene expression, and modulate nucleic acid synthesis might be critical in the development of new classes of mariners.


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