Pyrazole-Induced Thyroid Necrosis: A Distinct Organ Lesion

Abstract

One oral dose of pyrazole caused necrosis of rat thyroid follicular epithelial cells but spared the parafollicular (C) cells and the parathyroid glands. Serum thyroxine (T4) and triiodothyronine (T3) were significantly decreased on day 3 after pyrazole administration and were immeasurable on day 5. At day 5 the thyroid was enlarged and the concentration of thyroid-stimulating hormone in the serum was increased, indicating an appropriate pituitary response to a primary lesion in the thyroid. Doses of pyrazole which produced no morphologic change in the thyroids also significantly depressed the concentrations of T4 and T3 in the serum.

Zebrafish Eleutheroembryos Provide a Suitable Vertebrate Model for Screening Chemicals that Impair Thyroid Hormone Synthesis

“…In the zebrafish eleutheroembryo model, exposure to BPA at MTC did not modify the IT4C, so it was not classified as a TGFD. Pyrazole has been reported to induce necrosis in rat thyroid follicular cells and a significant decrease of about 80% in IT4C was observed in zebrafish eleutheroembryos using TIQDT. Finally, BP3 and linuron had no effect in thyroid-relevant in vitro assays and no thyroid disrupting effects have been reported in mammalian models.…”

Pyrazole: preclinical reassessment

“…Electron microscopy revealed that the lesions progressed from dilation of the endoplasmic reticulum of the follicular epithelial cells, to vesiculation, mitochondrial damage, clumping of chromatin along nuclear membranes and final necrosis and desquamation of the cells [6]. This effect of pyrazole on thyroid tissue did not occur in the trout [21].…”

“…In this species, pyrazole (1400 mg/kg) results in a 90-100% incidence of thyroid lesions [6]. In contrast to the rat, pyrazole did not cause a block of thyroid function in rainbow trout, where it was shown to only depress plasma T 3 [21].…”

“…Pyrazole has been found to significantly decrease the concentrations of serum thyroxine (T4) and triiodothyronine (T3) as well as increase the concentration of thyroid-stimulating hormone in SpragueDawley rats [6]. In this species, pyrazole (1400 mg/kg) results in a 90-100% incidence of thyroid lesions [6].…”

“…This effect was not noted in the other species stu- died [3]. In further study, Sprague-Dawley female rats were given pyrazole at 300, 700, 1000 or 1400 mg/kg (8400 mg/m 2) body weight by stomach tube [6]. The highest dose resulted in a 90-100% incidence of thyroid lesions and about 50% mortality by day 5.…”