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ToxSci Advance Access originally published online on December 2, 2003
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Toxicological Sciences 77, 368-374 (2004)
Copyright © 2004 by the Society of Toxicology

SAFETY EVALUATION

Comparative Study on Cardiotoxic Effect of Tinuvin 770: A Light Stabilizer of Medical Plastics in Rat Model

Péter Sótonyi*,1, Béla Merkely{dagger}, Márta Hubay{ddagger}, Jeno Járay*, Endre Zima{dagger}, Pál Soós{dagger}, Anikó Kovács§ and István Szentmáriay{ddagger}

* Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary, 1082; {dagger} Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary, 1122; {ddagger} Department of Forensic Pathology, Semmelweis University, Budapest, Hungary, 1091; and § National Institute of Forensic Toxicology, Budapest, Hungary, 1146

Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate], is a UV light stabilizer plastic additive used worldwide. It is a component of many plastic materials used in medical and food industries. Earlier studies demonstrated its in vitro L-type Ca2+ channel and nicotinic acetylcholine receptor blocking properties. Our previous experiments have proved the toxic effects of Tinuvin 770 on isolated rat cardiomyocytes. The present study investigates the cardiotoxic effects of Tinuvin 770 in vivo. Wistar rats were intraperitoneally injected with increasing doses of Tinuvin 770 (1, 10, 100 µg, and 1 mg) 15 times during a 5-week period. Myocardial samples were analyzed by light, electron, and fluorescent microscopy. The lead-acetate method was used to detect intracellular Ca2+, and glyoxylic acid technique to assess alteration in adrenergic innervation. Focal myocytolysis and hypercontraction necrosis could be observed in rats treated with higher doses of Tinuvin 770. In these groups, intracellular Ca2+ accumulation and increased catecholamine release were detected. Tinuvin 770 not only displays L-type Ca2+ channel blocking properties, but can also lead to catecholamine release, similar to effects of the first generation of L-type Ca2+ channel blockers. Morphological results correspond to catecholamine-induced myocardial damage. Current literature, as well as our study, indicates that more detailed toxicological analysis of Tinuvin 770 should be required, and current regulations in medical and food industries should adopt the new results.

Key Words: Tinuvin 770; cardiotoxicity; catecholamine; L-type Ca2+ channels, light-stabilizers; hemodialysis.


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