Geochemical speciation of metals (Cu, Pb, Cd) in fishpond sediments in Batan Bay, Aklan, Philippines.

Batan Bay in Aklan, Philippines supports a population largely dependent on coastal fisheries. The development of aquaculture technologies coupled with over-crowded fish pens has negatively affected its natural dynamics and environmental quality. Land-use activities including ports and shipyard further aggravate the problem by contributing to chemical pollution. The present study applied sequential extraction techniques to determine the geochemical speciation of metals in fishpond sediments. Samples were processed and analyzed for Cu, Cd, and Pb using flame atomic absorption spectroscopy. Copper (Cu) showed the highest concentration (10.61-66.81 µg/g-dry weight of sediment). Lead (Pb) content ranged from below detection limit to 15.14 µg/g, while Cd concentration ranged from below detection limit to 2.50 µg/g. Fractionation study showed that the Cu present in the fishpond sediments is mostly non-residual (50.03-73.34%) and significantly associated with the oxidizable fraction (33.89-64.75%). In contrast, the residual fraction served as the dominant host of Pb (33.55-62.68%) in the sediments. Comparison of the results with US EPA and NOAA sediment quality guidelines also revealed that the Batan Bay sediments may be considered generally non-polluted with respect Cu, Pb, and Cd, and not expected to cause adverse effects to aquatic organisms under normal conditions. However, under certain redox conditions, most of the sites may be considered moderately polluted as a result of Cu mobilization from the non-residual fractions of the sediments. Overall, geochemical speciation studies in an important fishery area like Batan Bay will provide valuable insights into the availability of metal contaminants to aquatic organisms under certain environmental conditions.

Toward Sustainable Environmental Quality: Priority Research Questions for Asia.

Environmental and human health challenges are pronounced in Asia, an exceptionally diverse and complex region where influences of global megatrends are extensive and numerous stresses to environmental quality exist. Identifying priorities necessary to engage grand challenges can be facilitated through horizon scanning exercises, and to this end we identified and examined 23 priority research questions needed to advance toward more sustainable environmental quality in Asia, as part of the Global Horizon Scanning Project. Advances in environmental toxicology, environmental chemistry, biological monitoring, and risk-assessment methodologies are necessary to address the adverse impacts of environmental stressors on ecosystem services and biodiversity, with Asia being home to numerous biodiversity hotspots. Intersections of the food-energy-water nexus are profound in Asia; innovative and aggressive technologies are necessary to provide clean water, ensure food safety, and stimulate energy efficiency, while improving ecological integrity and addressing legacy and emerging threats to public health and the environment, particularly with increased aquaculture production. Asia is the largest chemical-producing continent globally. Accordingly, sustainable and green chemistry and engineering present decided opportunities to stimulate innovation and realize a number of the United Nations Sustainable Development Goals. Engaging the priority research questions identified herein will require transdisciplinary coordination through existing and nontraditional partnerships within and among countries and sectors. Answering these questions will not be easy but is necessary to achieve more sustainable environmental quality in Asia. Environ Toxicol Chem 2020;39:1485-1505. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Stereoselective biotransformation of permethrin to estrogenic metabolites in fish.

This study investigated the stereoselective biotransformation and resulting estrogenic activity of the pyrethroid insecticide, permethrin (PM). Results of both in vivo (male Japanese medaka, vitellogenin (VTG) protein in plasma) and in vitro (primary rainbow trout hepatocyte VTG-mRNA expression) assays indicated stereoselective estrogenic activity of PM. 1S-cis-PM was observed to have significantly higher activity (P ≤ 0.05) than the 1R-cis enantiomer in both in vivo and in vitro evaluations. All enantiomers of PM were oxidized to a 4'-hydoxy PM (4OH PM) metabolite and underwent esterase cleavage to 3-phenoxybenzyl alcohol (3-PBOH) and 3-(4'-hydroxyphenoxy)-benzyl alcohol) (3,4'-PBOH). Racemic 4OH PM as well as 3-PBOH, and 3,4'-PBOH possessed significant (P ≤ 0.05) estrogenicity. 1S-trans-PM underwent esterase cleavage more extensively than the corresponding 1R-trans-PM. Inhibition studies with ketoconazole confirmed cytochrome P450-catalyzed hydroxylation as well as esterase cleavage of PM for all stereoisomers. These studies indicated stereoselectivity in the estrogenic activity of PM resulting from stereoselective biotransformation of the parent compound to more estrogenic metabolites.

Chirality of organophosphorus pesticides: analysis and toxicity.

Although the importance of chirality in organophosphorus compounds (OPs) is well recognized in relation to their biological effects, as with most chiral pesticides, OPs are generally marketed, used and released to the environment as racemates (i.e., equimolar mixtures of enantiomers). In addition, research on enantioselective environmental fate and effects of chiral OPs is still limited, particularly in the evaluation of enantioselectivity in their environmental degradation. A large number of OPs are chiral compounds, and yet enantioselectivity in their environmental fate and effects is rarely addressed. This paper highlights the current state of knowledge on the environmental occurrence and behavior of chiral OP pesticides. Developments in enantioselective analytical techniques, specifically gas chromatography (GC), high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE), as applied in the evaluation of enantiomer-specific fate and effects of chiral OPs, are also discussed.

Epimerization of cypermethrin stereoisomers in alcohols.

Isomerization induced by light, heat, and organic solvents has been shown to occur for some pyrethroid insecticides. Alcohols are popular solvents that are used in sample extraction, storage, and analysis. Thus, alcohol-induced epimerization may contribute to the incorrect interpretation of results from enantioselective chemical analysis and bioassay of pyrethroids like cypermethrin. In this study, we investigated the relationship between the rate of epimerization of cypermethrin stereoisomers: 1R-cis-alphaR and 1R-trans-alphaR and short-chain alkyl alcohol properties. In this study, complete epimerization of 1R-cis-alphaR produced an almost equal fraction of 1R-cis-alphaS, and that of 1R-trans-alphaR yielded 1R-trans-alphaS. For both stereoisomers, epimerization was most rapid in ethanol. The same stereoisomers underwent relatively rapid epimerization in methanol, n-propanol, 2-methyl-1-propanol, and n-butanol but were stable in 2-butanol, suggesting that secondary alcohols have reduced reactivity, likely due to steric hindrance. We further evaluated epimerization of 1R-cis-alphaR and 1R-trans-alphaR stereoisomers of cypermethrin as a function of water content in methanol. The presence of water in methanol generally increased the epimerization rate. For 1R-cis-alphaR, epimerization was most rapid with a water content of < or =2%, while for 1R-trans-alphaR, epimerization was most rapid with a water content of 10%. Results from this study clearly show that contact with commonly used primary alcohols may result in rapid abiotic epimerization, underscoring the importance of considering configurational stability in ensuring the analytical integrity and correct interpretation of bioassay data for stereoisomers of cypermethrin and similar pyrethroids.

Enantioselectivity in fipronil aquatic toxicity and degradation.

Fipronil and its transformation products are being increasingly detected in aquatic ecosystems as a result of widespread use. Fipronil is a chiral compound, and enantioselectivity may greatly impact its environmental fate and effects. In the present study, fipronil enantiomers were isolated and used to investigate the possibility of enantioselectivity in their acute toxicity to Japanese medaka (Oryzias latipes) and cytotoxicity to primary hepatocytes from rainbow trout (Oncorhynchus mykiss). Enantioselectivity was further evaluated in terms of fipronil degradation in sediments under aerobic and anaerobic conditions and in field-contaminated runoff water from urban watersheds. The 96-h median lethal concentrations to Japanese medaka were 94.2 (95% confidence interval [CI], 82.9-107.1), 98.3 (95% CI, 85.6-113.0), and 95.4 (95% CI, 74.7-121.9) microg/L for the racemic, R-(-)-, and S-(+)-fipronil, respectively, suggesting absence of enantioselectivity. The 24-h median effect concentration of racemic fipronil to primary rainbow trout hepatocytes was 26.7 (95% CI, 25.6-27.9) microg/ml. In contrast, exposure of the cells to the S-(+)- and R-(-)-enantiomers resulted in a 19.7 and 7.8% reduction in cell viability, respectively, at the highest treatment concentrations (100 microg/ml), potentially indicating a greater-than-additive interaction between enantiomers. Under aerobic or slightly reduced conditions, biodegradation of fipronil in sediments was essentially nonstereoselective, with the enantiomeric fraction (EF) similar to racemic (EF = 0.5) after 168 d of incubation. However, EF decreased to as low as less than 0.1 following short incubations under anaerobic conditions, suggesting preferential degradation of S-(+)-fipronil in strongly reduced sediments. A survey of urban runoff samples consistently showed near-racemic EF, indicating fipronil degradation that was not enantioselective. Results suggest that site-specific characteristics are critical in accurately predicting fipronil fate and toxicity in the environment.

Enantioselective acetylcholinesterase inhibition of the organophosphorous insecticides profenofos, fonofos, and crotoxyphos.

A large number of organophosphorous insecticides (OPs) are chiral compounds, and yet enantioselectivity in their environmental fate and effects is rarely addressed. In the present study, we isolated individual enantiomers of three OPs, profenofos, fonofos, and crotoxyphos, and evaluated enantioselectivity in their inhibition of acetylcholinesterase (AChE). Acetylcholinesterase inhibition by the enantiomers and racemates was determined in vivo in the aquatic invertebrate Daphnia magna and in Japanese medaka (Oryzias latipes) as well as in vitro with electric eel (Electrophorus electricus) and human recombinant AChEs. The overall results showed variable sensitivity between AChE enzymes from different species as well as variable magnitude of enantioselectivity in enzyme inhibition. The (-)-enantiomer of profenofos was 4.3- to 8.5-fold more inhibitory to AChE in vivo, whereas (-)-fonofos was 2.3- to 29-fold more potent than the corresponding (+)-enantiomer. The (+)-enantiomer of crotoxyphos was 1.1- to 11-fold more inhibitory to AChE than the (-)-enantiomer. In contrast, the in vitro results showed (+)-profenofos to be 2.6- to 71.8-fold more inhibitory than the (-)-enantiomer and (-)-crotoxyphos to be 1.6- to 1.9-fold more active than the (+)-enantiomer. The reversed direction of enantioselectivity observed between the in vivo and in vitro assays suggests enantioselectivity within toxicodynamic processes such as uptake, biotransformation, or elimination. Findings from the present study provide evidence of enantioselectivity in the AChE inhibition of chiral OPs in nontarget organisms and indicate the need to consider enantiomers individually when assessing environmental risk of these chiral pesticides.

Synthesis of fenthion sulfoxide and fenoxon sulfoxide enantiomers: effect of sulfur chirality on acetylcholinesterase activity.

Earlier reports have demonstrated that recombinant flavin-containing monooxygenase 1 (FMO1) catalyzes the oxidation of the organophosphate pesticide fenthion to (+)-fenthion sulfoxide in a stereoselective fashion. In order to elucidate the absolute configuration of the sulfoxide metabolite produced, we established an efficient synthesis of both enantiomers of fenthion sulfoxide, which were transformed into chiral fenoxon sulfoxides using a two-step protocol. The use of chiral oxidants, namely, N-(phenylsulfonyl)(3,3-dichlorocamphoryl) oxaziridines, afforded enantioenriched fenthion sulfoxides with high ee (>82%) from the parent sulfide. Single recrystallizations afforded chiral fenthion sulfoxides with >99% ee, measured by chiral HPLC analysis. The absolute configuration of the (+)-sulfoxide generated from fenthion metabolism by FMO1 was determined to be (R)-(+)-fenthion sulfoxide, confirmed by X-ray crystallographic analysis of the (S)-(-)-antipode. Inhibition of human recombinant (hrAChE) and electric eel (eeAChE) acetylcholinesterase were assayed with fenthion, fenoxon, and the racemates and enantiomers of fenthion sulfoxide and fenoxon sulfoxide. Results revealed stereoselective inhibition with (R)-(+)-fenoxon sulfoxide when compared with that of (S)-(-)-fenoxon sulfoxide (IC50 of 6.9 and 6.5 microM vs 230 and 111 microM in hrAChE and eeAChE, respectively). Fenthion sulfoxide (R or S enantiomers) did not present anti-AChE properties. Although the stereoselective sulfoxidation of fenthion to (R)-(+)-fenthion sulfoxide by FMO represents a detoxification pathway, the results of this study support the notion that subsequent oxidative desulfuration of (R)-(+)-fenthion sulfoxide (in vivo) may represent a critical bioactivation pathway, resulting in the production of (R)-(+)-fenoxon sulfoxide, a potent AChE inhibitor.