Trophic Transfer of Dechloranes in the Marine Food Web of Liaodong Bay, North China

Dechloranes are of particular concern because of their ubiquity in environmental matrices, but little is known about their trophic transfer in aquatic food web. This study investigated the trophic transfer of seven dechloranes in a marine food web from Liaodong Bay, China. Dechloranes were determined in sediments and 15 marine species including benthic invertebrates, fish and gulls collected from Liaodong Bay. Biomagnification factors (BMF_TL) of dechloranes in black-headed gulls were calculated to be 6.4, 1.7, 0.45, 0.36, 0.14, and 0.11 for mirex, Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603), antiundecachloropentacyclooctadecadiene (anti-Cl₁₁DP), syn-dechlorane plus (syn-DP), and anti-DP. Significantly positive relationships were found between lipid equivalent concentrations of mirex, Dec 602, and anti-Cl₁₁DP and trophic levels, and the trophic magnification factors (TMFs) were 13, 3.7, and 5.6, respectively, indicating that these compounds undergo trophic magnification in the aquatic food web. Lipid equivalent concentrations of Dec 603 and DP isomers did not exhibit a statistically significant correlation with trophic levels. The relatively low trophic magnification potentials of Dec 603 and DP isomers were possibly due to their extreme hydrophobicity (log<i>K</i>_OW: 11.2–11.3) and subsequent low bioavailabilities compared with mirex (7.0), Dec 602 (8.1) and anti-Cl₁₁DP. The results provided important information for understanding the ecological risk of dechloranes

<i>p</i>,<i>p</i>′‑DDE Induces Gonadal Intersex in Japanese Medaka (<i>Oryzias latipes</i>) at Environmentally Relevant Concentrations: Comparison with <i>o</i>,<i>p</i>′‑DDT

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (<i>p</i>-chlorophenyl)-ethylene (<i>p</i>,<i>p</i>′-DDE) and <i>o</i>,<i>p</i>′<i>-</i>DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (<i>Oryzias latipes</i>) from hatch for 100 days. While both <i>p</i>,<i>p</i>′-DDE and <i>o</i>,<i>p</i>′-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of <i>o</i>,<i>p</i>′-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of <i>p</i>,<i>p</i>′-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to <i>o</i>,<i>p</i>′-DDT resulted in much higher expression of vitellogenin in liver of males than <i>p</i>,<i>p</i>′-DDE, accordant with the higher potency of <i>o</i>,<i>p</i>′-DDT than <i>p</i>,<i>p</i>′-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to <i>o</i>,<i>p</i>′-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (<i>p</i> = 0.006) and hatchability (<i>p</i> = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of <i>p</i>,<i>p</i>′-DDE and <i>o</i>,<i>p</i>′-DDT at environmentally relevant concentrations

Isomer-Specific Accumulation of Perfluorooctanesulfonate from (<i>N</i>‑Ethyl perfluorooctanesulfonamido)ethanol-based Phosphate Diester in Japanese Medaka (Oryzias latipes)

While (<i>N</i>-ethyl perfluorooctanesulfonamido)­ethanol (FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation to PFOS has not been verified. Metabolism of diSPAP was investigated in Japanese medaka (Oryzias latipes) after exposure in water for 10 days, followed by 10 days of depuration. Branched isomers of diSPAP (B-diSPAP) were preferentially enriched in medaka exposed to diSPAP, with the proportion of branched isomers (BF) ranging from 0.56 to 0.80, which was significantly greater than that in the water to which the medaka were exposed (0.36) (<i>p</i> < 0.001). This enrichment was due primarily to preferential uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide (PFOSA), <i>N</i>-ethyl perfluorooctanesulfonamide (NEtFOSA), 2-(perfluorooctanesulfonamido)­acetic acid (FOSAA), NEtFOSAA, FOSE, and NEtFOSE were detected in medaka exposed to diSPAP, which indicated the potential for biotransformation of diSPAP to PFOS via multiple intermediates. Due to preferential metabolism of branched isomers, FOSAA and PFOSA exhibited greater BF values (>0.5) than those of NEtFOSA, NEtFOSAA, and NEtFOSE (<0.2). Such preferential metabolism of branched isomers along the primary pathway of metabolism and preferential accumulation of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka. Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl PFOS (P₃MPFOS, P₄MPFOS, and P₅MPFOS), for which values of BF were 0.58 ± 0.07, 0.62 ± 0.06, and 0.61 ± 0.05 (day 6), respectively; these values are 5.8-, 7.8-, and 6.4-fold greater than those of technical PFOS. This work provides evidence on the isomer-specific accumulation of PFOS from diSPAP and will be helpful to track indirect sources of PFOS in the future

Identification of Chemicals that Cause Oxidative Stress in Oil Sands Process-Affected Water

Oil sands process-affected water (OSPW) has been reported to cause oxidative stress in organisms, yet the causative agents remain unknown. In this study, a high-throughput in vitro Nrf2 reporter system was used, to determine chemicals in OSPW that cause oxidative stress. Five fractions, with increasing polarity, of the dissolved organic phase of OSPW were generated by use of solid phase extraction cartridges. The greatest response of Nrf2 was elicited by F2 (2.7 ± 0.1-fold), consistent with greater hydroperoxidation of lipids in embryos of Japanese medaka (<i>Oryzias latipes</i>) exposed to F2. Classic naphthenic acids were mainly eluted in F1, and should not be causative chemicals. When F2 was fractionated into 60 subfractions by use of HPLC, significant activation of Nrf2 was observed in three grouped fractions: F2.8 (1.30 ± 0.01-fold), F2.16 (1.34 ± 0.05-fold), and F2.25 (1.28 ± 0.15-fold). 54 compounds were predicted to be potential chemicals causing Nrf2 response, predominated by SO₃⁺ and O₃⁺ species. By use of high-resolution MS² spectra, these SO₃⁺ and O₃⁺ species were identified as hydroxylated aldehydes. This study demonstrated that polyoxygenated chemicals, rather than classic NAs, were the major chemicals responsible for oxidative stress in the aqueous phase of OSPW

Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025× equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of <i>AP2</i>, <i>LPL</i>, and <i>PPARγ</i> gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS¹ and MS² spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ

Detection, Identification, and Quantification of Hydroxylated Bis(2-ethylhexyl)-Tetrabromophthalate Isomers in House Dust

Ultra-High Resolution LC/mass spectrometry (LC-UHRMS; Thermo Fisher Q-Exactive) was used to identify two novel isomers of hydroxylated bis­(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) which were unexpectedly observed in a commercial standard of TBPH. By combining ultra-high resolution (UHR) mass spectra (MS¹), mass errors to theoretical [TBPH-Br+O]⁻ were 2.1 and 1.0 ppm for the two isomers, UHR-MS² spectra and NMR analysis; the structures of the two compounds were identified as hydroxylated TBPH with a hydroxyl group on the aromatic ring. Relatively great proportions of the two isomers of OH-TBPH were detected in two technical products, Firemaster 550 (FM-550; 0.1% and 6.2%, respectively) and Firemaster BZ 54 (BZ-54; 0.1% and 7.9%), compared to a commercial standard (0.4% and 0.9%). To simultaneously analyze OH-TBPH isomers and TBPH in samples of dust, a method based on LC-UHRMS was developed to quantify the two compounds, using negative and positive ion modes, respectively. The instrumental limit of detection for TBPH was 0.01 μg/L, which was 200–300 times better than traditional methods (2.5 μg/L) based on gas chromatography–mass spectrometry. The analytical method combined with a Florisil cleanup was successfully applied to analyze TBPH and OH-TBPH in 23 indoor dust samples from Saskatoon, Saskatchewan, Canada. Two OH-TBPH isomers, OH-TBPH1 and OH-TBPH2, were detected in 52% and 91% of dust samples, respectively. Concentrations of OH-TBPH2 (0.35 ± 1.0 ng/g) were 10-fold greater than those of OH-TBPH1 (0.04 ± 0.88 ng/g) in dust, which was similar to profiles in FM-550 and BZ-54. TBPH was also detected in 100% of dust samples with a mean concentration of 733 ± 0.87 ng/g. A significant (<i>p</i> < 0.001) log–linear relationship was observed between TBPH and OH-TBPH isomers, further supporting the hypothesis of a common source of emission. Relatively small proportions of OH-TBPH isomers were detected in dust (0.01% ± 0.67 OH-TBPH1 and 0.1% ± 0.60 OH-TBPH2), which were significantly less than those in technical products (<i>p</i> < 0.001). This result indicated different environmental behaviors of OH-TBPH and TBPH. Detection of isomers of OH-TBPH is important, since compounds with phenolic groups have often shown relatively greater toxicities than nonhydroxylated analogues. Further study is warranted to clarify the environmental behaviors and potential toxicities of OH-TBPH isomers

High Conservation in Transcriptomic and Proteomic Response of White Sturgeon to Equipotent Concentrations of 2,3,7,8-TCDD, PCB 77, and Benzo[a]pyrene

Adverse effects associated with exposure to dioxin-like compounds (DLCs) are mediated primarily through activation of the aryl hydrocarbon receptor (AHR). However, little is known about the cascades of events that link activation of the AHR to apical adverse effects. Therefore, this study used high-throughput, next-generation molecular tools to investigate similarities and differences in whole transcriptome and whole proteome responses to equipotent concentrations of three agonists of the AHR, 2,3,7,8-TCDD, PCB 77, and benzo­[a]­pyrene, in livers of a nonmodel fish, the white sturgeon (<i>Acipenser transmontanus</i>). A total of 926 and 658 unique transcripts were up- and down-regulated, respectively, by one or more of the three chemicals. Of the transcripts shared by responses to all three chemicals, 85% of up-regulated transcripts and 75% of down-regulated transcripts had the same magnitude of response. A total of 290 and 110 unique proteins were up- and down-regulated, respectively, by one or more of the three chemicals. Of the proteins shared by responses to all three chemicals, 70% of up-regulated proteins and 48% of down-regulated proteins had the same magnitude of response. Among treatments there was 68% similarity between the global transcriptome and global proteome. Pathway analysis revealed that perturbed physiological processes were indistinguishable between equipotent concentrations of the three chemicals. The results of this study contribute toward more completely describing adverse outcome pathways associated with activation of the AHR

Mutagenic Azo Dyes, Rather Than Flame Retardants, Are the Predominant Brominated Compounds in House Dust

Characterization of toxicological profiles by use of traditional targeted strategies might underestimate the risk of environmental mixtures. Unbiased identification of prioritized compounds provides a promising strategy for meeting regulatory needs. In this study, untargeted screening of brominated compounds in house dust was conducted using a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) approach, which used data-independent acquisition (DIA) and a chemometric strategy to detect peaks and align precursor ions. A total of 1008 brominated compound peaks were identified in 23 house dust samples. Precursor ions and formulas were identified for 738 (73%) of the brominated compounds. A correlation matrix was used to cluster brominated compounds; three large groups were found for the 140 high-abundance brominated compounds, and only 24 (17%) of these compounds were previously known flame retardants. The predominant class of unknown brominated compounds was predicted to consist of nitrogen-containing compounds. Following further validation by authentic standards, these compounds (56%) were determined to be novel brominated azo dyes. The mutagenicity of one major component was investigated, and mutagenicity was observed at environmentally relevant concentrations. Results of this study demonstrated the existence of numerous unknown brominated compounds in house dust, with mutagenic azo dyes unexpectedly being identified as the predominant compounds

Combined Transcriptomic and Proteomic Approach to Identify Toxicity Pathways in Early Life Stages of Japanese Medaka (Oryzias latipes) Exposed to 1,2,5,6-Tetrabromocyclooctane (TBCO)

Currently, the novel brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO) is considered a potential replacement for hexabromocyclododecane (HBCD). Therefore, use of TBCO could increase in the near future. To assess potential toxicological risks to aquatic organisms, embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100, or 1000 μg/L TBCO from 2 h postfertilization until 1 day post-hatch. TBCO accumulated in embryos in the order of 0.43–1.3 × 10⁴-fold, and the rate constant of accumulation was 1.7–1.8 per day. The number of days to hatch and the hatching success of embryos exposed to the medium and the greatest concentrations of TBCO were impaired. Responses of the transcriptome (RNA-seq) and proteome were characterized in embryos exposed to 100 μg/L TBCO because this was the least concentration of TBCO that caused an effect on hatching. Consistent with effects on hatching, proteins whose abundances were reduced by exposure to TBCO were enriched in embryo development and hatching pathways. Also, on the basis of the responses of transcriptome and proteome, it was predicted that TBCO might impair vision and contraction of cardiac muscle, respectively, and these effects were confirmed by targeted bioassays. This study provided a comprehensive understanding of effects of TBCO on medaka at early life stages and illustrated the power of “omics” to explain and predict phenotypic responses to chemicals

Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage Specific Differences in Sensitivity of White Sturgeon (<i>Acipenser transmontanus</i>) to Copper or Cadmium

Sensitivity of white sturgeon (<i>Acipenser transmontanus</i>) to copper (Cu) or cadmium (Cd) has been shown to significantly differ as a function of life-stage. This study investigated oxidative stress, metal homeostasis, and associated compensatory responses as potential mechanisms of this sensitivity pattern in three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch (dph), which was accompanied by a significant increase in lipid peroxidation (LPO). Genes involved with amelioration of oxidative stress were significantly less inducible at this stage than in older, less sensitive fry. At 48 dph, acute lethality of sturgeon exposed to Cd was greatest and body LPO was significantly induced by 3.5-fold at 5 μg Cd/L. Moreover, there was a small but significant increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to Cu and Cd and accumulation of these metals was least. Also, expression of metallothionein (MT) and apoptotic genes were greatest while expression of metal transporters was reduced and concentration of LPO was not different from controls. Our results suggest that life-stage specific sensitivity of white sturgeon to metals is complex, encompassing differences in the ability to mount compensatory responses important for metal homeostasis and combating oxidative stress and concomitant damages