Exposure to metal mixtures and telomere length in Bangladeshi children.

Telomere length is associated with chronic diseases and in younger populations, may represent a biomarker of disease susceptibility. As growing evidence suggests that environmental factors, including metals, may impact telomere length, we investigated the association between 17 metals measured in toenail samples and leukocyte relative telomere length (RTL), among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In single exposure linear regression models, a doubling of arsenic (As) and mercury (Hg) (µg/g) were associated with a -0.21 (95%CI: -0.032, -0.010; p=0.0005) and -0.017 (95%CI: -0.029, -0.004; p=0.006) difference in RTL, respectively. In Bayesian Kernel Machine Regression (BKMR) mixture models, the overall metal mixture was inversely associated with RTL (P-for-trend <0.001). Negative associations with RTL were observed with both log2-As and log2-Hg, while an inverted U-shaped association was observed for log2-zinc (Zn) with RTL. We found little evidence of interaction among metals. Sex-stratification identified stronger associations of the overall mixture and log2-As with RTL among females, compared to males. Our study suggests that As and Hg may independently influence RTL in mid-childhood. Further studies are needed to investigate potential long-term impacts of metal-associated telomere shortening in childhood on health outcomes in adult life.

Fish intake and mercury exposure in young children.

Fish consumption is one of the main sources of mercury (Hg) exposure, but few studies have examined Hg exposure from fish consumption among children. This study aimed to assess the frequency of fish intake and associations with Hg and other element concentrations among 700 three-year-old children from the New Hampshire Birth Cohort Study. Usual fish intake was derived from a validated food frequency questionnaire (Block Questionnaire for ages 2-7) and toenail element concentrations were determined using ICP-MS. Multiple linear regression analysis was used to assess the association between fish intake and toenail element concentrations. A mixture analysis, using Weighted quantile sum (WQS) regression, was used to estimate the relative contribution of fish consumption to element exposures. Twenty-three percent of children were reported to consume at least one fish meal/week on average during the previous 6 months. In adjusted linear regression models, children with any type of fish consumption versus no consumption had 108% (95% confidence interval (CI: 68%, 153%)) higher toenail Hg concentrations. To a lesser extent, children consuming "other fish (not fried) including tuna" and "fried fish or fish sticks" had 120% (95% CI: 82%, 164%), and 23% (95% CI: 2%, 51%) higher toenail concentrations, respectively, than those consuming no fish. Using WQS regression, Hg was the element most strongly related to fish consumption. Fish intake among young children was related to Hg exposure even at low levels of consumption. Future studies will need to determine the health consequences of this exposure.

Deciduous teeth from the New Hampshire birth cohort study: Early life environmental and dietary predictors of dentin elements.

BACKGROUND: Sparse research exists on predictors of element concentrations measured in deciduous teeth. OBJECTIVE: To estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. METHODS: Our analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. RESULTS: We measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SIGNIFICANCE: These findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

Gadolinium-based Contrast Agent Biodistribution and Speciation in Rats.

Background Gadolinium retention has been observed in organs of patients with normal renal function; however, the biodistribution and speciation of residual gadolinium is not well understood. Purpose To compare the pharmacokinetics, distribution, and speciation of four gadolinium-based contrast agents (GBCAs) in healthy rats using MRI, mass spectrometry, elemental imaging, and electron paramagnetic resonance (EPR) spectroscopy. Materials and Methods In this prospective animal study performed between November 2021 and September 2022, 32 rats received a dose of gadoterate, gadoteridol, gadobutrol, or gadobenate (2.0 mmol/kg) for 10 consecutive days. GBCA-naive rats were used as controls. Three-dimensional T1-weighted ultrashort echo time images and R2* maps of the kidneys were acquired at 3, 17, 34, and 52 days after injection. At 17 and 52 days after injection, gadolinium concentrations in 23 organ, tissue, and fluid specimens were measured with mass spectrometry; gadolinium distribution in the kidneys was evaluated using elemental imaging; and gadolinium speciation in the kidney cortex was assessed using EPR spectroscopy. Data were assessed with analysis of variance, Kruskal-Wallis test, analysis of response profiles, and Pearson correlation analysis. Results For all GBCAs, the kidney cortex exhibited higher gadolinium retention at 17 days after injection than all other specimens tested (mean range, 350-1720 nmol/g vs 0.40-401 nmol/g; P value range, .001-.70), with gadoteridol showing the lowest level of retention. Renal cortex R2* values correlated with gadolinium concentrations measured ex vivo (r = 0.95; P < .001), whereas no associations were found between T1-weighted signal intensity and ex vivo gadolinium concentration (r = 0.38; P = .10). EPR spectroscopy analysis of rat kidney cortex samples showed that all GBCAs were primarily intact at 52 days after injection. Conclusion Compared with other macrocyclic GBCAs, gadoteridol administration led to the lowest level of retention. The highest concentration of gadolinium was retained in the kidney cortex, but T1-weighted MRI was not sensitive for detecting residual gadolinium in this tissue. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Human placental microRNAs dysregulated by cadmium exposure predict neurobehavioral outcomes at birth.

BACKGROUND: Prenatal cadmium (Cd) exposure has been implicated in both placental toxicity and adverse neurobehavioral outcomes. Placental microRNAs (miRNAs) may function to developmentally program adverse pregnancy and newborn health outcomes in response to gestational Cd exposure. METHODS: In a subset of the Rhode Island Child Health Study (RICHS, n = 115) and the New Hampshire Birth Cohort Study (NHBCS, = 281), we used small RNA sequencing and trace metal analysis to identify Cd-associated expression of placental miRNAs using negative binomial generalized linear models. We predicted mRNAs targeted by Cd-associated miRNAs and relate them to neurobehavioral outcomes at birth through the integration of transcriptomic data and summary scores from the NICU Network Neurobehavioral Scale (NNNS). RESULTS: Placental Cd concentrations are significantly associated with the expression level of five placental miRNAs in NHBCS, with similar effect sizes in RICHS. These miRNA target genes overrepresented in nervous system development, and their expression is correlated with NNNS metrics suggestive of atypical neurobehavioral outcomes at birth. CONCLUSIONS: Gestational Cd exposure is associated with the expression of placental miRNAs. Predicted targets of these miRNAs are involved in nervous system development and may also regulate placental physiology, allowing their dysregulation to modify developmental programming of early life health outcomes. IMPACT: This research aims to address the poor understanding of the molecular mechanisms governing adverse pregnancy and newborn health outcomes in response to Gestational cadmium (Cd) exposure. Our results outline a robust relationship between Cd-associated placental microRNA expression and NICU Network Neurobehavioral Scales (NNNS) at birth indicative of atypical neurobehavior. This study utilized healthy mother-infant cohorts to describe the role of Cd-associated dysregulation of placental microRNAs as a potential mechanism by which adverse neurobehavioral outcomes are developmentally programmed.

Contribution of gut bacteria to arsenic metabolism in the first year of life in a prospective birth cohort.

Gut bacteria are at the interface of environmental exposures and their impact on human systems, and may alter host absorption, metabolism, and excretion of toxic chemicals. We investigated whether arsenic-metabolizing bacterial gene pathways related to urinary arsenic concentrations. In the New Hampshire Birth Cohort Study, urine and stool samples were obtained at six weeks (n = 186) and one year (n = 190) of age. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB) were quantified in infant urine samples using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Total arsenic exposure (tAs) was summarized as Σ(iAs, MMA, DMA) and log2-transformed. Fecal microbial DNA underwent metagenomic sequencing and the relative abundance of bacterial gene pathways were grouped as KEGG Orthologies (KOs) using BioBakery algorithms. Arsenic metabolism KOs with >80% prevalence were log2-transformed and modeled continuously using linear regression, those with <10% were not evaluated and those with 10-80% prevalence were analyzed dichotomously (detect/non-detect) using logistic regression. In the first set of models, tAs was regressed against KO relative abundance or detection adjusting for age at sample collection and child's sex. Effect modification by delivery mode was assessed in stratified models. In the second set of models, the association between the relative abundance/detection of the KOs and arsenic speciation (%iAs, %MMA, %DMA) was quantified with linear regression. Urinary tAs was associated with the increased relative abundance/detection odds of several arsenic-related KOs, including K16509, an arsenate reductase transcriptional regulator, with stronger associations among six-week-olds than one-year-olds. K16509 was also associated with decreased %MMA and increased %DMA at six weeks and one year. Notably, many associations were stronger among operatively-delivered than vaginally-delivered infants. Our findings suggest associations between arsenic-metabolizing bacteria in the infant gut microbiome and urinary arsenic excretion.

Association between placental toxic metal exposure and NICU Network Neurobehavioral Scales (NNNS) profiles in the Rhode Island Child Health Study (RICHS).

BACKGROUND: Prenatal exposure to heavy metals has been linked to a variety of adverse outcomes in newborn health and later life. Toxic metals such as cadmium (Cd), manganese (Mn) and lead (Pb) have been implicated to negatively affect newborn neurobehavior. Placental levels of these metals may provide additional understandings on the link between prenatal toxic metal exposures and neurobehavioral performances in newborns. OBJECTIVE: To evaluate associations between placental concentrations of toxic metals and newborn neurobehavioral performance indicated through the NICU Network Neurobehavioral Scales (NNNS) latent profiles. METHOD: In the Rhode Island Child Health Study cohort (n = 625), newborn neurobehavioral performance was assessed with NNNS, and a latent profile analysis was used to define five discrete neurobehavioral profiles based on summary scales. Using multinomial logistic regression, we determined whether increased levels of placental toxic metals Cd, Mn and Pb associated with newborns assigned to the profile demonstrating atypical neurobehavioral performances. RESULTS: Every doubling in placenta Cd concentration was associated with increased odds of newborns belonging to the atypical neurobehavior profile (OR: 2.72, 95% CI [1.09, 6.79]). Detectable placental Pb also demonstrated an increased odds of newborns assignment to the atypical profile (OR: 3.71, 95% CI [0.97, 13.96]) compared to being in the typical neurobehavioral profile. CONCLUSIONS: Toxic metals Cd and Pb measured in placental tissue may adversely impact newborn neurobehavior. Utilizing the placenta as a prenatal toxic metal exposure biomarker is useful in elucidating the associated impacts of toxic metals on newborn health.

The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice.

BACKGROUND: Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4-7 and 10-13 for 4 h/day. RESULTS: Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2. CONCLUSIONS: Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection.

Distribution and accumulation of mercury in pot-grown African rice cultivars (Oryza glaberrima Steud. and Oryza sativa L.) determined via LA-ICP-MS.

There is limited information concerning the distribution of mercury in rice, particularly in African rice. The objective was to compare the distribution of total mercury (THg) and methylmercury (MeHg) in African rice (Oryza glaberrima Steud.) and Asian rice (O. sativa L.). It is hypothesized that increased mineral accumulation and greater stress tolerance in O. glaberrima will affect the uptake and distribution of THg and MeHg, compared to O. sativa. Rice varieties from the Republic of Mali, including O. glaberrima (n =1) and O. sativa (n = 2), were cultivated in a greenhouse, in mercury-spiked soil (50 mg/kg) (n =3 replicates/variety). THg and MeHg concentrations were analyzed in the grain (brown rice), and the THg distribution was analyzed using laser ablation inductively coupled-plasma mass spectrometry (LA-ICP-MS). THg and MeHg concentrations did not differ between O. glaberrima and O. sativa grain. However, in both O. sativa varieties, THg was highly concentrated in the scutellum, which surrounds the embryo and is removed during polishing. Conversely, in O. glaberrima grain, THg was widely distributed throughout the endosperm, the edible portion of the grain. Differences in the THg distribution in O. glaberrima grain, compared to O. sativa, may elevate the risk of mercury exposure through ingestion of polished rice. The novelty of this study includes the investigation of a less-studied rice species (O. glaberrima), the use of a highly sensitive elemental imaging technique (LA-ICP-MS), and its finding of a different grain THg distribution in O. glaberrima than has been observed in O. sativa.

Quantification of local zinc and tungsten deposits in bone with LA-ICP-MS using novel hydroxyapatite-collagen calibration standards.

Tungsten has recently emerged as a potential toxicant and is known to heterogeneously deposit in bone as reactive polytungstates. Zinc, which accumulates in regions of bone remodeling, also has a heterogenous distribution in bone. Determining the local concentrations of these metals will provide valuable information about their mechanisms of uptake and action. A series of bone (BN), 7:3 hydroxyapatite:collagen (HC), and hydroxyapatite (HA) standards were spiked with tungsten and zinc and used as calibration standards for laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis of bone tissue. The analytical performance of these standards was studied and validated at different step sizes using NIST SRM 1486 Bone Meal. The effect of matrix-matched calibration was assessed by comparing the calibration with BN and HC standards, which incorporate both inorganic and organic components of bone, to that of HA standards. HC standards were found to be more homogenous (RSD < 10%) and provide a linear calibration with better accuracy (R2 > 0.994) compared to other standards. The limits of detection for HC at a 15 µm step size were determined to be 0.24 and 0.012 µg g-1 for zinc and tungsten, respectively. Using this approach, we quantitatively measured zinc and tungsten deposits in the femoral bone of a mouse exposed to 15 µg mL-1 tungsten for four weeks. Localized concentrations of zinc (942 µg g-1) and tungsten (15.7 µg g-1) at selected regions of enrichment were substantially higher than indicated by bulk measurements of these metals.

Addressing K/L-edge overlap in elemental analysis from micro-X-ray fluorescence: bioimaging of tungsten and zinc in bone tissue using synchrotron radiation and laser ablation inductively coupled plasma mass spectrometry.

Synchrotron radiation micro-X-ray fluorescence (SR-µXRF) is a powerful elemental mapping technique that has been used to map tungsten and zinc distribution in bone tissue. However, the heterogeneity of the bone samples along with overlap of the tungsten L-edge with the zinc K-edge signals complicates SR-µXRF data analysis, introduces minor artefacts into the resulting element maps, and decreases image sensitivity and resolution. To confirm and more carefully delineate these SR-µXRF results, we have employed laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to untangle the problem created by the K/L-edge overlap of the tungsten/zinc pair. While the overall elemental distribution results are consistent between the two techniques, LA-ICP-MS provides significantly higher sensitivity and image resolution compared with SR-µXRF measurements in bone. These improvements reveal tissue-specific distribution patterns of tungsten and zinc in bone, not observed using SR-µXRF. We conclude that probing elemental distribution in bone is best achieved using LA-ICP-MS, though SR-µXRF retains the advantage of being a non-destructive method with the capability of being paired with X-ray techniques, which determine speciation in situ. Since tungsten is an emerging contaminant recently found to accumulate in bone, accurately determining its distribution and speciation in situ is essential for directing toxicological studies and informing treatment regimes. Graphical abstract Tungsten and zinc localization and uptake in mouse femurs were imaged by synchrotron radiation, left, and by laser ablation ICP-MS, right. The increased resolution of the LA-ICP-MS technique resolves the problem of the overlap in tungsten's L-edge and zinc's K-edge.

Mercury and selenium concentrations, and selenium:mercury molar ratios in small cetaceans taken off St. Vincent, West Indies.

This study measured the concentration of total mercury (THg) and selenium (Se), and calculated the Se:Hg molar ratios in the muscle, blubber, liver, and kidney of small cetaceans (false killer whale, Pseudorca crassidens; killer whale, Orcinus orca; Risso's dolphin, Grampus griseus; short-finned pilot whale, Globicephala macrorhynchus; and dolphins of the genus Stenella) taken for human consumption off St. Vincent, West Indies. Overall, 122 samples were analyzed; mean THg concentrations (µg/g dry weight) were highest in the liver (730), followed by the kidney (274), muscle (76.4), and blubber (4.57). To explain variability in muscle THg concentrations, carbon (δ13C) and nitrogen (δ15N) stable isotope ratios were analyzed to explore differences in dietary carbon source and relative trophic position, respectively, among species. There was no relationship between δ15N and THg concentration, but there was a positive relationship between δ13C and THg concentration. On average for each species, the Se:Hg molar ratios were >1 in blubber and <1 in muscle. All liver samples and the majority of kidney, muscle, and blubber samples exceeded the FAO/WHO human consumption advisory level of 1 µg/g wet weight. Based on our estimations, consuming only 6.6 g of muscle a week would exceed the MeHg provisional tolerable weekly intake of 1.6 µg MeHg/kg body weight/week for a 60 kg person. Given the high THg concentration in these cetaceans and the frequency at which these tissues are consumed, this is a potential human health issue that warrants further investigation.

Metals and trace elements in relation to body mass index in a prospective study of US women.

BACKGROUND: Epidemiologic studies on the association between metals and body mass index (BMI) have been cross-sectional and have demonstrated inconsistent associations. Our study prospectively examined whether metals measured at baseline were associated with later BMI. We considered metals individually and as joint exposure to pre-defined metal groupings. METHODS: We measured concentrations of 16 metals in toenails collected at baseline (2003-2009) in a subset of 1221 women from the Sister Study. We calculated BMI from height and weight reported on a follow-up questionnaire an average of 5.2 years (range = 3.5-8.3) after baseline. Multivariable linear regression was used to estimate ß coefficients and 95% confidence intervals (CIs) for associations between BMI and individual metals (with estimates given per interquartile range (IQR) increase or in quartiles). Quantile g-computation was used to examine joint associations between groups of metals and BMI. Groups considered were (1) all metals combined, and metals classified as (2) non-essential or (3) essential. RESULTS: In individual metal models we found that, with the exception of cobalt, no single metal was strongly related to BMI. In our mixture analyses, a quartile increase in all non-essential metals was associated with higher BMI (ß = 0.32; 95%CI: 0.00, 0.63 kg/m2), whereas essential metals were suggestively associated with lower BMI (ß = -0.25; 95%CI: 0.58, 0.07 kg/m2). CONCLUSIONS: In this population of women who were, on average, overweight, essential metals were jointly associated with slightly healthier, lower BMI whereas non-essential metals were jointly associated with slightly higher, unhealthier BMI, after controlling for other health indicators and predictors of metals exposures.

Toenail-Based Metal Concentrations and Young-Onset Breast Cancer.

Several metals have carcinogenic properties, but their associations with breast cancer are not established. We studied cadmium, a metalloestrogen, and 9 other metals-arsenic, cobalt, chromium, copper, mercury, molybdenum, lead, tin, and vanadium--in relation to young-onset breast cancer (diagnosis age <50 years), which tends to be more aggressive than and have a different risk profile from later-onset disease. Recent metal exposure was measured by assessing element concentrations, via inductively coupled plasma mass spectrometry, in toenail clippings of 1,217 disease-discordant sister pairs in the US-based Sister (2003-2009) and Two Sister (2008-2010) studies. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After correcting for differential calendar time of sample collection, no statistically significant associations were observed between any metals and breast cancer. Vanadium had the largest odds ratio (for fourth vs. first quartile, odds ratio = 1.36, 95% confidence interval: 0.84, 2.21; P for trend = 0.17). Cadmium was associated with a small increase in risk, with no evidence of a dose-response relationship (for fourth vs. first quartile, odds ratio = 1.15, 95% confidence interval: 0.82, 1.60; P for trend = 0.67). Positive associations between urinary cadmium concentrations and breast cancer have been reported in case-control studies, but we observed no such association between young-onset breast cancer and toenail concentrations of any assessed metals.

Toenail-Based Metal Concentrations and Young-Onset Breast Cancer.

Several metals have carcinogenic properties, but their associations with breast cancer are not established. We studied cadmium, a metalloestrogen, and 9 other metals-arsenic, cobalt, chromium, copper, mercury, molybdenum, lead, tin, and vanadium--in relation to young-onset breast cancer (diagnosis age <50 years), which tends to be more aggressive than and have a different risk profile from later-onset disease. Recent metal exposure was measured by assessing element concentrations, via inductively coupled plasma mass spectrometry, in toenail clippings of 1,217 disease-discordant sister pairs in the US-based Sister (2003-2009) and Two Sister (2008-2010) studies. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After correcting for differential calendar time of sample collection, no statistically significant associations were observed between any metals and breast cancer. Vanadium had the largest odds ratio (for fourth vs. first quartile, odds ratio = 1.54, 95% confidence interval: 0.75, 3.16; P for trend = 0.21). The association between cadmium and young-onset breast cancer was near null, with no evidence of a dose-response relationship (for fourth vs. first quartile, odds ratio = 0.95, 95% confidence interval: 0.64, 1.43; P for trend = 0.64). Positive associations between urinary cadmium concentrations and breast cancer have been reported in case-control studies, but we observed no such association between young-onset breast cancer and toenail concentrations of any assessed metals.

Association between elevated placental polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts from Superfund sites in Harris County, and increased risk of preterm birth (PTB).

The preterm birth (PTB) rate in Harris County, Texas, exceeds the U.S. rate (11.4% vs.9.6%), and there are 15 active Superfund sites in Harris County. Polycyclic aromatic hydrocarbons (PAHs) are contaminants of concern (COC) at Superfund sites across the nation. In this investigation, we tested the hypothesis that higher levels of exposure to PAHs and PAH-DNA adducts in placenta of women living near Superfund sites contribute to the increased rate of PTBs. Levels of benzo[a]pyene (BP), benzo[b]fluorene (BbF) and dibenz[a,h]anthracene (DBA), were higher in placentae from preterm deliveries compared with term deliveries in women living near Superfund sites, whereas this was not the case for women living in non-Superfund site areas. Among the PAHs, DBA levels were significantly higher than BP or BbF, and DBA levels were inversely correlated with gestational age at delivery and birth weight. Bulky PAH-DNA adducts are more prevalent in placental tissue from individuals residing near Superfund sites. Expression of Ah receptor (AHR) and NF-E2-related factor 2 (NRF2) was decreased in preterm deliveries in subjects residing near Superfund sites. Unbiased metabolomics revealed alterations in pathways involved in pentose phosphate, inositol phosphate and starch and sucrose metabolism in preterm subjects in Superfund site areas. In summary, this is the first report showing an association between PAH levels, DNA adducts, and modulation of endogenous metabolic pathways with PTBs in subjects residing near Superfund sites, and further studies could lead to novel strategies in the understanding of the mechanisms by which PAHs contribute to PTBs in women.

Do Post-breast Cancer Diagnosis Toenail Trace Element Concentrations Reflect Prediagnostic Concentrations?

BACKGROUND: Exposure to trace elements may affect health, including breast cancer risk. Trace element levels in toenails are potentially useful biomarkers of exposure, but their reliability is not established. We assessed the reproducibility of toenail element concentrations over time and whether concentrations change following a breast cancer diagnosis. METHODS: We assessed trace element levels in toenails collected at two time points from 221 women (111 with and 110 without an intervening breast cancer diagnosis). We measured levels of arsenic, cadmium, chromium, cobalt, copper, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, tin, vanadium, and zinc using inductively coupled plasma mass spectrometry in samples collected at baseline and 4-10 years later. We compared trace element concentrations over time using Spearman's rank correlation coefficient (R). We used linear models to examine the magnitude and direction of changes and the influence of a breast cancer diagnosis. RESULTS: Overall, we observed positive correlations (R = 0.18-0.71) between paired samples for all trace elements. However, nickel (R = -0.02) and antimony (R = 0.12) were not correlated among cases. We observed decreases in cadmium, chromium, mercury, manganese, molybdenum, nickel, and lead between baseline and follow-up, but case status was unrelated to these changes. The declines are consistent with decreases over calendar time rather than age time. CONCLUSIONS: Toenail trace element concentrations were correlated over time, but many elements showed systematic decreases by calendar year. Aside from nickel and antimony, postdiagnostic toenail levels correlated with prediagnostic levels, providing support for using postdiagnostic toenail samples in retrospective studies.

The Impact of Inhaled Ambient Ultrafine Particulate Matter on Developing Brain: Potential Importance of Elemental Contaminants.

Epidemiological studies report associations between air pollution (AP) exposures and several neurodevelopmental disorders including autism, attention deficit disorder, and cognitive delays. Our studies in mice of postnatal (human third trimester brain equivalent) exposures to concentrated ambient ultrafine particles (CAPs) provide biological plausibility for these associations, producing numerous neuropathological and behavioral features of these disorders, including male-biased vulnerability. These findings raise questions about the specific components of AP that underlie its neurotoxicity, which our studies suggest could involve trace elements as candidate neurotoxicants. X-ray fluorescence analyses of CAP chamber filters confirm contamination of AP exposures by multiple elements, including iron (Fe) and sulfur (S). Correspondingly, laser ablation inductively coupled plasma mass spectrometry of brains of male mice indicates marked postexposure elevations of Fe and S and other elements. Elevations of brain Fe and S in particular are consistent with potential ferroptotic, oxidative stress, and altered antioxidant capacity-based mechanisms of CAPs-induced neurotoxicity, supported by observations of increased serum oxidized glutathione and increased neuronal cell death in nucleus accumbens with no corresponding significant increase in caspase-3, in male brains following postnatal CAP exposures. Understanding the role of trace element contaminants of particulate matter AP as a source of neurotoxicity is critical for public health protection.

Validity of retrospective occupational exposure estimates of lead and manganese in a case-control study.

OBJECTIVES: The validity of surrogate measures of retrospective occupational exposure in population-based epidemiological studies has rarely been evaluated. Using toenail samples as bioindicators of exposure, we assessed whether work tasks and expert assessments of occupational metal exposure obtained from personal interviews were associated with lead and manganese concentrations. METHODS: We selected 609 controls from a case-control study of bladder cancer in New England who had held a job for ≥1 year 8-24 months prior to toenail collection. We evaluated associations between toenail metal concentrations and five tasks extracted from occupational questionnaires (grinding, painting, soldering, welding, working near engines) using linear regression models. For 139 subjects, we also evaluated associations between the toenail concentrations and exposure estimates from three experts. RESULTS: We observed a 1.9-fold increase (95% CI 1.4 to 2.5) in toenail lead concentrations with painting and 1.4-fold increase (95% CI 1.1 to 1.7) in manganese concentrations with working around engines and handling fuel. We observed significant trends with increasing frequency of both activities. For lead, significant trends were observed with the ratings from all three experts. Their average ratings showed the strongest association, with subjects rated as possibly or probably exposed to lead having concentrations that were 2.0 and 2.5 times higher, respectively, than in unexposed subjects (ptrend <0.001). Expert estimates were only weakly associated with manganese toenail concentrations. CONCLUSIONS: Our findings support the ability of experts to identify broad contrasts in previous occupational exposure to lead. The stronger associations with task frequency and expert assessments support using refined exposure characterisation whenever possible.

Maternal urinary cadmium, glucose intolerance and gestational diabetes in the New Hampshire Birth Cohort Study.

BACKGROUND: Exposure to cadmium may contribute to the risk of gestational diabetes mellitus (GDM) and glucose intolerance during pregnancy. METHODS: We examined 917 women enrolled from 2009 to 2017 in the New Hampshire Birth Cohort Study. Lifestyle, diet, demographic factors and pregnancy outcomes were collected by questionnaire and medical record review. Cadmium concentrations were measured in urine samples collected at 24-28 weeks gestation. Women were classified as normal (n = 815), glucose intolerant (n = 86), or GDM (n = 16) based on clinical data (i.e., glucose challenge test, oral glucose challenge test). We calculated odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders, using multinomial logistic regression to examine disease severity (normal, glucose intolerant, GDM) and logistic regression to examine the combined outcome of gestational hyperglycemia. RESULTS: Little to no association was observed for glucose intolerance (OR = 1.11, 95%CI 0.85-1.45) or GDM (OR = 0.86, 95% CI 0.51-1.44) with a doubling of urinary cadmium as compared to normal women. The combined outcome of gestational hyperglycemia yielded similar results (OR = 1.07, 95% CI 0.84-1.35). However, when stratified by pre-pregnancy body mass index (BMI), there was a slight association with the combined outcome in normal weight women (OR = 1.32, 95% CI 0.88-1.98) and no association in the overweight or obese women. This positive association remained in restricted analyses of only women with no exposure to smoking during pregnancy and those who had never smoked. CONCLUSIONS: Cadmium exposure was suggestively associated with increased risk of gestational hyperglycemia among women not already at increased risk of GDM due to being overweight or obese; however, associations of cadmium with gestational hyperglycemia were not statistically significant.