New model helps estimate PAHs in zebrafish studies

A new biologically based model accurately predicts doses of polycyclic aromatic hydrocarbons (PAHs) in zebrafish embryos exposed to these toxic chemicals during development, according to an NIEHS-supported study. PAHs are a group of chemicals formed when organic materials such as coal, oil, and wood are burned incompletely. They are present in air, soil, food, and water, and can lead to a wide range of health problems such as cancer.

Zebrafish are frequently incorporated as a new approach method (NAM) in toxicology research because their early development is similar to humans. However, the exposure concentrations reported for waterborne PAHs in the plastic well plates used for developmental zebrafish toxicity assays do not reliably capture the actual tissue dose, making it difficult to interpret the results.

To overcome this problem, the researchers developed a mathematical model that could estimate PAH concentrations in developing zebrafish tissues. The model takes into account PAH binding to the plate walls, embryo growth and change, and loss of PAHs due to imperfectly sealed well-plates. The researchers tested the model across six developmental time points and found it accurately predicted doses of PAHs individually and in mixtures.

According to the authors, this new approach will enable scientists to better interpret toxic outcomes in developmental zebrafish assays, ultimately informing both human health and environmental decision-making.

Citation: Rude CI, Smith JN, Scott RP, Schultz KJ, Anderson KA, Tanguay RL. 2025. A mixture parameterized biologically based dosimetry model to predict body burdens of polycyclic aromatic hydrocarbons in developmental zebrafish toxicity assays. Toxicol Sci 205(2):326-43.

Chemical mixtures studies may require different statistical methods

New guidelines could help scientists choose the correct statistical technique when trying to answer research questions related to chemical mixtures, according to NIEHS-supported research.

Many studies have used various statistical techniques to examine chemical mixtures and how they affect health. This research poses several challenges, such as identifying the appropriate method to accomplish a specific scientific goal. Mixture analysis may have differing scientific goals, such as characterizing the overall effect of the mixture, discovering nonlinear associations, characterizing complex exposure by exposure interactions, or identifying which exposure(s) within the mixture is driving the association.

For this study, the researchers developed a software package called CompMix to automate and streamline approaches for analyzing environmental mixtures. By synthesizing findings from multiple methods, they created a more holistic picture. The researchers also used simulations to compare 11 existing methods for analyzing chemical mixtures. The findings suggest that there is no one-size-fits-all approach.

For example, to identify mixture components and their interactions, the researchers found the Elastic net (Enet) statistical method offered the best fit. Lasso performed best for Hierarchical Interactions (HierNet), and selection of nonlinear interactions by a forward stepwise algorithm (SNIF). Finaly, the Super Learner method may be the best choice to create a summary score for environmental risk. To enable seamless adoption of multiple mixtures methods, the authors created an R package for comprehensive mixtures analysis: CompMix. According to the authors, new interpretable and scalable statistical techniques are urgently needed to further understand the health effects of mixtures.

Citation: Hao W, Cathey AL, Aung MM, Boss J, Meeker JD, Mukherjee B. 2025. Statistical methods for chemical mixtures: a roadmap for practitioners using simulation studies and a sample data analysis in the PROTECT Cohort. Environ Health Perspect 133(6):67019.

Self-harvesting shellfish may lead to PFAS exposure

Recreational shellfish harvesting may contribute to exposure of certain per-and polyfluoroalkyl substances (PFAS), according to an NIEHS-supported study.

PFAS are chemicals that have been used in commercial, industrial, and consumer products for decades. They are persistent and ubiquitous in the environment and are linked to wide-ranging health problems. Consumption of contaminated water and food, such as seafood, is a major contributor to PFAS exposure in humans. However, relatively little is known about PFAS exposure among recreational shellfish harvesters, who may be exposed not only by eating the contaminated food but also through contact with PFAS in water and sediment while harvesting.

To better understand these risks, the researchers analyzed PFAS compounds in surface water, sediment, and bivalve shellfish samples collected from seven locations in New Hampshire’s Great Bay Estuary. All samples contained PFAS, although levels varied by location and sample type. Using an exposure model and conservative assumptions to estimate PFAS exposure from recreational shellfish harvesting, the study estimated that for adults, consumption contributed the most to overall exposure when compared to skin contact and incidental ingestion of sediments. For children, skin contact and incidental sediment ingestion were estimated to play a greater role in overall exposure. Among the species tested, razor clams from a specific site had the highest PFAS levels, but further study is needed. However, for recreational harvesters following existing harvest restrictions for shellfish in the region due to other environmental pressures, the contribution to overall PFAS exposure is small.

According to the authors, more research is needed on how PFAS accumulate in different shellfish species before establishing or revising seafood consumption guidance or region-specific restrictions.

Citation: Gardiner CL, Petali JM, Chen CY, Giffard NG, Fernando S, Holsen TM, Varghese JR, Romano ME, Crawford KA. 2025. Evaluating the environmental occurrence of per- and polyfluoroalkyl substances (PFAS) and potential exposure risk for recreational shellfish harvesters in the Great Bay Estuary, New Hampshire. Sci Total Environ 986:179747.

Food insecurity shapes interplay between gut microbes and brain health

Food insecurity may alter the relationship between the gut microbiome and risk of cognitive impairment in adults, according to a study supported in part by NIEHS.

Food insecurity refers to limited or uncertain access to enough nutritious food to maintain an active, healthy life. In 2022, approximately 17 million U.S. households experienced food insecurity at some point. This condition is associated with a range of health issues, including asthma, obesity, type 2 diabetes, cardiovascular disease, psychological distress, and neurological and cognitive problems.

Scientists are increasingly exploring how the gut microbiome — the community of microbes living in the digestive tract — might contribute to brain health. Although some research has suggested that gut microbes may play a role in cognitive health, little is known about how food insecurity might shape that relationship.

To explore this question, the researchers analyzed survey data and sequenced stool samples from 360 adults in Wisconsin. Using a machine-learning algorithm, they identified two distinct groups of gut bacteria — known as microbial cliques — whose link to risk of cognitive impairment depended on food insecurity status. Among adults who were food insecure, the clique containing either Eisenbergiella or Eubacterium was associated with increased risk of cognitive impairment. In contrast, a different clique, including Ruminococcus torques, Bacteroides, CAG-352F, or Eubacterium, was linked to risk of cognitive impairment for food-secure individuals.

The authors say their results suggest that future efforts to modify the gut microbiome to support brain health may need to consider food security status to be most effective.

Citation: Eggers S, Hoggarth ZE, Nagdeo K, Banas MJ, Lane JM, Rechtman E, Gennings C, O'Neal E, Peppard PE, Sethi AK, Safdar N, Malecki KM, Schultz AA, Midya V. 2025. Food insecurity modifies the association between the gut microbiome and the risk of cognitive impairment in adults. NPJ Aging 11(1):47.