@article{wallis_kotlarz_knappe_collier_lea_reif_mccord_strynar_dewitt_hoppin_2023, title={Estimation of the Half-Lives of Recently Detected Per- and Polyfluorinated Alkyl Ethers in an Exposed Community}, volume={57}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.2c08241}, DOI={10.1021/acs.est.2c08241}, abstractNote={To estimate half-lives for novel fluoroethers, the GenX Exposure Study obtained two serum measurements for per- and polyfluoroalkyl substances (PFAS) for 44 participants of age 12-86 years from North Carolina, collected 5 and 11 months after fluoroether discharges into the drinking water source were controlled. The estimated half-lives for these compounds were 127 days (95% confidence interval (95% CI) = 86, 243 days) for perfluorotetraoxadecanoic acid (PFO4DA), 296 days for Nafion byproduct 2 (95% CI = 176, 924 days), and 379 days (95% CI = 199, 3870 days) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). Using these estimates and the literature values, a model was built that predicted PFAS half-lives using structural properties. Three chemical properties predicted 55% of the variance of PFAS half-lives based on 15 PFAS. A model with only molecular weight predicted 69% of the variance. Some properties can predict the half-lives of PFAS, but a deeper understanding is needed. These fluoroethers had biological half-lives longer than published half-lives for PFHxA and PFHpA (30-60 days) but shorter than those for PFOA and PFOS (800-1200 days). These are the first and possibly only estimates of human elimination half-lives of these fluoroethers.}, number={41}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Wallis, Dylan J. and Kotlarz, Nadine and Knappe, Detlef R. U. and Collier, David N. and Lea, C. Suzanne and Reif, David and McCord, James and Strynar, Mark and DeWitt, Jamie C. and Hoppin, Jane A.}, year={2023}, month={Oct}, pages={15348–15355} }
 @article{wallis_barton_knappe_kotlarz_mcdonough_higgins_hoppin_adgate_2023, title={Source apportionment of serum PFASs in two highly exposed communities}, volume={855}, ISSN={["1879-1026"]}, DOI={10.1016/j.scitotenv.2022.158842}, abstractNote={Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals that are ubiquitous in environmental and biological systems, including human serum. PFASs are used in many products and industrial processes and are tied to numerous health effects. Due to multiple sources and exposure pathways, methods are needed to identify PFAS sources in communities to develop targeted interventions. We assessed effectiveness of three source apportionment methods (UNMIX, positive matrix factorization [PMF], and principal component analysis - multiple linear regression [PCA-MLR]) for identifying contributors to human serum PFAS concentrations in two highly exposed populations in Colorado and North Carolina where drinking water was contaminated via upstream sources, including a Space Force base and a fluorochemical manufacturing plant. UNMIX and PMF models extracted three to four potential PFAS exposure sources in the Colorado and North Carolina cohorts while PCA-MLR classified two in each cohort. No sources were characterized in NHANES (National Health and Nutrition Examination Study). Results suggest that these three methods can successfully identify sources in highly exposed populations. Future PFAS exposure research should focus on analyzing serum for an expanded PFAS panel, identifying cohorts with other distinct point source exposures, and combining biological and environmental data to better understand source apportionment results in the context of PFAS toxicokinetic behavior.}, journal={SCIENCE OF THE TOTAL ENVIRONMENT}, author={Wallis, Dylan J. and Barton, Kelsey E. and Knappe, Detlef R. U. and Kotlarz, Nadine and McDonough, Carrie A. and Higgins, Christopher P. and Hoppin, Jane A. and Adgate, John L.}, year={2023}, month={Jan} }
 @article{truong_rericha_thunga_marvel_wallis_simonich_field_cao_reif_tanguay_2022, title={Systematic developmental toxicity assessment of a structurally diverse library of PFAS in zebrafish}, volume={431}, ISSN={["1873-3336"]}, url={http://dx.doi.org/10.1016/j.jhazmat.2022.128615}, DOI={10.1016/j.jhazmat.2022.128615}, abstractNote={Per- and polyfluoroalkyl substances (PFAS) are a class of widely used chemicals with limited human health effects data relative to the diversity of structures manufactured. To help fill this data gap, an extensive in vivo developmental toxicity screen was performed on 139 PFAS provided by the US EPA. Dechorionated embryonic zebrafish were exposed to 10 nominal water concentrations of PFAS (0.015-100 µM) from 6 to 120 h post-fertilization (hpf). The embryos were assayed for embryonic photomotor response (EPR), larval photomotor response (LPR), and 13 morphological endpoints. A total of 49 PFAS (35%) were bioactive in one or more assays (11 altered EPR, 25 altered LPR, and 31 altered morphology). Perfluorooctanesulfonamide (FOSA) was the only structure that was bioactive in all 3 assays, while Perfluorodecanoic acid (PFDA) was the most potent teratogen. Low PFAS volatility was associated with developmental toxicity (p < 0.01), but no association was detected between bioactivity and five other physicochemical parameters. The bioactive PFAS were enriched for 6 supergroup chemotypes. The results illustrate the power of a multi-dimensional in vivo platform to assess the developmental (neuro)toxicity of diverse PFAS and in the acceleration of PFAS safety research.}, journal={JOURNAL OF HAZARDOUS MATERIALS}, publisher={Elsevier BV}, author={Truong, Lisa and Rericha, Yvonne and Thunga, Preethi and Marvel, Skylar and Wallis, Dylan and Simonich, Michael T. and Field, Jennifer A. and Cao, Dunping and Reif, David M. and Tanguay, Robyn L.}, year={2022}, month={Jun} }
 @misc{wallis_truong_la du_tanguay_reif_2021, title={Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions}, volume={9}, ISSN={["2305-6304"]}, url={https://doi.org/10.3390/toxics9040077}, DOI={10.3390/toxics9040077}, abstractNote={Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that communicate across the body to stimulate specific receptors that bind DNA and regulate the expression of a suite of genes. These mechanisms, including gene regulation, DNA binding, and protein binding, can be tied to differences in individual susceptibility across a genetically diverse population. In this review, we posit that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure. We begin by summarizing how the biology of EDCs has implications for genetically diverse populations. We then describe how gene-environment interactions (GxE) across the complex pathways of endocrine signaling could lead to differences in susceptibility. We survey examples in the literature of individual susceptibility differences to EDCs, pointing to a need for research in this area, especially regarding the exceedingly complex thyroid pathway. Following a discussion of experimental designs to better identify and study GxE across EDCs, we present a case study of a high-throughput screening signal of putative GxE within known endocrine disruptors. We conclude with a call for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility.}, number={4}, journal={TOXICS}, publisher={MDPI AG}, author={Wallis, Dylan J. and Truong, Lisa and La Du, Jane and Tanguay, Robyn L. and Reif, David M.}, year={2021}, month={Apr} }
 @article{kosnik_strickland_marvel_wallis_wallace_richard_reif_shafer_2020, title={Concentration-response evaluation of ToxCast compounds for multivariate activity patterns of neural network function}, volume={94}, ISSN={["1432-0738"]}, DOI={10.1007/s00204-019-02636-x}, abstractNote={The US Environmental Protection Agency's ToxCast program has generated toxicity data for thousands of chemicals but does not adequately assess potential neurotoxicity. Networks of neurons grown on microelectrode arrays (MEAs) offer an efficient approach to screen compounds for neuroactivity and distinguish between compound effects on firing, bursting, and connectivity patterns. Previously, single concentrations of the ToxCast Phase II library were screened for effects on mean firing rate (MFR) in rat primary cortical networks. Here, we expand this approach by retesting 384 of those compounds (including 222 active in the previous screen) in concentration–response across 43 network activity parameters to evaluate neural network function. Using hierarchical clustering and machine learning methods on the full suite of chemical-parameter response data, we identified 15 network activity parameters crucial in characterizing activity of 237 compounds that were response actives ("hits"). Recognized neurotoxic compounds in this network function assay were often more potent compared to other ToxCast assays. Of these chemical-parameter responses, we identified three k-means clusters of chemical-parameter activity (i.e., multivariate MEA response patterns). Next, we evaluated the MEA clusters for enrichment of chemical features using a subset of ToxPrint chemotypes, revealing chemical structural features that distinguished the MEA clusters. Finally, we assessed distribution of neurotoxicants with known pharmacology within the clusters and found that compounds segregated differentially. Collectively, these results demonstrate that multivariate MEA activity patterns can efficiently screen for diverse chemical activities relevant to neurotoxicity, and that response patterns may have predictive value related to chemical structural features.}, number={2}, journal={ARCHIVES OF TOXICOLOGY}, author={Kosnik, Marissa B. and Strickland, Jenna D. and Marvel, Skylar W. and Wallis, Dylan J. and Wallace, Kathleen and Richard, Ann M. and Reif, David M. and Shafer, Timothy J.}, year={2020}, month={Feb}, pages={469–484} }
 @article{anderson_wallis_aguirre_holliday_merkler_2019, title={Knockdown of arylalkylamine N-acetyltransferase-like 2 in Drosophila melanogaster}, volume={102}, ISSN={["1520-6327"]}, DOI={10.1002/arch.21608}, abstractNote={AbstractDrosophila melanogaster produces fatty acid amides, and thus, provides a model to unravel the pathways for their biosynthesis. We previously demonstrated that arylalkylamine N‐acetyltransferase‐like 2 (AANATL2) from D. melanogaster will catalyze the formation of long‐chain N‐acylserotonins and N‐acyldopamines in vitro. Generating silencing RNA via the UAS/GAL4 bipartite approach for targeted gene expression effectively decreased the endogenous levels of the AANATL2 transcripts in D. melanogaster, as shown by reverse transcription quantitative polymerase chain reaction. Consistent with these data, western blot analysis of the offspring of the AANATL2 knockdown flies using an anti‐AANATL2 antibody revealed a significant reduction in the expression of the AANATL2 protein. Reduced expression of AANATL2 decreased the cellular levels of N‐palmitoyldopamine (PALDA), providing strong evidence that AANATL2 is responsible for the biosynthesis of PALDA in vivo. This is the first time that the expression of an AANAT has been reduced in D. melanogaster to link one of these enzymes to the in vivo production of an N‐acylarylalkylamide.}, number={4}, journal={ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY}, author={Anderson, Ryan L. and Wallis, Dylan J. and Aguirre, Alexander and Holliday, Dean and Merkler, David J.}, year={2019}, month={Dec} }