Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.

Vogel, John S.; Keating, nd Garrett A; Buchholz, Bruce A.

doi:10.1289/ehp.02110s61031

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…Long-term retention of a compound arises from specific binding (26), lipid association (27), enterohepatic recirculation (24), or cellular uptake (28). This retention represents a neutral incorporation, an indicator of continued therapeutic effect, or a potential toxicity that requires further investigation.…”

Section: Ams For Absorption Distribution Metabolism and Excretion mentioning

confidence: 99%

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Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Vogel¹

2005

BioTechniques

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66Manuscript: 2910 AbstractAccelerator mass spectrometry (AMS) counts individual rare, usually radio-, isotopes such as radiocarbon at high efficiency and specificity in milligram-sized samples. AMS traces very low chemical doses (µg) and radiative doses (100 Bq) of isotope labeled compounds in animal models and directly in humans for pharmaceutical, nutritional, or toxicological research.Absorption, metabolism, distribution, binding, and elimination are all quantifiable with high precision after appropriate sample definition.

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Section: Ams For Absorption Distribution Metabolism and Excretion mentioning

confidence: 99%

“…The PK of subtoxic doses of 14 C-DFP (1 g/kg, by mouth) in plasma, red blood cells (RBCs), and brain tissue revealed a very rapid clearance of the parent and metabolites, followed by the slow loss of the bound fractions (26). The plasma-linked 14 C signal had a mean life in good agreement with the lifetime of plasma proteins in mice.…”

Section: Ams In Bindingmentioning

confidence: 99%

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Vogel¹

2005

BioTechniques

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“…This RFA, developed in collaboration with the U.S. Environmental Protections Agency (US EPA), encouraged innovative experimental approaches and computational, statistical or predictive strategies that focused on the mechanistic basis for chemical interactions, related health effects, and the development of biologically relevant risk assessment models for human exposure to chemical mixtures. Research resulting from the RFA included: development of targeted microarrays to screen chemicals for activity and mechanism (Bartosiewicz et al 2001); use of a monitor compound to probe low dose interactions among chemicals (Vogel et al 2002); and development of computer modeling tools for predicting the effects of complex mixtures (Liao et al 2002). …”

Section: Introductionmentioning

confidence: 99%

Mixtures research at NIEHS: An evolving program

et al. 2013

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The National Institute of Environmental Health Sciences (NIEHS) has a rich history in evaluating the toxicity of mixtures. The types of mixtures assessed by the Division of the National Toxicology Program (DNTP) and the extramural community (through the Division of Extramural Research and Training (DERT)) have included a broad range of chemicals and toxicants, with each study having a unique set of questions and design considerations. Some examples of the types of mixtures studied include: groundwater contaminants, pesticides/fertilizers, dioxin-like chemicals (assessing the toxic equivalency approach), drug combinations, air pollution, metals, polycyclic aromatic hydrocarbons, technical mixtures (e.g. pentachlorophenol, flame retardants), and mixed entities (e.g. herbals, asbestos). These endeavors have provided excellent data on the toxicity of specific mixtures and have been informative to the human health risk assessment process in general (e.g. providing data on low dose exposures to environmental chemicals). However, the mixtures research effort at NIEHS, to date, has been driven by test article nominations to the DNTP or by investigator-initiated research through DERT. Recently, the NIEHS has embarked upon an effort to coordinate mixtures research across both intramural and extramural divisions in order to maximize mixtures research results. A path forward for NIEHS mixtures research will be based on feedback from a Request for Information (RFI) designed to gather up-to-date views on the knowledge gaps and roadblocks to evaluating mixtures and performing cumulative risk assessment, and a workshop organized to bring together mixtures experts from risk assessment, exposure science, biology, epidemiology, and statistics. The future of mixtures research at NIEHS will include projects from nominations to DNTP, studies by extramural investigators, and collaborations across government agencies that address high-priority questions in the field of mixtures research.

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“…A recent paper quantified molecular damage to mouse sperm by acrylamide, a potential carcinogen and teratogen whose presence in fried foods has raised alarms about the quantity of fried potato products consumed in Western diets [19]. Low-copy biochemical events are also probed by AMS to quantify the effects of co-administered low doses of other, unlabeled chemical compounds, as in the cases of beneficial nutrients decreasing DNA damage from genotoxic compounds [20][21][22] or pesticides affecting nerve-agent binding to proteins in vivo [23,24]. Finally, AMS quantifies low probability natural chemical events, such as multiple oxidations, that yield mutagenic products in the DNA of cultured cancer cells [25].…”

Section: Molecular Assaysmentioning

confidence: 99%