In vitro evaluation of the metabolic stability of nine fragrance chemicals in trout and human hepatocytes. Issue 10 (3rd June 2020)

• Record Type: Journal Article
• Authors: Weeks, John; Li, Albert P.; Doshi, Utkarsh; Johanning, Karla; Guiney, Patrick D.
• Is Part Of: Journal of applied toxicology. Volume 40:Issue 10(2020)
• Page Start: 1421
• Page End: 1434
• Publication Date: 2020-06-03
• Subjects: bioaccumulation -- fish -- fragrance -- hepatocytes -- human -- metabolism; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3995
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: In vitro metabolic stability of nine fragrance chemicals: p‐tolyl acetate, cashmeran, ethylene brassylate, celestolide, galaxolide, traseolide, ambretone, tonalide and pentadecanolide, was evaluated in trout and human hepatocytes. The compounds were incubated with trout hepatocytes at 12°C and human hepatocytes at 37°C. Quantification of compound disappearance with time was performed using gas chromatography/mass spectrometry. in vivo hepatic intrinsic clearance values were calculated from the in vitro data. Significant metabolism was observed with trout hepatocytes for five of the nine fragrance chemicals, while all nine were metabolized significantly with human hepatocytes. Previously published models were used to examine expected bioaccumulation and persistence in whole organisms. Calculated half‐lives due to metabolism of the nine chemicals are significantly shorter for humans than trout: <1 hour and <1 day, respectively. For all chemicals with demonstrated hepatic metabolism, the models indicate a lack of accumulation. For those where metabolism was demonstrated in trout, calculated bioconcentration factors would not be classified as bioaccumulative under prevailing regulatory systems. Abstract : In vitro metabolic stability of nine fragrance chemicals was evaluated in trout and human hepatocytes. Compound disappearance with time was observed using gas chromatography/mass spectrometry. in vivo hepatic intrinsic clearances were calculated from the in vitro data. Significant metabolism was observed with trout hepatocytes for five of the nine chemicals, while all nine were metabolized significantly with human hepatocytes. Calculated half‐lives are shorter for humans than trout. For all chemicals with demonstrated hepatic metabolism, the models indicate a lack of accumulation.