雷帕霉素的水解行为及对4种非靶标生物的急性毒性

雷帕霉素为大环内脂类抗生素药剂,对多种人类疾病有效,近年发现其对多种植物病原真菌也有较好的抑制活性,有望开发为微生物源农药用于植物病害的防治,而目前关于雷帕霉素的水解行为及其对非靶标生物的急性毒性还未见报道。为评价雷帕霉素的水解行为及其对非靶标生物的急性毒性,本研究通过室内模拟试验,测定了雷帕霉素在不同pH值、温度、初始浓度及光源中的水解特性,同时测定了其对家蚕、意大利工蜂、斑马鱼及赤子爱胜蚯蚓4种非靶标生物的急性毒性。水解试验结果表明:碱性环境、紫外光照及高温有利于雷帕霉素的水解。当其初始质量浓度为10 mg/L时,半衰期分别为66.63、38.93及77.00 h;初始质量浓度为50 mg/L时,半衰期分别为144.38、105.00及165.00 h。急性毒性试验结果表明:雷帕霉素对家蚕和斑马鱼的96 h-LC₅₀值分别为 386.46和3.50 mg/L (有效成分,下同);对意大利工蜂的急性经口毒性48 h-LD₅₀值为8.95 μg/bee,急性接触毒性48 h-LD₅₀值为16.79 μg/bee;对赤子爱胜蚯蚓的14 d-LC₅₀值为223. 81 mg/kg。按照 “化学农药环境安全评价准则” (GB/T 31270—2014) 的毒性等级划分标准,雷帕霉素对家蚕、斑马鱼、赤子爱胜蚯蚓的急性毒性分别为 “低毒”、“中毒” 和 “低毒”,对意大利工蜂的急性经口毒性为 “中毒”,急性接触毒性为 “低毒”。研究表明,雷帕霉素属于易降解性药剂,对家蚕、意大利工蜂、斑马鱼及赤子爱胜蚯蚓4种非靶标生物安全。     

How to define green adjuvants

The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.     

甲草胺对非靶标生物的毒理学研究进展

甲草胺是一种选择性芽前除草剂,在20世纪末期被广泛应用于防治大豆、花生、水稻田等一年生禾本科及阔叶杂草.目前,甲草胺由于其致畸性及内分泌干扰活性已被多国禁用.文章综述了甲草胺进入环境后对非靶标生物的毒理学研究进展,主要包括急性毒性、慢性毒性和氧化应激效应等,旨在为甲草胺生态环境风险评估提供数据资料.     

Risk assessment to honey bees: a scheme developed in France for non-sprayed systemic compounds

BACKGROUND: Directive 91/414/EEC envisages that the systemic properties of active substances, if any, are taken into account in evaluating the risk posed to the environment by plant protection products. Among others, honey bees may be exposed to substances via this route, which may pose problems when substances with high toxicity are ingested through pollen or nectar. The guidance documents in support of the risk assessment to bees within the framework of Directive 91/414/EEC do not provide detailed technical guidance on how to proceed in a risk assessment for substances with systemic properties. RESULTS: A stepwise approach aiming specifically to assess the risk posed by non-sprayed systemic substances to bees is therefore proposed. This approach first identifies substances with systemic properties, which should be quantified in plant material as pollen and nectar. Exposure estimates calculated for different categories of bees (e.g. foraging bees), based on expected concentrations of the product in pollen or nectar, may be compared with several toxicity endpoints for acute or chronic effects on adults and/or larvae with a toxicity/exposure ratio, which is a measurement of potential risks. CONCLUSION: Such a ratio is proposed to be used as a trigger for any further refined assessment that would focus on the measurement of effects at the colony level.     

The toxicity of phosphine,methyl bromide, 1,1,1-trichloroethane and carbon dioxide alone and as mixtures to the pupae of red flour beetle,Tribolium castaneum herbst

The toxicity of phosphine, methyl bromide, 1,1,1-trichloroethane (methyl chloroform) and carbon dioxide and mixtures of phosphine + methyl bromide, methyl bromide + methyl chloroform, phosphine + carbon dioxide, and methyl bromide + carbon dioxide to one- to two-day-old pupae of Tribolium castaneum Herbst was studied. Joint action ratios estimated at LD₅₀ and LD₉₀ for a 24-h exposure indicated no enhancement of toxicity for mixtures of phosphine and methyl bromide, or methyl chloroform and methyl bromide on the pupae. Carbon dioxide up to 40% in air enhanced the toxic action of phosphine as well as of methyl bromide. Higher levels of carbon dioxide, however, failed to improve the toxicity of phosphine or methyl bromide proportionately. Carbon dioxide used alone produced a maximum of 11% mortality of the pupae exposed to 10–70% levels for 24 h. The order of toxicity of the fumigants both at LD₅₀ and LD₉₀ was phosphine > methyl bromide > methyl chloroform.     

Methyl bromide in natural fresh waters: Hydrolysis and volatilisation

The effect of some physical factors on the processes (hydrolysis, volatilisation) regulating the persistence of methyl bromide in fresh surface waters was investigated to complement previous research. It has been confirmed that electromagnetic radiation in the visible field has no influence on the hydrolysis kinetics of the fumigant. The removal of methyl bromide by volatilisation from stirred and ventilated solutions appears to be of greater importance in practice. It has been shown that under these conditions the half-life is directly proportional to the liquid depth. Without stirring volatilisation is greatly reduced, due to the low diffusivity of methyl bromide in the aqueous phase.     

Towards a tiered test strategy for plant protection products to address mixture toxicity by alternative approaches in human health assessment

Plant protection products (PPPs) consist of pesticide active substances and co‐formulants. Generally, active substance effects are assumed to dominate in PPP toxicity. Nevertheless, co‐formulants may well affect the toxicity of PPPs via toxicodynamic and toxicokinetic interaction. To account for potential mixture effects and improve PPP data requirements for application in risk assessment, a tiered test strategy is proposed. The strategy is based on a comparison of PPP and active substance toxicity, which enables the prioritisation of PPPs for further testing, adaptation of the toxicological threshold value or removal of toxic co‐formulants from the PPP. Moreover, it focuses on the integrative assessment of existing information and newly generated data using alternative test methods. The proposed strategy will improve PPP toxicological assessment by accounting for mixture toxicity, providing a set of regulatory options for risk assessment and the necessary data for hazard assessment. The predictivity of alternative methods for PPPs will improve by evaluation of their reliability and uncertainty. © 2020 The Authors. Pest Management Science published by JohnWiley & Sons Ltd on behalf of Society of Chemical Industry.     

Physical chemical properties of several organophosphates: Some implication in environmental and biological behavior

The organophosphates are a class of chemicals noted for high biological activity. Their potential for transport and persistence in the environment, based on physical chemical properties, has not been thoroughly studied. Certain physical chemical properties of several organophosphates were measured and compared to organochlorine compounds whose transport and persistence are better known. Of interest was the potential for toxicity to human and other nontarget organisms. Certain organophosphates were found to have surprisingly high partition coefficients. This suggested the possibility of uptake by organisms, as well as indicating a propensity for storage and hence, a longer persistence. Rates of hydrolysis are some indication of the likelihood of persistence.     

手性农药毒性机制的对映体选择性

综述了手性农药在急性毒性、慢性毒性、细胞毒性、藻类与植物毒性及生物体富集方面的对映体选择性差异。大量研究显示,手性农药的不同对映异构体对于非靶标作用体的毒性存在显著差异,这种选择性差异既取决于手性农药的对映异构体,同时又与作用的受体相关。探讨了手性农药毒理学研究的重点和发展方向——在对映体水平上对手性农药的毒理机制进行全面深入的研究,对于评价农药对健康的风险及生产绿色高效的单一或复合的对映体农药具有指导意义。     

磺酰脲类除草剂的降解机制及代谢产物的研究进展

磺酰脲类除草剂是一类高效,低毒和高选择性的除草剂,该类除草剂能有效防除阔叶杂草,其中有些品种对禾本科杂草也有一定的抑制作用。但同时因其用量低、对哺乳动物低毒以及独特的除草活性等特点而得到广泛应用。因此,了解磺酰脲类除草剂在土壤中的环境行为及归趋对于其科学合理使用、防止作物药害和保护农业生态环境具有非常重要的意义。根据笔者对磺酰脲类除草剂的深入研究,并总结归纳国内外的相关文献报道,对磺酰脲类除草剂的降解机制及其代谢产物的研究进行了综述,最后展望了磺酰脲类除草剂未来的发展趋势。     

Comparative hepatotoxicity of a herbicide,epyrifenacil, in humans and rodents by comparing the dynamics and kinetics of its causal metabolite

A new herbicide, epyrifenacil (S-3100), inhibits protoporphyrinogen oxidase (PPO) in plants. Repeated administration of epyrifenacil in laboratory animals led to some toxicological changes related to PPO inhibition, e.g., hepatotoxicity caused by porphyrin accumulation and anemia caused by the inhibition of heme biosynthesis. In vitro studies revealed that an ester-cleaved metabolite, S-3100-CA, is predominant in mammals, exhibits PPO-inhibitory activity, and thus is the cause of epyrifenacil-induced toxicity. To assess the human risk, the effects of species differences on the dynamics (PPO inhibition) and kinetics (liver uptake) of epyrifenacil were evaluated separately. The results of in vitro assays revealed an approximately tenfold weaker inhibition of PPO by S-3100-CA in humans than in rodents and six- to thirteen-fold less hepatic uptake of S-3100-CA in humans than in mice. Finally, it was suggested that humans are less sensitive to the toxicity of epyrifenacil than are rodents, although further mechanistic research is highly anticipated.     

新型土壤熏蒸剂二甲基二硫研究进展

采用熏蒸剂进行土壤消毒可有效控制设施作物及高附加值作物的土传有害生物,其中熏蒸效果突出的熏蒸剂溴甲烷由于会破坏臭氧层而被禁用,导致土传有害生物熏蒸治理过程中缺乏高效稳定的熏蒸产品。二甲基二硫是一种新型熏蒸剂,对有害线虫具有高活性,可兼治部分土传病原菌及杂草。广谱、安全和高效等优点使其成为最有推广应用前景的溴甲烷替代药剂,或将改善国内杀线虫熏蒸剂缺乏的局面。该文系统综述了国内外关于二甲基二硫对土传有害生物的防控活性、作用机制和降解、散发逃逸、扩散分布及残留等环境行为,以及对土壤养分、微生物及非靶标生物等方面的影响,以期为二甲基二硫的开发及推广应用提供参考。     

Selective determination of ionised bromide and organic bromides in Foodstuffs by gas-liquid chromatography with special reference to fumigant residues

A number of methods in common use for determining amounts of bromine-containing compounds occurring as residues in foodstuffs, primarily as a result of commodity or soil fumigation, do not distinguish between bromide ion and organically bound bromine. Although such compounds may differ widely in their toxicity, national and international schedules have included tolerances for total bromide determined as ‘inorganic bromide’. A method is described in which ionised bromide in foodstuffs is quantitatively converted to 2-brompethanol (ethylene bromohydrin) by reaction with ethylene oxide in an acid medium. The 2-bromoethanol produced is determined in processed extracts by gas-liquid chromatography. Residual methyl bromide and ethylene dibromide (1,2-dibromoethane), neither of which react with ethylene oxide under the conditions prescribed, are separated and determined concurrently. With foodstuffs which did not contain organo-bromine compounds, good agreement was observed between results obtained by the gas chromatographic method and by total bromide determination involving alkali digestion, controlled ashing, extraction of ash and wet oxidation. In the light of the more specific methods of determination now available, some clarification in tolerance schedules for residual bromine compounds in foodstuffs is suggested.     

农药对蚯蚓的生长和繁殖毒性及其在生态风险评价中的应用

蚯蚓占了陆生无脊椎生物生物量的绝大部分,是农田生态系统土壤物质循环中的重要一环,且蚯蚓对某些污染物比许多其它土壤动物更为敏感,是陆生生态系统中土壤农用化学品污染的理想指示生物。死亡率是最常用于评估化学品对蚯蚓毒性的参数,但大多数情况下蚯蚓死亡率变化对农用化学品暴露并不敏感,因此急性毒性测试结果并不能为评估化学品对蚯蚓种群危害提供最敏感的风险预测。因此,研究更多可应用于土壤污染评价的蚯蚓生物标志物十分有意义,可对保护整个土壤动物区系的安全阈值设定提供参考。本文从蚯蚓常用毒理学研究方法入手,重点综述了农药对蚯蚓的生长和繁殖毒性效应以及相关毒理学测试指标在农药土壤生物风险评价中的应用,并讨论了影响蚯蚓生态毒理学测试结果的各项因素,最后对该领域未来研究提出了展望和建议。     

Evaluation of propargyl bromide for control of barnyardgrass and Fusarium oxysporum in three soils

With the scheduled phasing out of methyl bromide, there is an urgent need for alternatives. We evaluated the efficacy of propargyl bromide as a potential replacement for methyl bromide for the control of barnyardgrass (Echinochloa crus-galli) and Fusarium oxysporum in an Arlington sandy loam, a Carsitas loamy sand and a Florida muck soil. Soil was mixed with barnyardgrass seeds or F oxysporum colonized on millet seeds, and treated with propargyl bromide at a range of concentrations. The mortality of the fungi and weed seeds was determined after 24 h of exposure at 30 degrees C. The concentrations required to inhibit 50% barnyard seed germination (LC50) were 2.8, 2.4 and 48.5 micrograms g-1 in the sandy loam, loamy sand and muck soil, respectively. In contrast, the LC50 values for F oxysporum were 11.2, 10.8 and 182.1 micrograms g-1 in the sandy loam, loamy sand and muck soil, respectively. The low efficacy of propargyl bromide in the muck soil was a result of the rapid degradation and high adsorption of the compound in the soil. The degradation half-life (t1/2) was only 7 h in the muck soil at an initial concentration of 6.8 micrograms g-1, compared to 60 and 67 h in the sandy loam and loamy sand, respectively. The adsorption coefficients (Kd) were 0.96, 0.87 and 5.6 cm3 g-1 in the sandy loam, loamy sand and muck soil, respectively. These results suggest that registration agencies should consider site-specific properties in recommending application rates for propargyl bromide.     

Health Aspects of Pesticides and their Residues1

Various important factors in the evaluation of the acute and chronic toxicity of agricultural pesticides are discussed. Special attention is drawn to the residues in food and fodder of active ingredients, including their degradation and reaction products. A general evaluation of the effects of pesticides on roan, animals and the environment is only possible if their properties and behaviour in the different fields of application and under various conditions are known. This is illustrated by a few examples. Manufacturers (especially involved in residue analysis), chemists, toxicologists, biologists, advisors, farmers and operators dealing with pesticides are faced with many questions and problems which can only be solved through close cooperation. Public authorities and responsible organizations have to elaborate national and international guide-lines, rules and regulations, which have to be constantly improved and adapted to the latest state of knowledge ‘for the sake of safety and efficacy.’ The expression « health aspects » is often used as a synonym for « toxicological aspects ». In order to avoid misunderstandings, it is pointed out that toxicology is merely one important part of general health aspects; this is illustrated by some examples.     

Non-destructive method for estimating methyl bromide residues in apples during aeration following fumigation

A method is presented for estimating the persistence and concentration of residual free methyl bromide (MB) present in apples during the aeration period following fumigation. The method is based on determining the rate of decline in concentration of methyl bromide in the exhaust air stream during aeration. The rate was shown to follow two consecutive pseudo-first-order decay curves. The first component of the curve resulted primarily from removal of MB from the free air space in the chamber, and the second component resulted from the desorption of MB from the apples. Estimates of the concentration of MB residue in apples were obtained from the regression parameters for the second decay curve. The technique gave good estimates of the residue concentration over a wide range of fumigation conditions and ventilation rates, and may be useful for determining the duration of aeration period required to achieve a proposed residue tolerance of 0.2 mg kg ^?1 methyl bromide.     

Enhancement of the toxicity of methyl bromide toTribolium castaneum adults by its admixture with carbon Monoxide

The effect of methyl bromide in admixture with 20%, 30% and 40% carbon monoxide (CO) onTribolium castaneum adults was tested. The combination of methyl bromide with 20% CO increased the toxicity of CH₃Br 1.4-fold, with 30% CO-1.5-fold, and with 40% CO-1.7-fold. It is supposed that the inhibitory effect of CO on the insect’s microsomal mixed-function oxidase and on other enzymatic systems causes this effect.     

三种双酰胺类杀虫剂制剂对环境非靶标生物的急性毒性

采用"OECD化学品测试准则"和"化学农药环境安全评价试验准则"方法,以赤子爱胜蚓、非洲爪蟾、斜生栅藻、大型溞、斑马鱼,意大利蜜蜂以及家蚕为受试生物,测定了20%氟虫双酰胺水分散粒剂、200g/L氯虫苯甲酰胺悬浮剂和200g/L溴氰虫酰胺悬浮剂3种双酰胺类杀虫剂对环境非靶标生物的急性毒性。结果表明:氟虫双酰胺、氯虫苯甲酰胺、溴氰虫酰胺3种药剂对赤子爱胜蚓、非洲爪蟾、斜生栅藻和斑马鱼的急性毒性均为低毒,但对大型溞的48 h-EC_(50)值分别为1.51×10~(-2)、2.58×10~(-3)、7.63×10~(-2)mg/L,对家蚕的96h-LC_(50)值分别为6.11×10~(-2)、0.12和0.30 mg/L,均为剧毒;氟虫双酰胺和氯虫苯甲酰胺对意大利蜜蜂为低毒,但溴氰虫酰胺对其的48h经口LC_(50)值和接触LD_(50)值分别为2.90 mg/L和3.71×10~(-2)μg/bee,均为高毒。研究表明,虽然双酰胺类杀虫剂对多数非靶标生物毒性较低,但在水体环境和桑蚕区以及作物开花期仍需谨慎使用。     

Larvicidal activity of Kaempferia galanga rhizome phenylpropanoids towards three mosquito species

BACKGROUND: This study was aimed at assessing the toxicity of ethyl cinnamate and ethyl p-methoxycinnamate (EMC) identified in Kaempferia galangal L. (Zingiberaceae) rhizome and another 12 known compounds to third-instar larvae from laboratory-reared Culex pipiens pallens Forskal, Aedes aegypti L. and Ochlerotatus togoi Theobald and field-collected C. pipiens pallens (Jinhae colony). Results were compared with those for fenthion and temephos. RESULTS: Ethyl p-methoxycinnamate was the most toxic of the test compounds to larvae of the three mosquito species (LC(50) 12.3-20.7 mg L(-1)) but less toxic than either fenthion (0.0096-0.021 mg L(-1)) or temephos (0.0039-0.0079 mg L(-1)). Ethyl cinnamate and 3-carene were highly active against C. pipiens pallens larvae (24.1 and 21.6 mg L(-1)) but less toxic to A. aegypti and O. togoi larvae (ca 40 and 60 mg L(-1) respectively). The toxicity of these compounds to larvae from the Jinhae colony of C. pipiens pallens was almost the same as their toxicity to the laboratory-reared larvae, although the larvae from the colony exhibited low levels of resistance to fenthion (resistance ratio 9.1) and temephos (5.8).CONCLUSION: Kaempferia galanga rhizome-derived materials, particularly ethyl p-methoxycinnamate, merit further study as potential mosquito control agents for protection of humans and domestic animals from vector-borne diseases and nuisance caused by mosquitoes.