Grantee Research Project Results
Final Report: Systems Approach to Assessing Cumulative Exposure to Endocrine Disrupting Chemicals
EPA Grant Number: R832739Title: Systems Approach to Assessing Cumulative Exposure to Endocrine Disrupting Chemicals
Investigators: LeBlanc, Gerald A.
Institution: North Carolina State University
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2005 through September 30, 2008 (Extended to September 30, 2009)
Project Amount: $585,206
RFA: Exposure Measurement Tools for Endocrine Disrupting Chemicals in Mixtures (2005) RFA Text | Recipients Lists
Research Category: Environmental Justice , Human Health , Safer Chemicals , Endocrine Disruptors
Objective:
The effective assessment of risk associated with endocrine‐disrupting chemicals (EDCs) requires the development and use of tools for assessing EDC exposure. The overall objective of this research program was to develop an approach for evaluating cumulative exposure to EDCs based upon changes in the expression profile and activity of a battery of endocrine‐related genes in exposed water fleas (Daphnia magna).
Summary/Accomplishments (Outputs/Outcomes):
Major accomplishments:
- Twenty five nuclear receptors were identified and annotated from the genome of Daphnia pulex. Several of these genes were selected for use in a gene battery designed to assess EDC exposure.
- Oligonucleotide primers were generated, for use with Daphnia magna and D. pulex, that can be used to assess changes in the expression of genes that are likely involved in endocrine signaling.
- Four nuclear receptor genes were cloned and characterized.
- Responsiveness of several of the genes, in the battery, to hormone exposure was established.
- Changes in expression of the gene battery in daphnids exposed to 28 different compounds were evaluated to identify characteristic changes in gene expression that would be indicative of exposure to specific classes or specific mode of action chemicals.
- Changes in expression of the gene battery among daphnids subjected to three non‐chemical environmental stressors (temperature, ionic strength of media, crowding) were evaluated to assess resilience of the exposure biomarkers to potential confounding stressors.
- Five transcription reporter assays were constructed that can be used to assess the effect of chemical exposure on the activity of specific hormone receptors.
- Gene induction and activation was used to evaluate exposure to an EDC combination.
Journal Articles on this Report : 11 Displayed | Download in RIS Format
| Other project views: | All 16 publications | 16 publications in selected types | All 16 journal articles |
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Hannas BR, Das PC, Li H, LeBlanc GA. Intracellular conversion of environmental nitrate and nitrite to nitric oxide with resulting developmental toxicity to the crustacean Daphnia magna. PLoS ONE 2010;5(8):e12453. |
R832739 (Final) |
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Hannas BR, LeBlanc GA. Expression and ecdysteroid responsiveness of the nuclear receptors HR3 and E75 in the crustacean Daphnia magna. Molecular and Cellular Endocrinology 2010;315(1-2):208-218. |
R832739 (Final) |
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Hannas BR, Wang YH, Baldwin WS, Li Y, Wallace AD, LeBlanc GA. Interactions of the crustacean nuclear receptors HR3 and E75 in the regulation of gene transcription. General and Comparative Endocrinology 2010;167(2):268-278. |
R832739 (Final) |
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Hannas BR, Wang YH, Thomson S, Kwon G, Li H, LeBlanc GA. Regulation and dysregulation of vitellogenin mRNA accumulation in daphnids (Daphnia magna). Aquatic Toxicology 2011;101(2):351-357. |
R832739 (Final) |
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LeBlanc GA. Crustacean endocrine toxicology: a review. Ecotoxicology 2007;16(1):61-81. |
R832739 (2007) R832739 (Final) R826129 (Final) R831300 (Final) |
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LeBlanc GA, Wang YH, Holmes CN, Kwon G, Medlock EK. A transgenerational endocrine signaling pathway in Crustacea. PLoS One 2013;8(4):e61715 (13 pp.). |
R832739 (Final) |
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Olmstead AW, LeBlanc GA. The environmental-endocrine basis of gynandromorphism (intersex) in a crustacean. International Journal of Biological Sciences 2006;3(2):77-84. |
R832739 (2006) R832739 (2007) R832739 (2008) R832739 (Final) R831300 (Final) |
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Thomson SA, Baldwin WS, Wang YH, Kwon G, LeBlanc GA. Annotation, phylogenetics, and expression of the nuclear receptors in Daphnia pulex. BMC Genomics 2009;10:500 (14 pp.). |
R832739 (Final) |
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Wang YH, Wang G, LeBlanc GA. Cloning and characterization of the retinoid X receptor from a primitive crustacean Daphnia magna. General and Comparative Endocrinology 2007;150(2):309-318. |
R832739 (2006) R832739 (2007) R832739 (Final) R831300 (2006) R831300 (Final) |
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Wang YH, LeBlanc GA. Interactions of methyl farnesoate and related compounds with a crustacean retinoid X receptor. Molecular and Cellular Endocrinology 2009;309(1-2):109-116. |
R832739 (2008) R832739 (Final) |
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Wang YH, Kwon G, Li H, LeBlanc GA. Tributyltin synergizes with 20‐hydroxyecdysone to produce endocrine toxicity. Toxicological Sciences 2011;123(1):71‐79. |
R832739 (Final) |
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Supplemental Keywords:
exposure assessment, endocrinology, computational toxicology,, Health, Scientific Discipline, POLLUTANTS/TOXICS, Health Risk Assessment, Chemicals, Risk Assessments, Environmental Monitoring, chemical exposure, cumulative exposure, endocrine disrupting chemicals, rapid detection, genetic analysis, chemical mixtures, endocrine disruptors, human exposure, deconvolution technique, biomarker based exposure inference, sensor, biochemical research, human health riskRelevant Websites:
http://projects.cals.ncsu.edu/toxicology/people/gerald-a-leblanc/ Exit
http://www.ncsu.edu/project/toxresearch/projects/ Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.