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).

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.

Cumulative Environmental Impacts: Science and Policy to Protect Communities.

Many communities are located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations. Populations in such locations are predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Environmental exposures may interact with social stressors, thereby worsening health outcomes. Age, genetic characteristics, and preexisting health conditions increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative exposures, cumulative risks, and cumulative health impacts. Although such approaches have merit, they also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and epidemiology, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve decision making.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Toxicity testing in the 21st century: a vision and a strategy.

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

Arsenic contamination in New Orleans soil: temporal changes associated with flooding.

The flooding of New Orleans in late August and September 2005 caused widespread sediment deposition in the flooded areas of the city. Post-flood sampling by US EPA revealed that 37% of sediment samples exceeded Louisiana corrective screening guidelines for arsenic of 12mg/kg, but there was debate over whether this contamination was pre-existing, as almost no pre-flood soil sampling for arsenic had been done in New Orleans. In this study, archived soil samples collected in 1998-1999 were location-matched with 70 residential sites in New Orleans where post-flood arsenic concentrations were elevated. Those same locations were sampled again during the recovery period 18 months later. During the recovery period, sampling for arsenic was also done for the first time at school sites and playgrounds within the flooded zone. Every sample of sediment taken 1-10 months after the flood exceeded the arsenic concentration found in the matched pre-flood soils. The average difference between the two sampling periods was 19.67mg/kg (95% CI 16.63-22.71) with a range of 3.60-74.61mg/kg. At virtually all of these sites (97%), arsenic concentrations decreased substantially by 18 months into the recovery period when the average concentration of matched samples was 3.26mg/kg (95% CI 1.86-4.66). However, 21 (30%) of the samples taken during the recovery period still had higher concentrations of arsenic than the matched sample taken prior to the flooding. In addition, 33% of samples from schoolyards and 13% of samples from playgrounds had elevated arsenic concentrations above the screening guidelines during the recovery period. These findings suggest that the flooding resulted in the deposition of arsenic-contaminated sediments. Diminution of the quantity of sediment at many locations has significantly reduced overall soil arsenic concentrations, but some locations remain of concern for potential long-term soil contamination.

The 2006 California heat wave: impacts on hospitalizations and emergency department visits.

BACKGROUND: Climate models project that heat waves will increase in frequency and severity. Despite many studies of mortality from heat waves, few studies have examined morbidity. OBJECTIVES: In this study we investigated whether any age or race/ethnicity groups experienced increased hospitalizations and emergency department (ED) visits overall or for selected illnesses during the 2006 California heat wave. METHODS: We aggregated county-level hospitalizations and ED visits for all causes and for 10 cause groups into six geographic regions of California. We calculated excess morbidity and rate ratios (RRs) during the heat wave (15 July to 1 August 2006) and compared these data with those of a reference period (8-14 July and 12-22 August 2006). RESULTS: During the heat wave, 16,166 excess ED visits and 1,182 excess hospitalizations occurred statewide. ED visits for heat-related causes increased across the state [RR = 6.30; 95% confidence interval (CI), 5.67-7.01], especially in the Central Coast region, which includes San Francisco. Children (0-4 years of age) and the elderly (> or = 65 years of age) were at greatest risk. ED visits also showed significant increases for acute renal failure, cardiovascular diseases, diabetes, electrolyte imbalance, and nephritis. We observed significantly elevated RRs for hospitalizations for heat-related illnesses (RR = 10.15; 95% CI, 7.79-13.43), acute renal failure, electrolyte imbalance, and nephritis. CONCLUSIONS: The 2006 California heat wave had a substantial effect on morbidity, including regions with relatively modest temperatures. This suggests that population acclimatization and adaptive capacity influenced risk. By better understanding these impacts and population vulnerabilities, local communities can improve heat wave preparedness to cope with a globally warming future.

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.