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Considerations and Criteria for the Incorporation of Mechanistic Sublethal Endpoints into Environmental Risk Assessment for Biologically Active Compounds

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Human Pharmaceuticals in the Environment

Part of the book series: Emerging Topics in Ecotoxicology ((ETEP,volume 4))

Abstract

Awareness about the presence and unintended consequence of biologically active organic contaminants in the environment was largely borne out of seminal observational works concerning pesticides in the early 1960s [19], eventually culminating in the establishment of protective legislation, government regulatory bodies and a rigorous, continually improving risk assessment paradigm [79, 80]. As a result of associated and necessary scientific advancement, a mounting inventory of novel sublethal endpoints has materialized, which has also precariously and inadvertently highlighted the critical lack of comprehensive and cohesive regulatory position and process with respect to consideration of these metrics in environmental risk assessment (ERA). Although recent attention concerning this issue has been championed largely by a relatively new term; “biomarkers,” the concept and importance of sublethal endpoints is certainly not new [18]. Moreover, the fundamental concept of biological context and causality concerning sublethal effects has been emphasized for decades, seemingly in concert with the environmental awareness movement itself [7] with reviews on the subject dating back to the early 1970s [76]. Yet with nearly 50 years of knowledge and experience, the maturing field of sublethal effects appears to be impeded by a corresponding ecological risk paradigm that is still comparatively less developed [89]. Although the conceptual barriers for consideration are well known [29, 36, 56, 76, 79], the actual process and criteria for consideration, incorporation, and integration of mechanistic sublethal effects remain poorly defined, and in many cases completely lacking, leading to considerable uncertainty and subjectivity.

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References

  1. Adams SM, Giesy JP, Tremblay LA, Eason CT (2001) The use of biomarkers in ecological risk assessment: recommendations from the Christchurch conference on biomarkers in ecotoxicology. Biomarkers 6:1–6

    Article  CAS  Google Scholar 

  2. Ahlers J, Riedhammer C, Vogliano M, Ebert R-U, Kuhne R, Schuurmann G (2006) Acute and chronic ratios in aquatic toxicity-variation across trophic levels and relationship with chemical structure. Environ Toxicol Chem 25:2937–2945

    Article  CAS  Google Scholar 

  3. Ankley GT, Black MC, Garric J, Hutchinson TH, Iguchi T (2005) A framework for assessing the hazard of pharmaceutical materials to aquatic species. In: Williams R (ed) Science for assessing the impacts of human pharmaceutical materials on aquatic ecosystems. SETAC Press, Pensacola, pp 183–238

    Google Scholar 

  4. Ankley GT, Brooks BW, Hugget DB, Sumpter JS (2007) Repeating history: pharmaceuticals in the environment. Environ Sci Technol 41:8211–8217

    Article  CAS  Google Scholar 

  5. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrano JA, Tietge JE, Villeneuve DL (2010) Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29:730–741

    Article  CAS  Google Scholar 

  6. Bach TJ, Lichtenthaler HK (1982) Inhibition of mevalonate biosynthesis and of plant growth by the fungal metabolite mevinolin. In: Wintermanns JFGM, Kuiper PJC (eds) Biochemistry and metabolism of plant lipids. Elsevier Biochemical Press, Amsterdam, pp 515–521

    Google Scholar 

  7. Bartholomew G (1964) The roles of physiology and behavior in the maintenance of homeostasis in the desert environment. In: Hughes GM (ed) Symposia of the society for experimental biology, vol 18, Homeostasis and feedback mechanisms (p 460). Academic, New York, pp 7–29

    Google Scholar 

  8. Basset GJC, Quinlivan EP, Gregory JF, Hanson AD (2005) Folate synthesis and metabolism in plants and prospects for biofortification. Crop Sci 45:449–453

    Article  CAS  Google Scholar 

  9. Berninger JP, Brooks BW (2010) Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals. Toxicol Lett 193:69–78

    Article  CAS  Google Scholar 

  10. Bradbury S (1994) Predicting modes of toxic action from chemical structure: an overview. SAR QSAR Environ Res 2:89–104

    Article  CAS  Google Scholar 

  11. Bradbury S (1995) Quantitative structure-activity relationships and ecological risk assessment: an overview of predictive aquatic toxicology research. Toxicol Lett 79:229–237

    Article  CAS  Google Scholar 

  12. Bradbury S, Feijtel T, van Leeuwen C (2004) Meeting the scientific needs of ecological risk assessment in a regulatory context. Environ Sci Technol 38:463A–470A

    Article  CAS  Google Scholar 

  13. Brain RA, Cedergreen N (2009) Biomarkers in plants: selection and utility. Rev Environ Contam Toxicol 198:49–110

    Google Scholar 

  14. Brain RA, Reitsma TS, Lissemore LI, Bestari B-J, Sibley PK, Solomon KR (2006) Herbicidal effects of statin pharmaceuticals in Lemna gibba. Environ Sci Technol 40:5116–5123

    Article  CAS  Google Scholar 

  15. Brain RA, Hanson ML, Solomon KR, Brooks BW (2008) Aquatic plants exposed to pharmaceuticals: effects and risks. Rev Environ Contam Toxicol 192:67–115

    Article  CAS  Google Scholar 

  16. Brain RA, Ramirez AJ, Fulton BA, Chambliss CK, Brooks BW (2008) Herbicidal effects of sulfamethoxazole in Lemna gibbaG3: using pABA as a biomarker of effect. Environ Sci Technol 42:8965–8970

    Article  CAS  Google Scholar 

  17. Brooks BW, Ankley GT, Hobson JF, Lazorchak JM, Meyerhoff RD, Solomon KR (2008) Assessing the aquatic hazards of veterinary medicines. In: Crane M, Barrett K, Boxall A (eds) Effects of veterinary medicines in the environment. CRC Press, Boca Raton, pp 97–128

    Google Scholar 

  18. Cairns J (1966) Don’t be half-safe-the current revolution in bio-assay techniques. In: Proceedings of the 21st industrial waste conference, Purdue University, Engineering Extension series, Richmond, pp 559–567

    Google Scholar 

  19. Carson R (1962) Silent spring. Houghton Mifflin, Boston

    Google Scholar 

  20. Christen V, Hickmann S, Rechenberg B, Fent K (2010) Highly active human pharmaceuticals in aquatic systems: a concept for their identification based on their mode of action. Aquat Toxicol 96:167–181

    Article  CAS  Google Scholar 

  21. Combes R, Barratt M, Balls M (2003) An overall strategy for the testing of chemicals for human hazard and risk assessment under the EU REACH system. Altern Lab Anim 31:7–19

    CAS  Google Scholar 

  22. Coppage D (1972) Organophosphate pesticides: specific level of brain AChE inhibition related to death in sheepshead minnows. Trans Am Fish Soc 101:534–536

    Article  CAS  Google Scholar 

  23. Coppage D, Matthews E (1974) Short-term effects of organophosphate pesticides on cholinesterases of estuarine fishes and pink shrimp. Bull Environ Contam Toxicol 11:483–488

    Article  CAS  Google Scholar 

  24. Coppage D, Matthews E, Cook G, Knight J (1975) Brain acetylcholinesterase inhibition in fish as a diagnosis of environmental poisoning by malathion, O, O-dimethyl s-(1,2-dicarbethoxyethyl) phosphorodithioate. Pestic Biochem Physiol 5:536–542

    Article  CAS  Google Scholar 

  25. Doll R, Hill A (1950) Smoking and carcinoma of the lung: preliminary report. Br Med J 4682:739–748

    Article  Google Scholar 

  26. Duquesne S (2006) Effects of an organophosphate on Daphnia magna at suborganismal and organismal levels: implications for population dynamics. Ecotoxicol Environ Saf 65:145–150

    Article  CAS  Google Scholar 

  27. Eads B, Andrews J, Colbourne J (2008) Ecological genomics in Daphnia: stress responses and environmental sex determination. Nat Heredity 100:184–190

    Article  CAS  Google Scholar 

  28. EMEA (2005) Guideline on the environmental risk assessment of medicinal products for human use. The European Agency for the Evaluation of Medicinal Products: Committee for Medicinal Products for Human Use, London

    Google Scholar 

  29. Ernst WHO, Peterson PJ (1994) The role of biomarkers in environmental assessment (4). Terrestrial plants. Ecotoxicology 3:180–192

    Article  Google Scholar 

  30. Escher B, Hermens J (2002) Modes of action in ecotoxicology: their role in body burdens, species sensitivity, QSARs, and mixture effects. Environ Sci Technol 36:4201–4217

    Article  CAS  Google Scholar 

  31. EUC (2002) Working document, Guidance document on risk assessment for birds and mammals under Council Directive 91/414/EEC. SANCO/4145/2000—final. European Commission Health & Consumer Protection Directorate-General, Directorate E—Food safety: plant health, animal health and welfare, international questions E1—Plant health, Brussels

    Google Scholar 

  32. EUC (2002) Working document, Guidance document on aquatic ecotoxicology in the context of the Directive 91/414/EEC. Sanco/3268/2001 rev.4 (final). European Commission Health & Consumer Protection Directorate-General, Directorate E—Food safety: plant health, animal health and welfare, international questions E1—Plant health, Brussels

    Google Scholar 

  33. EUC (2002) Working document, Guidance document on terrestrial ecotoxicology under Council Directive 91/414/EEC. SANCO/10329/2002 rev 2 final. European Commission Health & Consumer Protection Directorate-General, Directorate E—Food safety: plant health, animal health and welfare, international questions E1—Plant health, Brussels

    Google Scholar 

  34. Ferrat L, Pergent-Martini C, Roméo M (2003) Assessment of the use of biomarkers in aquatic plants for the evaluation of environmental quality: application to seagrasses. Aquat Toxicol 65:187–204

    Article  CAS  Google Scholar 

  35. Folmar L, Gardner G, Schreibman M, Magliulo-Cepriano L, Mills L, Zaroogian G, Gutjahr-Gobell R, Haebler R, Horowitz D, Denslow N (2001) Vitellogenin-induced pathology in male summer flounder (Paralichthys dentatus). Aquat Toxicol 51:431–441

    Article  CAS  Google Scholar 

  36. Forbes VE, Palmqvist A, Bach L (2006) The use and misuse of biomarkers in ecotoxicology. Environ Toxicol Chem 25:272–280

    Article  CAS  Google Scholar 

  37. Fulton M (1989) The effects of certain intrinsic and extrinsic variables on the lethal and sublethal toxicity of selected organophosphorus insecticides in the mummichog, Fundulus heteroclitus, under laboratory and field conditions. Thesis, University of South Carolina, Columbia

    Google Scholar 

  38. Fulton M, Key P (2001) Acetylcholinesterase inhibition in estuarine fish and invertebrates as an indicator of organophosphorous insecticide exposure and effects. Environ Toxicol Chem 20:37–45

    Article  CAS  Google Scholar 

  39. Grandmougin-Ferjani A, Schuller-Muller I, Hartmann MA (1997) Sterol modulation of the plasma membrane H+-ATPase activity from corn roots reconstituted into soyabean lipids. Plant Physiol 113:163–174

    CAS  Google Scholar 

  40. Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson J (2008) Evolutionary conservation of human drug targets in organisms used for environmental risk assessments. Environ Sci Technol 42:5807–5813

    Article  CAS  Google Scholar 

  41. Habig C, DiGiulio R (1991) Biochemical characteristics of cholinesterases in aquatic organisms. In: Mineau P (ed) Cholinesterase inhibiting insecticides: their impact on wildlife and the environment, vol 2, Chemicals in agriculture. Elsevier, New York, pp 19–34

    Google Scholar 

  42. Hanson AD, Roje S (2001) One-carbon metabolism in higher plants. Annu Rev Plant Physiol 52:119–137

    Article  CAS  Google Scholar 

  43. Hickey J, Anderson D (1968) Chlorinated hydrocarbons and eggshell changes in raptorial and fish-eating birds. Science 162:271–273

    Article  CAS  Google Scholar 

  44. Hill A (1965) The environment and disease: association or causation? Proc R Soc Med 58:295–300

    CAS  Google Scholar 

  45. Hoff D, Lehmann W, Pease A, Raimondo S, Russom C, Steeger T (2010) Predicting the toxicities of chemicals to aquatic animal species (White Paper). U.S. Environmental Protection Agency, Washington, DC, 127 p

    Google Scholar 

  46. Hugget DB, Cook JC, Ericson JF, Williams RT (2003) A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human pharmaceuticals to fish. Hum Ecol Risk Assess 9:1789–1799

    Article  Google Scholar 

  47. Jursinic P, Stemler A (1983) Changes in [14C]atrazine binding associated with the oxidation-reduction state of the secondary quinone acceptor of photosystem II. Plant Physiol 73:703–708

    Article  CAS  Google Scholar 

  48. Kavitha P, Rao V (2007) Oxidative stress and locomotor behaviour response as biomarkers for assessing recovery status of mosquito Wsh, Gambusia aYnis after lethal eVect of an organophosphate pesticide, monocrotophos. Pestic Biochem Physiol 87:182–188

    Article  CAS  Google Scholar 

  49. Kavitha P, Rao V (2008) Toxic effects of chlorpyrifos on antioxidant enzymes and target enzyme acetylcholinesterase interaction in mosquito fish, Gambusia affinis. Environ Toxicol Pharmacol 26:192–198

    Article  CAS  Google Scholar 

  50. Kidd K, Blanchfield P, Mills K, Palace V, Evans R, Lazorchak J, Flick R (2007) Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Sci U S A 104:8897–8901

    Article  CAS  Google Scholar 

  51. Köhler H-R, Kloas W, Schirling M, Lutz I, Reye A, Langen J-S, Triebskorn R, Nagel R, Schönfelder G (2007) Sex steroid receptor evolution and signalling in aquatic invertebrates. Ecotoxicology 16:131–143

    Article  Google Scholar 

  52. Kwekel J, Burgoon L, Zacharewski T (2008) Comparative toxicogenomics in mechanistic and predictive toxicology. In: Brown J (ed) Comparative genomics basic and applied research. CRC Press, Taylor and Francis Group, Boca Raton, p 400

    Google Scholar 

  53. Levine R (1991) Recognized and possible effects of pesticides in humans. In: Hayes W, Laws E (eds) Handbook of pesticide toxicology, vol 1. Academic, New York, pp 275–360

    Google Scholar 

  54. Lincer J (1975) DDE-induced eggshell-thinning in the American Kestrel: a comparison of the field situation and laboratory results. J Appl Ecol 12:781–793

    Article  CAS  Google Scholar 

  55. Magnusson M, Heimann K, Negri A (2008) Comparative effects of herbicides on photosynthesis and growth of tropical estuarine microalgae. Mar Pollut Bull 56:1545–1552

    Article  CAS  Google Scholar 

  56. McCarty LS, Munkittrick KR (1996) Environmental biomarkers in aquatic toxicology: fiction, fantasy, or functional? Hum Ecol Risk Assess 2:268–274

    Article  Google Scholar 

  57. McCarthy JF, Shugart LR (1990) Biomarkers of environmental contamination. Lewis Publishers, Boca Raton

    Google Scholar 

  58. McCarty LS, Power M, Munkittrick KR (2002) Bioindicator vs biomarkers in ecological risk assessment. Hum Ecol Risk Assess 8:159–164

    Article  Google Scholar 

  59. Miller D, Jensen K, Villeneuve D, Kahl M, Makynen E, Durhan E, Ankley G (2007) Linkage of biochemical response to population-level effects: a case study with vitellogenin in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 26:521–527

    Article  CAS  Google Scholar 

  60. Moreland D, Gentner W, Hilton J, Hill K (1959) Studies on the mechanism of herbicidal action of 2-chloro-4,6-bis(ethylamino)-S-triazine. Plant Physiol 34:432–435

    Article  CAS  Google Scholar 

  61. Muniswamy D, Patil V, Chebbi S, Marigoudar S, Chittaragi J, Halappa R (2009) Gas-liquid chromatography for fenvalerate residue analysis: in vivo alterations in the acetylcholinesterase activity and acetylcholine in different tissues of the fish, Labeo rohita (Hamilton). Toxicol Mech Methods 19:410–415

    Article  Google Scholar 

  62. Nathan S, Choi M, Seo H, Paik C, Kalaivani K, Kim J (2008) Effect of azadirachtin on acetylcholinesterase (AChE) activity and histology of the brown planthopper Nilaparvata lugens (Stal). Ecotoxicol Environ Saf 70:244–250

    Article  CAS  Google Scholar 

  63. Raimondo S, Montague BJ, Barron MG (2007) Determinants of the variability in acute to chronic toxicity ratios for aquatic invertebrates and fish. Environ Toxicol Chem 26:2019–2023

    Article  CAS  Google Scholar 

  64. Rand GM (1995) Fundamentals of aquatic toxicology: effects, environmental fate, and risk assessment. Taylor & Francis, Washington, DC

    Google Scholar 

  65. Rao V (2008) Brain acetylcholinesterase activity as a potential biomarker for the rapid assessment of chlorpyrifos toxicity in a euryhaline fish, Oreochromis mossambicus. Environ Bioindic 3:11–22

    Article  CAS  Google Scholar 

  66. Ratcliffe D (1967) Decrease in eggshell weight in certain birds of prey. Nature 215:208–210

    Article  CAS  Google Scholar 

  67. Rébeillé FD, Macherel D, Mouillon JM, Garin J, Douce R (1997) Folate biosynthesis in higher plants: purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria. EMBO Rep 16:947–957

    Article  Google Scholar 

  68. Robinson P (2009) Behavioural toxicity of organic chemical contaminants in fish: application to ecological risk assessments (ERAs). Can J Fish Aquat Sci 66:1179–1188

    Article  CAS  Google Scholar 

  69. Roex E, van Gestel C, Van Wezel AP, Van Straalen NM (2000) Ratios between acute aquatic toxicity and effects on population growth rates in relation to toxicant mode of action. Environ Toxicol Chem 19:685–693

    Article  CAS  Google Scholar 

  70. Russom C, Bradbury S, Broderius S, Hammermeister D, Drummond R (1997) Predicting modes of toxicity action from chemical structure: acute toxicity in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 16:948–967

    CAS  Google Scholar 

  71. Sandahl J, Baldwin D, Jenkins J, Scholz N (2005) Comparative thresholds for acetylcholinesterase inhibition and behavioral impairment in coho salmon exposed to chlorpyrofos. Environ Toxicol Chem 24:136–145

    Article  CAS  Google Scholar 

  72. Sanderson H, Thomsen M (2009) Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals: assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action. Toxicol Lett 187:84–93

    Article  CAS  Google Scholar 

  73. Schaller H (2004) New aspects of sterol biosynthesis in growth and development of higher plants. Plant Physiol Biochem 42:465–476

    Article  CAS  Google Scholar 

  74. Schwender J, Seemann M, Lichtenthaler HK, Rohmer M (1996) Biosynthesis of isoprenoids (carotenoids, sterols, prenyl side-chains of chlorophylls and plastoquinone) via a novel pyruvate/glyceraldehyde 3-phosphate non-mevalonate pathway in the green algae Scenedesmus obliquus. Biochem J 316:73–80

    CAS  Google Scholar 

  75. Shimabukuro R, Swanson H (1969) Atrazine metabolism, selectivity, and mode of action. J Agric Food Chem 17:199–205

    Article  CAS  Google Scholar 

  76. Sprague J (1971) Measurement of pollutant toxicity to fish-III sublethal effects and “safe” concentrations. Water Res 5:245–266

    Article  CAS  Google Scholar 

  77. Stephan CE, Mount DI, Hansen DJ, Gentile JH, Chapman GA, Brungs WA (1985) Guidelines for deriving numerical national water quality criteria for the protection of aquatic organisms and their uses. US EPA ORD ERL. PB 85-227049, Duluth, pp 1–97

    Google Scholar 

  78. Strum A, Wogram J, Segner H, Liess M (2009) Different sensitivity to organophosphates of acetylcholinesterase and butyrylcholinesterase from three-spined stickleback (Gasterosteus aculeatus): application in biomonitoring. Environ Toxicol Chem 19:1607–1615

    Google Scholar 

  79. USEPA (2004) Overview of the ecological risk assessment process in the Office of Pesticide Programs, U.S. Environmental Protection Agency: endangered and threatened species effects determinations. United States Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances Office of Pesticide Programs, Washington, DC

    Google Scholar 

  80. USEPA (2007) Federal Register. Part II. Environmental Protection Agency. 40 CFR Parts 9, 152, 156, 159 et al. Pesticides; data requirements for conventional chemicals, technical amendments, and data requirements for biochemical and microbial pesticides; final rules. United States Environmental Protection Agency, Washington, DC, 56 p

    Google Scholar 

  81. USEPA (2008) Aquatic life criteria for contaminants of emerging concern. Part I: general challenges and recommendations. U.S. Environmental Protection Agency, Washington DC. http://water.epa.gov/scitech/swguidance/waterquality/standards/upload/2008_06_03_criteria_sab-emergingconcerns.pdf. Accessed 04/2010

  82. USEPA (2009) Endocrine disruptor screening program test guidelines OPPTS 890.1350: fish short-term reproduction assay. Office of Prevention, Pesticides and Toxic Substances (7101), Washington, DC, 93 p

    Google Scholar 

  83. USEPA (2009) Federal Register/Vol. 74, No. 84/Monday, May 4, 2009/Rules and regulations, p 20422. http://edocket.access.gpo.gov/2009/pdf/E9-10203.pdf. Accessed 04/2010

  84. USFDA (1998) Guidance for industry; environmental assessment of human drug and biologics applications. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Rockville, CMC 6, 39 p

    Google Scholar 

  85. Vaal M, Van Leeuwen C, Hoekstra J (2000) Variation in sensitivity of aquatic species to toxicants: practical consequences for effect assessment of chemical substances. Environ Manage 25:415–423

    Article  Google Scholar 

  86. Verhaar H, van Leeuwen C, Bol J, Hermens J (1994) Application of QSARs in risk management of existing chemicals. SAR QSAR Environ Res 2:39–58

    Article  CAS  Google Scholar 

  87. VICH (2000) Environmental impact assessment (EIAS) for veterinary medicinal products (VMPS)—phase I. VICH GL6 (ecotoxicity phase I). VICH International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products, Brussels

    Google Scholar 

  88. VICH (2004) Environmental impact assessment for veterinary medicinal products: phase II guidance. VICH-GL38 (ecotoxicity phase II). VICH International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products, Brussels

    Google Scholar 

  89. Villeneuve DL, Garcia-Reyero N (2011) Predictive ecotoxicology in the 21st century. Environ Toxicol Chem 30:1–9

    Article  CAS  Google Scholar 

  90. Walker C (1995) Biochemical biomarkers in ecotoxicology—some recent developments. Sci Total Environ 171:189–195

    Article  CAS  Google Scholar 

  91. Weiss C (1958) The determination of cholinesterase in the brain tissue of three species of fresh water fish and its inactivation in vivo. Ecology 39:194–199

    Article  CAS  Google Scholar 

  92. Wheeler J, Gimeno S, Crane M, Lopez-Juez E, Morritt D (2005) Vitellogenin: a review of analytical methods to detect (anti) estrogenic activity in fish. Toxicol Mech Methods 15:293–306

    Article  CAS  Google Scholar 

  93. Williams ES, Panko J, Paustenbach DJ (2009) The European Union’s REACH regulation: a review of its history and requirements. Crit Rev Toxicol 39:553–575

    Article  Google Scholar 

  94. Maxwell K, Johnson GN (2000) Chlorophyll fluorescence—a practical guide. J Exp Bot 51:659–668

    Article  Google Scholar 

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Authors and Affiliations

  1. Ecological Risk Assessment, Syngenta Crop Protection LLC, 410 Swing Road, Greensboro, NC, 27409, USA

    Richard A. Brain

  2. Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, The Institute of Ecological, Earth and Environmental Sciences, and Institute of Biomedical Studies, Baylor University, One Bear Place #97266, Waco, TX, 76798, USA

    Bryan W. Brooks

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    Bryan W. Brooks

  2. University of North Texas, N/A, Denton, 76203, Texas, USA

    Duane B. Huggett

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Brain, R.A., Brooks, B.W. (2012). Considerations and Criteria for the Incorporation of Mechanistic Sublethal Endpoints into Environmental Risk Assessment for Biologically Active Compounds. In: Brooks, B., Huggett, D. (eds) Human Pharmaceuticals in the Environment. Emerging Topics in Ecotoxicology, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3473-3_7

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