Publications by authors named "Roy Irving"

Background: Per- and polyfluoroalkyl substances (PFAS) include thousands of manufactured compounds with growing public health concerns due to their potential for widespread human exposure and adverse health outcomes. While PFAS contamination remains a significant concern, especially from ingestion of contaminated food and water, determinants of the variability in PFAS exposure among regional and statewide populations in the United States remains unclear.

Objectives: The objective of this study was to leverage The Survey of the Health of Wisconsin (SHOW), the only statewide representative cohort in the US, to assess and characterize the variability of PFAS exposure in a general population.

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Background: Per- and polyfluoroalkyl substances (PFAS) are a growing class of manufactured chemical compounds found in a variety of consumer products. PFAS are ubiquitous in the environment and were found in many humans sampled in the United States (U.S.

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Background: Per- and polyfluoroalkyl substances (PFAS) are a growing class of manufactured chemical compounds found in a variety of consumer products. PFAS have become ubiquitous in the environment and were found in many humans sampled in the United States (U.S.

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The nephrotoxicity and nephrocarcinogenicity of trichloroethylene (TCE) and tetrachloroethylene (PCE) are believed to be mediated primarily through the cysteine S-conjugate β-lyase-dependent bioactivation of the corresponding cysteine S-conjugate metabolites S-(1,2-dichlorovinyl)-l-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-l-cysteine (TCVC), respectively. DCVC and TCVC have previously been demonstrated to be mutagenic by the Ames Salmonella mutagenicity assay, and reduction in mutagenicity was observed upon treatment with the β-lyase inhibitor aminooxyacetic acid (AOAA). Because DCVC and TCVC can also be bioactivated through sulfoxidation to yield the potent nephrotoxicants S-(1,2-dichlorovinyl)-l-cysteine sulfoxide (DCVCS) and S-(1,2,2-trichlorovinyl)-l-cysteine sulfoxide (TCVCS), respectively, the mutagenic potential of these two sulfoxides was investigated using the Ames Salmonella typhimurium TA100 mutagenicity assay.

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N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague-Dawley rats were dosed (i.p.

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Introduction: Reactive metabolite-mediated toxicity is frequently limited to the organ where the electrophilic metabolites are generated. Some reactive metabolites, however, might have the ability to translocate from their site of formation. This suggests that for these reactive metabolites, investigations into the role of organs other than the one directly affected could be relevant to understanding the mechanism of toxicity.

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S-(1,2-Dichlorovinyl)-L-cysteine sulfoxide (DCVCS) is a reactive and potent nephrotoxic metabolite of the human trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC). Because DCVCS covalent binding to kidney proteins likely plays a role in its nephrotoxicity, in this study biotin-tagged DCVCS, N-biotinyl-DCVCS (NB-DCVCS), was synthesized, and its stability in buffer alone and in the presence of rat blood or plasma was characterized in vitro. In addition, reactivity toward GSH and covalent binding to selected model enzymes and isolated kidney proteins were characterized.

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