Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-2 (of 2 Records) |
Query Trace: Witt KL[original query] |
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In silico toxicology protocols.
Myatt GJ , Ahlberg E , Akahori Y , Allen D , Amberg A , Anger LT , Aptula A , Auerbach S , Beilke L , Bellion P , Benigni R , Bercu J , Booth ED , Bower D , Brigo A , Burden N , Cammerer Z , Cronin MTD , Cross KP , Custer L , Dettwiler M , Dobo K , Ford KA , Fortin MC , Gad-McDonald SE , Gellatly N , Gervais V , Glover KP , Glowienke S , Van Gompel J , Gutsell S , Hardy B , Harvey JS , Hillegass J , Honma M , Hsieh JH , Hsu CW , Hughes K , Johnson C , Jolly R , Jones D , Kemper R , Kenyon MO , Kim MT , Kruhlak NL , Kulkarni SA , Kümmerer K , Leavitt P , Majer B , Masten S , Miller S , Moser J , Mumtaz M , Muster W , Neilson L , Oprea TI , Patlewicz G , Paulino A , Lo Piparo E , Powley M , Quigley DP , Reddy MV , Richarz AN , Ruiz P , Schilter B , Serafimova R , Simpson W , Stavitskaya L , Stidl R , Suarez-Rodriguez D , Szabo DT , Teasdale A , Trejo-Martin A , Valentin JP , Vuorinen A , Wall BA , Watts P , White AT , Wichard J , Witt KL , Woolley A , Woolley D , Zwickl C , Hasselgren C . Regul Toxicol Pharmacol 2018 96 1-17 The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. |
Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs
Roussel C , Witt KL , Shaw PB , Connor TH . Mutat Res Rev Mutat Res 2017 781 207-217 Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated levels of chromosomal aberrations, micronuclei, and DNA damage have been documented in cancer patients. Elevations in these same biomarkers of genetic damage have been reported in numerous studies of healthcare workers, such as nurses and pharmacists, who routinely handle these drugs, but results vary across studies. To obtain an overall assessment of the exposure effect, we performed a meta-analysis on data obtained from peer-reviewed publications reporting chromosomal aberration levels in healthcare workers exposed to antineoplastic drugs. A literature search identified 39 studies reporting on occupational exposure to antineoplastic drugs and measurement of chromosomal aberrations in healthcare workers. After applying strict inclusion criteria for data quality and presentation, data from 17 studies included in 16 publications underwent meta-analysis using Hedges' bias-corrected g and a random-effects model. Results showed the level of chromosomal aberrations in healthcare workers exposed to antineoplastic drugs was significantly higher than in controls. The standardized mean differences (difference of means divided by within sd) from all studies were pooled, yielding a value 1.006 (unitless) with p< 0.001. Thus, in addition to the documented genotoxic effects of antineoplastic drugs in cancer patients, this meta-analysis confirmed a significant association between occupational exposure to antineoplastics during the course of a normal work day and increases in chromosomal aberrations in healthcare workers. Based on the studies reviewed, we were unable to accurately assess whether appropriate use of protective measures might reduce the incidence of genetic damage in healthcare workers. However, given the potential for increased cancer risk linked to increases in chromosomal aberrations, the results of this study support the need to limit occupational exposure of healthcare workers to antineoplastic drugs as much as possible. |
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