Multi-generational toxicant exposures show cumulative, inherited health effects
Peer-Reviewed Publication
While exposure to a single substance like DDT has been shown to create inherited disease susceptibility, a recent study in animals found exposure to multiple different toxicants across generations can amplify those health problems.
In the study, published in the journal Environmental Epigenetics, an initial generation of pregnant rats was exposed to a common fungicide, then their progeny to jet fuel and the following generation to DDT. When those rats were then bred out to a fifth unexposed generation, the incidence of obesity as well as kidney and prostate diseases in those animals were compounded, rising by as much as 70%.
Researchers also found that their epigenetics, molecular processes independent of DNA that influence gene expression, were also greatly altered.
“We looked at multiple-generation exposures because these types of things are going on routinely, and previous research has only looked at single exposures,” said Michael Skinner, a WSU biology professor and the study’s corresponding author. “We found that if multiple generations get different exposures, then eventually there’s an amplification or compounded effect on some diseases.”
The study did show that for other diseases, those associated with the ovaries and the testes, the incidence rose in the first generation of progeny but appeared to plateau with the additional generational exposures.
Skinner and his colleagues also conducted epigenetic analysis of each generation of the animals, finding that the toxicant exposures shifted their entire epigenetics dramatically. Along with changes to genes themselves, inherited epigenetics which influence gene expression, are considered to have a significant impact on evolution.
“When we made the comparisons with different generations, we did not find a lot of overlap in epigenetics. In other words, every time each generation had a new exposure, it appeared to reprogram the whole epigenome,” Skinner said.
While the study does not exactly mimic what may have happened to human generations, people in the US have potentially been exposed to these particular toxicants at different times. The authors note a likely sequential exposure over human generations might involve an exposure to DDT which was widely used in the 1950s, then plastics in the 1970s, followed by many modern herbicides still in use today.
The study provides evidence that multiple toxicant exposures of past human generations likely had a compounded impact on grandchildren and great-grandchildren. Knowing about these possible impacts can help people and doctors address potential diseases before they develop, Skinner said.
Researchers including Skinner’s lab at WSU have been working to identify epigenetic biomarkers for inherited health conditions in humans including for obesity, autism and pre-term birth.
“We need to know to what degree our past generations activities that have affected us,” Skinner said. “We cannot necessarily fix this problem, but it's important to know that it happened so that we can try to better treat potential health problems through preventative medicine.”
This research received support from the John Templeton Foundation and the National Institutes of Health.
While exposure to a single substance like DDT has been shown to create inherited disease susceptibility, a recent study in animals found exposure to multiple different toxicants across generations can amplify those health problems.
In the study, published in the journal Environmental Epigenetics, an initial generation of pregnant rats was exposed to a common fungicide, then their progeny to jet fuel and the following generation to DDT. When those rats were then bred out to a fifth unexposed generation, the incidence of obesity as well as kidney and prostate diseases in those animals were compounded, rising by as much as 70%.
Researchers also found that their epigenetics, molecular processes independent of DNA that influence gene expression, were also greatly altered.
“We looked at multiple-generation exposures because these types of things are going on routinely, and previous research has only looked at single exposures,” said Michael Skinner, a WSU biology professor and the study’s corresponding author. “We found that if multiple generations get different exposures, then eventually there’s an amplification or compounded effect on some diseases.”
The study did show that for other diseases, those associated with the ovaries and the testes, the incidence rose in the first generation of progeny but appeared to plateau with the additional generational exposures.
Skinner and his colleagues also conducted epigenetic analysis of each generation of the animals, finding that the toxicant exposures shifted their entire epigenetics dramatically. Along with changes to genes themselves, inherited epigenetics which influence gene expression, are considered to have a significant impact on evolution.
“When we made the comparisons with different generations, we did not find a lot of overlap in epigenetics. In other words, every time each generation had a new exposure, it appeared to reprogram the whole epigenome,” Skinner said.
While the study does not exactly mimic what may have happened to human generations, people in the US have potentially been exposed to these particular toxicants at different times. The authors note a likely sequential exposure over human generations might involve an exposure to DDT which was widely used in the 1950s, then plastics in the 1970s, followed by many modern herbicides still in use today.
The study provides evidence that multiple toxicant exposures of past human generations likely had a compounded impact on grandchildren and great-grandchildren. Knowing about these possible impacts can help people and doctors address potential diseases before they develop, Skinner said.
Researchers including Skinner’s lab at WSU have been working to identify epigenetic biomarkers for inherited health conditions in humans including for obesity, autism and pre-term birth.
“We need to know to what degree our past generations activities that have affected us,” Skinner said. “We cannot necessarily fix this problem, but it's important to know that it happened so that we can try to better treat potential health problems through preventative medicine.”
This research received support from the John Templeton Foundation and the National Institutes of Health.
JOURNAL
Environmental Epigenetics
Environmental Epigenetics
DOI
Forever chemicals" in German drinking water - a hidden threat unveiled
IMAGE:
GRAPHICAL ABSTRACT.
view moreCREDIT: ECO-ENVIRONMENT & HEALTH
PFAS, commonly known as "forever chemicals," are a group of man-made substances that have been used in various industries since the 1940s due to their resistance to heat, water, and oil.These chemicals are found in products like non-stick cookware, waterproof fabrics, firefighting foams, and food packaging.Their persistence in the environment and their ability to accumulate in human and animal tissue make them a concern for potential adverse health impacts. Despite their widespread use, the knowledge about pose potential risks to drinking water quality, especially in Germany, has been limited.
In a landmark study (https://doi.org/10.1016/j.eehl.2023.08.004) published in "Eco-Environment & Health" (Volume 2, 2023), researchers screened German drinking water for 26 per- and polyfluoroalkyl substances (PFAS). This effort, notably supported by residents, marks a significant step in understanding PFAS presence in drinking water.
The study involved collecting 89 drinking water samples from various locations in Germany, analyzing them for 26 different PFAS using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The findings revealed that while the 20 recently regulated PFAS were below the detection limit, the sum concentrations varied widely, with some samples exceeding the threshold for certain PFAS.
This research is pivotal in informing future regulatory decisions and public health guidelines. It highlights the need for ongoing surveillance and stricter controls on PFAS in drinking water.
Dr. Aki Sebastian Ruhl, emphasizes the importance of this study in providing a comprehensive view of PFAS distribution in drinking water across Germany, a crucial aspect in evaluating environmental and health risks.
The collaborative effort in this study has provided valuable insights into PFAS levels in German drinking water, laying the groundwork for future environmental and public health initiatives, and underscores the necessity for further research to understand the long-term implications of PFAS in drinking water and to develop more efficient removal methods.
The collaborative effort in this study has provided valuable insights into PFAS levels in German drinking water, laying the groundwork for future environmental and public health initiatives, and underscores the necessity for further research to understand the long-term implications of PFAS in drinking water and to develop more efficient removal methods.
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References
DOI
Original Source URL
https://doi.org/10.1016/j.eehl.2023.08.004
Funding information
The project Spu-TriDa was funded by the German Ministry of Health.
About Eco-Environment & Health
Eco-Environment & Health (EEH) is an international and multidisciplinary peer-reviewed journal designed for publications on the frontiers of the ecology, environment and health as well as their related disciplines. EEH focuses on the concept of "One Health" to promote green and sustainable development, dealing with the interactions among ecology, environment and health, and the underlying mechanisms and interventions. Our mission is to be one of the most important flagship journals in the field of environmental health.
JOURNAL
Eco-Environment & Health
SUBJECT OF RESEARCH
Not applicable
ARTICLE TITLE
Screening for 26 per- and polyfluoroalkyl substances (PFAS) in German drinking waters with support of residents
Exposure to flame retardants linked to premature birth, higher birth weight
Organophosphate ester flame retardants are found in building materials, furniture, baby products, electronics and textiles
IMAGE: DEBORAH BENNETT, SENIOR AUTHOR OF THE STUDY, IS A PROFESSOR OF ENVIRONMENTAL HEALTH IN THE UC DAVIS DEPARTMENT OF PUBLIC HEALTH SCIENCES. view more
CREDIT: UC DAVIS HEALTH
(SACRAMENTO, Calif.) — In the largest study of its kind, researchers at UC Davis Health found that exposure to organophosphate ester flame retardants during pregnancy was associated with preterm birth, especially among females. The chemicals were also linked to higher birth weight, a concern for increased obesity risk. The major new research study was published in Environmental Health Perspectives.
“The importance of this study lies in unraveling the potential impact of exposure to environmental chemicals during pregnancy on fetal development. Our findings guide our understanding of how these chemicals may be silently seeding lasting challenges for the health of the next generation,” said Jiwon Oh, first author of the study and a postdoctoral scholar in the Department of Public Health Sciences, Division of Environmental and Occupational Health.
OPEs phased in as polybrominated flame retardants phased out
In the mid-2000s, one class of chemicals, polybrominated diphenyl ether flame retardants, were gradually phased out of use due to concerns about their potential toxicity.
Organophosphate esters, or OPEs, gradually took their place. They are now widely used in foams found in furniture, baby products, electronics, textiles and building materials to prevent fires and make plastics more flexible.
Because of their chemical structure, OPEs slowly degrade and become part of dust. Individuals are exposed to OPEs through their skin or when they ingest or inhale indoor dust.
The chemicals are frequently detected in urine samples from the U.S. general population, including samples from pregnant people. For this study, the researchers wanted to determine what impact OPEs might have on fetal development during pregnancy.
Research conducted across U.S.
Researchers at multiple institutions, including UC Davis, conducted the study. It included 6,646 mother-child pairs from 16 cohorts across the U.S. from the Environmental Influences on Child Health Outcome (ECHO) study. The participants came from various regions and had diverse backgrounds.
Researchers measured nine OPE biomarkers in urine samples of pregnant people collected between 2007 and 2020, with most samples obtained during the second and third trimesters.
They assessed birth outcomes, including gestational age at birth and birth weight, primarily using medical records or parent reports.
Preterm births and greater birth weight
The researchers found three of the nine OPEs were associated with increased risks of preterm birth (before 37 weeks of pregnancy), especially among female newborns. These included:
- dibutyl phosphate
- di-isobutyl phosphate
- bis(butoxyethyl) phosphate
Preterm births can put infants at risk of health issues, including breathing and feeding problems, developmental delays, cerebral palsy, and vision and hearing problems.
Three other OPEs — bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate — were linked to greater birth weight-for-gestational-age.
High birth weight is associated with childhood obesity, which increases the risk of health conditions like diabetes and cardiovascular disease.
“There were over 6,000 pregnancies included in this study, and with such a large study, we are very confident of our findings,” said Deborah Bennett, senior author of the study and a professor of environmental health in the Department of Public Health Sciences. “Policy options to reduce exposure to organophosphate ester flame retardants should be considered.”
OPEs are metabolic and endocrine-disrupting chemicals
The researchers noted that OPEs may affect thyroid hormone levels and cause inflammation and oxidative stress, which could play a role in the preterm births. OPEs are also endocrine disruptors, so they may contribute to abnormal placental development, and the impact may vary based on the sex of the fetus.
“Because OPEs are from building materials, textiles, electronics and other products, consumers cannot choose products that do not contain OPEs,” Oh said. “Only policy changes and regulations can mitigate their exposure.”
Resources
JOURNAL
Environmental Health Perspectives
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Associations of Organophosphate Ester Flame Retardant Exposures During Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program
ARTICLE PUBLICATION DATE
24-Jan-2024
COI STATEMENT
Rebecca J. Schmidt consults for the Beasley Law. Schmidt has received travel support to present at the 35th Annual Meeting of the Organization of Teratology Information Specialists (OTIS). Schmidt and Deborah H. Bennett consult for LinusBio. No other authors have anything to report.
