Health & Environmental Research Online (HERO)


Chloroprene


204 References Were Found:

Technical Report
Technical Report

Incorporation of in vitro metabolism data in a physiologically based pharmacokinetic (PBPK) model for chloroprene

Author: Ramboll (2019) HERO ID: 5467423

[Less] A physiologically based pharmacokinetic (PBPK) model for chloroprene in the mouse, rat and human has . . . [More] A physiologically based pharmacokinetic (PBPK) model for chloroprene in the mouse, rat and
human has been developed that relies solely on in vitro studies for the estimation of model
parameters describing tissue metabolism and partitioning. The PBPK model accurately predicts in
vivo pharmacokinetic data from a 6-hr, nose-only chloroprene inhalation study conducted with
female B6C3F1 mice, the most sensitive species/gender for lung tumors in the 2-year bioassays
conducted with chloroprene. This PBPK model has been developed to support an inhalation
cancer risk assessment for chloroprene using in vitro data on the metabolism of chloroprene to
reactive epoxides in the lung target tissue of mice and humans. The approach for calculating
target tissue (lung) dose metrics was based on the PBPK modeling performed in support of the
inhalation cancer risk assessment for methylene chloride and represents the best available
science for determining the impact of species differences in metabolism of chloroprene.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines

Authors: Gulec, C; Coban, N; Ozsait-Selcuk, B; Sirma-Ekmekci, S; Yildirim, O; Erginel-Unaltuna, N (2017) Experimental Cell Research 353:6-15. HERO ID: 3854369

[Less] ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. . . . [More] ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Weighted gene co-expression network analysis of pneumocytes under exposure to a carcinogenic dose of chloroprene

Authors: Guo, Y; Xing, Y (2016) Life Sciences 151:339-347. HERO ID: 3854370

[Less] AIMS: Occupational exposure to chloroprene via inhalation may lead to acute toxicity . . . [More] AIMS: Occupational exposure to chloroprene via inhalation may lead to acute toxicity and chronic pulmonary diseases, including lung cancer. Currently, most research is focused on epidemiological studies of chloroprene production workers. The specific molecular mechanism of carcinogenesis by chloroprene in lung tissues still remains obscure, and specific candidate therapeutic targets for lung cancer are lacking. The present study identifies specific gene modules and valuable hubs associated with lung cancer.

MAIN METHODS: We downloaded the dataset GSE40795 from the Gene Expression Omnibus (GEO) and divided the dataset into the non-carcinogenic dose chloroprene exposed mice group and the carcinogenic dose chloroprene exposed mice group. With a systemic biological view, we discovered significantly altered gene modules between the two groups and identified hub genes in the carcinogenic dose exposed group using weighted co-expression network analysis (WGCNA).

KEY FINDINGS: A total of 2434 differentially expressed genes were identified. Twelve gene modules with multiple biological activities were related to the carcinogenesis of chloroprene in lung tissue. Seven hub genes that were critical for the carcinogenesis of chloroprene in lung tissue were ultimately identified, including Cftr, Hip1, Tbl1x, Ephx1, Cbr3, Antxr2 and Ccnd2. They were implicated in inflammatory response, cell transformation, gene transcription regulation, phase II detoxification, angiogenesis, cell adhesion, motility and the cell cycle.

SIGNIFICANCE: The seven hub genes may become valuable candidates for risk assessment biomarkers and therapeutic targets in lung cancer.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions

Authors: Sterne, JAC; Hernán, MA; Reeves, BC; Savović, J; Berkman, ND; Viswanathan, M; Henry, D; Altman, DG; Ansari, MT; Boutron, I; Carpenter, JR; Chan, AW; Churchill, R; Deeks, JJ; Hróbjartsson, A; Kirkham, J; Jüni, P; Loke, YK; Pigott, TD; Ramsay, CR; Regidor, D; Rothstein, HR; Sandhu, L; Santaguida, PL; Schünemann, HJ; Shea, B; Shrier, I; Tugwell, P; Turner, L; Valentine, JC; Waddington, H; Waters, E; Wells, GA; Whiting, PF; Higgins, JPT (2016) British Medical Journal 355:i4919. HERO ID: 3220127


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Supplementary material: Hazardous air pollutants and breast cancer risk in California teachers: a cohort study

Authors: Garcia, E; Hurley, S; Nelson, DO; Hertz, A; Reynolds, P (2015) Environmental Health: A Global Access Science Source 14. [Supplemental Data] HERO ID: 4236109

[Less] BACKGROUND: Studies suggest that higher breast cancer rates in urban areas persist . . . [More] BACKGROUND: Studies suggest that higher breast cancer rates in urban areas persist after accounting for the prevalence of known risk factors, leading to speculation that urban environmental exposures, such as air pollution, may play a role in the etiology of breast cancer. Combining modeled ambient air concentrations with data from a large prospective cohort of California women with over 15 years of follow-up, we examined the relationship between breast cancer incidence and modeled concentrations of air pollutants shown to be mammary gland carcinogens (MGCs).

METHODS: The study population of 112,378 California Teachers Study participants included 5,676 women diagnosed with invasive breast cancer. Modeled annual average ambient air concentrations of 24 MGCs from the U.S. Environmental Protection Agency were linked to participants' addresses. Cox proportional hazards models were used to estimate hazard rate ratios and 95% confidence intervals associated with residential MGC levels. MGCs were examined individually and as a combined summary variable for all participants, in selected subsets, and by tumor hormone responsiveness.

RESULTS: Initial models yielded some evidence for increased risk for several compounds, including acrylamide, carbon tetrachloride, chloroprene, 4,4'-methylene bis(2-chloroaniline), propylene oxide, and vinyl chloride, but after adjustment for multiple comparisons, only results for propylene oxide and vinyl chloride remained statistically significant. In subset analyses, estrogen-receptor positive or progesterone-receptor positive (ER+/PR+) tumors were associated with higher ambient levels of acrylamide, benzidine, carbon tetrachloride, ethylidene dichloride, and vinyl chloride, while ER-/PR- tumors were associated with higher ambient levels of benzene. Interesting results for different compounds were observed within certain subsets of the population.

CONCLUSION: While our initial models yielded several elevated risk estimates, after adjusting for multiple comparisons and breast cancer risk factors, most hazard ratios were no longer statistically significant. Our subset analyses, however, suggest that elevated risk may be associated with some compounds for certain subgroups of interest. A summary variable for all 24 MGCs did not offer any advantage over the models for individual compounds. Results must be interpreted cautiously, as estimated exposure was limited to modeled annual average ambient air concentrations, and could not account for other sources or routes other than inhalation.

Journal Article
Journal Article

Carbamazepine-induced liver injury requires CYP3A-mediated metabolism and glutathione depletion in rats

Authors: Iida, A; Sasaki, E; Yano, A; Tsuneyama, K; Fukami, T; Nakajima, M; Yokoi, T (2015) 43:958-968. HERO ID: 5471440


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Toxicokinetic Triage for Environmental Chemicals

Authors: Wambaugh, JF; Wetmore, BA; Pearce, R; Strope, C; Goldsmith, R; Sluka, JP; Sedykh, A; Tropsha, A; Bosgra, S; Shah, I; Judson, R; Thomas, RS; Setzer, RW (2015) Toxicological Sciences 147:55-67. HERO ID: 3841222

[Less] Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput . . . [More] Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been “reverse dosimetry,” in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day). These doses are predicted to produce steady-state plasma concentrations that are equivalent to in vitro bioactive concentrations. In this study, we evaluate the impact of the approximations and assumptions necessary for reverse dosimetry and develop methods to determine whether HTTK tools are appropriate or may lead to false conclusions for a particular chemical. Based on literature in vivo data for 87 chemicals, we identified specific properties (eg, in vitro HTTK data, physico-chemical descriptors, and predicted transporter affinities) that correlate with poor HTTK predictive ability. For 271 chemicals we developed a generic HT physiologically based TK (HTPBTK) model that predicts non-steady-state chemical concentration time-courses for a variety of exposure scenarios. We used this HTPBTK model to find that assumptions previously used for reverse dosimetry are usually appropriate, except most notably for highly bioaccumulative compounds. For the thousands of man-made chemicals in the environment that currently have no TK data, we propose a 4-element framework for chemical TK triage that can group chemicals into 7 different categories associated with varying levels of confidence in HTTK predictions. For 349 chemicals with literature HTTK data, we differentiated those chemicals for which HTTK approaches are likely to be sufficient, from those that may require additional data.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Hazardous air pollutants and breast cancer risk in California teachers: A cohort study

Authors: Garcia, E; Hurley, S; Nelson, DO; Hertz, A; Reynolds, P (2015) Environmental Health: A Global Access Science Source 14:14. HERO ID: 3014082

[Less] BACKGROUND: Studies suggest that higher breast cancer rates in urban areas persist . . . [More] BACKGROUND: Studies suggest that higher breast cancer rates in urban areas persist after accounting for the prevalence of known risk factors, leading to speculation that urban environmental exposures, such as air pollution, may play a role in the etiology of breast cancer. Combining modeled ambient air concentrations with data from a large prospective cohort of California women with over 15 years of follow-up, we examined the relationship between breast cancer incidence and modeled concentrations of air pollutants shown to be mammary gland carcinogens (MGCs).

METHODS: The study population of 112,378 California Teachers Study participants included 5,676 women diagnosed with invasive breast cancer. Modeled annual average ambient air concentrations of 24 MGCs from the U.S. Environmental Protection Agency were linked to participants' addresses. Cox proportional hazards models were used to estimate hazard rate ratios and 95% confidence intervals associated with residential MGC levels. MGCs were examined individually and as a combined summary variable for all participants, in selected subsets, and by tumor hormone responsiveness.

RESULTS: Initial models yielded some evidence for increased risk for several compounds, including acrylamide, carbon tetrachloride, chloroprene, 4,4'-methylene bis(2-chloroaniline), propylene oxide, and vinyl chloride, but after adjustment for multiple comparisons, only results for propylene oxide and vinyl chloride remained statistically significant. In subset analyses, estrogen-receptor positive or progesterone-receptor positive (ER+/PR+) tumors were associated with higher ambient levels of acrylamide, benzidine, carbon tetrachloride, ethylidene dichloride, and vinyl chloride, while ER-/PR- tumors were associated with higher ambient levels of benzene. Interesting results for different compounds were observed within certain subsets of the population.

CONCLUSION: While our initial models yielded several elevated risk estimates, after adjusting for multiple comparisons and breast cancer risk factors, most hazard ratios were no longer statistically significant. Our subset analyses, however, suggest that elevated risk may be associated with some compounds for certain subgroups of interest. A summary variable for all 24 MGCs did not offer any advantage over the models for individual compounds. Results must be interpreted cautiously, as estimated exposure was limited to modeled annual average ambient air concentrations, and could not account for other sources or routes other than inhalation.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The constrained maximum likelihood approach to evaluate the impact of dose metric on cancer risk assessment: application to beta-chloroprene

Authors: Allen , BC; Landingham, CV; Yang, Y; Youk, AO; Marsh, GM; Esmen, N; Gentry, PR; Clewell III, HJ; Himmelstein, MW (2014) HERO ID: 4157310


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

A constrained maximum likelihood approach to evaluate the impact of dose metric on cancer risk assessment: application to β-chloroprene

Authors: Allen, BC; Van Landingham, C; Yang, Y; Youk, AO; Marsh, GM; Esmen, N; Gentry, PR; Clewell, HJ; Himmelstein, MW (2014) Regulatory Toxicology and Pharmacology 70:203-213. HERO ID: 3854460

[Less] β-Chloroprene (2-chloro-1,3-butadiene, CD) is used in the manufacture of polychloroprene rubber. Chronic . . . [More] β-Chloroprene (2-chloro-1,3-butadiene, CD) is used in the manufacture of polychloroprene rubber. Chronic inhalation studies have demonstrated that CD is carcinogenic in B6C3F1 mice and Fischer 344 rats. However, epidemiological studies do not provide compelling evidence for an increased risk of mortality from total cancers of the lung. Differences between the responses observed in animals and humans may be related to differences in toxicokinetics, the metabolism and detoxification of potentially active metabolites, as well as species differences in sensitivity. The purpose of this study was to develop and apply a novel method that combines the results from available physiologically based kinetic (PBK) models for chloroprene with a statistical maximum likelihood approach to test commonality of low-dose risk across species. This method allows for the combined evaluation of human and animal cancer study results to evaluate the difference between predicted risks using both external and internal dose metrics. The method applied to mouse and human CD data supports the hypothesis that a PBK-based metric reconciles the differences in mouse and human low-dose risk estimates and further suggests that, after PBK metric exposure adjustment, humans are equally or less sensitive than mice to low levels of CD exposure.