Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups

Chiu, Weihsueh A.; Guyton, Kathryn Z.; Martin, Matthew T.; Reif, David M.; Rusyn, Ivan

doi:10.14573/altex.1703231

Cited by 66 publications

(52 citation statements)

References 38 publications

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“…When the evidence from human epidemiologic studies is less than sufficient, strong mechanistic data can play a pivotal role in the overall carcinogen hazard classification ( 10 , 11 ). For instance, even though the evidence from rodent cancer bioassays provided ‘sufficient’ evidence of cancer in animals, d -limonene was classified in Group 3 (not classifiable as to its carcinogenicity to humans) on the basis of mechanistic and other relevant data because the probable mechanism of carcinogenicity in animals was unlikely to be operative in humans ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Application of the key characteristics of carcinogens in cancer hazard identification

et al. 2018

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Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.

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Section: Introductionmentioning

confidence: 99%

Application of the key characteristics of carcinogens in cancer hazard identification

et al. 2018

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“…Analysis of PFOA activity in high-throughput screening assays from the ToxCast and Tox21 programs identified that PFOA induced activity in four different estrogen receptor assays, seven peroxisome proliferator activated receptors (PPAR) and retinoid X receptor assays, one androgen receptor assay, as well as several metabolic enzyme assays [176]. PFNA, PFOS and PFHxS also activated PPARγ and estrogen receptor alpha in ToxCast assays and modulated expression of estrogen receptor-related transcriptional profiles in livers from mice exposed to these PFAS [177].…”

Section: Modulates Receptor-mediated Effectsmentioning

confidence: 99%

“…Animal Biosassay In Vitro PFOA Association: [153]; [154]; [155]; [156]; [157] Association: reviewed in [164]; [91]; [165]; [166]; [169]; [170]; [173]; [175]; [191]; [61] No association: [174] Association: [176]; [158]; [175]; [181]; [188]; [189]; [193]; [179]; [180] No association: [182] Long-chain PFAS a PFOS Association: [154]; [155]; [156]; [157]; [160]; reviwed in [163] No Association: [153] Association: [191]; [192] Association: [177]; [175]; [181]; [188]; [189]; [193]; [179]; [180] No association: [182] PFHxS Association: [159]; reviwed in [163] No association: [...…”

Section: Epidemiologicalmentioning

confidence: 99%

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

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Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

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“…In order to address the needs for prioritization of overall burden across communities as well as for prioritization of intervention opportunities within communities simultaneously, we adapted the Toxicological Prioritization Index (ToxPi) approach to integrate the multiple data streams incorporated into HGBEnviroScreen [9,10]. ToxPi is a visual, decision-support tool that has been used to communicate risk prioritization and profiling information between scientists, regulators, stakeholders, and the general public [11][12][13]. The overall ToxPi score and accompanying graphical profile simultaneously provide both a relative ranking in terms of overall vulnerability as well as an indicator of the specific drivers of increased vulnerability.…”

Section: Introductionmentioning

confidence: 99%

HGBEnviroScreen: Enabling Community Action through Data Integration in the Houston–Galveston–Brazoria Region

Bhandari

Lewis

Craft

et al. 2020

IJERPH

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The Houston-Galveston-Brazoria (HGB) region faces numerous environmental and public health challenges from both natural disasters and industrial activity, but the historically disadvantaged communities most often impacted by such risks have limited ability to access and utilize big data for advocacy efforts. We developed HGBEnviroScreen to identify and prioritize regions of heightened vulnerability, in part to assist communities in understanding risk factors and developing environmental justice action plans. While similar in objectives to existing environmental justice tools, HGBEnviroScreen is unique in its ability to integrate and visualize national and local data to address regional concerns. For the 1090 census tracts in the HGB region, we accrued data into five domains: (i) social vulnerability, (ii) baseline health, (iii) environmental exposures and risks, (iv) environmental sources, and (v) flooding. We then integrated and visualized these data using the Toxicological Prioritization Index (ToxPi). We found that the highest vulnerability census tracts have multifactorial risk factors, with common drivers being flooding, social vulnerability, and proximity to environmental sources. Thus, HGBEnviroScreen is not only helping identify communities of greatest overall vulnerability but is also providing insights into which domains would most benefit from improved planning, policy, and action in order to reduce future vulnerability.

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Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups

Cited by 66 publications

References 38 publications

Application of the key characteristics of carcinogens in cancer hazard identification

Application of the key characteristics of carcinogens in cancer hazard identification

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

HGBEnviroScreen: Enabling Community Action through Data Integration in the Houston–Galveston–Brazoria Region

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