Consideration In Risk Assessment Research Articles

Polymorphisms rs4673 and rs28714259 as predictors of anthracycline-mediated cardiotoxicity in patients with breast cancer.

12005 Background: Numerous pharmacogenetic studies have led to the identification of genetic polymorphisms associated not only with the development of cardiovascular disease, but also increase the risk of complications due to the use of anthracycline drugs, widely used in the treatment of cancer. The purpose of this study was to study the frequency of rs4673 and rs28714259 and possible associations with the risk of cardiovascular changes in patients with breast cancer during anthracycline therapy (anthracycline-mediated cardiotoxicity — AMC). Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer without diagnosed cardiovascular changes, who were treated with anthracyclines at the National Medical Research Center of Oncology in 2019-2020. For genotyping of rs4673 and rs28714259, DNA was extracted from blood using DNA-sorb-B (AmpliSens, Russia) and HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphisms was confirmed by Sanger sequencing on a Genetic Analyzer 3500 (ABI, USA). Results: During the follow-up period 21 (8.2%) patients were diagnosed with signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic AMC (changes developed within a year after completion of anthracycline therapy). In the group of patients without AOC the allelic frequency of rs4673 (c.214T > C CYBA) was 0.38, the frequency of genotypes C/C – 0.4, C/T – 0.43, and T/T – 0.17. In the same group, the frequency of the A allele rs28714259 was 0.07, the frequency of the G/G genotypes – 0.87, G/A – 0.13, and A/A – 0. The prevalence of genotypes T/T rs4673 and allele G rs28714259 in a cohort of Russian patients differed from the European population (p = 0.014 and p = 0.05, respectively). The risk of cardiovascular changes on the background of anthracycline therapy increased in the presence of the rs4673 polymorphic allele by 6.49 times, in the case of the G/A and A/A rs28714259 genotypes - by 3.27 times. The results of the ROC-analysis suggested high quality of the tests based on the dominant models rs4673 and rs28714259 (AUC was 71.9% and 76.3% correspondingly). Conclusions: In this study the prognostic efficiency of the genetic markers rs4673 and rs28714259 was shown for the prompt detection of the risks of AMC development in the management of cancer patients. However, population characteristics should be taken into consideration for risk assessment.

Natural attenuation along subsurface flow paths based on modeling and monitoring of a pesticide metabolite from three case studies

BackgroundGroundwater—especially for the use as drinking water—is a strictly protected resource in the existing guidelines for pesticide registration and drinking water protection in the EU. One aspect that has hardly played a role in this context so far is the attenuation of pesticide concentrations along the flow path from the regulatory leaching concentration at a depth of 1 m below the applied field to raw water abstraction systems. The soil metabolite N,N-dimethylsulfamide (DMS) is formed from two fungicidal substances: tolylfluanid and dichlofluanid. According to the EU guidance document on relevant metabolites in groundwater, DMS is a “non-relevant” metabolite. However, long-term application of the two active substances on permanent crops has resulted in elevated and quantifiable amounts of DMS in groundwater catchment areas of water supplying plants. Therefore, in the case of DMS, substantial monitoring data is available. This enables in combination with groundwater modeling, a quantitative analysis of the natural attenuation of DMS concentrations over time and distance. To this end, extensive real-world data from three case studies of drinking water catchment areas in Germany were analyzed.ResultsThe environmental fate of DMS in soil and groundwater was evaluated according to the respective data determined at the study sites. Analyses using monitoring data and combined modeling approaches as well, were performed to obtain comparable results. These merged outcomes from monitoring and modeling show total attenuation factors of 12–93 from leachate at 1 m depth down to monitoring wells—close to raw water collection. If concentration attenuation further downwards to collected raw water is considered, the overall attenuation factor is even higher (40–246).ConclusionsThe conditions at the catchment areas of the three case studies are very diverse, thus providing a wide range of attenuating conditions. When following the path of DMS from its formation in soil below a treated field, to its leaching into the aquifer, and within the aquifer down to the raw water collection site, its concentration in water is continuously and consistently decreasing. The results from DMS represent conservative estimations due to non-sorptive, quick transport processes. Extended to other sorptive solutes, it represents the lower end of expected attenuation. Therefore, natural pesticide concentration attenuation processes are suggested for the consideration in regulatory pesticide risk assessments for a more realistic yet still protective evaluation of expected concentrations in raw water.

Consideration of risk assessment required for collaborative safety

Consideration of risk assessment required for collaborative safety

Bidirectional Association Between Knee Osteoarthritis and Depressive Symptoms: A Nationwide Cohort Study

Both knee osteoarthritis (KOA) and depressive symptoms are common health issues affecting the quality of life of old adults. Although it is presumed that KOA has a bidirectional relationship with the depressive symptoms, no cohort study has proven it. This is the first study to determine the strength of association for the bidirectional relationship between KOA and depressive symptoms. Data were gathered from the nationally survey of China Health and Retirement Longitudinal Study in 2011-2015. The presence of depressive symptoms was defined by the 10-item Center for Epidemiologic Studies Depression Scale score of 10 or higher. The adjusted Cox proportional hazards regression model was conducted to estimate hazards ratios (HRs). Controlled covariates include gender, age, education, marital status, residence, number of chronic diseases, and disability. The analysis of KOA predicting the depressive symptoms onset consisted of 4,377 participants free from depressive symptoms at baseline. During 4 years follow-up, diagnosed KOA participants were more likely to have depressive symptoms than their peers without KOA (HR = 1.50, 95% CI: 1.23-1.83). The parallel analysis of depressive symptoms predicting KOA onset included 6,848 participants without KOA at baseline, those with depressive symptoms had a higher relative risk of developing KOA (HR = 1.64, 95% CI: 1.41-1.92). Our results provide compelling evidence that the KOA-depressive symptoms association is bidirectional, highlighting the importance of evaluating the relationship between physical and mental health among older people. Particularly, taking this association into consideration in the risk assessment and primary prevention of KOA and depression symptoms.

Modeling Downward Counterfactual Events: Unrealized Disasters and why they Matter

Disaster risk research's reliance on past events has proved inadequate when it comes to extreme events. This shortcoming stems from limited records (for example, due to the vast differences in timescales between geological processes and human records) and the dynamic nature of all three components of risk -- drivers of change in hazard (e.g., climate change), exposure (e.g., urban growth), and vulnerability (e.g., aging infrastructure). This paper provides a framework for modeling key unrealized events through downward counterfactual changes for consideration in future risk modeling and assessment. Past disasters are typically viewed as fixed events, and the resulting lessons-learned are inherently limited by this definition; downward counterfactual thought provides a means to harvest additional insights and capture a larger consequence space. As such, we have identified a need for a guiding framework in order to incorporate downward counterfactual thought in the context of disaster risk modeling applied to both natural and anthropogenic hazards. The downward counterfactual framework relies first on identifying a past event, which may or may not have been considered a major disaster. After an event has been identified, historical parameters from the past event are relaxed in order to identify small changes that result in downward, worsening consequences. This can be continued for multiple changes until an end-of-search criteria is reached. The framework is especially relevant for regions that may have a sparse past catalog, either due to limited data or limited occurrences of natural hazards. As such, the framework is demonstrated in the context of Singapore, a city-nation that has historically had limited recorded natural hazards events, through five case studies on past anthropogenic, environmental, seismic, volcanic, and storm hazard events. This framework can help harness lessons-learned from unrealized disasters to support a more resilient future through informed policies and plans.

Target screening of plant secondary metabolites in river waters by liquid chromatography coupled to high-resolution mass spectrometry (LC\u2013HRMS)

BackgroundSubstantial efforts have been made to monitor potentially hazardous anthropogenic contaminants in surface waters while for plant secondary metabolites (PSMs) almost no data on occurrence in the water cycle are available. These metabolites enter river waters through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation and might add to the biological activity of the chemical mixture. To reduce this data gap, we conducted a LC–HRMS target screening in river waters from two different catchments for 150 plant metabolites which were selected from a larger database considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards.ResultsThe screening revealed the presence of 12 out of 150 possibly toxic PSMs including coumarins (bergapten, scopoletin, fraxidin, esculetin and psoralen), a flavonoid (formononetin) and alkaloids (lycorine and narciclasine). The compounds narciclasine and lycorine were detected at concentrations up to 3 µg/L while esculetin and fraxidin occurred at concentrations above 1 µg/L. Nine compounds occurred at concentrations above 0.1 µg/L, the Threshold for Toxicological Concern (TTC) for non-genotoxic and non-endocrine disrupting chemicals in drinking water.ConclusionsOur study provides an overview of potentially biologically active PSMs in surface waters and recommends their consideration in monitoring and risk assessment of water resources. This is currently hampered by a lack of effect data including toxicity to aquatic organisms, endocrine disruption and genotoxicity and demands for involvement of these compounds in biotesting.

Trust Based Approach and Risk Management for IT Systems in Cloud Service Selection

Cloud computing, which is amidst the new approaching fields of computers. There is a boom of this technology at present which can be easily seen as every organization outsource for most resources. As everyday life is known as, ranging from business applications to commercial functions, from students to professionals, the Cloud is giving uncountable advantages to users. Organizations often have concerns about the migration and utilization of cloud computing due to the loss of control over their outsourced resources, and cloud computing is vulnerable to risks. As per financial aspects, persons move to the cloud area because of their works, but security and privacy for data remain to be questionable. Hiding information related to trade and business bargains is utmost important as it might give a substantial profit or loss as the critical information may go too wrong hands. This paper focuses on the risk management frameworks for cloud computing and to the comparison between them to determine the strengths and weakness of each techniques. The proposed system deployed trust evaluation model in different conditions to reduce the complex evaluation procedures, while a substantial improvement recorded with the consideration of risk assessment.

Prevalence, elicitors, and expression of anger in 21st century mass shootings

As mass shootings increase in frequency, they continue to baffle public officials and the media who often portray such incidents as random and senseless acts of violence. Abundant evidence points to a co-occurrence or association of violence and anger; yet, anger is inadequately examined in mass shootings. This study was designed to determine the presence of anger in US mass shootings between 2000 and 2015, the elicitors of such anger, and aspects of the expression of such anger. The Stanford MSA database was accessed for information on these variables. A total of 132 cases were evaluated by two independent judges using a coding system for presence/absence of anger, elicitors of anger, and dimensions of anger expression. Kappa coefficients were computed to establish reliability of judgments. The Chi-square tested whether a statistically significant number of mass shootings evidenced anger. Clear presence of anger was identified in 70% of cases (p < .001) the majority of whom were demographically similar in age, sex, and race. Most common elicitors were abandonment/rejection (38%) and insults/affronts (34%) whereas the least common was physical assault (5%). In most cases, the anger expression was regarded as controlled (80%), externalizing (72%) and punitive (81%). Inter-judge reliability ranged from κ = 0.80–0.97. Findings indicate a high prevalence of anger in mass shootings and the predominantly psychological rather than physical provocation therein. The modal expression style does not suggest random and senseless acts but relatively controlled behavior intended to inflict serious harm in retaliation for perceived wrongdoing. These features of anger and demographics of mass shooters warrant consideration in risk assessment and treatment of this population.

A Section on Service Animals in the Microbiology Teaching Laboratory Has Been Included in the 2019 Update to the Guidelines for Biosafety in Teaching Laboratories

The accommodation of service animals in microbiology teaching labs has been included in the 2019 update to the American Society of Microbiology (ASM) Guidelines for Safety in Microbiology Laboratories. This commentary includes a legal framework related to service animals, the elements included in the 2019 ASM update, and additional risk-assessment considerations for the biosafety professional.

Summary of Discussions From the 2019 OECD Conference on RNAi Based Pesticides

RNA interference (RNAi) is a biological process in which double-stranded ribonucleic acid (dsRNA) molecules inhibit protein expression. In recent years, the application of dsRNA has been used in the development of agricultural products for pest control. The 2019 Organisation for Economic Cooperation and Development (OECD) Conference on RNAi Based Pesticides (“the Conference”) brought together academic, industry, and government experts in various aspects of RNAi to discuss the current state of knowledge and topics to help in developing considerations for risk assessment. The Conference focused on environment, with some discussion of human health. Along with presentations on the use of dsRNA-based products in agriculture, government regulation, risk assessment, and a background on the Draft OECD Working Paper on “Considerations for the Environmental Risk Assessment of the Application of Sprayed or Externally Applied dsRNA-Based Pesticides” (“OECD Working Paper”), the Conference included panel discussions from presenters at the end of each session and a larger discussion session with Conference participants on the environmental fate of dsRNA, non-target organism (NTO) risk assessment, and human health risk assessment. This paper summarizes input from presenters and Conference participants during these discussions. Key considerations from these discussions have already been incorporated into the OECD Working Paper, that once finalized and published, will facilitate regulators in evaluating externally applied dsRNA-based products for potential environmental risks.

Risk Assessment Considerations for Genetically Modified RNAi Plants: EFSA's Activities and Perspective.

Genetically modified plants (GMPs) intended for market release can be designed to induce “gene silencing” through RNA interference (RNAi). The European Food Safety Authority (EFSA) and other international risk assessment bodies/regulatory agencies have taken several actions to determine whether the existing risk assessment approaches for GMPs are appropriate for the risk assessment of RNAi-based GMPs or require complementary or alternative approaches. To our knowledge, at the international level, no dedicated guidelines have been developed for the risk assessment and regulation of RNAi-based GMPs, confirming that existing science-based risk assessment approaches for GMPs are generally considered suitable for RNAi-based GMPs. However, some specificities have been identified for the risk assessment of RNAi-based GMPs. Here, we report on some of these specificities as identified and addressed by the EFSA GMO Panel for the molecular characterisation, food/feed safety assessment and environmental risk assessment of RNAi-based GMPs, using the DvSnf7 dsRNA-expressing maize MON87411 as a case study.

Integrated fate assessment of aromatic amines in aerobic sewage treatment plants

The fate and exposure of chemicals in sewage treatment plants (STPs) are major considerations in risk assessment and environmental regulation. The biodegradability and removal of seven aromatic amines were systematically evaluated using a three-tiered integrated method: a standard ready biodegradability test, an aerobic sewage treatment simulation method, and model prediction. In tier 1, the seven aromatic amines were not readily biodegraded after 28 days. In adapted aerobic active sludge, 4-isopropyl aniline, 2,4-diaminotoluene, and 4-nitroaniline among them exhibited the degradation half-life time less than 20 h, the other four aromatic amines exhibited persistent with degradation half-life of > 60 h. In tier 2 of the aerobic sewage treatment simulation testing, 2,4-diaminotoluene, 4-nitroaniline, and 4-isopropylaniline demonstrated moderately to high overall removal. Hydraulic retention time (HRT) affects the removal with the optimum HRT was determined to be 12 h to 24. 2,6-Dimethyl aniline, 2-chloro-4-nitroaniline, 2,6-diethylaniline, and 3,4-dichloroaniline were not removed during the test, indicting these four aromatic amines will enter surface water and hence pose a potential risk to aquatic ecology. Considering the lack of an STP model in China for regulation purposes, in tier 3, we developed a Chinese STP (aerobic) (abbreviated as C-STP(O)) model that reflects a universal scenario for China to predict the fate. The predicted degradation, volatilization, and absorption showed a close relationship to the physicochemical properties of the chemicals, and had same tendency with tier 2 simulation test. The prediction showed that biodegradation rather than absorption or volatilization was the main removal process of aromatic amines in aerobic STP. With the combination of modified kinetics test with C-STP (O) model, the chemical fate can be more accurately predicted than using only the readily biodegradation result.

Degradation of Carbendazim in Soil: Effect of Sewage Sludge-Derived Biochars.

Application of biochar in soils can affect the soil properties and, in turn, the fate of pesticides. Batch experiments were conducted to investigate the effect of sewage sludge-derived biochars on the dissipation of a fungicide carbendazim in soil, and the transformation of carbendazim in soil was also studied. Results showed that the dissipation of carbendazim was fastest in a loamy soil SD with a half-life of 11.0 d among the three kinds of soils tested in this study. A dual effect (both acceleration and inhibition) of sewage sludge-derived biochars on carbendazim degradation in soil was reported. The addition of 10% biochars produced at 700 °C (BC 700) in soil could accelerate the carbendazim degradation, but an inhibitory effect was observed for 10% BC 300 or BC 500. Degradation of carbendazim was significantly inhibited when 0.5 or 5% BC 700 was added in soil but accelerated when the amendment ratio of BC 700 was increased to 10%. Such complex effects of the sewage sludge biochar should be taken into consideration in risk assessment of pesticides and the biochar effects on soil remediation. Eight metabolites of carbendazim were characterized, seven of which were reported in unamended soil for the first time. The metabolic pathways of carbendazim in soil are proposed.

Toxicity of pesticides in lizards.

Many threats exist to reptile populations, environmental pollutants being one of them. Lizards and other reptiles are usually not taken into consideration in environmental risk assessments, with the use of surrogate species for their estimates. Unfortunately, not all pesticides have the same effects in the reptile species and on these surrogates, birds and mammals, some being more toxic in lizards. This difference brings the need to evaluate their toxicity in lizards to safeguard its protection. Studies in the last decades involving contaminants' toxicity in lizard species have increased, thus we proposed to gather these information in this comprehensive review. Through searches in databases about the toxicity of pesticides in lizards, 16 scientific articles were found. Most studies investigated locomotor performance, histopathology, oxidative stress, neurotoxicology, and genetic damage from diverse pesticides with different modes of action. Progress has been made to acquire data on lizard ecotoxicology and more research is needed to cover more variables, such as studies in the embryologic stage and different pesticides.

Organoarsenicals in Seafood: Occurrence, Dietary Exposure, Toxicity, and Risk Assessment Considerations - A Review.

Diet, especially seafood, is the main source of arsenic exposure for humans. The total arsenic content of a diet offers inadequate information for assessment of the toxicological consequences of arsenic intake, which has impeded progress in the establishment of regulatory limits for arsenic in food. Toxicity assessments are mainly based on inorganic arsenic, a well-characterized carcinogen, and arsenobetaine, the main organoarsenical in seafood. Scarcity of toxicity data for organoarsenicals, and the predominance of arsenobetaine as an organic arsenic species in seafood, has led to the assumption of their nontoxicity. Recent toxicokinetic studies show that some organoarsenicals are bioaccessible and cytotoxic with demonstrated toxicities like that of pernicious trivalent inorganic arsenic, underpinning the need for speciation analysis. The need to investigate and compare the bioavailability, metabolic transformation, and elimination from the body of organoarsenicals to the well-established physiological consequences of inorganic arsenic and arsenobetaine exposure is apparent. This review provides an overview of the occurrence and assessment of human exposure to arsenic toxicity associated with the consumption of seafood.

Climate Risks and Financial Stability

Climate change has been recently recognised as a new source of risk for the financial system. Several financial supervisors with a financial stability mandate have recently recommended that investors and financial institutions need to assess their exposure to climate-related financial risks and conduct climate stress-tests. Nevertheless, they fall short of methodologies to do so. Indeed, the characteristics of climate risks (like deep uncertainty, non-linearities and endogeneity) challenge traditional approaches to macroeconomic and financial risk analysis. Embedding climate change in macroeconomic and financial analysis is fundamental for a comprehensive understanding of risks and opportunities in the era of the climate crisis. This Special Issue is devoted to the relations between climate risks and financial stability and represents the first comprehensive attempt to fill methodological gaps in this area and to shed light on the financial implications of climate change. It includes original contributions that use a range of methodologies, like network modelling, dynamic evolutionary macroeconomic modelling and financial econometrics, to analyse the impacts of climate-related financial risks, as well as of financial policies and instruments aiming at the low-carbon transition. The research insights of these contributions inform financial supervisors about the integration of climate change considerations in financial risk assessment.

FAMILY CAREGIVER CONTRIBUTIONS TO HOME HEALTH FOR OLDER ADULTS: PREDICTORS OF ADEQUATE SUPPORT

Family caregivers play a crucial role in supporting older adults through home health (HH) episodes; yet no prior research examines factors affecting the adequacy of caregiver support during HH. We use a novel dataset linking nationally-representative survey data with HH assessment data for community-dwelling older adults (n=2,128) to identify older adult characteristics associated with adequate caregiver support in four task categories (Activities of Daily Living, medication management, medical tasks, and safety/oversight) during a subsequent HH episode. Weighted, multivariable logistic regression is used to model the likelihood of adequate caregiver support in each category. Multiple older adult characteristics prior to the HH episode were associated with greater likelihood of adequate caregiver support during HH, including: prior caregiver assistance with mobility, self-care, and health care tasks, living with others, and cognitive impairment. These findings reveal new risk factors for consideration in risk assessment and payment adjustments related to social determinants of health.

Current risk assessment approaches for environmental and food and feed safety assessment.

Foundational activities at the international level underlie current risk and safety assessment approaches for genetically engineered/modified organisms (GEOs/GMOs). Early risk assessment considerations beginning with the OECD 'Blue Book' established risk/safety assessment as the characterization of the organism and its environmental release; establishment and persistence in the environment; and human and ecological effects, analyzed in principle through existing methods. Important in this context was recognition that GEOs/GMOs as a class did not represent new risks relative to products of traditional plant breeding and that any incremental risk would need to be established on a stepwise case-by-case comparative basis with existing crops and derived-foods as the baseline. Accordingly, concepts of familiarity and substantial equivalence were advanced by OECD and WHO as ways to establish a risk analysis baseline for determining whether and to what extent risk/safety assessment was needed. Regulatory implementations of this paradigm have skewed to increasingly complex portfolios of studies rather than adhering to analysis which is formulated to fit the risk/safety questions relevant to a given case. Plants produced through genome editing technology will benefit from risk analysis that implements sound problem formulation to guide the need for and nature of risk/safety assessments.

Thrombotic episodes in myeloproliferative neoplasms: A population based study.

e18554 Background: Myeloproliferative neoplasms (MPN) are complicated with high incidence of thrombotic episodes, often requiring chronic anticoagulation in high risk patients (pts). To improve our knowledge on risk stratification, we undertook a large population study on National Inpatient Sample (NIS) to investigate the demographic and health factors associated with venous thromboembolism (VTE) and acute coronary syndrome (ACS) in pts with MPN. Methods: In this retrospective cohort study using the most recent 2016 NIS, we included all pts with discharge diagnosis (dx) of MPN with or without current or prior dx of VTE and ACS using appropriate ICD-10 codes. Demographic and health characteristics were compared between groups. Multivariate logistic regression was done to compare length of stay and cost of care. STATA 13.0 was used for statistical analysis. Results: Among 162,435 pts with MPN, 3750 (2.3%) had VTE and 2820 (1.73%) had ACS. MPN pts with VTE had significantly higher age (mean 61.3 years) compared to those without VTE (mean 59.3 years). Smoking, obesity, and JAK2 mutation were significantly more common in MPN with VTE group. Pts with MPN and ACS were significantly older than those without ACS (67.85 vs. 59.2 years). These pts were mostly males and more likely to have hypertension, diabetes, smoking, dyslipidemia, obesity, and chronic kidney disease as comorbidities. Total hospital cost was significantly higher in MPN pts with VTE and ACS. Conclusions: In agreement with prior reports, age, smoking, and presence of JAK-2 mutation seem to be an important prognostic factors for both VTE and ACS in MPN. Other common comorbidities mandate critical consideration in assessment of thrombotic risk in MPN pts. [Table: see text]

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment.

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.