Case study approach to modeling historical disinfection by-product exposure in Iowa drinking waters

In the 1980 s, a case–control epidemiologic study was conducted in Iowa(USA) to analyze the association between exposure to disinfection by-products(DBPs) and bladder cancer risk. Trihalomethanes(THMs), the most commonly measured and dominant class of DBPs in drinking water, served as a primary metric and surrogate for the full DBP mixture.Average THM exposure was calculated, based on rough estimates of past levels in Iowa. To reduce misclassification, a follow-up study was undertaken to improve estimates of past THM levels and to re-evaluate their association with cancer risk. In addition, the risk associated with haloacetic acids, another class of DBPs, was examined. In the original analysis, surface water treatment plants were assigned one of two possible THM levels depending on the point of chlorination. The re-assessment considered each utility treating surface or groundwater on a case-by-case basis. Multiple treatment/disinfection scenarios and water quality parameters were considered with actual DBP measurements to develop estimates of past levels. The highest annual average THM level in the re-analysis was156 μg/L compared to 74 μg/L for the original analysis. This allowed the analysis of subjects exposed at higher levels( 96 μg/L). The re-analysis established a new approach, based on case studies and an understanding of the water quality and operational parameters that impact DBP formation, for determining historical exposure.     

Nontargeted identification of peptides and disinfection byproducts in water

A broad range of organic compounds are known to exist in drinking water sources and serve as precursors of disinfection byproducts(DBPs).Epidemiological findings of an association of increased risk of bladder cancer with the consumption of chlorinated water has resulted in health concerns about DBPs.Peptides are thought to be an important category of DBP precursors in water.However,little is known about the actual presence of peptides and their DBPs in drinking water because of their high sample complexity and low concentrations.To address this challenge and identify peptides and non-chlorinated/chlorinated peptide DBPs from large sets of organic compounds in water,we developed a novel high throughput analysis strategy,which integrated multiple solid phase extraction(SPE),high performance liquid chromatography(HPLC)separation,and non-target identification using precursor ion exclusion(PIE)high resolution mass spectrometry(MS).After MS analysis,structures of candidate compounds,particularly peptides,were obtained by searching against the Human Metabolome Database(HMDB).Using this strategy,we successfully detected 625 peptides(out of 17,205 putative compounds)and 617 peptides(out of 13,297)respectively in source and finished water samples.The source and finished water samples had 501 peptides and amino acids in common.The remaining 116 peptides and amino acids were unique to the finished water.From a subset of 30 putative compounds for which standards were available,25 were confirmed using HPLC-MS analysis.By analyzing the peptides identified in source and finished water,we successfully confirmed three disinfection reaction pathways that convert peptides into toxic DBPs.     

Evaluation of disinfection byproducts for their ability to affect mitochondrial function

In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts (DBPs) in water; evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential (ΔΨm) and cytoplasmic adenosine triphosphate (C-ATP) was investigated with human carcinoma (HepG2) cells. Within 90 min of cell exposure, only the haloacetic acid (HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups (haloacetonitriles (HANs), trihalomethanes (THMs), nitrosamines (NOAs), and HAAs) responded well to ΔΨm, R² > 0.70. Based on the half-maximum concentration that evoked a 50% response in ΔΨm, the response gradient was HANs >> HAAs ∼ THM > NOAs. The inhibition of the ΔΨm by HANs is driven by dibromoacetonitrile (DBAN), while dichloroacetonitrile (DCAN) did not cause a significant change in the ΔΨm at less than 2000 µM. A mixture of HANs exhibited an antagonistic behavior on the ΔΨm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then ΔΨm could be used as a biomonitoring tool for DBP toxicity.     

Identification of unknown disinfection byproducts in drinking water produced from Taihu Lake source water

Although disinfection byproducts(DBPs) in drinking water have been suggested as a cancer causing factor, the causative compounds have not yet been clarified. In this study, we used liquid chromatography quadrupole-time-of-flight spectrometry(LC-QTOF MS) to identify the unknown disinfection byproducts(DBPs) in drinking water produced from Taihu Lake source water, which is known as a convergence point for the anthropogenic pollutants discharged from intensive industrial activities in the surroundi...     

Impact of pre-oxidation on the formation of byproducts in algae-laden water disinfection: Insights from fluorescent and molecular weight

Pre-oxidation has been reported to be an effective way to remove algal cells in water, but the released algal organic matter (AOM) could be oxidized and lead to the increment in disinfection by-product (DBP) formation. The relationship between pre-oxidation and AOM-derived DBP formation needs to be approached more precisely. This study compared the impact of four pre-oxidants, ozone (O₃), chlorine dioxide (ClO₂), potassium permanganate (KMnO₄) and sodium hypochlorite (NaClO), on the formation of nitrogenous (N-) and carbonaceous (C-) DBPs in AOM chlorination. The characterization (fluorescent properties, molecular weight distribution and amino acids concentration) on AOM samples showed that the characterization properties variations after pre-oxidation were highly dependent on the oxidizing ability of oxidants. The disinfection experiments showed that O₃ increased DBP formation most significantly, which was consistent with the result of characterization properties variations. Then canonical correspondent analysis (CCA) and Pearson's correlation analysis were conducted based on the characterization data and DBP formation. CCA indicated that C-DBPs formation was highly dependent on fluorescent data. The formation of haloacetic acids (HAAs) had a positive correlation with aromatic protein-like component while trichloromethane (TCM) had a positive correlation with fulvic acid-like component. Pearson's correlation analysis showed that low molecular weight fractions were favorable to form N-DBPs. Therefore, characterization data could provide the advantages in the control of DBP formation, which further revealed that KMnO₄ and ClO₂ were better options for removing algal cells as well as limiting DBP formation.     

邻苯二甲酸酯暴露的大鼠尿液生物标志物研究

建立了检测尿液中邻苯二甲酸酯类化合物(PAEs)共同水解产物邻苯二甲酸(PA)的分析方法;通过雄性成年SD大鼠代谢试验,检测了邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)单独暴露、以及联合暴露条件下大鼠尿液中PA总量,并分析了PA与暴露总量之间的关系.结果显示,随着暴露剂量的增大,尿液中排出的PA总量也不断增大;DBP单独暴露、DEHP单独暴露以及两者联合暴露时尿液PAEs代谢物平均排泄总量占摄入量的百分比分别为65.04%、55.00%和38.35%;大鼠尿液中PA的摩尔总量与DBP、DEHP、以及两者联合暴露的摩尔量之间的相关系数分别为0.92(P<0.01)、0.56(P<0.01)、0.93(P<0.01).尿液水解后的PA能够反映PAEs类物质的总暴露水平,将来可能作为一种潜在的暴露生物标志物用于人群的PAEs暴露监测.     

Method to assess component contribution to toxicity of complex mixtures: Assessment of puberty acquisition in rats exposed to disinfection byproducts

A method based on regression modeling was developed to discern the contribution of component chemicals to the toxicity of highly complex, environmentally realistic mixtures of disinfection byproducts(DBPs). Chemical disinfection of drinking water forms DBP mixtures.Because of concerns about possible reproductive and developmental toxicity, a whole mixture(WM) of DBPs produced by chlorination of a water concentrate was administered as drinking water to Sprague–Dawley(S–D) rats in a multigenerational study. Age of puberty acquisition,i.e., preputial separation(PPS) and vaginal opening(VO), was examined in male and female offspring, respectively. When compared to controls, a slight, but statistically significant delay in puberty acquisition was observed in females but not in males. WM-induced differences in the age at puberty acquisition were compared to those reported in S–D rats administered either a defined mixture(DM) of nine regulated DBPs or individual DBPs. Regression models were developed using individual animal data on age at PPS or VO from the DM study. Puberty acquisition data reported in the WM and individual DBP studies were then compared with the DM models. The delay in puberty acquisition observed in the WM-treated female rats could not be distinguished from delays predicted by the DM regression model, suggesting that the nine regulated DBPs in the DM might account for much of the delay observed in the WM. This method is applicable to mixtures of other types of chemicals and other endpoints.     

Impact of chlorine exposure time on disinfection byproduct formation in the presence of iopamidol and natural organic matter during chloramination

Chloramines,in practice,are formed onsite by adding ammonia to chlorinated drinking water to achieve the required disinfection.While regulated disinfection byproducts(DBPs)are reduced during chloramine disinfection,other DBPs such as iodinated(iodo-)DBPs,that elicit greater toxicity are formed.The objective of this study was to investigate the impact of prechlorination time on the formation of both halogen-specific total organic halogen(TOX)and iodo/chlorinated(chloro-)DBPs during prechlorination/chloramination in source waters(SWs)containing iopamidol,an X-ray contrast medium.Barberton SW(BSW)and Cleveland SW(CSW)containing iopamidol were prechlorinated for 5–60 min and afterwards chloraminated for 72 hr with ammonium chloride.Chlorine contact time(CCT)did not significantly impact total organic iodine(TOI)concentrations after prechlorination or chloramination.Concentrations of total organic chlorine(TOCl)formed during prechlorination did not significantly change regardless of pH and prechlorination time,whileTOClappearedtodecreaseafter 72 hrchloraminationperiod.Dichloroiodomethane(CHCl_2I)formation during prechlorination did not exhibit any significant trends as a function of p H or CCT,but after chloramination,significant increases were observed at pHs 6.5 and 7.5 with respect to CCT.Iodo-HAAs were not formed during prechlorination but were detected after chloramination.Significant quantities of chloroform(CHCl_3)and trichloroacetic acid(TCAA)were formed during prechlorination but formation ceased upon ammonia addition.Therefore,prechlorination studies should measure TOX and DBP concentrations prior to ammonia addition to obtain data regarding the initial conditions.     

Body fluid analog chlorination: Application to the determination of disinfection byproduct formation kinetics in swimming pool water

Disinfection by-products(DBPs) are formed in swimming pools by the reactions of bather inputs with the disinfectant.Although a wide range of molecules has been identified within DBPs,only few kinetic rates have been reported.This study investigates the kinetics of chlorine consumption,chloroform formation and dichloroacetonitrile formation caused by human releases.Since the flux and main components of human inputs have been determined and formalized through Body Fluid Analogs(BFAs),it is possible to model the DBPs formation kinetics by studying a limited number of precursor molecules.For each parameter the individual contributions of BFA components have been quantified and kinetic rates have been determined,based on reaction mechanisms proposed in the literature.With a molar consumption of 4 mol Cl_2/mol,urea is confirmed as the major chlorine consumer in the BFA because of its high concentration in human releases.The higher reactivity of ammonia is however highlighted.Citric acid is responsible for most of the chloroform produced during BFA chlorination.Chloroform formation is relatively slow with a limiting rate constant determined at 5.50 × 10~(-3) L/mol/sec.L-histidine is the only precursor for dichloroacetonitrile in the BFA.This DBP is rapidly formed and its degradation by hydrolysis and by reaction with hypochlorite shortens its lifetime in the basin.Reaction rates of dichloroacetonitrile formation by L-histidine chlorination have been established based on the latest chlorination mechanisms proposed.Moreover,this study shows that the reactivity toward chlorine differs whether L-histidine is isolated or mixed with BFA components.     

金坛地区五氯酚的人体暴露评价

以五氯酚及其钠盐(统称为PCP)为研究对象,选择曾长期使用五氯酚钠杀灭钉螺的江苏省金坛地区为研究区域,使用膳食暴露模型计算评价了当地居民的人体暴露水平.结果表明,该地区成年人日均PCP摄入量最高值为8μg·d-1,该值低于世界卫生组织推荐的每日允许摄入量180μg·d-1;饮水和植物类食物是人体摄入PCP的主要途径,分别占总摄入量的42%和39%.此外,不确定性分析表明,模式运算结果呈偏态分布,偏度、峰度系数分别为3.51和19.7.     

广州市多污染物联合暴露的健康效应评估

本研究应用贝叶斯核机器回归(BKMR)分析了广州市2015~2018年大气主要污染物(SO₂、NO₂、PM₁₀、PM_2.5、CO和O₃)与非意外死亡之间的联合健康效应。结果表明,6种污染物对健康结局均存在较大影响。随着其它污染物固定百分位数浓度的增加,SO₂、O₃或NO₂的浓度从第25百分位数变化到第75百分位数导致的效应值的绝对值逐渐升高;相反,PM_2.5、CO或PM₁₀的浓度从第25百分位数变化到第75百分位数导致的效应值的绝对值逐渐减少。在累积滞后0~1d时,多种空气污染物的混合暴露对非意外死亡人数的影响效应值为正,与最低浓度相较,当所有污染物的浓度增至第90百分位数时,人数非意外死亡人数将增加21.98%(95%CI:3.04%,44.41%)。通过应用BKMR模型,本研究证实多种污染物的暴露可对广州市人群公共健康造成联合的综合影响。在污染物的防控治理上,不仅需要针对当地主要空气污染物,还需加强对多污染物暴露的防控。     

Assessment of potential dermal and inhalation exposure of workers to the insecticide imidacloprid using whole-body dosimetry in China

In China, although improvements to the pesticide registration process have beenmade in last thirty years, no occupational exposure data are required to obtain a commercial license for a pesticide product. Consequently, notably little research has been conducted to establish an exposure assessment procedure in China. The present study monitored the potential dermal operator exposure from knapsack electric sprayer wheat field application of imidacloprid in Liaocheng City, Shandong Province and in Xinxiang City, Henan Province, China, using whole-body dosimetry. The potential inhalation exposure was determined using a personal air pump and XAD-2 sample tubes. The analytical method was developed and validated, including such performance parameters as limits of detection and quantification, linear range, recovery and precision. The total potential dermal and inhalation exposures were 14.20, 16.80, 15.39 and 20.78 mL/hr, respectively, for the four operators in Liaocheng and Xinxiang, corresponding to 0.02% to 0.03% of the applied volume of spray solution. In all trials, the lower part (thigh, lower leg) of the body was the most contaminated, accounting for approximately 76% to 88% of the total exposure. The inhalation exposure was less than 1% of the total exposure. Such factors as the application pattern, crop type, spray equipment, operator experience and climatic conditions have been used to explain the exposure distribution over the different parts of the body. As indicated by the calculated Margin of Exposure, the typical wheat treatment scenarios when a backpack sprayer was used are considered to be safe in terms of imidacloprid exposure.     

Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure

Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose(0.1 μg/(kg?bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the differentially expressed genes. And the changes of several picked genes have been verified by real-time PCR. A total of 145 up-regulated and 64 down-regulated genes were identified. The metabolic processes, interleukin-1 secretion and production were significantly associated with the differentially expressed genes. And the genes regulated by dioxin also clustered to cholinergic synapse and long-term potentiation. Candidate biomarker genes such as egr1, gad2, gabrb3, abca1, ccr5 and pycard may be toxicological targets for dioxin. Furthermore, synaptic plasticity and neuro-immune system may be two principal affected areas by dioxin.     

Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human–hamster hybrid cells

Microcystin-LR(MC-LR) is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen(Group 2B) by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human–hamster hybrid(AL) cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher(p 0.01) in ALcells exposed to a cytotoxic concentration(1 μmol/L) of MC-LR for 30 days than in untreated control cells, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide(NO) production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor NG-methyl-L-arginine(L-NMMA), which suppressed MC-LRinduced mutations as well. The survival of mitochondrial DNA-depleted(ρ0) ALcells was markedly decreased by MC-LR treatment compared to that in ALcells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.     

Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells

Microcystin-LR (MC-LR) is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen (Group 2B) by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human-hamster hybrid (A_L) cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher (p < 0.01) in A_L cells exposed to a cytotoxic concentration (1 μmol/L) of MC-LR for 30 days than in untreated control cells, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide (NO) production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor N^G-methyl-_L-arginine (L-NMMA), which suppressed MC-LRinduced mutations as well. The survival of mitochondrial DNA-depleted (ρ⁰) A_L cells was markedly decreased by MC-LR treatment compared to that in A_L cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.     

中国PM2.5人口暴露风险时空格局

采用PM_2.5和人口格网数据,计算了2000~2016年中国PM_2.5人口暴露风险值,并利用Theil-Sen Median趋势分析、标准偏差和Hurst指数等,分析了17a间中国PM_2.5人口暴露风险的时空变化特征.结果表明：①17a间PM_2.5人口暴露风险在胡焕庸线两侧差异巨大,东部高、西部低,东部多年风险均值为2.787,西部为0.065;②17a间PM_2.5人口暴露风险在胡焕庸线两侧的变化幅度具有较显著差异,西部整体呈下降趋势,而在2011年和2015年有明显回升,东部自2001年迅速增加且保持平稳状态,直至2015年出现大幅度回落.③PM_2.5人口暴露风险的稳定性与持续性差异显著,东部以不稳定与弱反持续性为主,西部则以稳定与强反持续性为主要特征.④暴露等级为危险与极危险水平下的人口总量与人口密度在空间上呈现出东部高西部低的分布状态.     

全球PM2.5人口暴露风险时空格局

基于PM_2.5遥感数据和人口格网数据,利用污染物人口暴露风险模型、Theil-Sen Media和Mann-Kendall等方法,分析了2000~2016年全球PM_2.5人口暴露风险时空分布特征,并识别出暴露高风险区域.结果表明,PM_2.5遥感数据和人口格网数据可以客观地评价暴露风险程度.全球PM_2.5平均浓度在各大洲差异显著,PM_2.5污染的高值区域主要分布在东亚、南亚和东南亚.PM_2.5质量浓度的多年平均值从高到低分别是亚洲14.7μg/m³、非洲8.1μg/m³、欧洲8.03μg/m³、南美洲5.69μg/m³、北美洲4.41μg/m³和大洋洲1.27μg/m³.2000~2016年,全球PM_2.5人口暴露风险在宏观尺度上呈逐渐减少的趋势,而在区域内则呈现出差异性.空间上,全球PM_2.5人口暴露风险各大洲从高到低依次为亚洲5.94、非洲0.62、欧洲0.45、南美洲0.32、北美洲0.27和大洋洲0.01.时间上,2000~2016年,亚洲和非洲PM_2.5人口暴露风险呈增长趋势,欧洲和北美洲呈减少趋势,大洋洲和南美洲变化幅度较小.     

上海室内外灰尘中多氯联苯及其人体暴露评估

2008年11月~2009年6月以气象学分4个季度测定了上海地区居民家庭室内外灰尘中多氯联苯(PCBs)的浓度.研究表明,春季和冬季室内灰尘中PCBs平均含量高于夏季和秋季,而室外灰尘中PCBs含量表现相反特征.单个室内样品∑PCBs浓度范围为1.0×103~1.97×106pg/g,室外为n.d.~1.96×106pg/g.此外,通过生理学的体外实验模拟人体胃肠消化过程,并利用响应面法研究影响PCBs生物有效性的因素,发现胆汁浓度相对于消化时间、液固比和污染物浓度对PCBs生物有效性影响最大.依据室内外灰尘中PCBs年平均浓度、生物有效性及灰尘摄入量计算得出,上海地区儿童和成人通过摄入灰尘人均PCBs的日暴露量分别为2.657×102~1.078×104pg/d和1.328×102~ 5.392×103pg/d.     

Characterization of personal exposure concentration of fine particles for adults and children exposed to high ambient concentrations in Beijing, China

In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a personal exposure study was conducted for school children, and office workers in Beijing, China. For all participants (N = 114), the mean personal 24-hr exposure concentration was 102.5, 14.7, 0.093, 0.528, 0.934, 0.174 and 0.703 μg/m 3 for PM 2.5 , black carbon, Mn, Al, Ca, Pb, and Fe. Children's exposure concentrations of PM 2.5 were 4-5 times higher than those in related studies. The ambient concentration of PM 2.5 (128.5 μg/m 3 ) was significantly higher than the personal exposure concentration (P 0.05), and exceed the reference concentration (25 μg/m 3 ) of WHO air quality guideline. Good correlation relationships and significant differences were identified between ambient concentration and personal exposure concentration. The relationships indicate that the ambient concentration is the main factor influencing personal exposure concentration, but is not a good indicator of personal exposure concentration. Outdoor activities (commute mode, exposure to heating, workday or weekend travel) influenced personal exposure concentrations significantly, but the magnitude of the influence from indoor activities (exposure to cooking) was masked by the high ambient concentrations.     

Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos

In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at di erent time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 g/L and 0.01 to 2.00 g/L, respectively. For exposure to triazophos, ChE was induced up to 176.5% at 1.5 g/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 g/L and day 10 when measured by butyrylthiocholine (BTCh). For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectively, with both maximal inductions detected at 0.1 g/L and day 8. Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days. Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition. In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture. This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population.