Environ. Sci. Technol. 2006, 40, 1086-1087
Response To Comment on “Lessons from Endocrine Disruption and Their Application to Other Issues Concerning Trace Organics in the Aquatic Environment” We thank Segner (1) for his interest in, and kind comments on, our article (2). We wrote our article to try to stimulate discussion about what has been learned from all the research on endocrine disruption that has been done in the past decade. We put forward our personal views in a series of “lessons”, 10 in all, to which Segner has added number 11. Lesson 11 states that ecotoxicology needs to be based on an understanding of the mechanisms underlying toxic effects of chemicals on wildlife. Segner considers that if these mechanisms are understood, it may well be possible to predict what effects a chemical will have on important physiological processes (such as growth and reproduction), and hence it should be possible to design and apply ecotoxicological tests that are appropriate to the particular chemical under investigation. He has called this a “knowledge-based testing scheme”, which essentially means thinking before testing, rather than testing all chemicals in the same standard way without trying to utilize any existing knowledge or prediction about them, to conduct “intelligent ecotoxicology”. For example, if it had been realized long ago, as it could and probably should have been (3), that nonylphenol is weakly estrogenic (because some isomers have a close structural resemblance to the natural estrogen 17β-estradiol), then any possible effects of the chemical could have been investigated in ecotoxicological tests that incorporated estrogen-dependent endpoints, such as vitellogenin synthesis in oviparous vertebrates (4). Such an approach might have prevented some of the problems caused by the presence of nonylphenol and its ethoxylates in the aquatic environment (5). Ethinylestradiol is an even clearer example of a hormonally active (and very potent) compound which was, in retrospect, almost certain to have some impact on the endocrine system of nontarget recipients such as fish. Thus, it is fair to say that this (Segner’s “Lesson 11”) is indeed a valid lesson to arise from the endocrine disruption story. What is less clear is how useful this lesson might be in terms of protecting our aquatic environment in the future. There are probably about one hundred hormones known to date, with new ones still being discovered with surprising frequency. Often little is known about exactly what these hormones do in fish and other aquatic organisms (i.e., their mechanisms of action are unclear). If there are chemicals in the environment that in any way prevent these hormones from carrying out their functions, it will not be easy, based on what we know now, to incorporate knowledge about their mechanisms of action into ecotoxicology. A second problem concerns our lack of knowledge about the biochemical and physiological processes regulating the lives of most of our wildlife. We do know that these processes are quite similar throughout the vertebrates (fish to mammals). Hence, a chemical that is an estrogen to a human, or frog, is probably also estrogenic in fish. Put another way, mechanisms of action can probably be extrapolated across all vertebrates. But what about invertebrates? What about molluscs, crustaceans, and arthropods: these groups of animals (and others) are a vital component of the diverse ecosystems that ecotoxicologists are attempting to protect. How can we use knowledge of mechanisms of action to protect these animals from chemicals, when we know so 1086
9
ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 3, 2006
little about them? For example, it is still unclear whether estrogenic chemicals in the environment affect invertebrates, and if they do (or can), what mechanisms of action lie behind the effects. It appears that at least some invertebrate groups have estrogen or estrogen-like receptors (6), although even this basic piece of information is not as firmly established as one would like. Further, what these receptors do (control) in those invertebrates is currently completely unknown. It is worth keeping in mind the fact that it took about 35 years from the discovery that tributyltin (TBT) caused imposex in molluscs to the discovery of what appears to be the mode of action of this chemical (7). Only now, decades after the local extinction of mollusc populations around the world, can we begin to incorporate knowledge of how this chemical causes its effects into a more intelligent strategy for (hopefully) predicting such mechanisms and consequential effects before the chemical is released into the environment, and it is too late. Our knowledge about the molecular, biochemical, and physiological processes of invertebrates (which may not be the same for all groups) will need to increase dramatically before it will be possible to extrapolate mechanisms of action from vertebrates (such as fish) to invertebrates. Hence, protecting invertebrates from chemicals will remain problematic for some time. Interrogating (mining) the genomes of invertebrates may enable us to deduce how similar, or dissimilar, mechanisms of action are across all animals, vertebrates and invertebrates. Modern molecular techniques, such as use of microarrays, may provide rapid, efficient, and effective ways of deducing the mechanisms of action of toxicants. However, this approach to obtaining the required mechanistic information may not be the panacea some people hope and/or expect. The recent report that the expression levels of over 3500 genes in a single organ are altered by just one injection of estradiol (8) demonstrates the complexity that can be expected when an organism responds to a chemical. Extracting from all that information a mechanism of action that can be utilized in ectoxicological testing will not be an easy task. In summary, we support the addition of Segner’s “Lesson 11” onto our list. Such a mechanism of action test (knowledgebased ecotoxicology) could, and probably should, be an additional step in a risk assessment of new and emerging chemicals. We agree with him that if ecotoxicology is to progress, such that it provides data that can be used to better protect wildlife, the current “one size fits all” methodology for assessing the effects of chemicals must be changed to a strategy that begins utilizing knowledge about mechanisms of action to develop more appropriate testing strategies. We should remain aware, however, that our “knowledge base” on the physiology (endocrinology) of freshwater organisms still remains pitifully small!
Literature Cited (1) Segner, H. Comment on “Lessons from endocrine disruption and their application to other issues concerning trace organics in the aquatic environment.” Environ. Sci. Technol. 2006, 40, 1084-1085. (2) Sumpter, J. P.; Johnson, A. C. Lessons from endocrine disruption and their application to other issues concerning trace organics in the aquatic environment. Environ. Sci. Technol. 2005, 39, 4321-4332. (3) Dodds, E. C.; Lawson, W. Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proc. R. Soc. London, Ser. B 1938, 125, 222-232. (4) Sumpter, J. P.; Jobling, S. Vitellogenesis as a biomarker of oestrogenic contamination of the aquatic environment. Environ. Health Perspect. 1995, 103, 173-178. 10.1021/es0523082 CCC: $33.50
2006 American Chemical Society Published on Web 12/27/2005
(5) Sheahan, D. A.; Brighty, G. C.; Daniel, M.; Jobling, S.; Harries, J. E.; Hurst, M. R.; Kennedy, J.; Kirby, S. J.; Morris, S.; Routledge, E. J.; Sumpter, J. P.; Waldock, M. J. Reduction in the estrogenic activity of a treated sewage effluent discharge to an English river as a result of a decrease in the concentration of industrially-derived surfactants. Environ. Toxicol. Chem. 2002, 21, 515-519. (6) Thornton, J. W.; Need, E.; Crews, D. Resurrecting the ancestral steroid receptor: ancient origin of estrogen signalling. Science 2003, 301, 1714-1717. (7) Nishikawa, J.-I.; Mamiya, S.; Kanayama, T.; Nishikawa, T.; Shiraishi, F.; Horiguchi, T. Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods. Environ. Sci. Technol. 2004, 38, 6271-6276. (8) Moggs, J. G.; Tinwell, H.; Spurway, T.; Chang, H.-S.; Pate, Lim, F. L.; Moore, D. J.; Soames, A.; Stuckey, R.; Currie, R.; Zhu, T.; Kimber, I.; Ashby, J.; Orphanides, G. Phenotypic anchoring of
gene expression changes during estrogen-induced uterine growth. Environ. Health Perspect. 2004, 112, 1589-1606.
John P. Sumpter* Institute for the Environment Brunel University Uxbridge, Middlesex UB8 3PH, U.K.
Andrew C. Johnson Centre for Ecology and Hydrology Wallingford, Oxfordshire OX10 8BB, U.K. ES0523082
VOL. 40, NO. 3, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
1087
