Evaluation of the diphenyl herbicide, oxyfluorfen, for effects on thyroid hormones in the juvenile rat

IF 2.9 Q2 TOXICOLOGY Current Research in Toxicology Pub Date : 2024-01-01 DOI:10.1016/j.crtox.2023.100146
T.E. Stoker , G.D. DeVane , A.R. Buckalew , J.R. Bailey , J.L. Ford , A.S. Murr
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Abstract

Recently, oxyfluorfen, a pre- and post-emergent diphenyl ether herbicide, was identified in our laboratory as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), the first key step in the synthesis of thyroid hormones (THs). This inhibition was observed in vitro, using both a human NIS engineered cell line (hNIS-HEK293T-EPA) and a rat thyroid follicular cell line (FRTL-5). Oxyfluorfen was found to be a potent inhibitor of NIS activity with an EC50 of approximately 2 µM in both cell lines with no observed cytotoxicity at any concentration tested up to 100 μM. The current research tested the hypothesis that oxyfluorfen alters circulating concentrations of THs. This hypothesis was first tested in a pilot study with both juvenile male and female rats exposed to oxyfluorfen for 4 days at 0, 125, 250 and 500 mg/kg/day. Once we identified that this short-term 4-day oxyfluorfen exposure suppressed both total serum thyroxine (T4) and triiodothyronine (T3) at all doses, we tested seven lower concentrations of oxyfluorfen (0.8125 to 62.5 mg/kg day) in an 8-day exposure paradigm to more closely evaluate the dose–response. We found that oxyfluorfen suppressed serum T4 with a LOEL of 3.25 mg/kg/day and T3 with a LOEL 62.5 mg/kg/day. Analytical chemistry of the serum showed an accumulation over time following oral exposure to oxyfluorfen in both the 4- and 8-day groups. Analytical chemistry of the thyroid glands in the 8-day study revealed higher accumulation in the thyroid as compared to the serum (2 to 3- fold at 62.5 mg/kg). No changes in thyroid weight or serum TSH were observed following the 8-day exposure. This study is the first to demonstrate an effect of oxyfluorfen on serum thyroid hormones in the rat. Additional studies are needed to further evaluate the effects on thyroid homeostasis with extended exposures and the potential implications of the observed effects.

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评估二苯基除草剂 Oxyfluorfen 对幼鼠甲状腺激素的影响
最近,我们的实验室发现,一种芽前和芽后二苯醚除草剂 oxyfluorfen 是碘化钠交感器(NIS)摄取碘化物的抑制剂,而碘化钠交感器是合成甲状腺激素(THs)的第一个关键步骤。我们使用人类 NIS 工程细胞系(hNIS-HEK293T-EPA)和大鼠甲状腺滤泡细胞系(FRTL-5)在体外观察到了这种抑制作用。研究发现,氧氟草醚是一种强效的 NIS 活性抑制剂,在两种细胞系中的 EC50 值均约为 2 µM,在高达 100 μM 的任何测试浓度下均未观察到细胞毒性。目前的研究测试了氧氟草醚会改变血液循环中 THs 浓度的假设。这一假设首先在一项试验性研究中得到了验证,研究对象是幼年雄性大鼠和雌性大鼠,暴露于氧氟草醚4天,剂量分别为0、125、250和500毫克/千克/天。当我们确定短期接触氧氟草醚 4 天会抑制所有剂量的血清甲状腺素总量(T4)和三碘甲状腺原氨酸(T3)后,我们又在为期 8 天的接触范例中测试了 7 种较低浓度的氧氟草醚(0.8125 至 62.5 毫克/千克/天),以更密切地评估剂量反应。我们发现,氧氟草醚抑制血清 T4 的最低观测效应水平为 3.25 毫克/千克/天,抑制血清 T3 的最低观测效应水平为 62.5 毫克/千克/天。口服氧氟草醚4天组和8天组的血清化学分析结果显示,氧氟草醚会随着时间的推移而累积。在为期8天的研究中,甲状腺的化学分析结果显示,甲状腺中的蓄积量高于血清中的蓄积量(62.5毫克/千克时为2至3倍)。暴露 8 天后,甲状腺重量或血清促甲状腺激素没有发生变化。这项研究首次证明了氧氟草酯对大鼠血清甲状腺激素的影响。还需要进行更多的研究,以进一步评估长期暴露对甲状腺稳态的影响以及所观察到的影响的潜在影响。
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来源期刊
Current Research in Toxicology
Current Research in Toxicology Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
4.70
自引率
3.00%
发文量
33
审稿时长
82 days
期刊最新文献
Editorial Board Contents Evaluation of the diphenyl herbicide, oxyfluorfen, for effects on thyroid hormones in the juvenile rat Ethylene dimethanesulfonate effects on gene promoter activities related to the endocrine function of immortalized Leydig cell lines R2C and MA-10 Placental transfer of tofacitinib in the ex vivo dual-side human placenta perfusion model
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