Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor

Metabolites of methoxychlor such as 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1-trichloroethane (mono-OH-MXC) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which the carbon atom bridging two benzene rings is the chiral centre. In previous studies the estrogenic activity of racemic mono-OH-MXC has been measured, and the activity of each enantiomer of this compound has not yet been elucidated. In this study, we evaluated the estrogen receptor-binding activity of each enantiomer of mono-OH-MXC to clarify the enantioselective recognition by the estrogen receptor. (S)-mono-OH-MXC showed 3-fold higher binding activity than that of the (R) enantiomer. The activity of bis-OH-MXC was only 1.7-fold higher than that of (S)-mono-OH-MXC. This result suggests that the one hydroxy group and the orientation of the CCl3 group of mono- and bis-OH-MXCs are important for the interaction with the estrogen receptor. The result also points out the estrogenic activity of methoxychlor after metabolic activation in vivo, which predominantly produces the (S)-mono-OH-MXC, may be higher than estimated from the in vitro activity of racemic mixtures.     

Chromatographic enantiomer separation of chiral xenobiotics and their metabolites--a versatile tool for process studies in marine and terrestrial ecosystems

A review discussing methodical aspects of enantioselective chromatographic separation of chiral environmental xenobiotics as well as examples for process studies reported in literature. The process studies include microbial transformation of chiral pollutants in aquatic ecosystems, their enzymatic transformation in biota, their photochemical degradation, air/sea exchange processes and atmospheric long range transport, and enantioselective toxic effects.     

Toxicity of fipronil and its enantiomers to marine and freshwater non-targets

Fipronil is a phenylpyrazole insecticide used in agricultural and domestic settings for controlling various insect pests in crops, lawns, and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this study, the acute toxicity of the (S,+) and (R,-) enantiomers and the racemic mixture of fipronil were assessed using Simulium vittatum IS-7 (black fly), Xenopus laevis (African clawed frog), Procambarus clarkii (crayfish), Palaemonetes pugio (grass shrimp), Mercenaria mercenaria (hardshell clam), and Dunaliella tertiolecta (phytoplankton). Results showed that S. vittatum IS-7 was the most sensitive freshwater species to the racemic mixture of fipronil (LC50 = 0.65 microg/L) while P. pugio was the most sensitive marine species (LC50 = 0.32 microg/L). Procambarus clarkii were significantly more sensitive to the (S,+) enantiomer while larval P. pugio were significantly more sensitive to the (R,-) enantiomer. Enantioselective toxicity was not observed in the other organisms tested. Increased mortality and minimal recovery was observed in all species tested for recovery from fipronil exposure. These results indicate that the most toxic isomer of fipronil is organism-specific and that enantioselective toxicity may be more common in crustaceans than in other aquatic organisms.     

Chiral signatures of PCB#s 95 and 149 in indoor air, grass, duplicate diets and human faeces

Chiral signatures of PCB#s 95 and 149 are reported for indoor air, grass, omnivorous and vegan duplicate human diet homogenates, and human faeces. Comparison of chiral signatures of both congeners in grass with those reported previously for outdoor air (measured at a height of 1.5 m) and soil at the same location suggest that volatilisation of PCBs present in soil may exert a significant influence on concentrations in grass. Duplicate diet homogenates display racemic signatures for both congeners. Alongside the racemic signatures in both outdoor and indoor air, this implies that human intake via diet and inhalation is racemic, and that the previously observed variation between individuals in the extent of enantioselective degradation in human liver samples indicates possible inter-individual variation in ability to metabolise PCBs. Chiral signatures of PCB# 95 in the 10 human faecal samples analysed indicate 8 to be racemic, but 2 to display an excess of the 2nd eluting enantiomer. This is consistent with the excess of the 1st eluting enantiomer reported elsewhere for human liver samples, as it implies enantioselective excretion of the 2nd eluting enantiomer. However, the racemic residues for PCB# 95 in the majority of faecal samples are a possible indication that enantioselective interaction of chiral PCBs with cytochrome P450 occurs slowly. The racemic or near-racemic signatures observed for PCB# 95 and 149 in indoor air match closely those in outdoor air, but differ from those in soil, adding to the weight of evidence that ventilation of indoor air is a far more significant contributor to outdoor air concentrations than volatilisation of PCBs from soil.     

Enantioselectivity in environmental risk assessment of modern chiral pesticides

Chiral pesticides comprise a new and important class of environmental pollutants nowadays. With the development of industry, more and more chiral pesticides will be introduced into the market. But their enantioselective ecotoxicology is not clear. Currently used synthetic pyrethroids, organophosphates, acylanilides, phenoxypropanoic acids and imidazolinones often behave enantioselectively in agriculture use and they always pose unpredictable enantioselective ecological risks on non-target organisms or human. It is necessary to explore the enantioselective toxicology and ecological fate of these chiral pesticides in environmental risk assessment. The enantioselective toxicology and the fate of these currently widely used pesticides have been discussed in this review article.     

Toxicokinetics of chiral polychlorinated biphenyls across different species—a review

Nineteen polychlorinated biphenyls (chiral or C-PCBs) exist as two stable rotational isomers (atropisomers) that are non-superimposable mirror images of each other. C-PCBs are released into the environment as racemic (i.e., equal) mixtures of both atropisomers and undergo atropisomeric enrichment due to biological, but not abiotic, processes. In particular, toxicokinetic studies provide important initial insights into atropselective processes involved in the disposition (i.e., absorption, distribution, biotransformation, and excretion) of C-PCBs. The toxicokinetic of C-PCBs is highly congener and species dependent. In particular, at lower trophic levels, abiotic processes play a predominant role in C-PCB toxicokinetics. Biotransformation plays an important role in the elimination of C-PCBs in mammals. The elimination of C-PCB follows the approximate order mammals > birds > amphibians > fish, mostly due to a corresponding decrease in metabolic capacity. A few studies have shown differences in the toxicokinetics of C-PCB atropisomers; however, more work is needed to understand the toxicokinetics of C-PCBs and the underlying biological processes. Such studies will not only contribute to our understanding of the fate of C-PCBs in aquatic and terrestrial food webs but also facilitate our understanding of human exposures to C-PCBs.     

Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI FT-ICR MS): Characterization of Complex Environmental Mixtures

Structural and chemical characterization of compounds within complex environmental mixtures provides unique insights into the roles of these compounds in different environmental processes. Here, an emerging technique in environmental chemistry, electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS), is described and its applications to the molecular characterization of humic acids and petroleum products are reviewed and examined. ESI is a low-fragmentation ionization technique that preferentially ionizes polar functional groups prior to mass spectrometric analysis. This technique allows the characterization of intact polar macromolecules that are inaccessible to standard chromatographic techniques. ICR MS is an ultrahigh resolution and mass accuracy MS technique based on the detection of ion cyclotron motion within a magnetic field. The combination of ESI FT-ICR MS with other structural techniques such as nuclear magnetic resonance (NMR) allows the unprecedented identification and characterization of polar macromolecules in environmental mixtures and will find numerous applications within environmental chemistry and forensics.     

Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI FT-ICR MS): Characterization of Complex Environmental Mixtures

Structural and chemical characterization of compounds within complex environmental mixtures provides unique insights into the roles of these compounds in different environmental processes. Here, an emerging technique in environmental chemistry, electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS), is described and its applications to the molecular characterization of humic acids and petroleum products are reviewed and examined. ESI is a low-fragmentation ionization technique that preferentially ionizes polar functional groups prior to mass spectrometric analysis. This technique allows the characterization of intact polar macromolecules that are inaccessible to standard chromatographic techniques. ICR MS is an ultrahigh resolution and mass accuracy MS technique based on the detection of ion cyclotron motion within a magnetic field. The combination of ESI FT-ICR MS with other structural techniques such as nuclear magnetic resonance (NMR) allows the unprecedented identification and characterization of polar macromolecules in environmental mixtures and will find numerous applications within environmental chemistry and forensics.     

2,5,6,9,10-Pentabromocyclododecanols (PBCDOHs): a new class of HBCD transformation products

Pentabromocyclododecanols (PBCDOHs) are potential environmental transformation products of hexabromocyclododecanes (HBCDs). They are also potential stage one metabolites of biological HBCD transformations. Herein, we present analytical evidence that PBCDOHs are also constituents of technical HBCDs and flame-proofed polystyrenes (FP-PSs). PBCDOHs are possibly formed during the synthesis of technical HBCD, presumably during the bromination of cyclododecatrienes in aqueous isobutanol together with isobutoxypentabromocyclododecanes (iBPBCDs), which have been identified in these materials recently. Of the 64 stereoisomers possible, eight pairs of enantiomers, named α-, β-, γ-, δ-, ε-, ζ-, η-, and θ-PBCDOHs were separated with a combination of normal-, reversed- and chiral-phase LC. Crystal structure analysis revealed the stereochemistry of the α-PBCDOH pair of enantiomers, which was assigned to (1S,2S,5R,6S,9S,10R)-2,5,6,9,10-pentabromocyclododecanol and its enantiomer. Mass spectrometric data are in accordance with the expected isotope patterns. On a C₁₈-RP-column, the polar PBCDOHs eluted before the HBCD and iBPBCD classes of compounds. PBCDOHs were also found in FP-PS materials. The stereoisomer patterns varied considerably in these materials like those of HBCDs and iBPBCDs. Expanded polystyrenes were rich in late-eluting stereoisomers, similar to technical HBCD mixtures. Extruded polystyrenes contained more of the polar, faster-eluting isomers. The presented chromatographic and analytical methods allow a stereoisomer-specific search for PBCDOHs in biota samples, which might have experienced metabolic HBCD transformation reactions. Besides this potential source, it has to be recognized that PBCDOHs are by-products in technical HBCDs and in flame-proofed polystyrenes. Therefore, it is likely that PBCDOHs and iBPBCDs are released to the environment together with HBCD-containing plastic materials.     

Enantiomer fractions of polychlorinated biphenyls in three selected Standard Reference Materials

The enantiomer composition of six chiral polychlorinated biphenyls (PCBs) were measured in three different certified Standard Reference Materials (SRMs) from the US National Institute of Standards and Technology (NIST): SRM 1946 (Lake Superior fish tissue), SRM 1939a (PCB Congeners in Hudson River Sediment), and SRM 2978 (organic contaminants in mussel tissue--Raritan Bay, New Jersey) to aid in quality assurance/quality control methodologies in the study of chiral pollutants in sediments and biota. Enantiomer fractions (EFs) of PCBs 91, 95, 136, 149, 174, and 183 were measured using a suite of chiral columns by gas chromatography/mass spectrometry. Concentrations of target analytes were in agreement with certified values. Target analyte EFs in reference materials were measured precisely (<2% relative standard deviation), indicating the utility of SRM in quality assurance/control methodologies for analyses of chiral compounds in environmental samples. Measured EFs were also in agreement with previously published analyses of similar samples, indicating that similar enantioselective processes were taking place in these environmental matrices.     

Methylsulfonyl PCB and DDE metabolites and their enantioselective gas chromatographic separation in human adipose tissues, seal blubber and pelican muscle

In the present investigation, eleven human adipose tissue samples, two seal blubber samples and two pelican muscles samples were analyzed with regard to their concentrations of PCB parent compounds as well as to the respective chiral methylsulfonyl metabolites 3-MeSO2-CB 91, 4-MeSO2-CB 91, 3-MeSO2-CB 95, 4-MeSO2-CB 95, 3-MeSO2-CB 149, 4-MeSO2-CB 149, 3-MeSO2-CB 132, 4-MeSO2-CB 132, 3-MeSO2-CB 174, and 4-MeSO2-CB 174 and the achiral metabolites 3-MeSO2-CB 49, 4-MeSO2-CB 49, 3-MeSO2-CB 101, 4-MeSO2-CB 101, 3-MeSO2-CB 110, 4-MeSO2-CB 110 and 3-MeSO2-DDE. In order to verify enantioselective transformation processes and to compare the different enzymatic transformation pathways in birds and mammals, the enantioselective excesses of the chiral PCB-metabolites were determined by enantioselective gas chromatography with electron capture and mass spectrometric detection using modified cyclodextrin phases, including heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl-)-beta-cyclodextrin/OV1701 (1:1) for the parent PCBs and heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl-)-beta-cyclodextrin/SE52 (1:4) for the metabolites, respectively.     

The synthetic pyrethroid isomers I. Preparation

Abstract

Enantiomers and racemic mixtures of selected benzilic esters using resolved and raceme permethrinic or chrysanthemic acids of high purity were synthesised via improved methods based on conventional steps. Nine basic structures of selected derivatives having hydrogen, bromo or phenoxy group at meta position were prepared including the well known insecticides of phenothrin, permethrin and cypermethrin. The optical purity of these compounds were determined via an NMR method applying chiral shift reagents. The configuration of the isomers of new a‐cyano‐benzyl esters were assigned via a rule realized by comparing the characteristic 1H NMR shifts of the dimethyl groups attached to the cyclopropane ring.     

Preliminary evaluation of bitumen contamination in environmental samples using comprehensive gas chromatography GcxGc – Time of flight mass spectrometry (GCxGC-TOFMS)

Abstract

Bitumen and bitumen impacted soil and water samples were investigated for their relative chemical composition using comprehensive gas chromatography GcxGc – time of flight mass spectrometry (GCxGC-TOFMS). The results reveal the presence of key compounds which could serve as environmental biomarkers for bitumen impacted soils and aquifers. Prominent alkanes such as 3-methylpentane; 2,2,4-trimethylpentane; 1,3,5-trimethyladamantane; 2,6,10-trimethyldodecane; 3-ethyl-2,2-dimethyl pentane were tentatively identified and are likely potent biomarkers in environmental forensic assessment of bitumen contamination while the presence of some aromatic compounds: 1,2-benzenedicarboxylic acid, 1,2-dimethyl-3-propylbenzene; 3,4-bis(methoxycarbonyl)benzoic acid; 1,3-bezenedicarboxylic acid, 1,2-benzenediol; 1,3-dimethylbenzene; 1,2-2-(2-ethylhexoxycarbonyl)benzoic acid; (4-methylpentan-2-yl)benzene; 2,4-dimethyl benzo(H)quinolone will further confirm the bitumen contamination in an area under investigation. A host of additional compounds were tentatively identified, mainly in the bitumen samples. The results obtained in this study provides baseline data for effective monitoring, and source apportionment of oil/oil products spills.     

The environmental fate of the primary degradation products of alkylphenol ethoxylate surfactants in recycled paper sludge.

Alkylphenol ethoxylates (APEOs) are a group of non-ionic surfactants that are degraded microbially into more lipophilic degradation products with estrogenic potential, including nonylphenol monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO), octylphenol (4-tOP) and nonylphenol (4-NP). Nonylphenol ethoxylates are used in paper recycling plants for de-inking paper and have the potential to be released into the environment through spreading of wastewater treatment sludge for soil amendment. Three samples of recycled paper sludge were collected from farmers' fields and analyzed for concentrations of NP1EO, NP2EO, 4-NP and 4-tOP. Each sample differed in the amount of time elapsed since the sludge was placed on farmers' fields. Primary degradation products of APEOs were present at low micrograms/g concentrations in the sludge samples. Differences in the concentrations of these analytes in sludge samples indicated that APEO concentrations declined by 84% over a period of 14 weeks on farmers' fields. Changes in the chromatographic patterns of acetylated 4-NP indicated that there is a group of recalcitrant nonylphenol isomers that degrades more slowly than other isomers. These data indicate that microbial degradation may reduce the risk of environmental contamination by these compounds, but more work is required to assess the toxic potential of APEOs in sludges used for soil amendment.     

Enantioselective separation and determination of single nonylphenol isomers

It has recently become clear that an isomer specific view of technical 4-nonylphenol (NP) is absolutely necessary for the evaluation of the biological behavior of NP, raising additional questions concerning enantiomer specific effects. For the first time, in this study enantioselective HPLC was applied to enantiomeric separation of chiral NP isomers. A semipreparative separation of two NP isomers could be achieved. A GC-MS method has been developed for the simultaneous detection of three chiral NP isomers in water samples. Investigation of influent and effluent samples from a wastewater treatment plant in Germany indicated that enantioselective degradation could occur in the environment. In one examined influent, an enantiomer ratio of 1.7 for two different isomers was determined.     

Enantioselectivity in toxicity and degradation of dichlorprop-methyl in algal cultures

Enantioselectivity in the toxicity and degradation of the herbicide dichlorprop-methyl (2,4-DCPPM) in algal cultures was studied. Enantioselectivity was clearly observed in the toxicity of racemic 2,4-DCPPM and its two enantiomers. R-2,4-DCPPM showed low toxicity to Chlorella pyrenoidosa and Chlorella vulgaris, but higher toxicity to Scenedesmus obliquus. The observed toxicity was ranked: R-2,4-DCPPM>S-2,4-DCPPM>Rac-2,4-DCPPM; the toxicity of R-2,4-DCPPM was about 8-fold higher than that of Rac-2,4-DCPPM. Additionally, 2,4-DCPPM was quickly degraded, in the initial 12 h, and different algae cultures had different enantioselectivity for the 2,4-DCPPM enantiomers. There was no significant enantioselectivity for 2,4-DCPPM in Chlorella vulgaris in the initial 7 h. However, racemic 2,4-DCPPM was degraded by Scenedesmus obliquus quickly, in the initial 4 h, much quicker, in fact, than the S- or R-enantiomers (racemate>R->S-), indicating that the herbicide 2,4-DCPPM was absorbed enantioselectively by Scenedesmus obliquus. The rapid formation of 2,4-DCPP suggested that 2,4-DCPPM adsorbed by algal cells was catalytically hydrolyzed to the free acid, a toxic metabolite. The production rates of 2,4-DCPP were as follows: Scenedesmus obliquus>Chlorella pyrenoidosa>Chlorella vulgaris, consistent with the degradability of 2,4-DCPPM. Scenedesmus obliquus had quick, but different, degradative and uptake abilities for R-, S-, and Rac-2,4-DCPPM. The R- and S- enantiomers were not hydrolyzed in the first 12 h, while both enantiomers were hydrolyzed slowly after that. These results indicate that some physical and chemical properties of compounds are of importance in determining their enantioselective toxicity and degradation. The ester and its metabolite likely played an important role in enantioselective toxicity to the three algae.     

Progestagens for human use, exposure and hazard assessment for the aquatic environment

Little information is available on the environmental occurrence and ecotoxicological effects of pharmaceutical gestagens released in the aquatic environment. Since eighteen different gestagens were found to be used in France, preliminary exposure and hazard assessment were done. Predicted environmental concentrations (PECs) suggest that if parent gestagens are expected to be found in the ng l⁻¹ range, some active metabolites could be present at higher concentrations, although limited data on metabolism and environmental fate limit the relevance of PECs. The biological effects are not expected to be restricted to progestagenic activity. Both anti-androgenic activity (mainly for cyproterone acetate, chlormadinone acetate and their metabolites) and estrogenic activity (mainly for reduced metabolites of levonorgestrel and norethisterone) should also occur. All these molecules are likely to have a cumulative effect among themselves or with other xenoestrogens. Studies on occurrence, toxicity and degradation time are therefore needed for several of these compounds.     

Degradation of 1,2-dichloroethane from wash water of ion-exchange resin using Fenton’s oxidation

Background, aim, and scope  

Chlorinated volatile organic compounds (CVOCs), widely used in industry as solvents and chemical intermediates in the production of synthetic resins, plastics, and pharmaceuticals, are highly toxic to the environment and public health. Various studies reported that Fenton’s oxidation could degrade a variety of chlorinated VOCs in aqueous solutions. In acidic conditions, ferrous ion catalyzes the decomposition of H₂O₂ to form a powerful ^•OH radical. In this study, wastewater from wash of ion-exchange resin containing typical CVOC, 1,2-dichloroethane, was treated using Fenton’s oxidation. To reduce environmental load and processing costs of wastewater, Fenton process as a simple and efficient treatment method was applied to degrade 1,2-dichloroethane of wash water.     

Biodegradation of potential diesel oxygenate additives: dibutyl maleate (DBM), and tripropylene glycol methyl ether (TGME)

The addition of oxygen-bearing compounds to diesel fuel considerably reduces particulate emissions. TGME and DBM have been identified as possible diesel additives based on their physicochemical characteristics and performance in engine tests. Although these compounds will reduce particulate emissions, their potential environmental impacts are unknown. As a means of characterizing their persistence in environmental media such as soil and groundwater, we conducted a series of biodegradation tests of DBM and TGME. Benzene and methyl tertiary butyl ether (MTBE) were also tested as reference compounds. Primary degradation of DBM fully occurred within 3 days, while TGME presented a lag phase of approximately 8 days and was not completely degraded by day 28. Benzene primary degradation occurred completely by day 3 and MTBE did not degrade at all. The total mineralized fractions of DBM and TGME achieved constant values as a function of time of approximately 65% and approximately 40%, respectively. Transport predictions show that, released to the environment, DBM and TGME would concentrate mostly in soils and waters with minimal impact to air. From an environmental standpoint, these results combined with the transport predictions indicate that DBM is a better choice than TGME as a diesel additive.