毒理性
_topramezone_具有低急性毒性，无论是口服、皮肤接触还是吸入途径。它对眼睛和皮肤有轻微刺激性，但不会引起皮肤过敏。口服给药后，_topramezone_会被迅速吸收，并通过尿液和粪便排出。_topramezone_是4-羟基苯基丙酮酸双加氧酶（4-HPPD）的抑制剂；这导致血清中的酪氨酸水平升高。然而，没有数据能够确定酪氨酸水平升高到何种程度会导致有害（不良反应）效应。由于酪氨酸水平升高，_topramezone_已在眼睛、肝脏、肾脏、胰腺和甲状腺中显示出不良反应。组织病理学评估显示，在大鼠和狗的甲状腺（滤泡细胞增生）、大鼠的胰腺（弥漫性变性）、大鼠和小鼠的肝脏（肝细胞肥大和局部坏死）以及大鼠的眼睛（慢性角膜炎）中，不良反应随剂量增加而增加。大鼠的生殖毒性研究没有显示出生殖不良反应；然而，在大鼠和兔子的发育毒性研究中，骨骼变异和骨骼骨化部位的改变发生率增加。动物研究表明，骨骼变异与4-HPPD抑制剂除草剂（甲磺草酮和异恶唑草酮）有关。对技术用_topramezone_及其主要代谢物进行的致突变性研究没有显示出任何致突变潜力。在大鼠的致癌性研究中，无论雌雄，都观察到了甲状腺滤泡细胞腺瘤和腺瘤及/或腺癌的组合发生率增加。根据美国环保署（EPA）最终致癌风险评估指南（2005年3月29日），EPA健康效应司（HED）将_topramezone_分类为“在不会改变大鼠甲状腺激素稳态的剂量下，不太可能对人类致癌”。HED确定，由于非癌症风险评估的无明显有害作用水平（NOAEL，0.4 mg/kg/天）预计不会改变甲状腺激素稳态也不会导致甲状腺肿瘤形成，因此不需要量化人类癌症风险。
Topramezone has a low acute toxicity via the oral, dermal, or inhalation route. It is a slight eye and dermal irritant, and it is not a skin sensitizer. Following oral administration, topramezone is rapidly absorbed and excreted via urine and feces. Topramezone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD); this results in elevated serum tyrosine levels. However, no data could determine at what level increases of tyrosine levels would result in detrimental (adverse) effects. As a consequence of the elevated tyrosine levels, topramezone has been shown to cause adverse effects in the eye, liver, kidney, pancreas, and thyroid. Histopathological evaluations showed dose-dependent increases of adverse effects in the thyroid (follicular cell hyperplasia) in rats and dogs, pancreas (diffuse degeneration) in rats, liver (hepatocellular hypertrophy and focal necrosis) in rats and mice, and eyes (chronic keratitis) in rats. The reproductive toxicity study in rats did not demonstrate adverse reproductive effects; however, developmental toxicity studies in rats and rabbits showed increased incidences of skeletal variation and alterations in skeletal ossification sites. Animal studies show that skeletal variations are associated with 4-HPPD inhibitor herbicides (mesotrione and isoxaflutole). Mutagenicity studies conducted on technical topramezone and its major metabolites did not demonstrate any mutagenic potential. Increased incidences of thyroid follicular cell adenomas and adenoma and/or adenocarcinomas combined were observed in the carcinogenicity study in rats of both sexes. In accordance with the EPA Final Guidelines for Carcinogen Risk Assessment (March 29, 2005), the /EPA Health Effects Division (HED)/ classified topramezone as "not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis". HED determined that quantification of human cancer risk is not required since the NOAEL (0.4 mg/kg/day) for non-cancer risk assessment is not expected to alter thyroid hormone homeostasis nor result in thyroid tumor formation.
来源:Hazardous Substances Data Bank (HSDB)
