A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat

Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes

“…Like Phenobarbital, the proposed modes of action for Pyrethrins-induced rat liver and thyroid tumour formation are associated with induction of hepatic xenobiotic metabolising enzymes, cell proliferation, hypertrophy and also for the thyroid gland hormonal dysfunction (Finch et al, 2006;Price et al, 2007). The objective of the present study was to obtain additional information, employing rat and human hepatocytes, to support the proposed modes of action for Pyrethrinsinduced rat liver and thyroid gland tumour formation.…”

“…In a mode of action study the effect of Pyrethrins on rat liver and thyroid gland were compared with those of sodium Phenobarbital (Finch et al, 2006;Price et al, 2007). Several studies have demonstrated that Phenobarbital is a non-genotoxic agent which can promote liver and thyroid gland tumours in rodents (IARC, 2001;Meek et al, 2003;Whysner et al, 1996).…”

Thyroid Function Tests in Persons with Occupational Exposure to Fipronil

“…S everal studies have showed that pesticide exposures can be associated with a significantly increased incidence of thyroid tumors in rats (1)(2)(3)(4)(5)(6). This increase has not been demonstrated in humans after occupational exposure to pesticides (7)(8)(9)(10)(11), except for a case-control study (12), a longitudinal epidemiological survey (13), and a descriptive study (14).…”

Mode of action and human relevance of pronamide-induced rat thyroid tumors

“…The decrease in serum T4 stimulates the HPT axis to reestablish thyroid hormone homeostasis by increasing circulating levels of TSH, which induce thyroid follicular cells to produce and release more thyroid hormone (IARC, 1999(IARC, , 2001McClain, 1995;Hurley et al, 1998). This MoA is generally accepted as a secondary mechanism responsible for the increased thyroid tumors observed in rats with a number of compounds (Finch et al, 2006;Hill et al, 1989;Dellarco et al, 2006). As mentioned, numerous compounds operate by this MoA, including phenobarbital, carbamazepine, nicardipine, polycyclic and polyhalogenated aromatic hydrocarbons (e.g., PBB), etc.…”

“…c. Rats have a shorter thyroid hormone half-life due to the absence of thyroxine-binding globulin (T4 half-life is 5-9 days in humans vs. 0.5-1 day in rats Jahnke et al, 2004); therefore, the rat HPT axis is activated more easily. For example, rats have higher constitutive TSH levels than humans, reflecting the higher activity of the HPT axis in rats (McClain, 1992;Finch et al, 2006). (Lans et al, 1993;Zoeller and Tan, 2007) PCBs Plausible but there is no data to support this MoA and a quantitative species difference exists between rodents and humans raising the question of its relevance to humans d. The increased rate of T4 clearance results in a more ''functionally active'' thyroid in rats than humans, which is reflected in different thyroid histopathology between the two species (i.e., tall cuboidal follicular cells in rats vs. short cuboidal follicular cells in humans) (McClain, 1995).…”