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A Scripps Institution of Oceanography at the University of California San Diego-led research team discovered for the first time that a common marine sponge hosts bacteria that specialize in the production of toxic compounds nearly identical to man-made fire retardants. The new findings put the research team one step closer to unraveling the mystery of this powerful group of chemical compounds, known as polybrominated diphenyl ethers (PBDEs), in the marine environment. PBDEs are a subgroup of brominated flame retardants that are combined into foam, textiles, and electronics to raise the temperature at which the products will burn. These man-made industrial chemicals are powerful endocrine disruptors that mimic the activity of the human body's most active thyroid hormone. Vinayak Agarwal, a postdoctoral researcher at Scripps, picked up a cold case first started nearly 50 years ago by Scripps chemist John Faulkner, an early pioneer in the study of natural products from the sea, to continue the investigation into the source of these toxic compounds that are found in large quantities in the world’s oceans. “For the first time we were able to conclusively show that genes and enzymes produced in bacteria from sponges are responsible for the production of these compounds toxic to humans,” said Agarwal, co-first author of the paper along with Scripps PhD student Jessica Blanton. The study was part of the National Science Foundation (NSF)/ National Institute of Environmental Health Sciences (NIEHS)-funded Center for Oceans and Human Health research being conducted at Scripps. In 2014, Agarwal and colleagues at Scripps Oceanography were the first to discover that unrelated free-living marine bacteria produce these fire retardant compounds naturally, albeit in very small quantities. In this new study, the researchers employed two modern-day techniques—genome “mining” pioneered by Scripps marine chemist Brad Moore and an environmental DNA sequencing approach pioneered by Scripps biologist Eric Allen—to take the investigation a step further and identify the specific genes and enzymes involved in the overproduction of the toxic molecules in sponges. Marine sponges obtain food and oxygen by filtering seawater through the pores and channels in their bodies. This constant water flow means that these immobile animals host many bacteria, viruses, and fungi in their complex microbiomes. The research team collected 18 sponge samples for the study during two research expeditions to Guam. They then isolated the various components of this complex mixture of organisms from the sponge’s tissues to identify the specific genes and enzymes that code for the production of PBDEs. “For many years scientists were finding clues that suggested nature was making these compounds,” said Bradley Moore, a professor at the Scripps Center of Marine Biotechnology and Biomedicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego, and a senior author of the study. “Now that we understand how they are produced in the marine environment, we are exploring why they exist, and the human health concerns associated with them.” Moore’s genome "mining" approach along with Allen’s metagenomic sequencing gives scientists a way to connect the natural chemicals produced by organisms back to the enzymes that construct them. The study, which appears on the cover of the May issue of the journal Nature Chemical Biology, was a unique collaboration among chemists and biologists at UC San Diego and elsewhere. “This study is a powerful combination of chemical, biological and environmental research,” said Henrietta Edmonds of the NSF’s Division of Ocean Sciences, which supported the research. “It has the potential to help us understand the production, fate and health consequences of natural and pollutant compounds in the marine environment.” “We care about naturally produced PBDEs because they end up in the food chain,” said Frederick Tyson, Ph.D., of the NIEHS, which helped to fund the research. “Preliminary data from this research team suggest that some naturally occurring PDBEs may be even more toxic than those that are man-made, so we need to develop a better understanding of these compounds.” These ocean-dwelling microbes have been found in habitats as diverse as sea grasses, corals and whales. The next step of the investigation for the researchers is to mine the genes and enzymes in other marine hosts to find out what other organisms are making similar toxic compounds and why. Co-authors from Scripps Oceanography include Sheila Podell, Michelle Schorn, Julia Busch, and Paul Jensen. Researchers Arnaud Taton and James Golden from UC San Diego’s Division of Biological Sciences, Jason Biggs from University of Guam’s Marine Laboratory, Zhenjian Lin and Eric Schmidt from the University of Utah, and Valerie Paul from the Smithsonian Marine Station also contributed to the study. Funding for the research was provided through: National Science Foundation grants OCE-1313747, DGE-1144086, IOS-1120113, MCB-1149552; National Institutes of Health grants P01-ES021921, K99-ES026620, R01-GM107557, R01-CA172310, S10-OD010640; the U.S. Department of Energy grant DE-EE0003373; and a Helen Hay Whitney Foundation postdoctoral fellowship.


News Article | May 11, 2017
Site: www.chromatographytechniques.com

Researchers have discovered for the first time that a common marine sponge hosts bacteria that specialize in the production of toxic compounds nearly identical to man-made fire retardants, a finding that could help scientists better understand the human health implications of these common additives. The new findings, by scientists at the Scripps Institution of Oceanography (SIO) at the University of California, San Diego, moved the research team a step closer to unraveling the mysteries of this powerful group of chemical compounds, known as polybrominated diphenyl ethers (PBDEs). The National Science Foundation's (NSF) Division of Ocean Sciences and the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health jointly funded the research through SIO's Center for Oceans and Human Health. "For many years scientists have been finding clues that suggested nature was making these compounds," said SIO marine chemist Brad Moore, a senior author of the study. "Now that we understand how they are produced in the marine environment, we are exploring why they exist, and the human health concerns associated with them." The results, which appear in the May issue of the journal Nature Chemical Biology, came from a unique collaboration among chemists and biologists at SIO and elsewhere. "This study is a powerful combination of chemical, biological and environmental research," said Henrietta Edmonds of NSF's Division of Ocean Sciences. "It has the potential to help us understand the production, fate and health consequences of natural and pollutant compounds in the marine environment." Manufacturers add PBDEs to foam, textiles, electronics and other products to make them less flammable. These industrial chemicals are powerful endocrine disruptors that mimic the activity of the human body's most active thyroid hormone. Vinayak Agarwal, a researcher at SIO, picked up a cold case first started nearly 50 years ago by SIO chemist John Faulkner, an early pioneer in the study of natural products from the sea. Agarwal continued Faulkner's investigation into the source of toxic PDBEs, found in large quantities in the world's oceans. "For the first time we were able to conclusively show that genes and enzymes produced in bacteria from sponges are responsible for the production of these compounds toxic to humans," said Agarwal, co-first author of the paper along with Scripps researcher Jessica Blanton. In 2014, Agarwal and colleagues were the first to discover that unrelated free-living marine bacteria produce the fire retardant compounds naturally. In the new study, researchers employed two modern-day techniques -- genome "mining" and environmental DNA sequencing -- to take the investigation a step farther and identify the specific genes and enzymes involved in the overproduction of the toxic molecules in sponges. Marine sponges obtain food and oxygen by filtering seawater through the pores and channels in their bodies. This constant flow of water means that these immobile animals host many bacteria, viruses and fungi in their complex microbiomes. The research team collected 18 sponge samples for the study during two research expeditions to Guam. They then isolated the various components in the complex mixture of organisms from the sponge's tissues to identify the specific genes and enzymes that code for the production of PBDEs. The genome "mining" approach along with metagenomic sequencing gave the scientists a way to connect the natural chemicals produced by organisms back to the enzymes that constructed them. "We care about naturally produced PBDEs because they end up in the food chain," said NIEHS's Frederick Tyson. "Preliminary data from this research team suggest that some naturally occurring PDBEs may be even more toxic than those that are man-made, so we need to develop a better understanding of these compounds." The next step in the investigation is to mine the genes and enzymes in other marine species to found out what other organisms are making similar toxic compounds and why.


News Article | May 15, 2017
Site: www.eurekalert.org

Researchers from North Carolina State University have demonstrated that molecular dynamics simulations and machine learning techniques could be integrated to create more accurate computer prediction models. These "hyper-predictive" models could be used to quickly predict which new chemical compounds could be promising drug candidates. Drug development is a costly and time-consuming process. To narrow down the number of chemical compounds that could be potential drug candidates, scientists utilize computer models that can predict how a particular chemical compound might interact with a biological target of interest - for example, a key protein that might be involved with a disease process. Traditionally, this is done via quantitative structure-activity relationship (QSAR) modeling and molecular docking, which rely on 2- and 3-D information about those chemicals. Denis Fourches, assistant professor of computational chemistry, wanted to improve upon the accuracy of these QSAR models. "When you're screening a set of 30 million compounds, you don't necessarily need a very high reliability with your model - you're just getting a ballpark idea about the top 5 or 10 percent of that virtual library. But if you're attempting to narrow a field of 200 analogues down to 10, which is more commonly the case in drug development, your modeling technique must be extremely accurate. Current techniques are definitely not reliable enough." Fourches and Jeremy Ash, a graduate student in bioinformatics, decided to incorporate the results of molecular dynamics calculations - all-atom simulations of how a particular compound moves in the binding pocket of a protein - into prediction models based on machine learning. "Most models only use the two-dimensional structures of molecules," Fourches says. "But in reality, chemicals are complex three-dimensional objects that move, vibrate and have dynamic intermolecular interactions with the protein once docked in its binding site. You cannot see that if you just look at the 2-D or 3-D structure of a given molecule." In a proof-of-concept study, Fourches and Ash looked at the ERK2 kinase - an enzyme associated with several types of cancer - and a group of 87 known ERK2 inhibitors, ranging from very active to inactive. They ran independent molecular dynamics (MD) simulations for each of those 87 compounds and computed critical information about the flexibility of each compound once in the ERK2 pocket. Then they analyzed the MD descriptors using cheminformatics techniques and machine learning. The MD descriptors were able to accurately distinguish active ERK2 inhibitors from weakly actives and inactives, which was not the case when the models used only 2-D and 3-D structural information. "We already had data about these 87 molecules and their activity at ERK2," Fourches says. "So we tested to see if our model was able to reliably find the most active compounds. Indeed, it accurately distinguished between strong and weak ERK2 inhibitors, and because MD descriptors encoded the interactions those compounds create in the pocket of ERK2, it also gave us more insight into why the strong inhibitors worked well. "Before computing advances allowed us to simulate this kind of data, it would have taken us six months to simulate one single molecule in the pocket of ERK2. Thanks to GPU acceleration, now it only takes three hours. That is a game changer. I'm hopeful that incorporating data extracted from molecular dynamics into QSAR models will enable a new generation of hyper-predictive models that will help bringing novel, effective drugs onto the market even faster. It's artificial intelligence working for us to discover the drugs of tomorrow." The work appears in the Journal of Chemical Information and Modeling. Ash is first author of the paper and is funded by an NIEHS grant (T32ES007329). Other funding was provided by the NC State Chancellor's Faculty Excellence Program. Note to editors: An abstract of the paper follows. "Characterizing the Chemical Space of ERK2 Kinase Inhibitors Using Descriptors Computed from Molecular Dynamics Trajectories" Quantitative Structure-Activity Relationship (QSAR) models typically rely on 2D and 3D molecular descriptors to characterize chemicals and forecast their experimental activities. Previously, we showed that even the most reliable 2D QSAR models and structure-based 3D molecular docking techniques were not capable of accurately ranking a set of known inhibitors for the ERK2 kinase, a key player in various types of cancer. Herein, we calculated and analyzed a series of chemical descriptors computed from the molecular dynamics (MD) trajectories of ERK2-ligand complexes. First, the docking of 87 ERK2 ligands with known binding affinities was accomplished using Schrodinger's Glide software; then, solvent-explicit MD simulations (20 ns, NPT, 300K, TIP3P, 1fs) were performed using the GPU-accelerated Desmond program. Second, we calculated a series of MD descriptors based on the distributions of 3D descriptors computed for representative samples of the ligand's conformations over the MD simulations. Third, we analyzed the dataset of 87 inhibitors in the MD chemical descriptor space. We showed that MD descriptors (i) had little correlation with conventionally used 2D/3D descriptors, (ii) were able to distinguish the most active ERK2 inhibitors from the moderate/weak actives and inactives, and (iii) provided key and complementary information about the unique characteristics of active ligands. This study represents the largest attempt to utilize MD-extracted chemical descriptors to characterize and model a series of bioactive molecules. MD descriptors could enable the next generation of hyper-predictive MD-QSAR models for computer-aided lead optimization and analogue prioritization.


News Article | May 16, 2017
Site: www.eurekalert.org

CHICAGO --- The brave new world of 3-D printed organs now includes implanted ovary structures that, true to their design, actually ovulate, according to a study by Northwestern University Feinberg School of Medicine and McCormick School of Engineering. By removing a female mouse's ovary and replacing it with a bioprosthetic ovary, the mouse was able to not only ovulate but also give birth to healthy pups. The moms were even able to nurse their young. The bioprosthetic ovaries are constructed of 3-D printed scaffolds that house immature eggs, and have been successful in boosting hormone production and restoring fertility in mice, which was the ultimate goal of the research. "This research shows these bioprosthetic ovaries have long-term, durable function," said Teresa K. Woodruff, a reproductive scientist and director of the Women's Health Research Institute at Feinberg. "Using bioengineering, instead of transplanting from a cadaver, to create organ structures that function and restore the health of that tissue for that person, is the holy grail of bioengineering for regenerative medicine." The paper will be published May 16 in Nature Communications. How is this research different from other 3-D printed structures? What sets this research apart from other labs is the architecture of the scaffold and the material, or "ink," the scientists are using, said Ramille Shah, assistant professor of materials science and engineering at McCormick and of surgery at Feinberg. That material is gelatin, which is a biological hydrogel made from broken-down collagen that is safe to use in humans. The scientists knew that whatever scaffold they created needed to be made of organic materials that were rigid enough to be handled during surgery and porous enough to naturally interact with the mouse's body tissues. "Most hydrogels are very weak, since they're made up of mostly water, and will often collapse on themselves," Shah said. "But we found a gelatin temperature that allows it to be self-supporting, not collapse, and lead to building multiple layers. No one else has been able to print gelatin with such well-defined and self-supported geometry." That geometry directly links to whether or not the ovarian follicles, organized hormone-producing support cells surrounding an immature egg cell, will survive in the ovary, which was one of the bigger findings in the study. "This is the first study that demonstrates that scaffold architecture makes a difference in follicle survival," Shah said. "We wouldn't be able to do that if we didn't use a 3-D printer platform." How does this impact humans? The scientists' sole objective for developing the bioprosthetic ovaries was to help restore fertility and hormone production in women who have undergone adult cancer treatments or those who survived childhood cancer and now have increased risks of infertility and hormone-based developmental issues. "What happens with some of our cancer patients is that their ovaries don't function at a high enough level and they need to use hormone replacement therapies in order to trigger puberty," said Monica Laronda, co-lead author of this research and a former post-doctoral fellow in the Woodruff lab. "The purpose of this scaffold is to recapitulate how an ovary would function. We're thinking big picture, meaning every stage of the girl's life, so puberty through adulthood to a natural menopause." Laronda is now an assistant professor at the Stanley Manne Children's Research Institute at the Ann & Robert H. Lurie Children's Hospital. Additionally, the successful creation of 3-D printed implants to replace complex soft tissue could significantly impact future work in soft tissue regenerative medicine. 3-D printing an ovary structure is similar to a child using Lincoln Logs, said Alexandra Rutz, co-lead author of the study and a former biomedical engineering graduate fellow in Shah's Tissue Engineering and Additive Manufacturing (TEAM) lab at the Simpson Querrey Institute. Children can lay the logs at right angles to form structures. Depending on the distance between the logs, the structure changes to build a window or a door, etc. "3-D printing is done by depositing filaments," said Rutz, who is now a Whitaker International Postdoctoral Scholar at École Des Mines De Saint-Étienne in Gardanne, France. "You can control the distance between those filaments, as well as the advancing angle between layers, and that would give us different pore sizes and different pore geometries." In Northwestern's lab, the researchers call these 3-D printed structures "scaffolds," and liken them to the scaffolding that temporarily surrounds a building while it undergoes repairs. "Every organ has a skeleton," said Woodruff, who also is the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "We learned what that ovary skeleton looked like and used it as model for the bioprosthetic ovary implant." In a building, the scaffolding supports the materials needed to repair the building until it's eventually removed. What's left is a structure capable of holding itself up. Similarly, the 3-D printed "scaffold" or "skeleton" is implanted into a female and its pores can be used to optimize how follicles, or immature eggs, get wedged within the scaffold. The scaffold supports the survival of the mouse's immature egg cells and the cells that produce hormones to boost production. The open structure also allows room for the egg cells to mature and ovulate, as well as blood vessels to form within the implant enabling the hormones to circulate within the mouse bloodstream and trigger lactation after giving birth. The all-female McCormick-Feinberg collaboration for this research was "very fruitful," Shah said, adding that it was motivational to be part of an all-female team doing research towards finding solutions to female health issues. "What really makes a collaboration work are the personalities and being able to find the humor in the research," Shah said. "Teresa and I joked that we're grandparents of these pups." This work was supported by the Northwestern University Watkins Chair of Obstetrics and Gynecology; the National Institutes of Health (NIH) National Center for Translational Research in Reproduction and Infertility (NCTRI); grant P50HD076188 from the Center for Reproductive Health After Disease; grant UH3TR001207 from the National Center for Advancing Translational Sciences (NCATS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Office of Women's Health Research (ORWH), and NIH Common Fund; grant 1K01DK099454-01 from the NIH; the Burroughs Welcome Fund Career Award at the Scienti?c Interface; and grant DGE-1324585 from the National Science Foundation Graduate Research Fellowship Program. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by grant P50-HD28934 from the NICHD/NIH (NCTRI). Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. This work made use of the EPIC facility of the NUANCE Center at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN.


News Article | May 26, 2017
Site: www.eurekalert.org

New research from the University of Cincinnati (UC) reveals that residents of the Mid-Ohio River Valley (from Evansville, Indiana, north to Huntington, West Virginia) had higher than normal levels of perfluorooctanoic acid (PFOA) based on blood samples collected over a 22-year span. The exposure source was likely from drinking water contaminated by industrial discharges upriver. The study, appearing in the latest publication of Environmental Pollution, looked at levels of PFOA and 10 other per- and polyfluoroalkyl substances (PFAS) in 931 Mid-Ohio River Valley residents, testing blood serum samples collected between 1991 and 2013, to determine whether the Ohio River and Ohio River Aquifer were sources of exposure. This is the first study of PFOA serum concentrations in U.S. residents in the 1990s. "These Mid-Ohio River Valley residents appear to have had concentrations of PFOA in their bloodstream at higher than average U.S. levels," says Susan Pinney, PhD, professor in the Department of Environmental Health at the UC College of Medicine, a member of both the Cincinnati Cancer Consortium and UC Cancer Institute and senior author of the study. Ohio River PFOA concentrations downstream were elevated, suggesting Mid-Ohio River Valley residents were exposed through drinking water, primarily contaminated by industrial discharges as far as 666 kilometers (413 miles) upstream. Industrial discharges of PFOA to the Ohio River, contaminating water systems near Parkersburg, West Virginia, were previously associated with nearby residents' serum PFOA concentrations above U.S. general population medians. The article notes that use of granular activated carbon filtration (GAC) by water treatment facilities reduced PFOA exposure by as much as 60 percent. "Where GAC has been used, the blood level concentration of PFOA was decreased significantly," says co-author Robert Herrick, a UC doctoral student in the Department of Environmental Health. Nearly all of the samples tested positive for some level of PFOA (99.9%) but 47 percent of the samples had PFOA levels higher than the 95th national percentile. The study additionally looked at information about municipal water distribution systems and the zones that were serviced by each of the water treatment plants. "We conducted statistical analyses to determine if factors such as location and years of residence, drinking water source and breast feeding were predictors of the person's serum PFC concentration," says Herrick. PFCs have had wide consumer use and industrial applications. They are surfactants used in fire-fighting foams and in the manufacture of stain and water resistant coatings, on cookware, furniture and carpeting. PFOA, or C-8, can be found as a residual impurity in some paper coatings used on containers for processed food. As a byproduct of commercial production, PFCs/PFOA are released into the environment and, although no longer used in manufacturing in the U.S., are considered persistent in the environment. Pinney points out that the primary concern with PFCs/PFOA is that they take a very long time to leave the human body, and studies indicate that exposure to PFOA and PFOS over certain levels may result in adverse health effects, including developmental effects, liver and tissue damage and immune and thyroid impacts. "Because the elimination time could be several years, it is hard to determine what impact these environmental exposures may have on our health and children's health," says Pinney. "These data from the 1990s demonstrate that that the contaminants have been in our water a long time, at unchecked levels, before anyone was paying attention to it." Pinney cites projects like this one as having the translational potential to make improvements in public health. "Studies like these provide evidence to support changes in water treatment practices." An earlier study looking at samples from girls and young women from Northern Kentucky showed that about half of the samples from the girls were much higher than the national average for U.S. children (the 95th percentile) concentration. The Northern Kentucky Water department has since then implemented the use of GAC at their plants to meet new federal regulations, and Cincinnati Water Works used the study's findings to check their treatment regulations and filtration usage. The Mid-Ohio River Valley study was conducted by researchers within the UC College of Medicine Department of Environmental Health, at Cincinnati Children's Hospital Medical Center and the National Institute of Environmental Health Sciences (NIEHS). Research was made possible by the Breast Cancer and the Environment Research Program awards U01ES012770 and U01ES019453 from the NIEHS and the National Cancer Institute; P30-ES006096, R21 ES017176 and T32-ES10957 from NIEHS; EPA-RD-83478801 from the United States Environmental Protection Agency, and CSTAUL1RR026314 from the National Center for Research Resources. Pinney cites no conflict of interest.


News Article | May 2, 2017
Site: www.eurekalert.org

WASHINGTON (May 2, 2017) - Some scientific reports have a profound impact on government policy. Sometimes, however, there are significant shortcomings in the research - yet the policy impact continues. Critically analyzing scientific research that underlies regulatory decision making and generating new information to ensure decisions are based on sound science are crucial. A recent analysis by Checkoway et al. has been awarded the Kammer Merit in Authorship Award for its review of the data from a critical epidemiological study used by scientific agencies to assess health risk from formaldehyde exposure. The findings from Checkoway et al call into question the original study's conclusions; the analysis further demonstrates the importance of data availability, research reproducibility and adherence to study design when drawing scientific conclusions. The Kammer Merit in Authorship Award recognizes an outstanding scientific contribution published in the American College of Occupational and Environmental Medicine (ACOEM's) Journal of Occupational and Environmental Medicine (JOEM) during a given year. The winning paper, titled Formaldehyde Exposure and Mortality Risks from Acute Myeloid Leukemia and Other Lymphohematopoietic Malignancies in the US National Cancer Institute Cohort Study of Workers in Formaldehyde Industries, concluded that there is no epidemiological evidence from the National Cancer Institute (NCI) cohort supporting an association between formaldehyde exposure and acute myeloid leukemia (AML). The award was announced late last week. "The findings from this analysis do not support a finding that formaldehyde exposure is a cause of leukemia," said Harvey Checkoway, Ph.D., lead author of the reanalysis and Professor of Family Medicine & Public Health at the University of California, San Diego. "This reanalysis identifies how critical data interpretation is, given that the risk assessments that rely on these analyses ultimately set occupational and environmental exposure standards." Checkoway and his colleagues performed analyses of raw data in an attempt to replicate findings reported from a NCI cohort mortality study of workers from 10 US plants producing or using formaldehyde. The NCI study has been influential in the classification of formaldehyde as a human leukemogen by the International Agency for Research on Cancer (IARC) and the National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP). In the original analysis NCI investigators defined "peak" exposure to formaldehyde on a relative basis with respect to individual workers' exposures histories. This complicates data interpretations. Using this definition, analyses of updated mortality data for the NCI cohort reported tentative associations of "peak" exposures with myeloid leukemia (ML) and Hodgkin lymphoma (HL) that are inconsistent with other studies. The new research found no association between acute myeloid leukemia (AML) and cumulative, average or frequency of "peak" exposures. This became clear in the new analysis where AML and chronic myeloid leukemia (CML) were evaluated separately, as two types of leukemia are different diseases and have different risk factors. The award-winning Checkoway et al. study conducted more comprehensive analyses of associations of specific lymphohematopoietic malignancies (LHM), especially AML, with peak exposure, using a standard definition of peak exposure. Peak was defined in terms of absolute exposure dose and duration, which permitted direct comparisons among similar studies, strengthening the analysis. Checkoway et al. concluded that no clear associations for peak or cumulative formaldehyde exposures were observed in this cohort for any of the specific LHM, including AML The result of this analysis adds to the weight of evidence that formaldehyde exposure in the workplace does not cause AML, the LHM of greatest concern. It also underscores the need to ensure new information is effectively considered and incorporated into chemical assessments by IARC, NTP and other agencies. "Having this work recognized by ACOEM as a significant contribution in occupational medicine shows how important these findings are to understanding and interpreting the formaldehyde science," said Kimberly White, Ph.D., Senior Director of the American Chemistry Council Formaldehyde Panel. To learn more, view this fact sheet or visit americanchemistry.com/formaldehyde. The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible Care®, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for fourteen percent of all U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure.


News Article | May 2, 2017
Site: www.prnewswire.com

"The findings from this analysis do not support a finding that formaldehyde exposure is a cause of leukemia," said Harvey Checkoway, Ph.D., lead author of the reanalysis and Professor of Family Medicine & Public Health at the University of California, San Diego. "This reanalysis identifies how critical data interpretation is, given that the risk assessments that rely on these analyses ultimately set occupational and environmental exposure standards." Checkoway and his colleagues performed analyses of raw data in an attempt to replicate findings reported from a NCI cohort mortality study of workers from 10 US plants producing or using formaldehyde. The NCI study has been influential in the classification of formaldehyde as a human leukemogen by the International Agency for Research on Cancer (IARC) and the National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP). In the original analysis NCI investigators defined "peak" exposure to formaldehyde on a relative basis with respect to individual workers' exposures histories. This complicates data interpretations. Using this definition, analyses of updated mortality data for the NCI cohort reported tentative associations of "peak" exposures with myeloid leukemia (ML) and Hodgkin lymphoma (HL) that are inconsistent with other studies. The new research found no association between acute myeloid leukemia (AML) and cumulative, average or frequency of "peak" exposures. This became clear in the new analysis where AML and chronic myeloid leukemia (CML) were evaluated separately, as two types of leukemia are different diseases and have different risk factors. The award-winning Checkoway et al. study conducted more comprehensive analyses of associations of specific lymphohematopoietic malignancies (LHM), especially AML, with peak exposure, using a standard definition of peak exposure. Peak was defined in terms of absolute exposure dose and duration, which permitted direct comparisons among similar studies, strengthening the analysis. Checkoway et al. concluded that no clear associations for peak or cumulative formaldehyde exposures were observed in this cohort for any of the specific LHM, including AML. The result of this analysis adds to the weight of evidence that formaldehyde exposure in the workplace does not cause AML, the LHM of greatest concern. It also underscores the need to ensure new information is effectively considered and incorporated into chemical assessments by IARC, NTP and other agencies. "Having this work recognized by ACOEM as a significant contribution in occupational medicine shows how important these findings are to understanding and interpreting the formaldehyde science," said Kimberly White, Ph.D., Senior Director of the American Chemistry Council Formaldehyde Panel. To learn more, view this fact sheet or visit americanchemistry.com/formaldehyde. The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible Care®, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for fourteen percent of all U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/acc-research-shows-no-link-between-formaldehyde-and-leukemia-300449140.html

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