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The International Program on Chemical Safety (IPCS), a collaborative program of the United Nations Environment Program, the International Labour Organization (ILO), and the World Health Organization (WHO), includes the Environmental Health Criteria (EHC) Program inaugurated in 1973 by WHO. These EHC are integrated evaluations of the human health and environmental risks from exposure to specific chemicals carried out by a group of international scientists. Boron (B) was evaluated at an IPCS Task Group (TG) convened in November 1996. All TGs are convened under WHO rules and procedures. These procedures relate the overall process used to prepare an EHC including transparency of the process, conflict of interest, the roles of Members and Observers, and the conduct of the TG. The scope and purpose of an EHC, for an element such as B, and its possible role in national and international chemical safety programs will be discussed. In the early 1990s, countries asked that IPCS request TGs to prepare, where data permit, health-based guidance values (GVs) (both total daily intake and to recommend health-based guidelines for various environmental media). This final evaluation in an EHC reflects the collective consensus view of the TG Members. To foster the use of consistent methodology by TGs, IPCS prepared in 1994 an EHC on the methodology for the preparation of GVs for human exposure limits (EHC 170). In developing their final evaluation, TGs have been asked to consider using this methodology. This was done by the TG on B, and a total daily intake for humans of 0.4 mg/kg body wt was derived from animal studies of reproductive and developmental effects in rodents and pharmacokinetic data from both animals and humans. The application of the methodology described in EHC 170 regarding choice of critical effect and uncertainty factors will be discussed.

Eleven recently completed toxicological studies were critically reviewed to identify toxicologically significant endpoints and dose-response information. Dose-response data were compiled and entered into the USEPA's benchmark dose software (BMDS) for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). After assessing 91 endpoints across the nine studies, a total of 23 of these endpoints were identified for BMD modeling, and BMDL estimates corresponding to various dose-response models were compiled for these separate endpoints. Thyroid, neurobehavior and reproductive endpoints for BDE-47, -99, -209 were quantitatively evaluated. According to methods and feature of each study, different uncertainty factor (UF) value was decided and subsequently reference doses (RfDs) were proposed. Consistent with USEPA, the lowest BMDLs of 2.10, 81.77, and 1698 µg/kg were used to develop RfDs for BDE-47, -99, and -209, respectively. RfDs for BDE-99 and BDE-209 were comparable to EPA results, and however, RfD of BDE-47 was much lower than that of EPA, which may result from that reproductive/developmental proves to be more sensitive than neurobehavior for BDE-47 and the principal study uses very-low-dose exposure.

There is a growing concern about the potential health effects of exposure to various environmental chemicals during pregnancy and infancy. The placenta is expected to be an effective barrier protecting the developing embryo against some endocrine disruptors (EDs) circulating in maternal blood. The current study was designed to assess in utero exposure levels of non-persistent organic pollutants (non-POPs) and persistent organic pollutants (POPs) in Chinese newborns and potential role of placenta barrier against fetal exposure to these commonly-used environmental endocrine disruptors. A total of 230 newborn-mother pairs were enrolled during 2010–2011, 201 pairs of which were recruited from Shanghai, and the other 29 pairs came from Wenzhou. Maternal blood, cord blood, and meconium specimens were collected in the subject population from Shanghai and analyzed for non-POPs, including mono-2-ethylhexyl phthalate (MEHP), octylphenol (OP) and 4-nonylphenol (4-NP). A total of 19 polybrominated diphenyl ethers (PBDEs) congeners, which belong to POPs, were detected in maternal and cord blood specimens from the other 29 pairs. Fetal-maternal ratios (F-M ratios) and regression coefficients were presented to assess potential function of placenta on barricading the mother/fetal transfer of these EDs. Concentrations of the detected non-POPs in cord blood samples were approximately 20% lower than those in maternal blood, and regression coefficients of which were all over 0.80. In contrast, PBDEs levels in cord blood samples were significantly higher than those in maternal blood. MEHP levels in meconium were much higher than those in cord blood samples, and highly correlated. Therefore, observations demonstrated that the placental barrier slightly decreased the fetal exposure to most non-POPs, while PBDEs seemed to be totally transferred across the placenta and finally reached the fetus. For in utero exposure assessment of Di-2-ethylhexyl phthalate (DEHP), MEHP level in meconium may be a useful biomarker.

To estimate the frequency of daily average PM10 concentrations exceeding the air quality standard (AQS) and the reduction of particulate matter emission to meet the AQS from the statistical properties (probability density functions) of air pollutant concentration.The daily PM10 average concentration in Beijing, Shanghai, Guangzhou, Wuhan, and Xi'an was measured from 1 January 2004 to 31 December 2008. The PM10 concentration distribution was simulated by using the lognormal, Weibull and Gamma distributions and the best statistical distribution of PM10 concentration in the 5 cities was detected using to the maximum likelihood method.The daily PM10 average concentration in the 5 cities was fitted using the lognormal distribution. The exceeding duration was predicted, and the estimated PM10 emission source reductions in the 5 cities need to be 56.58%, 93.40%, 80.17%, 82.40%, and 79.80%, respectively to meet the AQS.Air pollutant concentration can be predicted by using the PM10 concentration distribution, which can be further applied in air quality management and related policy making.

This work aimed to construct Shanghai air quality health index (SAQHI) and to grade the air quality in Shanghai.Daily average concentrations of particulate matter with aerodynamic diameter less than 10 micrometer (PM(10)), SO(2) and NO(2) from 2001 to 2008 in the central urban areas of Shanghai were collected from Shanghai Environmental Monitoring Center. Contemporaneous data of daily average temperature and relative humidity were obtained from Shanghai Meteorological Bureau. Contemporaneous daily non-accidental mortality of registered residents in central urban areas of Shanghai were obtained from Shanghai Municipal CDC, respectively. Time-series analysis was conducted to estimate the association between air pollution and daily non-accidental mortality in the central urban areas of Shanghai. SAQHI was then established and applied to grade the air quality in Shanghai.On average, there were 122 non-accidental daily deaths in the central urban areas of Shanghai from 2001 to 2008. The contemporaneous daily average concentrations of PM(10), SO(2) and NO(2) for the same period were (97.3 ± 59.5), (50.1 ± 27.8) and (64.7 ± 23.9) µg/m(3), respectively. Daily average temperature was (17.7 ± 8.8)°C, and daily average relative humidity was (71.4 ± 11.8)%. Based on results of time series analysis, formula for SAQHI was SAQHI = 10/17× (exp (0.000 153×PM(10))-1+exp (0.000 662×NO(2))-1)×100. Air quality in Shanghai was graded according to SAQHI values as low health risk (SAQHI: 0 ∼ 3), moderate health risk (SAQHI: 4-6), high health risk (SAQHI: 7-10) and very high health risk (SAQHI:10).SAQHI could be applied in grading air quality in Shanghai, and reflect the effects of the overall air quality on health.

To evaluate the loss of disability adjusted life years (DALYs) due to particulate air pollution in Chinese urban residents.DALYs was applied to evaluate the health effects due to particulate air pollution in the residents of 656 Chinese cities, and the data of annual average concentrations of inhalable particle (PM(10)) in 2006 were collected from the state-owned air quality monitoring network.Particulate air pollution in Chinese urban areas in 2006, could cause (506.6 +/- 95.2) thousand premature deaths, (156.6 +/- 41.2) thousand new cases of chronic bronchitis, (12.6 +/- 5.2) million outpatient visits for internal medicine, (99.9 +/- 50.4) thousand and (72.0 +/- 8.2) thousand hospital admissions for cardiovascular diseases and respiratory diseases respectively. The attributable DALYs loss in urban residents amounted up to (5.26 +/- 0.99) million person years in 2006, of which, 96.26% (506.55/526.22) were caused by premature deaths. The attributable loss of DALYs increased with more seriously PM-polluted atmosphere and larger urban population.Substantial adverse health effects due to outdoor particulate air pollution were observed in China urban areas, thus strengthening air pollution control still remains an imperative and urgent matter in public health perspective.

To examine the effect of particulate matter (PM) less than 10 microns in diameter (PM10) and ozone (O3) on daily mortality in Shanghai, China.A generalized additive model with penalized spline function was used to observe the acute effect of PM10 and O3 on daily mortality.Higher PM10 significantly increased the effect of O3 on total mortality, and O3 also increased the effect of PM10 although the estimated increment was statistically insignificant.Our findings provide further evidence for the effect of PM10 and O3 on daily mortality.

To investigate the relation between air pollution exposure and preterm birth in Shanghai, China.We examined the effect of ambient air pollution on preterm birth using time-series approach in Shanghai in 2004. This method can eliminate potential confounding by individual risk factors that do not change over a short period of time. Daily numbers of preterm births were obtained from the live birth database maintained by Shanghai Municipal Center of Disease Control and Prevention. We used the generalized additive model (GAM) with penalized splines to analyze the relation between preterm birth, air pollution, and covariates.We observed a significant effect of outdoor air pollution only with 8-week exposure before preterm births. An increase of 10 microg/m3 of 8-week average PM10, SO2, NO2, and O3 corresponded to 4.42% (95%CI 1.60%, 7.25%), 11.89% (95%CI 6.69%, 17.09%), 5.43% (95%CI 1.78%, 9.08%), and 4.63% (95%CI 0.35%, 8.91%) increase of preterm birth. We did not find any significant acute effect of outdoor air pollution on preterm birth in the week before birth.Ambient air pollution may contribute to the risk of preterm birth in Shanghai. Our analyses also strengthen the rationale for further limiting air pollution level in the city.

To investigate the effect of ambient air pollution on human health and the subsequent disability-adjusted life years (DALYs) lost in Shanghai.We used epidemiology-based exposure-response functions to calculate the attributable number of cases due to air pollution in Shanghai in 2000, and then we estimated the corresponding DALYs lost in Shanghai based on unit DALYs values of the health consequences.Ambient air pollution caused 103,064 DALYs lost in Shanghai in 2000. Among all the health endpoints, premature deaths and chronic bronchitis predominated in the value of total DALYs lost.The air pollution levels have an adverse effect on the general population health and strengthen the rationale for limiting the levels of air pollution in outdoor air in Shanghai.

To monitor the level of phthalates in human semen samples and to analyze the relationship between phthalate levels and semen parameters.Concentrations of three kinds of commonly used phthalates (di-ethyl phthalate, DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) were measured using reversed-phase HPLC. Semen parameters were measured by computer aided sperm analysis (CASA).The three phthalates were detected in most of the biological samples, with median levels of 0.30 mg/L (0.08-1.32 mg/L) in semen specimens. There was a significant positive association between liquefied time of semen and phthalate concentrations of semen. The correlation coefficient was 0.456 for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no significant difference between phthalate concentrations of semen and sperm density or livability, though the correlation coefficients were negative.These results suggest that people who reside in Shanghai are exposed to phthalates, especially to DBP and DEHP. Although the level of phthalates is relatively mild, an association of phthalate levels and reduced quality of human semen has been shown in the present study.

To obtain the exposure-response functions that could be used in health-based risk assessment of particulate air pollution in China.Meta analysis was conducted on the literatures on air particulate matter and its adverse health outcomes in China and worldwide.For each health outcome from morbidity to mortality changes, the relative risks were estimated when the concentration of air particulate matter increased to some certain units.The exposure-response functions recommended here can be further applied to health risk assessment of air particulate matter in China.

To study the relationship between ambient air pollution and daily mortality of SARS in Beijing.The approach of time-series Poisson regression was used to assess the relationship between daily SARS mortality, ambient air pollution, and other factors from April 25 to May 31, 2003 in Beijing.An increase of each 10 microg/m3 over a 5-day moving average of PM10, SO2 and NO2 corresponded to 1.06 (1.00-1.12), 0.74 (0.48-1.13) and 1.22 (1.01-1.48) relative risks (RRs) of daily SARS mortality, respectively. The relative risks (RRs) values depended largely on the selection of lag days.The daily mortality of SARS might be associated with certain air pollutants in Beijing.

To determine the best statistical distribution of concentration data of major air pollutants in Shanghai.Four types of theoretic distributions (lognormal, gamma, Pearson V and extreme value) were chosen to fit daily average concentration data of PM10, SO2 and NO2 from June 1, 2000 to May 31, 2003 in Shanghai by using the maximum likelihood method. The fit results were evaluated by Chi-square test.The best-fit distributions for PM10, SO2 and NO2 concentrations in Shanghai were lognormal, Pearson V, and extreme value distributions, respectively.The results can be further applied to local air pollution prediction and control, e.g., the probabilities exceeding the air quality standard and emission source reduction of air pollutant concentration to meet the standard.

To investigate the effects of copper on permeability and P-glycoprotein (P-gp) of Caco-2 cell monolayers.The differentiated Caco-2 cell model was used in this study. Permeability of cell monolayers was reflected by monitoring transepithelial electrical resistance (TEER); distribution of tight junctional protein ZO-1 was measured by immunofluorescent staining; F actin was measured by fluorescence staining; and Activity of P-gp was reflected by changes of transcellular transport and accumulation of Rho-123 in Caco-2 cells.Apical treatment with copper (30 - 100 micromol/L, Hanks' buffered salt solution, up to 3 hours) induced a time- and concentration-dependent increase in permeability reflected by progressive decrease of TEER of Caco-2 cell monolayers, accompanied by deorganization of F actin, but without significant effects on tight junctional protein ZO-1; at a dose without any adverse effects on viability and permeability of Caco-2 monolayers, copper treatment (300 micromol/L, complete medium, 24 hours) decreased Papp(BL--AP) from 7.37 +/- 0.20 x 10(-6) cm/s (controls) to (6.43 +/- 0.27) x 10(-6) cm/s, the increased Papp(AP--BL) from (1.23 +/- 0.05) x 10(-7) cm/s (controls) to (3.41 +/- 0.08) x 10(-7) cm/s, and enhanced the intracellular Rho-123 from (0.31 +/- 0.01) nmol/filter (controls) to (0.50 +/- 0.03) nmol/filter.Copper might alter the barrier functions of Caco-2 cells through increasing the permeability and inhibiting P-gp of Caco-2 cells.

To study the reversibility of di-n-butyl phthalate (DBP) effects on F(1) generation rat testes.Pregnant rats were treated with different dose of DBP (0, 50, 250 and 500 mg per kg per day) by gavage from GD1 to PND21. The adverse effects of DBP on testes of F(1) male rats in different developmental period (PND14, 21 and 70) were observed by anatomy and pathological methods.There was no difference in rat testis weight and testis/body weight between DBP-treated group and the control. From the results of pathology and sertoli cell counting, comparing with the control, thinner seminiferous epithelium, decreased cell number and vacuole cells were observed in PND14 male DBP-treated rats. In PND21 rats, the number and form of sertoli cells were recovered and few exfoliated spermatogenic cells were found. When maturing to PND70, few rats were found irreversible damages such as seminiferous tubule degeneration, seminiferous epithelium atrophy, etc.These results suggest that adverse effects of DBP on young rat testes should be reversibility.

By using Benchmark Dose (BMD) approach to explore the relations among drinking water fluoride, urine fluoride, serum fluoride and dental fluorosis; and to evaluate the significance of urine fluoride and serum fluoride in control and prevention of endemic fluorosis.512 children (290 in Xinhuai Village, 222 in Wamiao Village) aged 8-13 years were recruited in the study. Epidemiological methods were used to investigate the prevalence of dental fluorosis, and the levels of urine fluoride, serum fluoride, and drinking water fluoride in superficial well. The children were divided into six subgroups by the concentration of fluoride in drinking water:0.5 mg/L, 0.5-mg/L, 1.0-mg/L, 2.0-mg/L, 3.0-mg/L andor = 4.0 mg/L.There was significant dose-response relationship between the drinking water fluoride and the prevalence of dental fluorosis or the prevalence of defect dental fluorosis. The BMDLs (Benchmark Dose Lower Bound) were 1.01 and 1.30 mg/L, respectively. Urine fluoride and serum fluoride also had significant dose-response relationship to the prevalence of dental fluorosis or defect dental fluorosis. The correlation coefficient between drinking water fluoride and urine fluoride was 0.717, and it was 0.855 between drinking water fluoride and serum fluoride, and 0.617 between urine fluoride and serum fluoride.The currently national standard of fluoride in drinking water in China is safe and reasonable. As a biological monitoring index, the levels of fluoride in serum may be more useful than that in urine in the control and prevention of endemic fluorosis.

To monitor the level of phthalates in human biological samples.The concentrations of three commonly-used phthalate (di-ethyl phthalate, DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) in the human biological samples were measured by using reversed-phase HPLC. The blood serum samples were collected from 52 women and 8 men, semen specimens from 36 men, and fat samples from 6 women and 5 men. All these people were randomly selected, from 23 to 50 years of age and residing in Shanghai. We also measured hormone levels of serum and conventional indices of semen specimens.The three phthalates were detected in most of the biological samples, with median levels of 5.71 mg/L (ND-37.91 mg/L) in blood serum, 0.30 mg/L (0.08 -1.32 mg/L) in semen specimens, and 0.72 mg/kg (ND-2.19 mg/kg) in fat samples. The spearman correlation coefficients between concentrations of phthalates and levels of hormone in serum were 0.442 for DBP and E(2), and -0.486 for DEP and testosterone. There was a positive association between liquefied time of semen and semen concentrations of phthalates. The correlation coefficients were 0.456 for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no significant difference between semen concentrations of phthalates and sperm density.These results suggest that people residing in Shanghai area are exposed to phthalates (particularly to DBP and DEHP) though the level is still relatively low.

Using case-crossover design to estimate the acute effect of ambient air pollution on daily mortality in Shanghai, and to explore the applicability of if in studying the acute health effects of air pollution.Case-crossover technique was used to evaluate the relationship between air pollution and daily mortality from June 2000 to December 2001 in Shanghai. The results of the bi-directional control sampling approach were compared with unidirectional approach.The validity of relative risks in case-crossover studies varied greatly depending on the strategy used in control sampling. When a bi-directional six control sampling approach was used an increase of relative risk of non-accident mortality on each 10 micro g/m(3) over a 48-hr moving average of PM(10), SO(2) and NO(2) corresponds to 1.003 (95% CI: 1.001 - 1.005), 1.016 (95% CI: 1.011 - 1.021), and 1.020 (95% CI: 1.012 - 1.027) respectively was seen.The results reinforced the deleterious role of current air pollution level on human health in Shanghai, and provided information on the applicability of case-crossover design in studying the acute health effects of air pollution.

To investigate the association between temperature and daily mortality in Shanghai from June 1, 2000 to December 31, 2001.Time-series approach was used to estimate the effect of temperature on daily total and cause-specific mortality. We fitted generalized additive Poisson regression using non-parametric smooth functions to control for long-term time trend, season and other variables. We also controlled for day of the week.A gently sloping V-like relationship between total mortality and temperature was found, with an optimum temperature (e.g. temperature with lowest mortality risk) value of 26.7 degrees C in Shanghai. For temperatures above the optimum value, total mortality increased by 0.73% for each degree Celsius increase; while for temperature below the optimum value, total mortality decreased by 1.21% for each degree Celsius increase.Our findings indicate that temperature has an effect on daily mortality in Shanghai, and the time-series approach is a useful tool for studying the temperature-mortality association.

Pulmonary macrophages ingest particles deposited onto lung surfaces from inhaled air. We describe an in vitro assay which examines the ability of these cells to ingest colloidal gold (198-Aulabelled). This system presents particles to the macrophage at a rate greater than possible when using larger beads. Macrophages were lavaged from Syrian golden hamster lungs, and aliquots of cells were incubated in suspension with colloidal gold in concentrations from 0.1 to 10.0 μg/ml. Cell-associated particles were separated from free particles by filtration. Uptake of gold was linear in time, and endocytosis as a function of particle concentration followed saturation kinetics with Vmax = 53 part/cell/min and KM = 4.1 part/pl. Electron microscopy showed gold internalized as individual particles within small vesicles, and incubation with trypsin (0.5%) failed to release the gold. Endocytosis was inhibited by incubation at 0 °C and by the addition of sodium azide, dinitrophenol, N-ethylmaleimide, iodoacetic acid, cytochalasin B (CB), and colchicine. For this incubation system, we calculated the number of collisions between cells and colloidal gold (30 nm) as compared with cells and large particles (3 μm latex). The collision rate of 3 μm latex beads with cells is nearly equal to the measured uptake rate. Hence endocytosis of large particles in suspension may be limited by presentation of particles to cells and not macrophage ability. However, for colloidal gold, the number of collisions exceeds the uptake rate by two orders of magnitude, suggesting that here the endocytic capacity of the cells is rate-limiting.