Papers of the Month
By Adeline Lopez
Air pollution affects children’s brain structure
Exposure to fine particulate matter (PM2.5) in childhood can change the architecture of the brain, according to an NIEHS-funded study. This study was the first to document links between exposure to air pollution at levels below regulatory standards and white matter connectivity in children across the U.S. White matter connectivity is critical for communication between cognitive and emotional regions of the brain.
Researchers used data from nearly 8,000 nine- and 10-year-old children across the U.S. They estimated exposure to PM2.5 by integrating advanced machine learning models and each child’s address of residence. They examined brain white matter architecture using magnetic resonance imaging, advanced diffusion weighted imaging, and biophysical modeling, and analyzed associations with air pollution exposure.
There were strong associations between PM2.5 levels and differences in white matter structure and diffusivity. Diffusivity is used to examine structural integrity and variations in the space between cells and cerebrospinal fluid. PM2.5 increased a type of diffusion that indicates changes in the cellular composition of white matter tracts in brain regions important in attention, emotional processing, and memory. Some regions were affected only in the left side of the brain, which controls language and logic, and others were affected in both sides of the brain.
Because most of the study population had PM2.5 exposures below regulatory levels set by the U.S. Environmental Protection Agency, the team suggested further improvements in air quality are needed to protect the developing brain.
Citation: Burnor E, Cserbik D, Cotter DL, Palmer CE, Ahmadi H, Eckel SP, Berhane K, McConnell R, Chen JC, Schwartz J, Jackson R, Herting MM. 2021. Association of outdoor ambient fine particulate matter with intracellular white matter microstructural properties among children. JAMA Netw Open 4(12):e2138300.
Phthalate exposure linked to high cholesterol, cardiovascular disease
NIEHS-funded researchers found that phthalate exposure was associated with higher plasma cholesterol levels and markers of cardiovascular disease. They also shed light on the role of the protein pregnane X receptor (PXR) in the underlying mechanism.
PXR is involved in the process of breaking down components in the diet, pharmaceutical drugs, and harmful chemicals in the liver and intestines. However, the protein has only recently been linked to changes in cholesterol and other lipids related to cardiovascular disease.
To better understand this role, the team exposed mice with variations in PXR to dicyclohexyl phthalate (DCHP), a widely used phthalate plasticizer. They looked at normal mice, mice carrying human PXR proteins, mice lacking PXR, and mice with deficient PXR in the intestines. They measured circulating cholesterol levels and used targeted lipidomics to measure biomarkers of cardiovascular disease.
DCHP strongly activated PXR, resulting in higher cholesterol levels in normal mice and mice with human PXR. Mice lacking PXR and those with deficient PXR in the intestines did not have high cholesterol. DCHP-exposed mice with higher PXR also had higher blood levels of lipids called ceramides, which are associated with higher cardiovascular disease risk in humans. Similarly, increased expression of genes involved in producing cholesterol and ceramides was associated with higher DCHP exposure based on PXR status.
According to the authors, these findings provide novel insights into how exposure to phthalates and other endocrine-disrupting chemicals (EDCs) increase cardiovascular disease risk in humans and enhance our understanding of gene–EDC interactions in individuals predisposed to cardiovascular disease.
Citation: Sui Y, Meng Z, Chen J, Liu J, Hernandez R, Gonzales MB, Gwag T, Morris AJ, Zhou C. 2021. Effects of dicyclohexyl phthalate exposure on PXR activation and lipid homeostasis in mice. Environ Health Perspect 129(12):127001.
Database reveals toxic metals in private well water in NC
Leveraging two decades of well water data in North Carolina (NC), NIEHS-funded researchers reported residents are exposed to arsenic and lead above the U.S. Environmental Protection Agency (EPA) standards. Their publicly available database offers a valuable tool for researchers and citizens in the state to identify areas of highest concern.
The team constructed the NCWELL database to house information on tests for 28 metals in nearly 118,000 geocoded wells in NC collected over 20 years. They analyzed the data to identify populations and areas at highest risk for single and co-occurring toxic metal contamination.
Arsenic and lead were detected above the EPA limits of 10 and 15 parts per billion (ppb), respectively, in more than 2,500 tests. Manganese was detected above the EPA lifetime health advisory limit in nearly 5 percent of samples and above secondary standards for aesthetics, such as taste and smell, in nearly 25 percent of tests. According to the authors, maximum detection levels of 806 ppb for arsenic, 105,440 ppb for lead, and 46,300 ppb for manganese are concerning.
Geographic differences across the state allowed the team to rank populations at risk by county based on metal concentrations and the proportion of residents relying on well water. In mixtures analysis, they identified four clusters of counties with distinct exposure attributes. For example, one cluster had high co-occurrence of arsenic and manganese and one had high occurrence of lead.
According to the team, the database and methodology can be used to identify priority geographic regions for contaminants and call for universal screening of private wells.
Citation: Eaves LA, Keil AP, Rager JE, George A, Fry RC. 2021. Analysis of the novel NCWELL database highlights two decades of co-occurrence of toxic metals in North Carolina private well water: public health and environmental justice implications. Sci Total Environ; doi:10.1016/j.scitotenv.2021.151479 [Online 9 November 2021].
Researchers document benefits of NYC ban on heating oil
NIEHS-funded researchers linked the New York City (NYC) ban on a type of heating oil with improved air quality. Using sophisticated statistical approaches and combining multiple data sources, the researchers provided a useful framework for evaluating the benefits of this policy.
The team quantified reductions in air pollution between 2011 and 2016 attributable to the Clean Heat Program, which was established in 2012 to eliminate the use of certain heating oils and move toward cleaner energy forms. They analyzed data on air pollution from the NYC Air Community Survey and used a land regression model to estimate pollutant levels for areas where no measurements were directly taken.
They included census level data on fuel conversion in buildings and the average year they were built. The researchers also incorporated data on miles traveled by different vehicles to account for traffic-related pollution. Finally, the team considered median household income to determine whether and how these reductions vary by neighborhood socioeconomic status. Using advanced statistical methods, they investigated the association between fuel conversion following the ban and changes in air pollution concentrations.
They found significant reductions in particulate matter, nitrogen dioxide, and sulfur dioxide attributable to the ban, independent of other sources of pollution, such as traffic. These reductions were similar regardless of neighborhood socioeconomic status.
According to the team, these changes are likely to result in potential health benefits and improve population health outcomes in the city.
Citation: Zhang L, He MZ, Gibson EA, Perera F, Lovasi GS, Clougherty JE, Carrión D, Burke K, Fry D, Kioumourtzoglou MA. 2021. Evaluating the impact of the Clean Heat Program on air pollution levels in New York City. Environ Health Perspect 129(12):127701.
(Adeline Lopez is a science writer for MDB Inc., a contractor for the NIEHS Superfund Research Program.)