Toxicogenomic solutions for assessing exposure and effects of environmental contaminants in wildlife

Funding period: 2020-2024
Lead: Doug Crump
Total GRDI funding: $193,000

Environment and Climate Change Canada has identified the determination and prediction of the toxic effects of a wide range of environmental contaminants to be of high priority. To address this need, our laboratory is developing sensitive, high-throughput assays that elucidate molecular and biochemical modes of action of individual chemicals and complex environmental mixtures that occur upstream of overt toxicological effects (e.g. death, deformity). Novel toxicogenomic tools and in vitro screening approaches are developed for laboratory and wild avian species (e.g. domestic chicken, thick-billed murre, double-crested cormorant) for use in effects-based monitoring in priority ecosystems, assessing exposure, and determining cumulative effects of chemical mixtures and other stressors. The knowledge obtained from such assays will aid the development of regulatory criteria and decisions that will help protect the health of wildlife and humans exposed to complex mixtures of environmental contaminants. Outreach with local Indigenous groups in the Arctic and using toxicogenomics for strategic environmental assessments and disaster responses will enhance the policy implications of this research across Canada.

Publications
  • Alcaraz AJ, Baraniuk S, Mikulášek K, Park B, Lane T, Burbridge C, Ewald J, Potěšil D, Xia J, Zdráhal Z, Schneider D, Crump D, Basu N, Hogan N, Brinkmann M, Hecker M. 2022. Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine. Environ. Poll. 295: 118667. https://doi.org/10.1016/j.envpol.2021.118667
  • Alcaraz AJ, Mikulášek K, Potěšil D, Park B, Shekh K, Ewald J, Burbridge C, Zdráhal Z, Schneider D, Xia J, Crump D, Basu N, Hecker M. 2021. Assessing the toxicity of 17α-ethinylestradiol in rainbow trout using a four-day transcriptomics benchmark dose (BMD) embryo assay. Environ. Sci. Tech. 55(15): 10608-10618. https://doi.org/10.1021/acs.est.1c02401
  • Alcaraz AJ, Potěšil D, Mikulášek K, Green D, Park B, Burbridge C, Bluhm K, Soufan O, Lane T, Pipal M, Brinkmann M, Xia J, Zdráhal Z, Schneider D, Crump D, Basu N, Hogan N, and Hecker M. 2021. Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows (Pimephales promelas). Environ. Sci. Technol. 55(8): 5024–5036. https://doi.org/10.1021/acs.est.0c05942
  • Colville C, Alcaraz AJ, Green D, Park B, Xia J, Soufan O, Hruṧka P, Potěšil D, Zdráhal Z, Crump D, Basu N, Hogan N, Hecker M. 2022. Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas). Sci. Tot. Environ. 817: 152747. https://doi.org/10.1016/j.scitotenv.2021.152747
  • Crump D, Sharin T, Chiu S, O'Brien JM. 2021. In vitro screening of 21 BPA replacement alternatives: Compared to BPA, the majority are more cytotoxic and dysregulate more genes in avian hepatocytes. Environ. Toxicol. Chem. 40(7):2026-2033. https://doi.org/10.1002/etc.5032
  • Desforges JP, Legrand E, Boulager E, Liu P, Xia J, Butler H, Chandramouli B, Basu N, Hecker M, Head J, Crump D. 2021. Using transcriptomics and metabolomics to understand species differences in sensitivity to chlorpyrifos in Japanese quail and double-crested cormorant embryos. Environ Tox Chem 40 (11): 3019-3033. https://doi.org/10.1002/etc.5174
  • Ewald JD, Basu N, Crump D, Boulanger E, Head J. 2022. Characterizing variability and uncertainty associated with transcriptomic dose-response modeling. Enviro Sci Tech 56: 15960-15968. https://doi.org/10.1021/acs.est.2c04665
  • Ha K, Xia P, Crump D, Saini A, Harner T, O'Brien JM. 2021. Cytotoxic and transcriptomic effects in avian hepatocytes exposed to a complex mixture from air samples, and their relation to the organic flame retardant signature. Toxics 9 (12): 324. https://doi.org/10.3390/toxics9120324
  • Jeon YS, Crump D, Boulanger E, Soufan O, Park B, Basu N, Hecker M, Xia J, Head J. 2022. Hepatic Transcriptomic Responses to Ethinylestradiol in Two Life Stages of Japanese Quail. Enviro Tox Chem 41(11): 2769-2781. https://doi.org/10.1002/etc.5464
  • Jeon YS, Sangiovanni J, Boulanger E, Crump D, Liu P, Ewald J, Basu N, Xia J, Hecker M, Head J. 2023. Hepatic Transcriptomic Responses to Ethinylestradiol in Embryonic Japanese Quail and Double-crested Cormorant. 43(4)772-783. https://doi.org/10.1002/etc.5811
  • King MD, Elliott JE, Marlatt V, Crump D, Idowu I, Wallace SJ, Tomy GT, Williams TD. 2022. Effects of avian eggshell oiling with diluted bitumen show sub-lethal embryonic polycyclic aromatic compound exposure. Environ. Tox. Chem. 41 (1): 159-174. https://doi.org/10.1002/etc.5250
  • King M, Su G, Crump D, Farhat A, Marlatt V, Lee S, Williams T, Elliott J. 2023. Contaminant biomonitoring augmented with a qPCR array indicates hepatic mRNA gene expression effects in wild-collected seabird embryos. Sci. Tot. Environ. 904: 166784. https://doi.org/10.1016/j.scitotenv.2023.166784
  • Legrand E, Basu N, Hecker M, Crump D, Xia J, Chandramouli B, Butler H, Head J. 2021. Targeted metabolomics to assess exposure to environmental chemicals of concern in Japanese quail at two life stages. Metabolites 11(12): 850. https://doi.org/10.3390/metabo11120850
  • Legrand E, Jeon Y, Basu N, Hecker M, Crump D, Xia J, Chandramouli B, Butler H, Head J. 2022. Consideration of metabolomics and transcriptomics data in the context of using avian embryos for toxicity testing. Comp Biochem. Physiol. Part C 258: 109370. https://doi.org/10.1016/j.cbpc.2022.109370
  • Malala Irugal Bandaralage S, Bertucci, JI, Park B, Green D, Brinkmann M, Masse A, Crump D, Basu N, Hogan N, Hecker M. 2022. Maternal transfer and apical and physiological effects of dietary hexabromocyclododecane exposure in parental fathead minnows (P. promelas). Enviro. Tox Chem 42(1):143-153. https://doi.org/10.1002/etc.5506
  • Mittal K, Ewald J, Crump D, Head J, Hecker M, Hogan N, Xia J, Basu N. 2023. Comparing Transcriptomic Responses to Chemicals Across Six Species using the EcoToxChip RNASeq database. https://doi.org/10.1002/etc.5803
  • Nian K, Yang W, Zhang X, Xiong W, Crump D, Zhang R, Su G, Zhang X, Feng M, Shi J. 2022. Occurrence, Partitioning, and Bioaccumulation of an Emerging Class of PBT Substances (Polychlorinated Diphenyl Sulfides) in Chaohu Lake, Southeast China. Water Res. 218: 118498. https://doi.org/10.1016/j.watres.2022.118498
  • Salat A, Williams KL, Chiu S, Eickmeyer DC, Kimpe LE, Blais JM, Crump D. 2021. Extracts from Dated Lake Sediment Cores in the Athabasca Oil Sands Region Alter Ethoxyresorufin-O-deethylase Activity and Gene Expression in Avian Hepatocytes. Environ. Toxicol. Chem. 40(7):1883-1893. https://doi.org/10.1002/etc.5040
  • Sarma SN, Thomas PJ, Naz S, Pauli B, Crump D, Zahaby Y, O'Brien J, Mallory ML, Franckowiak RP, Gendron M, Provencher JF. 2022. Metabolomic profiles in relation to benchmark polycyclic aromatic compounds (PACs) and trace elements in two seabird species from Arctic Canada. Environ. Res. 204 (part B): 112022. https://doi.org/10.1016/j.envres.2021.112022
  • Sharin T, Crump D, O'Brien JM. 2022. Toxicity Screening of Bisphenol A Replacement Compounds: Cytotoxicity and mRNA Expression in LMH 3D Spheroids. Environ Sci Pollut Res Int. 29 (29): 44769-44778. https://doi.org/10.1007/s11356-022-18812-z
  • Sharin T, Gyasi H, Jones SP, Crump D, O'Brien JM. 2021. Concentration- and Time-Dependent Induction of CYP1A and DNA Damage Response by Benzo[a]pyrene in LMH 3D Spheroids. Environ. Mol. Mutagen. 62(5):319-327 https://doi.org/10.1002/em.22433
  • Sharin T, Gyasi H, Williams K, Crump D, O'Brien JM. 2021. Effects of Two Bisphenol A Replacement Compounds, Bisphenol AF and 1,7-bis (4-Hydroxyphenylthio)-3,5-dioxaheptane, on Pipping Success, Development, and mRNA Expression Levels in Chicken Embryos. Ecotoxicol. Environ. Saf. 1(215):112140. https://doi.org/10.1016/j.ecoenv.2021.112140
  • Sharin T, Leinen LJ, Schreiber D, Swenson VA, Emsley SA, Trammell EJ, Videau P, Crump D, Gaylor MO. 2024. Description of solvent-extractable chemicals in thermal receipts and toxicological assessment of bisphenol S and diphenyl sulfone. Bull. Envir. Contam. Toxicol. 112:63. https://doi.org/10.1007/s00128-024-03871-4
  • Sharin T, Williams KL, Chiu S, Crump D, O'Brien JM. 2021. Toxicity Screening of Bisphenol A Replacement Compounds: Cytotoxicity and mRNA Expression in Primary Hepatocytes of Chicken and Double-Crested Cormorant. Environ. Toxicol. Chem. 40(5):1368-1378. https://doi.org/10.1002/etc.4985
  • Yang W, Huang X, Wu Q, Shi J, Zhang X, Ouyang L, Crump D, Zhang X, Zhang R.  2022. Acute toxicity of polychlorinated diphenyl ethers (PCDEs) in three model aquatic organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Sci. Tot. Environ 805: 150366. https://doi.org/10.1016/j.scitotenv.2021.150366
  • Zahaby Y, Xia Pu, Crump D, Provencher J, Thomas P, Pauli B, Braune B, Franckowiak R, Gendron M, Savard G, Sarma S, Mallory M, O'Brien J. 2021. ToxChip PCR Arrays for Two Arctic-Breeding Seabirds: Applications for Regional Environmental Assessments. Environ. Sci. Technol. 55(11): 7521-7530. https://doi.org/10.1021/acs.est.1c00229
  • Zhang R, Wu Q, Qi X, Wang X, Zhang X, Song C, Peng Y, Crump D, Zhang X. 2021. Using In Vitro and Machine Learning Approaches to Determine Species-Specific Dioxin-like Potency and Congener-Specific Relative Sensitivity among Birds for Brominated Dioxin Analogues. Envir. Sci. Tech. 55 (23): 16056-16066. https://doi.org/10.1021/acs.est.1c05951
  • Zhang X, Xiong W, Wu Q, Nian K, Pan X, Crump D, Zhang X, Zhang R. 2023. Bioaccumulation, Trophic Transfer and Biotransformation of Polychlorinated Diphenyl Ethers in a Simulated Aquatic Food Chain. Environ. Sci. Tech. 57(14): 5751-5760. https://doi.org/10.1021/acs.est.2c08216

Contact us

For additional information, please contact:
Genomics R&D Initiative
Email: info@grdi-irdg.collaboration.gc.ca

From: Genomics R&D Initiative

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