Fine particulate matter is a potential determinant of Alzheimer's disease: A systemic review and meta-analysis.

Air pollution is a modifiable and preventable factor, and it is a possible risk factor for dementia. However, evidence from epidemiological studies is still limited. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence for long-term effects of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) on dementia/Alzheimer's disease (AD). Our inclusion criteria for eligible studies were: longitudinal cohort study design, no overlap in study population, age of study subject ≥50 years, detailed description of exposure assessment for PM2.5, outdoor assessment of exposure to PM2.5, usage of a clear definition of dementia/AD, and accessibility of sufficient information for meta-analysis. Six databases were searched for eligible studies. The random-effect model was used to synthesize the associations between PM2.5 and dementia. After exclusion of all irrelevant studies, we analyzed the results of four cohort studies conducted in Canada, Taiwan, the UK, and the US during 2015-2018 among more than 12 million elderly subjects aged ≥50 years (N = 12,119,853). Our meta-analysis reveals that exposure to a 10 µg/m3 increase in PM2.5 was significantly and positively associated with dementia (pooled HR = 3.26, 95% CI: 1.20, 5.31). In subgroup analyses, exposure to a 10 µg/m3 increase in PM2.5 was found to be positively associated with AD (pooled HR = 4.82, 95% CI: 2.28, 7.36). Analysis of current epidemiological research on PM2.5 and dementia confirmed that exposure to PM2.5 was positively associated with a higher risk for dementia. However, it is to be noted that the included studies mainly relied on claim-based diagnosis and showed large differences in methods of exposure assessment, hence further epidemiological studies with well validated outcomes and with standardized exposure assessment models are required to ascertain the relationship between PM2.5 and dementia/AD.

Relationship between dioxin and steroid hormones in sera of Vietnamese men.

A recent study found an inverse correlation between serum TCDD levels and serum testosterone in the US veterans, while there is little known on the dioxin and steroid hormones about Vietnamese men. We collected blood samples from 48 men who had resided in a hotspot when exposure happened and 38 men in a non-sprayed area. Some steroid hormones levels showed significant differences between two areas. There were no correlations between steroid hormones and dioxin TEQ, after ajusting for age and other factors. Our findings indicate that steroid hormones of Vietnamese men did not correlate with dioxin TEQ in two areas.

Current Situation and Causes Analysis of Cadmium Pollution in the Kakehashi River Basin.

Cadmium (Cd) pollution is a public environmental problem worthy of attention. Long-term exposure to Cd may have adverse effects on human health. Our previous study showed that urinary concentration of Cd (U-Cd) in the residents decreased when Cd-polluted paddy soil was removed. However, from 2008 to 2014, the concentration of U-Cd increased. At the same time, the concentration of urinary ß2-microglobulin (ß2-MG), which is considered to be an early sign of cadmium-induced renal dysfunction, increased continuously. To find the cause of elevated urinary cadmium (U-Cd) in residents of cadmium-contaminated areas, we measured the concentration of cadmium in the blood (B-Cd) of 29 elderly residents (15 female and 14 male) and edible rice (R-Cd), and correlations between R-Cd, B-Cd, and U-Cd were analyzed in the formerly cadmium-polluted areas (the Kakehashi River basin). In 2016, we collected blood, urine, and rice samples from each participant. The analysis showed a significant correlation between age and B-Cd, U-Cd, and ß2-MG. However, there was no significant correlation between R-Cd and U-Cd, B-Cd, or ß2-MG concentrations. Although we found a slightly higher level of Cd in rice and urine than reported in 2008, we cannot be sure that it indicates an increased Cd contamination in the Kakehashi River basin because larger studies are required for such a conclusion. The increased urinary Cd concentrations in this area may be because Cd in tissues and organs returns to blood and urine as participants age, which leads to an increasing trend.

A 30-year follow-up study in a former cadmium-polluted area of Japan: the relationship between cadmium exposure and ß2-microglobulin in the urine of Japanese people.

Cadmium (Cd) is an environmental pollutant. Long-term exposure to Cd may lead to adverse health effects in humans. Our epidemiological studies showed that urinary Cd (U-Cd) concentrations increased from 2008 through 2014, although they decreased from 1986 through 2008. The aim of this study was to elucidate the long-term effects of the changing trend of cadmium exposure levels (U-Cd) on residents' renal function within 30 years after Cd exposure ceased. In 2016, urine samples were collected from each subject by visiting 20 elderly Japanese people (9 females and 11 males) living in the Kakehashi River basin, a previously Cd-polluted area in Ishikawa, Japan. The geometric means of the ß2-microglobulin (ß2-MG) and urinary Cd (U-Cd) continued to increase from 2014 until 2016. Furthermore, Cd concentration and ß2-MG in urine were still higher than those in the non-polluted areas in Japan. Multivariate linear regression was performed to associate ß2-MG (dependent variable) and U-Cd with sex and age (independent variables). Significant correlations were found among age, U-Cd, and ß2-MG, and these were clearer in females than in males. In summary, we propose that three decades after Cd exposure ceased, age is associated with ß2-MG more strongly than Cd for bodily impact. Moreover, renal tubular dysfunction is irreversible and worsens after exposure to Cd, with females being more sensitive to exposure.

Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children.

BACKGROUND: Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated. METHODS: Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone. RESULTS: The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (ß = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures. SIGNIFICANCE: Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels. IMPACT STATEMENT: Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children's health in e-waste areas are needed.

Prenatal Exposure to Heavy Metals and Adverse Birth Outcomes: Evidence From an E-Waste Area in China.

Electronic waste that has not been properly treated can lead to environmental contamination including of heavy metals, which can pose risks to human health. Infants, a sensitive group, are highly susceptible to heavy metals exposure. The aim of this study was to investigate the association between prenatal heavy metal exposure and infant birth outcomes in an e-waste recycling area in China. We analyzed cadmium (Cd), chromium (Cr), manganese (Mn), lead (Pb), copper (Cu), and arsenic (As) concentrations in 102 human milk samples collected 4 weeks after delivery. The results showed that 34.3% of participants for Cr, which exceeds the World Health Organization (WHO) guidelines, as well as the mean exposure of Cr exceeded the WHO guidelines. We collected data on the birth weight (BW) and length of infants and analyzed the association between metal concentration in human milk and birth outcomes using multivariable linear regression. We observed a significant negative association between the Cd concentration in maternal milk and BW in female infants (ß = -162.72, 95% CI = -303.16, -22.25). In contrast, heavy metals did not associate with birth outcomes in male infants. In this study, we found that 34.3% of participants in an e-waste recycling area had a Cr concentration that exceeded WHO guidelines, and there was a significant negative association between prenatal exposure to the Cd and infant BW in females. These results suggest that prenatal exposure to heavy metals in e-waste recycling areas may lead to adverse birth outcomes, especially for female infants.

Relationship between dioxins and steroid hormone in 6-year-olds: A follow-up study in an e-waste region of China.

We conducted a follow-up observational study on the effects of dioxin exposure on the synthesis of steroid hormones in infants during the perinatal period. The participants included 42 pairs of mothers and infants that were previously studied in 2015. We analyzed four types of steroid hormones including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA) in the serum samples of 6-year-olds and the concentration of dioxins in breast milk. A multivariate linear regression was performed to associate steroid hormones (dependent variables) and dioxins with the body mass index (BMI), sex, age, and residence of participants (independent variables). The results were reported as ß (standardized coefficient) and p-values. We found that dioxins have a significant negative correlation with DHEA and A-dione but no significant relationship with progesterone and testosterone. However, in previous studies, we found that testosterone and progesterone levels were significantly related to dioxins in 4-year-olds. We concluded that dioxins can affect the level of steroid hormones, but their effects fluctuate, and the harm caused by dioxins in children requires further long-term monitoring.

Evaluating postnatal exposure to six heavy metals in a Chinese e-waste recycling area.

This study is the first to assess postnatal exposure to heavy metals using breast milk in an electronic waste (e-waste) recycling area. From January to April 2021, 102 and 97 breastfeeding women were recruited from an e-waste recycling area and a control area, respectively. Four weeks after delivery, medical staff collected 20 mL of breast milk from each participant. The breast milk was tested for six heavy metals (lead, cadmium, chromium, arsenic, copper, and manganese) using inductively coupled plasma mass spectrometry (ICP-MS). The estimated daily intake (EDI) of infants during breastfeeding was calculated to assess the impact of postnatal exposure to heavy metals on infant health. The concentrations of chromium and lead in the breast milk were significantly higher in the e-waste recycling area than in the control area. Chromium concentrations in breast milk was 34.3%, exceeding the permissible limits set by the World Health Organization (WHO), in the e-waste recycling area, which is 16 times higher than that in the control areas. The EDIs of lead and chromium in the e-waste area were twice as those in the control area. This strongly indicates that the potential impact of postnatal exposure to lead and chromium on infant and child health in e-waste recycling areas cannot be ignored. Infants and children in e-waste recycling areas are at risk of long-term exposure to heavy metals. Therefore, ongoing health monitoring is necessary.

Cold Spells and Cause-Specific Mortality in 47 Japanese Prefectures: A Systematic Evaluation.

BACKGROUND: Many studies have investigated the devastating health effects of heat waves, but less is known about health risks related to cold spells, despite evidence that extreme cold may contribute to a larger proportion of deaths. OBJECTIVES: We aimed to systematically investigate the association between cold spells and mortality in Japan. METHODS: Daily data for weather conditions and 12 common causes of death during the 1972-2015 cold seasons (November-March) were obtained from 47 Japanese prefectures. Cold spells were defined as ≥2 consecutive days with daily mean temperatures ≤5th percentile for the cold season in each prefecture. Quasi-Poisson regression was combined with a distributed lag model to estimate prefecture-specific associations, and pooled associations at the national level were obtained through random-effects meta-analysis. The potential influence of cold spell characteristics (intensity, duration, and timing in season) on associations between cold spells and mortality was examined using a similar two-stage approach. Temporal trends were investigated using a meta-regression model. RESULTS: A total of 18,139,498 deaths were recorded during study period. Mortality was significantly higher during cold spell days vs. other days for all selected causes of death. Mortality due to age-related physical debilitation was more strongly associated with cold spells than with other causes of death. Associations between cold spells and mortality from all causes and several more specific outcomes were stronger for longer and more intense cold spells and for cold spells earlier in the cold season. However, although all outcomes were positively associated with cold spell duration, findings for cold spell intensity and seasonal timing were heterogeneous across the outcomes. Associations between cold spells and mortality due to cerebrovascular disease, cerebral infarction, and age-related physical debility decreased in magnitude over time, whereas temporal trends were relatively flat for all-cause mortality and other outcomes. DISCUSSION: Our findings may have implications for establishing tailored public health strategies to prevent avoidable cold spell-related health consequences. https://doi.org/10.1289/EHP7109.

The relationship between cadmium exposure and renal volume in inhabitants of a cadmium-polluted area of Japan.

This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-ß-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

Dioxins in breast milk of Chinese mothers: A survey 40 years after the e-waste recycling activities.

In the past two decades, numerous studies on dioxin concentrations in breast milk have been conducted in China. However, information concerning dioxin concentrations in breast milk from women living in e-waste recycling sites remains limited. Thus, this study aimed to evaluate health risk owing dioxin intake in e-waste recycling areas in China. In 2015, 42 mothers were recruited from an e-waste recycling site, and the same number of mothers were recruited from a reference site. We collected 10-mL breast milk samples from each participant. Breast milk concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs) were significantly higher in the exposed group than in the reference group. The total toxic equivalents (TEQ) of PCDDs/DFs were 9.68 pg/g lipid in the exposed group, a value two times higher than those in the reference group (4.18 pg/g lipid). The estimated daily intake (EDI) of PCDD/DFs was calculated to assess the risk of dioxins through breastfeeding. The infant EDI level was two times higher in the exposed group (54.21 pg TEQ/kg body wt/day) than in the reference group (23.41 pg TEQ/kg body wt/day). Our findings suggest that mothers and their breastfeeding infants living in an e-waste recycling site were exposed to higher dioxin concentrations than those living in a reference site.

The relationship between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children at an e-waste region in China.

Perinatal exposure to dioxins affects steroid hormone synthesis. The purpose of the present study was to evaluate the associations between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children from an e-waste recycling region in China. In the present study, we enrolled 50 pairs of mothers and infants from the Taizhou, Luqiao region in 2015. Of the 50 pairs of mothers and infants, 42 pairs participated in this study when the children were 4 years old. We measured breast milk dioxin concentrations using high-resolution gas chromatography/mass spectrometry. Additionally, we used liquid chromatography-tandem mass spectrometry to measure the concentrations of progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA) in serum samples from the 4-year-old children. We used multivariate linear regressions to assess the associations between dioxin congeners and steroid hormones. Results were reported as beta estimates and 95% confidence intervals by bootstrapping. We observed sex-related differences between breast milk dioxins and serum steroid hormone levels in 4-year-old children. An increase in breast milk dioxins was associated with a decrease in testosterone in serum samples from boys. Similarly, an increase in breast milk dioxins was associated with a decrease in progesterone levels in serum samples from girls. However, dioxins were not associated with changes in the levels of testosterone, DHEA, or A-dione in girls. Based on these results, we conclude that perinatal exposure to dioxins modifies steroidogenesis in preschool-aged children. However, the long-term impact of dioxins requires further large-scale studies to assess these effects in school-going children and adolescents.

The association between dioxins and steroid hormones in general adult males: a cross-sectional study in an e-waste region of China.

As observed among residents in electronic waste (e-waste) recycling areas, dioxins can disrupt the homeostasis of endocrine hormones and the balance of thyroid hormones. Few studies, however, have examined whether e-waste recycling activities influence steroid hormone equilibrium in the general adult male population. This study evaluated the association between steroid hormones and the physical burdens of dioxins in the general adult male population residing in an e-waste region. In September 2017, 74 adult males residing in an e-waste dismantling region were enrolled in the current study. Approximately 10 mL of blood was collected from each adult male, and the serum samples were separated through centrifugation. Then, the levels of dioxin and steroid hormones in the serum of the participants were measured. We treated dioxin levels as categorical variables in the general linear model according to quartiles (25, 50, and 75 percentile). Comparing the findings with a reference group (< 25th percentile), we noted significantly higher dehydroepiandrosterone (DHEA) level in men with low serum polychlorinated dibenzofuran-toxic equivalent (PCDFs-TEQ) level between 3.80 and 6.31 pg/g lipid (1933 vs. 1447 pg/ml) and low polychlorinated dibenzo-p-dioxins and dibenzofurans-TEQ (PCDD/PCDFs-TEQ) between 8.57 and 15.11 pg/g lipid (1996 vs. 1360 pg/ml). Moreover, a significantly higher androstenedione (A-dione) level was found in men whose serum PCDFs-TEQ ≥ 11.34 pg/g lipd (2404 vs. 1848). What's more, there were significantly higher 3ß-hydroxysteroid dehydrogenase (3ß-HSD) concentrations in low- and high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) groups (1.30-1.67 and ≥ 2.64 pg-TEQ/g lipid, respectively with 719 and 807 vs. 496, respectively). Our findings suggest that specific dioxin exposure may disturb normal DHEA, A-dione levels, and enzyme activity in the general adult male population in an e-waste region of China.

Association of dioxin in maternal breast milk and salivary steroid hormone levels in preschool children: A five-year follow-up study of a Vietnam cohort.

Recent studies have found elevated dioxin levels inside some former US military air bases in Vietnam, known as hotspots. The aim of the present study was to evaluate the association of dioxin exposure and steroid hormone in preschool children in Vietnam. In 2010, 2011, 52 primiparae mother-infant pairs in the hotspot and 52 pairs in a non-exposure region were enrolled. For the final analysis, 26 vs 26 pairs were selected, who participated at all three surveys. Univariable and multivariable linear regressions were used to evaluate associations between hormone and dioxin congeners. Geometric mean total TEQ of PCDD/DFs in the hotspot were significantly higher than in the non-exposure region, 8.7 and 3.4 pg TEQ/g lipid, respectively. In the hotspot, salivary dehydroepiandrosterone (DHEA) was significantly higher in 1-year-old children (Boys = 123 pg/mL, Girls = 120 pg/mL) than in the non-exposure region (Boys = 28 pg/mL, Girls = 27 pg/mL). In contrast, DHEA was significantly lower in 5-year-old children (Boys = 70 pg/mL, Girls = 106 pg/mL) in the hotspot than in the non-exposure region (Boys = 496 pg/mL, Girls = 654 pg/mL). Salivary testosterone was significantly lower in the hotspot (Boys = 1.9 pg/mL, Girls = 1.9 pg/m; Boys = 1.0 pg/mL, Girls = 1.1 pg/mL, respectively) than in the non-exposure region (Boys = 3.7 pg/mL, Girls = 3.8 pg/m; Boys = 5.7 pg/mL, Girls = 7.0 pg/mL, respectively) at 3 years and 5 years of age. Higher levels of highly chlorinated dioxins in breast milk were associated with higher DHEA in 1-year-old and lower DHEA and testosterone levels in 5-year-old children. Our findings indicated that dioxins were associated with changes of DHEA and testosterone levels in preschool Vietnamese children.

Effects of perinatal dioxin exposure on development of children: a 3-year follow-up study of China cohort.

The purpose of this study was to investigate the longitudinal effects of perinatal exposure to dioxin on physical growth in a 3-year follow-up study. In 2015, 27 mother-infant pairs living in an electronic waste (e-waste) dismantling region and 35 pairs living in a control region were enrolled in the present study. Breast milk samples were collected at 4 weeks after birth. Physical growth, including weight, height, and head and chest circumferences, was measured at 6 months and 3 years of age. Dioxin levels in the breast milk were measured by gas chromatography/high-resolution mass spectrometry. Levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and toxic equivalency values in maternal breast milk of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCDDs/PCDFs were significantly higher in women residing in the e-waste dismantling region. In 3-year-old boys, inverse associations were found between height and PCDDs-TEQ. In girls, positive associations were found between height and 2,3,7,8-TetraCDD, PCDDs-TEQ, and PCDDs/PCDFs-TEQ, and for weight and PCDDs-TEQ and PCDDs/PCDFs-TEQ at 3 years of age. In this study, sex-specific differences were observed in children, in whom dioxin exposure decreased growth in boys but increased growth in girls during the first 3 years of life.

The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men.

Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56-81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5-11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3ß-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3ß-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3ß-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels >3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further.

Influence of dioxin exposure upon levels of prostate-specific antigen and steroid hormones in Vietnamese men.

Most studies on the relationship between Agent Orange and prostate cancer have focused on US veterans of the Vietnam War. There have been few studies focusing on the relationship between levels of prostate-specific antigen (PSA) and dioxins or steroid hormones in Vietnamese men. In 2009-2011, we collected blood samples from 97 men who had resided in a "dioxin hotspot" and 85 men from a non-sprayed region in Vietnam. Then levels of PSA, dioxins, and steroid hormones were analyzed. Levels of most dioxins, furans, and non-ortho polychlorinated biphenyls were higher in the hotspot than those in the non-sprayed region. Levels of testosterone, dehydroepiandrosterone, and estradiol differed significantly between the hotspot and the non-sprayed region, but there were no correlations between levels of PSA and steroid hormones and dioxins in either of the two regions. Our findings suggest that PSA levels in Vietnamese men are not associated with levels of dioxin or steroid hormones in these two regions.