Enhancing the chemical mixture methodology in emergency preparedness and consequence assessment analysis

Yu, Xiao‐Ying; Glantz, C.S.; Yao, Juan; He, Hua; Petrocchi, Achille J.; Craig, D.K.; Ciolek, John T.; Booth, Alexander E.

doi:10.1016/j.tox.2012.10.011

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…A similar strategy to develop segregated HI for emergency preparedness has been developed (Yu et al , ). Yu and colleagues used health code numbers (HCN) to prescribe adverse effects to target organs that could then be summed; the approach was termed “chemical mixture methodology” (CMM).…”

Section: Discussionmentioning

confidence: 99%

Implementation of the basic hazard index screening for health risks associated with simultaneous exposure to multiple chemicals using a standardized target organ and systems framework

Adams

McAtee

Johnson

2017

Integr Envir Assess & Manag

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Environmental health risk assessments often involve assessing the potential health effects of exposure to multiple chemicals at once (i.e., complex mixtures). Because the possible number of chemical combinations is very large, few controlled in vivo toxicological studies with chemical mixtures are relevant or practical. In lieu of specific mixture toxicity data, the segregated hazard index (HI) approach has been used to determine whether simultaneous exposures may warrant further investigation due to their combined adverse effects. Each chemical is assigned to one or more target organs based on critical effects; HIs for each target organ are generated by summing the individual hazard quotients for each of the chemicals assigned to that organ or organ system. To conduct this phased risk assessment approach in a consistent manner, a comprehensive, systematized list of toxicity targets for implementing this approach is needed. We present a comprehensive and standardized list of toxicity target organs and systems (TTOS), with example data sets, for consistent implementation of the segregated HI method. This method is designed to facilitate the standardization of the widespread use of the basic segregated HI approach. The basic hazard index mixtures screening (BHIMS) tool allows for rapid identification of exposure concerns that may warrant further and more sophisticated assessment. Integr Environ Assess Manag 2017;13:852-860. Published 2017. This article is a US Government work and is in the public domain in the USA.

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Section: Discussionmentioning

confidence: 99%

Implementation of the basic hazard index screening for health risks associated with simultaneous exposure to multiple chemicals using a standardized target organ and systems framework

Adams

McAtee

Johnson

2017

Integr Envir Assess & Manag

View full text Add to dashboard Cite

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“…The findings that the expression of CYP4A/4F enzymes are elevated in human thyroid, ovarian, breast, and colon cancers (211), pancreatic adenocarcinoma (212) further support that 20-HETE may play a role in vascularization and growth of cancerous tumors. More recent studies indicate that inhibition of the synthesis of 20-HETE are effective in reducing the growth of glioblastoma, lung, prostate, renal, breast and colon cancer in experimental animals (206,(213)(214)(215)(216)(217).…”

Section: -Hete and Angiogenesismentioning

confidence: 99%

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology

Fan

et al. 2016

Front Biosci

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Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K + channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

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Mixtures Risk Assessment: Available Methods and Future Directions

et al. 2023

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Humans are simultaneously or sequentially exposed to many chemicals throughout their life, intentionally or unintentionally. These could include pesticides, pharmaceuticals, household products, and food additives. Individual control over exposure varies across personal, occupational, and environmental chemical exposure pathways. Personal lifestyle exposures such as firsthand tobacco smoke or alcohol are voluntary. Occupational exposure is “voluntary,” but the individual generally has less control over these exposures. On the other hand, individuals usually have few options for controlling environmental exposures under ordinary circumstances.

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Enhancing the chemical mixture methodology in emergency preparedness and consequence assessment analysis

Cited by 5 publications

References 9 publications

Implementation of the basic hazard index screening for health risks associated with simultaneous exposure to multiple chemicals using a standardized target organ and systems framework

Implementation of the basic hazard index screening for health risks associated with simultaneous exposure to multiple chemicals using a standardized target organ and systems framework

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology

Mixtures Risk Assessment: Available Methods and Future Directions

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