Environmental Factor – August 2022: Extramural Papers of the Month

Modified sea urchins open the door to exploring developmental toxicity

NIEHS-funded scientists established a new approach to study susceptibility to contaminants during early development using modified sea urchins, which are commonly used to study the mechanisms of early development. However, more advanced studies using genetically altered urchins have not previously been possible due to their slow growth — also referred to as a long generation time.

The researchers used a species known as a painted urchin, which has a shorter generation time than any currently used species. With the help of CRISPR/Cas9 gene editing tools, they generated a mutant line with a large genomic deletion that could be readily identified by routine polymerase chain reaction without sacrificing the animal. Specifically, they targeted and inactivated a gene called ABCB1, which, until now, has only been successfully deleted in mice. The ABCB1 gene encodes a transporter called ABCB1, or P-glycoprotein. Transporters are responsible for moving drugs and other chemicals across cellular membranes. In this case, ABCB1 plays a crucial role in embryos’ susceptibility to environmental contaminants.

Next, the scientists selected animals with the desired mutation in both normal and reproductive cells and bred them for two generations to achieve offspring that were homozygous, meaning each carried two identical copies of the mutated gene. Using a test called the CAM efflux assay, they confirmed the animals lacked ABCB1 function compared with normal urchins.

According to the authors, their modified sea urchin model can be reproduced in most labs using standard culturing and gene editing methods, representing a major step toward more sophisticated genetic manipulation to explore the underlying mechanisms involved in developmental toxicity.

Citation: Vyas H, Schrankel CS, Espinoza JA, Mitchell KL, Nesbit KT, Jackson E, Chang N, Lee Y, Warner J, Reitzel A, Lyons DC, Hamdoun A. 2022. Generation of a homozygous mutant drug transporter (ABCB1) knockout line in the sea urchin Lytechinus pictus. Development 149(11):dev200644.

Silicone wristbands highlight chemical exposures following Hurricane Harvey

An NIEHS-funded study was the first to reveal higher personal chemical exposures immediately following Hurricane Harvey compared with an estimated baseline. Hurricane Harvey caused flood-related damage to chemical plants and oil refineries, and flooded hazardous waste sites, including 13 Superfund sites. The study used silicone wristband personal sampling devices developed previously with NIEHS funding.

To better understand individual exposures to organic pollutants, silicone wristbands were given to nearly 100 participants within 45 days of the hurricane and again one year later in the Houston metropolitan area. Because personal exposure data before the hurricane were not available, data collected a year later were used to estimate baseline for comparison. Using gas chromatography-mass spectroscopy, each wristband was screened for 1,500 volatile organic chemicals (VOCs) and 63 polycyclic aromatic hydrocarbons (PAHs).

Chemical exposure levels found on the wristbands were generally higher immediately following Hurricane Harvey compared with the one-year follow-up. In total, 188 VOCs were detected, 29 of which were detected in at least 30% of the study population. Of those 29 chemicals, 23 were found in significantly higher concentrations post-Hurricane Harvey compared with a year later. Similarly, 51 PAHs were detected, 31 of which were detected in at least 30% of the study population. Of those, 12 were found at statistically higher concentrations immediately following the hurricane compared with the follow-up.

According to the team, this study successfully demonstrated the use of a post-disaster timepoint to act as an estimated baseline and documented increased personal chemical exposures after Hurricane Harvey among Houston residents.

Citation: Samon SM, Rohlman D, Tidwell LG, Hoffman PD, Oluyomi AO, Anderson KA. 2022. Associating increased chemical exposure to Hurricane Harvey in a longitudinal panel using silicone wristbands. Int J Environ Res Public Health 19(11):6670.

New mechanistic model predicts liver toxicity

Researchers funded by NIEHS developed a new model for predicting whether chemicals are toxic to the liver. The tool also identified a cellular pathway that might be involved in the process.

Because the liver plays a critical role in detoxification and metabolism, it is vulnerable to injury by environmental chemicals, commercial products, and drugs. In fact, liver toxicity is the leading cause of drug failure in clinical trials. However, traditional methods of testing for these effects are time-consuming and expensive.

To build their model, the team gathered data from reference drug lists on hundreds of chemicals known to cause liver toxicity and others with no known liver effects. They refined their tool by separating the chemicals into two groups: those that activate a specific cellular pathway in the liver that causes oxidative stress — a sign of injury — and those that do not. The team also incorporated information about chemical structural features that are involved in triggering oxidative stress.

The researchers validated the model by exposing human liver cells to 16 chemicals either implicated in oxidative stress or not, and then compared their experimental results with the model’s predictions for those compounds. Next, they entered five chemicals previously shown to cause liver toxicity and seven nontoxic chemicals into the model. Overall, the model successfully predicted the liver toxicity potential for most chemicals tested.

According to the team, this novel strategy can be used to develop additional models that consider other pathways involved in liver toxicity as well as models that predict toxicity in different organs.

Citation: Jia X, Wen X, Russo DP, Aleksunes LM, Zhu H. 2022. Mechanism-driven modeling of chemical hepatotoxicity using structural alerts and an in vitro screening assay. J Hazard Mater 436:129193.

Arctic Indigenous Peoples exposed to PFAS and PBDEs in food

Arctic Indigenous Peoples may be exposed to persistent organic pollutants (POPs), including polybrominated diphenyl ethers (PBDEs) and per- and polyfluoroalkyl substances (PFAS), through traditional food sources, found an NIEHS-funded study. PBDEs are a group of chemicals added to certain products to reduce their flammability, and PFAS are used in a variety of industrial and consumer products, including cookware, stain repellants, and food packaging.

The Arctic has been characterized as a sink for POPs, which are carried there by wind and ocean currents from all over the globe and accumulate in animals higher in the food chain, such as whales and seals.

The research team worked with community partners to identify volunteer households and hunters in St. Lawrence Island, Alaska, who donated tissues from traditionally harvested animals, including bowhead whales, Pacific walrus, reindeer, and three species of seal. Then they assessed concentrations of PBDEs and PFAS in the samples.

PBDEs were detected in all species and tissues analyzed, with greater concentrations found in the fatty tissues of animals compared to lean muscles, and the highest levels found in seals. PFAS were detected less frequently, with no obvious patterns among species or tissues. However, this was the first study to find PFAS in bowhead whales, and the team reported that total PFAS levels were highest in lean muscles of seals.

According to the researchers, future work should assess the risks of consuming traditional foods holistically, considering both contaminant exposure and the cultural, spiritual, and economic benefits of these practices in Arctic communities.

Citation: Byrne S, Seguinot-Medina S, Waghiyi V, Apatiki E, Immingan T, Miller P, von Hippel FA, Buck CL, Carpenter DO. 2022. PFAS and PBDEs in traditional subsistence foods from Sivuqaq, Alaska. Environ Sci Pollut Res Int; doi:10.1007/s11356-022-20757-2 [Online 8 June 2022].