A refined approach to estimate exposure for use in calculating the Maximum Residue Limit of veterinary drugs

Maximum Residue Limits (MRLs) are standards that represent the maximum residue concentration expected to be found if a veterinary drug is administered according to good practice in the use of veterinary drugs (GVP). MRLs are established only where the exposure to residues in food resulting from particular use patterns of the veterinary drug pass a public health risk assessment. The current model diet as used by major regulators overstates mean consumption of food for populations when compared to results from food surveys of actual consumption. Exposure to residues is overestimated when calculating long-term (chronic) exposure using the model diet leading to the risk to consumers being overstated. Additionally the model diet underestimates the size of large portions eaten by the group of consumers that eat large quantities of a particular food in a single meal potentially leading to understating of risks associated with exposure to residues of drugs that produce an adverse effect after a single exposure. A revision of dietary consumption figures is proposed that will better match the consumption figures used in point-estimates of dietary exposure to the timeframe for consumption that is relevant to the reference dose.     

A descriptive bibliometric study on bioavailability of pesticides in vegetables,food or wine research (1976–2018)

A bibliometric analysis based on the Web of Science© (WOS) database was performed on bioavailability of pesticides in vegetables, food or wine related studies published from inception to 2018. A total of 1202 articles were subjected to examination. The results reveal that yearly production of scientific articles increased steadily. Journal and institution production, and author's keywords frequencies followed the Lotka’s Law. Khan SU and White JC were the most productive authors. The most productive journals were Journal of Agricultural and Food Chemistry (55), and Journal of Ethnopharmacology (48), and the most common WOS subject category was Pharmacology & Pharmacy (419). USA (h-index of 40) produced 21.7 % of all articles, closely followed by China (20.6 %). Chinese Academy of Sciences (34) was the most productive research institutions. Finally, current and future trends in this area should focus on keywords such as pharmacokinetics, curcumin, in-vitro, nanoparticles, oral (bioavailability) and cell.     

气相色谱法测定阿莫西林残留溶媒的含量

本文用气相色谱分析法检查阿莫西林在生产过程中引入的有机溶剂二氯甲烷和丙酮的含量。这些溶媒不能完全被应用的生产技术所去除。控制残留尽量减少对人体的危害。     

Toxicological assessment of biological pesticides

The majority of pesticides are based on synthetic chemicals. Regulatory assessments are performed by comparing the findings in a range of routine toxicity studies, designed for testing chemicals, with estimates of exposures. Recently there have been significant moves towards developing natural/biological alternatives. Biological pesticides (those based on viable organisms) present the regulator with a different set of challenges to those raised by most chemical pesticides. The concerns associated with biological pesticides can vary greatly from one organism to another, requiring an almost case-by-case approach. The known toxicity of certain bio-molecules and the pathogenicity of certain organisms underlines the need for a risk assessment of biological pesticides. The main aspects of a health risk assessment are characterisation of the organism, infectivity, pathogenicity, sensitisation and production of toxic secondary metabolites. Obtaining information or data on these areas is not always easy as there are no widely accepted test schemes or protocols for organisms, though guidelines are being developed for the European Commission (EC). Predicting exposure following pesticidal use of an organism is made more complex if it multiplies or secretes toxic metabolites. Reliable data on effects (lack of) associated with naturally occurring (background) exposures can sometimes provide considerable reassurance. This paper describes the background to the proposed EC scheme, which has much in common with current UK practices, and presents three examples of biological pesticides which have been assessed under the existing UK procedures.     

气相色谱法测定对氨基苯乙醚中杂质对氯苯胺的含量

目的 建立对氨基苯乙醚的质量控制标准。方法 采用气相色谱法测定对氨基苯乙醚中杂质对氯苯胺的含量。结果 该方法的最大相对误差不超过3％。结论 该方法准确、简便、快捷、重现性好及精密度好，可做为对氨基苯乙醚的质量控制标准。     

Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties

Recent EU legislation has introduced endocrine disrupting properties as a hazard-based “cut-off” criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling.Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans.Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties.The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.     

头孢噻肟钠原粉中残留溶媒含量的测定

残留溶煤是药品中不可避免的成分,而且常常是药品一部分。头孢噻肟钠原粉中的残留溶媒是甲醇和醋酸乙酯,它们属于三级溶媒,无特别毒性,对人体健康有低风险,本文用气相色谱分析法测定头孢噻肟钠原粉中甲醇和醋酸乙酯的含量。     

Maximum Likelihood Estimation in Survival Studies Under Progressive Interval Censoring with Random Removals

Censoring occurs commonly in clinical trials. This article investigates a new censoring scheme, namely, Type II progressive interval censoring with random removals to cope with the setting that patients are examined at fixed regular intervals and dropouts may occur during the study period. We discuss the maximum likelihood estimation of the model parameters and derive the corresponding asymptotic variances when survival times are assumed to be Weibull distributed. An example is discussed to illustrate the application of the results under this censoring scheme.     

The mutagenic effects of organophosphorus pesticides on micro-organisms

Nine organophosphorus pesticides and twelve known chemical mutagens were applied to agar plate cultures ofEscherichia coli WP 2. After incubation, the cultures were examined for an increase in reverse mutation rate.Dicrotophos and dichlorvos, and four alkylating agents were tested against two mutant strains of Serratia marcescens using the paper disc technique.The organophosphorus pesticides did not increase the reversion rate inEscherichia coli WP 2. Dicrotophos was also negative when tested against Serratia marcescens. Dichlorvos induced a dose-related increase in reversion rate in both strains of Serratia marcescens.The significance of the results are discussed in relation to the rapid metabolism of dichlorvosin vivo and the absence of any mutagenic effect in mammalian test systems.     

Functionalized gold nanoparticles for sensing of pesticides: A review

Pesticides are a family of non-biodegradable chemical compounds which widely used in agriculture to control pests and increase yield production. However, overuse or abuse of pesticides and their metabolites may cause potential toxicity for the environment as well as human health and all other living organisms, even at deficient concentrations. Consequently, the development of sensors for monitoring these compounds is significant. Recently, nanoparticles-based sensors have been extensively employed as a potential alternative or complementary analytical tool to conventional detection methods for pesticides. Among them, gold nanoparticles (AuNPs) owing to their unique optical properties have been developed as smart sensors with high selectivity, sensitivity, simplicity, and portability. These comprehensive reviews have summarized various studies performed based on different detection strategies, i.e., colorimetric, fluorescence, surface-enhanced Raman scattering, and electrochemical, using AuNPs as sensing probes for pesticide analysis in various matrices. Additionally, the current challenges and future trends for developing novel AuNPs-based sensors for the detection of pesticides are also discussed.     

加米霉素注射液在猪体内残留消除研究

目的 为了探讨自制加米霉素注射液在猪体内的残留消除规律，验证休药期。方法 本试验将选取体质健康的28 头猪，随机分为2 组，对照组4 头，试验组24 头。试验组猪按6mg/kg B.W. 单次肌注射加米霉素，对照组不做处理。在注射后 第0.5、7、14、21、28 和35d 时，采集肌肉、肝脏、肾脏、皮脂及注射部位肌肉。UPLC-MS/MS 法测定组织中的加米霉素残留量， 并用WT 1.4 软件计算休药期。结果 加米霉素在猪肌肉、肝脏、肾脏、皮脂和注射部位肌肉的休药期分别是9.68、11.62、17.37、 24.35 和26.75d。结论 为保证兽药使用安全、食品安全，推荐加米霉素注射液在猪的休药期为27d。     

青霉素残渣中砷的离子排斥色谱测定法

利用高效离子排斥色谱法（ＨＰＩＣＥ）和电导检测器测定砷的研究,排除了大量无机阴离子的干扰,该法对青霉素残渣中砷的测定,结果令人满意。     

长托宁救治急性有机磷农药中毒临床观察

目的：比较新型抗胆碱药长托宁与传统抗胆碱药阿托品对救治急性有机磷农药中毒的疗效。方法：将急性有机磷农药中毒患者随机分为长托宁治疗组与阿托品对照组,采用推荐剂量按轻、中、重分组治疗,对其疗效进行比较。结果：与对照组相比,长托宁治疗组达到阿托品化时间无显著差异（P〉0.05）;重度患者昏迷时间及呼吸衰竭时间明显减短（P〈0.05）;长托宁用药量及用药次数明显减少（P〈0.01）,不良反应发生率明显减少（P〈0.01）。结论：长托宁同时具有中枢与外周抗胆碱作用,用量少,不良反应轻,给药方便,是目前救治急性有机磷农药中毒最理想的抗胆碱药。     

我院手术室注射用麻醉药品使用剩余量初探

摘 要 目的： 统计并分析医院手术室注射用麻醉药品剩余情况,探讨流弊风险和规范化管理麻醉药品的可能性。方法: 采用回顾性研究方法对我院手术室2014年6月 8月10 268张注射用麻醉药品处方进行统计和分析。结果: 剩余量最多（剩余占比最高）的药品为氯胺酮注射液,其次为哌替啶注射液和瑞芬太尼粉针。而单次余量占规格比最高的药品为氯胺酮注射液,其次为吗啡注射液和哌替啶注射液。结论:对剩余量较大或单次余量占规格比大的药品,如氯胺酮注射液,建议降低规格、减少余量;对手术室内麻醉药品使用,建议精细化管理。     

Biomarkers of occupational exposure to pesticides: Systematic review of insecticides

IntroductionPesticides are widely used around the world, and rural workers have greater risk of poisoning. The use of biomarkers for insecticides can contribute to the diagnosis and prevention of poisoning.ObjectiveTo identify, in the scientific literature, the biomarkers of occupational exposure to insecticides of different insecticide classes.MethodsThe PubMed, Lilacs and Embase databases were analyzed using a systematic search strategy and in accordance with the criteria established by the PRISMA methodology. Articles with information related to the use of biomarkers to identify active ingredients, or insecticide metabolites, or effects on the human biological matrices were analyzed.ResultsA total of 840 studies was found, and 30 met the selection criteria. The search identified 118 results for insecticide biomarkers, of which 45% were of exposure, 42% of effect, and 14% of susceptibility. Additionally, 78 were possible biomarkers, and only 67 confirmed to be different biomarkers for insecticides. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 3,5,6-trichloro-2-pyridinol (TCP-y), specific for Chlorpyrifos, were among the most common biomarkers identified; however, most metabolites found were non-specific.ConclusionVarious insecticide biomarkers were mentioned; nonetheless, only a few are specific and used to identify the wide range of insecticides to which farm workers are exposed.     

Association between organophosphate pesticides exposure and thyroid hormones in floriculture workers

The ability of organophosphate pesticides to disturb thyroid gland function has been demonstrated by experimental studies on animal, but evidence of such effects on human remains scarce. The aim of this study was to assess the association between exposure to organophosphate compounds and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the State of Mexico and Morelos, Mexico, occupationally exposed to organophosphate pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Urine and blood samples were taken the day after pesticide application to determine urine dialkylphosphate (DAP) levels, serum levels of TSH, total T₃, total T₄, serum PON1 activity, and serum p,p′-DEE levels. The analysis of the association between DAP levels and thyroid hormonal profile was carried out using multivariate generalized estimating equation (GEE) models. Our results showed an increase in both TSH and T₄ hormones in serum associated with a increase in total dimethylphosphate levels (ΣDMP) in urine (p-trend < 0.001) and a decrease in total T₃ serum levels with an increase of ΣDMP levels in the urine (p-trend = 0.053). These results suggest that exposure to organophosphate pesticides may be responsible of increasing TSH and T₄ serum hormone levels and decreasing T₃ serum hormone levels, therefore supporting the hypothesis that organophosphate pesticides act as endocrine disruptors in humans.     

Stereochemical considerations on the inhibition of hepatic epoxide hydrolase by some pesticides and their epoxides

The present studies identify the steric factors involved in the hydration of epoxide intermediates of some pesticides by hepatic epoxide hydrolase. Investigations were carried out regarding the formation of reactive epoxide intermediates and their different interactions with the hepatic epoxide hydrolase. Some pesticides and their parent epoxides were selected on he basis of the steric hindrance on the oxirane ring. The results indicate that the inhibition of this enzyme depends on the steric hindrance produced by substituents on the oxirane ring of these pesticides. Mono- and di-substituted oxiranes are good substrates of the epoxide hydrolase and non-competitive inhibitors of the hydration of styrene oxide, while tri-substituted epoxides are virtually inactive on inhibiting the hepatic epoxide hydrolase activity.     

Derivation of an oral Maximum Allowable Dose Level for Bisphenol A

Bisphenol A (BPA) is a high production volume chemical that is used in plastics and epoxy coatings. In 2015, California's Office of Environmental Health Hazard Assessment (OEHHA) added BPA to the Proposition 65 list of chemicals “known to cause reproductive toxicity” based on its Developmental and Reproductive Toxicant Identification Committee's (DART-IC) conclusion that BPA has been shown to cause female reproductive toxicity. A critical factor in determining compliance with Proposition 65 is a Maximum Allowable Dose Level (MADL), which is the exposure level at which a chemical would have no observable reproductive effect even if a person were exposed to 1000 times that level. We performed a comprehensive review of the literature, including the studies reviewed by DART-IC, and derived an oral MADL. Of all the studies we identified, Delclos et al. (2014) is of sufficient quality, has the lowest no observed effect level (NOEL), and results in the most conservative MADL of 157 μg/d. This is generally supported by other studies, including those that were considered by DART-IC. Also, the oral MADL provides a similar margin of safety as OEHHA's dermal MADL and other regulatory guidelines. Taken together, the scientific data support an oral MADL of 157 μg/d.     

气相顶空色谱法测定原料样6-APA中的残留溶媒

目的：建立测定原料药6-APA中残留溶媒的气相顶空色谱法。方法：选4-甲基-2-戊酮作内标物，以内标法在极性弹性石英毛细柱上进行各组分分离，效果好。柱温：120℃，进样口温度：200℃，检测器温度：250℃。结果：平均回收率：乙酸丁酯99．3％，结论：该方法克服了人工控温，进样不准的缺点。重现性好，精度高。     

Sustainable extraction of pesticides in food and environmental samples using emerging green adsorbents

There are many emerging adsorbents, with relatively high adsorption capacities, that can be used during the extraction of pesticides from complex matrices. Poly(ionic liquids) are among these emerging adsorbents. The applications of poly(ionic liquids) as adsorbents during pesticide pre-concentration are explored in this paper. Some researchers have taken advantage of the adhesive nature of polydopamine and used it to synthesise adsorbents with relatively high adsorption capacities. The use of polydopamine-based sorbents during pesticide pre-concentration is also reviewed in this paper. Deep eutectic solvents, on the other hand, can be used to synthesise adsorbents to extract pesticides in complex matrices. This is usually done either by immobilising it on a solid support or by polymerisation. Applications of deep eutectic solvent-based adsorbents during pesticide extraction are discussed in detail in this review. In addition, this review has explored the challenges associated with the use of these emerging adsorbents during the extraction of pesticides as well as the future prospects.