DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane

Toraason, Mark; Lynch, Dennis W.; DeBord, D. Gayle; Singh, Narendra P.; Krieg, Edward F.; Butler, Mary Ann; Toennis, Christine; Nemhauser, Jeffrey B.

doi:10.1016/j.mrgentox.2005.08.015

Cited by 25 publications

(13 citation statements)

References 37 publications

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“…Ultimately, genotypic selection will have the greatest impact on risk assessment if measurement of spontaneous mutations is possible.” ( 36 ) Importantly, numerous assays have been used routinely to screen for DNA damage, which have proven effective at identifying new carcinogens. ( 2 , 9 , 53 )…”

Section: Genetic Researchmentioning

confidence: 99%

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

Whittaker

Curran

2015

Journal of Occupational and Environmental Hygiene

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Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 × 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments.

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Section: Genetic Researchmentioning

confidence: 99%

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

Whittaker

Curran

2015

Journal of Occupational and Environmental Hygiene

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“…Als Einflussfaktoren wurden das Geschlecht (Frauen waren höher exponiert als Män-ner) und die Anlage (Anlage Am it höheren Expositionen) sowie die GSTM1 (der Nachweis des Gens war assoziiert mit einer Erhöhung des "Tail Moment Dispersion Coefficient")identifiziert. Die Autoren sehen es als möglich an, dass 1-Brompropan zu einer Depletion von GSH führt, was dazu beiträgt, dass die Empfindlichkeit gegenüber anderen Ursachen von oxidativem Stress erhöht wird (Toraason et al 2006). Für eine Aussage zu einer möglichen genotoxischen Wirkung von 1-Brompropan ist diese Studie nicht geeignet.…”

Section: Genotoxizitätunclassified

“…Positive Resultate mit 1mMwurden bei 4-und 8-stündiger Inkubation, nicht aber nach 1-oder 2-stündiger Inkubation festgestellt, was aufgrund der hohen Flüchtigkeit der Substanz und der Ve rwendung eines offenen Systems nicht plausibel erscheint. Ve rmehrt apoptotische Zellen wurden schon ab 0,1 mM beobachtet (Toraason et al 2006). In einem Mikronukleustest an CHO-Zellen wurden keine Mikronuklei nach Behandlung mit 1350, 3375 oder 6750 μg/ml induziert.…”

Section: In Vitrounclassified

1‐Brompropan [MAK Value Documentation in German language, 2011]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 50. Lieferung, Ausgabe 2011 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Bewertung

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“…Human exposure to 1-BP occurs primarily via inhalation or absorption through the skin. Although reports detailing the manifestation of adverse health effects in humans have been limited [162,163], numerous studies have reported that 1-BP is a potent neurological and reproductive toxicant in both male and female animals [164][165][166].…”

Section: Bromopropanementioning

confidence: 99%

Investigation of Xenobiotics Metabolism, Genotoxicity, and Carcinogenicity Using Cyp2e1-/- Mice

Ghanayem¹,

Hoffler²

2007

CDM

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Cytochromes P450 (CYPs) comprise a number of enzyme subfamilies responsible for the oxidative metabolism of a wide range of therapeutic agents, environmental toxicants, mutagens, and carcinogens. In particular, cytochrome P450 2E1 (CYP2E1) is implicated in the oxidative bioactivation of a variety of small hydrophobic chemicals including a number of epoxide-forming drugs and environmentally important toxicants including urethane, acrylamide, acrylonitrile, benzene, vinyl chloride, styrene, 1-bromopropane, trichloroethylene, dichloroethylene, acetaminophen, and butadiene. Until recently, chemical modulators (inducers and inhibitors) were used in order to characterize the enzymatic basis of xenobiotic metabolism and the relationships between CYP-mediated bioactivation and chemical-induced toxicity/carcinogenicity. With the advent of genetically engineered knockout mice, the ability to evaluate the roles of specific CYPs in the metabolism of xenobiotics has become more attainable. The main focus of the current review is to present studies that characterized the enzymatic, metabolic, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of various xenobiotics using Cyp2e1-/- mice. Data presented in this review demonstrated that the most comprehensive studies using Cyp2e1-/- mice, encompassing the entire paradigm of metabolism to toxicity, genotoxicity, and carcinogenicity were possible when a substrate was primarily metabolized via CYP2E1 (e.g. urethane and acrylamide). In contrast, when multiple CYP enzymes were prevalent in the oxidation of a particular substrate (e.g.: trichloroethylene, methacrylonitrile, crotononitrile), investigating the relationships between oxidative metabolism and biological activity became more complicated and required the use of chemical modulators. In conclusion, the current review showed that Cyp2e1-/- mice are a valuable animal model for the investigation of the metabolic and molecular basis of toxicity, genotoxicity, and carcinogenicity of xenobiotics.

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DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane

Cited by 25 publications

References 37 publications

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

1‐Brompropan [MAK Value Documentation in German language, 2011]

Investigation of Xenobiotics Metabolism, Genotoxicity, and Carcinogenicity Using Cyp2e1-/- Mice

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