Health & Environmental Research Online (HERO)


Chloroprene


204 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

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

Computational fluid dynamics (CFD) insights into agitation stress methods in biopharmaceutical development

Authors: Bai, G; Bee, JS; Biddlecombe, JG; Chen, Q; Leach, WT (2012) International Journal of Pharmaceutics 423:264-280. HERO ID: 5184502

[Less] Agitation of small amounts of liquid is performed routinely in biopharmaceutical process, formulation, . . . [More] Agitation of small amounts of liquid is performed routinely in biopharmaceutical process, formulation, and packaging development. Protein degradation commonly results from agitation, but the specific stress responsible or degradation mechanism is usually not well understood. Characterization of the agitation stress methods is critical to identifying protein degradation mechanisms or specific sensitivities. In this study, computational fluid dynamics (CFD) was used to model agitation of 1 mL of fluid by four types of common laboratory agitation instruments, including a rotator, orbital shaker, magnetic stirrer and vortex mixer. Fluid stresses in the bulk liquid and near interfaces were identified, quantified and compared. The vortex mixer provides the most intense stresses overall, while the stir bar system presented locally intense shear proximal to the hydrophobic stir bar surface. The rotator provides gentler fluid stresses, but the air-water interfacial area and surface stresses are relatively high given its low rotational frequency. The orbital shaker provides intermediate-level stresses but with the advantage of a large stable platform for consistent vial-to-vial homogeneity. Selection of experimental agitation methods with targeted types and intensities of stresses can facilitate better understanding of protein degradation mechanisms and predictability for "real world" applications.

Journal Article
Journal Article

Statistical inferences from serially correlated methylene chloride data

Authors: Klein, M; Neerchal, N; Sinha, B; Chiu, W; White, P (2012) Sankhya: Indian Journal of Statistics 74:211-237. HERO ID: 5486603

[Less] While physiologically-based pharmacokinetic (PBPK) modeling has become an important tool in environmental . . . [More] While physiologically-based pharmacokinetic (PBPK) modeling has become an important tool in environmental health risk assessment, a rigorous statistical methodology is not routinely incorporated into these analyses. This paper illustrates how to carry out a formal statistical analysis to obtain improved inference upon model parameters from time-dependent, serially correlated methylene chloride data combined from several experiments. Frequentist and Bayesian methods are both considered. We work with a well established PBPK model for disposition of inhaled dichloromethane (DCM, methylene chloride) gas within a closed chamber.

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 fatal intoxication by chloroprene

Authors: Rickert, A; Hartung, B; Kardel, B; Teloh, J; Daldrup, T (2012) Forensic Science International 215:110-113. HERO ID: 1788018

[Less] Objective: Chloroprene, 2-chloro-1,3 butadiene, is a volatile synthetic liquid. The chloroprene monomer . . . [More] Objective: Chloroprene, 2-chloro-1,3 butadiene, is a volatile synthetic liquid. The chloroprene monomer is extremely reactive and is used for the production of latexes and synthetic rubber such as Neoprene. Up to now an acute lethal human exposure has been described only once in the literature [19]. The intoxication is associated with nervous system depression, pulmonary edema, narcosis, and respiratory arrest.

Case report: A 29-year-old chemistry company worker was found unconscious in an empty vessel (depth: 3m) used for chloroprene. The man was dressed in shoes, trousers, a helmet and a respiratory mask. The upper part of the body was unclothed. In spite of reanimation, the man died three hours later in a hospital.

Material and methods: All analyses were performed by headspace gas chromatography (HS/GC/FID). In addition, brain, muscle and myocardial muscle were analysed by headspace GC-MS.

Results and discussion: Autopsy findings: The cause of death could not be determined as the macromorphological findings were unspecific.

Toxicology findings: The calibration curve of chloroprene in serum shows linearity from 1.0 to 200 μg/ml (r(2)=0.9999) using benzene as internal standard. The LOD is 0.28 μg/ml, the LLOQ is 0.99 μg/ml. Tissues and body fluids were stored at -20 °C till the analysis. Chloroprene was quantified after addition of benzene as the internal standard. It was found in nearly all tissues and body fluids except in the urine and lung. The highest concentrations were detected in the kidney, liver, myocardial muscle and especially in the brain. Furthermore, hexanal was found in all samples except in the urine. The amount of hexanal in some specimens is high, especially in the lung, bile, gastric content and myocardial muscle.

Conclusion: We assume that a significant amount of chloroprene was not only inhaled but also absorbed through the skin because the man wore a respiratory mask. Presumably the accident would not have happened if the works safety protocols had been followed. The reason why high concentrations of hexanal were found in the tissues could not be clarified.

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.

Technical Report
Technical Report

Toxicological review of Chloroprene (CASRN 126-99-8) in support of summary information on the Integrated Risk Information System (IRIS).

Author: U.S. EPA (2010) HERO ID: 625433


Technical Report
Technical Report

NIOSH pocket guide to chemical hazards: beta-Chloroprene

Author: NIOSH (2010) [Data]. Cincinnati, OH: National Institute for Occupational Safety and Health. [Database] HERO ID: 644448


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

DNA interstrand cross-linking activity of (1-Chloroethenyl)oxirane, a metabolite of beta-chloroprene

Authors: Wadugu, BA; Ng, C; Bartley, BL; Rowe, RJ; Millard, JT (2010) Chemical Research in Toxicology 23:235-239. HERO ID: 1508892

[Less] With the goal of elucidating the molecular and cellular mechanisms of chloroprene toxicity, we examined . . . [More] With the goal of elucidating the molecular and cellular mechanisms of chloroprene toxicity, we examined the potential DNA cross-linking of the bifunctional chloroprene metabolite, (1-chloroethenyl)oxirane (CEO). We used denaturing polyacrylamide gel electrophoresis to monitor the possible formation of interstrand cross-links by CEO within synthetic DNA duplexes. Our data suggest interstrand cross-linking at deoxyguanosine residues within 5'-GC and 5'-GGC sites, with the rate of cross-linking depending on pH (pH 5.0 > pH 6.0 > pH 7.0). A comparison of the cross-linking efficiencies of CEO and the structurally similar cross-linkers diepoxybutane (DEB) and epichlorohydrin (ECH) revealed that DEB > CEO > or = ECH. Furthermore, we found that cytotoxicity correlates with cross-linking efficiency, supporting a role for interstrand cross-links in the genotoxicology of chloroprene.

Technical Report
Technical Report

Toxicological review of Chloroprene (CASRN 126-99-8) [External Review Draft]

Author: U.S. EPA (2009) HERO ID: 625434