Toolkit―Endocrine Disruption

Shale gas air emissions and solid and liquid wastes have been found to contain endocrine disrupting chemicals (EDCs). EDCs disrupt normal hormone signals in two main ways. First, they change the amount of a specific hormone available by altering production, metabolism, or secretion. Second, they mimic or block the action of hormones and their receptors at target tissues.

EDC Cellular Graphic.jpg

When absorbed in the body, an endocrine disruptor can decrease or increase normal hormone levels (left), mimic the body's natural hormones (middle), or alter the natural production of hormones (right).

 

Graphic courtesy of the National Institute of Environmental Health Sciences (2022)

EDCs may contaminate air, water, soil, and food sources and therefore expose residents through inhalation, ingestion, and skin absorption. Health effects from exposure to EDCs include but are not limited to: abnormal development of sex organs; reduced ability to have children; changes to secondary sex characteristics; cancers such as breast, ovarian, prostate, and testicular; impaired intellectual development; altered behavior or response to stress; and increased buildup of fat and changes in ability to respond to insulin and regulate blood sugar.

WHAT THE RESEARCH SAYS

Nagel, S. C., Kassotis, C. D., Vanderberg, L. N., et al. (2020). Developmental exposure to a mixture of unconventional oil and gas chemicals: A review of experimental effects on adult health, behavior, and disease. 

Nagel and colleagues reviewed studies that evaluated the potential endocrine-mediated health impacts of exposure to a mixture of 23 unconventional oil and gas (UOG) chemicals, commonly found in wastewater, on laboratory animals and human tissue culture cells. They found:

  • UOG chemicals and wastewater disrupted hormone receptors.

  • Perinatal exposure to the UOG-mix altered adult health.

  • UOG-mix altered sperm counts, folliculogenesis, and pituitary hormones in adulthood.

  • UOG-mix altered mammary gland morphology and induced precancerous lesions.

  • UOG-mix altered frog antiviral immunity and the immune system in three mouse models.

Balise, V. D., Cornelius-Green, J. N., Parmenter, B., et al. (2019). Developmental Exposure to a Mixture of Unconventional Oil and Gas Chemicals Increased Risk-Taking Behavior, Activity and Energy Expenditure in Aged Female Mice After a Metabolic Challenge. 

Balise and colleagues found altered energy expenditure and activity in C57BL/6J mice that were preconceptionally, gestationally, and lactationally exposed to a UOG mixture. Mice were exposed via maternal drinking water to a laboratory-created mixture of 23 UOG chemicals from gestational day 1 to postnatal day 21 in 7-month-old female mice with no change in body composition. They found:

  • Developmental exposure to the 23 UOG mixture was associated with increased activity and non-resting energy expenditure.

  • There was increased exploratory behavior in the elevated plus maze test.

  • The mice showed decreased sleep in 12-month female mice.

  • Each of these effects was seen in the light cycle when mice are normally less active.

 

Bamberger, M., Nell, M., Ahmed, A. H., et al. (2019). Surface water and groundwater analysis using aryl hydrocarbon and endocrine receptor biological assays and liquid chromatography-high resolution mass spectrometry in Susquehanna County, PA. 

Bamberger and colleagues analyzed surface water and groundwater samples collected throughout Susquehanna County, Pennsylvania. The researchers identified certain chemicals, including disclosed hydraulic fracturing fluid (HFF) additives, in samples that were either near impaired gas wells or that exhibited a biological effect. Potential endocrine activity was assessed using four endocrine receptors (androgen, estrogen, progesterone, and glucocorticoid). They found:

  • 17 potential HFF additives or wastewater constituents that are associated with aryl hydrocarbon (Ah) receptor activity, estrogen (ER) activity, and proximity to impaired wells.

  • In samples with significant activity, the magnitude of the effects seen for both agonism and antagonism are like those observed previously in areas of intensive drilling activity.

  • Endocrine receptor agonism was present in 22 samples associated with estrogen.

 

Kassotis, C. D., Nagel, S. C., Stapleton, H. M. (2018). Unconventional oil and gas chemicals and wastewater-impacted water samples promote adipogenesis via PPARγ-dependent and independent mechanisms in 3T3-L1 cells.

Kassotis and colleagues assessed adipogenic activity (both triglyceride accumulation and pre-adipocyte proliferation) for a mixture of 23 commonly used unconventional oil and gas (UOG) chemicals and a small subset of UOG wastewater-impacted surface water extracts from Colorado and West Virginia. They found:

  • Potent and efficacious adipogenic activity was induced by both a laboratory-created UOG chemical mixture and UOG-impacted water samples at concentrations below environmental levels. 

  • Activation of PPARγ at similar concentrations for some samples, suggesting a causative molecular pathway for the observed effects, but not for other adipogenic samples, implicating PPARγ-dependent and independent effects from UOG-associated chemicals.

  • Taken together, these results suggest that UOG wastewater has the potential to impact metabolic health at environmentally relevant concentrations.

 

Kassotis, C. D., Vu, D. C., Vo, P. H., et al. (2018). Endocrine-Disrupting Activities and Organic Contaminants Associated with Oil and Gas Operations in Wyoming Groundwater.

Kassotis and colleagues characterized endocrine activities and measured select organic contaminants in groundwater from conventional oil and gas and UOG production regions of Wyoming. Groundwater samples were assessed for endocrine activities (estrogen, androgen, progesterone, glucocorticoid, and thyroid receptor agonism and antagonism). The researchers found:

  • Groundwater extracts from Pavillion, WY, had the presence of putative UOG VOCs (2-ethylhexanol, naphthalene, and styrene) and increased endocrine bioactivities in this area relative to controls.

  • Water samples from UOG and conventional oil areas exhibited greater estrogen antagonist activities than water samples from conventional gas areas.

  • Samples from UOG areas tended to exhibit progesterone receptor antagonism more often, suggesting there may be a UOG-related impact on these endocrine activities.

 

Bolden, A. L., Schultz, K., Pelch, K. E., et al. (2018). Exploring the endocrine activity of air pollutants associated with unconventional oil and gas extraction.

Bolden and colleagues researched PubMed and Web of Science to identify studies that measured chemicals in air near sites of unconventional oil and gas (UOG) activity and their possible endocrine active chemicals. They evaluated 48 studies that sampled air sites and identified 106 chemicals. They found:

  • 200 air chemicals were identified in association with UOG activity at sites in the US. They identified 26 as being on the TEDX list, which identifies chemicals with endocrine activity, and an additional eight of the most frequently detected air pollutants were identified as having potential endocrine activity.

  • 21 chemicals have been shown to have endocrine activity including estrogenic and androgenic activity and ability to alter steroidogenesis.

  • Literature also suggested pollutants affecting reproduction, development, and neurophysiological function, all endpoints which can be modulated by hormones.

  • Water collected near UOG operations such as spill sites and surface water near wastewater injection sites were shown to have activity in estrogen, androgen, progesterone, glucocorticoid, and thyroid hormone in vitro receptor assays.

 

Webb, E., Moon, J., Dyrszka, L., et al. (2018). Neurodevelopmental and neurological effects of chemicals associated with unconventional oil and natural gas operations and their potential effects on infants and children.

Webb and colleagues reviewed scientific literature relevant to the potential neurodevelopmental health effects of UOG emissions on children and newborns. They reviewed human and animal studies and focused on five air and water pollutants (heavy metals, particulate matter, polycyclic aromatic hydrocarbons, BTEX, and endocrine disrupting compounds) that have been associated with potential permanent learning and neuropsychological disorders and neurological birth defects. They found:

  • Neurodevelopmental effects such as prenatal exposure to EDCs may cause permanent changes in the brain and behavior. 

  • EDCs could cause neurocognitive effects such as compromised learning and memory.

  • EDCs could also cause neuropsychological effects such as impaired social interaction, increased aggression and anxiety, increased susceptibility to sex- and/or hormonally differentiated behavioral disorders such as autism spectrum disorder, ADHD, and depression.

  • Exposure to EDCs during the perinatal period has been shown to cause permanent changes in the brain and behavior.

FULL CITATIONS

Bamberger, M., Nell, M., Ahmed, A. H., Santoro, R., Ingraffea, A. R., Kennedy, R. F., Nagel, S. C., Helbling, D. E., Oswald, R. E. (2019). Surface water and groundwater analysis using aryl hydrocarbon and endocrine receptor biological assays and liquid chromatography-high resolution mass spectrometry in Susquehanna County, PA. Environmental Science: Processes & Impacts, 21(6), 988-998. https://pubmed.ncbi.nlm.nih.gov/31093631

 

Balise, V. D., Cornelius-Green, J. N., Parmenter, B., Baxter, S., Kassotis, C. D., Rector, R. S., Thyfault,

J. P., Paterlini, S., Palanza, P., Ruiz, D., Sargis, R., & Nagel, S. C. (2019). Developmental Exposure to a

Mixture of Unconventional Oil and Gas Chemicals Increased Risk-Taking Behavior, Activity and Energy

Expenditure in Aged Female Mice After a Metabolic Challenge. Frontiers in Endocrinology, 10.

https://doi.org/10.3389/fendo.2019.00460

 

Bolden, A. L., Schultz, K., Pelch, K. E., Kwiatkowski, C. F. (2018). Exploring the endocrine activity of air pollutants associated with unconventional oil and gas extraction. Environmental Health, 17, 26. https://doi.org/10.1186/s12940-018-0368-z

 

Kassotis, C. D., Nagel, S. C., Stapleton, H. M. (2018). Unconventional oil and gas chemicals and wastewater-impacted water samples promote adipogenesis via PPARγ-dependent and independent mechanisms in 3T3-L1 cells. Science of The Total Environment, 640–641:1601-1610. https://www.sciencedirect.com/science/article/abs/pii/S0048969718316620

 

Kassotis, C. D, Vu, D. C., Vo, P. H., Lin, C. H., Cornelius-Green, J. N., Patton, S., Nagel, S. C. (2018). Endocrine-Disrupting Activities and Organic Contaminants Associated with Oil and Gas Operations in Wyoming Groundwater. Archives of environmental contamination and toxicology. 75, 247–258. https://link.springer.com/article/10.1007/s00244-018-0521-2

 

Nagel, S., Kassotis, C., Vandenberg, L., Lawrence, B., Robert, J., & Balise, V. (2020). Developmental

exposure to a mixture of unconventional oil and gas chemicals: A review of experimental effects on

adult health, behavior, and disease. Molecular and Cellular Endocrinology, 513, 110722.

https://doi.org/10.1016/j.mce.2020.110722

 

Webb, E., Moon, J., Dyrszka, L., Rodriquez, B., Coz, C., Patisaul, H., Bushkin, S., London, E. (2018). Neurodevelopmental and neurological effects of chemicals associated with unconventional oil and natural gas operations and their potential effects on infants and children. Reviews on Environmental Health, 33(1), 3-29. https://pubmed.ncbi.nlm.nih.gov/29068792/