Historical Prediction Modeling Approach for Estimating Long-Term Concentrations of PM _2.5 in Cohort Studies before the 1999 Implementation of Widespread Monitoring

Kim, Sun-Young,Olives, Casey,Sheppard, Lianne,Sampson, Paul D.,Larson, Timothy V.,Keller, Joshua P.,Kaufman, Joel D. National Institute of Environmental Health Science 2017 Environmental health perspectives Vol.125 No.1

<P><B>Introduction:</B></P><P>Recent cohort studies have used exposure prediction models to estimate the association between long-term residential concentrations of fine particulate matter (PM2.5) and health. Because these prediction models rely on PM2.5 monitoring data, predictions for times before extensive spatial monitoring present a challenge to understanding long-term exposure effects. The U.S. Environmental Protection Agency (EPA) Federal Reference Method (FRM) network for PM2.5 was established in 1999.</P><P><B>Objectives:</B></P><P>We evaluated a novel statistical approach to produce high-quality exposure predictions from 1980 through 2010 in the continental United States for epidemiological applications.</P><P><B>Methods:</B></P><P>We developed spatio-temporal prediction models using geographic predictors and annual average PM2.5 data from 1999 through 2010 from the FRM and the Interagency Monitoring of Protected Visual Environments (IMPROVE) networks. Temporal trends before 1999 were estimated by using a) extrapolation based on PM2.5 data in FRM/IMPROVE, b) PM2.5 sulfate data in the Clean Air Status and Trends Network, and c) visibility data across the Weather Bureau Army Navy network. We validated the models using PM2.5 data collected before 1999 from IMPROVE, California Air Resources Board dichotomous sampler monitoring (CARB dichot), the Children’s Health Study (CHS), and the Inhalable Particulate Network (IPN).</P><P><B>Results:</B></P><P>In our validation using pre-1999 data, the prediction model performed well across three trend estimation approaches when validated using IMPROVE and CHS data (R2 = 0.84–0.91) with lower R2 values in early years. Model performance using CARB dichot and IPN data was worse (R2 = 0.00–0.85) most likely because of fewer monitoring sites and inconsistent sampling methods.</P><P><B>Conclusions:</B></P><P>Our prediction modeling approach will allow health effects estimation associated with long-term exposures to PM2.5 over extended time periods ≤ 30 years.</P><P><B>Citation:</B></P><P>Kim SY, Olives C, Sheppard L, Sampson PD, Larson TV, Keller JP, Kaufman JD. 2017. Historical prediction modeling approach for estimating long-term concentrations of PM2.5 in cohort studies before the 1999 implementation of widespread monitoring. Environ Health Perspect 125:38–46; http://dx.doi.org/10.1289/EHP131</P>

Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic

Lind, Lars,Lind, P. Monica,Lejonklou, Margareta H.,Dunder, Linda,Bergman, Å,ke,Guerrero-Bosagna, Carlos,Lampa, Erik,Lee, Hong Kyu,Legler, Juliette,Nadal, Angel,Pak, Youngmi Kim,Phipps, Richard P. National Institute of Environmental Health Science 2016 Environmental health perspectives Vol.124 No.5

<P>Summary: From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8–9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.</P>

Long-Term Fine Particulate Matter Exposure and Major Depressive Disorder in a Community-Based Urban Cohort

Kim, Kyoung-Nam,Lim, Youn-Hee,Bae, Hyun Joo,Kim, Myounghee,Jung, Kweon,Hong, Yun-Chul National Institute of Environmental Health Science 2016 Environmental health perspectives Vol.124 No.10

<P><B>Background:</B></P><P>Previous studies have associated short-term air pollution exposure with depression. Although an animal study showed an association between long-term exposure to particulate matter ≤ 2.5 μm (PM2.5) and depression, epidemiological studies assessing the long-term association are scarce.</P><P><B>Objective:</B></P><P>We aimed to determine the association between long-term PM2.5 exposure and major depressive disorder (MDD).</P><P><B>Methods:</B></P><P>A total of 27,270 participants 15–79 years of age who maintained an address within the same districts in Seoul, Republic of Korea, throughout the entire study period (between 2002 and 2010) and without a previous MDD diagnosis were analyzed. We used three district-specific exposure indices as measures of long-term PM2.5 exposure. Cox proportional hazards models adjusted for potential confounding factors and measured at district and individual levels were constructed. We further conducted stratified analyses according to underlying chronic diseases such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary disease.</P><P><B>Results:</B></P><P>The risk of MDD during the follow-up period (2008–2010) increased with an increase of 10 μg/m3 in PM2.5 in 2007 [hazard ratio (HR) = 1.44; 95% CI: 1.17, 1.78], PM2.5 between 2007 and 2010 (HR = 1.59; 95% CI: 1.02, 2.49), and 12-month moving average of PM2.5 until an event or censor (HR = 1.47; 95% CI: 1.14, 1.90). The association between long-term PM2.5 exposure and MDD was greater in participants with underlying chronic diseases than in participants without these diseases.</P><P><B>Conclusion:</B></P><P>Long-term PM2.5 exposure increased the risk of MDD among the general population. Individuals with underlying chronic diseases are more vulnerable to long-term PM2.5 exposure.</P><P><B>Citation:</B></P><P>Kim KN, Lim YH, Bae HJ, Kim M, Jung K, Hong YC. 2016. Long-term fine particulate matter exposure and major depressive disorder in a community-based urban cohort. Environ Health Perspect 124:1547–1553; http://dx.doi.org/10.1289/EHP192</P>

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Cho, Soo-Churl,Bhang, Soo-Young,Hong, Yun-Chul,Shin, Min-Sup,Kim, Boong-Nyun,Kim, Jae-Won,Yoo, Hee-Jung,Cho, In Hee,Kim, Hyo-Won National Institute of Environmental Health Science 2010 Environmental health perspectives Vol.118 No.7

<P><B>Background</B></P><P>Concern over phthalates has emerged because of their potential toxicity to humans.</P><P><B>Objective</B></P><P>We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.</P><P><B>Methods</B></P><P>This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.</P><P><B>Results</B></P><P>We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-<I>n</I>-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.</P><P><B>Conclusion</B></P><P>Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.</P>

The Protective Mechanism of Antioxidants in Cadmium-Induced Ototoxicity <i>in Vitro</i> and <i>in Vivo</i>

Kim, Su-Jin,Jeong, Hyun-Ja,Myung, Noh-Yil,Kim, Min-chol,Lee, Jeong-Han,So, Hong-seob,Park, Rae-Kil,Kim, Hyung-Min,Um, Jae-Young,Hong, Seung-Heon National Institute of Environmental Health Science 2008 Environmental health perspectives Vol.116 No.7

<P><B>Background</B></P><P>Several heavy metals have been shown to have toxic effects on the peripheral and central auditory system. Cadmium (Cd<SUP>2+</SUP>) is an environmental contaminant showing a variety of adverse effects. Given the current rate of release into the environment, the amount of Cd<SUP>2+</SUP> present in the human body and the incidence of Cd<SUP>2+</SUP>-related diseases are expected to increase.</P><P><B>Objective</B></P><P>The overall aim of this study was to gain further insights into the mechanism of Cd<SUP>2+</SUP>-induced ototoxicity.</P><P><B>Methods</B></P><P>Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse cochlea after Cd<SUP>2+</SUP> exposure were measured by flow cytometry, immunohistochemical staining, Western blot analysis, and auditory brainstem response (ABR) recording. Mechanisms underlying Cd<SUP>2+</SUP>ototoxicity were studied using inhibitors of different signaling pathways, caspases, and antioxidants.</P><P><B>Results</B></P><P>Cd<SUP>2+</SUP> exposure caused cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK activation, apoptosis, and finally auditory threshold shift. Cd<SUP>2+</SUP> toxicity interfered with inhibitors of cellular signaling pathways, such as ERK and c-<I>jun N</I>-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase-9 and caspase-3. The antioxidants <I>N</I>-acetyl-<SMALL>L</SMALL>-cysteine and ebselen showed a significant protective effect on the Cd<SUP>2+</SUP> toxicity.</P><P><B>Conlcusions</B></P><P>Cd<SUP>2+</SUP> is ototoxic with a complex underlying mechanism. However, ROS generation may be the cause of the toxicity, and application of antioxidants can prevent the toxic effect.</P>

Interaction between <i>GSTM1</i> / <i>GSTT1</i> Polymorphism and Blood Mercury on Birth Weight

Lee, Bo-Eun,Hong, Yun-Chul,Park, Hyesook,Ha, Mina,Koo, Bon Sang,Chang, Namsoo,Roh, Young-Man,Kim, Boong-Nyun,Kim, Young-Ju,Kim, Byung-Mi,Jo, Seong-Joon,Ha, Eun-Hee National Institute of Environmental Health Science 2010 Environmental health perspectives Vol.118 No.3

<P><B>Background</B></P><P>Mercury (Hg) is toxic to both the reproductive and nervous systems. In addition, glutathione <I>S</I>-transferases (GSTs), which conjugate glutathione to a variety of electrophilic compounds, are involved in the detoxification of Hg.</P><P><B>Objective</B></P><P>In this study we examined the association between prenatal exposure to Hg and birth weight as well as the influence of GST polymorphisms.</P><P><B>Methods</B></P><P>The total Hg concentration in maternal and cord blood was measured from 417 Korean women and newborns in the Mothers and Children’s Environmental Health study from 2006 to 2008. Information on birth weight was collected from the patients’ medical records. The genotyping of glutathione <I>S</I>-transferase M1 (<I>GSTM1</I>) and glutathione <I>S</I>-transferase T1 (<I>GSTT1</I>) polymorphisms was carried out using polymerase chain reaction. Regression analysis was performed to determine the association between the blood Hg concentration and birth weight in mothers with <I>GSTM1</I> and <I>GSTT1</I> polymorphisms.</P><P><B>Results</B></P><P>The geometric mean levels of Hg in the maternal blood during late pregnancy and in cord blood were 3.30 μg/L and 5.53 μg/L, respectively. For mothers with the <I>GSTT1</I> null genotype, elevated Hg levels in maternal blood during late pregnancy were associated with an increased risk of lower birth weight. For mothers with both <I>GSTM1</I> and <I>GSTT1</I> null genotype, both maternal and cord blood Hg levels were associated with lower birth weight.</P><P><B>Conclusions</B></P><P>This study suggests that the interactions of Hg with <I>GSTM1</I> and <I>GSTT1</I> polymorphisms play a role in reducing birth weight.</P>

Benzo[ <i>a</i> ]pyrene Reduces Testosterone Production in Rat Leydig Cells via a Direct Disturbance of Testicular Steroidogenic Machinery

Chung, Jin-Yong,Kim, Yoon-Jae,Kim, Ji Young,Lee, Seung Gee,Park, Ji-Eun,Kim, Won Rok,Yoon, Yong-Dal,Yoo, Ki Soo,Yoo, Young Hyun,Kim, Jong-Min National Institute of Environmental Health Science 2011 Environmental health perspectives Vol.119 No.11

<P>Background: Benzo[<I>a</I>]pyrene (B[<I>a</I>]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells.</P><P>Objective: We hypothesized that long-term exposure to low concentrations of B[<I>a</I>]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins.</P><P>Results: Oral exposure to B[<I>a</I>]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[<I>a</I>]P <I>in vivo</I> produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate <I>in vitro</I>. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[<I>a</I>]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[<I>a</I>]P can negatively target 3β-HSD, which is required for testosterone production.</P><P>Conclusions: B[<I>a</I>]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[<I>a</I>]P or other PAHs.</P>

Bisphenol A Exposure during Adulthood Causes Augmentation of Follicular Atresia and Luteal Regression by Decreasing 17β-Estradiol Synthesis via Downregulation of Aromatase in Rat Ovary

Lee, Seung Gee,Kim, Ji Young,Chung, Jin-Yong,Kim, Yoon-Jae,Park, Ji-Eun,Oh, Seunghoon,Yoon, Yong-Dal,Yoo, Ki Soo,Yoo, Young Hyun,Kim, Jong-Min National Institute of Environmental Health Science 2013 Environmental health perspectives Vol.121 No.6

<P>Background: Bisphenol A (BPA) has been detected in human body fluids, such as serum and ovarian follicular fluids. Several reports indicated that BPA exposure is associated with the occurrence of several female reproductive diseases resulting from the disruption of steroid hormone biosynthesis in the adult ovary.</P><P>Objective: We hypothesized that long-term exposure to low concentrations of BPA disrupts 17β-estradiol (E2) production in granulosa cells via an alteration of steroidogenic proteins in ovarian cells.</P><P>Methods: Adult female rats received BPA for 90 days by daily gavage at doses of 0, 0.001, or 0.1 mg/kg body weight. We determined serum levels of E2, testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). We also analyzed the expressions of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase isomerase (3β-HSD), and aromatase cytochrome P450 (P450arom) in the ovary.</P><P>Results: Exposure to BPA significantly decreased E2 serum concentration, which was accompanied by augmented follicular atresia and luteal regression via increase of caspase-3–associated apoptosis in ovarian cells. After BPA exposure, P450arom and StAR protein levels were significantly decreased in granulosa cells and theca-interstitial (T-I) cells, respectively. However, P450scc and 3β-HSD protein levels remained unchanged. The increase in LH levels appeared to be associated with the decreased synthesis of T in T-I cells after BPA exposure via homeostatic positive feedback regulation.</P><P>Conclusions: BPA exposure during adulthood can disturb the maintenance of normal ovarian functions by reducing E2. The steroidogenic proteins StAR and P450arom appear to be targeted by BPA.</P>

Metals in Particulate Pollutants Affect Peak Expiratory Flow of Schoolchildren

Hong, Yun-Chul,Hwang, Seung-Sik,Kim, Jin Hee,Lee, Kyoung-Ho,Lee, Hyun-Jung,Lee, Kwan-Hee,Yu, Seung-Do,Kim, Dae-Seon National Institute of Environmental Health Science 2007 Environmental health perspectives Vol.115 No.3

<P><B>Background</B></P><P>The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Moreover, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function.</P><P><B>Objectives</B></P><P>This study was conducted to assess lung function decrement associated with metal components in particulate pollutants and genetic polymorphisms of glutathione <I>S-</I>transferase M1 and T1.</P><P><B>Methods</B></P><P>We studied 43 schoolchildren who were in the 3rd to 6th grades. Each student measured peak expiratory flow rate three times a day for 42 days. Particulate air concentrations were monitored every day, and the concentrations of iron, manganese, lead, zinc, and aluminum in the particles were measured. Glutathione <I>S</I>-transferase M1 and T1 genetic polymorphisms were determined using DNA extracted from participant buccal washings. We used a mixed linear regression model to estimate the association between peak expiratory flow rate and particulate air pollutants.</P><P><B>Results</B></P><P>We found significant reduction in the peak expiratory flow rate after the children’s exposure to particulate pollutants. The effect was shown most significantly 1 day after exposure to the ambient particles. Manganese and lead in the particles also reduced the peak expiratory flow rate. Genetic polymorphisms of glutathione <I>S</I>-transferase M1 and T1 did not significantly affect peak expiratory flow rate.</P><P><B>Conclusions</B></P><P>This study demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of glutathione <I>S</I>-transferase.</P>

Air Pollution and Symptoms of Depression in Elderly Adults

Lim, Youn-Hee,Kim, Ho,Kim, Jin Hee,Bae, Sanghyuk,Park, Hye Yin,Hong, Yun-Chul National Institute of Environmental Health Science 2012 Environmental health perspectives Vol.120 No.7

<P>Background: Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.</P><P>Objectives: We investigated the effect of air pollution on symptoms of depression in an elderly population.</P><P>Methods: We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.</P><P>Results: SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM<SUB>10</SUB>) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0–7 day moving average of nitrogen dioxide [NO<SUB>2</SUB>; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O<SUB>3</SUB>; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.</P><P>Conclusions: Our study suggests that increases in PM<SUB>10</SUB>, NO<SUB>2</SUB>, and O<SUB>3</SUB> may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.</P>