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Human and environmental risk assessment of pharmaceuticals: differences, similarities, lessons from toxicology

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Abstract

The presence of human and veterinary pharmaceuticals in the environment has caused increasing concern due their effects on ecological receptors. Improving the risk assessment of these compounds necessitates a quantitative understanding of their metabolism and elimination in the target organism (toxicokinetics), particularly via the ubiquitous cytochrome P-450 (CYP) system and their mechanisms of toxicity (toxicodynamics). This review focuses on a number of pharmaceuticals and veterinary medicines of environmental concern, and the differences and similarities between ecological and human risk assessment. CYP metabolism is discussed with particular reference to its ubiquity in species of ecological relevance. The important issue of pharmaceutical mixtures is discussed to assess how emerging technologies such as ecotoxicogenomics may assist in moving towards a more mechanism-based environmental risk assessment of pharmaceuticals.

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References

  1. Carlsson C, Johansson AK, Alvan G, Bergman K, Kuhler T (2006) Sci Total Environ 364:67–87

    Article  CAS  Google Scholar 

  2. Lisitsa A, Archakov A, Lewi P, Janssen P (2003) Methods Find Exp Clin Pharmacol 25:733–745

    Article  CAS  Google Scholar 

  3. Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:667–680

    Article  CAS  Google Scholar 

  4. Dorne JL, Renwick AG (2005) Toxicol Sci 86:20–26

    Article  CAS  Google Scholar 

  5. Crane M, Watts C, Boucard T (2006) Sci Total Environ 367:23–41

    Article  CAS  Google Scholar 

  6. Tyler CR, Jobling S, Sumpter JP (1998) Crit Rev Toxicol 28:319–361

    Article  CAS  Google Scholar 

  7. Boxall AB, Sinclair CJ, Fenner K, Kolpin D, Maund SJ (2004) Environ Sci Technol 38:368A–375A

    Article  CAS  Google Scholar 

  8. Floate KD, Wardhaugh KG, Boxall AB, Sherratt TN (2005) Annu Rev Entomol 50:153–179

    Article  CAS  Google Scholar 

  9. Fent K, Weston AA, Caminada D (2006) Aquat Toxicol 76:122–159

    Article  CAS  Google Scholar 

  10. Kummerer K (2004) J Antimicrob Chemother 54:311–320

    Article  CAS  Google Scholar 

  11. Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Environ Toxicol Chem 24:464–469

    Article  CAS  Google Scholar 

  12. Lawrence JR, Swerhone GD, Wassenaar LI, Neu TR (2005) Can J Microbiol 51:655–669

    Article  CAS  Google Scholar 

  13. Court MH, Greenblatt DJ (1997) Biochem Pharmacol 53:1041–1047

    Article  CAS  Google Scholar 

  14. Savarie PJ, Shivik JA, White, GC, Hurley JC, Clark L (2001) J Wildl Manage 65:356–365

    Article  Google Scholar 

  15. Johnston JJ, Savarie PJ, Primus TM, Eisemann JD, Hurley JC, Kohler DJ (2002) Environ Sci Technol 36:3827–3833

    Article  CAS  Google Scholar 

  16. EC (2003) Technical guidance document on risk assessment. Office for Official Publications of the European Communities (EC), Luxembourg

  17. Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJ, Arshad M, Mahmood S, Ali A, Khan AA (2004) Nature 427:630–633

    Article  CAS  Google Scholar 

  18. Shultz S, Baral HS, Charman S, Cunningham AA, Das D, Ghalsasi GR, Goudar MS, Green RE, Jones A, Nighot P, Pain DJ, Prakash V (2004) Proc Biol Sci 271(Suppl 6):S458–S460

    Google Scholar 

  19. Green RE, Newton I, Shultz S, Cunningham AA, Gilbert M, Pain DJ, Prakash V (2004) J App Ecol 41:793–800

    Article  CAS  Google Scholar 

  20. Swan G, Naidoo V, Cuthbert R, Green RE, Pain DJ, Swarup D, Prakash V, Taggart M, Bekker L, Das D, Diekmann J, Diekmann M, Killian E, Meharg A, Patra RC, Saini M, Wolter K (2006) PLoS Biol 4:e66

    Article  CAS  Google Scholar 

  21. Gambaro G, Perazella MA (2003) J Intern Med 253:643–652

    Article  CAS  Google Scholar 

  22. Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D (2002) Arch Environ Contam Toxicol 43:229–235

    Article  CAS  Google Scholar 

  23. Dzialowski EM, Turner PK, Brooks BW (2006) Arch Environ Contam Toxicol 50:503–510

    Article  CAS  Google Scholar 

  24. Wollenberger L, Halling-Sorensen B, Kusk KO (2000) Chemosphere 40:723–730

    Article  CAS  Google Scholar 

  25. Lanzky PF, Halling-Sorensen B (1997) Chemosphere 35:2553–2561

    Article  CAS  Google Scholar 

  26. Ash RJ, Mauck B, Morgan M (2002) Emerg Infect Dis 8:713–716

    Google Scholar 

  27. Nash JP, Kime DE, Van der Ven LT, Wester PW, Brion F, Maack G, Stahlschmidt-Allner P, Tyler CR (2004) Environ Health Perspect 112:1725–1733

    Article  CAS  Google Scholar 

  28. Purdom C, Hardiman P, Bye V, Eno N, Tyler C, Sumpter J (1994) Estrogenic effects of effluent from sewage treatment works. Chem Ecol 8:275–285

    CAS  Google Scholar 

  29. Metcalfe CD, Metcalfe TL, Kiparissis Y, Koenig BG, Khan C, Hughes RJ, Croley TR, March RE, Potter T (2001) Environ Toxicol Chem 20:297–308

    Article  CAS  Google Scholar 

  30. Stumpf M, Ternes TA, Haberer, Baumann W (1996) Vom Wasser 87:235–250

    Google Scholar 

  31. Desbrow C, Rutledge EJ, Brighty GC, Sumpter JP, Waldock M (1998) Environ Sci Technol 32:1549–1558

    Article  CAS  Google Scholar 

  32. Segner H, Chesne C, Cravedi JP, Fauconneau B, Houlihan D, LeGac F, Loir M, Mothersill C, Part P, Valotaire Y, Prunet P (2001) Aquat Toxicol 53:153–158

    Article  CAS  Google Scholar 

  33. Dorne JLCM, Ragas A, Lokke H (2006) Toxicology 226:75–76

    Article  Google Scholar 

  34. Ragas A, Dorne JLCM, Lokke H (2006) Harmonisation of analytical frameworks for meta-analysis of human and ecological toxicity data (Report to the European Commission deliverable under the Sixth Framework Project NOMIRACLE: Novel methods for integrated risk assessment of cumulative stressors in Europe; project no. 003956).

  35. Posthuma L, Suter GW, Traas TP (2002) Species sensitivity distributions in ecotoxicology. Lewis, Boca Raton, FL, p 587

    Google Scholar 

  36. Dorne JLCM (2006) J Appl Toxicol (in press)

  37. Renwick AG (1993) Food Addit Contam 10:275–305

    CAS  Google Scholar 

  38. Dorne JL, Walton K, Renwick AG (2005) Food Chem Toxicol 43:203–216

    Article  CAS  Google Scholar 

  39. Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:667–680

    Article  Google Scholar 

  40. Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:1175–1190

    Article  Google Scholar 

  41. Walton K, Dorne JL, Renwick AG (2004) Food Chem Toxicol 42:261–274

    Article  CAS  Google Scholar 

  42. Dorne JL, Walton K, Renwick AG (2001) Food Chem Toxicol 39:1153–1173

    Article  CAS  Google Scholar 

  43. Dorne JL, Walton K, Renwick AG (2001) Food Chem Toxicol 39:681–696

    Article  CAS  Google Scholar 

  44. Dorne JL, Walton K, Slob W, Renwick AG (2002) Food Chem Toxicol 40:1633–1656

    Article  CAS  Google Scholar 

  45. Dorne JL, Walton K, Renwick AG (2003) Food Chem Toxicol 41:201–224

    Article  CAS  Google Scholar 

  46. Dorne JL, Walton K, Renwick AG (2003) Food Chem Toxicol 41:225–245

    Article  CAS  Google Scholar 

  47. Dorne JL, Walton K, Renwick AG (2004) Food Chem Toxicol 42:397–421

    Article  CAS  Google Scholar 

  48. Dorne JL, Walton K, Renwick AG (2004) Food Chem Toxicol 42:275–298

    Article  CAS  Google Scholar 

  49. Dorne JL (2004) Fundam Clin Pharmacol 18:609–620

    Article  CAS  Google Scholar 

  50. Paulson SK, Engel L, Reitz B, Bolten S, Burton EG, Maziasz TJ, Yan B, Schoenhard GL (1999) Drug Metab Dispos 27:1133–1142

    CAS  Google Scholar 

  51. Sakai N, Saito K, Kim HS, Kazusaka A, Ishizuka M, Funae Y, Fujita S (2005) Drug Metab Dispos 33:1657–1660

    Article  CAS  Google Scholar 

  52. Williams M, Saison CL, Williams DB, Kookana RS (2006) Chemosphere (in press)

  53. Venkatakrishnan K, Von Moltke LL, Greenblatt DJ (2001) J Clin Pharmacol 41:1149–1179

    Article  CAS  Google Scholar 

  54. David P, Uphin-Villemant C, Mesneau A, Meyran JC (2003) Mol Ecol 12:2473–2481

    Article  CAS  Google Scholar 

  55. Khalil WF, Saitoh T, Shimoda M, Kokue E (2001) J Vet Pharmacol Ther 24:343–348

    Article  CAS  Google Scholar 

  56. McArthur AG, Hegelund T, Cox RL, Stegeman JJ, Liljenberg M, Olsson U, Sundberg P, Celander MC (2003) J Mol Evol 57:200–211

    Article  CAS  Google Scholar 

  57. van Hezik CM, Letcher RJ, de Geus HJ, Wester PG, Goksoyr A, Lewis WE, Boon JP (2001) Aquat Toxicol 51:319–333

    Article  Google Scholar 

  58. Thibaut R, Schnell S, Porte C (2006) Environ Sci Technol 40:5154–5160

    Article  CAS  Google Scholar 

  59. Goldstone HM, Stegeman JJ (2006) J Mol Evol 62:708–717

    Article  CAS  Google Scholar 

  60. Vaccaro E, Meucci V, Intorre L, Soldani G, Di BD, Longo V, Gervasi PG, Pretti C (2005) Aquat Toxicol 75:293–305

    Article  CAS  Google Scholar 

  61. Murakami T, Sato A, Inatani M, Sakurai H, Yumoto R, Nagai J, Takano M (2004) Drug Metab Pharmacokinet 19:96–102

    Article  CAS  Google Scholar 

  62. Jager W, Correia MA, Bornheim LM, Mahnke A, Hanstein WG, Xue L, Benet LZ (1999) Drug Metab Dispos 27:1505–1511

    CAS  Google Scholar 

  63. You L (2004) Chem Biol Interact 147:233–246

    Article  CAS  Google Scholar 

  64. Sawada Y, Takedomi S, Matsuo H, Yamano K, Iga T, Ohtani H (2002) Drug Metab Pharmacokinet 17:275–283

    Article  CAS  Google Scholar 

  65. Kanazu T, Okamura N, Yamaguchi Y, Baba T, Koike M (2005) Xenobiotica 35:305–317

    Article  CAS  Google Scholar 

  66. Cleuvers M (2004) Ecotoxicol Environ Saf 59:309–315

    Article  CAS  Google Scholar 

  67. Pennie W, Pettit SD, Lord PG (2004) Environ Health Perspect 112:417–419

    Google Scholar 

  68. Fielden MR, Eynon BP, Natsoulis G, Jarnagin K, Banas D, Kolaja KL (2005) Toxicol Pathol 33:675–683

    Article  CAS  Google Scholar 

  69. Fielden MR, Pearson C, Brennan R, Kolaja KL (2005) Am J Pharmacogenomics 5:161–171

    Article  CAS  Google Scholar 

  70. Griffin JL, Walker L, Shore RF, Nicholson JK (2001) Xenobiotica 31:377–385

    Article  CAS  Google Scholar 

  71. Renn SC, Ubin-Horth N, Hofmann HA (2004) BMC Genomics 5:42

    Article  CAS  Google Scholar 

  72. Jones M, Baxter M (2005) Nature 434:1076–1077

    Article  CAS  Google Scholar 

  73. van Delft JH, van Agen E, van Breda SG, Herwijnen MH, Staal YC, Kleinjans JC (2004) Carcinogenesis 25:1265–1276

    Article  CAS  Google Scholar 

  74. Bundy JG, Lenz EM, Bailey NJ, Gavaghan CL, Svendsen C, Spurgeon D, Hankard PK, Osborn D, Weeks JM, Trauger SA, Speir P, Sanders I, Lindon JC, Nicholson JK, Tang H (2002) Environ Toxicol Chem 21:1966–1972

    Article  CAS  Google Scholar 

  75. Knacker T, Duis K, Ternes T, Fenner K, Escher B, Schmitt H, Rombke J, Garric J, Hutchinson T, Boxall AB (2005) Environ Sci Pollut Res Int 12:62–65

    Article  Google Scholar 

  76. Dorne JLCM, Frampton G, Spurgeon D, Lewis D, Ragas A (2006) Anal Bioanal Chem (this issue)

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Acknowledgments

This manuscript is dedicated to the memory of Yann Minard (1970–2006).

Some of the authors (JLCMD, AMJR, DSS) are grateful to the European Commission (2004–2006 under the NO MIRACLE project Number 003956) for funding this work. The opinions reflected in this review are the authors only.

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Authors and Affiliations

  1. Division of Developmental Origins of Health and Disease, Institute of Human Nutrition, Clinical Pharmacology Group, School of Medicine, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton, SO16 7PX, UK

    J. L. C. M. Dorne & L. Skinner

  2. Ecology and Evolutionary Biology Group, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton, SO16 7PX, UK

    G. K. Frampton

  3. Center for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire, PE28 2LS, UK

    D. J. Spurgeon

  4. Department of Environmental Science, Institute for Wetland and Water Research, Faculty of Sience, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands

    A. M. J. Ragas

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  1. J. L. C. M. Dorne
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  2. L. Skinner
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  3. G. K. Frampton
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  5. A. M. J. Ragas
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Correspondence to J. L. C. M. Dorne.

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Dorne, J.L.C.M., Skinner, L., Frampton, G.K. et al. Human and environmental risk assessment of pharmaceuticals: differences, similarities, lessons from toxicology. Anal Bioanal Chem 387, 1259–1268 (2007). https://doi.org/10.1007/s00216-006-0963-7

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  • DOI: https://doi.org/10.1007/s00216-006-0963-7

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