Bad habits die hard: The NOEC's persistence reflects poorly on ecotoxicology

Ecotoxicologists generally rely on simple measures to express the toxicity of chemicals to organisms, such as the no-observed-effect concentration (NOEC) and the exposure concentration associated with x% effect (ECx). The origin of these toxicity metrics probably relates to the real or presumed needs of risk assessment. Regulators prefer simple and well-accepted tools to help them manage the huge number of chemicals released into the environment. Ecotoxicology, however, does not exist for the sole purpose of supporting regulators; it should also be a field of scientific research. Unfortunately, science and regulation are so tightly intertwined in ecotoxicology that they are often difficult to separate. The ‘‘bad habits’’ ecotoxicological pioneers have developed to support risk assessment have survived into present-day scientific research and have proven surprisingly hard to break. The NOEC is the most obvious example of such a habit. The NOEC is the highest tested concentration that does not lead to significant deviation from the control response. The lack of a statistically significant effect, however, does not mean that there is no effect. The actual level of effect at the NOEC varies between individual tests; actually between nearly 0 and nearly 100% [1]. The problems with the NOEC concept are well known and have been discussed extensively in the open literature, with a peak in the 1990s (see the recent editorial of Landis and Chapman in Integrated Environmental Assessment and Management [2] and references therein). In 1998, a workshop of the Organisation for Economic Co-operation and Development (OECD) [3] concluded that the NOEC should be phased out completely. A resolution to the same effect came from the International Organization for Standardization (ISO). Clearly, the NOEC is a poor indicator of no effect, and because the level of effect at the NOEC varies so much between tests, it is also a poor relative measure of toxicity. With the surge of criticism in the 1990s, and the obvious nature of the disadvantages, one would expect the NOEC to be discarded by now. So what is the situation in regulatory settings? In recent ISO and OECD guidance on dose–response analysis [4], the phase out is stressed again, but guidance for NOEC derivation is still included because many regulatory frameworks still rely on this metric. In recent guidance of the European Chemicals Agency (ECHA) [5], the problems with the NOEC are recognized clearly and the phase out recommendation of the OECD is mentioned. Furthermore, the guidance states that for long-term studies, ‘‘EC10. will be used preferentially. ’’ Clearly, the NOEC has not been banned yet, but at least its shortcomings are being recognized in these frameworks. What is the situation in our scientific community? I made a quick survey of the publications in Environmental Toxicology and Chemistry (ET&C) in 1990 and 2010 to see how 20 years of progress affects the use of the NOEC and similar concepts (lowest observed effect concentration [LOEC], no observed effect level [NOEL], and no observed adverse effect level [NOAEL]). The 1990 volume of ET&C includes 164 publications (including errata and letters) of which seven mention the NOEC (or a similar concept) in the main text. Of these, one is a letter (discussing an earlier article), one reports literature values, and five derive NOECs from experimental data. The 2010 volume of ET&C includes more than twice the number of publications in total (352). In 46 articles, the NOEC (or similar concept) is mentioned in the main text. Of these, three only mention the NOEC briefly, 16 mention or use literature NOECs, and the remaining 27 actually derive NOECs from experimental toxicity data. Interestingly, in two articles a small-effect concentration (derived using regression analysis) was used as NOEC, one derives the NOEC ‘‘graphically from average values,’’ which leaves 24 articles that relied on hypothesis testing. Only two articles add some critical comment to their use of the NOEC (but still conclude it is a good estimate for no effects), and I spotted only one analysis of statistical power. This small and admittedly limited analysis shows that the NOEC concept still occurs regularly in our scientific journal in 2010, and I am sure that ET&C is not an exception. Furthermore, there is no indication that the popularity of the NOEC has decreased over the last 20 years; this analysis even indicates the opposite trend. And finally, the absence of critique among the authors that use or derive NOECs is striking. How is this possible? It is true that regulatory contexts worldwide still rely on the NOEC. Changing a well-established risk assessment practice is a slow and painful process, with its own political and legal constraints. As scientists, however, we are not bound by the same constraints; we do not have to continue using the NOEC to study the effects of chemicals. Surprisingly, the regulatory guidance of ISO, OECD, and ECHA reveals more of a critical attitude than our own scientific community. There is no scientific justification for the NOEC whatsoever, so why can’t we break this bad habit? Warne and Van Dam [6] suggested it is a lack of understanding the limitations, a lack of understanding the statistics, and the fact that no organization has clearly and categorically banned the NOEC. I would like to add to this list the lure of large numbers of existing NOEC values in the literature and in databases. However, the problems associated with the NOEC should force us to extreme caution. If there is a solid reason to report an NOEC (which I fail to see), its calculation should be accompanied by a rigorous statistical treatment, as is necessary for any type of hypothesis testing [7]. Using NOECs from the literature or databases for quantitative structure–activity relationships (QSARs) and speciessensitivity distributions (SSDs) is of limited scientific value. Even though these approaches certainly have their merits, it is unlikely that any useful structure can be built on such shaky foundations. Such analyses should thus, at the very least, be Environmental Toxicology and Chemistry, Vol. 31, No. 2, pp. 228–229, 2012 # 2011 SETAC Printed in the USA DOI: 10.1002/etc.746