Abstract
A combined chemical and biological analysis of samples from a major obsolete pesticide and persistent organic pollutant (POP) dumpsite in Northern Tajikistan was carried out. The chemical analytical screening focused on a range of prioritized compounds and compounds known to be present locally. Since chemical analytics does not allow measurements of hazards in complex mixtures, we tested the use of a novel effect-based approach using a panel of quantitative high-throughput CALUX reporter assays measuring distinct biological effects relevant in hazard assessment. Assays were included for assessing effects related to estrogen, androgen, and progestin signaling, aryl hydrocarbon receptor-mediated signaling, AP1 signaling, genotoxicity, oxidative stress, chemical hypoxia, and ER stress. With this panel of assays, we first quantified the biological activities of the individual chemicals measured in chemical analytics. Next, we calculated the expected sum activity by these chemicals in the samples of the pesticide dump site and compared the results with the measured CALUX bioactivity of the total extracts of these samples. The results showed that particularly endocrine disruption-related effects were common among the samples. This was consistent with the toxicological profiles of the individual chemicals that dominated these samples. However, large discrepancies between chemical and biological analysis were found in a sample from a burn place present in this site, with biological activities that could not be explained by chemical analysis. This is likely to be caused by toxic combustion products or by spills of compounds that were not targeted in the chemical analysis.
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Ameyar M, Wisniewska M, Weitzman JB (2003) A role for AP-1 in apoptosis: the case for and against. Biochimie 85:747–752
Ashida R, Tominaga K, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Mitsuyama S, Iwao H, Arakawa T (2005) AP-1 and colorectal cancer. Inflammopharmacology 13:113–125
Beck M, Schmidt A, Malmstroem J, Claassen M, Ori A, Szymborska A, Herzog F, Benigni R, Battistelli CL, Bossa C, Tcheremenskaia O, Crettaz P (2013) New perspectives in toxicological information management, and the role of ISSTOX databases in assessing chemical mutagenicity and carcinogenicity. Mutagenesis 28:401–409. doi:10.1093/mutage/get016
Benigni R, Battistelli CL, Bossa C, Tcheremenskaia O, Crettaz P (2013) New perspectives in toxicological information management, and the role of ISSTOX databases in assessing chemical mutagenicity and carcinogenicity. Mutagenesis 28(4):401–9. doi:10.1093/mutage/get016
Besselink HT, Schipper C, Klamer H, Leonards P, Verhaar H, Felzel E, Murk AJ, Thain J, Hosoe K, Schoeters G, Legler J, Brouwer B (2004) Intra- and interlaboratory calibration of the DR CALUX bioassay for the analysis of dioxins and dioxin-like chemicals in sediments. Environ Toxicol Chem 23(12):2781–2789
Brand W, de Jongh CM, van der Linden SC, Mennes W, Puijker LM, van Leeuwen CJ, van Wezel AP, Schriks M, Heringa MB (2013) Trigger values for investigation of hormonal activity in drinking water and its sources using CALUX bioassays. Environ Int 55:109–118
De Coster S, van Larebeke N (2012) Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health 2012:713696
Dutch Government (2014) Annex B to the Dutch guidelines on soil qualities: background values and maximum values for soil and dredging sludge. http://wetten.overheid.nl/BWBR0023085/BijlageB/geldigheidsdatum_15-05-2014
Feng S, Cao Z, Wang X (2013) Role of aryl hydrocarbon receptor in cancer. Biochim Biophys Acta 1836:197–210. doi:10.1016/j.bbcan.2013.05.001
Food and Agriculture Organization of the United Nations (FAO) (2001) The ticking time bomb: toxic pesticide waste dumps. Newsroom 9 http://www.fao.org/english/newsroom/highlights/2001/010502-e.htm
Food and Agriculture Organization of the United Nations (FAO) (2014) Where are the stocks? http://www.fao.org/agriculture/crops/obsolete-pesticides/where-stocks/en/
Garrison PM, Tullis K, Aarts JM, Brouwer A, Giesy JP, Denison MS (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Fundam Appl Toxicol 30(2):194–203
Geiger T, Wehner A, Schaab C, Cox J, Mann M (2012) Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Mol Cell Proteomics 11(3):M111.014050. doi:10.1074/mcp.M111.014050
Gibson DA, Saunders PT (2013) Endocrine disruption of estrogen action and female reproductive tract cancers. Endocr Relat Cancer. Oct 25. [Epub ahead of print]
Giesy JP, Kannan K (1998) Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment. Crit Rev Toxicol 28(6):511–569
Gregoraszczuk EL, Ptak A (2013) Endocrine-disrupting chemicals: some actions of POPs on female reproduction. Int J Endocrinol 2013:828532
Holt E, Weber R, Stevenson G, Gaus C (2010) Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) impurities in pesticides: a neglected source of contemporary relevance. Environ Sci Technol 44(14):5409–5415. doi:10.1021/es903915k
Holt E, Weber R, Stevenson G, Gaus C (2012) Formation of dioxins during exposure of pesticide formulations to sunlight. Chemosphere 88:364–370
Huang J, Gao J, Yu G, Yamazaki N, Deng S, Wang B, Weber R (2014) Unintentional formed PCDDs, PCDFs and DL-PCBs as impurities in Chinese pentachloronitrobenzene products. Environ Sci Pollut Res in print
Italian Ministry for the Environment, Land and Sea (2006) Transboundary risk assessment on the hazardous waste sites of Kanibadam, Khaidarken, Kadamjai in the Ferghana Valley, Regional Synthesis Report. 2006. http://enrin.grida.no/htmls/ferghana_valley/ferghana_valley_soe/pdf/rehra-eng.pdf
Jiang L, Sheikh MS, Huang Y (2010) Decision making by p53: life versus death. Mol Cell Pharmacol 2:69–77
Kortenkamp A (2007) Ten years of mixing cocktails: a review of combination effects of endocrine-disrupting chemicals. Environ Health Perspect 115(Suppl 1):98–105. doi:10.1289/ehp.9357
Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426. doi:10.1146/annurev-pharmtox-011112-140320
Marhefka CA, Moore BM 2nd, Bishop TC, Kirkovsky L, Mukherjee A, Dalton JT, Miller DD (2001) Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands. J Med Chem 24:1729–1740
Marlowe JL, Puga A (2005) Aryl hydrocarbon receptor, cell cycle regulation, toxicity, and tumorigenesis. J Cell Biochem 96(6):1174–1184
Matsusue K, Ariyoshi N, Oguri K, Koga N, Yoshimura H (1996) Involvement of cytochrome b5 in the metabolism of tetrachlorobiphenyls catalyzed by CYP2B1 and CYP1A1. Chemosphere 32(3):517–523
Mostafalou S, Abdollahi M (2013) Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol 268:157–177. doi:10.1016/j.taap.2013.01.025
Mrema EJ, Rubino FM, Brambilla G, Moretto A, Tsatsakis AM, Colosio C (2013) Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology 307:74–88. doi:10.1016/j.tox.2012.11.015
Muller PA, Vousden KH (2013) p53 mutations in cancer. Nat Cell Biol 15(1):2–8. doi:10.1038/ncb2641
Nakatsuru Y, Wakabayashi K, Fujii-Kuriyama Y, Ishikawa T, Kusama K, Ide F (2004) Dibenzo[A, L]pyrene-induced genotoxic and carcinogenic responses are dramatically suppressed in aryl hydrocarbon receptor-deficient mice. Int J Cancer 112:179–183
Netherlands Standardization Institute (NEN) (2010) NEN 6980:2008+C1:2010+C2:2011 nl: Soil—quantitative analysis of organochlorine pesticides, pentachlorobiphenyls, and semi-volatile chlorobenzenes by gas chromatography. (in Dutch). http://www.nen.nl/NEN-Shop/Norm/NEN-69802008C12010C22011-nl-1.htm
Papadopoulou E, Vafeiadi M, Agramunt S, Mathianaki K, Karakosta P, Spanaki A, Besselink H, Kiviranta H, Rantakokko P, Sarri K, Koutis A, Chatzi L, Kogevinas M (2013) Maternal diet, prenatal exposure to dioxins and other persistent organic pollutants and anogenital distance in children. Sci Total Environ 461–462:222–229
Piersma AH, Bosgra S, van Duursen MB, Hermsen SA, Jonker LR, Kroese ED, van der Linden SC, Man H, Roelofs MJ, Schulpen SH, Schwarz M, Uibel F, van Vugt-Lussenburg BM, Westerhout J, Wolterbeek AP, van der Burg B (2013) Evaluation of an alternative in vitro test battery for detecting reproductive toxicants. Reprod Toxicol 38:53–64. doi:10.1016/j.reprotox.2013.03.002
Pieterse B, Felzel E, Winter R, van der Burg B, Brouwer A (2013) PAH-CALUX, an optimized bioassay for AhR-mediated hazard identification of polycyclic aromatic hydrocarbons (PAHs) as individual compounds and in complex mixtures. Environ Sci Technol 47:11651–11659. doi:10.1021/es403810w
Porpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, Ferro A, Ingelido AM, Maggi A, Panici PB, De Felip E (2009) Endometriosis and organochlorinated environmental pollutants: a case–control study on Italian women of reproductive age. Environ Health Perspect 117(7):1070–1075
Pyrzynska B, Mosieniak G, Kaminska B (2000) Changes of the trans-activating potential of AP-1 transcription factor during cyclosporin A-induced apoptosis of glioma cells are mediated by phosphorylation and alterations of AP-1 composition. J Neurochem 74(1):42–51
Quaedackers ME, Van Den Brink CE, Wissink S, Schreurs RH, Gustafsson JA, Van Der Saag PT, Van Der Burg BB (2001) 4-hydroxytamoxifen trans-represses nuclear factor-kappa B activity in human osteoblastic U2-OS cells through estrogen receptor (ER)alpha, and not through ER beta. Endocrinology 142:1156–1166
Ritter L, Solomon KR, Forget J (1995) A review on selected persistent organic pollutants. Prepared for The International Programme on Chemical Safety (IPCS). http://cdrwww.who.int/ipcs/assessment/en/pcs_95_39_2004_05_13.pdf
Salnikow K, Davidson T, Zhang Q, Chen LC, Su W, Costa M (2003) The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis. Cancer Res 63(13):3524–3530
Scheringer M, Strempel S, Hukari S, Ng CA, Blepp M, Hungerbühler K (2012) How many persistent organic pollutants should we expect? Atmos Pollut Res 3:383–391
Schrader TJ, Boyes BG, Matula TI, Héroux-Metcalf C, Langlois I, Downie RH (1998) In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese hamster V79 lung fibroblasts. Mutat Res 413:159–168
Semenza GL, Agani F, Feldser D, Iyer N, Kotch L, Laughner E, Yu A (2000) Hypoxia, HIF-1, and the pathophysiology of common human diseases. Adv Exp Med Biol 475:123–130
Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4(5):E131–E136
Shuttleworth KL, Cerniglia CE (1995) Environmental aspects of PAH biodegradation. Appl Biochem Biotechnol 54(1–3):291–302
Simmons SO, Fan CY, Yeoman K, Wakefield J, Ramabhadran R (2011) Nrf2 oxidative stress induced by heavy metals is cell type dependent. Curr Chem Genom 5:1–12. doi:10.2174/1875397301105010001
Sonneveld E, Jansen HJ, Riteco JA, Brouwer A, van der Burg B (2005) Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. Toxicol Sci 83(1):136–148
Sonneveld E, Riteco JA, Jansen HJ, Pieterse B, Brouwer A, Schoonen WG, van der Burg B (2006) Comparison of in vitro and in vivo screening models for androgenic and estrogenic activities. Toxicol Sci 89(1):173–187
Stockholm Convention (2001) Stockholm Convention on persistent organic pollutants. http://www.pops.int/documents/convtext/convtext_en.pdf
Suzuki G, Tue NM, van der Linden S, Brouwer A, van der Burg B, van Velzen M, Lamoree M, Someya M, Takahashi S, Isobe T, Tajima Y, Yamada TK, Takigami H, Tanabe S (2011) Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals. Environ Sci Technol 45(23):10203–10211
UNEP (2013) Toolkit for identification and quantification of releases of dioxins, furans and other unintentional POPs under Article 5 of the Stockholm Convention on Persistent Organic Pollutants. http://chm.pops.int/Portals/0/download.aspx?d=UNEP-POPS-TOOLKIT-TOOLK-PCDD-PCDF-2012.En.pdf
Vakharia DD, Gierthy JF (2000) Use of a combined human liver microsome-estrogen receptor binding assay to assess potential estrogen modulating activity of PCB metabolites. Toxicol Lett 114(1–3):55–65
Van der Burg B, Pieterse B, Buist H, Lewin G, Van der Linden SC, Man HY, Rorije E, Piersma AH, Mangelsdorf I, Wolterbeek AP, Kroese ED, Van Vugt-Lussenburg B (2014) A high throughput screening system for predicting chemically-induced reproductive organ deformities. Reprod Toxicol. doi:10.1016/j.reprotox.2014.11.011
van der Linden SC, von Bergh AR, van Vught-Lussenburg BM, Jonker LR, Teunis M, Krul CA, van der Burg B (2014) Development of a panel of high-throughput reporter-gene assays to detect genotoxicity and oxidative stress. Mutat Res 760:23–32
Vivat V, Gofflo D, Garcia T, Wurtz JM, Bourguet W, Philibert D, Gronemeyer H (1997) Sequences in the ligand-binding domains of the human androgen and progesterone receptors which determine their distinct ligand identities. J Mol Endocrinol 18(2):147–160
Weber R, Gaus C, Tysklind M, Johnston P, Forter M, Hollert H, Heinisch H, Holoubek I, Lloyd-Smith M, Masunaga S, Moccarelli P, Santillo D, Seike N, Symons R, Torres JPM, Verta M, Varbelow G, Vijgen J, Watson A, Costner P, Wölz J, Wycisk P, Zennegg M (2008) Dioxin- and POP-contaminated sites—contemporary and future relevance and challenges. Environ Sci Pollut Res 15:363–393
Weber R, Watson A, Forter M, Oliaei F (2011) Persistent organic pollutants and landfills—a review of past experiences and future challenges. Waste Manag Res 29(1):107–121
Wei J, Rahman S, Ayaub EA, Dickhout JG, Ask K (2013) Protein misfolding and endoplasmic reticulum stress in chronic lung disease. Chest 143(4):1098–1105. doi:10.1378/chest.12-2133
White SS, Birnbaum LS (2009) An overview of the effects of dioxins and dioxin-like compounds on vertebrates, as documented in human and ecological epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27:197–211. doi:10.1080/10590500903310047
WHO, UNEP (2013) State of the science of endocrine disrupting chemicals-2012. http://unep.org/pdf/9789241505031_eng.pdf
World Health Organization (2011) Guidelines for drinking water-quality; chemical fact sheets. http://www.who.int/water_sanitation_health/publications/2011/9789241548151_ch12.pdf?ua=1
Xia M, Huang R, Sun Y, Semenza GL, Aldred SF, Witt KL, Inglese J, Tice RR, Austin CP (2009) Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci 112(1):153–163. doi:10.1093/toxsci/kfp123
Zahov S, Hollert H, Seiler T-B, Weber R, Holt E (2014) Distinguishing between the mutagenicity, cytotoxicity and dioxin-like activity of pesticides and their impurities. Env. Sci Pollut Res submitted
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Part of this work was funded by the BE-Basic foundation, which was granted a FES subsidy from the Dutch Ministry of Economic Affairs, Agriculture and Innovation (EL&I).
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Pieterse, B., Rijk, I.J.C., Simon, E. et al. Effect-based assessment of persistent organic pollutant and pesticide dumpsite using mammalian CALUX reporter cell lines. Environ Sci Pollut Res 22, 14442–14454 (2015). https://doi.org/10.1007/s11356-015-4739-5
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DOI: https://doi.org/10.1007/s11356-015-4739-5