基本职业卫生服务试点前后五类企业使用有机溶剂情况调查

目的 为了解宝安区福永街道开展基本职业卫生服务（BOHS）试点后控制有机溶剂作用的成效.方法 用回顾性定群研究方法,随机抽取电子、塑胶、五金、印刷、家俱5类企业61间,对他们使用的有机溶剂及接触人员情况进行调查.结果 2009年使用苯系物、三氯乙烯、正己烷三种溶剂的企业比2007年明显减少（P〈0.05）,接触三种溶剂的工人也比2007年明显减少（P〈0.05）.结论 开展BOHS试点减少了接触有机溶剂的人数,降低了由此引起职业病危害.     

格列奇特中残留溶媒甲醇、乙酸乙酯的测定

目的：建立一种气相色谱法测定原料药格列奇特中甲醇和乙酸乙酯有机溶剂残留量的方法。方法：选正丙醇作内标物．以N,N-二甲基甲酰胺为溶剂在极性弹性石英毛细柱上进行各组分分离,效果良好。(采用程序升温)柱温100℃保留3分钟,以25℃／min的速率升160C保留5分钟。进样口温度200℃,检测器温度250℃,分流比70：1,载气：高纯氮气,流速：2．0ml／min。结果：平均回收率甲醇105．1％乙酸乙酯101．5％。结论：该方法克服了进样量不准确的缺点,重现性好,精度高。     

Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action.Pregnant rat dams were exposed during gestation and lactation to mixtures of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined.Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.     

Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations

Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng/ml and was effective at this concentration in decreasing the sensitivities of the embryos to estradiol and estrogenic EDCs. The complete antagonist ICI 182,780 inhibited development at concentrations as low as 0.03 ng/ml but increased embryo sensitivity to estradiol and estrogenic EDCs. Estradiol and estrogenic EDCs all cause developmental toxicity in sea urchins through a TAM-sensitive but an ICI-insensitive mechanism. It remains to be demonstrated whether this mechanism involves an estrogen-responsive nuclear receptor (NR), a membrane receptor (NR or non-NR-related) or a completely different mechanism of toxicity. However, early embryo sensitivity and the differential response to SERM co-incubation further suggests more than one mode of EDC action in the developing sea urchin embryo.     

吉非罗齐中残留溶媒丙酮的测定

目的 建立一种气相色谱法测定原料药吉非罗齐中丙酮有机溶剂残留量的方法[1]。选正丙醇作内标物[2],以N,N二甲基甲酰胺为溶剂在极性弹性石英毛细柱上进行各组分分离,效果良好。(采用程序升温)柱温100℃保留2分钟,以20℃／min的速率升180℃保留5分钟。进样口温度200℃,检测器温度250℃,分流比70：1。载气：高纯氮气流速：2．0ml／min结果平均回收率丙酮105．1％.结论 该方法克服了进样量不准确的缺点,重现性好,精度高。     

An environmentally relevant mixture of organochlorines, their metabolites and effects on preimplantation development of porcine embryos

Environmental exposure of human populations to organochlorines is still widespread despite several international regulations banning or restricting their use. This study tested the hypothesis that an environmentally relevant complex mixture of organochlorines comprising polychlorinated biphenyls (PCBs), technical chlordane, dichlorodiphenyldichloroethylene and 12 other components is toxic for porcine embryos (at relative concentrations of 1-10000-fold the environmental organochlorine levels of contamination or 4.2 microg/l total PCBs). We also tested the embryotoxicity of a metabolised organochlorine mixture (relative concentrations of 0.9, 1.8, 2.7, 3.6 and 4.5 microg/l hydroxy-PCBs (OH-PCBs)) obtained by extracting plasma samples from sows treated with the native mixture. Embryos produced in vitro were exposed to either the organochlorine mixture or the metabolised extract for 9 days. The organochlorine mixture reduced embryonic development at the 10000x concentration (relative concentration of 42 mg/l PCBs; p=0.05). The organochlorine mixture also reduced the mean number of blastomeres per expanded blastocyst in a dose-dependent manner (p=0.038) but did not induce blastomere apoptosis (p>0.05). In contrast, the metabolised extract did not affect development or blastomere number at the concentrations tested, although the highest level of this mixture (4.5 microg/l OH-PCBs) was still very low (i.e. similar to the 1x concentration of the organochlorine mixture, which also did not alter embryo parameters). These data lead to the conclusion that while high concentrations of the native organochlorine mixture are toxic for porcine embryos, concentrations of either the native or the metabolised mixture that bear some relevance to exposure of human populations in the Arctic were without observable effect.     

UV–Vis spectroscopic quantification of residual acetone during the development of nanoparticulate drug delivery systems

Methods for nanoparticles preparation often employ organic solvents in order to solubilize the non-polar constituents of the final nanostructures. In the research process, nanoparticles are assayed as aqueous suspensions in several cases, so that an excessive residual concentration of the organic solvent needs to be avoided since may lead to undesired secondary effects during biological tests. Despite the importance, residual solvent concentration is rarely determined, making necessary the development of quantification methods suitable for this purpose. Acetone is frequently used in drug delivery systems preparation, being capable to exert significant toxicities both, in vitro and in vivo. Thus, a simple and inexpensive UV–Vis spectrophotometric method is proposed to directly determine acetone from nanoparticles suspensions employing its reaction with vanillin. Central composite designs were employed to correct and optimize the quantification method, which was then validated according to international guidelines. The optimized method resulted accurate, precise, and linear in the range of 10–50?µg/mL, with an R² of 0.998 and limits of detection and quantification of 2.6 and 7.8?µg/mL, respectively. The effect of several surfactants employed during nanoparticles preparation was not detrimental to the method. The proposed procedure can be successfully applied to directly quantify acetone from nanoparticles suspensions.     

药物中的残留溶剂

目的介绍药物中的残留溶剂。方法对ICH、欧洲药典、美国药典和中国药典有关残留溶剂等问题进行讨论。结果与结论对药物中的残留溶剂应引起重视并应规定其允许残留量。第3类溶剂的残留量可用干燥失重法测定,而大多数第1类和第2类溶剂的残留量则用顶空气相色谱法测定。     

Deep eutectic solvents comprising active pharmaceutical ingredients in the development of drug delivery systems

Introduction: Deep eutectic solvents comprising or acting as solvents of active pharmaceutical ingredients (API-DES) emerged as promising alternatives to improve therapeutic efficiency, with the additional possibility to integrate them in (bio)polymer-based systems to enhance their delivery.

Areas covered: A critical review of the API-DES field evolution is herein presented, namely on the capacity of DES to integrate APIs in their composition and on the use of DES as solvents for APIs. These strategies avoid a current major concern related to drugs and APIs, i.e. polymorphism, and increase the solubility and bioavailability of the target API which leads to increased bioavailability. Owing to their composition versatility, polymerizable API-DES can also be prepared. Finally, the incorporation of API-DES in (bio)polymer-based systems to improve drug delivery is presented and discussed.

Expert opinion: The relatively easy preparation of API-DES and their capacity to tune the API’s release profile when incorporated in (bio)polymer-based systems represent an effective alternative to improve the APIs therapeutic action and to develop controlled drug delivery systems. Given the potential and progress demonstrated so far, the authors foresee further research on novel API-DES and on their delivery routes, envisaging the development of alternative therapies and final approval as therapeutics.     

The Influence of Trichloroethylene and Related Drugs on the Vestibular System

A previously described experimental model for studying the effect of industrial solvents on the vestibular system of rabbits has been applied to trichloroethylene. Estimation of trichloroethylene and its metabolites in blood and cerebrospinal fluid was performed by gas chromatography. Vestibular function was studied by recording nystagmus, induced by positional changes or accelerated rotation. At blood levels of trichloroethylene above 30 p.p.m. “positional nystagmus” develops. Two metabolites of trichloroethylene, chloral hydrate and trichloro-ethanol, which are known as central nervous system (CNS) depressants, did not induce this abnormal nystagmus. However, α-chloralose, a derivative of chloral hydrate, induced positional nystagmus and also a markedly exaggerated nystagmus developed during rotatory acceleration. It is suggested that solvents like trichloroethylene elicit vestibular disturbances by stimulation of central subcortical vestibulo-oculomotor connections. The stimulation may be caused by a blockage of inhibitory systems.     

Derivation of acceptable concentrations for the protection of aquatic organisms

Derivation of quality standards to protect aquatic ecosystems demands a minimum set of toxicity data to allow the risk assessor to take some account of: (1) variable responses to toxicants; (2) variable environmental characteristics; (3) interactions between duration of exposure and effects; and (4) ecological significance of impacts. Extrapolation from limited experimental data to predict a concentration protective in diverse ecosystems can employ either statistical models (consistent but rather rigid and may not protect all species) or empirical factors (more flexible and possibly more protective, but require expert judgment in their application). However derived, quality standards must be tailored to the specific conditions of release and environmental fate which influence a chemical's impact in aquatic ecosystems. It must also be recognised that protection of all individuals and even of all aquatic species may not be achievable or necessary to maintain a healthy ecosystem. Some possible future advances in the determination of water quality standards are suggested.     

Synthesis of the perdeuterated cellulose solvents 1‐ethyl‐3‐methylimidazolium acetate (EMIM‐OAc‐d14) and 1‐butyl‐3‐methylimidazolium acetate (BMIM‐OAc‐d18) and of 2‐13C‐butyl‐3‐methylimidazolium acetate

The syntheses of two perdeuterated ionic liquids (ILs), which have found use as solvents for cellulose derivatization and processing in addition, are described: 1‐ethyl‐3‐methylimidazolium acetate (EMIM‐OAc‐d₁₄) and 1‐butyl–3‐methylimidazolium acetate (BMIM‐OAc‐d₁₈). The targets were obtained from imidazole in three‐step sequences starting with butylation and ethylation, respectively. The resulting 1‐alkyl imidazoles were purified, and subsequently methylated according to a novel protocol using dimethylcarbonate‐d₆. To obtain the 1‐alkyl‐3‐methylimidazolium moiety, methylation of 1‐alkylimidazoles proved to be superior to the conventional approach of alkylating 1‐methylimidazole. Addition of acetic acid‐d₄ caused traceless degradation of the methylcarbonate counter anions, which were neatly exchanged for acetate. The IL 2‐¹³C‐butyl‐3‐methylimidazolium acetate, in which the isotopically enriched C‐2 is a good NMR‐indicator of side reactions and solvent–solute interactions, was synthesized according to the same reaction sequence, starting from 2‐¹³C‐1‐alkylimidazole which, in turn, was obtained by reaction of glyoxale, alkylamine, ammonia and paraformaldehyde‐¹³C. Copyright © 2009 John Wiley & Sons, Ltd.     

氯雷他定原料药中残留溶剂检测方法的研究

建立氯雷他定原料药中有机溶剂残留量测定方法。以Agilent FFAP弹性石英毛细管柱(聚乙二醇为固定液,50 m×320μm×0.5μm)为色谱柱,进样口温度为220℃;氢火焰离子化检测器(FID)温度为240℃;柱温为程序升温,初始温度40℃,保持10 min,以20℃.min-1升温至200℃,保持3 min;载气为氮气,流速3 mL.min-1。此色谱条件下被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好,可用于氯雷他定原料药中有机溶剂残留量检测。     

顶空气相色谱法测定中药提取物的有机溶剂残留量

目的建立中药提取物XDD-2的有机溶剂正丁醇、乙醇和石油醚残留量检查法。方法用顶空气相色谱法测定XDD-2的有机溶荆残留量。采用HP-5固定相的开口毛细管柱，以高纯氮为载气，FID为检测器。结果标准液质量浓度在一定范围内与各组分峰面积线性关系良好。序在0．9909-0．9999之间，精密度、重现性RSD均小于5％，平均回收率为95％-105％。结论顶空气相色谱法简便，快速，准确，可用于中药制荆的正丁醇、乙醇和石油醚残留量测定。     

气相色谱法测定吡喹酮及片剂的残留溶剂

目的建立气相色谱法测定吡喹酮及片剂中的四种残留溶剂。方法采用DB-624(30 m×0.5 mm,0.5μm)色谱柱,柱温箱程序升温,采用FID检测器对乙醇和乙酸乙酯进行检测,采用ECD检测器对三氯甲烷和二氯甲烷进行检测。结果乙醇、乙酸乙酯、三氯甲烷、二氯甲烷四种残留溶剂分别在0.051 0⁵.102 4 mg·mL-1,0.050 05.102 4 mg·mL-1,0.050 0⁴.995 0 mg·mL-1,0.515 84.995 0 mg·mL-1,0.515 8⁵1.58μg·mL-1,5.008 051.58μg·mL-1,5.008 0⁵00.8μg·mL-1范围内呈良好的线性关系,相关系数均大于0.999 5。结论建立的气相色谱法简单、快速、准确,可用于吡喹酮原料及其制剂中的残留溶剂的检测,为国家评价性抽验工作提供技术支持。     

Enhanced effects by mixtures of three estrogenic compounds at environmentally relevant levels on development of Chinese rare minnow (Gobiocypris rarus)

The combined effects of 17β-estradiol, diethylstilbestrol and nonylphenol at environmentally relevant levels were studied on development of Chinese rare minnow. No effects on hatchability of embryos, survival of larvae, body length and body weight were found in the fish exposed to the single chemicals and their mixtures. But significant vitellogenin induction and testis somatical index reduction were observed in adult males exposed to the mixtures. Meanwhile, the sex ratio of adult fish skewed to female was found in the fish exposed to high concentration of the mixture. These results revealed not only that the co-exposure of xenoestrogens can enhance the adverse effects on the development of fish, but that the adverse effects were induced by co-exposure of xenoestrogens below the threshold of similar detectable effects for single xenoestrogen. The observations in the present study highlight the potential ecological hazard posed by the coexistence of xenobiotics in the realistic aquatic environment.     

Decomposition of environmentally persistent cyclic methylsiloxanes in subcritical water

The cyclic methylsiloxanes octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were reacted in subcritical water at temperatures of 150–350 °C under argon, under O₂, or in the presence of H₂O₂. When the reactions were performed in pure subcritical water (under argon) at 300 °C for 6 h, both D4 and D5 were almost completely hydrolyzed to water-soluble and hexane-non-extractable compounds such as dimethylsilanediol (DMSD). However, the high percentages of total organic carbon (TOC) remained in the aqueous phase [87% and 81% of the carbon atoms in the initial D5 (26.6 μmol) and D4 (30.6 μmol), respectively] and the low silicate yields (both 3% of the silicon atoms in the initial D5 and D4) indicated that little mineralization had occurred. Although the presence of O₂ had no significant effect on the reactivity of these substrates in subcritical water at temperatures up to 300 °C, the presence of H₂O₂ enhanced the decomposition of these substrates. Raising the temperature to 350 °C greatly enhanced the mineralization. Specifically, when the reactions were performed in 2.0 M H₂O₂ for 2 h, the percentages of TOC that remained in the aqueous phase decreased markedly (to 2% and 10% of the carbon atoms in the initial D5 and D4, respectively) and IR spectral measurements indicated that most of the substrates had been oxidized to silicate.