Trends of the internal phthalate exposure of young adults in Germany—Follow-up of a retrospective human biomonitoring study

The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24 h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19–29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988–2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 μg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 μg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 μg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 μg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 μg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 μg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 μg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 μg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 μg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 μg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 μg/l (2008) for cx-MiNP. The investigation of the time series 1988–2008 indicates a decrease of the internal exposure to DnBP by the factor of 7–8 and to DEHP and BzBP by the factor of 2–3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV.     

Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study

In a retrospective human biomonitoring study we analyzed 24h urine samples taken from the German Environmental Specimen Bank for Human Tissues (ESBHum), which were collected from 634 subjects (predominantly students, age range 20-29 years, 326 females, 308 males) in 9 years between 1988 and 2003 (each n >or= 60), for the concentrations of primary and/or secondary metabolites of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP). Based on the urinary metabolite excretion we estimated daily intakes of the parent phthalates and investigated the chronological course of the phthalate exposure. In over 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of the German population to all five phthalates throughout the last 20 years. The median daily intakes in the subsets between 1988 and 1993 were quite constant for DnBP (approx. 7 microg/kg bw/d) and DEHP (approx. 4 microg/kg bw/d). However, from 1996 the median levels of both phthalates decreased continuously until 2003 (DnBP 1.9 microg/kg bw/d; DEHP 2.4 microg/kg bw/d). By contrast, the daily intake values for DiBP were slightly increasing over the whole time frame investigated (median 1988: 1.1 microg/kg bw/d; median 2003: 1.4 microg/kg bw/d), approximating the levels for DnBP and DEHP. For BBzP we observed slightly decreasing values, even though the medians as of 1998 levelled off at around 0.2 microg/kg bw/d. Regarding daily DiNP exposure we found continuously increasing values, with the lowest median being 0.20 microg/kg bw/d for the subset of 1988 and the highest median for 2003 being twice as high. The trends observed in phthalate exposure may be associated with a change in production and usage pattern. Female subjects exhibited significantly higher daily intakes for the dibutyl phthalates (DnBP p=0.013; DiBP p=0.004). Compared to data from US National Health and Nutrition Examination Surveys (NHANES) exposure levels of the dibutyl phthalates were generally higher in our German study population, while levels of BBzP were somewhat lower. Overall, for a considerable 14% of the subjects we observed daily DnBP intakes above the tolerable daily intake (TDI) value deduced by the European Food Safety Authority (EFSA) (10 microg/kg bw/d). However, the frequency of exceedance decreased during the years and was beneath 2% in the 2003 subset. Even though transgressions of the exposure limit values of the EFSA and the US Environmental Protection Agency (US EPA) occurred only in a relatively small share of the subjects, one has to take into account the cumulative exposure to all phthalates investigated and possible dose-additive endocrine effects of these phthalates.     

Identifying sources of phthalate exposure with human biomonitoring: Results of a 48 h fasting study with urine collection and personal activity patterns

Human biomonitoring studies measuring phthalate metabolites in urine have shown widespread exposure to phthalates in the general population. Diet is thought to be a principle route of exposure to many phthalates. Therefore, we studied urinary phthalate metabolite patterns over a period of strict fasting and additionally recorded personal activity patterns with a diary to investigate non-dietary routes of exposure. Five individuals (3 female, 2 male, 27–47 years of age) fasted on glass-bottled water only over a 48-h period. All urine void events were captured in full, and measured for metabolites of the high molecular weight (HMW) di-(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP) and di-isodecyl phthalate (DiDP), and the low molecular weight (LMW) di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), dimethyl phthalate (DMP), and diethyl phthalate (DEP). In all, 21 metabolites were measured in a total of 118 urine events, including events before and after the fasting period. At the onset of the study all phthalate metabolite concentrations were consistent with levels found in previous general population studies. Metabolites of the HMW phthalates (DEHP, DiNP and DiDP) showed a rapid decline to levels 5–10 times lower than initial levels within 24 h of the fast and remained low thereafter. After food consumption resumed, levels rose again. By contrast, metabolites of the LMW phthalates including DMP, DEP, BBzP, DnBP and DiBP showed a cyclical pattern of rising and declining concentrations suggestive of ongoing non-food exposures. Furthermore, metabolites of most of the LMW phthalates (BBzP, DnBP and DiBP) tracked each other remarkably well, suggesting concurrent exposures. Diary entries could not help explain exposure sources for these phthalates, with one exception: rises in MEP concentrations around males’ showers suggest personal care products as a major source of DEP. Exposure to HMW phthalates in this cohort appears to be driven by dietary intake, while non-dietary routes such as use of personal care products and ubiquitous sources including dust and indoor air appear to explain exposure to LMW phthalates.     

Internal exposure of the general population to DEHP and other phthalates--determination of secondary and primary phthalate monoester metabolites in urine

A number of phthalates and their metabolites are suspected of having teratogenic and endocrine disrupting effects. Especially the developmental and reproductive effects of di(2-ethylhexyl)phthalate (DEHP) are under scrutiny. In this study we determined the concentrations of the secondary, chain oxidized monoester metabolites of DEHP, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) in urine samples from the general population. The utilization of the secondary metabolites minimized any risk of contamination by the ubiquitously present phthalate parent compounds. Included in the method were also the simple monoester metabolites of DEHP, dioctylphthalate (DOP), di-n-butylphthalate (DnBuP), butylbenzylphthalate (BBzP) and diethylphthalate (DEP). Automated sample preparation was performed applying a column switching liquid chromatography system enabling online extraction of the urine on a restricted access material (RAM) and separation on a reversed phase analytical column. Detection was performed by negative ESI-tandem mass spectrometry in multiple reaction monitoring mode and quantification by isotope dilution. The excretion of DEHP and the other phthalates was studied by analyzing first morning urine samples from 53 women and 32 men aged 7-64 years (median: 34.2 years) living in northern Bavaria (Germany) who were not occupationally exposed to phthalates. Phthalate metabolites, secondary and primary ones, were detected in all specimens. Concentrations were found to vary strongly from phthalate to phthalate and subject to subject with differences spanning more than three orders of magnitude. Median concentrations for excretion of DEHP metabolites were 46.8 microg/L for 5OH-MEHP (range 0.5-818 microg/L), 36.5 microg/L for 5oxo-MEHP (range 0.5-544 microg/L), and 10.3 microg/L for MEHP (range:<0.5 (limit of quantification, LOQ) to 177 microg/L). A strong correlation was found between the excretion of 5OH-MEHP and 5oxo-MEHP with a correlation coefficient of r=0.991, indicating close metabolic proximity of those two parameters but also the absence of any contaminating interference. Median concentrations for the other monoester metabolites were for mono-n-butylphthalate (MnBuP) 181 microg/L, for monobenzylphthalate (MBzP) 21.0 microg/L, for monoethylphthalate (MEP) 90.2 microg/L and for mono-n-octylphthalate (MOP)<1.0 microg/L (LOQ). These results will help to perform health risk assessments for the phthalate exposure of the general population.     

Human biomonitoring of phthalate exposure in Austrian children and adults and cumulative risk assessment

Phthalates are a class of chemicals widely used as plasticisers in a multitude of common consumer products. Through contact with such products, people are regularly exposed to phthalates, which are suspected to contribute to adverse health effects, particularly in the reproductive system.In the present study, 14 urinary phthalate metabolites of 10 parent phthalates were analysed by HPLC–MS/MS among the Austrian population aged 6–15 and 18–81 years in order to assess phthalate exposure. In the total study population, ranges of urinary phthalate metabolite concentrations were n.d.–2,105 μg/l (median 25 μg/l) for monoethyl phthalate (MEP), n.d.–88 μg/l (10 μg/l) for mono-n-butyl phthalate (MnBP), n.d.–248 μg/l (28 μg/l) for mono-isobutyl phthalate (MiBP), n.d.–57 μg/l (1.8 μg/l) for mono-benzyl phthalate (MBzP), n.d.–20 μg/l (n.d.) for mono-(2-ethylhexyl) phthalate (MEHP), n.d.–80 μg/l (2.6 μg/l) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), n.d.–57 μg/l (1.9 μg/l) for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), n.d.–219 μg/l (11 μg/l) for mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), n.d.–188 μg/l (1.6 μg/l) for 3-carboxy-mono-proply phthalate (3cx-MPP), n.d.–5.5 μg/l (n.d.) for mono-cyclohexyl phthalate (MCHP), n.d.–4.5 μg/l (n.d.) for mono-n-pentyl phthalate (MnPeP), n.d.–3.4 μg/l (n.d.) for mono-n-octyl phthalate (MnOP), n.d.–13 μg/l (n.d.) for mono-isononyl phthalate (MiNP), and n.d.–1.1 μg/l (n.d.) for mono-isodecyl phthalate (MiDP). Generally, children exhibited higher levels of exposure to the majority of investigated phthalates, except to MEP, which was found in higher concentrations in adults and senior citizens at a maximum concentration of 2,105 μg/l. Individual daily intakes were estimated based on urinary creatinine and urinary volume excretion and were then compared to acceptable exposure levels, leading to the identification of exceedances of mainly the Tolerable Daily Intakes (TDI), especially among children. The execution of a cumulative risk assessment based on Hazard Indices showed cause for concern mainly for children, as well as in rare cases for adults.Although phthalate exposure seems to have decreased in previous years, the wide distribution and existing exceedances of acceptable levels indicate that phthalate exposure should be further monitored in order to identify exposure sources and enable appropriate minimisation measures.     

Vasectomy effectiveness in Nepal: a retrospective study

The main purpose of this retrospective, cross-sectional study was to evaluate the effectiveness of vasectomy in an ongoing public sector program in Nepal. We evaluated semen samples from men who had previously had a vasectomy, and asked about the occurrence of pregnancies in the men's partners. In addition, the surgeons who performed the vasectomies completed a questionnaire about their techniques. A two-stage stratified sampling procedure was used to select 1263 men from among over 30,000 men, who had previously undergone a no-scalpel vasectomy, mostly by ligation and excision, in 32 districts between July 1996 and June 1999. Semen samples were preserved and analyzed at a central laboratory. A US andrology laboratory validated the lab results. Twenty-three men (2.3%, 95% confidence interval [CI] 1.1-3.6) had >/=500,000 sperm/mL in their semen. Fifteen of those men reported pregnancies conceived after their vasectomy. In addition, six men with azoospermia reported pregnancies for which conception occurred within 3 months after vasectomy. Eleven men with azoospermia reported pregnancies for which conception occurred more than 3 months after vasectomy. Reported pregnancy was more likely in younger partners. The life table pregnancy rates for all men interviewed were 0.7 (95% CI 0.2-1.1), 1.7 (95% CI 1.4-2.1) and 4.2% (95% CI 3.2-5.2) at 3, 12 and 36 months, respectively. In low-resource, programmatic settings, vasectomy failure rates may be higher than commonly cited rates, especially in younger populations. Additional research is needed to determine if other occlusion techniques could reduce failure rates. Counseling on vasectomy should always convey the possibility of failure and partner pregnancy.     

Concept of the Flemish human biomonitoring programme

Since 2002 a human biomonitoring network has been established in Flanders (Belgium) as part of a programme on environmental health surveillance. The human biomonitoring network should support environmental health policy by identifying priorities for further action. The first cycle of the programme (2002-2006) confirmed the hypotheses that living in areas with different environmental pressure is reflected in different loads of environmental chemicals in the residents. In the second cycle of the programme (2007-2011) the number of environmental chemicals for which human biomonitoring data were obtained was expanded substantially. The goal of the Flemish programme is to use and translate the scientific results into policy actions. Its further orientation in the second cycle to human biomonitoring in hot spots and sensitive age groups or susceptible persons with underlying complications (e.g. persons with diabetes) are linked to these goals. Interaction with stakeholders is embedded in the programme emphasizing transparency of the choices that are made and direct communication. The Flemish human biomonitoring programme is organized centrally with major involvement of research partners from different disciplines which allows engrafting environmental health research on the programme. One of the major focuses is the question whether combinations of pollutants in the general population are associated with biological effects. The objective of this paper is to review and discuss the options that were taken in the human biomonitoring programme in order to achieve its goals.     

我院15年人才培养的回顾性研究

目的 通过分析医院近15年的人才培养情况,阐述医院人才培养的创新性制度.方法 整理15年人才培养的基本情况,运用配对T检验和Wilcoxon秩和检验等统计方法分析培养前后人才医、教、研、管理能力的变化状况.结果 通过培养,人才的医、教、研、管理能力有显著性的提升.结论 只有建立创新性的人才培养制度,才能提升医院的综合竞争力,更好地服务于患者.     

天津市成年人流感疫苗免疫效果回顾性评价

流感的广泛流行给社会造成巨大危害[1],而应用疫苗免疫预防是世界普遍认同的措施[2].为了评价成年人接种流感疫苗的效果,我们在2007年9月与北京科兴生物制品有限公司合作的流感裂解疫苗安尔来福安全性与免疫原性研究基础上,进行成年人流感疫苗免疫效果研究,旨在评价成年人接种流感疫苗的效果.     

Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry

Objectives: We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS₂ and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. Methods: Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at ∼4 pm. In total, 386 urine samples were successfully analyzed. Results: Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value <0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 μg/l and 5 μmol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). Conclusions: The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels of CS₂ (∼0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in factories. Therefore, when estimating exposures to phthalates and CS₂ detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithiocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the occupational contribution to total phthalate exposure.     

Personal status of general health checkups and medical expenditure: A large-scale community-based retrospective cohort study

Background

We sought to clarify the association between the personal utilization of general health checkups (GHCs) and medical expenditures (MEs) in a middle-aged Japanese population.

中国中部地区两县既往有偿献血人群艾滋病回顾性队列研究

目的研究既往有偿采供血人群艾滋病感染者的发病死亡规律。方法采用回顾性队列研究的方法，对178例确认的通过献血(浆)感染艾滋病病毒(HIV)的感染者进行回顾性调查，利用Kaplan—Meier乘积极限法计算平均潜伏期和生存时间及其分布。结果HIV感染者的平均潜伏期为8．31年(95％CI：8．04～8．58)(Kaplan—Meier法)。感染后艾滋病总发病率为6．41／100人年。艾滋病发病后平均生存时间为9．90个月(95％CI：8．20～11．60)(Kaplan—Meier法)。结论研究发现既往有偿采供血人群HIV感染者的平均潜伏期短于联合国艾滋病规划署(UNAIDS)研究结果(9．5年)；艾滋病发病率在感染后6年内均显著低于UNAIDS研究结果，第7年后高于UNAIDS结果。感染者发病后平均生存时间短于UNAIDS研究结果。     

京津冀自然人群队列研究的经验与展望

京津冀自然人群队列研究是一项大规模前瞻性队列研究, 2017年在北京市、天津市和河北省开展基线调查, 覆盖了从生命早期直至老年的114 850名调查对象。截至2021年12月, 106 031人已完成至少1次随访, 总体随访率为92.3%。本队列结合三地环境和健康问题特点, 重点围绕儿童青少年生长发育、心血管代谢疾病及其危险因素、老龄化及共病、空气污染的健康效应等主题进行了系统研究。京津冀自然人群队列中全生命期多样化人群的长期随访将为我国健康与疾病研究提供独特和宝贵的科研资源以及丰富的生物样品。本文描述了京津冀自然人群队列的产生背景和战略意义、研究现状和成果、不足和挑战以及未来规划和展望等, 以期为国内外学者开展相关研究提供参考。     

我国北方两卷烟厂职工死亡回顾性调查

为分析烟草尘对卷烟厂职工恶性肿瘤、呼吸系疾病死亡专率的影响，采用回顾性队列研究的方法，对河南、黑龙江两省某两卷烟厂１９８２～１９９４年间在册的职工进行恶性肿瘤、呼吸系疾病死因分析。以队列成员中的非暴露于烟草尘组为内对照，比较两组间的各死因死亡专率的差异。结果表明：男、女职工暴露组的恶性肿瘤、呼吸系疾病死亡专率均显著高于非暴露组。按接触烟草水平分为非接触组、低剂量接触组和高剂量接触组分析发现：恶性肿瘤、呼吸系疾病死亡与其暴露烟草尘水平可能存在剂量－效应关系。提示：接触烟草尘可能是恶性肿瘤、呼吸系疾病死亡的危险因素。吸烟和接触烟草尘的协同作用分析表明：吸烟和接触烟草尘对恶性肿瘤、呼吸系疾病可能存在协同作用。     

The Geriatric Nutritional Risk Index predicts increased healthcare costs and hospitalization in a cohort of community-dwelling older adults: Results from the MONICA/KORA Augsburg cohort study, 1994-2005

Objective

To determine if the Geriatric Nutritional Risk Index (GNRI), an index for the risk of nutrition-related complications, is associated with healthcare costs and risk of hospitalization at baseline and after 10 y.

Methods

Data from a German population-based cohort of 1999 subjects 55 to 74 y of age at baseline were used. Self-reported physician visits, length of hospital stay, and drug intake were used to estimate costs. The GNRI is based on serum albumin values and the discrepancy between real and ideal body weights. Low GNRI values were defined as mean minus 2 times standard deviation. Mean GNRI values were regarded as normal.

Results

Low baseline GNRI was consistently associated with increased total costs, probability of hospitalization, inpatient costs, and pharmaceutical costs at baseline and follow-up, after adjustment for socioeconomic characteristics, lifestyle factors, and coexisting conditions. Subjects with low GNRI at baseline had approximately 47% higher total costs, 50% higher risk of hospitalization, 62% higher inpatient costs and 27% higher pharmaceutical costs at follow-up than subjects with normal GNRI values.

Conclusion

The GNRI risk predicted increased future healthcare costs and higher risk of hospitalization in independent-living older adults. The GNRI is a rapid and low-cost tool that might be routinely used in population-based settings.     

某石棉矿接尘工人恶性肿瘤10年回顾性调查

目的了解接触石棉粉尘工人恶性肿瘤患病情况,为制定石棉所致肿瘤的防护措施提供依据。方法选择某石棉矿1972—1981年接触石棉粉尘1年以上工人为调查对象,同时选择该矿附近县城关镇11个村居民作为对照组,采用统一方法进行流行病学调查,研究资料进行回顾性对比分析和统计学处理。结果①某石棉矿恶性肿瘤年平均粗死亡率55.82/10万,标化死亡率(SMR)70.82/10万;②石棉接尘工恶性肿瘤相对危险度(RR12.42)与对照组(RR3.76)对比分析差异有显著性(P<0.01);③石棉接尘工和对照组肺癌SMR比两者差异有显著性(P<0.01);④肺癌患病与接尘工龄长短呈正相关(r=0.87,P<0.025);⑤肺癌死亡工种分布:选矿最高、辅助工次之,采矿第3位,包装和生产管理人员未见肺癌患者;⑥吸烟工人肺癌高于不吸烟者(P<0.05)。结论接触石棉粉尘可引起肺癌患病率升高,消化道癌患病率也可升高,肺癌患病率与接尘工龄长短呈正相关,与接触粉尘浓度高低(工种)有关,粉尘浓度越大、接触时间越长,肺癌患病率越高,石棉粉尘接触是引起石棉矿肺癌高发的原因,吸烟对石棉所致肺癌有协同作用。     

广西隆安县2006-2014年原发性肝癌回顾性调查研究

目的 探讨广西隆安县原发性肝癌流行病学特征及危险因素.方法 回顾性调查隆安县2006-2014年发病的原发性肝癌患者共2 170例,通过查阅纸质报告表、病案、肿瘤直报系统等方法收集其基本人口学资料、诊断与报告情况、乙肝病毒和丙肝病毒感染以及免疫接种情况,并对上述资料进行统计分析.结果 病例以35岁以上中老年男性为主,平均年龄(57.22±14.61)岁,男女性别比为3.50:1,壮族占绝大多数.2 170名研究对象中,457例(21.06％)患者乙型肝炎病毒表面抗原(hepatitis B surface antigen,HBsAg)阳性,10例(0.46％)抗-丙肝病毒抗体(anti-hepatitis C virus IgG,anti-HCV IgG)阳性,3例HBsAg和抗-HCV IgG均为阳性.HBsAg感染率为65.76％(457/695),丙肝病毒(hepatitis C virus,HCV)感染率为1.79％ (10/558).除24例研究对象乙肝疫苗接种史不详以外,其余均无乙肝疫苗接种史.2006-2014年粗发病率为60.50/10万,中国人口标化发病率为32.11/10万,世界人口标化发病率为43.60/10万.2012-2014年发病率出现逐年上升趋势.结论 隆安县是肝癌高发区,且近年发病上升.乙肝病毒感染是隆安县肝癌发病主要危险因素之一.     

Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany

Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.     

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.