Renal toxicology

The use of various in vitro models in studying renal toxicology is well documented in the literature (Ware et al., 1979 Kacew and Hirsch, 1981 Hassall et al., 1983 Hook and Hewitt, 1986 Smith et al., 1987 Tay et al., 1988 Williams, 1989). A listing of the available in vitro models is provided in Table 17.6. Each model system possesses its own advantages and disadvantages, and all have demonstrated their usefulness and application in renal toxicology. 

An understanding of how and why chemicals induce nephrotoxicity requires some familiarity with the anatomy and physiology of the kidney. In addition, interpretation of renal toxicology studies will require a working knowledge of the various techniques used for evaluating renal function. It is also important to be aware of which nephrotoxicants require biotransformation before they induce nephrotoxicity, nephrotoxic mechanisms when known, and the site(s) of renal damage for the various nephrotoxicants. 

Elfarra AA (1997) Halogenated hydrocarbons. In Goldstein RS (ed.) Comprehensive Toxicology - Renal Toxicology, pp. 601-616. New York Elsevier. 

Lockwood TD, Bosmann FIB. The use of urinary N-acetyl-B-D-glucosaminidase in human renal toxicology I. Partial biochemical characterization and excretion in humans and release from the isolated perfused rat kidney. Toxicol AppI Pharmacol 1979 49 323-336. 

Zalups, R. K., and L. H. Lash. 1996. Methods in renal toxicology. Boca Raton, FL CRC Press. 

Smith DR, McNeill F (1995) In vivo measurement and speciation of nephrotoxic metals. In Fowler BA, Chang L (eds) Target Organ Toxicology (Vol. II) Renal Toxicology of Metals. CRC Press, Boca Raton, FL (in press). 

In the ED setting, the diagnosis of ketamine intoxication is a clinical one. Ketamine is not routinely detected by urine toxicology tests, although it can be detected with high-performance liquid chromatography (Koesters et al. 2002). As with MDMA, the initial assessment for ketamine intoxication includes the use of routine laboratory tests to detect electrolyte abnormalities and to evaluate renal and hepatic functioning (Koesters et al. 2002). 

Biagini G, Caudarelia R, Vangelista A. 1977. Renal morphological and functional modification in chronic lead poisoning. In Brown SS, ed. Clinical chemistry and chemical toxicology of metals. Elsevier/North-Holland Biomedical Press, 123-126. 

Bellemann, P. (1980). Primary monolayer culture of liver parenchymal cells and kidney cortical tubules as a useful new model for biochemical pharmacology and experimental toxicology. Studies in vitro on hepatic membrane transport, induction of liver enzymes, and adaptive changes in renal cortical enzymes. Arch. Toxicol. 44 63-84. 

Chatteijee, S., Trifillis, A. and Regec, A. (1984). Morphological and biochemical effects of gentamicin on cultured human-kidney renal tubular cells. Human Toxicology 3 455. 

Rylander, L.A., Gandolfi, A.J. and Brendel, K. (1985). Inhibition of organic acid/base transport in isolated rabbit renal tubules by nephrotoxins. In In Vitro Toxicology. A progress report from Johns Hopkins Center for Alternatives to Animal Testing. Vol. 3 (Goldberg, A.M., Ed.). Mary Ann Liebert, New York, pp. 235-247. 

Smith JH, Malta K, Sleight SD, et al. 1984. Effect of sex hormone status on chloroform nephrotoxicity and renal mixed function oxidases in mice. Toxicology 30 305-316. 

Based on the calculated Maximum Dietary Exposure (MDE) of PAEs, and the Non Observed Adverse Effect Level (NOAEL) calculated from the available toxicology evidence, mainly hepatic, renal changes and reproductive toxicity in animals [88, 89,130-133], and making an uncertainty factor between 100 and 200, the EFSA panel calculated the Tolerable Daily Intake (TDI) for DBP, BBP, DEHP,... 

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