毒理性
草甘膦异丙胺盐是一种无色无味的白色粉末，通常用作除草剂，用于控制阔叶杂草和禾本科杂草，在许多食品和非食品作物中都有应用。它是除草剂“农达”中的活性成分。人类暴露和毒性：研究人员报告了意外接触或故意摄入农达的患者临床经验。使用产品时皮肤接触导致的症状包括眼周水肿和结膜水肿、心血管效应（心动过速和血压升高）、接触部位肿胀和感觉异常以及持续的皮肤刺激。故意摄入导致更严重的效应，包括由于明显的呼吸和心脏骤停导致的致命性。在含有草甘膦的除草剂中，腹痛伴恶心、呕吐和/或腹泻是急性中毒最常见的表现。这些症状可能是轻微的，可以自行解决，但在严重中毒时可能会出现炎症、溃疡或梗死。严重的腹泻和反复呕吐可能导致脱水。高剂量的浓缩配方可能导致胃肠道烧伤和坏死，并可能伴有出血。上消化道广泛糜烂与更严重的系统性中毒和长期住院有关。含有草甘膦的除草剂引起的严重中毒表现为低血压、心脏心律失常、肾脏和肝脏功能障碍、高血钾、胰腺炎、肺水肿或肺炎、意识水平改变和代谢性酸中毒。这些效应可能是短暂的或严重的，在12到72小时内进展到休克和死亡。低血压的机制可能与血容量减少（液体转移和增加丢失）和直接的心脏毒性有关。仅摄入农达导致的死亡是由于一种综合症，表现为低血压，对静脉输液或血管收缩药物无反应，有时伴有肺水肿，而中心静脉压正常。动物研究：将10只雄性家兔分为6组，每周5天，连续21天，每天给予76或114毫克/千克体重的未稀释草甘膦异丙胺盐。仅在皮肤变化上表现出毒性，这种变化在磨损皮肤上更为明显，但在所有情况下，在28天的恢复期结束时都已愈合。在含有表面活性剂的草甘膦异丙胺配方中，急性毒性是由表面活性剂引起的。在一项急性雌性犬研究中，农达配方中草甘膦和表面活性剂的共同作用导致心脏抑制，这主要是由表面活性剂引起的，因为草甘膦本身增加了心肌收缩力。对大鼠进行了一项为期4周的吸入研究，使用1:3稀释的农达配方。将50、160和360毫克/立方米的稀释配方作为气溶胶喷雾，每天6小时，每周5天。仅在最高剂量组的雌性中观察到鼻甲（亚急性炎症）、气管（单核细胞浸润）和肺（血管周围淋巴滤泡/聚集）刺激增加的发病率。没有发现系统性毒性的迹象（参数：存活、生长、有限的血液学和血液生化、器官重量、有限的组织病理学）。研究了除草剂农达和草甘膦异丙胺盐的遗传毒性潜力，使用了三种不同的试验。两种剂量的小鼠骨髓微核试验均未发现断裂效应。在沙门氏菌试验中，仅测试了农达。在TA98中浓度为360微克/板（无代谢激活）和TA100中浓度为720微克/板（有代谢激活）时，显示出弱的突变效应。草甘膦异丙胺盐的后期-末期葱试验未显示效果，但在以草甘膦异丙胺盐计算浓度为1.44和2.88毫克/升时，经农达处理后，染色体畸变显著增加。观察到的最常见畸变可以特征化为纺锤体干扰。生态毒性研究：在处理森林一年后，农达对鹿鼠的繁殖、生长或存活没有明显的不利影响。Townsend花栗鼠（EuTAmias townsendii）的种群密度在处理区似乎最初下降，但这种反应是短暂的。在成体虹鳟鱼中，即使处理剂量高达2.0毫克/升的草甘膦异丙胺盐，也未观察到繁殖力或性腺体指数的变化。在回避研究中，虹鳟鱼不回避高达10.0毫克/升的异丙胺盐浓度。对于虹鳟鱼和渠道鲶鱼来说，卵期是最不敏感的早期生活阶段。总体而言，农达配方的毒性是技术级材料的3到42倍。
IDENTIFICATION AND USE: Glyphosate isopropylamine salt is a white odorless powder that is commonly used as a herbicide to control broadleaf weeds and grasses, in many food and non-food crops. It is an active ingredient in the herbicide Roundup. HUMAN EXPOSURE AND TOXICITY: Clinical experiences with patients exposed to Roundup either accidentally or through deliberate ingestion have been reported by investigators. Symptoms resulting from dermal exposure incidental to the use of the product included periorbital edema and chemosis of the eye, cardiovascular effects (tachycardia and elevated blood pressure), swelling and paraesthesia at the site of dermal contact and prolonged skin irritation. Deliberate ingestion resulted in more severe effects, including lethality from apparent respiratory and cardiac arrest. In glyphosate-containing herbicides abdominal pain with nausea, vomiting, and/or diarrhea are the most common manifestations of acute poisoning. These may be mild self-resolving, but in severe poisoning there may be inflammation, ulceration, or infarction. Severe diarrhea and recurrent vomiting may induce dehydration. Gastrointestinal burns and necrosis occurs with high doses of concentrated formulations and may be associated with hemorrhage. Extensive erosions of the upper gastrointestinal tract are associated with more severe systemic poisoning and a prolonged hospitalization. Severe poisonings by glyphosate-containing herbicides manifests as hypotension, cardiac dysrhythmias, renal and hepatic dysfunction, hyperkalemia, pancreatitis, pulmonary edema or pneumonitis, altered level of consciousness, and metabolic acidosis. These effects may be transient or severe, progressing over 12 to 72 hours to shock and death. The mechanism of hypotension may relate to both hypovolemia (fluids shifts and increased losses) and direct cardiotoxicity. Deaths following ingestion of Roundup alone were due to a syndrome that involved hypotension, unresponsive to iv fluids or vasopressor drugs, and sometimes pulmonary edema, in the presence of normal central venous pressure. ANIMAL STUDIES: Six groups of 10 male rabbits were treated with 76 or 114 mg/kg b.w. undiluted glyphosate isopropylamine salt for 5 days/week for 21 days. Toxicity was apparent only as dermal changes, which were more pronounced on abraded skin, but which in all cases had healed by the end of a 28-day recovery period. In glyphosate isopropylamine formulations containing surfactants, acute toxicity was due to the surfactant. In acute female dog study the joint effect of both glyphosate and the surfactant in Roundup formulation resulted in cardiac depression, which was mostly due to the surfactant since glyphosate itself increased myocardial contractility. A 4-week inhalation study was carried out on rats with a 1:3 dilution of Roundup formulation. Test concentrations of 50, 160 and 360 mg/cu m of the diluted formulation were administered as an aerosol spray for 6 hr/day, 5 days/week. An increased incidence of irritation of the nasal turbinates (subacute inflammation), trachea (mononuclear cell infiltration) and lungs (perivascular lymphoid infiltrates/aggregates) was observed among the high-dose females only. No signs of systemic toxicity were found (parameters: survival, growth, limited hematology and blood biochemistry, organ weights, limited histopathology). The genotoxic potential of the herbicide Roundup and glyphosate isopropylamine salt was studied in three different assays. No clastogenic effects were found in the mouse bone marrow micronucleus test for either of the two agents. In the Salmonella assay only Roundup was tested. It showed a weak mutagenic effect for the concn 360 ug/plate in TA98 (without metabolic activation) and 720 ug/plate in TA100 (with metabolic activation). The anaphase-telophase Allium test showed no effect for the glyphosate isopropylamine salt, but a significant increase in chromosome aberrations appeared after treatment with Roundup at concn of 1.44 and 2.88 mg/L when calculated as glyphosate isopropylamine. The most frequent aberrations observed could be characterized as disturbances of the spindle. ECOTOXICITY STUDIES: Roundup had no apparent adverse effects on reproduction, growth, or survival of deer mice 1 year after treatment of forest. The population density of Townsend chipmunks (Eutamias townsendii) appeared to initially decline in the treated area, although this response was short lived. No changes in fecundity or gonadosomatic index were observed in adult rainbow trout treated with up to 2.0 mg/L of glyphosate isopropylamine salt. In avoidance studies, rainbow trout did not avoid concentrations of the isopropylamine salt up to 10.0 mg/L. The egg stage was the least sensitive early life stage for both rainbow trout and channel catfish. Overall, the Roundup formulation was 3 to 42 times more toxic than the technical grade material.
来源:Hazardous Substances Data Bank (HSDB)
