邻苯二甲酸二异癸酯 | 89-16-7

• 物质功能分类: 化学试剂 - 硅烷试剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 邻苯二甲酸二异癸酯
• 中文别名: DIDP；酞酸二异癸酯；1,2-苯二甲酸二异癸酯；邻苯二甲酸二异癸酯(DIDP)；邻苯二甲酸二(丙基庚)酯；1,2-苯二甲酸二异癸酯,酞酸二异癸酯；邻酞酸二异癸酯；活性黄1；DPHP
• 英文名称: diisodecyl phthalate
• 英文别名: 1,2-benzenedicarboxylic acid bis(8-methylnonyl) ester；1,2-benzenedicarboxylic acid diisodecyl ester；bis(8-methylnonyl) phthalate；di-iso-decyl phthalate；DIDP；bis(8-methylnonyl) benzene-1,2-dicarboxylate
• CAS: 89-16-7；119394-45-5；26761-40-0
• 化学式: C₂₈H₄₆O₄
• 分子量: 446.671
• InChiKey: ZVFDTKUVRCTHQE-UHFFFAOYSA-N

物化性质

• 熔点：
  235°C
• 沸点：
  475.97°C (rough estimate)
• 密度：
  0.965 g/mL at 20 °C (lit.)
• 闪点：
  235 °C
• 溶解度：
  0.00028g/l
• LogP：
  10.554 (est)
• 物理描述：
  Diisodecyl phthalate appears as colorless liquid. May float or sink in water. (USCG, 1999)
• 颜色/状态：
  Clear liquid
• 气味：
  Mild odor
• 蒸汽密度：
  15.4 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  5.28X10-7 mm Hg at 25 °C
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 自燃温度：
  755 °F (402 °C)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating vapors.
• 粘度：
  108 cP at 20 °C
• 腐蚀性：
  MAY ATTACK SOME FORMS OF PLASTICS
• 燃烧热：
  -16,600 Btu/lb = -9,200 cal/g = -386X10+5 Joules/kg (est)
• 折光率：
  Index of refraction: 1.483 at 25 °C/D

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  32
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

邻苯二甲酸二异癸酯（DiDP）是一种主要含有10个碳原子的支链二烷基链的邻苯二甲酸酯同分异构体混合物，广泛用作聚氯乙烯的塑化剂。人类对DiDP的暴露程度尚不明确，部分原因是缺乏足够的DiDP暴露生物标志物。我们在成年雌性Sprague-Dawley大鼠单次口服DiDP（300 mg/kg）后，在尿液中鉴定出了DiDP的几个主要代谢物。这些代谢物可能被用作DiDP暴露的生物标志物。尿液中的代谢物通过色谱法分离并经色谱行为和全扫描负离子电喷雾电离质谱鉴定。对于具有相似分子量的代谢物，我们进一步在精确质量模式下进行了鉴定。对于一些代谢物，我们使用真实标准进行了明确的鉴定。其中一个是DiDP的水解单酯，单异癸基邻苯二甲酸酯（MiDP），检测为次要代谢物，以及MiDP的一个omega氧化产物，单（羧基-异壬基）邻苯二甲酸酯（MCiNP），它是尿液中含量最丰富的代谢物。我们还暂时鉴定了MiDP的其他次要代谢物，包括单（羟基-异癸基）邻苯二甲酸酯、单（氧代-异癸基）邻苯二甲酸酯、单（羧基-异庚基）邻苯二甲酸酯、单（羧基-异己基）邻苯二甲酸酯、单（羧基-异戊基）邻苯二甲酸酯、单（羧基-异丁基）邻苯二甲酸酯和单（羧基-乙基）邻苯二甲酸酯。还检测到了二异十一烷基邻苯二甲酸酯（DiUdP）和二异壬基邻苯二甲酸酯（DiNP）的氧化代谢物，这表明DiDP配方中存在DiUdP和DiNP。在DiDP给药后的4天内，所有这些代谢物的尿浓度逐渐降低。MCiNP和其他DiDP次要代谢物在尿液中的含量比MiDP更丰富，这表明这些氧化产物作为DiDP暴露评估的生物标志物比MiDP更好。为了了解人类通过尿液中MCiNP和其他DiDP次要代谢物的浓度对DiDP的暴露程度，需要对这些代谢物的毒代动力学进行进一步研究。

Diisodecyl phthalate (DiDP) is an isomeric mixture of phthalates with predominantly 10-carbon branched-dialkyl chains, widely used as a plasticizer for polyvinyl chloride. The extent of human exposure to DiDP is unknown in part because adequate biomarkers of exposure to DiDP are not available. We identified several major metabolites of DiDP in urine of adult female Sprague-Dawley rats after a single oral administration of DiDP (300 mg/kg). These metabolites can potentially be used as biomarkers of exposure to DiDP. The metabolites extracted from urine were chromatographically resolved and identified by their chromatographic behavior and full scan negative ion electrospray ionization mass spectrum. The identity of metabolites with similar molecular weights was further examined in accurate mass mode. For some metabolites, unequivocal identification was done using authentic standards. Among these were the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), detected as a minor metabolite, and one omega oxidation product of MiDP, mono(carboxy-isononyl) phthalate (MCiNP), which was the most abundant urinary metabolite. We also tentatively identified other secondary metabolites of MiDP, mono(hydroxy-isodecyl) phthalate, mono(oxo-isodecyl) phthalate, mono(carboxy-isoheptyl) phthalate, mono(carboxy-isohexyl) phthalate, mono(carboxy-isopentyl) phthalate, mono(carboxy-isobutyl) phthalate, and mono(carboxy-ethyl) phthalate. Oxidative metabolites of diisoundecyl phthalate (DiUdP) and diisononyl phthalate(DiNP) were also detected suggesting the presence of DiUdP and DiNP in the DiDP formulation. The urinary concentrations of all these metabolites gradually decreased in the 4 days following the administration of DiDP. MCiNP and other DiDP secondary metabolites are more abundant in urine than MiDP, suggesting that these oxidative products are better biomarkers for DiDP exposure assessment than MiDP. Additional research on the toxicokinetics of these metabolites is needed to understand the extent of human exposure to DiDP from the urinary concentrations of MCiNP and other DiDP secondary metabolites.

来源:Hazardous Substances Data Bank (HSDB)

代谢

...将碳-14标记的DIDP（羧基-(14)C）通过灌胃方式给予Sprague Dawley大鼠（体重200克）以0.1-11.2和1000毫克/千克的剂量。收集24小时内的粪便。收集12小时内的尿液。在尿液中，检测到邻苯二甲酸和氧化单酯衍生物，但在任何剂量下均未检测到单碘癸基邻苯二甲酸酯（MIDP）或DIDP。与单酯衍生物相关的放射性百分比随剂量的增加从0.1毫克/千克的52%增加到1000毫克/千克的72%。同时，与邻苯二甲酸相关的放射性比例从38%下降到1000毫克/千克剂量的18%。在粪便中，检测到单酯的氧化衍生物、MIDP和DIDP。由于粪便中DIDP或其代谢物可能发生细菌降解，数据的量化较为困难。然而，很明显，随着剂量的增加，粪便中恢复的母体化合物的百分比增加：0.1、11和1000毫克/千克后分别为30%、55%和60%。单酯的氧化衍生物和MIDP的百分比分别为0.1、11和1000毫克/千克后的25和30%、14和26%、13和13%。在给药后0-24小时采集胆汁样本或在给药后72小时采集肝脏和肾脏样本时，提取物中未检测到DIDP。基于最终产物的数据表明，代谢方案与报告的DEHP的代谢方案相似：在吸收前，通过明显的非特异性胰腺脂肪酶和肠粘膜酯酶将酯分解为单酯形式和一个醇基团；粪便中MIDP的高含量与这一提出的机制一致。单酯在肝脏中可能通过ω或ω-1氧化发生进一步代谢。与0.1至1000毫克/千克剂量相比，与母体化合物相关的粪便放射性百分比增加了两倍。因此，酯酶的容量可能部分饱和。即使在最低剂量下，母体化合物也可以从粪便中回收，而对于DEHP，据报道单次摄入的吸收阈值为200毫克/千克。低于这个值，母体DEHP未被检测到。相比之下，即使在极低剂量下，DIDP对吸收前必须经历的酯水解步骤的敏感性可能较低。在尿液中鉴定出邻苯二甲酸和MIDP的明显氧化产物。在胆汁中，仅检测到单酯代谢物，这部分解释了粪便中的含量。随着剂量的增加，胆汁中的代谢物组成没有改变，这表明通过该途径的代谢能力没有得到补偿。在尿液中，与邻苯二甲酸相关的放射性百分比随剂量的增加而减少，而单酯的氧化衍生物有所增加。邻苯二甲酸的百分比从0.1毫克/千克的38%降至1000毫克/千克的18%，远超过与DEHP暴露相关的3%的邻苯二甲酸值。显著较高的邻苯二甲酸产量表明，DIDP衍生物可能在体内更容易发生酯水解，这可能是由于酯键由于酯基团的高度支链性质而导致的酯键不稳定。然而，随着DIDP剂量的增加，邻苯二甲酸含量的减少可能表明代谢物容量的部分饱和。...

... Radiolabeled DIDP (carboxyl-(14)C) was administered /to Sprague Dawley rats (200 g body weight)/ in corn oil by gavage at doses of 0.1-11.2 and 1,000 mg/kg. Feces were collected over 24-hour periods. Urine was collected over 12-hour periods. ... In urine, phthalic acid and the oxidized monoester derivative were detected but not monoisodecyl phthalate (MIDP) or DIDP at any of the doses. The percentage of radioactivity associated with the monoester derivative group increased with increasing dose from 52% after 0.1 mg/kg to 72% after 1,000 mg/kg. Concurrently, the proportion of radioactivity associated with phthalic acid was observed to decrease from 38 to 18% after 0.1 and 1,000 mg/kg doses, respectively. In feces, the monoester oxidative derivative, MIDP and DIDP were detected. Because of potential bacterial degradation of DIDP or its metabolites in feces, quantification of the data is difficult. It was readily apparent, however, that with increasing dose the percentage of parent compound recovered in feces increased: 30%, 55% and 60% after 0.1, 11 and 1,000 mg/kg, respectively. The percentage of oxidative derivatives of the monoester and of MIDP were respectively 25 and 30%, 14 and 26%, 13 and 13% after 0.1, 11 and 1,000 mg/kg, respectively. When bile samples were taken from 0-24 hours following dosing or when liver and kidneys samples were taken 72 hours following dosing, DIDP was not detected in extracts. The data based on end products suggest a metabolic scheme comparable to the one reported for DEHP: de-esterification to monoester form and an alcohol moiety by apparent non-specific pancreatic lipase and intestinal mucosa esterases prior to absorption; the high content of MIDP in feces is consistent with this proposed mechanism. Further metabolism of the monoester by omega or omega-1 oxidation probably occurred in the liver. With increasing dose, the percentage of fecal radioactivity associated with the parent compound was increased by a factor of two comparing 0.1 to 1,000 mg/kg doses. Therefore it is probable that esterases capacity has been partially saturated. The parent compound is recoverable from feces even at the lowest dose, which is not the case for DEHP, for which an absorption threshold of 200 mg/kg in a single intake was reported. Below this value, the parent DEHP was not detected. In contrast, even at extremely low doses, DIDP may be less susceptible to the hydrolysis step prerequisite to absorption. Phthalic acid and apparent oxidative products of MIDP were identified in urine. In bile, it is indicated that only monoester metabolites were detected accounting in part for the content in feces. With increasing dose the metabolite composition in bile was not altered, suggesting that metabolic capacity by that route was not compensated. In urine the percentage of radioactivity associated with phthalic acid decreased with dose while an increase was observed in the oxidative derivatives of the monoester. The percentage of phthalic acid ranged from 38% at 0.1 mg/kg to 18% at 1,000 mg/kg, far exceeding the value of 3% phthalic acid associated with DEHP exposures. The markedly higher production of phthalic acid suggests that DIDP derivatives may be more susceptible to de-esterification within the body perhaps due to destabilisation of the ester bond resulting from the highly branched nature of the ester groups. However, the decrease in phthalic acid content with increasing DIDP dose may suggest partial saturation of metabolite capacity. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

高分子量邻苯二甲酸酯，如邻苯二甲酸二异壬酯（DINP）和邻苯二甲酸二异癸酯（DIDP），在制造聚合物和消费品时被广泛用作塑化剂。人体生物监测研究已经使用DINP和DIDP的代谢物作为生物标志物来评估人体暴露。在本次综述中，我们总结并分析了公开可获得的关于DINP和DIDP的化学、代谢和排泄动力学的科学数据，以确定特定和敏感的代谢物。对DINP和DIDP的人体生物监测数据进行了审查，以评估这些代谢物作为暴露生物标志物的适用性。在动物和人体中进行的研究结果表明，邻苯二甲酸酯被迅速代谢并且不会生物累积。在第一阶段代谢中，DINP和DIDP的酯水解导致水解单酯的形成。这些初级代谢物会进一步发生氧化反应产生次级代谢物。因此，尿液中DINP和DIDP的次级代谢物水平始终高于初级代谢物。人体生物监测研究的结果显示，尿液中DINP和DIDP的次级代谢物几乎在所有测试样本中被检测到，而初级代谢物仅在约10%的样本中被检测到。这表明次级代谢物是DINP/DIDP暴露的非常敏感的生物标志物，而初级代谢物则不是。NHANES数据显示，在人群水平上，MCIOP和MCINP（DINP和DIDP的次级代谢物）的中位浓度分别约为5.1微克/升和2.7微克/升。此外，可用的生物监测数据表明，婴儿/儿童接触到的邻苯二甲酸酯水平高于成人。

High molecular-weight phthalates, such as diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP), are widely used as plasticizers in the manufacturing of polymers and consumer products. Human biological monitoring studies have employed the metabolites of DINP and DIDP as biomarkers to assess human exposure. In this review, we summarize and analyze publicly available scientific data on chemistry, metabolism, and excretion kinetics, of DINP and DIDP, to identify specific and sensitive metabolites. Human biological monitoring data on DINP and DIDP are scrutinised to assess the suitability of these metabolites as biomarkers of exposure. Results from studies carried out in animals and humans indicate that phthalates are metabolised rapidly and do not bioaccmulate. During Phase-I metabolism, ester hydrolysis of DINP and DIDP leads to the formation of hydrolytic monoesters. These primary metabolites undergo further oxidation reactions to produce secondary metabolites. Hence, the levels of secondary metabolites of DINP and DIDP in urine are found to be always higher than the primary metabolites. Results from human biological monitoring studies have shown that the secondary metabolites of DINP and DIDP in urine were detected in almost all tested samples, while the primary metabolites were detected in only about 10% of the samples. This indicates that the secondary metabolites are very sensitive biomarkers of DINP/DIDP exposure while primary metabolites are not. The NHANES data indicate that the median concentrations of MCIOP and MCINP (secondary metabolites of DINP and DIDP, resp.) at a population level are about 5.1 ug/L and 2.7 ug/L, respectively. Moreover, the available biological monitoring data suggest that infants/children are exposed to higher levels of phthalates than adults.

来源:Hazardous Substances Data Bank (HSDB)

代谢

二异癸基酞酸酯（DiDP）主要用作塑料增塑剂，是一种主要由十碳支链异构体组成的混合物。由于缺乏足够的生物标志物，之前尚未对DiDP暴露进行评估。在129名未知的DiDP暴露的成年志愿者中，通过固相萃取结合高效液相色谱-串联质谱（HPLC-MS/MS）技术，估计了三种DiDP的氧化代谢物：单羧基异壬基酞酸酯（MCiNP）、单氧代异癸基酞酸酯（MOiDP）和单羟基异癸基酞酸酯（MHiDP）的尿液中浓度，这些代谢物之前在DiDP给药的大鼠中已经识别。由于缺乏DiDP氧化代谢物的真实标准，使用了二（2-乙基己基）酞酸酯的相应氧化代谢物作为替代。有趣的是，DiDP的水解单酯，单异癸基酞酸酯（MiDP），在所有样本中均未检测到，而MCiNP、MHiDP和MOiDP分别检测到了98%、96%和85%的样本。MCiNP主要以自由形式排泄，而MOiDP则以葡萄糖苷酸形式排泄。MCiNP、MHiDP和MOiDP从HPLC柱中作为多个峰的簇洗脱，这可能是由于商业DiDP配方中存在大量结构上相似的同分异构体。这些氧化代谢物的尿液中浓度显著相关（p < 0.0001），从而证实了一个共同的先驱物。DiDP氧化代谢物的尿液中浓度也与二异壬基酞酸酯（DiNP）的氧化代谢物显著相关（p < 0.0001），这表明商业DiDP中可能存在DiNP同分异构体，或者DiDP和DiNP可能同时用于消费品中。所呈现的浓度是半定量估计，应谨慎解读。尽管如此，MCiNP、MHiDP和MOiDP的检测频率和尿液浓度高于MiDP，这表明这些氧化代谢物是DiDP暴露评估的更好生物标志物。这些数据还表明，除非测量氧化代谢物，否则DiDP暴露的普遍性可能会被低估。

Di-isodecyl phthalate (DiDP), primarily used as a plasticiser, is a mixture of isomers with predominantly ten-carbon branched side chains. Assessment of DiDP exposure has not been conducted before because adequate biomarkers were lacking. In 129 adult volunteers with no known exposure to DiDP, the urinary concentrations of three oxidative metabolites of DiDP: monocarboxyisononyl phthalate (MCiNP), monooxoisodecyl phthalate (MOiDP) and monohydroxyisodecyl phthalate (MHiDP), previously identified in DiDP-dosed rats, were estimated by solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using the respective oxidative metabolites of di(2-ethylhexyl)phthalate since authentic standards of the DiDP oxidative metabolites were unavailable. Interestingly, the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), was not detected in any of the samples, while MCiNP, MHiDP and MOiDP were detected in 98%, 96% and 85%, respectively, of the samples tested. MCiNP was excreted predominantly in its free form, whereas MOiDP was excreted as its glucuronide. MCiNP, MHiDP and MOiDP eluted as clusters of multiple peaks from the HPLC column probably due to the presence of numerous structurally similar isomers present in commercial DiDP formulations. The urinary concentrations of these oxidative metabolites correlated significantly (p < 0.0001) with each other, thus confirming a common precursor. The urinary concentrations of these DiDP oxidative metabolites also correlated significantly (p < 0.0001) with oxidative metabolites of di-isononyl phthalate (DiNP) suggesting the potential presence of DiNP isomers in commercial DiDP or simultaneous use of DiDP and DiNP in consumer products. The concentrations presented are semiquantitative estimates and should be interpreted cautiously. Nevertheless, the higher frequency of detection and higher urinary concentrations of MCiNP, MHiDP and MOiDP than of MiDP suggest that these oxidative metabolites are better biomarkers for DiDP exposure assessment than MiDP. These data also suggest that unless oxidative metabolites are measured, the prevalence of exposure to DiDP will probably be underestimated.

来源:Hazardous Substances Data Bank (HSDB)

代谢

邻苯二甲酸酯首先被水解为其单酯衍生物。一旦形成，单酯衍生物可以在体内进一步水解为邻苯二甲酸或与葡萄糖醛酸结合，这两种物质随后都可以被排出体外。单酯中的末端或倒数第二个碳原子也可以被氧化成醇，这种醇可以原样排出，或者首先被氧化成醛、酮或羧酸。单酯和氧化代谢物通过尿液和粪便排出体外。（A2884）

Phthalate esters are first hydrolyzed to their monoester derivative. Once formed, the monoester derivative can be further hydrolyzed in vivo to phthalic acid or conjugated to glucuronide, both of which can then be excreted. The terminal or next-to-last carbon atom in the monoester can also be oxidized to an alcohol, which can be excreted as is or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and oxidative metabolites are excreted in the urine and faeces. (A2884)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

鉴定和使用：邻苯二甲酸二异癸酯（DIDP）是一种无色液体，具有轻微的气味。它被用作聚氯乙烯（PVC）的通用型增塑剂；在电线电缆应用中，它是PVC的首选增塑剂。DIDP在PVC的最终用途包括：压延（薄膜、片材和涂层产品、地板、屋顶、墙面覆盖物），挤出（软管和型材、电线电缆、透明、医疗、薄膜），注射成型（鞋类和其他杂项），塑料溶胶涂布，其他塑料溶胶应用（汽车底漆和密封剂、旋转/倾倒成型）。非PVC应用包括除PVC外的其他乙烯树脂/丙烯酸塑料树脂，基本上是聚甲基丙烯酸甲酯，以及纤维素酯塑料和其他含有聚合物的产品，如压敏胶粘剂和印刷油墨。此外，DIDP还应用于非聚合物领域，如防腐和防污涂料。人类暴露和毒性：在21天的重复刺激贴片测试中，没有证据表明人类志愿者出现了临床致敏或皮肤刺激。在一项流行病学研究中，儿童当前的哮喘与两种高分子量邻苯二甲酸酯的代谢物最高四分位数相关，这两种邻苯二甲酸酯分别是邻苯二甲酸二异壬酯和邻苯二甲酸二异癸酯。所有塑料溶胶工人的班后DIDP代谢物值大约是背景暴露的20倍，班前值大约是背景暴露的5-10倍。动物研究：在急性吸入研究中，大鼠、小鼠和豚鼠暴露于0.13 mg/L的标称浓度下6小时。没有死亡，没有系统效应的证据，也没有明显的呼吸道刺激。在一项为期90天的亚慢性毒性研究中，大鼠通过饲料摄入DIDP，剂量分别为0.05%，0.3%和1%（大约相当于30、200和650 mg/kg/天）。主要效果是最高剂量组动物的肝脏重量增加。中等剂量组动物（大约200 mg/kg/天）没有观察到效果。其他从3周到90天的研究也证实肝脏是目标器官。其中一项研究中，大约350 mg/kg/天的剂量下，动物的肝脏重量和肝脏酶诱导有显著影响。在其他研究中，最低有效剂量更高。雄性大鼠的饲料中DIDP含量高达2.5%（大约相当于2600 mg/kg/天）治疗三周，并未导致睾丸重量显著减少或组织学变化。在浓度为1X10^-3 M时，DIDP在重组酵母雌激素活性筛选中无活性。在发育研究中，DIDP在1000 mg/kg/天的剂量下对胎儿的影响边缘显著。DIDP没有显示出致突变潜力。在沙门氏菌鼠伤寒菌株TA98、TA100、TA1535和TA1537中，浓度高达10 mg/板的DIDP（无论有无代谢活化）均无活性。由于DIDP在诱导过氧化物酶体增殖方面的潜力有限，因此在大鼠中不具有致癌性。然而，在摄入1% DIDP的雄性rasH2小鼠中，它确实引起了肝细胞腺瘤，这与对照rasH2小鼠或野生型小鼠肝脏的发现相比。生态毒性研究：DIDP对水蚤的繁殖没有影响。环境研究表明，在几种水生生物的急性毒性研究中，观察到的是低分子量邻苯二甲酸酯的毒性模式，而不是高分子量邻苯二甲酸酯。在实验室实验中，研究了九种邻苯二甲酸酯对金鱼（Carassius auratus）肝脏的抗氧化反应，其毒性顺序如下：邻苯二甲酸二丁酯（DBP）>邻苯二甲酸二乙酯（DEP）>邻苯二甲酸二异癸酯（DIDP）>邻苯二甲酸二苯酯（DPP）>邻苯二甲酸丁苄酯（BBP）>邻苯二甲酸二烯丙酯（DAP）>邻苯二甲酸二环己酯（DCHP）>邻苯二甲酸二甲酯（DMP）>邻苯二甲酸二（2-乙基己基）酯（DEHP）。

IDENTIFICATION AND USE: Diisodecyl phthalate (DIDP) is a clear liquid with mild odor. It is used as a general purpose plasticizer for polyvinyl chloride; preferred plasticizer for PVC in wire and cable applications. DIDP in the PVC end-use includes: calendering (film, sheet and coated products, flooring, roofing, wall covering), extrusion (hose and profile, wire and cable, clear, medical, film), injection moulding (footwear and miscellaneous), plastisol spread coating, other plastisol applications (car undercoating and sealants, slush/rotational moulding). Non-PVC applications are in other vinyl resins than PVC /acrylic plastic resins, which are basically polymethyl methacrylate/, cellulose ester plastics and other polymer containing products, such as pressure sensitive adhesives and printing inks. Otherwise DIDP is applied in non-polymer applications, such as anti-corrosion and anti-fouling paints. HUMAN EXPOSURE AND TOXICITY: There was no evidence of clinical sensitization or dermal irritation in human volunteers participating in a 21-day repeated insult patch test. In an epidemiology study, current asthma in children was associated with the highest quartiles of metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate. All plastisol workers had post shift values of DIDP metabolites that were approx. 20-times higher, and pre-shift values that were approx. 5-10 times higher than those of the general background exposure. ANIMAL STUDIES: In acute inhalation studies, rats, mice and guinea pigs were exposed to a nominal concentration of 0.13 mg/L for 6 hr. There was no mortality, no evidence of systemic effects, and no apparent respiratory irritation. In one 90-day subchronic toxicity study in rats, DIDP was given in the feed at levels of 0.05, 0.3, and 1% (approximately 30, 200, and 650 mg/kg/day). The predominant effect was an increase in liver weight in animals treated with the highest dose. There were no effects noted in the mid-dose animals (approximately 200 mg/kg/day). Other studies ranging from 3 wk to 90 day have confirmed the liver as the target organ. In one of these studies, significant effects on liver weight and liver enzyme induction were noted in animals treated with approximately 350 mg/kg/day. In other studies, the lowest effect levels were higher. Treatment for three weeks at levels up to 2.5% DIDP in the diet (approximately 2600 mg/kg/day) did not result in significantly decreased testicular weight or histological changes in male rats. At concentrations up to 1X10-3 M, DIDP was inactive in a recombinant yeast screen for estrogenic activity. In developmental studies DIDP showed fetal effects of borderline significance at 1000 mg/kg/day. DIDP shows no evidence of mutagenic potential. It was inactive in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 at concentrations up to 10 mg/plate (with and without metabolic activation). DIDP was non-carcinogenic in rats due to its limited potential for peroxisomal proliferating activity. It did produce hepatocellular adenomas in the male rasH2 mice receiving 1% DIDP, compared with the findings in the liver of control rasH2 mice or wild-type mice. ECOTOXICITY STUDIES: DIDP had no effect on reproduction of Daphnia. Environmental studies demonstrate pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters in acute toxicity studies for several aquatic species. In laboratory experiments performed to determine the antioxidant responses to nine phthalates in the liver of the goldfish Carassius auratus the toxicity order was as follows: dibutyl phthalate (DBP)>diethyl phthalate (DEP)>diisodecyl phthalate (DIDP)>diphenyl phthalate (DPP)>butyl benzyl phthalate (BBP)>diallyl phthalate (DAP)>dicyclohexyl phthalate (DCHP)>dimethyl phthalate (DMP)>di(2-ethylhexyl) phthalate (DEHP).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

邻苯二甲酸酯类是内分泌干扰物。它们会降低胎儿睾丸的睾酮生产，并通过降低mRNA表达来减少类固醇生成基因的表达。一些邻苯二甲酸酯还被证明可以减少胰岛素样肽3（insl3）的表达，这是一种由莱迪希细胞分泌的重要激素，对胎儿发育中的阴囊韧带至关重要。动物研究显示，这些效应会干扰生殖发育，并可能导致受影响的幼崽出现多种畸形。(A2883)

Phthalate esters are endocrine disruptors. They decrease foetal testis testosterone production and reduce the expression of steroidogenic genes by decreasing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide 3 (insl3), an important hormone secreted by the Leydig cell necessary for development of the gubernacular ligament. Animal studies have shown that these effects disrupt reproductive development and can cause a number of malformations in affected young. (A2883)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

邻苯二甲酸酯类是内分泌干扰物。动物研究显示它们会干扰生殖发育，并可能导致受影响幼崽出现多种畸形，例如会阴距缩短（AGD）、隐睾、尿道下裂和生育能力下降。与邻苯二甲酸酯相关的影响组合被称为“邻苯二甲酸酯综合症”。(A2883)

Phthalate esters are endocrine disruptors. Animal studies have shown that they disrupt reproductive development and can cause a number of malformations in affected young, such as reduced anogenital distance (AGD), cryptorchidism, hypospadias, and reduced fertility. The combination of effects associated with phthalates is called 'phthalate syndrome’. (A2883)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

该物质可以通过吸入其蒸汽被身体吸收。

The substance can be absorbed into the body by inhalation of its vapour.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

吸收、分配和排泄

这项研究检查了一系列邻苯二甲酸酯二酯在大鼠皮肤吸收的程度。测试的包括二甲酯、二乙酯、二丁酯、二异丁酯、二己酯、二(2-乙基己基)酯、二癸酯和苯甲基丁酯。从雄性F344大鼠背部的皮肤区域（直径1.3厘米）剪下毛发，应用14C标记的邻苯二甲酸酯二酯，剂量为157微摩尔/千克，并在涂抹区域覆盖一个有孔的帽子。大鼠被限制在一个代谢笼中，该笼允许分别收集尿液和粪便，持续7天。每隔24小时收集一次尿液和粪便，将排出的14C量作为经皮吸收的指标。在24小时内，二乙酯的排出量最高（26%）。随着烷基侧链长度的增加，第一个24小时内排出的14C量显著减少。7天内累计百分比剂量排出最多的是二乙酯、二丁酯和二异丁酯，约为施加的14C的50-60%；中等的是二甲酯、苯甲基丁酯和二己酯，约为20-40%。除二癸酯外，所有邻苯二甲酸酯二酯的主要排泄途径是尿液。这种化合物吸收不良，几乎没有尿液排出。7天后，每个邻苯二甲酸酯在体内的百分比剂量最小，没有特定的组织分布。大部分未排出的剂量留在应用区域。这些数据表明，邻苯二甲酸酯二酯的结构决定了皮肤吸收的程度。吸收在二乙酯时最大化，随后随着烷基侧链长度的增加而显著减少。

This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the 14(C)phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of (14)C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of (14)C excreted in the first 24 hr decreased signficantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied (14)C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中，80%的通过皮肤应用的（14）C-DIDP（环标记）在应用7天后在应用部位被回收。只有2%的施用剂量在其他组织或排泄物中被回收，总回收率仅为82%。在另一项大鼠研究中，总回收率更高（94%或更高），也得到了类似的结果。

In rats, 80% of dermally applied (14)C-DIDP (ring-label) was recovered at the site of application 7 days after the application. Only 2% of the applied dose was recovered in other tissues or excreta with a total recovery of only 82% reported. In another study in rats in which total recoveries were better (94% or greater), similar results were obtained.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C-DIDP应用于皮肤上，并封闭给药部位。在1、3和7天后，分别有96%、92%和93%的剂量仍留在给药部位。在其他组织和排泄物中仅发现微量的放射性。总吸收剂量约为给药剂量的4%。

(14)C-DIDP was applied to the skin and the dose site was occluded. At 1, 3, and 7 days, 96, 92, and 93% of the doses, respectively, were still at the application site. Only trace amounts of radioactivity were found in other tissues and excreta. The total absorbed dose was approximately 4% of the administered dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

六只雄性Sprague Dawley大鼠通过吸入（仅头部）暴露于91 mg/立方米(14)C-DIDP 6小时。在72小时内收集排泄物，并在暴露后立即和暴露后72小时对3只动物进行放射性分析。假设大鼠的分钟体积为200毫升，估计吸入的DIDP总量大约为14.4微摩尔。初始体内负荷为8.3微摩尔，表明大约58%的吸入量保留在体内。初始体内负荷的12%在肠道中，85%在肺中。肺部的剂量在头72小时内清除了73%，这表明DIDP或其代谢物从肺吸收到身体其他部位的比例约为73%。

Six male Sprague Dawley rats were exposed for 6 hours by inhalation (head only) to 91 mg/cu m of (14)C-DIDP. Excreta were collected over a 72-hour period and 3 animals were analyzed for radioactivity immediately after the exposure and at 72 hours after the exposure. Assuming a minute volume of 200 mL for the rats, the estimated total amount of DIDP inhaled would be approximately 14.4 umoles. The initial body burden was 8.3 umoles, indicating that approximately 58% of what was inhaled was retained in the body. Twelve percent of the initial body burden was in the gut and 85% was in the lung. 73% of the dose to the lung was cleared during the first 72 hours, indicating that absorption of DIDP or its metabolites from the lung into the rest of the body was about 73%.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  1

制备方法与用途

用途：用作色谱固定液。

类别：有毒物品

毒性分级：高毒

急性毒性（口服）：大鼠 LD₅₀ 为 64 毫克/公斤

可燃性危险特性：可燃；燃烧时产生刺激烟雾

储运特性：需在通风、低温和干燥条件下储存，并与库房食品原料分开存放

灭火剂：干粉、泡沫、沙土、二氧化碳及雾状水

职业标准：

• 时间加权平均容许浓度（TWA）：3 毫克/立方米
• 短时间接触容许浓度（STEL）：5 毫克/立方米

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  邻苯二甲酸二甲酯	phthalic acid dimethyl ester	131-11-3	C10H10O4	194.187
  苯酐	phthalic anhydride	85-44-9	C8H4O3	148.118

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  1,2-苯二羧酸双十一烷基酯	di-n-undecyl phthalate	3648-20-2	C30H50O4	474.725

反应信息

• 作为反应物：
  描述：

  1,2-cyclohexanedicarboxylic acid diisodecyl ester 、 邻苯二甲酸二异癸酯 、 邻苯二甲酸二(2-丙基庚)酯 生成 1,2-苯二羧酸双十一烷基酯
  参考文献：
  名称：

  THERMOPLASTIC COMPOSITIONS HAVING IMPROVED FLOWABILITY

  摘要：

  本发明涉及一种组合物，包括(i) 作为组分(I)的至少一种模塑组合物，其中包括成分A和B，其中A）是作为组分A的嵌段共聚物，而B）是作为组分B的热塑性共聚物;以及(ii) 至少一种环己烷多羧酸衍生物，其化学式为(I)的组分(II)，其中R1为C1-C10烷基或C3-C8环烷基，m为0、1、2或3，n为2、3或4，R为氢或C1-C30烷基;或者，基团—(COOR)n形成公式的酐： 在本发明中，组分(I)包括由成分A的重量占11至19.9%和成分B的重量占80.1至89%的组分，其中每个重量百分比值都基于成分A和B的总量，这些值的总和为100%的重量，并且本发明还涉及一种生产该组合物的方法，使用该组合物制造模塑、薄膜、泡沫或纤维，并且包括该组合物的模塑、薄膜、泡沫或纤维。

  公开号：

  US20120220678A1
• 作为产物：
  描述：

  异十醇 、 邻苯二甲酸二甲酯 在 Ethylenediamine titanium 作用下， 以 水 为溶剂， 反应 4.0h， 生成 邻苯二甲酸二异癸酯
  参考文献：
  名称：

  一种钛螯合物催化酯交换制备邻苯二甲酸高 碳醇酯的方法

  摘要：

  本发明涉及一种钛螯合物催化酯交换制备邻苯二甲酸高碳醇酯的方法，以邻苯二甲酸二甲酯、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯等邻苯二甲酸低碳醇酯和异壬醇、异癸醇、2‑丙基庚醇等高碳醇为原料，以邻菲罗啉、2,2’‑联吡啶、乙二胺、N,N‑二甲基乙二胺、N,N′‑二甲基乙二胺、N,N,N′,N′‑四甲基乙二胺、1,2‑环己二胺等氮氮双齿配体的钛螯合物为催化剂，催化剂用量为邻苯二甲酸低碳醇酯质量的0.01～0.1％，高碳醇和邻苯二甲酸低碳醇酯摩尔比为2～4，反应温度160～220℃，反应时间2～5小时，邻苯二甲酸低碳醇酯转化率以及邻苯二甲酸高碳醇酯选择性最高达99％以上。本发明具有原料储运稳定性好、进料方便、副反应少、原料消耗低、催化剂无腐蚀且用量少等优点。

  公开号：

  CN108976116B

文献信息

• Process for the preparation of olmesartan medoxomil
  申请人：KRKA, tovarna zdravil, d.d., Novo mesto

  公开号：EP1816131A1

  公开（公告）日：2007-08-08

  The present invenion relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.

  本发明涉及一种改进的工艺，用于制造奥美沙坦及其药用可接受的盐和酯，作为治疗高血压及相关疾病和症状的药物的活性成分。
• PROCESS FOR THE PREPARATION OF OLMESARTAN MEDOXOMIL
  申请人：Zupancic Silvo

  公开号：US20090131680A1

  公开（公告）日：2009-05-21

  The present invention relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.

  本发明涉及一种改进的工艺，用于制造奥美沙坦及其药用可接受的盐和酯，作为治疗高血压和相关疾病和症状的药物的活性成分。
• PESTICIDAL COMPOSITION
  申请人：Mitsui Chemicals, Inc.

  公开号：EP1872658A1

  公开（公告）日：2008-01-02

  An object of the present invention is to provide a composition for preventing harmful organisms exerting an excellent control effect against plant diseases and/or insecticidal effect. Disclosed is a composition for preventing harmful organisms comprising a diamine derivative represented by the formula (1), and one or more compounds selected from the group consisting of other fungicides, insecticides and acaricides as active ingredients, wherein, in the formula, R1 represents a hydrocarbon having 1 to 6 carbon atoms which is substituted with halogen or the like; R2 and R7 each independently represent a hydrogen atom, a hydrocarbon having 1 to 6 carbon atoms or the like; R3 and R4 each independently represent a hydrogen atom, a hydrocarbon having 1 to 6 carbon atoms which may be substituted or the like, or R3 and R4 represent a cycloalkyl group having 3 to 6 carbon atoms containing a carbon atom bonded thereto; R5 and R6 each independently represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or the like; and R8 represents an arylalkyl group which may be substituted, an aryl group which may be substituted or a heteroaryl group which may be substituted.

  本发明的目的是提供一种用于防止有害生物对植物病害和/或杀虫效果具有优异控制效果的组合物。公开了一种用于防止有害生物的组合物，包括由式（1）表示的二胺衍生物，以及作为活性成分的从其他杀菌剂、杀虫剂和螨虫剂组成的化合物中选择的一种或多种化合物， 其中，在该式中，R1代表具有1至6个碳原子的烃，其被卤素或类似物取代；R2和R7各自独立地代表氢原子，具有1至6个碳原子的烃或类似物；R3和R4各自独立地代表氢原子，具有1至6个碳原子的烃，可能被取代或类似物，或者R3和R4代表含有与之相结合的碳原子的3至6个碳原子的环烷基；R5和R6各自独立地代表氢原子，具有1至6个碳原子的烃基或类似物；R8代表可能被取代的芳基烷基，可能被取代的芳基或可能被取代的杂芳基。
• Aspartic ester functional compounds
  申请人：Danielmeier Karsten

  公开号：US20060011295A1

  公开（公告）日：2006-01-19

  A functional aspartate prepared by A) reacting an aziridine with a Michael-acceptor molecule to form an aziridinyl aspartate, and B) reacting the aziridinyl aspartate with an active hydrogen containing compound to form the functional aspartate. The functional aspartate can be used in adhesive, sealant or coating compositions that also include an isocyanate functional material. The composition can be used in a method of bonding a first substrate to a second substrate that includes applying a coating of the above-identified adhesive composition to at least one surface of the first substrate or the second substrate, and contacting a surface of the first substrate with a surface of the second substrate, where at least on of the contacting surfaces has the coating applied thereto. The composition can also be used to coat substrates.

  通过将环氧丙烷与一种迈克尔受体分子反应以形成环氧丙烷基天冬氨酸，然后将环氧丙烷基天冬氨酸与含有活性氢的化合物反应以形成功能性天冬氨酸，可以制备一种功能性天冬氨酸。这种功能性天冬氨酸可用于包括异氰酸酯功能材料的粘合剂、密封剂或涂料组合物中。该组合物可用于粘合第一基材到第二基材的方法，包括将上述识别的粘合剂组合物涂覆至第一基材或第二基材的至少一个表面，并使第一基材的表面与第二基材的表面接触，其中至少一个接触表面上涂有该涂层。该组合物也可用于涂覆基材。
• HYDROXYMETHYL-CARBOXAMIDO-SUBSTITUTED SILANE AND ITS USE FOR CURABLE, SILANE-TERMINATED POLYMERS
  申请人：SIKA TECHNOLOGY AG

  公开号：US20160159833A1

  公开（公告）日：2016-06-09

  Specific hydroxysilanes of formula (I), a method for the production thereof, the use thereof as a constituent of moisture-curing compositions, and silane-functional compounds produced therefrom, in particular silane-functional polymers and isocyanatosilanes. The hydrosilanes can be produced in a simple process with a high degree of purity and are storage-stable after production. Production from the reaction of lactides with aminosilanes is particularly advantageous. Hydroxysilane of formula (I), where n is 1 or 2.

  公式（I）的特定羟基硅烷，其生产方法，其用作湿固化组合物成分的用途，以及由此产生的硅烷官能化化合物，特别是硅烷官能化聚合物和异氰酸硅烷。这些氢硅烷可以通过简单的过程以高纯度生产，并且在生产后具有储存稳定性。从乳酸酯与氨基硅烷的反应中生产是特别有利的。公式（I）的羟基硅烷，其中n为1或2。

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