Environmental Health Perspectives最新文献

Background: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life.

Objective: We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet.

Methods: Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn.

Results: Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [$\beta =0.009$; 95% confidence interval (CI): 0.002, 0.016 and $\beta =0.002$; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [$\beta =-0.24$; 95% CI: $-0.33$, $-0.15$ and $\beta =-0.032$; 95% CI: $-0.048$, $-0.016$, respectively] and $n-3$ PUFA with longer ($\beta =0.34$; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer ($\beta =0.15$; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn.

Discussion: Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.

Background: The 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The International Agency for Research on Cancer (IARC) Monographs programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.

Objectives: We sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations.

Methods: A group of experts from different disciplines reviewed the IARC Monographs experience with the KCs of carcinogens, discussing three main themes: a) the interpretation of end points forming the evidence base for the KCs, b) the incorporation of data from novel assays on the KCs, and c) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.

Discussion: Consensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the IARC Monographs or in other contexts. https://doi.org/10.1289/EHP15389.

Background: People who live near airports are exposed to higher concentrations of ultrafine particles (UFPs) from aviation. Pregnant women and their fetuses, in particular, are considered to be highly susceptible to environmental exposures.

Objective: Using existing national databases, we investigated associations between adverse birth outcomes and exposure to UFPs from aviation (UFP-aviation) at the residential address during pregnancy.

Methods: We identified $\sim \mathrm{286,000}$ singleton birth records (from between 2006 and 2018) from mothers who, for at least 6 months during pregnancy, lived in a $50\times 56\mathrm{km}$ area around Schiphol Airport. This information was linked to modeled monthly averaged UFP-aviation concentrations at the residential address during pregnancy. We modeled the association between exposure to UFP-aviation during pregnancy and pregnancy outcomes through logistic regression, adjusting for individual and neighborhood level covariates. We performed a number of sensitivity analyses to investigate the robustness of the results, including adjustment for other air pollutants and noise.

Results: Effect estimates, expressed per 3,500 particles/cm³ (approximately the 5th-9th percentile difference) increase, were generally positive in the main model for preterm birth (PTB) and small for gestational age (SGA) [PTB $\text{OR}=$ 1.02 (95% CI: 0.96, 1.07) and SGA $\text{OR}=$ 1.02 (95% CI: 0.98, 1.07)] and congenital anomalies (CAs) at birth [any CA $\text{OR}=$ 1.05 (95% CI: 0.98, 1.07)]. Associations with UFP-aviation became stronger in some of the sensitivity analyses, such as when the four municipalities with the lowest exposure were excluded (for PTB, SGA, and CA), when the population was restricted to mothers with a Dutch background (PTB), after nonlinear adjustment for nitrogen dioxide (${\mathrm{NO}}_2$) and elemental carbon (EC) (PTB), after including municipality as a random effect (CA), and in some specific strata of the population. No associations were found with infant mortality, low Apgar score, and low birth weight.

Conclusions: We found suggestive evidence for associations between exposure to UFP-aviation during pregnancy and pregnancy outcomes. https://doi.org/10.1289/EHP14398.

Background: Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric pathogen infections and diarrhea are highly seasonal and climate-sensitive, which could explain heterogeneous findings. Understanding how season influences the effectiveness of WASH interventions is critical for informing intervention approaches that will be resistant under the varying weather conditions that climate change will bring.

Methods: We conducted a systematic review of the literature and meta-analysis to test whether and to what extent the impact of WASH interventions on diarrhea differs by season. We searched the literature for randomized and nonrandomized controlled WASH intervention trials and identified the season in which data were collected-rainy, dry, or both-for each study using proximate land station weather datasets. We compared the relative risk (RR) estimates for the impact of interventions on diarrhea for each study, stratified by season, and analyzed estimates using meta-analysis and meta-regression. This study is registered with PROSPERO, CRD42021231137.

Results: A total of 50 studies met the inclusion criteria, resulting in 34 drinking water intervention estimates, 8 sanitation intervention estimates, and 14 handwashing intervention estimates. Of the total studies, 60% ($n=30$) spanned more than one season, with most single-season studies (75%, $n=15$) occurring exclusively in the dry season. The effect of WASH interventions was stronger in dry seasons than in rainy seasons, with a 33% [95% confidence interval (CI): 24%, 41%] and 18% reduction (95% CI: 5%, 29%) in diarrhea risk, respectively. When stratified by type of intervention, the stronger effect size in dry seasons was consistent for water and handwashing interventions but not for sanitation interventions.

Conclusions: Estimates of the seasonal impact of WASH interventions revealed larger effects in the dry season than in the rainy season overall and for water and handwashing interventions in particular. These patterns likely affected previous estimates of intervention effectiveness, which included more dry season estimates. These findings suggest the need to collect data across seasons and report seasonally stratified results to allow for more accurate estimates of the burden of disease impacted by WASH investments and to improve projections of potential impacts of these interventions under future climate conditions. These findings also underscore the need for robust WASH interventions designed to be resistant to seasonal variations in temperature and rainfall now and under future climate change scenarios. https://doi.org/10.1289/EHP14502.

Background: Coccidioidomycosis, caused by inhalation of Coccidioides spp. spores, is an emerging infectious disease that is increasing in incidence throughout the southwestern US. The pathogen is soil-dwelling, and spore dispersal and human exposure are thought to co-occur with airborne mineral dust exposures, yet fundamental exposure-response relationships have not been conclusively estimated.

Objectives: We estimated associations between fine mineral dust concentration and coccidioidomycosis incidence in California from 2000 to 2017 at the census tract level, spatiotemporal heterogeneity in exposure-response, and effect modification by antecedent climate conditions.

Methods: We acquired monthly census tract-level coccidioidomycosis incidence data and modeled fine mineral dust concentrations from 2000 to 2017. We fitted zero-inflated distributed-lag nonlinear models to estimate overall exposure-lag-response relationships and identified factors contributing to heterogeneity in exposure-responses. Using a random-effects meta-analysis approach, we estimated county-specific and pooled exposure-responses for cumulative exposures.

Results: We found a positive exposure-response relationship between cumulative fine mineral dust exposure in the 1-3 months before estimated disease onset and coccidioidomycosis incidence across the study region [incidence rate ratio (IRR) for an increase from 0.1 to $1.1{\mu g/m}^3=1.60$; 95% CI: 1.46, 1.74]. Positive, supralinear associations were observed between incidence and modeled fine mineral dust exposures 1 [$\text{IRR}=1.13$ (95% CI: 1.10, 1.17)], 2 [$\text{IRR}=1.15$ (95% CI: 1.09, 1.20)] and 3 [$\text{IRR}=1.08$ (95% CI: 1.04, 1.12)] months before estimated disease onset, with the highest exposures being particularly associated. The cumulative exposure-response relationship varied significantly by county [lowest IRR, western Tulare: 1.05 (95% CI: 0.54, 2.07); highest IRR, San Luis Obispo: 3.01 (95% CI: 2.05, 4.42)]. Season of exposure and prior wet winter were modest effect modifiers.

Discussion: Lagged exposures to fine mineral dust were strongly associated with coccidioidomycosis incidence in the endemic regions of California from 2000 to 2017. https://doi.org/10.1289/EHP13875.