Accuracy of Trauma Surgeons Prospective Estimation of the Injury Severity Score: A Pilot Study.

Injury Severity Score (ISS) has limited utility as a prospective predictor of trauma outcomes as it is currently scored by abstractors post-discharge. This study aimed to determine accuracy of ISS estimation at time of admission. Attending trauma surgeons assessed the Abbreviated Injury Scale of each body region for patients admitted during their call, from which estimated ISS (eISS) was calculated. The eISS was considered concordant to abstracted ISS (aISS) if both were in the same category: mild (<9), moderate (9-15), severe (16-25), or critical (>25). Ten surgeons completed 132 surveys. Overall ISS concordance was 52.2%; 87.5%, 30.8%, 34.8%, and 61.7% for patients with mild, moderate, severe, and critical aISS, respectively; unweighted k = .36, weighted k = .69. This preliminarily supports attending trauma surgeons' ability to predict severity of injury in real time, which has important clinical and research implications.

Improving Statewide Post-Operative Sepsis Performance Measurement Using Hospital Risk Adjustment Within a Surgical Collaborative.

Background: The Georgia Quality Improvement Program (GQIP) surgical collaborative participating hospitals have shown consistently poor performance in the post-operative sepsis category of National Surgical Quality Improvement Program data as compared with national benchmarks. We aimed to compare crude versus risk-adjusted post-operative sepsis rankings to determine high and low performers amongst GQIP hospitals. Patients and Methods: The cohort included intra-abdominal general surgery patients across 10 collaborative hospitals from 2015 to 2020. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) sepsis definition was used among all hospitals for case abstraction and NSQIP data were utilized to train and validate a multivariable risk-adjustment model with post-operative sepsis as the outcome. This model was used to rank GQIP hospitals by risk-adjusted post-operative sepsis rates. Rankings between crude and risk-adjusted post-operative sepsis rankings were compared ordinally and for changes in tertile. Results: The study included 20,314 patients with 595 cases of post-operative sepsis. Crude 30-day post-operative sepsis risk among hospitals ranged from 0.81 to 5.11. When applying the risk-adjustment model which included: age, American Society of Anesthesiology class, case complexity, pre-operative pneumonia/urinary tract infection/surgical site infection, admission status, and wound class, nine of 10 hospitals were re-ranked and four hospitals changed performance tertiles. Conclusions: Inter-collaborative risk-adjusted post-operative sepsis rankings are important to present. These metrics benchmark collaborating hospitals, which facilitates best practice exchange from high to low performers.

Epidemiology and Post-Discharge Resource Utilization of Isolated Traumatic Brain Injury in Geriatric Patients.

Benchmark data on traumatic brain injury (TBI) are potentially confounded by morbidity and rehabilitation needs associated with coincident extracranial injuries. Using data on isolated head injuries from 13 trauma centers in Georgia over 3 years, we studied the epidemiology and natural history of isolated TBI in geriatric vs non-geriatric patients in order to identify potential areas for quality improvement. We identified 8 512 patients, 3 895 of whom were geriatric. Geriatric patients had higher baseline comorbidity burden, mostly presented after ground level falls, had higher mortality despite equivalent ICU admission rates, and had higher rates of post-discharge resource utilization than non-geriatric counterparts. Geriatric patients are more likely to require post-discharge services and/or facility placement, regardless of pre-injury functional status. These data highlight the importance of streamlined protocols that place an early focus on post-discharge needs and goals of care, informed by cohort-specific prognosis data.

A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a "safe" or "no-risk" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Advancing the science on chemical classes.

BACKGROUND: Hazard identification, risk assessment, regulatory, and policy activity are usually conducted on a chemical-by-chemical basis. Grouping chemicals into categories or classes is an underutilized approach that could make risk assessment and management of chemicals more efficient for regulators. OBJECTIVE AND METHODS: While there are some available methods and regulatory frameworks that include the grouping of chemicals (e.g.,same molecular mechanism or similar chemical structure) there has not been a comprehensive evaluation of these different approaches nor a recommended course of action to better consider chemical classes in decision-making. This manuscript: 1) reviews current national and international approaches to grouping; 2) describes how groups could be defined based on the decision context (e.g., hazard/risk assessment, restrictions, prioritization, product development) and scientific considerations (e.g., intrinsic physical-chemical properties); 3) discusses advantages of developing a decision tree approach for grouping; 4) uses ortho-phthalates as a case study to identify and organize frameworks that could be used across agencies; and 5) discusses opportunities to advance the class concept within various regulatory decision-making scenarios. RESULTS: Structural similarity was the most common grouping approach for risk assessment among regulatory agencies (national and state level) and non-regulatory organizations, albeit with some variations in its definition. Toxicity to the same target organ or to the same biological function was also used in a few cases. The phthalates case study showed that a decision tree approach for grouping should include questions about uses regulated by other agencies to encourage more efficient, coherent, and protective chemical risk management. DISCUSSION AND CONCLUSION: Our evaluation of how classes of chemicals are defined and used identified commonalities and differences based on regulatory frameworks, risk assessments, and business strategies. We also identified that using a class-based approach could result in a more efficient process to reduce exposures to multiple hazardous chemicals and, ultimately, reduce health risks. We concluded that, in the absence of a prescribed method, a decision tree approach could facilitate the selection of chemicals belonging to a pre-defined class (e.g., chemicals with endocrine-disrupting activity; organohalogen flame retardants [OFR]) based on the decision-making context (e.g., regulatory risk management).

Depression, anxiety, and burnout among hospital workers during the COVID-19 pandemic: A cross-sectional study.

OBJECTIVES: Healthcare personnel have faced unprecedented mental health challenges during the COVID-19 pandemic. The study objective is to assess differences in depression, anxiety, and burnout among healthcare personnel with various occupational roles and whether financial and job strain were associated with these mental health outcomes. METHODS: We employed an anonymous survey between July and August 2020 at an urban county hospital in California, USA. We assessed depression, anxiety, and burnout using validated scales, and asked questions on financial strain and job strain. We performed logistic and linear regression analyses. RESULTS: Nurses (aOR 1.93, 95% CIs 1.12, 3.46), social workers (aOR 2.61, 95% CIs 1.35, 5.17), service workers (aOR 2.55, 95% CIs 1.20, 5.48), and administrative workers (aOR 2.93, 95% CIs 1.57, 5.61) were more likely than physicians to screen positive for depression. The odds of screening positive for anxiety were significantly lower for ancillary workers (aOR 0.32, 95% CIs 0.13-0.72) compared with physicians. Ancillary (aB = -1.77, 95% CIs -1.88, -0.47) and laboratory and pharmacy workers (aB -0.70, 95% CI -1.34, -0.06) reported lower levels of burnout compared with physicians. Financial strain partially accounted for differences in mental health outcomes across job categories. Lack of time to complete tasks and lack of supervisory support were associated with higher odds of screening positive for depression. Less job autonomy was associated with higher odds of screening positive for anxiety and higher burnout levels. CONCLUSIONS: We found significant disparities in mental health outcomes across occupational roles. Policies to mitigate the adverse impact of COVID-19 on health workers' mental health should include non-clinical staff and address financial support and job characteristics for all occupational roles.

Tracking Environmental and Health Disparities to Strengthen Resilience Before the Next Crisis.

The COVID-19 pandemic has underscored how underlying disparities in environmental and health conditions exacerbate vulnerability during public health emergencies in low-income and communities of color. Neglected epidemics-high rates of pollution, chronic disease, and racial and socioeconomic health disparities-have continued amid persistent systemic racism and declining investment in public health. Recognized too late due to shortcomings in public health data tracking, COVID-19 has surged through vulnerable communities. Improved public health tracking is critical for informing the country's recovery from COVID-19, and it can be leveraged to measure and reduce health disparities and strengthen community resilience to respond more effectively to the next public health crisis. We emphasize how public health tracking agencies can engage communities in data collection and reporting; we also discuss the complementary role that communities can take to mobilize data to change policies and institutions, strengthening resilience through increased information and capacity driven by community priorities. Success requires the continuous collection of timely data at a community scale, and public health agencies partnering with communities to use the information in decision making and evaluation to ensure progress over time. We highlight community-engaged data collection and reporting-community air monitoring in Imperial County, CA-as an example of working with communities to improve public health data collection and reporting, increase community dialogue and engagement in governmental decision making, and inform public health tracking to reduce health disparities and strengthen community resilience.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

Organic Chemical Contaminants in Water System Infrastructure Following Wildfire.

Wildfires have destroyed multiple residential communities in California in recent years. After fires in 2017 and 2018, high concentrations of benzene and other volatile organic compounds (VOCs) were found in public drinking water systems in fire-affected areas. The sources of the contamination and appropriate remediation have been urgent matters for investigation. This study characterizes target and non-target VOCs and semi volatile organic compounds (SVOCs) in water from a highly contaminated service line after the 2018 Camp Fire (Paradise, CA). Ninety-five organic compounds were identified or tentatively identified in the service line. Laboratory combustion experiments with drinking water pipes made of polyvinyl chloride (PVC), cross-linked polyethylene (PEX) and high-density polyethylene (HDPE) and a review of the literature were used to evaluate potential sources of the detected chemicals. Among the service line contaminants were thirty-two compounds associated with PVC pyrolysis and twenty-eight organic compounds also associated with the pyrolysis of polyethylene. The service line sample also contained fifty-five compounds associated with uncontrolled burning of biomass and waste materials. The findings support hypotheses that wildfires can contaminate drinking water systems both by thermal damage to plastic pipes and intrusion of smoke. Residual chlorine disinfectant in the water system modifies the contaminant distribution observed.

Georgia Quality Improvement Programs Multi-Institutional Collection of Postoperative Opioid Data Using ACS-NSQIP Abstraction.

BACKGROUND: Excessive postoperative opioid prescribing contributes to opioid misuse throughout the US. The Georgia Quality Improvement Program (GQIP) is a collaboration of ACS-NSQIP participating hospitals. GQIP aimed to develop a multi-institutional opioid data collection platform as well as understand our current opioid-sparing strategy (OSS) usage and postoperative opioid prescribing patterns. METHODS: This study was initiated 7/2019, when 4 custom NSQIP variables were developed to capture OSS usage and postoperative opioid oral morphine equivalents (OMEs). After pilot collection, our discharge opioid variable required optimization for adequate data capture and was expanded from a free text option to 4 drop-down selection variables. Data collection then continued from 2/2020-5/2021. Logistic regression was used to determine associations with OSS usage. Average OMEs were calculated for common general surgery procedures and compared to national guidelines. RESULTS: After variable optimization, the percentage where a total discharge prescription OME could be calculated increased from 26% to 70% (P < .001). The study included 820 patients over 10 operations. There was a significant variation in OSS usage between GQIP centers. Laparoscopic cases had higher odds of OSS use (1.92 (1.38-2.66)) while OSS use had lower odds in black patients on univariate analysis (.69 (.51-.94)). On average 7 out of the 10 cases had higher OMEs prescribed compared to national guidelines recommendations. CONCLUSION: Developing a multi-institutional opioid data collection platform through ACS-NSQIP is feasible. Preselected drop-down boxes outperform free text variables. GQIP future quality improvement targets include variation in OSS use and opioid overprescribing.

The Interplay of Environmental Exposures and Mental Health: Setting an Agenda.

BACKGROUND: To date, health-effects research on environmental stressors has rarely focused on behavioral and mental health outcomes. That lack of research is beginning to change. Science and policy experts in the environmental and behavioral health sciences are coming together to explore converging evidence on the relationship-harmful or beneficial-between environmental factors and mental health. OBJECTIVES: To organize evidence and catalyze new findings, the National Academy of Sciences, Engineering, and Medicine (NASEM) hosted a workshop 2-3 February 2021 on the interplay of environmental exposures and mental health outcomes. METHODS: This commentary provides a nonsystematic, expert-guided conceptual review and interdisciplinary perspective on the convergence of environmental and mental health, drawing from hypotheses, findings, and research gaps presented and discussed at the workshop. Featured is an overview of what is known about the intersection of the environment and mental health, focusing on the effects of neurotoxic pollutants, threats related to climate change, and the importance of health promoting environments, such as urban green spaces. DISCUSSION: We describe what can be gained by bridging environmental and psychological research disciplines and present a synthesis of what is needed to advance interdisciplinary investigations. We also consider the implications of the current evidence for a) foundational knowledge of the etiology of mental health and illness, b) toxicant policy and regulation, c) definitions of climate adaptation and community resilience, d) interventions targeting marginalized communities, and e) the future of research training and funding. We include a call to action for environmental and mental health researchers, focusing on the environmental contributions to mental health to unlock primary prevention strategies at the population level and open equitable paths for preventing mental disorders and achieving optimal mental health for all. https://doi.org/10.1289/EHP9889.

Returning Individual Tap Water Testing Results to Research Study Participants after a Wildfire Disaster.

After the devastating wildfire that destroyed most of the town of Paradise, California in 2018, volatile organic compounds were found in water distribution pipes. Approximately 11 months after the fire, we collected tap water samples from 136 homes that were still standing and tested for over 100 chemicals. Each participant received a customized report showing the laboratory findings from their sample. Our goal was to communicate individual water results and chemical information rapidly in a way that was understandable, scientifically accurate, and useful to participants. On the basis of this process, we developed a framework to illustrate considerations and priorities that draw from best practices of previous environmental results return research and crisis communication, while also addressing challenges specific to the disaster context. We also conducted a follow-up survey on participants' perceptions of the results return process. In general, participants found the results return communications to be understandable, and they felt less worried about their drinking water quality after receiving the information. Over one-third of the participants reported taking some kind of action around their water usage habits after receiving their results. Communication with participants is a critical element of environmental disaster research, and it is important to have a strategy to communicate results that achieves the goals of timeliness, clarity, and scientific accuracy, ultimately empowering people toward actions that can reduce exposure.

Fire and Water: Assessing Drinking Water Contamination After a Major Wildfire.

We investigated patterns of volatile organic compound (VOC) contamination in drinking water systems affected by the California 2018 Camp Fire. We performed spatial analysis of over 5000 water samples collected over a 17 month period by a local water utility, sampled tap water for VOCs in approximately 10% (N = 136) of standing homes, and conducted additional nontargeted chemical analysis of 10 samples. Benzene contamination was present in 29% of service connections to destroyed structures and 2% of service connections to standing homes. A spatial pattern was apparent. Tap water in standing homes 11 months after the fire contained low concentrations of benzene in 1% of samples, but methylene chloride was present in 19% of samples, including several above regulatory limits. Elevated methylene chloride was associated with greater distance from the water meter to the tap, longer stagnation time, and the presence of a destroyed structure on the service connection; it was inversely associated with certain trihalomethanes. Nontargeted analysis identified multiple combustion byproducts in the water at 2/10 homes. Our findings support the hypothesis that pyrolysis and smoke intrusion from depressurization contributed to the benzene contamination. Further research is needed to test the hypothesis that methylene chloride may be generated from the dehalogenation of disinfection byproducts stagnating in galvanized iron pipes.

New Toxicology Tools and the Emerging Paradigm Shift in Environmental Health Decision-Making.

BACKGROUND: Numerous types of rapid toxicity or exposure assays and platforms are providing information relevant to human hazard and exposure identification. They offer the promise of aiding decision-making in a variety of contexts including the regulatory management of chemicals, evaluation of products and environmental media, and emergency response. There is a need to consider both the scientific validity of the new methods and the values applied to a given decision using this new information to ensure that the new methods are employed in ways that enhance public health and environmental protection. In 2018, a National Academies of Sciences, Engineering, and Medicine (NASEM) workshop examined both the toxicological and societal aspects of this challenge. OBJECTIVES: Our objectives were to explore the challenges of adopting new data streams into regulatory decision-making and highlight the need to align new methods with the information and confidence needs of the decision contexts in which the data may be applied. METHODS: We go beyond the NASEM workshop to further explore the requirements of different decision contexts. We also call for the new methods to be applied in a manner consistent with the core values of public health and environmental protection. We use the case examples presented in the NASEM workshop to illustrate a range of decision contexts that have applied or could benefit from these new data streams. Organizers of the NASEM workshop came together to further evaluate the main themes from the workshop and develop a joint assessment of the critical needs for improved use of emerging toxicology tools in decision-making. We have drawn from our own experience and individual decision or research contexts as well as from the case studies and panel discussions from the workshop to inform our assessment. DISCUSSION: Many of the statutes that regulate chemicals in the environment place a high priority on the protection of public health and the environment. Moving away from the sole reliance on traditional approaches and information sources used in hazard, exposure, and risk assessment, toward the more expansive use of rapidly acquired chemical information via in vitro, in silico, and targeted testing strategies will require careful consideration of the information needed and values considerations associated with a particular decision. In this commentary, we explore the ability and feasibility of using emerging data streams, particularly those that allow for the rapid testing of a large number of chemicals across numerous biological targets, to shift the chemical testing paradigm to one in which potentially harmful chemicals are more rapidly identified, prioritized, and addressed. Such a paradigm shift could ultimately save financial and natural resources while ensuring and preserving the protection of public health. https://doi.org/10.1289/EHP4745.

Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.

BACKGROUND: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. OBJECTIVE: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. METHODS: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell­cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.

How much green does it take to be orange? Determining the cost associated with trauma center readiness.

BACKGROUND: Readiness costs are real expenses incurred by trauma centers to maintain essential infrastructure to provide emergent services on a 24/7 basis. Although the components for readiness are well described in the American College of Surgeons' Resources for Optimal Care of the Injured Patient, the cost associated with each component is not well defined. We hypothesized that meeting the requirements of the 2014 Resources for Optimal Care of the Injured Patient would result in significant costs for trauma centers. METHODS: The state trauma commission in conjunction with trauma medical directors, program managers, and financial officers of each trauma center standardized definitions for each component of trauma center readiness cost and developed a survey tool for reporting. Readiness costs were grouped into four categories: administrative/program support staff, clinical medical staff, in-house operating room, and education/outreach. To verify consistent cost reporting, a financial auditor analyzed all data. Trauma center outliers were further evaluated to validate variances. All level I/level II trauma centers (n = 16) completed the survey on 2016 data. RESULTS: Average annual readiness cost is US $10,078,506 for a level I trauma center and US $4,925,103 for level IIs. Clinical medical staff was the costliest component representing 55% of costs for level Is and 64% for level IIs. Although education/outreach is mandated, levels I and II trauma centers only spend approximately US $100,000 annually on this category (1%-2%), demonstrating a lack of resources. CONCLUSION: This study defines the cost associated with each component of readiness as defined in the Resources for Optimal Care of the Injured Patient manual. Average readiness cost for a level I trauma center is US $10,078,506 and US $4,925,103 for a level II. The significant cost of trauma center readiness highlights the need for additional trauma center funding to meet the requirements set forth by the American College of Surgeons. LEVEL OF EVIDENCE: Economic and value-based evaluations, level III.

An Integrated Approach Using Publicly Available Resources for Identifying and Characterizing Chemicals of Potential Toxicity Concern: Proof-of-Concept With Chemicals That Affect Cancer Pathways.

We developed an integrated, modular approach to predicting chemical toxicity relying on in vitro assay data, linkage of molecular targets to disease categories, and software for ranking chemical activity and examining structural features (chemotypes). We evaluate our approach in a proof-of-concept exercise to identify and prioritize chemicals of potential carcinogenicity concern. We identified 137 cancer pathway-related assays from a subset of U.S. EPA's ToxCast platforms. We mapped these assays to key characteristics of carcinogens and found they collectively assess 5 of 10 characteristics. We ranked all 1061 chemicals screened in Phases I and II of ToxCast by their activity in the selected cancer pathway-related assays using Toxicological Prioritization Index software. More chemicals used as biologically active agents (eg, pharmaceuticals) ranked in the upper 50% versus lower 50%. Twenty-three chemotypes are enriched in the top 5% (n = 54) of chemicals; these features may be important for their activity in cancer pathway-related assays. The biological coverage of the ToxCast assays related to cancer pathways is limited and short-term assays may not capture the biology of some key characteristics. Metabolism is also minimal in the assays. The ability of our approach to identify chemicals with cancer hazard is limited with the current input data, but we expect that our approach can be applied with future iterations of ToxCast and other data for improved chemical prioritization and characterization. The novel approach and proof-of-concept exercise described here for ranking chemicals for potential carcinogenicity concern is modular, adaptable, and amenable to evolving data streams.