Joseph W. Gorsuch

The biotic ligand model: a historical overview

During recent years, the biotic ligand model (BLM) has been proposed as a tool to evaluate quantitatively the manner in which water chemistry affects the speciation and biological availability of metals in aquatic systems. This is an important consideration because it is the bioavailability and bioreactivity of metals that control their potential to cause adverse effects. The BLM approach has gained widespread interest amongst the scientific, regulated and regulatory communities because of its potential for use in developing water quality criteria (WQC) and in performing aquatic risk assessments for metals. Specifically, the BLM does this in a way that considers the important influences of site-specific water quality. This journal issue includes papers that describe recent advances with regard to the development of the BLM approach. Here, the current status of the BLM development effort is described in the context of the longer-term history of advances in the understanding of metal interactions in the environment upon which the BLM is based. Early developments in the aquatic chemistry of metals, the physiology of aquatic organisms and aquatic toxicology are reviewed first, and the degree to which each of these disciplines influenced the development of water quality regulations is discussed. The early scientific advances that took place in each of these fields were not well coordinated, making it difficult for regulatory authorities to take full advantage of the potential utility of what had been learned. However, this has now changed, with the BLM serving as a useful interface amongst these scientific disciplines, and within the regulatory arena as well. The more recent events that have led to the present situation are reviewed, and consideration is given to some of the future needs and developments related to the BLM that are envisioned. The research results that are described in the papers found in this journal issue represent a distinct milestone in the ongoing evolution of the BLM approach and, more generally, of approaches to performing ecological assessments for metals in aquatic systems. These papers also establish a benchmark to which future scientific and regulatory developments can be compared. Finally, they demonstrate the importance and usefulness of the concept of bioavailability and of evaluative tools such as the BLM.

Environmental estrogens and reproductive health: A discussion of the human and environmental data

Estrogenic activity of certain xenobiotics is an established mechanism of toxicity that can impair reproductive function in adults of either sex, lead to irreversible abnormalities when administered during development, or cause cancer. The concern has been raised that exposure to ambient levels of estrogenic xenobiotics may be having widespread adverse effects on reproductive health of humans and wildlife. The purpose of this review is to evaluate (a) the nature of the evidence supporting this concern, and (b) the adequacy of toxicity screening to detect, and risk assessment procedures to establish safe levels for, agents acting by this mechanism. Observations such as adverse developmental effects after maternal exposure to therapeutic levels of the potent estrogen diethylstilbestrol or male fertility problems after exposure to high levels of the weak estrogen chlordecone clearly demonstrate that estrogenicity is active as a toxic mechanism in humans. High level exposures to estrogenic compounds have also been shown to affect specific wildlife populations. However, there is little direct evidence to indicate that exposures to ambient levels of estrogenic xenobiotics are affecting reproductive health. Reports of historical trends showing decreasing reproductive capacity (e.g., decreased sperm production over the last 50 years) are either inconsistent with other data or have significant methodologic inadequacies that hinder interpretation. More reliable historical trend data show an increase in breast cancer rate, but the most comprehensive epidemiology study to data failed to show an association between exposure to persistent, estrogenic organochlorine compounds and breast cancer. Clearly, more work needs to be done to characterize historical trends in humans and background incidence of abnormalities in wildlife populations, and to test hypotheses about ambient exposure to environmental contaminants and toxic effects, before conclusions can be reached about the extent or possible causes of adverse effects. It is unlikely that current lab animal testing protocols are failing to detect agents with estrogenic activity, as a wide array of estrogen-responsive endpoints are measured in standard testing batteries. Routine testing for aquatic and wildlife toxicity is more limited in this respect, and work should be done to assess the validity of applying mammalian toxicology data for submammalian hazard identification. Current risk assessment methods appear to be valid for estrogenic agents, although the database for evaluating this is limited. In conclusion, estrogenicity is an important mechanism of reproductive and developmental toxicity; however, there is little evidence at this point that low level exposures constitute a human or ecologic health risk. Given the potential consequences of an undetected risk, more research is needed to investigate associations between exposures and effects, both in people and animals, and a number of research questions are identified herein. The lack of evidence demonstrating widespread xenobiotic-induced estrogenic risk suggests that far-reaching policy decisions can await these research findings.

An assessment of the toxicity of phthalate esters to freshwater benthos. 2. Sediment exposures

Tests were performed with the freshwater invertebrates Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus to determine the acute toxicity of six phthalate esters, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), di-n-hexyl phthalate (DHP), and di-2-ethylhexyl phthalate (DEHP). It was possible to derive 10-d LC50 (lethal concentration for 50% of the population) values only for the four lower molecular weight esters (DMP, DEP, DBP, and BBP), for which toxicity increased with increasing octanol-water partition coefficient (Kow) and decreasing water solubility. The LC50 values for DMP, DEP, DBP, and BBP were 28.1, 4.21, 0.63, and 0.46 mg/L for H. azteca; 68.2, 31.0, 2.64, and > 1.76 mg/L for C. tentans; and 246, 102, 2.48, and 1.23 mg/L for L. variegatus, respectively. No significant survival reductions were observed when the three species were exposed to either DHP or DEHP at concentrations approximating their water solubilities.

Modeling and interpreting biological effects of mixtures in the environment: Introduction to the metal mixture modeling evaluation project

The fate and biological effects of chemical mixtures in the environment are receiving increased attention from the scientific and regulatory communities. Understanding the behavior and toxicity of metal mixtures poses unique challenges for incorporating metal-specific concepts and approaches, such as bioavailability and metal speciation, in multiple-metal exposures. To avoid the use of oversimplified approaches to assess the toxicity of metal mixtures, a collaborative 2-yr research project and multistakeholder group workshop were conducted to examine and evaluate available higher-tiered chemical speciation-based metal mixtures modeling approaches. The Metal Mixture Modeling Evaluation project and workshop achieved 3 important objectives related to modeling and interpretation of biological effects of metal mixtures: 1) bioavailability models calibrated for single-metal exposures can be integrated to assess mixture scenarios; 2) the available modeling approaches perform consistently well for various metal combinations, organisms, and endpoints; and 3) several technical advancements have been identified that should be incorporated into speciation models and environmental risk assessments for metals.

Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO(3) , pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72 µg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267 µg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61 µg Cu/L for survival; 8.8-38 µg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215 µg Cu/L) for survival or approximately fourfold (12-42 µg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agencys ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran from chronic exposure.

First in a special series: Analysis of the impact of papers published in Environmental Toxicology and Chemistry over the past 30 years—an overview and coming attractions

The Publications Advisory Committee (PAC) within the Society of Environmental Toxicology and Chemistry (SETAC) is involved in several activities related to SETAC publications, including books, the Globe (society newsletter) and, of course, the two society-sponsored journals, Environmental Toxicology and Chemistry (ET&C) and Integrated Environmental Assessment and Management (IEAM). One of the PAC’s tasks is to increase the visibility of the journals both to Society membership and the broader scientific community. One way to do this, for example, is to assess the impacts of their content on science and regulation in the field of environmental sciences. A common metric of journal impact in social, physical, and biological sciences is the Impact Factor (IF). The IF, calculated annually for a journal, is defined as the total number of indexed citations to papers a journal has published over the prior two years, divided by the total number of papers published by that journal during that same period. The current IF for ET&C is about 3. An IF is not available for IEAM because the journal is not yet indexed. The IF has become an increasingly important determinant of where authors publish their work; hence, it is highly linked with journal visibility. Although the IF can provide important insights, using this metric in isolation to judge the impact of a journal is limited. For example, due to the relatively slow pace of change in regulatory procedures/ activities in response to new science, highly applied papers in environmental toxicology and chemistry might be prone to delayed acknowledgments in terms of significant citations, which would not be captured by use measurements, such as the IF, which are focused on the shorter term. To help address the challenge of assessing the long-term impact of ET&C publications, the PAC recently analyzed the citations of all papers published in the journal since its inception in 1982. The analysis used the Thompson-Reuters Web of Science database and software. Over the course of its 30-year history, ET&C has published a total of 7,674 indexed (citable) papers as of February 2012 when the analysis was conducted. The top 100 cited papers from that analysis (actually 102 papers—the 100th position was a tie) are listed in Table 1. Notably, all papers had been cited more than 100 times, ranging from 117 citations for papers published by Nebeker et al. ([1]; toxicity test methods for sediments), Meylan et al. ([2]; predicting water solubility of chemicals), and Arukwe et al. ([3]; effects of nonylphenol on Atlantic salmon) to a manuscript by Jobling et al. ([4]; concerning estrogenicity of nonylphenol in fish), which had been cited 818 times. This top 100 list spans a substantial time period, featuring two papers from as early as 1984 (Nebeker et al. [1] and Mount and Norberg [5], which are arguably ‘‘classics’’ in the areas of sediment and effluent test methods, respectively), to a comparatively recent review (2008) on nanomaterials by Klaine et al. [6]. Perusing the topical content of the top 100 papers reveals a broad range of topics have been covered in environmental chemistry, toxicology, and risk assessment, with authors from several countries in North America and Europe represented. Not unexpectedly, the authors of many of the papers are highly accomplished scientists in their fields. Taken as a whole, the papers on the top 100 list are an excellent reflection of the high-visibility scientific and regulatory issues published over the past 30 years relative to evaluating the risk of wide-ranging inorganic and organic contaminants in both terrestrial and aquatic environments. It is impossible in this short editorial to address the significance and impacts of the individual papers and topical areas encompassed on the list. As such, we are implementing an innovative communication strategy to share some of this information with SETAC members and other environmental scientists. Specifically, we have asked prominent scientists involved with the work captured on the top 100 list to write short essays on the specific topic areas reflected in the highly-cited papers. For this effort, the PAC collated representative papers from the top 100 list into a manageable number of topical areas (24) as a basis for the essays. Examples of topical areas for which essays are being developed include: occurrence, causes, and significance of endocrine-disrupting chemicals in the environment; chemical and biological approaches for assessing the effects of effluent or sediment-associated contaminants; advances in risk assessment practices; and detecting and evaluating contaminants of historical and emerging concern. In the coming calendar year, ET&C will publish 24 essays derived from the top 100 analysis that the PAC conducted. These essays will describe the science/regulatory challenge the research/analysis sought to address, explain how the research/ paper(s) met this challenge, account for the practical impacts of the papers on science and regulatory activities, and identify remaining uncertainties/future directions for the line of research described in the cited papers. In addition to being published in ET&C, the essays will be archived and readily available electronically; details on this portion of the effort are being finalized and will be communicated to Society membership in the near future. The PAC feels that developing and publishing the various essays derived from the list of top 100 papers will have the dual benefit of highlighting the impact of past ET&C publications and providing an important and unique historical accounting of high-impact environmental research conducted by scientists associated with SETAC. In addition, we feel that the essays will provide significant insights regarding evolving Environmental Toxicology and Chemistry, Vol. 32, No. 1, pp. 1–6, 2013 # 2013 SETAC Printed in the USA DOI: 10.1002/etc.2053

Chronic toxicity of silver to the sea urchin (Arbacia punctulata).

The chronic toxicity of silver to the sea urchin (Arbacia punctulata) was determined in 30 per thousand salinity seawater during a three-part study: A fertilization test (1-h sperm exposure), a 48-h embryo test, and a 30-d adult test. Combined data from the three tests resulted in a lowest-observed-effect concentration of 19 microg/L, a no-observed-effect concentration of 8.6 microg/L, and a maximum acceptable toxicant concentration of 13 microg/L, based on measured concentrations of dissolved silver. The 96-h median effective concentration was 40 microg/L, and the acute to chronic toxicity ratio was 3.1. During the tests, measured concentrations of free ionic silver (Ag+) were only 0.0027 to 0.0046% of dissolved silver concentrations, as predicted by ion-speciation theory. Some measured Ag+ concentrations were lower than predicted, indicating the presence of other ligands in the seawater test media. These strong sulfide ligands were exuded by the exposed sea urchins into the seawater (where Ag-sulfide complexes formed) in amounts that increased in direct proportion to the silver concentration during the toxicity test. This suggests a toxicity-defense mechanism that functioned by modifying the chemistry of the surrounding external medium.

Effects of sodium chloride on chronic silver toxicity to early life stages of rainbow trout (Oncorhynchus mykiss)

The chronic (early life stage) toxicity of silver to rainbow trout (Oncorhynchus mykiss) was determined in flow-through exposures. Rainbow trout embryos were exposed to silver (as AgNO3) from 48 h or less postfertilization to 30 d postswimup in soft water in the presence and absence of 49 mg/L of NaCl (30 mg/L of Cl). The studies determined effect levels for rainbow trout exposed throughout an extended development period and assessed possible protective effects of sodium chloride. Lowest-observed-effect concentrations were greater than 1.25 microg/L of dissolved silver for survival, mean day to hatch, mean day to swimup, and whole-body sodium content in both studies. Whole-body silver concentrations increased significantly at 0.13 microg/L of dissolved silver in unmodified water and at 1.09 microg/L of dissolved silver in amended water. The maximum-acceptable toxicant concentration for growth was greater than 1.25 microg/L of dissolved silver in unmodified water and 0.32 microg/L of dissolved silver in amended water. Whole-body silver concentrations were more sensitive than survival and growth end points in unmodified water. Interpretation of sodium chloride effects on chronic silver toxicity to rainbow trout was complicated by differences in measured effect levels that were potentially the result of strain differences between test organisms in the two studies.

Influence of salinity and organic carbon on the chronic toxicity of silver to mysids (Americamysis bahia) and silversides (Menidia beryllina)

Tests were conducted with mysids (Americamysis bahia) and silversides (Menidia beryllina) to evaluate the influence of salinity and organic carbon on the chronic toxicity of silver. During 7- and 28-d tests conducted at 10, 20, and 30% per hundred salinity, higher concentrations of dissolved silver generally were required to cause a chronic effect as the salinity of the seawater was increased. The 28-d mysid and silverside 20%-effective concentration values (expressed as dissolved silver) ranged from 3.9 to 60 and from 38 to 170 microg/L, respectively, over the salinity range. This pattern was not observed when the same test results were evaluated against the concentrations of free ionic silver (measured directly during toxicity tests), as predicted by the free-ion activity model. Increasing the concentration of dissolved organic carbon from 1 mg/L to the apparent maximum achievable concentration of 6 mg/L in seawater caused a slight decrease in chronic toxicity to silversides but had no effect on the chronic toxicity to mysids. The possible additive toxicity of silver in both food and water also was investigated. Even at the maximum achievable foodborne concentration, the chronic toxicity of silver added to the water was not affected when silver was also added to the food, based on the most sensitive endpoint (growth). However, although fecundity was unaffected at all five tested concentrations during the test with silver in water only, it was significantly reduced at the two highest waterborne silver concentrations (12 and 24 microg/L) during the test with silver dosed into food and water.

Celebrating 50 Years of Publication

We are honored to introduce this issue as the first in the Golden Anniversary year of the Bulletin of Environmental Contamination and Toxicology. Several changes during 2016 may be noted in commemoration of this special year. For example, the Bulletin’s cover has been changed from the traditional orange to gold. Editorials by former and present editors-in-chief will appear in several of the forthcoming issues. These editorials will reflect on the history and expansion of the journal. Several past authors have offered to contribute articles on the advancement of science and regulations to protect the environment, and some of the general articles that are published may be flavored with a bit more historical perspective than usual. The first issue of the Bulletin was published in 1966, at a time when chemicals such as chlorinated pesticides were common subject matter. Analytical instruments were archaic by current standards, and computerization of laboratory instruments and libraries was essentially in its infancy. The internet and digital publishing did not yet exist. Many of the environmental organizations and regulatory agencies that exist around the world today had not yet been formed. The 1970s, a decade for passage of major environmental laws in the United States, was still a few years ahead. Some universities and colleges were only starting to consider the offering of environmental science, environmental engineering or environmental toxicology as majors. It was a time when the environment had become seriously polluted by a host of chemicals, and the demand existed to address these issues. Fortunately, certain far-sighted individuals saw the need for a vehicle to provide rapid communication amongst scientists involved in analyzing the contaminants and studying their effects upon the biota. It was in this setting that the Bulletin was launched. As the Bulletin became known among scientists, more articles were submitted for publication, and the journal expanded from the original six issues per year to twelve. The physical size of the pages grew, as well as the number of pages per issue, to accommodate the rapidly expanding field of environmental contamination and toxicology. The demographics of authorship also changed over time. A recent analysis (Drouillard and Bennett 2015) of the most highly cited papers in the Bulletin revealed that North American authors predominated for about the first 30 years, with highly cited contributions from Europe, Asia, and the Middle East increasing in number during this period. For the most recent period for which data were included in their study (2004–2009), the order for region of origin of the 50 top-cited papers was Asia, North America, Middle East, Europe, South America and Australia. This analysis has demonstrated the increasingly global nature of the Bulletin in its authorship over time. The Bulletin is truly a well recognized international journal today. In the inaugural issue of the journal (Editorial Board 1966), it was stated in the ‘‘Aims and Scope’’ that the Bulletin ‘‘will provide rapid publication of significant advances and discoveries in the fields of pesticide research, air, soil and water contamination and pollution, methodology, and other disciplines concerned with the introduction, presence and effects of toxicants in the total environment.’’ Articles suitable for publication were to be short, of less than 2000 words. While the wording has evolved some (see ‘‘Aims and Scope’’ for 2015; www. & Daniel J. Call dcall@enviro-analysts.com