Each and every one of us is exposed to chemicals on a daily basis and contributes to the global issue of chemical pollution. Humankind has become heavily dependent on the use of man-made chemicals in order to sustain the increased quality of life that is generally seen globally. There is however a price to pay in that we generally live in a world that is polluted by anthropogenic chemicals. From the water we drink to the food we eat there will be some trace of chemical residues; you just need to look closely enough and/or know what you’re looking for. With many hundreds of thousands of man-made chemicals approved within Europe for use in various ways, it is no surprise that we come into daily contact with them. What is also important to understand is that the presence of a man-made chemical is not enough to establish whether it poses a risk to environmental or human health; it needs to be present in sufficient amounts to elicit an effect. Over the past 20 years the focus of my research been on understanding which chemicals we should be concerned with, which pose the greatest risk and why do they pose such a risk. This work is of major societal and scientific significance as it protects the world we live in whilst teaching us about the better regulation of the chemicals we have become so dependent. To understand the nature of my research it is important to understand that prior to the mid-nineteen nineties hazardous organic chemicals were typically restricted to lists comprising of a number of banned (and typically chlorinated) pesticides, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans and the antifouling biocide tributyltin (TBT). One of the major enigmas that faced environmental scientists at the time was that even though it was possible to quantify and monitor the presence of the above hazardous substances in the environment, they often didn´t explain the environmental quality measured though biological effects on organisms. Chemicals are globally regulated on an individual substance level and subsequently within the context of influencing these regulations, for the improved protection of environmental and human health, it is therefore essential to know which chemical contaminants are actually causing biological effects. It is also necessary to know the levels at which any organism will be exposed and what the consequences of these levels. My research subsequently became focused on two separate approaches; identifying which substances actually cause the biological effects unexplained by hazardous substances and evaluating the occurrence, environmental fate and ecotoxicity of those chemicals not routinely monitored or present on priority lists of hazardous substances; a group of chemical contaminants later termed contaminants of emerging concern (CECs). An effect-directed non-target approach A targeted approach to environmental analysis infers that we know exactly what we should be looking for. Whilst this is a suitable approach for chemicals that we suspect may be of concern, it does not help us understand which other contaminants may be present in the environment and potentially causing harm. When embryos of oysters exposed to estuarine surface waters developed deformities and this could not be attributable to the levels of priority hazardous substances a bioassay-directed non-target approach to environmental analysis was developed to identify chlorinated and alkylphenols as responsible [5, 6]. This approach has subsequently evolved into the approach termed effect-directed analysis (EDA) and is widely used globally for the identification of CECs. My own research has successfully applied the approach to identify for the first time a number of important environmental contaminants; steroidal androgens [10, 13, 14] as environmental contaminants, the phthalate ester bis(2-ethylhexyl)phthalate [10], cinnarizine, cholesta-4,6.dien-3-one [19], C1-C5 and C9 alkylphenols [21], petrogenic naphthenic acids [57] as environmental estrogen receptor agonists, C1-C5 and C9 alkylphenols [21], PAHs and petrogenic naphthenic acids [57] as androgen receptor antagonists and unresolved polar aromatic compounds as important environmental genotoxins [15]. Another focus of my effects-directed research has been identifying environmental contaminants that exert the same effects as dibenzo-p-dioxins and polychlorinated dibenzofurans in that they are aryl hydrocarbon receptor (AhR) agonists. Dioxin-like chemicals are ubiquitous in the environment and in addition to those that are routinely monitored there are a large number of other compounds that exert dioxin-like effects [26, 28, 32, 33, 37, 52, 64, 82, 93, 98, 99]. Better understanding of AhR agonists will in the long run help protect the environment and humans from a particularly hazardous group of chemicals. A targeted approach The early- to mid-nineteen nineties saw the widespread introduction of liquid chromatography coupled to mass spectrometry (LC-MS) to the environmental analytical toolbox. Robust instruments typically using electrospray and atmospheric pressure chemical ionisation were well suited to the analysis of the more polar CECs, such as alternative antifouling biocides to TBT, pharmaceuticals, personal care products, veterinary medicines, illicit drugs and rodenticides. Robust analytical methodology is key to my research [2, 4, 18, 31, 34, 35, 42, 49, 66, 69, 72, 73, 86, 94, 102] as it allows the better understanding of how contaminants behave and interact with the environment. Development of robust, specific and sensitive methods for the analysis of alternative antifouling biocides [2, 4] allowed for the first time an evaluation of their life-cycle from release at the paint surface, and the factors that influence this [3], their occurrence in the environment [7, 8, 12, 29], fate and behaviour [12, 16] and subsequent effects [36, 41]. Assessment of the environmental risks based upon these data showed that both Irgarol 1051 and diuron were a threat to freshwater and marine algae. The significance of this research is that it subsequently led to restrictions being placed on the use of Irgarol 1051 and diuron in antifouling products in a number of European countries [58] and an awareness of the hazards associated with the deliberate release of biocidal products into the environment [86]. Observations of human pharmaceutical residues in the chromatograms of wastewater effluent samples being analysed by EDA and reports of their occurrence in German wastewaters motivated the development of LC- tandem MS methods for the quantification of pharmaceutical residues in waste- and surface waters [18]. Pharmaceuticals, we showed, occur in treated wastewater effluents and marine and freshwater recipients [24, 25, 30, 42, 43, 51, 66] and that, to no great surprise, the per capita pharmaceutical loads from hospitals were greater than the general population [43, 51]. Other highlights include understanding the processes that occur within sewer systems and what influences pharmaceutical occurrence in the final treated effluent [59, 60, 81, 85, 105], all of which allow for a better assessment of the overall risk posed to the environment. Even though several hundred papers have been published on pharmaceuticals in the environment since my early work, this has almost exclusively been focused on the parent pharmaceutical ingredient in aqueous matrices from developed counties. To remedy this shortfall more recent work has focused on quantifying the proportion of pharmaceutical metabolites released as compared to the parent [66], pharmaceutical occurrence in sludges and sediments [69], as well as evaluating occurrence in less studied water cycles [101]. My studies have shown that the risks associated with pharmaceutical metabolites are largely neglected and poorly understood and while we understand the releases of pharmaceuticals in Asia, Europe and North America, emissions of pharmaceuticals (and illicit drugs) in newly industrialised regions are also of significance [101]. As with biocides we were eager to understand the risks associated with the pharmaceutical exposure levels we were determining, however only acute short-term toxicity data were available which limited the possibility of evaluating any chronic long-term risks. A situation that is sadly not much better today. Linking causality to occurrence becomes easier however when the there is knowledge about the levels that can inflict a particular response in an organism, particularly when that response is mortality. An awareness of the potential of certain chemicals and their use has more recently led to better successes in linking occurrence with a particular response [86, 102]. For example my research has shown that second generation anticoagulant rodenticides (SGARs) occur at levels above the potential lethal range in the livers of raptors found dead in Norway [86] and that chitin synthesis inhibitors used in controlling sea-lice in Norwegian fish farms pose a serious risk to any species that undergoes moulting during its lifecycle [102]. With so many pharmaceuticals in use, prioritising which pharmaceuticals to target posed a new challenge and one which led to the use of prescription data to predict influent loads [44]. These estimations proved to be effective and combined with reports of the occurrence of cocaine in Italian rivers and wastewaters stimulated an interest in illicit drugs and one of the earliest publications of a robust analytical method for the quantification of a number of commonly used drugs [42]. With a focus on generating quality data representative of that occurring within a specific community our initial focus was on understanding the temporal fluxes in drug loads and what influenced such changes [71, 72, 74, 85]. After being convinced that wastewater analyses offered an alternative to conventional epidemiological methods for generating population level data we proceeded to develop the first wastewater biomarker for alcohol consumption, based upon ethylsufate [73], include for the first time new psychoactive substances in our analyses and a strategy for their identification [94, 97] and proposed that wastewater-based epidemiology had the potential to tell more about a community than just their drug use, provided the first comparison with conventional epidemiological data [84] and for the first time presented the hypothesis that wastewater contained indigenous and exogenous biomarkers of human interactions with their environment and that quantitative measurements of these biomarkers could be used to relate to health, diet, lifestyle and environment [75]. Large spatial studies were necessary to demonstrate that wastewater-based epidemiology had a role to play in providing useful data to drug and crime monitoring agencies. In 2010, I initiated the first Europe-wide spatial study that has generated comparable drug use data for up to 50 European cities from 2011 and is ingoing [79, 100], and allowed for the first time an assessment of the uncertainties associated with a wastewater-based approach [95]. Integrated sampling for improved characterisation Accurate characterisation of chemical contamination very much requires that the samples we analyse are representative of the environment. A complementary focus of my research has been the application of passive sampling techniques [46, 47, 53, 55, 71, 88, 89]. Such techniques can provide time-integrated samples that better describe the environments that I am characterising. They are particularly suitable for monitoring in hostile and difficult environments, such as off-shore around oil platforms [46, 47, 53, 55], whilst providing an effective tool for the long term monitoring of CECs [71] and cleaner extracts for coupling with non-targted analytical approaches for identifying unknown contaminants that are potentially bioaccumulative [88, 89]. A particularly novel passive sampling tool that we have used is explanted silicone implants that have huge potential for biomonitoring and have also led to a potential tool for cleaning contaminated bodies of chemicals [133]. Summary The presented body of work represents 20 years research to better understand the influence of chemicals on environmental and human health. My research has resulted in the improved understanding of which chemicals affect the environment and pose the greatest risk. As described above, I was one of the first researchers to report the environmental risks posed by certain CECs that provoked the major research effort that we see today. This includes some of the earliest works on the presence of specific environmental endocrine disrupters, in particular androgen receptor agonists and antagonists, pharmaceuticals and personal care products, and engineered nanoparticles that has lead to the implementation of improved wastewater treatment and better societal awareness of chemicals in consumer goods. Direct impacts of this work have been restrictions in the use of Irgarol 1051 and diuron in most European countries following my seminal work on antifouling paint biocides and their inclusion in the Water Framework Directive´s list of priority substances, banning the use of second generation anticoagulant rodenticides (SGARs) for amateur use in Norway and brought focus on the dependence of the Norwegian fish farming industry on veterinary medicines. My influential work with using sewage to estimate illicit drug use has lead to a new paradigm as to how this is performed in Europe and afield and reported to the European Monitoring Centre for Drugs and Drug Addiciton and the United Nations Office on Drugs and Crime. At the time of writing these papers have been cited over 5,600 times.

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