阿特拉津 | 1912-24-9

• 物质功能分类: 化学农药原药 - 除草剂 - 三氮苯类除草剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 中文名称: 阿特拉津
• 中文别名: 莠去津；6-氯-N2-乙基-N4-异丙基-1,3,5-三嗪-2,4-二胺；园保净；2-氯-4-乙胺基-6-异丙氨基-1,3,5-三嗪；阿特拉嗪；莠去尽；2-氯-4-乙胺基-6-异丙胺基-均三氮苯；莠去津可湿性粉剂；阿特拉津可湿性粉剂；莠去津悬浮剂
• 英文名称: 6-chloro-N-ethyl-N'-isopropyl-1,3,5-triazine-2,4-diamine
• 英文别名: atrazin；atrazine；ATZ；6-chloro-4-N-ethyl-2-N-propan-2-yl-1,3,5-triazine-2,4-diamine
• CAS: 1912-24-9
• 化学式: C₈H₁₄ClN₅
• mdl: MFCD00041810
• 分子量: 215.686
• InChiKey: MXWJVTOOROXGIU-UHFFFAOYSA-N

物化性质

• 熔点：
  175°C
• 沸点：
  200°C
• 密度：
  1.187
• 闪点：
  11 °C
• 溶解度：
  二甲基亚砜：83.33 mg/mL（386.36 mM）
• 暴露限值：
  OSHA PEL: TWA 5 mg/m3; ACGIH TLV: TWA 5 mg/m3.
• LogP：
  2.59 at 20℃ and pH7.31-7.51
• 表面张力：
  57.6mN/m at 30mg/L and 21℃
• 解离常数：
  1.56 at 20℃
• 物理描述：
  Atrazine is a white crystalline solid. Melting point 173-175°C. Sinks in water. A selective herbicide used for season-long weed control in a variety of crops.
• 颜色/状态：
  Colorless powder
• 气味：
  Odorless
• 蒸汽压力：
  2.89X10-7 mm Hg at 25 °C
• 稳定性/保质期：
  如果按照规格正确使用和储存，则不会发生分解，并且没有已知的危险反应。应避免与氧化物接触。致畸和致癌试验结果均为阴性。这种物质对鸟类和鱼类低毒，对眼睛无刺激性，但对皮肤有轻微刺激。
• 分解：
  Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas.
• 腐蚀性：
  Atrazine technical and formulated products are noncorrosive to equipment and metal surfaces.
• 燃烧热：
  -9,500 btu/lb = -5,300 cal/g = -220X10+5 J/kg (est)
• 碰撞截面：
  150.74 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]
• 保留指数：
  1696;1708;1712;1729;1724;1711;1710;1726;1705;1726;1724.1;1720.6;1715.3;1696.8;1691;1724.2;1699;1699;1711;1718.5;1700;1700;1718.3;1714.6

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.625
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

阿特拉津（ATR）是一种广泛使用的氯三嗪类除草剂，是一种普遍存在的环境污染物，也是一种潜在的发展性毒物。为了定量评估阿特拉津及其主要代谢物在胎盘/哺乳期转移和胎儿/新生儿组织剂量学，为大鼠母体、胎儿和新生儿开发了基于生理的药代动力学模型。这些模型使用来自反复接触阿特拉津（口服灌胃；5毫克/千克）的大鼠母体的药代动力学数据进行校准，然后对模型进行评估，以对抗其他可用的大鼠数据。模型模拟与大多数可用实验数据相符，并表明：（1）胎儿接触到与母体血浆水平相似的阿特拉津及其主要代谢物二去烷基阿特拉津（DACT），（2）新生儿主要接触到比母体血浆或胎儿水平低三分之二的DACT，而哺乳期接触阿特拉津的最小，以及（3）妊娠期DACT的延续极大地影响了其新生儿剂量学直到哺乳中期。为了测试模型的跨物种外推能力，对妊娠C57BL/6小鼠进行了药代动力学研究，从妊娠第12天到第18天口服灌胃接触阿特拉津（5毫克/千克）。通过使用小鼠特异性参数，模型预测与测量数据拟合良好，包括胎盘ATR/DACT水平。然而，胎儿DACT浓度被模型高估了10倍。这种高估表明，到达胎儿的DACT中只有大约10%是组织结合的。这些啮齿动物模型可用于胎儿/新生儿组织剂量学的预测，以帮助设计/解释阿特拉津的早期生命毒性/药代动力学研究，并作为向人类放大的基础。

Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

阿特拉津（ATR）是一种广泛使用的除草剂。在其代谢过程中存在几种类型的反应。本文将介绍其代谢中三条水解反应路径的机制以及对这三条路径中代谢物毒性的预测。密度泛函理论中的一种方法，B3LYP（Becke, 3参数, Lee-Yang-Parr）的计算结果表明：（1）在ATR的三条水解路径中有三种模型。C(9/11)-N(8/10)，C(4/6)-N(8/10)和C-Cl的解离机制分别是脱烷基化、脱氨和氯取代。（2）C-Cl解离的能量障碍较低。解离在动力学上是有利的，是三条水解路径中的主要反应。在这些水解反应中，由于反应速率的影响，不同的中间体具有不同的浓度。（3）此外，为了研究水解反应，有必要考虑溶剂效应。由于溶剂效应，使用了类似于导体极化连续体模型（CPCM）来模拟水解反应中的键长和能量障碍。实验或预测结果表明，阿特拉津及其三条水解路径中的代谢物具有致癌性。

Atrazine (ATR) is a widely used herbicide. There are several types of reactions in its metabolism. Herein, the mechanism of three paths of hydrolysis reactions in its metabolism and predictions of toxicities of its metabolites in the three paths will be presented. The calculation results by B3LYP (Becke, 3-parameter, Lee-Yang-Parr), one of the approaches in density functional theory, indicated that (1) there were three models in the three hydrolysis paths of ATR. The dissociation mechanisms of C(9/11)-N(8/10), C(4/6)-N(8/10), and C-Cl were dealkylation, deamination, and Cl substitution, respectively. (2) The energy barrier of C-Cl dissociation was lower. The dissociation was advantageous in dynamics and the primary reaction in the three hydrolysis paths. In these hydrolysis reactions, the different intermediates had different concentrations because of the impact of the reaction rate. (3) In addition, it was necessary to consider the solvent effect to investigate hydrolysis reaction. The conductor-like polarizable continuum model (CPCM) was used to simulate the hydrolysis reaction in bond length and energy barrier because of the solvent effect. Experimental or predictive results showed that atrazine and its metabolites in the three hydrolysis paths were carcinogenic.

来源:Hazardous Substances Data Bank (HSDB)

代谢

s-三嗪家族的化合物是过去30年使用最频繁的除草剂之一。其中一些衍生物被怀疑是致癌物质。在这项研究中，确定了参与人肝微粒体代谢s-三嗪衍生物（阿特拉津、特丁津、氨硫磷和特丁磷）的具体一期酶的身份。动力学研究表明，所有检查的途径（S-氧化、N-脱烷基化和侧链C-氧化）都具有双相动力学。低Km值在大约1-20微摩尔范围内，而高Km值则高出两个数量级。为了进行相关性研究，对30个人肝微粒体制备物进行了七种特定P450活性的筛选，并将这些活性与这些s-三嗪衍生物的代谢物活性进行了比较。在高亲和力浓度范围内，与细胞色素P450 1A2活性显著相关。化学抑制在低三嗪浓度下对α-萘黄酮和呋拉非林最为有效，在高底物浓度下对酮康唑和孕酮也有效。对10种异源表达的P450形式的研究表明，几种P450酶能够以不同的亲和力和区域选择性氧化这些s-三嗪，P450 1A2被确认为参与这些s-三嗪代谢的低Km P450酶。还评估了黄素含单加氧酶（FMOs）在氨硫磷和特丁磷的亚磺酰化反应中在人体肝脏中的潜在参与。人体抑制的亚磺酰化反应表明黄素含单加氧酶没有显著参与。最后，纯化的重组FMO3，人肝中主要的黄素含单加氧酶，在氨硫磷和特丁磷的母亚磺酰化物的形成中表现出无显著活性（< 0.1 nmol (nmol of FMO3)-1 min-1）。因此，P450 1A2可能是负责暴露人类肝脏氧化一期代谢s-三嗪衍生物的唯一酶。

Compounds of the s-triazine family are among the most heavily used herbicides over the last 30 years. Some of these derivatives are suspected to be carcinogens. In this study the identity of specific phase-I enzymes involved in the metabolism of s-triazine derivatives (atrazine, terbuthylazine, ametryne, and terbutryne) by human liver microsomes was determined. Kinetic studies demonstrated biphasic kinetics for all pathways examined (S-oxidation, N-dealkylation, and side-chain C-oxidation). Low Km values were in a range of about 1-20 uM, whereas high Km values were up to 2 orders of magnitude higher. For a correlation study, 30 human liver microsomal preparations were screened for seven specific P450 activities, and these were compared to activities for the metabolites derived from these s-triazines. A highly significant correlation in the high-affinity concentration range was seen with cytochrome P450 1A2 activities. Chemical inhibition was most effective with alpha-naphthoflavone an furafylline at low s-triazine concentrations and additionally with ketoconazole and gestodene at high substrate concentrations. Studies with 10 heterologously expressed P450 forms demonstrated that several P450 enzymes are capable of oxidizing these s-triazines, with different affinities and regioselectivities. P450 1A2 was confirmed to be the low-Km P450 enzyme involved in the metabolism of these s-triazines. A potential participation of flavin-containing monooxygenases (FMOs) in sulfoxidation reactions of the thiomethyl derivatives ametryne and terbutryne in human liver was also evaluated. Sulfoxide formation in human inhibition indicated no significant involvement of flavin-containing monooxygenases. Finally, purified recombinant FMO3, the major flavin-containing monooxygenase in human liver, exhibited no significant activity (< 0.1 nmol (nmol of FMO3)-1 min-1) in the formation of the parent sulfoxides of ametryne and terbutryne. Therefore, P450 1A2 alone is likely to be responsible for the hepatic oxidative phase-I metabolism of the s-triazine derivatives in exposed humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大量的尿液代谢物被分离出来，并在暴露后72小时内的尸体中检测到15.8%。在体外，莠去津的去烷基化作用占主导地位，超过了与谷胱甘肽的结合。从大鼠和家兔尿液中鉴定出的代谢物含有一个完整的三嗪环，这表明最初是从烷基侧链上失去乙基或甲基基团。在小型猪中，莠去津及其代谢物在尿液中的存在时间略超过24小时；还鉴定出了二乙莠去津。羊和牛的排泄速度很快，在饮食中摄入5 ppm莠去津4天的奶牛的牛奶中没有残留物。

A large number of urinary metabolites was isolated and 15.8% was detected in the carcasses at 72 hr post-exposure. Dealkylation of atrazine in vitro, predominated over glutathione conjugation. Metabolites identified from rat and rabbit urine contained an intact triazine ring suggesting initial loss of ethyl or methyl groups from the alkyl side chains. In the miniature pig, atrazine and its metabolites were seen in urine for slightly more than 24 hr; diethylatrazine was also identified. Excretion by sheep and cattle is rapid with no residues seen in the milk of cows receiving 5 ppm atrazine in the diet for 4 days.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：阿特拉津是一种无色粉末。它用于一年生阔叶杂草和一年生草类的苗前和苗后控制。它也与其他许多除草剂配合使用。人类研究：过度暴露的潜在症状包括眼睛和皮肤的刺激、皮炎、皮肤敏感化、呼吸困难、虚弱、不协调、流涎、低体温和肝脏损伤。来自意大利北部的两项研究表明，接触三嗪类除草剂（包括阿特拉津）的妇女患卵巢肿瘤的风险增加。与接触未指明的三嗪类除草剂或特定地接触阿特拉津相关的癌症风险略有增加。饮用水中的阿特拉津暴露与早产有关。阿特拉津在体外培养的人类淋巴细胞代谢激活中未能诱导裂变和异常损伤。然而，阿特拉津在使用人类外周血淋巴细胞（有或没有代谢激活）的单细胞凝胶电泳试验中表现出遗传毒性。阿特拉津还诱导了人类EUE细胞系的非计划DNA合成。动物研究：阿特拉津对兔子的皮肤有轻微刺激性，对眼睛有轻度刺激性。一种50%的配方显示出对皮肤的弱刺激性，但确实在豚鼠、兔子和猫的眼睛中产生了强烈的刺激性，包括眼睑和结膜的水肿。牛和羊在连续两天服用250 mg/kg阿特拉津后死亡。急性中毒的羊和牛表现出肌肉痉挛、肌肉颤动、步态僵硬和呼吸频率增加。观察到肾上腺退化和肺、肝和肾的充血。大鼠在6个月内食用相当于10或50 mg/kg的饮食，表现出生长迟缓和轻微的白细胞减少，以及选择性器官重量的改变。在大鼠中，通过口服灌胃以每天100-600 mg/kg体重的剂量给予阿特拉津，持续七天或十四天，引起了肾毒性和肝毒性。阿特拉津扰乱了大鼠正常的4天发情周期。在大鼠进行的短期和长期研究中发现，在饮食中给予高剂量阿特拉津的大鼠所诱导的乳腺肿瘤可能是由于加速了正常的、与年龄相关的发情周期紊乱，导致内源性雌激素和催乳素暴露增加的结果。在对最高测试剂量（400 ppm）的卵巢切除大鼠进行的饮食中，阿特拉津对乳腺肿瘤发生率和其他增殖活动的影响表明，其作用机制与非遗传毒性机制和激素失衡有关。阿特拉津在小鼠中被发现对免疫系统有不利影响。在大鼠妊娠的第3、6和9天皮下注射800 mg/kg/天的阿特拉津，导致每个胎儿的某些或全部死亡和吸收。通过此途径给予的最高剂量为200 mg/kg并不影响每胎的仔数或断奶时的体重。饮食水平高达1000 ppm（约50 mg/kg/天）也是无害的。急性处理阿特拉津（100 mg/kg体重）的大鼠显示出自发浦肯野细胞放电率显著降低。阿特拉津还降低了由同侧桡神经电刺激引起的脑桥电位，主要影响攀爬纤维输入的反应。对从妊娠第14天到出生后第21天每天接触1或100微克/公斤体重的阿特拉津的雌性和雄性小鼠的神经行为发展进行了研究。观察到探索性行为和亲和/探究行为的改变，揭示了阿特拉津暴露雄性的行为特征的雌性化。成年时的学习表现也明显受损。阿特拉津改变了大鼠的类固醇生成，导致血清皮质酮、孕酮和雌激素升高。阿特拉津通过植物酶激活产生对Schizosaccharomyces pombe（正向突变）和中国仓鼠细胞（正向突变）的诱变代谢物。阿特拉津在宿主介导试验（小鼠，酵母通过静脉注射）中呈阳性，并在小鼠单次剂量为1 g/kg和2 g/kg后诱导骨髓细胞染色体畸变。生态毒性研究：在口服阿特拉津后1小时，野鸭出现了虚弱、震颤、共济失调和体重下降，并持续了多达11天。在雉鸡中，治疗5天后症状缓解。在成年雄性日本鹌鹑中，口服500 mg/kg体重阿特拉津后，在白细胞和分离的肝细胞中记录了显著更长的DNA损伤的彗星尾。阿特拉津没有模仿雌二醇或他莫昔芬在雄性鹌鹑中的效果。因此，阿特拉津没有表现出明显的雌激素或抗雌激素活性。相反，阿特拉津增强了睾酮和雌二醇对睾丸退缩的影响。可以认为，阿特拉津在饮食中达到1000 ppm可能会对性成熟雄鸟的生殖发育产生一些影响。在实验室控制的实验中，对幼年澳洲肺鱼（Lates calcarifer）进行了短期、急性暴露于阿特拉津的内分泌和生理效应的研究。肝脏卵黄蛋白原的表达没有受到影响，支持阿特拉津没有通过介导雌激素受体产生直接雌激素效应的观点。阿特拉津暴露对暴露斑马鱼的氧化

IDENTIFICATION AND USE: Atrazine is a colorless powder. It is used for pre- and post-emergence control of annual broad-leaved weeds and annual grasses. It is also used in combinations with many other herbicides. HUMAN STUDIES: Potential symptoms of overexposure are irritation of eyes and skin, dermatitis, skin sensitization, dyspnea, weakness, incoordination, salivation, hypothermia, and liver injury. Two studies from northern Italy showed elevated risks of ovarian tumors among women exposed to triazine herbicides including atrazine. Small excess risks for cancer at a number of sites were associated with exposure either to unspecified triazine herbicides or specifically to atrazine. There was a positive association between atrazine exposure in drinking water and preterm birth. Atrazine failed to induce clastogenic and aneugenic damage in cultured human lymphocytes with metabolic activation. However, atrazine was found genotoxic in single-cell gel electrophoresis assay by using human peripheral blood lymphocytes with and without metabolic activation. Atrazine also induced unscheduled DNA synthesis in human EUE line cells. ANIMAL STUDIES: Atrazine is minimally irritating to skin and mildly irritating to eyes of rabbits. A 50% formulation was shown to be weakly irritating to the skin but did produce strong eye irritation including edema of the eyelid and conjuctivae of guinea pigs, rabbits, and cats. Cattle and sheep were killed by two daily doses of 250 mg/kg atrazine. Acutely poisoned sheep and cattle exhibited muscular spasms, fasciculations, stiff gait and increased respiratory rates. Adrenal degeneration and congestion of lung, liver and kidneys were observed. Rats fed diets that contained an equivalent of 10 or 50 mg/kg for 6 months showed growth retardation and slight leukopenia along with alterations of selective organ weights. Administration of atrazine by oral gavage at 100-600 mg/kg bw per day to rats for seven or 14 days induced both nephrotoxicity and hepatotoxicity. Atrazine disrupted the regular 4-day estrous cycles in rats. Short- and long-term studies performed with rats have shown that the mammary tumors induced in rats given high doses of atrazine in the diet are likely to be the result of an accelerating effect on normal, age-related perturbations of the estrous cycle, with resultant increase in exposure to endogenous estrogen and prolactin. The lack of effect of atrazine on the incidence of mammary tumors and other evidence of proliferative activity in ovariectomized rats fed the highest dose tested (400 ppm) suggests a non-genotoxic mechanism of action associated with hormonal imbalance. Atrazine was found to adversely affect the immune system in mice. Subcutaneous injection of atrazine at 800 mg/kg/day on days 3, 6, and 9 of gestation resulted in the death and resorption of some or all of the pups in each litter of rats. Dosages as high as 200 mg/kg by this route did not affect the number of pups per litter nor weight at weaning. Dietary levels up to 1000 ppm (about 50 mg/kg/day) also were harmless. Rats acutely treated with atrazine (100 mg/kg, bw) showed a significant decrease in spontaneous Purkinje cell firing rate. Atrazine also decreased the cerebellar potentials evoked by electrical stimulation of the ipsilateral radial nerve, affecting mostly the response to climbing fiber input. Neurobehavioral development of female and male mice daily exposed from Gestational Day 14 until Postnatal Day 21 to 1 or 100 ug/kg bw atrazine was investigated. Changes in exploratory profile and in affiliative/investigative behavior were observed, revealing a feminization of behavioral profile in atrazine-exposed males. Alteration in learning performance at adulthood was also evident. Atrazine alters steroidogenesis in male rats resulting in elevated serum corticosterone, progesterone, and estrogens. Atrazine is activated by plant enzymes to produce a mutagenic metabolite for Schizosaccharomyces pombe (forward mutation) and Chinese hamster cells (forward mutation). Atrazine is positive in the host mediated assay (mouse, yeast injected intrasanguineously) and induced chromosome aberrations in bone marrow cells of mice after single dose of 1 g/kg and 2 g/kg, respectively. ECOTOXICITY STUDIES: Weakness, tremors, ataxia, and weight loss occurred in mallards 1 hr after oral treatment with atrazine and persisted up to 11 days. In pheasants, remission had occurred by 5 days after treatment. In adult male Japanese quail, significantly longer comet tails of DNA damage in leukocytes and isolated hepatocytes were recorded with 500 mg/kg bw atrazine oral treatment. Atrazine did not mimic the effects of either estradiol or tamoxifen in male quail. Thus, atrazine did not exhibit overt estrogenic or anti-estrogenic activity. Conversely, atrazine augmented the effects of testosterone and estradiol on testis regression. It is concluded that atrazine up to 1000 ppm in the diet may exert some effects on reproductive development in sexually maturing male birds. Both endocrine and physiological effects of short-term, acute exposure to atrazine in juvenile barramundi (Lates calcarifer) was conducted in a controlled laboratory experiment. Expression of hepatic vitellogenin was not affected, supporting the notion that atrazine does not have a direct estrogenic effect via mediation of estrogen receptors. Atrazine exposure had profound influence on the oxidative stress markers and detoxifying enzyme of the exposed zebrafish. Sheepshead minnow embryo-juvenile exposure to atrazine found that a mean measured atrazine concentration of 3.4 mg/L had no effect on hatching success of embryos or growth of juveniles, but significantly reduced juvenile survival. The decrease in amphibian length and weight at metamorphosis may indicate a reduction in fitness in wild populations of anurans exposed to atrazine at 200 to 2,000 ug/L. Atrazine was found nontoxic to bees. Exposure and accumulation of atrazine caused oxidative toxicity and antioxidant response in maize.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：不太可能对人类致癌

Cancer Classification: Not Likely to be Carcinogenic to Humans

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于阿特拉津对人类致癌性的证据不足。对于阿特拉津对实验动物致癌性的证据是充分的。总体评估：在进行总体评估时，工作组得出结论，与阿特拉津暴露相关的乳腺肿瘤涉及非DNA反应性、激素介导的机制。在得出结论时，考虑了以下证据：（A）阿特拉津仅在大鼠（而非Fischer 344大鼠、CD-1小鼠或切除卵巢的大鼠）中产生乳腺肿瘤（纤维腺瘤、腺癌），并不增加其他肿瘤类型的发病率。（b）阿特拉津影响下丘脑的神经内分泌途径，加速雌性大鼠的生殖衰老，但对Fischer 344大鼠则不然。（c）阿特拉津没有固有的雌激素活性。（d）在生殖衰老相关的激素变化中，存在关键的种间差异。因此，有强有力的证据表明，阿特拉津增加Sprague-Dawley大鼠乳腺肿瘤发病率的机制与人类无关。阿特拉津的致癌性对人不可分类（第3组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of atrazine. There is sufficient evidence in experimental animals for the carcinogenicity of atrazine. Overall evaluation: In making the overall evaluation, the Working Group concluded that the mammary tumors associated with exposure to atrazine involve a non-DNA reactive, hormonally mediated mechanism. In reaching the conclusion, the following evidence was considered: (A) Atrazine produces mammary tumors (fibroadenomas, adenocarcinomas) only in intact female Sprague-Dawley rats (not Fischer 344 rats, CD-1 mice or ovariectomized Sprague-Dawley rats) and does not increase the incidences of other tumor types. (b) Atrazine affects neuroendocrine pathways of the hypothalamus to accelerate the onset of reproductive senescence in female Sprague-Dawley rats but not Fischer 344 rats. (c) Atrazine does not have intrinsic estrogenic activity. (d) There are critical interspecies differences in the hormonal changes associated with reproductive senescence. Therefore, there is strong evidence that the mechanism by which atrazine increased the incidence of mammary gland tumors in Sprague-Dawley rats is not relevant to humans. Atrazine is not classifiable as to its carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3：已确认的动物致癌物，对人类的相关性未知。

A3: Confirmed animal carcinogen with unknown relevance to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：阿特拉津

IARC Carcinogenic Agent:Atrazine

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

阿特拉津（ATR）是一种广泛使用的氯三嗪类除草剂，是一种普遍存在的环境污染物，也是一种潜在的发展性毒物。为了定量评估阿特拉津及其主要代谢物在胎盘/哺乳期转移和胎儿/新生儿组织剂量学，为大鼠母体、胎儿和新生儿开发了基于生理的药代动力学模型。这些模型使用大鼠母体重复暴露（口服灌胃；5毫克/千克）ATR的药代动力学数据进行校准，然后对其他可用的大鼠数据进行模型评估。模型模拟与大多数可用实验数据相符，并建议：（1）胎儿同时暴露于ATR及其主要代谢物二去烷基阿特拉津（DACT），水平与母体血浆水平相似，（2）新生儿主要暴露于DACT，其水平比母体血浆或胎儿水平低三分之二，而哺乳期暴露于ATR的最小，以及（3）妊娠期DACT的残留极大地影响其新生儿剂量学直至哺乳中期。为了测试模型的跨物种外推能力，对怀孕的C57BL/6小鼠进行了药代动力学研究（口服灌胃；5毫克/千克），从妊娠第12天到第18天暴露于ATR。通过使用小鼠特异性参数，模型预测与测量数据拟合良好，包括胎盘ATR/DACT水平。然而，胎儿DACT浓度被模型高估了（10倍）。这种高估表明，只有大约10%的达到胎儿的DACT是组织结合的。这些啮齿动物模型可用于胎儿/新生儿组织剂量学的预测，以帮助设计/解释阿特拉津的早期生命毒性/药代动力学研究，并作为向人类放大的基础。

Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

从草甘膦厂收集的工人的尿样中草甘膦（ATZ）的浓度是通过气相色谱-电子捕获检测器方法测定的，用于检测尿液中草甘膦及其代谢物（去乙基草甘膦（DEA）、去异丙基草甘膦（DIA）、去乙基去异丙基草甘膦（DEDIA））。浓度范围分别为：DEDIA为0.003 - 0.301毫克/升，DEA为0.005 - 0.011毫克/升，DIA为0.006 - 0.276毫克/升，ATZ为0.005 - 0.012毫克/升。

... The atrazine (ATZ) concentrations in urine samples of the workers collected from an atrazine plant were determined by /a gas chromatograph-electron capture detector/ method /for detecting ATZ and its metabolites (deethylatrazine (DEA), deisopropylatrazine (DIA), deethyldeisopropylatrazine (DEDIA)) in human urine/. The concentration ranges were 0.003 -0.301 mg/L for DEDIA, 0.005 -0.011 mg/L for DEA, 0.006 -0.276 mg/L for DIA, and 0.005 -0.012 mg/L for ATZ.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

少量母体...阿特拉津...在喂食未标记除草剂4天的牛尿中被排出。

Small amount of parent ... atrazine ... /was/ excreted in urine of cows fed unlabeled herbicide for 4 days.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

摄入72小时后，在大鼠尿液中发现了65.5%的放射性标记阿特拉津，而20.3%在粪便中。在呼出的空气中发现的不到0.1%，这表明三嗪环并没有显著代谢成二氧化碳。组织分析显示，有15.8%的反应性保留，在肝脏、肾脏和肺中观察到高浓度，而在肌肉组织和脂肪中观察到较低浓度。

Seventy-two hr /after ingestion/ 65.5% of radiolabeled atrazine was found in urine of rats, while 20.3% was found in the feces. Less than 0.1% was found in expired air, thus indicating s-triazine ring was not appreciably metabolized to carbon dioxide. Tissue analysis revealed that 15.8% of reactivity was retained, with high concentrations observed in the liver, kidney, and lung, and lower concentrations observed in muscle tissue and fat.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露等级：
  B
• 职业暴露限值：
  TWA: 5 mg/m3
• 危险等级：
  9
• 危险品标志：
  Xn,N
• 安全说明：
  S16,S2,S36/37,S45,S60,S61,S7
• 危险类别码：
  R48/22,R50/53,R43
• WGK Germany：
  3
• 海关编码：
  2933699011
• 危险品运输编号：
  3077
• RTECS号：
  XY5600000
• 包装等级：
  III
• 危险类别：
  9
• 储存条件：
  请将贮藏器保持密封状态，并将其存放在阴凉、干燥处。同时，确保工作环境具备良好的通风或排气设施。

SDS

国标编号:	61898
ＣＡＳ:	1912-24-9
中文名称:	阿特拉津
英文名称:	Atrazine；2-Chloro-4-ethylamino-6-isopropylamino-s-triazine
别 名:	2-氯-4-乙氨基-6-异丙氨基-1，3，5-三嗪；莠去津
分子式:	C 8 H 14 ClN 5
分子量:	215.72
熔 点:	171～174℃
密 度:	相对密度(水=1)1.2(20
蒸汽压:
溶解性:	难溶于水，微溶于多数有机溶剂
稳定性:	稳定
外观与性状:	纯品为无色结晶，原药为白色粉末
危险标记:	15(有害品，远离食品)
用 途:	农用除草剂

2.对环境的影响:

一、健康危害

侵入途径：吸入、食入、经皮吸收。 健康危害：本品对皮肤和眼睛有刺激作用。属低毒除草剂。动物实验致癌、致畸为阳性。对人有致突变作用。

二、毒理学资料及环境行为

急性毒性：LD50672mg/kg(大鼠经口)；850mg/kg(小鼠经口)；750mg/kg(兔经口)；7500mg/kg(兔经皮) 刺激性：人经皮500mg，中等刺激；人经眼100mg，严重刺激。

危险特性：不易燃烧。受高热分解，放出有毒的烟。 燃烧(分解)产物：一氧化碳、二氧化碳、氮氧化物、氯化氢。

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3.现场应急监测方法:

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4.实验室监测方法:

气相色谱法《水和废水标准检验方法》15版，中国建筑工业出版社，1985年高效液相色谱法(中国环境监测总站，水质)

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5.环境标准:

前苏联	车间空气中有害物质的最高容许浓度	2mg/m 3
前苏联(1978)	环境空气中最高容许浓度	0.02mg/m 3
中国(GHZB1-1999)	地面水环境质量标准(I、II、III类水域)	0.003mg/L
前苏联(1978)	渔业用水中最高容许浓度	5μg/L

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6.应急处理处置方法:

一、泄漏应急处理

隔离泄漏污染区，周围设警告标志，建议应急处理人员戴自给式呼吸器，穿化学防护服。不要直接接触泄漏物，小心扫起，避免扬尘，运至废物处理场所。用水刷洗泄漏污染区，经稀释的污水放入废水系统。如大量泄漏，收集回收或无害处理后废弃。

二、防护措施

呼吸系统防护：生产操作或农业使用时，必须佩戴防毒口罩。紧急事态抢救或逃生时，应该佩戴自给式呼吸器。 眼睛防护：戴化学安全防护眼镜。 防护服：穿相应的防护服。 手防护：戴防护手套。 其它：工作现场禁止吸烟、进食和饮水。工作后，淋浴更衣。注意个人清洁卫生。实行就业前和定期的体检。

三、急救措施

皮肤接触：用肥皂水及清水彻底冲洗。就医。 眼睛接触：拉开眼睑，用流动清水冲洗15分钟。就医。 吸入：脱离现场至空气新鲜处。就医。 食入：误服者，饮适量温水，催吐。洗胃。就医。

灭火方法：泡沫、干粉、砂土。

制备方法与用途

概述

阿特拉津为无色结晶，熔点173～175℃。溶于水、甲醇、氯仿，在中性、微酸性及微碱性介质中稳定，但碱和无机酸在高温下可将其水解为无除草活性的羟基衍生物，无腐蚀性。其由2,4,6-三氯-1,3,5-三嗪先后与乙胺、异丙胺反应制得。

毒性

大鼠急性经口LD₅₀为3080mg/kg，小鼠为850mg/kg；口服- 大鼠 LD50: 672毫克/公斤; 口服- 小鼠 LD50: 850 毫克/ 公斤。皮肤刺激数据：兔子38毫克轻度；眼睛刺激数据：兔子6.32毫克重度。可燃性危险特性：燃烧产生有毒氮氧化物和氯化物气体。储运特性：库房通风低温干燥; 与食品原料分开储运。

急性毒性

• 大鼠口服LD₅₀: 672 毫克/公斤
• 小鼠口服LD₅₀: 850 毫克/ 公斤

刺激数据

• 皮肤刺激：兔子38毫克轻度
• 眼睛刺激：兔子6.32毫克重度

可燃性危险特性

燃烧产生有毒氮氧化物和氯化物气体。

储运特性

库房通风低温干燥; 与食品原料分开储运。

灭火剂

干粉、泡沫、砂土。

职业标准

• TWA: 5 毫克/立方米
• STEL: 20 毫克/立方米

农药分类

农药，毒性分级：中毒。

反应信息

• 作为反应物：
  描述：

  阿特拉津 在 氧气 作用下， 生成 硫丙磷
  参考文献：
  名称：

  Estimation of dioxin emission from fires in chemicals

  摘要：

  The formation of the 17 toxic 2,3,7,8-substituted PCDDs and PCDFs during combustion of selected chemicals were measured by high-resolution GC/MS. The 16 chemicals studied were commonly used chlorinated pesticides, industrial chemicals, and PVC. In a series of experiments carried out in a DIN 53,436 furnace, 2.5 g of these compounds were burned at 500 degrees C and 900 degrees C, respectively. The resultant yields ranged from 740 ng ITEQ/g for pentachlorophenol, to below 0.01 ng ITEQ/g for PVC and dichlobenil. The results show that some chemicals generate PCDD/F in very high possibly dangerous - amounts during burning, whereas others generate insignificant amounts. The influence of scale were studied for chlorobenzene and 4-chloro-3-nitro-benzoic acid in additional experiments, carried out in a cone calorimeter burning 20 g substance, and in ISO 9705 room test burning about 50 kg. A good agreement between the results for large and small scale indicated that formation of PCCD/F during a fire may be estimated from laboratory experiments. This suggest laboratory test may be used to screen for chemicals posing a hazard for release of PCDD/F during fires. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0045-6535(99)00231-3
• 作为产物：
  描述：

  三聚氯氰 生成 阿特拉津
  参考文献：
  名称：

  Gontscharuk W. W., Wakulenko W. F., Taran P. N., Samsoni-Todorow A. O., Khimija i tekhnol. wody, 16 (1994) N 3, S 250-255

  摘要：

  DOI：

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] 3-[(HYDRAZONO)METHYL]-N-(TETRAZOL-5-YL)-BENZAMIDE AND 3-[(HYDRAZONO)METHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE DERIVATIVES AS HERBICIDES<br/>[FR] DÉRIVÉS DE 3-[(HYDRAZONO))MÉTHYL]-N-(TÉTRAZOL-5-YL)-BENZAMIDE ET DE 3-[(HYDRAZONO)MÉTHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE UTILISÉS EN TANT QU'HERBICIDES
  申请人：SYNGENTA CROP PROTECTION AG

  公开号：WO2021013969A1

  公开（公告）日：2021-01-28

  The present invention related to compounds of Formula (I): or an agronomically acceptable salt thereof, wherein Q, R2, R3, R4, R5 and R6 are as described herein. The invention further relates to compositions comprising said compounds, to methods of controlling weeds using said compositions, and to the use of compounds of Formula (I) as a herbicide.

  本发明涉及以下式（I）的化合物或其农业上可接受的盐，其中Q、R2、R3、R4、R5和R6如本文所述。该发明还涉及包含所述化合物的组合物，使用这些组合物控制杂草的方法，以及将式（I）的化合物用作除草剂的用途。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• [EN] HERBICIDALLY ACTIVE HETEROARYL-S?BSTIT?TED CYCLIC DIONES OR DERIVATIVES THEREOF<br/>[FR] DIONES CYCLIQUES SUBSTITUÉES PAR HÉTÉROARYLE À ACTIVITÉ HERBICIDE OU DÉRIVÉS DE CELLES-CI
  申请人：SYNGENTA LTD

  公开号：WO2011012862A1

  公开（公告）日：2011-02-03

  The invention relates to a compound of formula (I), which is suitable for use as a herbicide wherein G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or latentiating group; Q is a unsubstituted or substituted C3-C8 saturated or mono-unsaturated heterocyclyl containing at least one heteroatom selected from O, N and S, or Q is heteroaryl or substituted heteroaryl; m is 1, 2 or 3; and Het is an optionally substituted monocyclic or bicyclic heteroaromatic ring; and wherein the compound is optionally an agronomically acceptable salt thereof.

  该发明涉及一种化合物，其化学式为(I)，适用作为除草剂，其中G为氢或农业可接受的金属、磺酸盐、铵盐或潜伏基团；Q为未取代或取代的含有至少一个来自O、N和S的杂原子的饱和或单不饱和的C3-C8杂环烷基，或Q为杂芳基或取代的杂芳基；m为1、2或3；Het为可选择地取代的单环或双环杂芳环；且该化合物可选择地为其农学上可接受的盐。
• TRIAZOLE ACC INHIBITORS AND USES THEREOF
  申请人：Gilead Apollo, LLC

  公开号：US20170166584A1

  公开（公告）日：2017-06-15

  The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了三唑化合物，可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及其组合物和使用方法。

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