Abstract
During a sub-chronic dermal toxicity study, hepatic and ocular toxicity were detected unrelated to the compound being tested. The changes in the liver were characterized by hepatic centrilobular degeneration and fibrosis due to chronic passive congestion. Clinical chemistry results confirmed the active hepatic damage and cholestasis. The ocular changes were limited to the retina where diffuse retinal atrophy was seen originating adjacent to the optic nerve and progressing centrifugally. It is suggested that as a consequence of the bandaging technique, a state of passive congestion and cholestasis resulted. The decrease in flow of bile acids to the intestine caused disturbances in vitamin E absorption. The deficiency of the antioxidant vitamin was responsible for the retinal changes seen.
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The work was carried out at: Life Science Research, PO Box 139, Ness Ziona 70451, Israel and Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
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Nyska, A., Waner, T., Wormser, U. et al. Possible pitfalls in rat extended dermal toxicity testing: An hepatic-ocular syndrome. Arch Toxicol 66, 339–346 (1992). https://doi.org/10.1007/BF01973629
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DOI: https://doi.org/10.1007/BF01973629