The effects of oral treatment with transfluthrin on the urothelium of rats and its metabolite, tetrafluorobenzoic acid on urothelial cells in vitro

Masanao Yokohira, Lora L. Arnold, Sophie Lautraite, Larry Sheets, Sheila Wason, Bernhard Stahl, David Eigenberg, Karen L. Pennington, Satoko Kakiuchi-Kiyota, Samuel M. Cohen

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Transfluthrin, a pyrethroid insecticide, induced urinary bladder tumors in rats but not in mice in 2-year bioassays. We investigated the urothelial effects of transfluthrin in vivo in rats and the effects of its major metabolite tetrafluorobenzoic acid (TFBA) in vitro on rat (MYP3) and human (1T1) urothelial cell lines. Rats were fed diet containing 0, 2000 or 5000 (with and without 1.25% NH4Cl) ppm transfluthrin for 4weeks or 0 or 2000ppm transfluthrin for 13weeks. After 4weeks, there was no evidence of hyperplasia or increased proliferation in any treatment group. After 13weeks treatment with 2000ppm, cytotoxicity and necrosis of the rat urothelial superficial layer were detected by scanning electron microscopy. The urinary concentration of TFBA in rats fed 2000ppm transfluthrin was 2.94±0.67mM. The LC50 of TFBA was 2.25mM for MYP3 cells and 2.43mM for 1T1 cells. These studies support cytotoxicity and regenerative proliferation as the mechanism for induction of bladder tumors with high oral doses of transfluthrin due to metabolism of transfluthrin to the weakly cytotoxic TFBA which is excreted at high concentrations in the urine of rats administered high doses of transfluthrin (≥2000ppm) for an extended period.

Original languageEnglish (US)
Pages (from-to)1215-1223
Number of pages9
JournalFood and Chemical Toxicology
Volume49
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Cytotoxicity
  • Rat
  • Tetrafluorobenzoic acid
  • Transfluthrin
  • Urinary bladder

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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    Yokohira, M., Arnold, L. L., Lautraite, S., Sheets, L., Wason, S., Stahl, B., Eigenberg, D., Pennington, K. L., Kakiuchi-Kiyota, S., & Cohen, S. M. (2011). The effects of oral treatment with transfluthrin on the urothelium of rats and its metabolite, tetrafluorobenzoic acid on urothelial cells in vitro. Food and Chemical Toxicology, 49(6), 1215-1223. https://doi.org/10.1016/j.fct.2011.02.022