HCHs

六氯环己烷
  • 文章类型: Journal Article
    这项研究首次评估了有机马改良剂在被废弃农药林丹(α-六氯环己烷(α-HCH)=80mgkg-1,β-HCH=40mgkg-1,γ,δ,ε-HCH≈10mgkg-1)寻求自给自足的生物经济。实施了四种处理:污染(PS,ΣHCHs=130mgkg-1)和对照(CS,ΣHCHs=1.24mgkg-1)土壤和相应的改良土壤(APS和ACS)。商业修正案,来自有机废物,用于土壤生物刺激(5%干重),和酶活性的时间演变(脱氢酶,β-葡萄糖苷酶活性,酚氧化酶,芳基酰胺酶,磷酸酶和脲酶)和土壤中的HCHs浓度在受控的湿度和温度条件下进行了55天的评估。马改良剂通过降低pH(从8.3到8)并增加有机质(TOC从0.5到3.3%)和养分含量(P和NH4从24.1到13.7到142.1和41.2分别对土壤的理化性质产生了积极影响。mgkg-1)。因此,土壤生物活性显著增强,特别是在脱氢酶的酶活性中,酚氧化酶,磷酸酶和脲酶,因此,在六氯环己烷降解中,在潜伏期后从<1增加到75%。根据环己烷环上的氯位置,六氯环己烷降解的排序如下:β-六氯环己烷(46%)<ε-六氯环己烷(57%)<α-六氯环己烷(91%)≈δ-六氯环己烷(91%)<γ-六氯环己烷(100%)。五氯环己烯(PCCH)和1,2,4-三氯苯(1,2,4-TCB)被鉴定为HCHs降解代谢产物,并在孵育时间结束时消失。虽然还需要进一步的研究,这些初步发现表明,有机修正案代表了一种可持续的,无害,和具有成本效益的生物刺激方法,用于修复被顽固的六氯环己烷污染的土壤,推动循环经济。
    This study assessed for the first time the bioremediation potential of an organic horse amendment in soils contaminated with solid wastes of the obsolete pesticide lindane (α-hexachlorocyclohexane (α-HCH) = 80 mg kg-1, β-HCH = 40 mg kg-1, γ,δ,ε-HCH≈10 mg kg-1) searching for a self-sufficient bio-based economy. Four treatments were implemented: polluted (PS, ΣHCHs = 130 mg kg-1) and control (CS, ΣHCHs = 1.24 mg kg-1) soils and the respective amended soils (APS and ACS). A commercial amendment, coming from organic wastes, was used for soil biostimulation (5% dry weight), and the temporal evolution of the enzymatic activity (dehydrogenase, β-glucosidase activity, phenoloxidase, arylamidase, phosphatase, and urease) and HCHs concentration of the soils was evaluated over 55 days under controlled humidity and temperature conditions. The horse amendment positively influenced the physicochemical properties of the soil by reducing pH (from 8.3 to 8) and increasing the organic matter (TOC from 0.5 to 3.3%) and nutrient content (P and NH4+ from 24.1 to 13.7 to 142.1 and 41.2 mg kg-1, respectively). Consequently, there was a notable enhancement in the soil biological activity, specifically in the enzymatic activity of dehydrogenase, phenol-oxidase, phosphatase, and urease and, therefore, in HCH degradation, which increased from <1 to 75% after the incubation period. According to the chlorine position on the cyclohexane ring, the following ranking has been found for HCHs degradation: β-HCH (46%) < ε-HCH (57%) < α-HCH (91%) ≈ δ-HCH (91%) < γ-HCH (100%). Pentachlorocyclohexene (PCCH) and 1,2,4-trichlorobenzene (1,2,4-TCB) were identified as HCHs degradation metabolites and disappeared at the end of the incubation time. Although further research is required, these preliminary findings suggest that organic amendments represent a sustainable, harmless, and cost-effective biostimulation approach for remediating soils contaminated with recalcitrant HCHs, boosting the circular economy.
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  • 文章类型: Journal Article
    目标:直接的生活环境可能,像其他生活方式因素一样,与心理健康显著相关。当前的研究解决了五个相关的主观家庭环境变量(即,保护免受干扰的夜灯,日光进入家中,家里的安全,窗户景观的质量,和噪声干扰)与自我报告的抑郁水平相关,而不是众所周知的社会人口统计学和常见的生活方式变量。
    方法:分析了汉堡市健康研究(HCHS)的数据。在N=8757时,有可用的PHQ-9抑郁数据,计算了多元线性回归模型,有了人口统计数据,生活方式变量,和描述家庭环境主观评价的变量。
    结果:该模型解释了抑郁水平变化的15%,家庭环境主观评价的评分占6%。更好地保护夜晚免受干扰的光线,更多的日光进入家中,感觉更安全,以及窗户景观的感知质量,都与较低的显著相关,而更多的噪音烦恼与更高水平的自我报告的抑郁有关。如果检查HCHS中最年轻(中年参与者:46-50岁)和最年长(70-78岁)参与者的样本,结果没有差异。
    结论:除了研究与自我报告的抑郁症相关的生活方式因素的作用,人们的家园可能是重要的亚临床水平的抑郁症在中老年,尽管不能从本研究中推断影响或因果关系的方向。需要为标准化的家庭环境评估制定共识和工具。
    OBJECTIVE: The immediate living environment might, like other lifestyle factors, be significantly related to mental well-being. The current study addresses the question whether five relevant subjective home environment variables (i.e., protection from disturbing nightlight, daylight entering the home, safety at home, quality of window views, and noise disturbance) are associated with levels of self-reported depression over and above well-known sociodemographic and common lifestyle variables.
    METHODS: Data from the Hamburg City Health Study (HCHS) were analyzed. In N = 8757 with available PHQ-9 depression data, multiple linear regression models were computed, with demographic data, lifestyle variables, and variables describing the subjective evaluation of the home environment.
    RESULTS: The model explained 15% of variance in depression levels, with ratings for the subjective evaluation of home environment accounting for 6%. Better protection from disturbing light at night, more daylight entering the home, feeling safer, and perceived quality of the window views, were all significantly associated with lower, while more annoyance by noise was associated with higher levels of self-reported depression. Results did not differ if examining a sample of the youngest (middle-aged participants: 46-50 years) versus oldest (70-78 years) participants within HCHS.
    CONCLUSIONS: Beyond studying the role of lifestyle factors related to self-reported depression, people\'s homes may be important for subclinical levels of depression in middle and older age, albeit the direction of effects or causality cannot be inferred from the present study. The development of a consensus and tools for a standardized home environment assessment is needed.
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  • 文章类型: Journal Article
    在农药中使用六氯环己烷(HCHs)在中国已经被禁止了数十年。从那以后,城市化和许多遗址功能区的改造,以前参与六氯环己烷行业。然而,有可能,除非管理得当,这些地点仍可能在土壤中含有六氯环己烷残留物,从而对周围环境和地下水质量构成威胁。这项研究旨在描述中国南方一个历史上参与六氯环己烷生产的典型地点的土壤残留物,通过分析甲型六氯环己烷,β-HCH,和土壤中γ-HCH含量。结果表明,HCHs在环境中持续存在并具有长期影响。发现许多样品中存在的α-HCH和β-HCH的浓度与中国第1类筛选值规定的浓度相当或更高。残留物的分布与该地区历史上的六氯环己烷生产活动密切相关。不同土层深度的α-HCH/γ-HCH和β-HCH/(α+γ)-HCH特征比分别为1.4-3.7和0.21-1.04,这表明存在显著的HCHs局部残基。六氯环己烷在土壤中的存在表明向下迁移,随着上层土壤(0-5m)中浓度的快速降低,但在更深的土壤(5-14米)逐渐增加。在超过24米的深度检测到六氯环己烷,表明严重渗透。γ-六氯环己烷和β-六氯环己烷的比例随着土壤深度的增加而变化,这与它们相对易挥发和稳定的分子结构有关,分别。结果强烈表明,即使在数十年之后,HCHs仍对土壤和地下水造成了广泛的污染。因此,在城市规划过程中应充分考虑土壤中残留六氯环己烷的可能性,以限制对人类和环境健康的风险。
    The use of hexachlorocyclohexanes (HCHs) in pesticides has been prohibited for decades in China. Since then, there have been urbanization and transformation of the functional areas of many sites, which were formerly involved in the HCH industry. However, it is possible that, unless properly managed, these sites may still contain HCH residues in the soil and thus pose a threat to the surrounding environment and the quality of groundwater. This study aimed to characterize soil residues in a typical site that was historically involved in HCH production in southern China, by analyzing the α-HCH, β-HCH, and γ-HCH contents of the soil. The results suggested that HCHs persist in the environment and can have long-term effects. It was found that α-HCH and β-HCH were present in many samples in concentrations that were comparable or higher than those specified by China\'s Class 1 screening values. The distribution of residues was significantly correlated with the historical HCH production activities in the areas. The characteristic ratios of α-HCH/γ-HCH and β-HCH/(α + γ)-HCH at different soil depths were 1.4-3.7 and 0.21-1.04, respectively, which indicated the presence of significant localized residues of HCHs. The presence of HCHs in the soil suggested a downward migration, with concentrations rapidly decreasing in the upper layer soil (0-5 m), but a gradual increase in the deeper soil (5-14 m). HCHs were detected at depths exceeding 24 m, indicating heavy penetration. The proportions of γ-HCH and β-HCH changed with increasing soil depth, which was related to their relatively volatile and stable molecular structures, respectively. The results strongly suggested that there is widespread contamination of both soil and groundwater by HCHs even after decades. The likelihood of residual HCHs in the soil should therefore be taken into full consideration during urban planning to limit risks to human and environmental health.
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  • 文章类型: Journal Article
    水文地质系统中的化学农药是全球关注的问题,因为它们对人类和其他生物构成严重威胁。在农业方面,2018年,全球使用了约412万吨农药,比20世纪90年代增加了50%。自1990年代以来在印度水文地质系统中检测到的各种农药已被记录在案,并进行了审查,以了解其流行情况。来源,历史和退化途径。这篇综述有助于更好地了解现有农药污染和水文地质资源恶化的状况。在地下水中检测到少量到过量的农药残留,地表水,土壤,和沉积物。在水文地质系统中最常见和主要发现的农药是六氯环己烷,DDTs,硫丹,七氯,drins(艾氏剂,狄氏剂,异狄氏剂),氯丹等.六氯环己烷中的β和γ-六氯环己烷异构体,而P,p'-DDT和p,在DDT中检测到的p'-DDE最为普遍。在许多地区,水中农药残留水平已超过世卫组织和国际清算银行的最大残留限值,而土壤和沉积物中的那些已经超过了阈值效应水平和可能效应水平。与城市周边地区或城市地区相比,农村农业地区的水资源中检测到更高的农药残留。在某些地区,水资源与土壤之间的农药残留呈正相关,表明有类似的污染源。农药的诊断比率揭示了它们的来源,历史和退化途径。在印度进行的各种研究中观察到的诊断比率表明,历史上以及最近使用的禁用农药。加强现行政策法规建设,监测农药使用情况,农药应用实践的变化,农民的意识,并且使用突出的去除技术对于解决印度的农药污染是必要的。
    Chemical pesticides in the hydrogeological system are a global concern as they pose a severe threat to humans and other organisms. In agriculture, around 4.12 million tonnes of pesticides were used globally in 2018, which is 50% more than in the 1990s. Various pesticides detected in the hydrogeological system of India since the 1990s have been documented and reviewed to understand the prevalence, source, history and degradation pathways. This review contributes to a better understanding of existing pesticide pollution and the state of hydrogeological resource deterioration. Small to excess levels of pesticide residues were detected in groundwater, surface water, soil, and sediments. Pesticides that were most commonly and predominantly found in the hydrogeological system were HCHs, DDTs, endosulfan, heptachlor, drins (aldrin, dieldrin, endrin), chlordane etc. β and γ-HCH isomers among HCHs, whereas p,p\'-DDT and p,p\'-DDE among the DDTs were detected most prevalently. In many regions, pesticide residue levels in water have exceeded the maximum residue limits of WHO and BIS, while those in soils and sediments have exceeded the threshold effect level and probable effect level. Higher pesticide residues were detected in the water resources of rural agricultural areas compared to peri-urban or urban areas. A positive correlation of pesticide residues between water resources and soil has been observed in some regions, suggesting a similar contamination source. Diagnostic ratios of pesticides reveal their source, history and degradation pathways. Diagnostic ratios observed in various studies conducted in India suggest historical as well as recent use of banned pesticides. Strengthening current policies and regulations, monitoring pesticide use, changes in pesticide application practices, awareness among farmers, and the use of prominent removal techniques are necessary to tackle pesticide contamination in India.
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  • 文章类型: Journal Article
    对高度人为河口沿海地区的微塑料(MP)进行了采样,以评估其在沿海沉积物中的分布及其作为潜在污染媒介的作用。平均MP密度为1693±2315MPs/kg,主要积聚在海滩的涨潮和风暴护堤区域。微塑料污染指数(MPPI)微塑性冲击系数(CMPI),层次聚类分析和主成分分析揭示了MP污染的空间变化。在两个海滩(192±218MP/kg沉积物),高密度聚乙烯塑料颗粒很丰富。此外,通过GC-MS评估颗粒上吸附的化学物质的存在,显示0.95±0.09ng/g的∑7OCPs,4.03±0.89ng/g的∑7PCBs,108.76±12.88ng/g的∑16PAHs和122.79±11.13g/g的∑29PAHs。塑料的吸附能力,结合它们的丰富,提出了环境问题,并强调了它们作为化学品暴露指标的适用性。
    Microplastics (MPs) from the coastal areas of a highly anthropised estuary were sampled to assess their distribution in coastal sediments and their role as potential vectors of pollution. The average MP density was 1693 ± 2315 MPs/kg, which mainly accumulated in the high tide and storm berm areas of the beach. The Microplastic Pollution Index (MPPI), Microplastic Impact Coefficient (CMPI), Hierarchical Cluster Analysis and Principal Component Analysis revealed spatial variation in MPs pollution. High-density polyethylene plastic pellets were abundant at two beaches (192 ± 218 MPs/kg sediment). Furthermore, the presence of sorbed chemicals on pellets was assessed through GC-MS, showing 0.95 ± 0.09 ng/g of ∑7OCPs, 4.03 ± 0.89 ng/g of ∑7PCBs, 108.76 ± 12.88 ng/g of ∑16 PAHs and 122.79 ± 11.13 g/g of ∑29 PAHs. The sorption capacity of plastics, combined with their abundance, poses an environmental concern and also highlights their suitability as indicators of chemical exposure.
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  • 文章类型: Journal Article
    这项研究研究了林丹制造废物中有害的氯化有机化合物(COCs)对实际污染土壤(表土和底土)的急性毒性。Microtox®生物测定法用于确定土壤的毒性(改进的基本固相测试),土壤淘析物(基本试验),和有机提取物(适用于有机溶剂样品溶解测试),其中疏水性有机化合物是可溶的。这些持久性污染物的急性毒性(六氯环己烷,HCH异构体,作为表层土壤中的颗粒物,和COCs,从致密的非水相液体,DNAPL,在底土中)和商业化合物也进行了测量。测试的土壤显示出不同的污染物水平(表土:0.9-1149mg/kg,底土:20-9528mg/kg)。土壤污染物分布,浓度和急性毒性与污染源(HCHs或DNAPL)高度相关。土壤,有机提取物,底土淘析物表现出很高的毒性,强调需要对这些网站进行补救。在应用于所测试的土壤的三次测试中计算EC50。EC50vs.土壤和土壤淘析物中的COCs浓度呈渐近趋势,解释为污染物在水相中的低溶解度。相反,EC50vs.在有机提取物的情况下,土壤COCs浓度更线性。从统计分析来看,该测试是最可靠的。这三种方法揭示了有趣和互补的信息,对于全面概述受污染土壤的急性毒性是必要的。
    This research studies the acute toxicity of real contaminated soils (topsoil and subsoil) with hazardous chlorinated organic compounds (COCs) from lindane manufacturing wastes. The Microtox® bioassay was used to determine the toxicity of soils (modified Basic Solid Phase Test), soil elutriates (Basic Test), and organic extracts (adapted Organic Solvent Sample Solubilization Test), in which hydrophobic organic compounds are soluble. The acute toxicity of these persistent contaminants (hexachlorocyclohexanes, HCH isomers, as particulate matter in topsoil, and COCs, from dense non-aqueous phase liquid, DNAPL, in subsoil) and the commercial compounds were also measured. Soils tested showed different contaminant levels (topsoil: 0.9-1149 mg/kg and subsoil: 20-9528 mg/kg). Soil contaminants distribution, concentration and acute toxicity were highly related to the contamination source (HCHs or DNAPL). Soils, organic extracts, and subsoil elutriates presented high toxicity, highlighting the need for remediation of these sites. EC50 was calculated in the three-test applied for the soils tested. EC50 vs. COCs concentration in soils and soil elutriates showed an asymptotic trend, explained by the low pollutants solubility in the aqueous phase. Contrarily, EC50 vs. soil COCs concentration was more linear in the case of the organic extracts. This test was the most reliable from statistical analysis. The three methods reveal interesting and complementary information and are necessary for a complete overview of the acute toxicity of contaminated soils.
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  • 文章类型: Journal Article
    射血分数保留的心力衰竭(HFpEF)在出现呼吸困难的患者中很常见。最近,临床工具的开发有助于HFpEF的诊断.这里,我们将欧洲心脏病学会(ESC)2016年心力衰竭指南以及H2FPEF和HFA-PEFF评分应用于普通人群的中年样本,并对不同组进行比较.
    这项研究包括以人口为基础的汉堡市健康研究的前10.000名参与者。共5613个科目,年龄62±8.7岁(51.1%为女性),有资格进行分析。407名(7.3%)受试者存在无法解释的呼吸困难。在那些,HFpEF的估计患病率为20.4%(ESC2016),12.3%(H2FPEF),和7.6%(HFA-PEFF)。根据HFA-PEFF(57.7%)和H2FPEF(59.2%)评分,大多数受试者被分类为不排除的HFpEF。对于所有算法,诊断为HFpEF的受试者显示年龄和体重指数升高以及房颤的患病率较高。糖尿病,与没有HFpEF或HFpEF的患者相比,动脉高血压不可排除。这些合并症和危险因素的分布在不同诊断的HFpEF组之间有所不同,HFpEF组中的负担最高,由H2FPEF评分定义。根据不同算法诊断为HFpEF的受试者的重叠非常有限。
    无法解释的呼吸困难在中年普通人群中很常见。ESC2016算法和H2FPEF和HFA-PEFF分数检测不同,先证者呼吸困难的不和谐亚群。需要对HFpEF综合征进行进一步分类。
    Heart failure with preserved ejection fraction (HFpEF) is common in patients presenting with dyspnoea. Recently, clinical tools were developed to facilitate the diagnosis of HFpEF. Here, we apply the European Society of Cardiology (ESC) 2016 heart failure guidelines and the H2 FPEF and HFA-PEFF scores to a middle-aged sample of the general population and compared the different groups with each other.
    This study included the first 10 000 participants of the population-based Hamburg City Health Study. A total of 5613 subjects, aged 62 ± 8.7 years (51.1% women), qualified for the analysis. Unexplained dyspnoea was present in 407 (7.3%) subjects. In those, the estimated prevalence of HFpEF was 20.4% (ESC 2016), 12.3% (H2 FPEF), and 7.6% (HFA-PEFF). The majority of subjects was classified as HFpEF not excludable according to the HFA-PEFF (57.7%) and H2 FPEF (59.2%) scores. For all algorithms, subjects diagnosed with HFpEF showed elevated age and body mass index as well as a higher prevalence of atrial fibrillation, diabetes, and arterial hypertension compared with those without HFpEF or HFpEF not excludable. The distribution of those co-morbidities and risk factors varied between the differently diagnosed HFpEF groups with the highest burden in the HFpEF group defined by the H2 FPEF score. The overlap of subjects diagnosed with HFpEF according to the different algorithms was very limited.
    Unexplained dyspnoea is common in the middle-aged general population. The ESC 2016 algorithm and the H2 FPEF and HFA-PEFF scores detect different, discordant subpopulations of probands with breathlessness. Further classification of the HFpEF syndrome is desirable.
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  • 文章类型: Journal Article
    在这里,我们生成了经胸超声心动图主动脉根尺寸与性别匹配的最新参考值,年龄,和体表面积(BSA)来自基于人群的汉堡市健康研究(HCHS)队列。在1687名健康受试者中(平均年龄57.1±7.7,男性681名,女性1006名),来自第一批前瞻性招募的10,000名HCHS参与者,使用最先进的二维经胸超声心动图在收缩期和舒张期测量主动脉根部的尺寸。在四个水平上评估了直径:主动脉瓣环,瓦尔萨尔瓦窦,窦管交界处,和升主动脉.女性与明显较小的绝对主动脉根尺寸相关,而BSA的索引在所有级别都会产生相反的效果。两性的所有主动脉根部直径以及主动脉瓣环/窦管连接比率都有很强的年龄依赖性。多变量分析显示年龄,性别,体重,高度,和BSA是主动脉根大小的重要决定因素。最后,生成了考虑年龄的个体主动脉根参考值的计算公式,性别,体重,和高度。我们根据基于人群的HCHS的标准化经胸超声心动图方案提供基于人群的主动脉根部直径参考值,这可能支持诊断,监测,和主动脉根部疾病的治疗。
    Here we generate up-to-date reference values of transthoracic echocardiographic aortic root dimensions matched by sex, age, and body surface area (BSA) derived from the population-based Hamburg City Health Study (HCHS) cohort. In 1687 healthy subjects (mean age 57.1 ± 7.7, 681 male and 1006 female), derived from the first prospectively-recruited 10,000 HCHS participants, dimensions of the aortic root were measured in systole and diastole using state-of-the-art 2-dimensional transthoracic echocardiography. Diameters were assessed at four levels: aortic annulus, Sinus of Valsalva, sinotubular junction, and ascending aorta. Female sex was associated with significantly smaller absolute aortic root dimensions, while indexing for BSA resulted in a reverse effect at all levels. There was a strong age dependency of all aortic root diameters as well as aortic annulus/sinotubular junction ratio for both sexes. Multivariate analysis revealed age, sex, weight, height, and BSA to be significant determinants of aortic root size. Finally, formulas were generated for the calculation of individual aortic root reference values considering age, sex, weight, and height. We provide population-based reference values of aortic root diameters based on a standardized transthoracic echocardiographic protocol of the population-based HCHS which may support the diagnosis, monitoring, and treatment of aortic root disease.
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  • 文章类型: Journal Article
    Bioaccessibility is essential for evaluating dietary intake of contaminants. However, there is insufficient information on the dependence of dietary intake and risk assessment of dichlorodiphenyltrichloroethane and its metabolites (DDXs) and hexachlorocyclohexane isomers (HCHs) on bioaccessibility. Here, we investigated the bioaccessibilities of DDXs and HCHs in various foods and their influences on assessing exposure in the residents of Beijing City, China. Forty-three major foods in five types (fruit, vegetables, cereals, aquatic food, and meat) were sampled, and the bioaccessibility of DDXs and HCHs was evaluated using a static in vitro gastrointestinal digestion model. The bioaccessibility of DDXs in different food types ranked in the order of meat > vegetables > fruit > cereals > aquatic food, with mean ± standard deviation values of 62.2 ± 22.1%, 20.5 ± 10.6%, 12.4 ± 3.66%, 11.2 ± 9.69%, and 10.7 ± 4.97%, respectively. The highest average bioaccessibility of HCHs was found in meat (83.4 ± 14.2%), followed by fruit (41.0 ± 12.5%), vegetables (37.6 ± 18.1%), aquatic foods (24.2 ± 9.22%), and cereals (8.73 ± 4.07%). The estimated daily intakes (EDI) of the sum of DDXs and the sum of HCHs based on the bioaccessible concentration were only about 17% and 55% of the total EDI based on the residual concentration, respectively. Meat was found to play a more important role in EDI after bioaccessibility correction. The proportion of the population with potential non-carcinogenic and carcinogenic risks markedly decreased when considering bioaccessibility. It was concluded that bioaccessibility should be integrated into dietary exposure evaluation.
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  • 文章类型: Journal Article
    One hundred and twenty samples of breast milk were collected from five northern governorates and districts in Jordan in 2019 and 2020 to monitor results for organochlorine pesticides as organic contaminants. The results showed that 36 samples (30%) of total 120 analyzed samples were contaminated as follows: 16 samples (13.3%) were contaminated with dieldrin, 4 samples (3.3%) with p,p\'-DDE, 4 samples (3.3%) with p,p\'-DDD, 8 samples (6.7%) with p,p\'-DDT and 4 samples (3.3%) with o,p\'-DDE. Comparing results of the current study with those of 2015 study, no residues for the HCHs in 2019/2020 study have been detected, an increase in the DDTs occurred and an increase in the cyclodiens in the 2019/2020 compared to the 2015 study.
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