Markus Hecker

University of Saskatchewan | U of S · School of Environment & Sustainability and Toxicology Centre

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a derivative of rubber tires which leaches into surface waters when tire particles are swept into roadway runoff. 6PPD-Q has been identified as a potential cause of urban runoff mortality syndrome in coho salmon, and subsequent research has determined a wide species variation in...

Efforts to use transcriptomics for toxicity testing have classically relied on the assumption that chemicals consistently produce characteristic transcriptomic signatures that are reflective of their mechanism of action. However, the degree to which transcriptomic responses are conserved across different test methodologies has seldom been explored....

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a ubiquitous and acutely toxic transformation product (TP) derived from the rubber tire antioxidant N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD). While not all salmonids are sensitive to acute lethality caused by 6PPD-Q, its potency can vary by several orders of mag...

Complex mixtures of chemicals present in groundwater at legacy-contaminated industrial sites can pose significant risks to adjacent surface waters. The combination of short-term molecular and chronic apical effect assessments is a promising approach to characterize the potential hazard of such complex mixtures. The objectives of this study were to:...

Urban stormwater runoff contains the tire-derived transformation product N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-quinone), which poses significant environmental risks due to its high toxicity toward certain salmonids. 6PPD-quinone biotransformation has been investigated to explain some of the stark interspecies differences...

Freshwater ecosystems face numerous conservation challenges due to anthropogenic pressures and environmental changes, necessitating advanced monitoring methods for effective conservation strategies. Traditional monitoring approaches have limitations, including low resolution and the inability to address emerging threats or understand the structure–...

Pharmaceuticals in aquatic environments pose threats to aquatic organisms because of their continuous release and potential accumulation. Monitoring methods for these contaminants are inadequate, with targeted analyses falling short in assessing water quality's impact on biota. The present study advocates for integrated strategies combining suspect...

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study...

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-q) is a rubber-tire derivative which leaches into surface waters from roadway runoff, from tire particles and has been identified as a possible driver of urban runoff mortality syndrome in coho salmon. Sensitivity to this toxicant is highly variable across fish species and life stages...

Glacier ecosystems are shrinking at an accelerating rate due to changes in climate and also increased darkening from allochthonous and autochthonous carbon leading to subsequent changes in the absorption of light, associated heat, and microbial communities. In this study, in combination with measurement of nutrients and polycyclic aromatic hydrocar...

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double‐crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). Here, we explore how this difference in sensitivity between species is reflected...

The EcoToxChip project includes RNA‐sequencing data from experiments involving model (Japanese quail, fathead minnow, African clawed frog) and ecological (double‐crested cormorant, rainbow trout, northern leopard frog) species, at multiple life stages (whole embryo and adult), exposed to eight chemicals of environmental concern known to perturb a w...

N-(1,3-Dimethylbutyl)-N-Phenyl-P-Phenylenediamine-Quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire anti-degradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations surpassing those measured in...

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) is an emerging contaminant of concern that is generated through the environmental oxidation of the rubber tire anti-degradant 6PPD. Since the initial report of 6PPD-quinone being the cause of urban runoff mortality syndrome of Coho salmon, numerous species have been identifie...

New approach methods (NAMs) are increasingly important to help accelerate the pace of ecological risk assessment and offer more ethical, affordable, and efficient alternatives to traditional toxicity tests. In the present study, we describe the development, technical characterization and initial testing of a toxicogenomics tool, EcoToxChip (384-wel...

Microbial communities are an important component of freshwater biodiversity that is threatened by anthropogenic impacts. Wastewater discharges pose a particular concern by being major sources of anthropogenic contaminants and microorganisms that may influence the composition of natural microbial communities. Nevertheless, the effects of wastewater...

Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource intensive and often use a large number of laboratory animals. Developing alternatives for in vivo tests is consistent with the 3Rs principles...

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then,...

Hexabromocyclododecane (HBCD) is a persistent organic pollutant (POP) that has been characterized as an endocrine disruptor, undergoes maternal transfer, and hinders development and growth in oviparous organisms. This study examined the apical effects of dietary HBCD (11.5, 36.4, 106 mg/kg, ww) on adult fathead minnow (FHMs) exposed for 49 days and...

In vitro cell systems can support hazard characterization and identify mechanisms involved in toxicity; however, using in vitro data for risk assessment still is challenging. As part of an effort to develop approaches for a complex operating site used for biocide packaging and distribution, we evaluated in vitro assays that could be used in a site...

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labour-intensive screens of all organs. This study examined soil extracts from a legacy contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples to ide...

Chemical risk assessment for avian species typically depends on information from toxicity tests performed in adult birds. Early‐life stage (ELS) toxicity tests have been proposed as an alternative, but incorporation of these data into existing frameworks will require knowledge about the similarities/differences between ELS and adult responses. The...

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-quinone), a rubber tire oxidation product found in road runoff, is highly and acutely toxic to selected salmonids including coho salmon, brook trout, and rainbow trout but not other fish species and invertebrates studied to date. Sensitive species displayed increased ventilation and g...

Early-life stage (ELS) avian toxicity tests have been proposed as a more ethical alternative to traditional standardized tests with adult birds. At the same time, 'omics approaches are gaining traction in the field of avian toxicology, but little has been done to characterize the metabolome and transcriptome at different life stages. The present st...

Selenium (Se) is an environmental contaminant of global concern that can cause adverse effects in fish at elevated levels. Fish gut microbiome play essential roles in gastrointestinal function and host health and can be perturbed by environmental contaminants, including metals and metalloids. Here, an in-situ Se exposure of female finescale dace (P...

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource-intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that t...

Current ecotoxicity testing programs are impeded as they predominantly rely on slow and expensive animal tests measuring adverse outcomes. Therefore, new approach methodologies (NAMs) increasingly involve short-term mechanistic assays that employ molecular endpoints to predict adverse outcomes of regulatory relevance. This study aimed to elucidate...

Reptiles represent the least-studied group of vertebrates with regards to ecotoxicology and no empirical toxicity data existed for dioxin-like chemicals (DLCs). This lack of toxicity data represents a significant uncertainty in ecological risk assessments of this taxon. Therefore, the present study assessed early-life sensitivity to select DLCs and...

This proof-of-concept study characterizes the Japanese quail (Coturnix japonica) hepatic metabolome following exposure to benzo[a]pyrene, chlorpyrifos, ethinylestradiol, fluoxetine hydrochloride, hexabromocyclododecane, lead(II)nitrate, seleno-L-methionine, and trenbolone in embryos and adults. The analysis revealed effects on lipid metabolism foll...

Hazardous chemicals are one of the greatest environmental challenges facing our planet, testing governments in the face of economic and social development. Chemical risks are often complex systemic risks, which require particular governance processes, stakeholder participation mechanisms, and communication procedures to manage. In this article we e...

Current approaches in chemical hazard assessment face significant challenges because they rely on live animal testing, which is time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored a molecular benchmark dose (...

The microbiome of the gut is vital for homeostasis of hosts with its ability to detoxify and activate toxicants, as well as signal to the immune and nervous systems. However, in the field of environmental toxicology, the gut microbiome has only recently been identified as a measurable indicator for exposure to environmental pollutants. Antidepressa...

Information on the effects of silver nanoparticles (AgNPs) in fish have mostly been generated from standard laboratory species and short‐term toxicity tests. However, there is significant uncertainty regarding AgNP toxicity to native species of concern in North America, particularly in northern freshwater ecosystems. Here, we assessed the chronic t...

The assessment of the exposure of aquatic wildlife to complex environmental mixtures of chemicals originating from both point and diffuse sources and evaluating the potential impact thereof constitutes a significant step towards mitigating toxic pressure and the improvement of ecological status. In the current proof-of-concept study, we demonstrate...

Modern 21st century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions...

While it is well recognized that the frequency and intensity of flood events are increasing worldwide, the environmental, economic, and societal consequences of remobilization and distribution of pollutants during flood events are not widely recognized. Loss of life, damage to infrastructure, and monetary cleanup costs associated with floods are im...

Standardized laboratory tests with a limited number of model species are a key component of chemical risk assessments. These surrogate species cannot represent the entire diversity of native species, but there are practical and ethical objections against testing chemicals in a large variety of species. In previous research, we have developed a mult...

Despite the global toxicology community discussing New Approach Methodologies (NAMs) for chemical hazard and risk assessment, such as in vitro, in silico, and ‘omics-based approaches, for some 30 years, their formal adoption by regulators remains limited. Previous research suggests that insufficient validation, complexity of interpretation, and lac...

There is increasing pressure to develop alternative ecotoxicological risk assessment approaches that do not rely on expensive, time-consuming, and ethically questionable live animal testing. This study aimed to develop a comprehensive early life stage toxicity pathway model for the exposure of fish to estrogenic chemicals that is rooted in mechanis...

Selenium (Se) is both an essential micronutrient and a contaminant of concern that is of particular interest in mining-influenced waterbodies in Canada. The objective of this research was to characterize the trophic dynamics of selenium along a gradient of exposure concentrations in a Canadian boreal lake ecosystem. From June 20 to August 22, 2018,...

Recent studies have shown that white sturgeon (Acipenser transmontanus) are more resistant to cadmium (Cd) compared to rainbow trout (Oncorhynchus mykiss), whereas they are more sensitive than rainbow trout when exposed to copper (Cu). Differences in the subcellular distribution of metals among species could be one of the factors responsible for th...

Although withdrawn from the market in the 1980s, polychlorinated biphenyls (PCBs) are still found ubiquitously in the aquatic environment and pose a serious risk to biota due to their teratogenic potential. In fish, early life-stages are often considered most sensitive with regard to their exposure to PCBs and other dioxin-like compounds. However,...

Environmental risk assessment is often challenged by a lack of toxicity data for ecological species. The overall goal of this research project was to employ an avian early‐life stage toxicity test to determine the effects of four chemicals (benzo[a]pyrene [BaP], chlorpyrifos [CPF], fluoxetine hydrochloride [FLX], ethinylestradiol [EE2]) in an ecolo...

Understanding internal dose metrics is integral to adequately assess effects environmental contaminants might have on aquatic wildlife, including fish. In silico toxicokinetic (TK) models are a leading approach for quantifying internal exposure metrics for fishes; however, they often do not adequately consider chemicals that are actively biotransfo...

Background: Some 20 y ago, scientific and regulatory communities identified the potential of omics sciences (genomics, transcriptomics, proteomics, metabolomics) to improve chemical risk assessment through development of toxicogenomics. Recognizing that regulators adopt new scientific methods cautiously given accountability to diverse stakeholders...

Uptake and effects of ionizable organic chemicals (IOCs) that are weak acids in aqueous solution by fish can differ as a function of pH. While the pH-dependent behavior of select IOCs is well-understood, complex mixtures of IOCs, e.g., from oil sands process-affected water (OSPW), have not yet been studied systematically. Here, we established an in...

Because compounds accumulate through dry periods and enter aquatic systems in just a few seasonal events such as snowmelt and summer storms, surface waters in semi-arid, cold regions, such as the Canadian Prairies, are particularly vulnerable to loading of contaminant from runoff events from surfaces. This study assessed concentrations of metals an...

In addition to aiding in digestion of food and uptake of nutrients, microbiota in guts of vertebrates are responsible for regulating several beneficial functions, including development of an organism and maintaining homeostasis. However, little is known about effects of exposures to chemicals on structure and function of gut microbiota of fishes. T...

Traditional results from toxicogenomics studies are complex lists of significantly impacted genes or gene sets, which are challenging to synthesize down to actionable results with a clear interpretation. Here we defined two sets of 21 custom gene sets, called the functional and statistical EcoToxModules, in fathead minnow (Pimephales promelas) to 1...

Early life-stages of the endangered white sturgeon (Acipenser transmontanus) have been shown to be among the most sensitive fishes to aqueous copper (Cu) exposure. In a recent analogous study, we examined the role of whole-body Cu accumulation and Na homeostasis in species-specific differences between the sensitivity of white sturgeon and a common...

Sturgeons (Acipenseridae) are ancient fishes that have tissue-specific profiles of transcriptional responses to dioxin-like compounds (DLCs) that are unique from those generally measured in teleost fishes. Because DLCs exert their critical toxicities through activation of the aryl hydrocarbon receptor (AHR), this transcription factor has been the s...

Background: Given current legislative mandates to assess the safety of thousands of chemicals and the slow pace at which conventional testing proceeds, there is a need to accelerate chemical risk assessment. Governments and businesses are increasingly interested in New Approach Methodologies (NAMs) that promise to reduce costs and delays. Aim: W...

The use of toxicogenomic endpoints and increased reliance on early-life stage (ELS) animal exposures are two strategies that have been proposed to improve toxicity testing for regulatory risk assessment. However, it is unknown whether transcriptomic measures in ELS organisms are predictive of those measured in their adult counterparts. The present...

Incorporation of toxicogenomics into ecological risk assessment requires a good understanding of the genes/pathways that are commonly affected by exposure to toxic chemicals. Studies comparing transcriptomic responses across environmental chemicals are available for fish but less research has been done for birds. The present study aims to reveal un...

There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards. Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets. Though several gene sets ha...

Selenium (Se) is a contaminant of concern in many aquatic ecosystems due to its narrow range between essentiality and toxicity in oviparous (yolk-bearing) vertebrates. The objective of the present study was to determine the effects of Se, experimentally added to in situ limnocorrals as selenite, on invertebrate communities and fathead minnow (Pimep...

Selenium (Se) enrichment has been demonstrated to vary by several orders of magnitude among species of planktonic algae. This is a substantial source of uncertainty when modelling Se biodynamics in aquatic systems. In addition, Se bioconcentration data are largely lacking for periphytic species of algae, and for multi-species periphyton biofilms, a...

Selenium (Se) is an essential trace element of concern that is known to contaminate aquatic ecosystems as a consequence of releases from anthropogenic activities. Selenium is of particular toxicological concern for egg-laying vertebrates as they bioaccumulate Se through the diet and deposit excess Se to embryo-offspring via maternal transfer, a pro...

Early‐life stage (ELS) toxicity tests are recognized as an advancement over current testing methodologies in terms of cost, animal use, and biological relevance. However, standardized ELS tests are not presently available for some vertebrate taxa, including birds. This manuscript describes a Japanese quail (Coturnix japonica) ELS test that is a pro...

Recent studies have demonstrated that white sturgeon are more sensitive to acute exposure to Cu than rainbow trout (Oncorhynchus mykiss), especially during early life-stages. However, the physiological mechanisms underlying this difference in sensitivity to Cu is not known. In the present study, we first confirmed the higher sensitivity (lower 96 h...

There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards. Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets.Though several gene sets hav...

There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards. Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets.Though several gene sets hav...

Nanosized alumina (Al2O3-NPs), a widely used nanoparticle in numerous commercial applications, is released into environment posing a threat to the health of wildlife and humans. Recent research has revealed essential roles of physicochemical properties of nanoparticles in determining their toxicity potencies. However, influence of shape on neurotox...

Legislation in North America and Europe, such as the Canadian Environmental Protection Act (CEPA), the US Safe Drinking Water Act (SDWA), and the European Registration, Evaluation, and Authorization of Chemicals (REACH) program, mandates the assessment of risks of chemicals to the environment and human health. Current testing strategies within thes...

Human activities have increased the release of selenium (Se) to aquatic environments, but information about the trophic transfer dynamics of Se in Canadian boreal lake systems is limited. In the present study, Se was added as selenite to limnocorrals (2 m diameter, 3000 L in situ enclosures) in a boreal lake in northwestern Ontario to reach nominal...

Understanding the mechanistic basis of differences in the sensitivity of fishes to metals is important for developing informed ecological risk assessment approaches for metals. Whole body metal accumulation, metallothionein induction, oxidative stress and associated antioxidant response, as well as heat shock proteins (mainly HSP70) are known to pl...

Hydroxylation of polyaromatic compounds through cytochromes P450 (CYPs) is known to result in potentially estrogenic transformation products. Recently, there has been an increasing awareness of the importance of alternative pathways such as aldehyde oxidases (AOX) or N-methyltransferases (NMT) in bioactivation of small molecules, particularly N-het...