Environmental Biodynamics

The book provides a new conceptual framework to explain the interaction of complex systems, specifically humans and their environment. It proposes that human physiology and the environment do not “connect” with each other in a direct, unidirectional manner, like a beaker pouring water into a cup. Rather, the authors propose the Biodynamic Interface Conjecture with the central axiom that complex systems cannot interact directly or exist in isolation due to temporally embedded functional interdependencies within and between systems. The authors propose that human physiology and the environment contribute to the formation of an interface, and by doing so they give rise to an intermediary that guides the interaction by letting some influences pass between the systems while restricting others. This proposition counters many structural approaches that assume that complex systems, such as the environment and humans, can transfer information directly between them while remaining discrete entities. Although developed for environmental health sciences, the conjecture has broader implications for the study of complex system interactions across various levels of organization, and the central role of time and temporal dynamics in system-to-system information exchange. This conjecture also argues against causal paradigms that (incorrectly) assume that systems are distinct entities interacting directly and ignore boundary conditions, and organizational levels, and complexity inherent in biological and environmental systems.

Mixture toxicity, cumulative risk, and environmental justice in United States federal policy, 1980–2016

Toxic chemicals — “toxicants” — have been studied and regulated as single entities, and, carcinogens aside, almost all toxicants, single or mixed and however altered, have been thought harmless in very low doses or very weak concentrations. Yet much work in recent decades has shown that toxicants can injure wildlife, laboratory animals, and humans following exposures previously expected to be harmless. Additional work has shown that toxicants can act not only individually and cumulatively but also collectively and even synergistically and that they affect disadvantaged communities inordinately — and therefore, as argued by reformers, unjustly. As late as December 2016, the last full month before the inauguration of a president promising to rescind major environmental regulations, the United States federal environmental-health establishment, as led by the Environmental Protection Agency (EPA), had not developed coherent strategies to mitigate such risks, to alert the public to their plausibility, or to advise leadership in government and industry about their implications. To understand why, we examined archival materials, reviewed online databases, read internal industry communications, and interviewed experts. We confirmed that external constraints, statutory and judicial, had been in place prior to EPA’s earliest interest in mixture toxicity, but we found no overt effort, certainly no successful effort, to loosen those constraints. We also found internal constraints: concerns that fully committing to the study of complex mixtures involving numerous toxicants would lead to methodological drift within the toxicological community and that trying to act on insights from such study could lead only to regulatory futility. Interaction of these constraints, external and internal, shielded the EPA by circumscribing its responsibilities and by impeding movement toward paradigmatic adjustment, but it also perpetuated scientifically dubious policies, such as those limiting the evaluation of commercial chemical formulations, including pesticide formulations, to only those ingredients said by their manufacturers to be active. In this context, regulators’ disregard of synergism contrasted irreconcilably with biocide manufacturers’ understanding that synergism enhanced lethality and patentability. In the end, an effective national response to mixture toxicity, cumulative risk, and environmental injustice did not emerge. In parallel, though, the National Institute of Environmental Health Sciences, which was less constrained, pursued with scientific investigation what the EPA had not pursued with regulatory action.

Catalyzing Knowledge-Driven Discovery in Environmental Health Sciences through a Community-Driven Harmonized Language

Harmonized language is critical for helping researchers to find data, collecting scientific data to facilitate comparison, and performing pooled and meta-analyses. Using standard terms to link data to knowledge systems facilitates knowledge-driven analysis, allows for the use of biomedical knowledge bases for scientific interpretation and hypothesis generation, and increasingly supports artificial intelligence (AI) and machine learning. Due to the breadth of environmental health sciences (EHS) research and the continuous evolution in scientific methods, the gaps in standard terminologies, vocabularies, ontologies, and related tools hamper the capabilities to address large-scale, complex EHS research questions that require the integration of disparate data and knowledge sources. The results of prior workshops to advance a harmonized environmental health language demonstrate that future efforts should be sustained and grounded in scientific need. We describe a community initiative whose mission was to advance integrative environmental health sciences research via the development and adoption of a harmonized language. The products, outcomes, and recommendations developed and endorsed by this community are expected to enhance data collection and management efforts for NIEHS and the EHS community, making data more findable and interoperable. This initiative will provide a community of practice space to exchange information and expertise, be a coordination hub for identifying and prioritizing activities, and a collaboration platform for the development and adoption of semantic solutions. We encourage anyone interested in advancing this mission to engage in this community.

Instructor Training on Opioids and the Workplace, Prevention and Response in the Plumbing and Pipe-Fitting Industry: An Interview With Cheryl Ambrose

Workers in the plumbing and pipe-fitting industry experience a wide variety of physical and emotional pain related to job hazards and lifestyle issues. Pain treatment and stress can lead to prescription or illicit substance use. The United Association of Journeymen and Apprentices of the Plumbing and Pipe-Fitting Industry of the United States and Canada has taken on these issues by adapting training developed by the National Institute of Environmental Health Sciences, Opioids and the Workplace, Prevention and Response Training. Under the leadership of Cheryl Ambrose, Health, Safety, and Environmental Administrator, the United Association of Journeymen and Apprentices of the Plumbing and Pipe-Fitting Industry of the United States and Canada has added an instructor training course and is tailoring the National Institute of Environmental Health Sciences curriculum to industry and union needs.

Opioids and the Workplace Prevention and Response Awareness Training: Mixed Methods Follow-Up Evaluation

The National Institute of Environmental Health Sciences Worker Training Program piloted an Opioids and the Workplace: Prevention and Response training tool and program in 2019. The pilot trainees ( N = 97) were surveyed ( n = 27) and interviewed ( n = 6) six months posttraining, and those who downloaded the training tool from the Worker Training Program website ( n = 87) were surveyed ( n = 19) and interviewed ( n = 1) two to six months postdownload, to evaluate the impact of the training program. Workplace policy and program-level actions were reported less frequently than individual-level actions by trainees, except for planning and conducting training and education. Barriers to taking actions included not being able to make changes on their own without supervisor support and lack of upper management support and approval. We found some evidence that the Opioids in the Workplace training program and materials contributed to helping workers introduce policies and programs related to opioids within their workplace or union.

Toxigenic Profile of Clostridium perfringens Strains Isolated from Natural Ingredient Laboratory Animal Diets

Clostridium perfringens is an anaerobic, gram-positive, spore-forming bacterium that ubiquitously inhabits a wide variety of natural environments including the gastrointestinal tract of humans and animals. C. perfringens is an opportunistic enteropathogen capable of producing at least 20 different toxins in various combinations. Strains of C. perfringens are currently categorized into seven toxinotypes (A, B, C, D, E, F & G) based on the presence/absence of four major toxins (alpha, beta, epsilon & iota) and two minor toxins (enterotoxin & netB). Each toxinotype is associated with specific histotoxic and enteric diseases. The Quality Assurance Laboratory (QAL) at the National Institute of Environmental Health Sciences (NIEHS) screens incoming animal feeds for aerobic, enteric pathogens, such as Salmonella spp. and E. coli. Recently, QAL has incorporated anaerobic screening of incoming animal feeds. To date, the lab has isolated numerous Clostridium species, including C. perfringens, from 23 lots of natural-ingredient laboratory animal diets.ImportancePublished reports of Clostridium perfringens isolation from laboratory animal feeds could not be found in the literature. Therefore, we performed a toxin profile screening of our isolated strains of C. perfringens to determine which toxinotypes were present in our laboratory animal diets. As studies progress with immunocompromised strains, gnotobiotic models, and animals with perturbed gut flora, the presence of C. perfringens could potentially lead to infection, disease and mortality which would substantiate the need to properly eliminate the bacterium and its spores from diets given to high risk animal populations.

A Biomedical Knowledge Graph System to Propose Mechanistic Hypotheses for Real-world Environmental Health Observations: Application (Preprint)

BACKGROUND Knowledge graphs are a common form of knowledge representation in biomedicine and many other fields. We developed an open biomedical knowledge graph–based system termed Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways, or ROBOKOP. ROBOKOP consists of both a front-end user interface and a back-end knowledge graph. The ROBOKOP user interface allows users to posit questions and explore answer subgraphs. Users can also posit questions through direct Cypher query of the underlying knowledge graph, which currently contains roughly 6M nodes or biomedical entities and 140M edges or predicates describing the relationship between nodes, drawn from >30 curated data sources. OBJECTIVE We aimed to apply ROBOKOP to survey data on workplace exposures and immune-medicated diseases from the Environmental Polymorphisms Registry (EPR) within the National Institute of Environmental Health Sciences. METHODS We analyzed EPR survey data focused on immune-mediated diseases and identified 45 associations between chemical workplace exposures and immune-mediated diseases, as self-reported by study participants (N = 4574), with 20 associations significant at P < .05 after a false discovery rate connection. We then used ROBOKOP to: (1) validate the associations by determining whether plausible connections exist within the ROBOKOP knowledge graph; and (2) propose biological mechanisms that might explain them and serve as hypotheses for subsequent testing. We highlight three exemplar associations: carbon monoxide – multiple sclerosis; ammonia – asthma; and isopropanol – allergic disease. RESULTS ROBOKOP successfully returned answer sets for three queries that were posed in the context of the driving examples. The answer sets included potential intermediary genes, as well as supporting evidence that might explain the observed associations. CONCLUSIONS We demonstrate a real-world application of ROBOKOP to generate mechanistic hypotheses for associations between chemical workplace exposure and immune-mediates diseases. We expect that ROBOKOP will find broad application across many biomedical fields and other scientific disciplines due to its generalizability, speed to discovery and generation of mechanistic hypotheses, and open nature.

Developing an Environmental Health Sciences COVID-19 Research Agenda: Results from the NIEHS Disaster Research Response (DR2) Work Group’s Modified Delphi Method

Leveraging the community of practice recently established through the U.S. National Institute of Environmental Health Sciences (NIEHS) Disaster Research Response (DR2) working group, we used a modified Delphi method to identify and prioritize environmental health sciences Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and associated Coronavirus Disease 2019 (COVID-19) research questions. Twenty-six individuals with broad expertise across a variety of environmental health sciences subdisciplines were selected to participate among 45 self-nominees. In Round 1, panelists submitted research questions and brief justifications. In Round 2, panelists rated the priority of each question on a nine-point Likert scale. Responses were trichotomized into priority categories (low priority; medium priority; and high priority). A research question was determined to meet consensus if at least 69.2% of panelists rated it within the same priority category. Research needs that did not meet consensus in round 2 were redistributed for re-rating. Fourteen questions met consensus as high priority in round 2, and an additional 14 questions met consensus as high priority in round 3. We discuss the impact and limitations of using this approach to identify and prioritize research questions in the context of a disaster response.

Modeled Air Pollution from In Situ Burning and Flaring of Oil and Gas Released Following the Deepwater Horizon Disaster

The GuLF STUDY, initiated by the National Institute of Environmental Health Sciences, is investigating the health effects among workers involved in the oil spill response and clean-up (OSRC) after the Deepwater Horizon (DWH) explosion in April 2010 in the Gulf of Mexico. Clean-up included in situ burning of oil on the water surface and flaring of gas and oil captured near the seabed and brought to the surface. We estimated emissions of PM2.5 and related pollutants resulting from these activities, as well as from engines of vessels working on the OSRC. PM2.5 emissions ranged from 30 to 1.33e6 kg per day and were generally uniform over time for the flares but highly episodic for the in situ burns. Hourly emissions from each source on every burn/flare day were used as inputs to the AERMOD model to develop average and maximum concentrations for 1-, 12-, and 24-h time periods. The highest predicted 24-h average concentrations sometimes exceeded 5000 µg m−3 in the first 500 m downwind of flaring and reached 71 µg m−3 within a kilometer of some in situ burns. Beyond 40 km from the DWH site, plumes appeared to be well mixed, and the predicted 24-h average concentrations from the flares and in situ burns were similar, usually below 10 µg m−3. Structured averaging of model output gave potential PM2.5 exposure estimates for OSRC workers located in various areas across the Gulf. Workers located nearest the wellhead (hot zone/source workers) were estimated to have a potential maximum 12-h exposure of 97 µg m−3 over the 2-month flaring period. The potential maximum 12-h exposure for workers who participated in in situ burns was estimated at 10 µg m−3 over the ~3-month burn period. The results suggest that burning of oil and gas during the DWH clean-up may have resulted in PM2.5 concentrations substantially above the U.S. National Ambient Air Quality Standard for PM2.5 (24-h average = 35 µg m−3). These results are being used to investigate possible adverse health effects in the GuLF STUDY epidemiologic analysis of PM2.5 exposures.