The Importance of Fostering and Funding Scientific Research, and its Relevance to Environmental Toxicology and Chemistry.

What do environmental contaminants and climate change have in common with the virus SARS-CoV-2 and the disease COVID-19? We argue that one common element is the wealth of basic and applied scientific research that provides the knowledge and tools essential in developing effective programs for addressing threats to humans and social-ecological systems. Research on various chemicals, including dichlorodiphenyltrichloroethane and per- and polyfluoroalkyl substances, resulted in regulatory action to protect environmental and human health. Moreover, decades of research on coronaviruses, mRNA, and recently SARS-CoV-2 enabled the rapid development of vaccines to fight the COVID-19 pandemic. In the present study, we explore the common elements of basic and applied scientific research breakthroughs that link chemicals, climate change, and SARS-CoV-2/COVID-19 and describe how scientific information was applied for protecting human health and, more broadly, socio-ecological systems. We also offer a cautionary note on the misuse and mistrust of science that is not new in human history, but unfortunately is surging in modern times. Our goal was to illustrate the critical role of scientific research to society, and we argue that research must be intentionally fostered, better funded, and applied appropriately. To that end, we offer evidence that supports the importance of investing in scientific research and, where needed, ways to counter the spread of misinformation and disinformation that undermines legitimate discourse. Environ Toxicol Chem 2023;42:581-593. © 2022 SETAC.

Metabolic transformation of environmentally-relevant brominated flame retardants in Fauna: A review.

Over the past few decades, production trends of the flame retardant (FR) industry, and specifically for brominated FRs (BFRs), is for the replacement of banned and regulated compounds with more highly brominated, higher molecular weight compounds including oligomeric and polymeric compounds. Chemical, biological, and environmental stability of BFRs has received some attention over the years but knowledge is currently lacking in the transformation potential and metabolism of replacement emerging or novel BFRs (E/NBFRs). For articles published since 2015, a systematic search strategy reviewed the existing literature on the direct (e.g., in vitro or in vivo) non-human BFR metabolism in fauna (animals). Of the 51 papers reviewed, and of the 75 known environmental BFRs, PBDEs were by far the most widely studied, followed by HBCDDs and TBBPA. Experimental protocols between studies showed large disparities in exposure or incubation times, age, sex, depuration periods, and of the absence of active controls used in in vitro experiments. Species selection emphasized non-standard test animals and/or field-collected animals making comparisons difficult. For in vitro studies, confounding variables were generally not taken into consideration (e.g., season and time of day of collection, pollution point-sources or human settlements). As of 2021 there remains essentially no information on the fate and metabolic pathways or kinetics for 30 of the 75 environmentally relevant E/BFRs. Regardless, there are clear species-specific and BFR-specific differences in metabolism and metabolite formation (e.g. BDE congeners and HBCDD isomers). Future in vitro and in vivo metabolism/biotransformation research on E/NBFRs is required to better understand their bioaccumulation and fate in exposed organisms. Also, studies should be conducted on well characterized lab (e.g., laboratory rodents, zebrafish) and commonly collected wildlife species used as captive models (crucian carp, Japanese quail, zebra finches and polar bears).

Distribution behaviour in body compartments and in ovo transfer of flame retardants in North American Great Lakes herring gulls.

Polybrominated diphenyl ethers (PBDEs) and other halogenated flame retardants (HFRs) continue to be an environmental concern. In the Laurentian Great Lakes, herring gulls (Larus argentatus) are an important wildlife sentinel species, although very little information is available regarding the body distribution (limited to e.g. liver and blood) of these contaminants and in relation to depuration via in ovo transfer. Maternal transfer rates and distribution were presently determined in six body compartments from eight female, Great Lakes herring gulls and separate egg compartments from their entire clutch. Among the 25 PBDEs and 23 non-PBDE HFRs assessed, only six PBDE congeners (BDE-47/99/100/153/154/209), hexabromocyclododecane (HBCDD), and Dechlorane Plus (syn- and anti-DDC-CO) were frequently detectable and quantifiable. Σ6BDE concentrations were an order of magnitude greater than non-PBDE HFR concentrations, and were greatest in the adipose (9641 ± 2436 ng/g ww), followed by egg yolk (699 ± 139 ng/g ww) > muscle (332 ± 545 ng/g ww) > liver (221 ± 65 ng/g ww) > plasma (85.4 ± 20.4 ng/g ww) > brain (54.6 ± 10.6 ng/g ww) > red blood cells (RBCs; 23.5 ± 5.6 ng/g ww) > albumen (7.3 ± 1.3 ng/g ww). Σ2DDC-CO and HBCDD were frequently below the method limit of quantification in the brain, RBCs, plasma, and albumen. Additionally, novel methoxylated-polybrominated diphenoxybenzene contaminants were detected and quantified in herring gull tissues and eggs. The primary difference in PBDE congener profiles was the resistance of both BDE-153 and -154 towards accumulation in the brain, and a corresponding increase in BDE-209 accumulation, which may suggest congener-specific differences in crossing the blood-brain barrier in herring gulls. Maternal transfer rates of PBDEs and non-PBDE HFRs were low (∼4.7 and ∼2.9 % respectively), suggesting that in ovo transfer is not a significant mode of depuration for these compounds.

Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation.

The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and ß-tetrabromoethylcyclohexane (ß-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC50 of 160 nM; no statistically significant inhibition of SULT activity was observed. ORD inhibition of 3,3'-T2 formation from rT3 was also observed (IC50 ∼ 100 nM). The kinetics of T4 O and IRD were also investigated, although a definitive mechanism could not be identified as the Michaelis-Menten parameters and maximal rate constants were not significantly different. Concentrations tested were intentionally above expected environmental levels, and this study suggests that these NBFRs are not potent human liver DIO and SULT inhibitors. To our knowledge, DBDPE is the first example of a nonhydroxylated contaminant inhibiting DIO activity, and further study of the mechanism of action is warranted.