Publications by authors named "Bradley Park"

8 Publications

  • Page 1 of 1

Assessing the Toxicity of 17α-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay.

Environ Sci Technol 2021 08 22;55(15):10608-10618. Epub 2021 Jul 22.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B3.

There is an urgent demand for more efficient and ethical approaches in ecological risk assessment. Using 17α-ethinylestradiol (EE2) as a model compound, this study established an embryo benchmark dose (BMD) assay for rainbow trout (RBT; ) to derive transcriptomic points-of-departure (tPODs) as an alternative to live-animal tests. Embryos were exposed to graded concentrations of EE2 (measured: 0, 1.13, 1.57, 6.22, 16.3, 55.1, and 169 ng/L) from hatch to 4 and up to 60 days post-hatch (dph) to assess molecular and apical responses, respectively. Whole proteome analyses of alevins did not show clear estrogenic effects. In contrast, transcriptomics revealed responses that were in agreement with apical effects, including excessive accumulation of intravascular and hepatic proteinaceous fluid and significant increases in mortality at 55.1 and 169 ng/L EE2 at later time points. Transcriptomic BMD analysis estimated the median of the 20th lowest geneBMD to be 0.18 ng/L, the most sensitive tPOD. Other estimates (0.78, 3.64, and 1.63 ng/L for the 10th percentile geneBMD, first peak geneBMD distribution, and median geneBMD of the most sensitive over-represented pathway, respectively) were within the same order of magnitude as empirically derived apical PODs for EE2 in the literature. This 4-day alternative RBT embryonic assay was effective in deriving tPODs that are protective of chronic effects of EE2.
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http://dx.doi.org/10.1021/acs.est.1c02401DOI Listing
August 2021

Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows ().

Environ Sci Technol 2021 04 23;55(8):5024-5036. Epub 2021 Mar 23.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada.

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 mechanistic toxicology. Embryo-larval fathead minnows (FHM; ) were exposed to graded concentrations of 17α-ethinylestradiol (water control, 0.01% DMSO, 4, 20, and 100 ng/L) for 32 days. Fish were assessed for transcriptomic and proteomic responses at 4 days post-hatch (dph), and for histological and apical end points at 28 dph. Molecular analyses revealed core responses that were indicative of observed apical outcomes, including biological processes resulting in overproduction of vitellogenin and impairment of visual development. Histological observations indicated accumulation of proteinaceous fluid in liver and kidney tissues, energy depletion, and delayed or suppressed gonad development. Additionally, fish in the 100 ng/L treatment group were smaller than controls. Integration of omics data improved the interpretation of perturbations in early life stage FHM, providing evidence of conservation of toxicity pathways across levels of biological organization. Overall, the mechanism-based embryo-larval FHM model showed promise as a replacement for standard adult live animal tests.
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http://dx.doi.org/10.1021/acs.est.0c05942DOI Listing
April 2021

Microplastics in aquatic environments: Implications for Canadian ecosystems.

Environ Pollut 2016 Nov 16;218:269-280. Epub 2016 Jul 16.

Stantec Consulting Ltd., 500-311 Portage Ave., Winnipeg, MB R3B 2B9, Canada.

Microplastics have been increasingly detected and quantified in marine and freshwater environments, and there are growing concerns about potential effects in biota. A literature review was conducted to summarize the current state of knowledge of microplastics in Canadian aquatic environments; specifically, the sources, environmental fate, behaviour, abundance, and toxicological effects in aquatic organisms. While we found that research and publications on these topics have increased dramatically since 2010, relatively few studies have assessed the presence, fate, and effects of microplastics in Canadian water bodies. We suggest that efforts to determine aquatic receptors at greatest risk of detrimental effects due to microplastic exposure, and their associated contaminants, are particularly warranted. There is also a need to address the gaps identified, with a particular focus on the species and conditions found in Canadian aquatic systems. These gaps include characterization of the presence of microplastics in Canadian freshwater ecosystems, identifying key sources of microplastics to these systems, and evaluating the presence of microplastics in Arctic waters and biota.
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http://dx.doi.org/10.1016/j.envpol.2016.06.074DOI Listing
November 2016

Assessment of the health status of wild fish from the Wheatley Harbour Area of Concern, Ontario, Canada.

Environ Toxicol Chem 2012 Dec 24;31(12):2798-811. Epub 2012 Oct 24.

Aquatic Contaminants Research Division, Water, Science, and Technology Directorate, Environment Canada, Burlington, Ontario, Canada.

The overall health and endocrine function of wild brown bullhead (Ameiurus nebulosus) and goldfish (Carassius auratus) from the Wheatley Harbour Area of Concern (Lake Erie, Ontario, Canada) was assessed using a suite of physiological and biochemical endpoints. Smaller gonads were detected in female brown bullhead and goldfish from Wheatley Harbour compared with Hillman Marsh (Ontario, Canada) reference fish. Female brown bullhead exhibited decreased in vitro synthesis of 17β-estradiol. Female goldfish had decreased plasma vitellogenin concentrations. Plasma testosterone and 11-ketotestosterone were significantly depressed in males of both species. Perturbations in the thyroid status were detected, but varied between sexes and species. Observed differences included lower plasma concentrations of thyroid hormones and/or elevated liver deiodinase activity. Histological evaluation of the thyroid tissue indicated that in the case of female goldfish, those perturbations stimulated the thyroid (as indicated by increased thyroid epithelial cell height) and partially depleted the thyroxine reserves, as indicated by decreased colloid and elevated thyroid activation index. Increased mixed-function oxygenase activity in brown bullhead from Wheatley Harbour was consistent with exposure to planar aromatic contaminants. A principal component analysis of selected variables showed the separation of fish by collection site. The endpoints most strongly associated with the separation were generally those exhibiting significant differences between sites. The results of the present study indicate that the health of fish populations within Wheatley Harbour warrants continued attention.
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http://dx.doi.org/10.1002/etc.2021DOI Listing
December 2012

Multimodality imaging in transcatheter aortic valve implantation and post-procedural aortic regurgitation: comparison among cardiovascular magnetic resonance, cardiac computed tomography, and echocardiography.

J Am Coll Cardiol 2011 Nov;58(21):2165-73

Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.

Objectives: The purpose of this study was to determine imaging predictors of aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and the agreement and reproducibility of cardiovascular magnetic resonance (CMR), cardiac computed tomography (CCT), and transthoracic echocardiography (TTE) in aortic root assessment.

Background: The optimal imaging strategy for planning TAVI is unclear with a paucity of comparative multimodality imaging data. The association between aortic root morphology and outcomes after TAVI also remains incompletely understood.

Methods: A total of 202 consecutive patients assessed by CMR, CCT, and TTE for TAVI were studied. Agreement and variability among and within imaging modalities was assessed by Bland-Altman analysis. Postoperative AR was assessed by TTE.

Results: Of the 202 patients undergoing TAVI assessment with both CMR and TTE, 133 also underwent CCT. Close agreement was observed between CMR and CCT in dimensions of the aortic annulus (bias, -0.4 mm; 95% limits of agreement: -5.7 to 5.0 mm), and similarly for sinus of Valsalva, sinotubular junction, and ascending aortic measures. Agreement between TTE-derived measures and either CMR or CCT was less precise. Intraobserver and interobserver variability were lowest with CMR. The presence and severity of AR after TAVI were associated with larger aortic valve annulus measurements by both CMR (p = 0.03) and CCT (p = 0.04) but not TTE-derived measures (p = 0.10). Neither CCT nor CMR measures of annulus eccentricity, however, predicted AR after TAVI (p = 0.33 and p = 0.78, respectively).

Conclusions: In patients undergoing imaging assessment for TAVI, the presence and severity of AR after TAVI were associated with larger aortic annulus measurements by both CMR and CCT, but not TTE. Both CMR and CCT provide highly reproducible information in the assessment of patients undergoing TAVI.
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http://dx.doi.org/10.1016/j.jacc.2011.09.010DOI Listing
November 2011

Thyroid axis disruption in juvenile brown trout (Salmo trutta) exposed to the flame retardant β-tetrabromoethylcyclohexane (β-TBECH) via the diet.

Environ Sci Technol 2011 Sep 18;45(18):7923-7. Epub 2011 Aug 18.

Fisheries and Oceans Canada, Freshwater Institute, 501 University Crescent, Winnipeg, Manitoba R3T 2N6 Canada.

Tetrabromoethylcyclohexane (TBECH) is an additive brominated flame retardant used in domestic and industrial applications. It has been detected in wildlife, and there is early evidence that it is an endocrine disruptor. Whereas other brominated flame retardants with similar physicochemical properties have been shown to disrupt the thyroid axis, no such evaluation has been conducted for TBECH. To elucidate this, juvenile brown trout (Salmo trutta) were fed either a control diet or diets containing low, medium, or high doses of β-TBECH, the isomer most frequently detected in wildlife, for 56 days (uptake phase) followed by a control diet for an additional 77 days (depuration phase). Eight fish per treatment were lethally sampled on uptake days 7, 14, 21, 35, 49, and 56 and on depuration days 7, 21, 35, 49, and 77 to assess fish condition, circulating free and total triiodothyronine and thyroxine, and thyroid epithelial cell height. Although there was no effect on condition factor, there was a significant reduction in total plasma thyroxine in the high dose group and a significant increase in mean thyroid epithelial cell height in the low, medium, and high dose groups during the uptake phase, whereas there were no differences in the depuration phase. These results indicate that β-TBECH may modulate the thyroid axis in fish at environmentally relevant concentrations.
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http://dx.doi.org/10.1021/es201530mDOI Listing
September 2011

Altered thyroxine metabolism in rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane (HBCD).

Chemosphere 2010 Jun 7;80(2):165-9. Epub 2010 Apr 7.

Fisheries and Oceans Canada, Winnipeg, Manitoba, Canada.

Hexabromocyclododecane (HBCD) is an additive flame retardant used in consumer and industrial applications. Our earlier work suggested that fish exposed to HBCD exhibited an increase in the rate of turnover of thyroxine (T4), the precursor molecule to the active thyroid hormone triiodothyronine (T3). To examine this further, juvenile rainbow trout were held in the laboratory and fed diets containing environmentally relevant concentrations of the individual alpha, beta or gamma isomers. Thirty-two days after feeding began, 20 fish from each group were gavaged with gelatin containing 1microCi [(125)I]-T4. Uptake of [(125)I]-T4 from the gut was low and recoveries of the initial [(125)I]-T4 were <10% after 2d and <3% and <2% after 6 and 14d respectively, with no differences among groups. However, measurements of the labeled T4 in tissues 2, 4, 6 and 14d after gavage showed that tissue disposition and elimination rates of the hormone were altered by HBCD. In particular, on day 14 after gavage feeding, there was significantly lower radioactivity in the thyroid of fish exposed to the HBCD isomers relative to the reference group. This implies that either there was lower iodide uptake by the gland in fish exposed to HBCD or that the rate of thyroid hormone turnover in HBCD treated fish was elevated. There was also a significantly higher type II outer ring deiodinase enzyme activity in livers of fish exposed to the beta and gamma isomers. Taken together, these results indicate that HBCD can potentially impact the thyroid system of fish.
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http://dx.doi.org/10.1016/j.chemosphere.2010.03.016DOI Listing
June 2010

Effects of the synthetic estrogen ethinylestradiol on early life stages of mink frogs and green frogs in the wild and in situ.

Environ Toxicol Chem 2005 Aug;24(8):2027-36

Department of Zoology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.

Estrogenic contaminants are known to disrupt growth and development in amphibians. Field-based research is needed to elucidate their potential impacts on wild populations. Hatch success, larval growth and development rates, and gonad development were examined in native amphibians exposed to low ng/L concentrations of 17alpha-ethinylestradiol (EE2) in a whole-lake addition experiment at the Experimental Lakes Area, northwestern Ontario, Canada. Egg masses were reared in situ in the EE2-amended lake and in two reference lakes in 2001 and 2002. Hatching success was reduced significantly in green frogs (Rana clamitans) but not in mink frogs (Rana septentrionalis) exposed to EE2. Ethinylestradiol had no consistent effect on mass or development stage of hatchlings in the early larval stages of the caging study. Ethinylestradiol had no effect on sex ratios of either species in situ, and no intersex gonads were observed in exposed or reference green frog tadpoles or in reference mink frog tadpoles. However, 5.6% (total n = 18) and 12.5% (total n = 56) of EE2-exposed mink frog tadpoles were intersex in the 2001 and 2002 caging studies, respectively. Wild mink frog tadpoles also were examined, and EE2 had no effect on sex ratios. No intersex gonads were observed in reference lake tadpoles or in tadpoles from the experimental lake prior to EE2 additions; however, 2.4, 0, and 28.6% of wild EE2-exposed first-year tadpoles had intersex gonads (2001, 2002, and 2003, respectively). These results indicate that exposure to EE2 in the wild and in situ at concentrations comparable to those detected in effluents and, occasionally, in surface waters can impact gonad development and hatch success in native amphibians.
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http://dx.doi.org/10.1897/04-227r.1DOI Listing
August 2005
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