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% NH(4)Cl) ppm transfluthrin for 4 weeks or 0 or 2000 ppm transfluthrin for 13 weeks. After 4 weeks, there was no evidence of hyperplasia or increased proliferation in any treatment group. After 13 weeks treatment with 2000 ppm, cytotoxicity and necrosis of the rat urothelial superficial layer were detected by scanning electron microscopy. The urinary concentration of TFBA in rats fed 2000 ppm transfluthrin was 2.94±0.67 mM. The LC(50) of TFBA was 2.25 mM for MYP3 cells and 2.43 mM 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 (≥2000 ppm) for an extended period.
Subject(s)
Benzoates/toxicity , Cyclopropanes/toxicity , Fluorobenzenes/toxicity , Insecticides/toxicity , Pyrethrins/toxicity , Urothelium/drug effects , Animals , Cell Line, Transformed , Cell Line, Tumor , Cell Survival/drug effects , Cyclopropanes/metabolism , Female , Fluorobenzenes/metabolism , Humans , Insecticides/metabolism , Organ Size/drug effects , Pyrethrins/metabolism , Rats , Rats, Wistar , Urinary Bladder/drug effects , Urinary Bladder/pathology , Urothelium/ultrastructureABSTRACT
To investigate the cutaneous distribution, localization, and persistence of imidacloprid in dogs, Advantage Topical Solution labeled with carbon 14 ((14)C) was topically applied as a single treatment at label rates and application pattern based on body weight to two adult beagles. One dog (8.5 kg) received 1.0 mL of the test solution at a single spot in the interscapular area (14 mg active ingredient/kg body weight); the second dog (12.3 kg) was treated with 2.5 mL of the test solution at four sites, each site receiving approximately 0.625 mL, along the dorsal thoracic and lumbar spine area (21 mg active ingredient/kg body weight). Samples of hair, skin surface residue, and skin taken from the application sites and/or distal body regions of the dogs at four intervals between 7 and 56 days after treatment demonstrated the migration of (14)C radioactivity from the application sites to distal areas of the canine haircoat and skin. The (14)C radioactivity concentrations in the skin biopsy and stratum corneum samples diminished steadily over 56 days after treatment. Microautoradiography of the skin showed focal concentrations of radioactivity in the superficial epidermis, hair follicles, and sebaceous glands. The presence of imidacloprid-derived radioactivity within hair follicles and sebaceous glands and on the skin surface is in good agreement with the reported efficacy of imidacloprid against fleas on dogs and cats for up to 1 month despite posttreatment bathing, shampooing, and/or swimming.
