The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses.
7-Acetyl-1,1,3,4,4,6-hexamethyl- 1,2,3,4-tetra-hydronaphthaline (AHTN) is one of the two most widely used fragrances of a group of substances known collectively as the polycyclic musks. In the last few years evidence has been accumulating that AHTN is hepatotoxic when administered at high doses. In the present study the subchronic hepatotoxicity of AHTN administered to rats at doses within the human exposure range was evaluated. For this purpose female and male juvenile Wistar rats were exposed to AHTN (300 microg/kg body weight per day, i.p.) alone or to a single dose of diethylnitrosamine (DEN) (100 mg/kg body weight, i.p.) followed by AHTN (1, 10, 100 or 300 microg/kg body weight per day, i.p.) for 90 days. Thereafter the liver architecture as well as the presence of placental glutathione S-transferase (GST-P)-positive hepatic lesions was assessed. In male animals receiving AHTN alone or in combination with DEN the number of GST-P-positive single hepatocytes was similar to that in untreated rats, while GST-P-positive mini-foci and foci were not observed. In the case of female rats the number of GST-P-positive single hepatocytes and mini-foci in AHTN-treated rats was similar to that in untreated animals, whereas in those animals receiving AHTN either alone or in combination with DEN, GST-P-positive foci could not be detected or were present in a number as similar to that in untreated rats. In conclusion, in the present study it has been shown that AHTN administered over a 90-day period in concentrations similar to those taken up daily by humans does not lead to hepatotoxicity.
Steinberg
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Lehrstuhl für Ernährungstoxikologie, Institut für Ernährungswissenschaft, Universität Potsdam, Arthur Scheunert Allee 114-116, 14558 Bergholz-Rehbrucke, Germany. steinber@rz.uni-potsdam.de
Zschaler
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Thom
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Kuna
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Wüst
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Schäfer-Schwebel
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Müller
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Kramer
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Weisse
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D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009281:Naphthalenes / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010476:Perfume / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013764:Tetrahydronaphthalenes
D014408:Biomarkers, Tumor; D002273:Carcinogens; D009281:Naphthalenes; D010476:Perfume; D013764:Tetrahydronaphthalenes; C033116:acetyl methyl tetramethyl tetralin; D004052:Diethylnitrosamine; D005982:Glutathione Transferase