Environmental Health Perspectives最新文献

Background: Increasing evidence supports an association of endocrine-disrupting chemical (EDC) exposures with adverse biological effects in humans and wildlife. Recent studies reveal that health consequences of environmental exposures may persist or emerge across generations. This creates a dual conundrum: that we are exposed to contemporary environmental chemicals overlaid upon the inheritance of our ancestors' exposure profiles. Even when legacy EDCs are phased out, they may remain relevant due to persistence in the environment together with intergenerational inheritance of their adverse biological effects. Thus, we all possess a body burden of legacy contaminants, and we are also increasingly exposed to new generations of EDCs.

Objectives: We assessed the effects of direct and ancestral exposures to EDCs across six generations on anxiety-like behaviors in male rats using our "two hits, three generations apart" multigenerational EDC exposure experimental model. We investigated two classes of EDCs with distinct hormonal actions and historical use-the weakly estrogenic polychlorinated biphenyl (PCB) mixture Aroclor 1221 (A1221) and the anti-androgenic fungicide vinclozolin (VIN)-in both the maternal and paternal line. We also determined if a hormonal mechanism drives these effects across generations.

Methods: Rats were gestationally exposed to A1221, VIN, or vehicle [dimethyl sulfoxide (DMSO)] in the F1 generation. Three generations later, the F4 generation was given the same or a different exposure. Anxiety-like behavior was measured in the open field test, light:dark box, and elevated plus maze across generations. Serum was collected at the end of the experiment, and concentrations of estradiol and corticosterone were analyzed.

Results: Although direct exposure did not affect behavior in F1 males, ancestral exposure to VIN decreased anxiety-like behavior in the F3 paternal line compared to vehicle. In the F4 paternal line, ancestral A1221 followed by direct exposure to VIN increased anxiety-like behavior compared to controls. In the F6 maternal line, relative to vehicle, the double ancestral hits of A1221/VIN decreased anxiety-like behavior. Serum hormones weakly predicted behavioral changes in the F4 paternal line and were modestly affected in the F4 and F6 maternal lines.

Discussion: Our data suggest that anxiety-like behavioral phenotypes emerge transgenerationally in male rats in response to EDC exposure and that multiple hits of either the same or a different EDC can increase the impact in a lineage-specific manner. https://doi.org/10.1289/EHP15684.

Background: Large prospective cohort studies have been fruitful for identifying exposure-disease associations. In a cohort where biospecimens (e.g., blood, urine) were collected at enrollment, analysts can exploit a case-cohort approach: Biospecimens from a random sample of cohort participants, called the "subcohort," plus a sample of incident cases that were not part of the subcohort are assayed. Reusing subcohort data for multiple disease outcomes can reduce costs and conserve specimen archives. Pooling biospecimen samples before assay could both save money and reduce depletion of the archive but has not been studied for cohort studies.

Objectives: We develop and evaluate a biospecimen pooling strategy for case-cohort analyses that relate an exposure to risk of a rare disease.

Methods: Our approach involves constructing pooling sets for cases not in the subcohort after grouping them according to time of diagnosis (e.g., age). In contrast, members of the subcohort are grouped by age at entry before constructing pooling sets. The analyst then fits a logistic regression model that jointly stratifies by age at risk and pooling set size and adjusts for confounders. We used simulations (288 sampling scenarios with 1,000 simulated datasets each) to evaluate the performance of this approach for several sizes of pooling sets and illustrated its application to environmental epidemiologic studies by reanalyzing Sister Study data.

Results: Parameter estimates were nearly unbiased, and 95% confidence intervals constructed using a bootstrap estimate of the standard error performed well. In statistical tests also based on the bootstrap standard error, pooling up to 8 specimens per pool caused only modest loss of power. Assigning more cohort members to the subcohort and commensurately increasing the number of specimens per pool improved power and precision substantially while reducing the number of assays.

Discussion: When using case-cohort analysis to study disease outcomes in relation to exposures assessed using biospecimens in a cohort study, epidemiologists should consider biospecimen pooling as a way to improve statistical power, conserve irreplaceable archives, and save money. https://doi.org/10.1289/EHP14476.

Background: Endocrine-disrupting chemicals (EDCs) are exogenous chemical compounds that interfere with the normal function of the endocrine system and are linked to direct and inherited adverse effects in both humans and wildlife. Legacy EDCs such as polychlorinated biphenyls (PCBs) are no longer used yet remain detectable in biological specimens around the world; concurrently, we are exposed to newer EDCs like the fungicide vinclozolin (VIN). This combination of individuals' direct environmental chemical exposures and any heritable changes caused by their ancestors' chemical exposures leads to a layered pattern of both direct and ancestrally inherited exposures that might have cumulative effects over generations.

Objectives: We assessed consequences of both direct and ancestral exposure to EDCs over six generations, examining anxiety-like behaviors in maternal and paternal lines of female rats. We used the "two hits, three generations apart" multigenerational exposure model to explore how two distinct EDCs-the weakly estrogenic PCB mixture Aroclor 1221 (A1221) and the antiandrogenic VIN-interact on behavior across generations. We also explored serum hormones as a potential mechanism.

Methods: Rats were prenatally exposed to A1221, VIN, or vehicle (DMSO) in the F1 generation, and a second exposure (same or different) was administered to the F4 generation. Anxiety-like behavior was measured in the Open Field test, Light:Dark box, and Elevated Plus Maze in the F1, F3, F4, and F6 generations. Serum concentrations of estradiol and corticosterone were analyzed.

Results: Behavioral effects were not detectable in the F1 generation but emerged and became more robust across generations. Rats with ancestral VIN exposure demonstrated less anxiety-like behavior in the F3 paternal line in comparison with controls. Rats exposed to ancestral then prenatal A1221/VIN and VIN/A1221 had more anxiety-like behavior in the F4 maternal line, and those with two ancestral hits of VIN/VIN had more anxiety in the F6 paternal line, in comparison with controls.

Discussion: Our findings suggest that anxiety-like behavioral phenotypes can manifest in rats following germline exposure to EDCs and that subsequent exposures across generations can intensify these effects in a lineage-dependent manner. https://doi.org/10.1289/EHP15621.

Higher ${\mathrm{NO}}_2$ exposure was associated with increased risk of ovarian cancer. Results hinted that age at exposure might matter.

Background: The Global Calculator is an open-source model of the world's energy, land, and food systems. It is a pioneering online calculator to project the impact of interventions to mitigate climate change on global temperature. A few studies have been conducted to evaluate the health co-benefits of climate change mitigation, though they are still fragmentary.

Objectives: Our objectives are to identify which sectors could yield the greatest results in terms of climate change mitigation and suggest whether existing evidence could be used to weight mitigation actions based on their ancillary impacts on human health or health co-benefits.

Methods: Using the International Energy Agency (IEA) 4DS scenario as a referent (i.e., the "4-degree Celsius increase scenario"), we simulated changes in different policy "levers" (encompassing 43 potential technological and behavioral interventions, grouped by 14 sectors) and assessed the relative importance of each lever in terms of changes in annual greenhouse gas emissions in 2050 and cumulative emissions by 2100. In addition, we examined existing estimates for the health co-benefits associated with different interventions, using evidence from the Lancet Pathfinder and four other tools.

Discussion: Our simulations suggest that-after accounting for demographic change-transition from fossil fuels to renewables and changes in agriculture, forestry, land use, and food production are key sectors for climate change mitigation. The role of interventions in other sectors, like carbon capture and storage (CCS) or nuclear power, is more modest. Our work also identifies mitigation actions that are likely to have large health co-benefits, including shifts to renewable energy and changes in land use as well as dietary and travel behaviors. In conclusion, some of the sectors/interventions which have been at the center of policy debate (e.g., CCS or nuclear power) are likely to be far less important than changes in areas such as dietary habits or forestry practices by 2050. https://doi.org/10.1289/EHP14906.

Racial and ethnic differences in exposures to phthalates and their replacements through use of soaps, lotions, etc. appear to begin in childhood.

Background: Benzene is classified as carcinogenic to humans based on evidence that benzene causes acute myeloid leukemia. However, there is limited evidence that benzene causes lung cancer.

Objectives: We performed a systematic review, quality assessment, and meta-analysis of published cohort and case-control studies on the association between occupational benzene exposure and lung cancer risk.

Methods: We reviewed the relevant human epidemiological studies from PubMed and Embase databases to 19 August 2024. Data extraction included study characteristics, effect estimates, and exposure assessment details. Two investigators independently evaluated study quality using the Newcastle-Ottawa scale (NOS) framework and exposure assessment quality based on a priori criteria. Six risk of bias (ROB) domains were constructed from the NOS criteria to identify and quantify possible biases and their impacts on parameter estimates. Meta-analysis relative risk (pooled RR) and associated confidence intervals were calculated using random-effects models, and a flexible exposure-response meta-regression was fitted to assess the shape of the association. Subgroup analyses were conducted to explore the consistency of results.

Results: Of 252 articles identified, 13 studies covering 366,975 participants (17,030 lung cancer cases) were included in our analysis. The meta-analysis of ever occupational benzene exposure showed an elevated risk of lung cancer (pooled $\text{RR}=1.14$; 95% CI: 1.03, 1.27; $I²=72$). Subgroup analyses revealed that larger pooled RRs in studies based on highly exposed groups had higher overall quality and better exposure assessments and included both males and females (as opposed to only males). A positive linear trend was observed in the exposure-response meta-analysis.

Discussion: Our meta-analysis supports an association between occupational benzene exposure and an increased risk of lung cancer. https://doi.org/10.1289/EHP15086.