Analytical and Bioanalytical Chemistry

, Volume 387, Issue 4, pp 1259–1268 | Cite as

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

  • J. L. C. M. Dorne
  • L. Skinner
  • G. K. Frampton
  • D. J. Spurgeon
  • A. M. J. Ragas
Review

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.

Keywords

Ecological risk assessment Human risk assessment Cytochrome P-450 Toxicokinetics Toxicodynamics Uncertainty factors Ecotoxicogenomics 

Notes

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.

References

  1. 1.
    Carlsson C, Johansson AK, Alvan G, Bergman K, Kuhler T (2006) Sci Total Environ 364:67–87CrossRefGoogle Scholar
  2. 2.
    Lisitsa A, Archakov A, Lewi P, Janssen P (2003) Methods Find Exp Clin Pharmacol 25:733–745CrossRefGoogle Scholar
  3. 3.
    Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:667–680CrossRefGoogle Scholar
  4. 4.
    Dorne JL, Renwick AG (2005) Toxicol Sci 86:20–26CrossRefGoogle Scholar
  5. 5.
    Crane M, Watts C, Boucard T (2006) Sci Total Environ 367:23–41CrossRefGoogle Scholar
  6. 6.
    Tyler CR, Jobling S, Sumpter JP (1998) Crit Rev Toxicol 28:319–361CrossRefGoogle Scholar
  7. 7.
    Boxall AB, Sinclair CJ, Fenner K, Kolpin D, Maund SJ (2004) Environ Sci Technol 38:368A–375ACrossRefGoogle Scholar
  8. 8.
    Floate KD, Wardhaugh KG, Boxall AB, Sherratt TN (2005) Annu Rev Entomol 50:153–179CrossRefGoogle Scholar
  9. 9.
    Fent K, Weston AA, Caminada D (2006) Aquat Toxicol 76:122–159CrossRefGoogle Scholar
  10. 10.
    Kummerer K (2004) J Antimicrob Chemother 54:311–320CrossRefGoogle Scholar
  11. 11.
    Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Environ Toxicol Chem 24:464–469CrossRefGoogle Scholar
  12. 12.
    Lawrence JR, Swerhone GD, Wassenaar LI, Neu TR (2005) Can J Microbiol 51:655–669CrossRefGoogle Scholar
  13. 13.
    Court MH, Greenblatt DJ (1997) Biochem Pharmacol 53:1041–1047CrossRefGoogle Scholar
  14. 14.
    Savarie PJ, Shivik JA, White, GC, Hurley JC, Clark L (2001) J Wildl Manage 65:356–365CrossRefGoogle Scholar
  15. 15.
    Johnston JJ, Savarie PJ, Primus TM, Eisemann JD, Hurley JC, Kohler DJ (2002) Environ Sci Technol 36:3827–3833CrossRefGoogle Scholar
  16. 16.
    EC (2003) Technical guidance document on risk assessment. Office for Official Publications of the European Communities (EC), LuxembourgGoogle Scholar
  17. 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 427:630–633CrossRefGoogle Scholar
  18. 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–S460Google Scholar
  19. 19.
    Green RE, Newton I, Shultz S, Cunningham AA, Gilbert M, Pain DJ, Prakash V (2004) J App Ecol 41:793–800CrossRefGoogle Scholar
  20. 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:e66CrossRefGoogle Scholar
  21. 21.
    Gambaro G, Perazella MA (2003) J Intern Med 253:643–652CrossRefGoogle Scholar
  22. 22.
    Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D (2002) Arch Environ Contam Toxicol 43:229–235CrossRefGoogle Scholar
  23. 23.
    Dzialowski EM, Turner PK, Brooks BW (2006) Arch Environ Contam Toxicol 50:503–510CrossRefGoogle Scholar
  24. 24.
    Wollenberger L, Halling-Sorensen B, Kusk KO (2000) Chemosphere 40:723–730CrossRefGoogle Scholar
  25. 25.
    Lanzky PF, Halling-Sorensen B (1997) Chemosphere 35:2553–2561CrossRefGoogle Scholar
  26. 26.
    Ash RJ, Mauck B, Morgan M (2002) Emerg Infect Dis 8:713–716Google Scholar
  27. 27.
    Nash JP, Kime DE, Van der Ven LT, Wester PW, Brion F, Maack G, Stahlschmidt-Allner P, Tyler CR (2004) Environ Health Perspect 112:1725–1733CrossRefGoogle Scholar
  28. 28.
    Purdom C, Hardiman P, Bye V, Eno N, Tyler C, Sumpter J (1994) Estrogenic effects of effluent from sewage treatment works. Chem Ecol 8:275–285Google Scholar
  29. 29.
    Metcalfe CD, Metcalfe TL, Kiparissis Y, Koenig BG, Khan C, Hughes RJ, Croley TR, March RE, Potter T (2001) Environ Toxicol Chem 20:297–308CrossRefGoogle Scholar
  30. 30.
    Stumpf M, Ternes TA, Haberer, Baumann W (1996) Vom Wasser 87:235–250Google Scholar
  31. 31.
    Desbrow C, Rutledge EJ, Brighty GC, Sumpter JP, Waldock M (1998) Environ Sci Technol 32:1549–1558CrossRefGoogle Scholar
  32. 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 53:153–158CrossRefGoogle Scholar
  33. 33.
    Dorne JLCM, Ragas A, Lokke H (2006) Toxicology 226:75–76CrossRefGoogle Scholar
  34. 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).Google Scholar
  35. 35.
    Posthuma L, Suter GW, Traas TP (2002) Species sensitivity distributions in ecotoxicology. Lewis, Boca Raton, FL, p 587Google Scholar
  36. 36.
    Dorne JLCM (2006) J Appl Toxicol (in press)Google Scholar
  37. 37.
    Renwick AG (1993) Food Addit Contam 10:275–305Google Scholar
  38. 38.
    Dorne JL, Walton K, Renwick AG (2005) Food Chem Toxicol 43:203–216CrossRefGoogle Scholar
  39. 39.
    Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:667–680CrossRefGoogle Scholar
  40. 40.
    Walton K, Dorne JL, Renwick AG (2001) Food Chem Toxicol 39:1175–1190CrossRefGoogle Scholar
  41. 41.
    Walton K, Dorne JL, Renwick AG (2004) Food Chem Toxicol 42:261–274CrossRefGoogle Scholar
  42. 42.
    Dorne JL, Walton K, Renwick AG (2001) Food Chem Toxicol 39:1153–1173CrossRefGoogle Scholar
  43. 43.
    Dorne JL, Walton K, Renwick AG (2001) Food Chem Toxicol 39:681–696CrossRefGoogle Scholar
  44. 44.
    Dorne JL, Walton K, Slob W, Renwick AG (2002) Food Chem Toxicol 40:1633–1656CrossRefGoogle Scholar
  45. 45.
    Dorne JL, Walton K, Renwick AG (2003) Food Chem Toxicol 41:201–224CrossRefGoogle Scholar
  46. 46.
    Dorne JL, Walton K, Renwick AG (2003) Food Chem Toxicol 41:225–245CrossRefGoogle Scholar
  47. 47.
    Dorne JL, Walton K, Renwick AG (2004) Food Chem Toxicol 42:397–421CrossRefGoogle Scholar
  48. 48.
    Dorne JL, Walton K, Renwick AG (2004) Food Chem Toxicol 42:275–298CrossRefGoogle Scholar
  49. 49.
    Dorne JL (2004) Fundam Clin Pharmacol 18:609–620CrossRefGoogle Scholar
  50. 50.
    Paulson SK, Engel L, Reitz B, Bolten S, Burton EG, Maziasz TJ, Yan B, Schoenhard GL (1999) Drug Metab Dispos 27:1133–1142Google Scholar
  51. 51.
    Sakai N, Saito K, Kim HS, Kazusaka A, Ishizuka M, Funae Y, Fujita S (2005) Drug Metab Dispos 33:1657–1660CrossRefGoogle Scholar
  52. 52.
    Williams M, Saison CL, Williams DB, Kookana RS (2006) Chemosphere (in press)Google Scholar
  53. 53.
    Venkatakrishnan K, Von Moltke LL, Greenblatt DJ (2001) J Clin Pharmacol 41:1149–1179CrossRefGoogle Scholar
  54. 54.
    David P, Uphin-Villemant C, Mesneau A, Meyran JC (2003) Mol Ecol 12:2473–2481CrossRefGoogle Scholar
  55. 55.
    Khalil WF, Saitoh T, Shimoda M, Kokue E (2001) J Vet Pharmacol Ther 24:343–348CrossRefGoogle Scholar
  56. 56.
    McArthur AG, Hegelund T, Cox RL, Stegeman JJ, Liljenberg M, Olsson U, Sundberg P, Celander MC (2003) J Mol Evol 57:200–211CrossRefGoogle Scholar
  57. 57.
    van Hezik CM, Letcher RJ, de Geus HJ, Wester PG, Goksoyr A, Lewis WE, Boon JP (2001) Aquat Toxicol 51:319–333CrossRefGoogle Scholar
  58. 58.
    Thibaut R, Schnell S, Porte C (2006) Environ Sci Technol 40:5154–5160CrossRefGoogle Scholar
  59. 59.
    Goldstone HM, Stegeman JJ (2006) J Mol Evol 62:708–717CrossRefGoogle Scholar
  60. 60.
    Vaccaro E, Meucci V, Intorre L, Soldani G, Di BD, Longo V, Gervasi PG, Pretti C (2005) Aquat Toxicol 75:293–305CrossRefGoogle Scholar
  61. 61.
    Murakami T, Sato A, Inatani M, Sakurai H, Yumoto R, Nagai J, Takano M (2004) Drug Metab Pharmacokinet 19:96–102CrossRefGoogle Scholar
  62. 62.
    Jager W, Correia MA, Bornheim LM, Mahnke A, Hanstein WG, Xue L, Benet LZ (1999) Drug Metab Dispos 27:1505–1511Google Scholar
  63. 63.
    You L (2004) Chem Biol Interact 147:233–246CrossRefGoogle Scholar
  64. 64.
    Sawada Y, Takedomi S, Matsuo H, Yamano K, Iga T, Ohtani H (2002) Drug Metab Pharmacokinet 17:275–283CrossRefGoogle Scholar
  65. 65.
    Kanazu T, Okamura N, Yamaguchi Y, Baba T, Koike M (2005) Xenobiotica 35:305–317CrossRefGoogle Scholar
  66. 66.
    Cleuvers M (2004) Ecotoxicol Environ Saf 59:309–315CrossRefGoogle Scholar
  67. 67.
    Pennie W, Pettit SD, Lord PG (2004) Environ Health Perspect 112:417–419Google Scholar
  68. 68.
    Fielden MR, Eynon BP, Natsoulis G, Jarnagin K, Banas D, Kolaja KL (2005) Toxicol Pathol 33:675–683CrossRefGoogle Scholar
  69. 69.
    Fielden MR, Pearson C, Brennan R, Kolaja KL (2005) Am J Pharmacogenomics 5:161–171CrossRefGoogle Scholar
  70. 70.
    Griffin JL, Walker L, Shore RF, Nicholson JK (2001) Xenobiotica 31:377–385CrossRefGoogle Scholar
  71. 71.
    Renn SC, Ubin-Horth N, Hofmann HA (2004) BMC Genomics 5:42CrossRefGoogle Scholar
  72. 72.
    Jones M, Baxter M (2005) Nature 434:1076–1077CrossRefGoogle Scholar
  73. 73.
    van Delft JH, van Agen E, van Breda SG, Herwijnen MH, Staal YC, Kleinjans JC (2004) Carcinogenesis 25:1265–1276CrossRefGoogle Scholar
  74. 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 21:1966–1972CrossRefGoogle Scholar
  75. 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 12:62–65CrossRefGoogle Scholar
  76. 76.
    Dorne JLCM, Frampton G, Spurgeon D, Lewis D, Ragas A (2006) Anal Bioanal Chem (this issue)Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • J. L. C. M. Dorne
    • 1
  • L. Skinner
    • 1
  • G. K. Frampton
    • 2
  • D. J. Spurgeon
    • 3
  • A. M. J. Ragas
    • 4
  1. 1.Division of Developmental Origins of Health and Disease, Institute of Human Nutrition, Clinical Pharmacology Group, School of MedicineUniversity of SouthamptonSouthamptonUK
  2. 2.Ecology and Evolutionary Biology GroupUniversity of SouthamptonSouthamptonUK
  3. 3.Center for Ecology and HydrologyHuntingdonUK
  4. 4.Department of Environmental Science, Institute for Wetland and Water Research, Faculty of SienceRadboud University NijmegenNijmegenThe Netherlands

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