Papers of the Month
By Megan Avakian
Novel method can reduce use of animals in eye safety tests
NIEHS-funded researchers demonstrated that a nonanimal test can predict whether substances in consumer products cause eye damage. Called OptiSafe, the method can help researchers avoid using animals in eye safety tests.
The method entails adding test substances to a vial containing molecules mimicking eye tissues. Based on those tests, potential eye irritants are classified into categories, such as substances that cause no eye damage (“no damage”) and those causing major, permanent damage (“extreme damage”).
The current study builds on earlier OptiSafe results suggesting that tears might combat eye damage from certain chemicals. To test the idea, the team added ascorbic acid, a protective compound that naturally occurs in tears, to the OptiSafe method. Using this updated method, the researchers tested 51 substances from the "no damage" category and 59 from the "extreme damage" category. Then they compared the results to publicly available data from animal tests.
The researchers found that the updated method was more accurate than their earlier approach as well as other common nonanimal eye irritation tests. Specifically, the updated method predicted “no damage” substances with nearly 93% accuracy. Predictions for “extreme damage” were about 79% accurate. Additionally, the updated method correctly identified substances labeled as extremely damaging about 90% of the time — a rate well above that of other common eye irritant tests.
According to the authors, OptiSafe is a rapid and shelf-stable method capable of detecting a substance’s potential to cause eye damage and can reduce the use of animals in eye toxicity tests.
Citation: Lebrun S, Chavez S, Nguyen L, Chan R. 2022. Expansion of the application domain of a macromolecular ocular irritation test (OptiSafe). Toxicol In Vitro 86:105515.
Racially segregated communities disproportionately exposed to toxic metals in air pollution
Americans living in racially segregated communities are exposed to higher levels of toxic metals in fine particulate matter (PM) air pollution than residents of well-integrated communities, NIEHS-funded researchers found. Past studies have established racial disparities among people exposed to PM. However, researchers know less about how exposure relates to neighborhood segregation or to toxic metals in PM.
The researchers focused on nine metals emitted from human activity, such as industrial processes, or from natural sources, such as wind-blown soil. They used publicly available air monitoring data to estimate PM metal exposure in about 230 counties. For each county, they used census tract data to calculate a segregation score based on how closely the racial makeup of individual census tracts mirrored overall county demographics.
Counties with higher racial residential segregation were exposed to greater levels of total PM and PM metals. Specifically, total PM was two times higher in racially segregated communities compared to well-integrated communities. Metal concentrations from human activity were nearly 10 times higher in segregated communities. That finding likely stems from the clustering of industrial and other human-related emission sources in urban areas with a history of racial residential segregation, said the authors.
The researchers further examined the metal vanadium, a component of fuel used in the marine shipping industry. Following regulations that lowered shipping-related emissions, vanadium exposure sharply declined in segregated communities. According to the authors, this trend demonstrates that targeted emission reduction strategies can reduce segregation-driven inequalities in metal exposures.
Citation: Kodros JK, Bell ML, Dominici F, L'Orange C, Godri Pollitt KJ, Weichenthal S, Wu X, Volckens J. 2022. Unequal airborne exposure to toxic metals associated with race, ethnicity, and segregation in the USA. Nat Commun 13(1):6329.
Bacteria that degrade PCBs in sediment can reduce chemical emissions to surrounding air
Adding bacteria that can break down polychlorinated biphenyls (PCBs) to contaminated sediments reduced the release of the chemicals into surrounding air, according to NIEHS-funded researchers. The approach may decrease PCB inhalation exposure near PCB-contaminated sites. PCBs are a family of more than 200 structurally similar chemicals that have been linked to a range of adverse health effects, including some cancers.
Researchers used a strain of bacteria called Paraburkholderia xenovorans, which can break down PCBs in the environment. They added the bacteria, along with samples of PCB-contaminated sediment, to a vessel called a bioreactor, which creates a controlled environment for the bacteria to degrade the pollutants. Then they compared airborne PCB levels — detected by passive samplers — in bioreactors with and without bacteria for 35 days. They also examined how adding a compound called saponin to sediment affected PCB emissions. Secreted by plants, saponins render PCBs more available for bacterial degradation.
PCB emissions from sediments were 57% lower, on average, in bioreactors containing bacteria compared to those without. The bacteria preferentially degraded PCBs with fewer chlorine compounds in their chemical structure. Of those, P. xenovorans favored the most abundant PCB in the sediment, called PCB 4, as evidenced by a 90% drop in related emissions. When saponin was added, the bacteria were 24% more effective at reducing PCB emissions compared to the bacteria-only scenario.
Study results suggest that amending sediment at PCB-contaminated sites with certain bacterial species can lower airborne PCB levels and reduce exposure to nearby communities, said the authors.
Citation: Bako CM, Martinez A, Ewald JM, Hua JBX, Ramotowski DJ, Dong Q, Schnoor JL, Mattes TE. 2022. Aerobic bioaugmentation to decrease polychlorinated biphenyl (PCB) emissions from contaminated sediments to air. Environ Sci Technol 56(20):14338–14349.
Systems approach points to mechanisms by which herbicide increases inflammatory bowel disease risk
Exposure to the herbicide propyzamide may increase inflammation in the intestine and the risk of inflammatory bowel disease (IBD), NIEHS-funded researchers found. Importantly, the team developed a platform that combines publicly available databases, zebrafish and mouse studies, and machine learning to pinpoint environmental factors and mechanisms that drive IBD development.
The team used the ToxCast database, which contains information on the biological activity of thousands of chemicals, to identify substances linked to intestinal inflammation. Then they tested how exposure to those compounds affected gut inflammation in zebrafish. By integrating the zebrafish test results into a machine learning model, the researchers identified additional chemicals likely to boost inflammation in the intestine. This process generated 20 top chemical candidates linked to intestinal inflammation, including 11 agriculture-related chemicals. Of these, the researchers selected propyzamide for further study in mice because it is broadly used on crop and sports fields.
Propyzamide increased inflammation in both the small and large mouse intestine. The team discovered that the herbicide worsened intestinal inflammation by targeting a pathway that regulates immune cell activity in the gut. Specifically, propyzamide exposure reduced activity of the aryl hydrocarbon receptor (AHR), a protein that plays an important role in controlling inflammation following pollutant exposures. Suppression of AHR then activated a pathway in immune cells to promote intestinal inflammation.
According to the authors, this study showed that by systematically examining environmental factors that could affect health, researchers can identify mechanisms that drive IBD and other inflammatory diseases, as well as potential therapeutic targets.
Citation: Sanmarco LM, Chao CC, Wang YC, Kenison JE, Li Z, Rone JM, Rejano-Gordillo CM, Polonio CM, Gutierrez-Vazquez C, Piester G, Plasencia A, Li L, Giovannoni F, Lee HG, Faust Akl C, Wheeler MA, Mascanfroni I, Jaronen M, Alsuwailm M, Hewson P, Yeste A, Andersen BM, Franks DG, Huang CJ, Ekwudo M, Tjon EC, Rothhammer V, Takenaka M, de Lima KA, Linnerbauer M, Guo L, Covacu R, Queva H, Fonseca-Castro PH, Bladi MA, Cox LM, Hodgetts KJ, Hahn ME, Mildner A, Korzenik J, Hauser R, Snapper SB, Quintana FJ. 2022. Identification of environmental factors that promote intestinal inflammation. Nature 611(7937):801-809.
(Megan Avakian is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)