Health & Environmental Research Online (HERO)


Chloroprene


197 References Were Found:

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-randomized studies of interventions, Version 7 March 2016

Authors: Sterne, J; Higgins, J; Reeves, B (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

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

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.

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.

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

Excretion of mercapturic acids in human urine after occupational exposure to 2-chloroprene

Authors: Eckert, E; Leng, G; Gries, W; Göen, T (2013) Archives of Toxicology 87:1095-1102. HERO ID: 3854501

[Less] A pilot study was conducted for human biomonitoring of the suspected carcinogen 2-chloroprene. For this . . . [More] A pilot study was conducted for human biomonitoring of the suspected carcinogen 2-chloroprene. For this purpose, urine samples of 14 individuals occupationally exposed to 2-chloroprene (exposed group) and of 30 individuals without occupational exposure to alkylating substances (control group) were analysed for six potential mercapturic acids of 2-chloroprene: 4-chloro-3-oxobutyl mercapturic acid (Cl-MA-I), 4-chloro-3-hydroxybutyl mercapturic acid (Cl-MA-II), 3-chloro-2-hydroxy-3-butenyl mercapturic acid (Cl-MA-III), 4-hydroxy-3-oxobutyl mercapturic acid (HOBMA), 3,4-dihydroxybutyl mercapturic acid (DHBMA) and 2-hydroxy-3-butenyl mercapturic acid (MHBMA). In direct comparison with the control group, elevated levels of the mercapturic acids Cl-MA-III, MHBMA, HOBMA and DHBMA were found in the urine samples of the exposed group. Cl-MA-I and Cl-MA-II were not detected in any of the samples, whereas HOBMA and DHBMA were found in all analysed urine samples. Thus, for the first time, it was possible to detect HOBMA and Cl-MA-III in human urine. The mercapturic acid Cl-MA-III could be confirmed as a specific metabolite of 2-chloroprene in humans providing evidence for the intermediate formation of a reactive epoxide during biotransformation. The main metabolite, however, was found to be DHBMA showing a distinct and significant correlation with the urinary Cl-MA-III levels in the exposed group. The obtained results give new scientific insight into the course of biotransformation of 2-chloroprene in humans.

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

Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene

Authors: Thomas, RS; Himmelstein, MW; Clewell, HJ; Yang, Y; Healy, E; Black, MB; Andersen, ME (2013) Toxicological Sciences 131:629-640. HERO ID: 3854358

[Less] β-Chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is . . . [More] β-Chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of neoprene elastomers, is of regulatory interest due to the production of multiorgan tumors in mouse and rat cancer bioassays. A significant increase in female mouse lung tumors was observed at the lowest exposure concentration of 12.8 ppm, whereas a small, but not statistically significant increase was observed in female rats only at the highest exposure concentration of 80 ppm. The metabolism of chloroprene results in the generation of reactive epoxides, and the rate of overall chloroprene metabolism is highly species dependent. To identify potential key events in the mode of action of chloroprene lung tumorigenesis, dose-response and time-course gene expression microarray measurements were made in the lungs of female mice and female rats. The gene expression changes were analyzed using both a traditional ANOVA approach followed by pathway enrichment analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways related to glutathione biosynthesis and metabolism were the primary pathways consistent with cross-species differences in tumor incidence. Transcriptional BMD values for the pathway were more similar to differences in tumor response than were estimated target tissue dose surrogates based on the total amount of chloroprene metabolized per unit mass of lung tissue per day. The closer correspondence of the transcriptional changes with the tumor response is likely due to their reflection of the overall balance between metabolic activation and detoxication reactions, whereas the current tissue dose surrogate reflects only oxidative metabolism.

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

Kinetic modeling of β-chloroprene metabolism: Probabilistic in vitro-in vivo extrapolation of metabolism in the lung, liver and kidneys of mice, rats and humans

Authors: Yang, Y; Himmelstein, MW; Clewell, HJ (2012) Toxicology In Vitro 26:1047-1055. HERO ID: 3854472

[Less] β-Chloroprene (chloroprene) is carcinogenic in inhalation bioassays with B6C3F1 mice and Fischer rats, . . . [More] β-Chloroprene (chloroprene) is carcinogenic in inhalation bioassays with B6C3F1 mice and Fischer rats, but the potential effects in humans have not been adequately characterized. In order to provide a better basis for evaluating chloroprene exposures and potential effects in humans, we have explored species and tissue differences in chloroprene metabolism. This study implemented an in vitro-in vivo extrapolation (IVIVE) approach to parameterize a physiologically based pharmacokinetic (PBPK) model for chloroprene and evaluate the influence of species and gender differences in metabolism on target tissue dosimetry. Chloroprene metabolism was determined in vitro using liver, lung and kidney microsomes from male or female mice, rats, and humans. A two compartment PK model was used to estimate metabolism parameters for chloroprene in an in vitro closed vial system, which were then extrapolated to the whole body PBPK model. Two different strategies were used to estimate parameters for the oxidative metabolism of chloroprene: a deterministic point-estimation using the Nelder-Mead nonlinear optimization algorithm and probabilistic Bayesian analysis using the Markov Chain Monte Carlo technique. Target tissue dosimetry (average amount of chloroprene metabolized in lung per day) was simulated with the PBPK model using the in vitro-based metabolism parameters. The model-predicted target tissue dosimetry, as a surrogate for a risk estimate, was similar between the two approaches; however, the latter approach provided a measure of uncertainty in the metabolism parameters and the opportunity to evaluate the impact of that uncertainty on predicted risk estimates.