DEHP metabolites in urine of children and DEHP in house dust

Urine samples from the 2001/2002 pilot study for the German Environmental Survey on children (GerES IV) were analysed for concentrations of the primary DEHP metabolite MEHP (mono(2-ethylhexyl)phthalate) and two secondary DEHP metabolites SOH-MEHP (2-ethyl-5-hydroxy-hexylphthalate) and 5oxo-MEHP (2-ethyl-5-oxo-hexylphthalate). Urine samples had been taken from 254 children aged 3 to 14. In addition, DEHP was analysed in house dust samples. These samples had been collected with vacuum cleaners in the homes of the children. The geometric mean (GM) was 7.9 microg/l for MEHP in urine, and the GMs for the secondary metabolites 5OH-MEHP and 5oxo-MEHP were 52.1 microg/l and 39.9 microg/l. 5OH-MEHP and 5oxo-MEHP concentrations were highly correlated (r = 0.98). The correlations of 5OH-MEHP and 5oxo-MEHP with MEHP were also high (r = 0.72 and r = 0.70). The concentrations of 5OH-MEHP and 5oxo-MEHP were 8.0-fold and 6.2-fold higher than the concentrations of MEHP. The ratios 5OH-MEHP/Soxo-MEHP and 5oxo-MEHP/MEHP decreased with increasing age. Boys showed higher concentrations than girls for all three metabolites of DEHP in urine. Children aged 13-14 had the lowest mean concentrations of the secondary metabolites in urine. The house dust analyses revealed DEHP contamination of all samples. The GM was 508 mg/kg dust. No correlation could be observed between the levels of any of the urinary DEHP metabolites and those of DEHP in house dust.     

An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population.

We analyzed 85 urine samples of the general German population for human specific metabolites of phthalates. By that we avoided contamination with the parent phthalates being omnipresent in the environment and for the first time could deduce each individual's internal exposure to phthalates without contamination. Determined were the secondary metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) of di(2-ethylhexyl)phthalate (DEHP) and the primary monoester metabolites of DEHP, di-noctylphthalate (DnOP), di-n-butylphthalate (DnBP), butylbenzylphthalate (BBzP) and diethylphthalate (DEP). Based on these internal exposure values we calculated the daily intake of the parent phthalates using urinary metabolite excretion factors. For DEHP we determined a median intake of 13.8 micrograms/kg body weight/day and an intake at the 95th percentile of 52.1 micrograms/kg body weight/day. The tolerable daily intake (TDI) value settled by the EU Scientific Committee for Toxicity, Ecotoxicity and the Environment (CSTEE) is 37 micrograms/kg body weight/day. Twelve percent of the subjects (10 out of 85 samples) within our collective of the general population are exceeding this value. Thirty-one percent of the subjects (26 out of 85 samples) had values higher than the reference dose (RfD) of 20 micrograms/kg body weight/day of the U.S. Environmental Protection Agency (EPA). For DnBP, BBzP, DEP and DnOP intake values at the 95th percentile were 16.2, 2.5, 22.1 and 0.42 micrograms/kg body weight/day respectively. Our results unequivocally prove that the general German population is exposed to DEHP to a much higher extent than previously believed. This is of greatest importance for public health since DEHP is not only the most important phthalate with respect to its production, use, occurrence and omnipresence but also the phthalate with the greatest endocrine disrupting potency. DEHP is strongly suspected to be a developmental and reproductive toxicant. We are not aware of any other environmental contaminant for which the TDI and RfD are exceeded to such an extent within the general population. The transgressions of the TDI and RfD for DEHP are accompanied by considerable ubiquitous exposures to DnBP and BbzP, two phthalates under scrutiny for similar toxicological mechanisms.     

Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP)

Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.     

Nitrous oxide in blood and urine of operating theatre personnel and the general population

Nitrous oxide (N₂O) was assayed in 676 urine samples and 101 blood samples provided after exposure by operating theatre personnel from nine hospitals. The blood and urine assays were repeated in 25 subjects 18 h after the end of exposure. For 80 subjects, environmental N₂O was also measured during intraoperative exposure. Mean urinary N₂O in the 676 subjects at the end of exposure was 40 g/l (range 1–3805 g/l); in 10 of the 676 subjects, urinary N₂O was in the range 279–3805 g/l (mean 1202 /l). The 98^th percentile was 120 g/l. Mean blood N₂O at the end of exposure, measured in 101 subjects, was 21 g/l (median 16 g/l, range 1–75 g/l). Blood and urine N₂O (1.5 g/l and 4.9 g/l, respectively) in 25 subjects, 18 h after exposure, was significantly higher than in occupationally non-exposed subjects (blood 0.91 g/l, urine 1 g/l). Environmental exposure was significantly related to blood and urinary N₂O (r = 0.59 andr = 0.64, respectively). Blood and urinary N₂O were significantly related to each other (r = 0.71), and were equivalent to about 25% of the environmental exposure level. The mean urinary N₂O of 1202 g/l in 10/676 subjects was not related to environmental exposure in the operating theatre. The highest urinary N₂O levels measured in these 10/676 subjects could be explained by an asymptomatic urinary infection.     

Determination of four metabolites of the plasticizer di (2-ethylhexyl) phthalate in human urine samples

Summary A method for biological monitoring of exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) is described. In this method the four main metabolites of DEHP [i.e., mono (2-ethylhexyl) phthalate (MEHP), mono (5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)-phthalate] are determined in urine samples. The procedure includes enzymatic hydrolysis, ether extraction, and derivatization with triethyloxonium tetrafluoroborate. Analysis is performed by gas chromatography electron impact mass spectrometry. The detection limit for all four metabolites is less than 25 g/l urine. The coefficient of variation based on duplicate determinations of urine samples of workers occupationally exposed to DEHP was 16% for MEHP (mean concentration 0.157 mg/l) and 6% -9% for the other three metabolites (mean concentrations 0.130-0.175 mg/1). The method described here was used to study DEHP metabolism in man. Most persons excrete mono(2-ethyl-5-oxohexyl)-phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate as a (glucuronide) conjugate. Mono (5-carboxy-2-ethyl-pentyl)phthalate is mainly excreted in free form, while for MEHP a large interindividual variation in conjugation status was observed. Of the four metabolites quantified, 52% are products of a ((-l)-hydroxylation reaction of MEHP [i.e., mono (2-ethyl-5-oxohexyl)phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate], 22% is the product of a -hydroxylation reaction of MEHP [i.e., mono (5-carboxy-2-ethylpentyl)phthalate], and 26% is not oxidized further (i.e., MEHP). A good correlation is obtained when the amount of MEHP -hydroxylation products is compared with the amount of MEHP (-1)hydroxylation products in urine samples. When the internal dose of DEHP has to be established we recommend that the levels of all four metabolites of DEHP be studied in urine samples.     

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.     

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.     

Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors

Each year thousands of healthy volunteers undergo apheresis procedures to donate blood components and safe lives. However, many disposables used in apheresis contain di(2-ethylhexyl)phthalate (DEHP). This way, donors are exposed to DEHP, which is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. We quantified the DEHP exposure of six plasma donors, six discontinuous-flow platelet donors and six continuous-flow platelet donors by determining three specific metabolites in urine (5OH-MEHP: mono(2-ethyl-5-hydroxyhexyl)phthalate; 5oxo-MEHP: mono(2-ethyl-5-oxo-hexyl)phthalate and MEHP: mono(2-ethylhexyl)phthalate). We found maximum concentrations in urine samples after the discontinuous-flow plateletpheresis procedure with 826 microg/l for 5OH-MEHP, 774 microg/l for 5oxo-MEHP and 266 microg/l for MEHP (mean of the six volunteers). Metabolite excretions were found to be significantly (p<0.0001) higher for both plateletpheresis techniques compared to plasmapheresis and controls. Continuous-flow plateletpheresis led to significantly higher (p<0.0001) excretions than discontinuous-flow plateletpheresis. Mean absolute DEHP exposures were 1.2 mg for discontinuous- and 2.1 mg for continuous-flow plateletpheresis. Exposure for plasmapheresis (0.37 mg) was in the range of the controls (0.41 mg). Mean DEHP doses for both plateletpheresis techniques (18.1 and 32.3 microg/kg/day) were close to or exceeded the reference dose (RfD) of the US EPA and tolerable daily intake (TDI) value of the EU on the day of the apheresis. Therefore, margins of safety might be insufficient to protect especially young men and women in their reproductive age from effects on reproductivity. At present, discontinuous-flow devices should be preferred to avert conceivable health risks from plateletpheresis donors. Strategies to avoid DEHP exposure of donors during apheresis need to be developed.     

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.     

2019年湖北省中小学校生活与教学环境卫生现状分析

目的 分析湖北省中小学校生活与教学环境卫生现状,为政府部门制定干预策略提供支持.方法 采用分层随机抽样的方法,抽取湖北省30个区县175所中小学校的1 032间教室,统计描述生活与教学环境卫生指标的合格率,使用x2检验比较各组间差异.结果 课桌椅分配合格率仅5.2％,教室人均面积合格率为21.3％,黑板反射比合格率为3...     

Reference values for metabolites of pyrethroid and organophosphorous insecticides in urine for human biomonitoring in environmental medicine

Pesticides are widely used throughout the world in agriculture to protect crops, and in public health to control diseases transmitted by vectors or intermediate hosts. After the prohibition of organochlorines, such as DDT, today mainly pyrethroids and organophosphorous insecticides are used. With reliable and sensitive analytical methods for detecting metabolites of organophosphorous and pyrethroid insecticides in urinary specimens of the general population several studies have been published on internal exposure to these insecticides of the population in Germany. In total, data on levels of metabolites of organophosphorous acids in urine of about 1200 children and adults have been published, as well as data on levels of pyrethroid metabolites in urine of about 2100 children and adults. In Germany, reference values for environmental pollutants related to the population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency, preferably based on data gained by representative studies. Reference values are defined as the 95th percentile, rounded off within the 95% confidence interval of the population studied. Since there is a need for reference values to characterise the population's exposure to organophosphates and pyrethroids, and since there are different studies available from Germany that agree quite well with data from other industrialised countries, the Commission has derived reference values from the available data, though none of the studies had fulfilled criteria on representativity. Reference values for metabolites of organophosphorous acids are as follows: DMP 135 microg/l, DMTP 160 microg/l and DEP 16 microg/l and for metabolites of pyrethroids: cis-Cl2CA 1 microg/l, trans-Cl2CA 2 microg/l and 3-PBA 2 microg/l. As the volume-related concentrations of organophosphate and pyrethroid metabolites show no significant age-dependence, the reference values derived are not age-stratified. Though based merely on statistical and not on toxicological data, levels analysed above the reference levels, when reliably measured (verified several times), should prompt environmental health practitioners to search for sources, within the bounds of proportionality. In addition to accidental poisoning, possible sources include indoor contamination following improper pest control operations in homes as well as in pets and food products contaminated by these pesticides.     

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.     

Use of hormone replacement therapy by menopausal women: a comparison between primary care patients and the general population

OBJECTIVES: To compare frequency and patterns of hormone replacement therapy (HRT) between primary care patients and the local community. METHODS: Comparison of data from a questionnaire survey of 107 peri- and postmenopausal patients in an academic primary care clinic during 1998 to similar data from a sample (n = 241) of an ongoing annual epidemiological survey representative of the general population. RESULTS: Mean age, menopause status, age of initiation of HRT, and prior use of contraceptive pill were similar in both groups. Current HRT use tended to be lower among patients in the clinic than in the community. HRT users in the clinic were more likely to have had a surgical menopause (34.4% vs. 16.1%, p = 0.04) and to have used hormones for shorter periods than in the general population. Differences remained significant after adjustment in multivariate analysis. CONCLUSIONS: Compared to the general population, patterns of HRT use in the outpatient clinic were more restrictive than recommendations on HRT that were published at the time. This is an example of how comparison of health issues between patients in medical care and a local epidemiological survey can help to understand clinical practice.     

Trends in the musk xylene concentrations in plasma samples from the general population from 1992/1993 to 1998 and the relevance of dermal uptake

Objectives: Musk xylene (MX), an environmentally important nitromusk compound, is used in different fragrances and soaps as substitute for natural musk. MX is known to occur in breast milk and plasma samples from the general population. Biological monitoring was carried out to study the change in MX concentrations in plasma from the general population over a period of about 6 years. Methods: Forty-one human plasma samples from the general population were collected and analyzed in 1998. The MX concentrations in plasma were compared with those in samples collected from the general population in 1992/1993. In order to␣study possible routes of exposure, we also analyzed perfumes (n=8), various body-care products (n=17), and detergents (n=5) in the households from the persons who were exposed in 1998. The body-care products or the detergents were used every day or at least 3–4 times per week. Results and Discussion: A remarkable decrease in MX levels was found on comparing the values from 1992/1993 and 1998. In 1998 12% (five out of 41) of the samples analyzed yielded positive results for MX (median: <0.1 μg/l, range: <0.1–0.29 μg/l), while in 1993 MX was found in 92% (66 out of 72) of the samples (median: 0.24 μg/l, range: <0.1–1.12 μg/l). The observed decrease is explained by the discontinued use of MX in detergents in Germany since 1993. As a consequence, no MX could be found in the investigated detergents in the present study. However, MX could be analyzed in at least one perfume and/or perfumed body-care product of the exposed individuals. The concentrations were in the range between 8.8 and 28.8 mg/kg in the investigated products. Because other confounding factors, e.g. diet and occupational exposure, could be excluded, the results point to the possibility that MX can be taken up through the skin. However, the small number of investigated persons limits this assumption. Received: 23 October 2000 / Accepted: 18 April 2001     

Possible effects of environmental cadmium exposure on kidney function in the Japanese general population

Objectives: To examine whether the current level of environmental exposure to cadmium (Cd) is associated with kidney dysfunction among general populations in Japan. Methods: A nationwide survey was conducted in Japan from 1991 to 1997 at 30 survey sites (with no known environmental heavy metal pollution), by the collection of 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples. In practice, 607 non-smoking adult women provided these samples. After being wet-ashed, the samples were analyzed for Cd in food duplicates (Cd-F), in blood (Cd-B) and urine (Cd-U) by inductively-coupled plasma mass spectrometry (ICP-MS). Urine samples were also analyzed for α₁-microglobulin (α₁-MG), β₂-microglobulin (β₂-MG) and retinol-binding protein (RBP), creatinine (cr) and specific gravity. Possible tubular dysfunction in association with Cd exposure was examined by simple, multiple and logistic regression analyses, and comparison among three different Cd-dose groups. To minimize the confounding effects of aging, 367 women from 41 to 60 years old were selected and subjected to the same statistical analyses. Results: The analysis of a whole population of 607 women showed that α₁-MG and possibly β₂-MG increased as a function of Cd-F, Cd-B and Cd-U. When the analysis was repeated with the selected population of 367 women aged 41–60, the Cd dose-dependent changes in α₁-MG and β₂-MG became less evident. The distribution of the selected population with α₁-MG above two low cut-off values of >4.9 and >8.4 mg/g cr or with β₂-MG above the lowest cut-off value of >400 μg/g cr, was biased toward the group with higher Cd-Ucr, but such bias was not significant for both α₁-MG and β₂-MG when higher cut-off values were employed. No bias was detected with RBP. Logistic regression analysis with α₁-MG, β₂-MG and RBP (with cut-off values given above) in combination with age, Cd-F, Cd-B and Cd-Ucr gave essentially the same results. Conclusions: The evidence for kidney dysfunction was of borderline significance in the present study population for which geometric mean Cd-F, Cd-B and Cd-U were 24.7 μg/day, 1.76 μg/l, and 3.94 μg/g cr, respectively. The findings might suggest at the same time that the safety margin is small for the Japanese general population regarding environmental Cd exposure. Received: 26 February 1999 / Accepted: 24 July 1999     

Biological monitoring of occupational exposure to polycyclic aromatic hydrocarbons (PAH) by determination of monohydroxylated metabolites of phenanthrene and pyrene in urine

Objectives The aim of our study was to assess individual polycyclic aromatic hydrocarbon (PAH) exposure of workers coming from three different industrial branches by several parameters of external and internal exposure. By analysing the relationships between those markers the suitability of individual parameters [e.g. monohydroxylated phenanthrene (Phe) metabolites] for exposure surveillance should be evaluated. Methods The total study population consisted of 255 male workers (age: 19-62, mean: 39.61 years), who were employed in coke production (n = 40), production of graphite electrodes and special carbon products (92), or production of refractory materials (123), respectively. For each worker external PAH exposure was determined by personal air sampling of 16 PAH, including Phe, pyrene (Pyr) and benzo[a]pyrene (BaP). For determination of internal PAH exposure the excretion of the PAH metabolites 1-, 2 + 9-, 3-, 4-hydroxyphenanthrene and 1-hydroxypyrene was measured in post-shift urine samples of all workers. Results In the total study population median total PAH exposure and exposure to BaP were 30.62 and 0.27 μg/m3, respectively. A calculation of PAH profiles resulted in substantial branch-related variations with Phe being a major component. Considering all branches the median excretions of 1-hydroxypyrene and hydroxyphenanthrenes (sum) were 6.68 and 11.22 μg/g creatinine. A correlation analysis yielded a good correlation between total ambient PAH exposure and excretion of hydroxyphenanthrenes in urine (r = 0.662; P < 0.01), but no significant correlation between Phe metabolites and the carcinogenic BaP. For 1-hydroxypyrene and BaP a weak but significant association was found (r = 0.235; P < 0.01). Conclusions Considering the results of the correlation analysis hydroxyphenanthrenes in urine should reflect an uptake of lowly condensed volatile PAH rather than an incorporation of highly condensed PAH like BaP which should be reflected better by 1-hydroxypyrene. Therefore, the determination of hydroxyphenanthrenes in addition to the well-established marker 1-hydroxypyrene could offer some further information about the exposure situation at a particular work place.     

我国7城市中小学生零食消费行为分析

目的了解我国城市中小学生零食消费现状,为学生营养干预工作提供基础资料。方法采用三阶段分层随机整群抽样方法,从北京等7个城市选取7260名三年级及以上的中小学生作为研究对象,对他们的零食消费行为进行问卷调查。结果城市中小学生在家里、学校和其他地方的零食消费率分别为98．0％、78．1％和84．3％,中小学生在家常吃的零食以新鲜果蔬、奶制品、冷饮和饮料为主,而在学校和其他地方则以冷饮、饮料和糖果为主。女生消费新鲜果蔬、奶及奶制品、糖果等零食的比例较高,而男生消费饮料和肉蛋类等零食的比例较高。16．3％的城市中小学生看电视、使用电脑／上网时总是或经常吃零食。结论城市中小学生普遍存在吃零食的现象,零食种类不合理,需要通过营养干预帮助中小学生科学、合理地消费零食,促进其健康生长。     

中小学心理健康教育存在的问题及其对策

我国中小学心理健康教育起步较晚,发展较慢,存在着区域发展不平衡,活动开展欠科学、社会家庭不重视等问题,而加强心理学学科及师资队伍建设,加强心理健康教育活动以及营造良好的家庭和社会环境等是解决问题基本路径和策略。     

中小学营养教育的问题与对策

我国中小学营养教育存在宣传和法律保障不到位、课堂教学薄弱、教育效果不佳、师资和课程资源缺乏等突出问题。目前主要解决对策为营造教育氛围、完善学校立法、研制教学大纲、完善教育评估体系、开展教育教学研究、研究师资培养和培训模式、开发利用课程资源。     

兰州市部分中小学生意外伤害情况调查分析

目的探讨中小学生意外伤害的流行特征和中小学生意外伤害认知与行为特点,为开展意外伤害健康促进提供依据。方法采用分层整群抽样的方法抽取甘肃省兰州市4所中小学共1680名学生进行最近1年意外伤害发生情况的调查,同时调查研究对象意外伤害相关知识掌握情况与安全行为习惯养成情况。结果意外伤害年发生率为28．41％,男生伤害发生率为35．82％,女生伤害发生率为19．70％,不同性别学生各类伤害构成比有统计学差异（P〈0．05）。小学生伤害发生率为23．70％,中学生伤害发生率为32．33％,有统计学差异（P〈0．05）。独生子女与非独生子女间伤害发生率比较无统计学差异（P〉0．05）。中小学生伤害的类型前4位分别是跌伤、碰撞伤、车辆伤和运动创伤,引起伤害的主要原因是学生之间互相嬉戏、追逐玩耍、体育运动中。意外伤害相关知识测试题满分为50分,平均得分为38．3分,男、女学生比较无统计学差异;中学生高于小学生,有统计学差异。结论中小学生伤害发生率较高,应针对其意外伤害认知与行为特点,有的放矢地开展健康促进工作,降低中小学生意外伤害的发生。