A 90-day repeated oral dose toxicity study of four stereoisomers of 2,4-dimethyl-4-phenyltetrahydrofuran, a synthetic flavoring substance, in F344 rats.
2,4-Dimethyl-4-phenyltetrahydrofuran (CAS no. 82461-14-1) is a food additive used as a synthetic flavoring substance. To investigate the toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral dose toxicity study of 2,4-dimethyl-4-phenyltetrahydrofuran containing four stereoisomers was conducted in F344 rats at doses of 0, 6, 24, and 96 mg/kg body weight (BW)/day. No mortality or abnormal clinical signs related to treatment in any group was observed. At a dose of 96 mg/kg BW, fluctuated serum total protein and total cholesterol and increased absolute and relative liver weights and relative kidney weights were observed in both sexes. Increased serum albumin in males and decreased Na and Cl in females were also observed. On histopathological assessment, at a dose of 96 mg/kg BW, diffuse hepatocellular hypertrophy in the liver in both sexes and tubular regeneration with scattered proximal tubular degeneration and/or necrosis throughout the cortex in the kidney in males were detected. Based on these findings, the NOAEL for 2,4-dimethyl-4-phenyltetrahydrofuran used in the current study was found to be 24 mg/kg BW/day for both sexes.
['Ide|Tetsuya|T|', 'Mizuta|Yasuko|Y|', 'Akagi|Jun-Ichi|JI|', 'Masumoto|Naoko|N|', 'Sugimoto|Naoki|N|', 'Sato|Kyoko|K|', 'Ogawa|Kumiko|K|', 'Cho|Young-Man|YM|']
D000284:Administration, Oral D000818:Animals D004305:Dose-Response Relationship, Drug D005260:Female D005421:Flavoring Agents D007668:Kidney D008099:Liver D008297:Male D008968:Molecular Conformation D019055:No-Observed-Adverse-Effect Level D051381:Rats D011916:Rats, Inbred F344 D013237:Stereoisomerism D013997:Time Factors
2,4-Dimethyl-4-phenyltetrahydrofuran Flavoring substance F344 rats Food additive Subchronic toxicity test