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John P Sumpter

Publications and source records attributed to John P Sumpter.

13 recordsLinked to original sources
PubMed2006

Modeling effects of mixtures of endocrine disrupting chemicals at the river catchment scale.

For endocrine disrupting chemicals in the environment, concerns arise primarily from the effects that may be induced in wildlife. A well studied example is estrogenic chemicals in the aquatic environment and their effects on fish. Directly measuring effects, in fieldwork studies, is an expensive and time-consuming approach that is fraught with many difficulties, ranging from study design right through to data analysis and interpretation. An alternative approach would be to predict the scale of effect(s) using suitable modeling techniques. We have attempted to do this using estrogenic chemicals as an example. We chose this group of aquatic pollutants because of the current considerable interest in them and the wealth of biological data available on them. Using the established GREAT-ER hydrological model,we have first predicted the concentrations and then the estrogenic effects on fish, of estrone, estradiol, ethinyl estradiol, and nonylphenol individually throughout an entire river catchment. We then show that knowledge of the biological responses of fish to mixtures of these chemicals can be used to predict the effect of environmentally realistic mixtures of them. To determine the degree of risk posed by this group of chemicals, it was necessary to take into account mixture effects: assessment on a chemical by chemical basis led to underestimations of the risk. Finally, we show that the approach can be used to predict how the risk will be affected by changes in the concentration of one chemical in the mixture. Although we have used only one endpoint (vitellogenin induction as an estrogenic response) and one group of similarly acting chemicals, we suggest that this general approach could prove extremely useful to regulatory authorities and other parties charged with protecting aquatic wildlife from adverse effects caused by chemicals in their environment.

Endocrine Disruptors↗
PubMed2005

Lessons from endocrine disruption and their application to other issues concerning trace organics in the aquatic environment.

In the past 10 years, many thousands of research papers covering the many different aspects of endocrine disruption in the environment have been published. What has been learned from all this research? We have tried to reduce this very large volume of research into a relatively small number of "lessons". Hence, this paper is not a typical review, but instead it summarizes our personal opinions on what we consider are the major messages to have come from all this research. We realize that what has been a lesson to us may have been obvious from the outset to someone more knowledgeable on that particular aspect of the burgeoning field of endocrine disruption. In addition, it is inevitable that others will consider that we have "missed" some lessons that they would have expected to find included in our list. If so, we encourage them to submit them as responses to our paper. Our own lessons range widely, from the design and interpretation of data from fieldwork studies, through some key messages to come out of the very many laboratory studies that have been conducted, to issues around the sources and fates in the environment of endocrine-disrupting chemicals, and finally to the key role of sewage treatment in controlling the concentrations of these chemicals in the aquatic environment. Having (hopefully) learned our lessons, we have then applied them to the difficult issue of how best to approach future concerns about the potential impacts of other new and emerging contaminants (e.g., pharmaceuticals) on wildlife.

Animals↗
PubMed2005

Accurate prediction of the response of freshwater fish to a mixture of estrogenic chemicals.

Existing environmental risk assessment procedures are limited in their ability to evaluate the combined effects of chemical mixtures. We investigated the implications of this by analyzing the combined effects of a multicomponent mixture of five estrogenic chemicals using vitellogenin induction in male fathead minnows as an end point. The mixture consisted of estradiol, ethynylestradiol, nonylphenol, octylphenol, and bisphenol A. We determined concentration-response curves for each of the chemicals individually. The chemicals were then combined at equipotent concentrations and the mixture tested using fixed-ratio design. The effects of the mixture were compared with those predicted by the model of concentration addition using biomathematical methods, which revealed that there was no deviation between the observed and predicted effects of the mixture. These findings demonstrate that estrogenic chemicals have the capacity to act together in an additive manner and that their combined effects can be accurately predicted by concentration addition. We also explored the potential for mixture effects at low concentrations by exposing the fish to each chemical at one-fifth of its median effective concentration (EC50). Individually, the chemicals did not induce a significant response, although their combined effects were consistent with the predictions of concentration addition. This demonstrates the potential for estrogenic chemicals to act additively at environmentally relevant concentrations. These findings highlight the potential for existing environmental risk assessment procedures to underestimate the hazard posed by mixtures of chemicals that act via a similar mode of action, thereby leading to erroneous conclusions of absence of risk.

Animals↗
PubMed2005

Endocrine (sexual) disruption is not a prominent feature in the pike (Esox lucius), a top predator, living in English waters.

The high incidence of intersex roach (Rutilus rutilus) in some United Kingdom rivers that has been associated with exposure to sewage treatment works (STWs) effluent led us to hypothesize that top predator fish also may be affected by estrogenic chemicals, because they are likely to bioaccumulate lipophilic compounds through a predator-prey relationship. To investigate this possibility, pike (Esox lucius) were sampled both upstream and downstream of STWs and then examined for total estrogenic activity of their bile, as measured using a yeast-based estrogen assay to determine the degree of recent exposure of the pike to estrogens and vitellogenin induction, and for possible disruption of sexual development, as measured using histological analysis of the gonads. No evidence of severe disruption was found in the sampled fish, which came from 16 sampling sites that were representative of English rivers. However, 14% of pike were intersex, of which 15 of 16 showed patches of male germ cells among predominantly female gonadal tissue. The incidence of masculinization was independent of whether the pike had been sampled upstream or downstream of STWs. Although pike are gonochoristic, it is not known if this masculinization of presumptive female pike is normal or, instead, indicative of endocrine disruption. Vitellogenin concentrations were not elevated in male pike at sites either upstream or downstream of STWs. The results suggest that sexual disruption is not common in pike, a fish at the top of the food chain in the freshwaters of England.

Animals↗
PubMed2003

Route of exposure affects the oestrogenic response of fish to 4-tert-nonylphenol.

When toxicants cause effects to aquatic organisms, it is often unclear by what route, or routes, the toxicant entered the affected organism. The toxicity of a compound depends on its degree of uptake, distribution and metabolism, as well as its molecular interactions at the site of action. It was hypothesised, that a hydrophobic chemical such as 4-tert-nonylphenol (4-NP), entering via the gills/skin, may be more oestrogenic than one entering through the diet, because in the latter case it will undergo metabolism in the small intestine and liver before entering the bloodstream. In this way, metabolism may reduce or eliminate the oestrogenic potential of 4-NP before it reaches target organs such as the gonads or liver. To compare the potency of 4-tert-nonylphenol when administered via different routes, male fathead minnows (Pimephales promelas) were exposed to 4-NP either through waterborne exposure (experiment 1), or via the diet (experiment 2). Fish were exposed to 4-NP for 2 weeks either via the water at one of three nominal concentrations: 1, 10 or 50 microg/l (experiment 1) or 100, 500 or 1000 microg/day via the diet (experiment 2). Liver and blood samples were taken for vitellogenin mRNA and plasma vitellogenin quantification, respectively. Exposure of male fathead minnows to 50 microg/l of 4-NP in the water (experiment 1) and 500 and 1000 microg/day of 4-NP via the diet (experiment 2) induced vitellogenin mRNA. A similar pattern occurred for plasma vitellogenin induction, however, there was also a significant increase in plasma vitellogenin concentration in the fish exposed via the water to 10 microg/l of 4-NP. Using data from pharmacokinetics studies, an estimate for the total amount of 4-NP that entered the fish during each exposure was compared with the concentrations of plasma vitellogenin in each group of fish. The result showed a 10-fold greater sensitivity for 4-NP in fish exposed via the water compared with exposure via the oral route.Results obtained from this study indicate that a chemical such as 4-NP has a higher oestrogenic potential when it enters the bloodstream via the gills/skin of a fish compared with exposure through the diet.

Absorption↗
PubMed2003

Relative potencies and combination effects of steroidal estrogens in fish.

The natural steroids estradiol-17beta (E2) and estrone (E1) and the synthetic steroid ethynylestradiol-17alpha (EE2) have frequently been measured in waters receiving domestic effluents. All of these steroids bind to the estrogen receptor(s) and have been shown to elicit a range of estrogenic responses in fish at environmentally relevant concentrations. At present, however, no relative potency estimates have been derived for either the individual steroidal estrogens or their mixtures in vivo. In this study the estrogenic activity of E2, E1, and EE2, and the combination effects of a mixture of E2 and EE2 (equi-potent fixed-ratio mixture), were assessed using vitellogenin induction in a 14-day in vivo juvenile rainbow trout screening assay. Median effective concentrations, relative to E2, for induction of vitellogenin were determined from the concentration-response curves and the relative estrogenic potencies of each of the test chemicals calculated. Median effective concentrations were between 19 and 26 ng L(-1) for E2, 60 ng L(-1) for E1, and between 0.95 and 1.8 ng L(-1) for EE2, implying that EE2 was approximately 11 to 27 times more potent than E2, while E2 was 2.3 to 3.2 times more potent than E1. The median effective concentration, relative to E2, for the binary mixture of E2 and EE2 was 15 ng L(-1) (comprising 14.4 ng L(-1) E2 and 0.6 ng L(-1) EE2). Using the model of concentration addition it was shown that this activity of the binary mixture could be predicted from the activity of the individual chemicals. The ability of each individual steroid to contribute to the overall effect of a mixture, even at individual no-effect concentrations, combined with the high estrogenic potency of the steroids, particularly the synthetic steroid EE2, emphasizes the need to consider the total estrogenic load of these chemicals in our waterways.

Animals↗
PubMed2003

Stress status of gudgeon (Gobio gobio) from rivers in Switzerland with and without input of sewage treatment plant effluent.

To assess the importance of sewage treatment plant effluents on fish health, we studied gudgeon in two rivers in the Swiss midlands (Canton Lucerne). Both rivers receive pollution from diffuse sources, while one also receives the effluent of a sewage treatment plant. Male and female gudgeon during and outside of the spawning season were compared with respect to reproductive parameters and health status across both rivers as well as upstream and downstream of the STP. Several biomarkers were studied, including cytochrome P4501A, 7-ethoxyresorufin-O-deethylase, plasma vitellogenin, ovotestis, lipid, liver histology, condition factor, gonadosomatic index, splenosomatic index, parasites of spleen and liver, population structure, and species diversity. Gudgeons of both rivers exhibited signs of a moderately impaired health status. By a stepwise backward analysis, the cytochrome P4501A content, the splenosomatic index, and the incidence of parasites in the liver were found to provide the best discrimination of the three sampling sites. Evidence of a significant elevation in response to the sewage treatment plant effluent was found neither in vitellogenin concentration nor in the ovotestis rate. While population structure was analyzed upstream and downstream of the sewage treatment plant, only gudgeons of the latter site revealed a disturbed population structure, most probably caused by a former nitrite discharge.

Animals↗
PubMed2002

Utility of a juvenile fathead minnow screening assay for detecting (anti-)estrogenic substances.

The European Chemical Industry's aquatic research program for endocrine disrupters includes the development of an in vivo juvenile fathead minnow (Pimephales promelas) screening assay. Working within the Organization for Economic Cooperation and Development's (OECD, Paris, France) tiered approach to endocrine disrupter evaluation in fish, the juvenile fish screening protocol was adapted from the OECD test guideline 204. Six chemicals, with different (anti-)estrogenic potencies, were used to develop the in vivo juvenile fish screening protocol: diethylstilbestrol, 17alpha-ethynylestradiol, genistein, methoxychlor, 4-tert-pentylphenol, and ZM189,154 (a novel pharmaceutical antiestrogen). Mixed-sex juvenile fathead minnows were exposed to individual chemicals (with chemical analyzes) and sampled after 4, 7, 14, and 21 d of exposure. Wet weight, total length, condition factor, and whole-body homogenate concentrations of vitellogenin (VTG) were determined. Estrogens and antiestrogens were detected in this screen by virtue of the VTG response (an elevation or suppression, respectively) after 14 d. The study showed that the use of VTG concentrations in mixed-sex juvenile fish provides a sensitive and robust assay for the detection of both estrogenic and antiestrogenic chemicals, with widely divergent potencies.

Animals↗
PubMed2002

Estrogenic activity measured in a sewage treatment works treating industrial inputs containing high concentrations of alkylphenolic compounds--a case study.

Chemical analyses were combined with a biological assay to investigate the main estrogenic chemicals as they passed through a sewage treatment works (STW) and entered a river. The STW studied was unusual in that it received wastewater from the textile trade. This wastewater was shown to contain high concentrations of alkylphenol polyethoxylates and their degradation products, such as nonylphenol. High-performance liquid chromatography fractionation, combined with biological assay, showed that the majority of the estrogenic activity was contributed by the alkylphenolic chemicals and the natural estrogens 17beta-estradiol and estrone. Despite removal of a high proportion of the alkylphenolic chemicals by the various treatment processes within the STW, concentrations in the final effluent were still high compared to most other STW effluents in the United Kingdom. The effluent was very estrogenic to caged fish, as was the river water 2 and 5 km downstream of the STW, even though less so. Using various approaches, attempts were made to determine which group of chemicals contributed most to the estrogenic activity of the effluent. The analysis suggested that, in this unusual situation, the alkylphenolic chemicals may contribute the majority of the estrogenic activity of the effluent. However, this conclusion was based on a number of uncertainties that are presently unresolved and hence can be considered only tentative.

Animals↗
PubMed2002

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.

As a result of the introduction of tighter discharge limits and effluent treatment processes at source, the concentration of alkylphenol ethoxylates and nonylphenol present in the final effluent discharge from a sewage treatment works that treats trade effluent from the textiles industry was reduced. The estrogenic effects of the final effluent discharge to the Aire River were compared over a four-year period during which various treatment measures were introduced. Male rainbow trout exposed to the effluent on four occasions in consecutive years (1994-1997) showed a reduction in the level of induced vitellogenesis between 1994 and 1997. A marked decrease in gonadosomatic index (GSI) and increase in heptaosomatic index (HSI) was measured in fish exposed to the effluent in 1994. In successive years, these differences diminished, and in the case of the GSI no measurable difference was observed between fish exposed to the final effluent or those in the control group in 1997. However, an increase in HSI was still measurable in 1997 in fish exposed to the final effluent and at sites farther downstream. The reduction in the effects of the effluent paralleled the reduction in the concentration of nonylphenol as well as its mono- and diethoxylates, which have been demonstrated to produce estrogenic effects in trout exposed to these compounds in the laboratory. This study demonstrates that the setting of more restricted discharge limits for known estrogenic chemicals of industrial origin can lead to significant reductions in the estrogenic activity of the watercourses into which the effluents are discharged.

Animals↗
PubMed2002

Changes in estrogenic and androgenic activities at different stages of treatment in wastewater treatment works.

Estrogenic and androgenic activities of wastewater were determined during treatment in five wastewater treatment works (WWTWs) in the Untied Kingdom. With one exception, both estrogenic and androgenic activities decreased markedly as wastewater progressed through the plants; removal rates were generally 70% or higher, sometimes reaching 100%. Most of the reduction in activity occurred during secondary (biological) treatment. In both influents and effluents, estrogenic and androgenic activities were appreciably lower in samples collected in August, when the amount of rain had been substantial, compared with samples collected in April and May. Most final effluents contained very low (or nondetectable) estrogenic activity (undetectable to 13 ng/L of estradiol equivalents) and androgenic activity (undetectable to 143 ng/L of dihydrotestosterone [DHT] equivalents), although one (from a WWTW that had only primary treatment) contained relatively high activities (40 ng/L of estradiol equivalents; 4,033 ng/L of DHT equivalents). The type of treatment available at the various WWTWs also affected the activity of the final effluent. The biological significance of these results will depend upon which chemicals contribute to the estrogenic and androgenic activities, because of widely different potencies of different estrogenic chemicals, and on the degree of dilution of the effluents in their receiving waters.

Biological Assay↗