Toxicology in Vitro 29 (2015) 415
Contents lists available at ScienceDirect
Toxicology in Vitro journal homepage: www.elsevier.com/locate/toxinvit
Letter to the Editor Short commentary to ‘‘Human in vivo database now on ACuteTox home page’’ [Toxicol. In Vitro 27 (2013) 2350–2351]
Dear Editor, The aim of this short note is to express our disagreement with the statement ‘‘However, animal and in vitro data from the ACuteTox project are not yet available’’ written by Ada Kolman and Cecilia Clemedson in their publication ‘‘Human in vivo database now on ACuteTox home page’’ [Toxicology In Vitro 27 (2013) 2350–2351]. We have been very actively involved in the ACuteTox project throughout its whole duration, as project partners and leaders of two major work-packages. In fact, properly evaluated and quality checked in vivo oral LD50 and in vitro data from this EU FP6 project have been available to the public since 2010 and 2013, respectively. We would like to draw readers’ attention to the following: (A) The acute oral toxicity animal in vivo data relevant to the 97 reference chemicals selected for the ACuteTox project were available since 2010 in the publication by Hoffmann et al. where summaries of oral rodent LD50 data collected in ACuteTox for the 97 reference chemicals are provided in tables. In addition to the summary LD50 data, the article presents also a comprehensive statistical analysis of the collected LD50 values in which the variability and reliability, interspecies correlation, predictive capacities with regard to official acute oral toxicity categories, and deduction of performance criteria for in vitro methods were evaluated. (B) The in vitro data generated during the course of the ACuteTox project were published in 2013 in a dedicated Special Issue of Toxicology In Vitro, way before the publication of the aforementioned article of Kolman and Clemedson about the human data. In fact, all the IC50 summary values from the relevant in vitro endpoints are available in the supplementary material provided in two publications (both accessible online already in 2012). The article by Kinsner-Ovaskainen et al. (2013) presents and discusses in detail the results of the statistical analysis performed to identify suitable in vitro and in silico methods to be used as building blocks for a non-animal testing strategy for classification of chemicals into the official acute oral toxicity categories. An Excel spreadsheet can be downloaded from the TIV website, which contains IC50 summary values calculated in a harmonised way by Department of Biostatistics, German Cancer Research Center (DKFZ) for all the 50 relevant endpoints evaluated during the first phase of the project with a common set of 57 chemicals. The publication by Prieto et al. (2013) presents the outcome of the prevalidation phase of the project aimed to assess the
DOI of original article: http://dx.doi.org/10.1016/j.tiv.2013.10.009 http://dx.doi.org/10.1016/j.tiv.2014.11.016 0887-2333/Ó 2014 Elsevier Ltd. All rights reserved.
predictive capacity of the developed testing strategies and final identification of the most promising ones. As above, an Excel spreadsheet can be downloaded with IC50 summary values calculated in a harmonised way for the 34 endpoints evaluated with a common set of 32 chemicals. Moreover, the in vivo oral LD50 values, the estimated human intestinal absorption and passage through the blood brain barrier (by neural networks) and relevant in vitro kinetic parameters are also available for the 32 chemicals. Conflict of Interest The authors declare that there are no conflicts of interest. Transparency Document The Transparency document associated with this article can be found in the online version. References Hoffmann, S., Kinsner-Ovaskainen, A., Prieto, P., Mangelsdorf, I., Bieler, C., Cole, T., 2010. Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project. Regul. Toxicol. Pharmacol. 58, 395–407. Kinsner-Ovaskainen, A., Prieto, P., Stanzel, S., Kopp-Schneider, A., 2013. Selection of test methods to be included in a testing strategy to predict acute oral toxicity: an approach based on statistical analysis of data collected in phase 1 of the ACuteTox project. Toxicol. In Vitro 27, 1377–1394 (epub 2012 November 21). Prieto, P., Kinsner-Ovaskainen, A., Stanzel, S., Albella, B., Artursson, P., Campillo, N., Cecchelli, R., Cerrato, L., Díaz, L., Di Consiglio, E., Guerra, A., Gombau, L., Herrera, G., Honegger, P., Landry, C., O’Connor, J.E., Páez, J.A., Quintas, G., Svensson, R., Turco, L., Zurich, M.G., Zurbano, M.J., Kopp-Schneider, A., 2013. The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox. Toxicol. In Vitro 27, 1357–1376 (epub 2012 August 16).
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Pilar Prieto Agnieszka Kinsner-Ovaskainen Institute for Health and Consumer Protection (IHCP), Joint Research Centre, European Commission, Via E. Fermi 2749, 21027 Ispra, VA, Italy ⇑ Corresponding author. Tel.: +39 0332 78 5534; fax: +39 0332 78 6297. E-mail address: [email protected] (P. Prieto) Available online 9 December 2014
Contents lists available at ScienceDirect
Toxicology in Vitro journal homepage: www.elsevier.com/locate/toxinvit
Letter to the Editor Short commentary to ‘‘Human in vivo database now on ACuteTox home page’’ [Toxicol. In Vitro 27 (2013) 2350–2351]
Dear Editor, The aim of this short note is to express our disagreement with the statement ‘‘However, animal and in vitro data from the ACuteTox project are not yet available’’ written by Ada Kolman and Cecilia Clemedson in their publication ‘‘Human in vivo database now on ACuteTox home page’’ [Toxicology In Vitro 27 (2013) 2350–2351]. We have been very actively involved in the ACuteTox project throughout its whole duration, as project partners and leaders of two major work-packages. In fact, properly evaluated and quality checked in vivo oral LD50 and in vitro data from this EU FP6 project have been available to the public since 2010 and 2013, respectively. We would like to draw readers’ attention to the following: (A) The acute oral toxicity animal in vivo data relevant to the 97 reference chemicals selected for the ACuteTox project were available since 2010 in the publication by Hoffmann et al. where summaries of oral rodent LD50 data collected in ACuteTox for the 97 reference chemicals are provided in tables. In addition to the summary LD50 data, the article presents also a comprehensive statistical analysis of the collected LD50 values in which the variability and reliability, interspecies correlation, predictive capacities with regard to official acute oral toxicity categories, and deduction of performance criteria for in vitro methods were evaluated. (B) The in vitro data generated during the course of the ACuteTox project were published in 2013 in a dedicated Special Issue of Toxicology In Vitro, way before the publication of the aforementioned article of Kolman and Clemedson about the human data. In fact, all the IC50 summary values from the relevant in vitro endpoints are available in the supplementary material provided in two publications (both accessible online already in 2012). The article by Kinsner-Ovaskainen et al. (2013) presents and discusses in detail the results of the statistical analysis performed to identify suitable in vitro and in silico methods to be used as building blocks for a non-animal testing strategy for classification of chemicals into the official acute oral toxicity categories. An Excel spreadsheet can be downloaded from the TIV website, which contains IC50 summary values calculated in a harmonised way by Department of Biostatistics, German Cancer Research Center (DKFZ) for all the 50 relevant endpoints evaluated during the first phase of the project with a common set of 57 chemicals. The publication by Prieto et al. (2013) presents the outcome of the prevalidation phase of the project aimed to assess the
DOI of original article: http://dx.doi.org/10.1016/j.tiv.2013.10.009 http://dx.doi.org/10.1016/j.tiv.2014.11.016 0887-2333/Ó 2014 Elsevier Ltd. All rights reserved.
predictive capacity of the developed testing strategies and final identification of the most promising ones. As above, an Excel spreadsheet can be downloaded with IC50 summary values calculated in a harmonised way for the 34 endpoints evaluated with a common set of 32 chemicals. Moreover, the in vivo oral LD50 values, the estimated human intestinal absorption and passage through the blood brain barrier (by neural networks) and relevant in vitro kinetic parameters are also available for the 32 chemicals. Conflict of Interest The authors declare that there are no conflicts of interest. Transparency Document The Transparency document associated with this article can be found in the online version. References Hoffmann, S., Kinsner-Ovaskainen, A., Prieto, P., Mangelsdorf, I., Bieler, C., Cole, T., 2010. Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project. Regul. Toxicol. Pharmacol. 58, 395–407. Kinsner-Ovaskainen, A., Prieto, P., Stanzel, S., Kopp-Schneider, A., 2013. Selection of test methods to be included in a testing strategy to predict acute oral toxicity: an approach based on statistical analysis of data collected in phase 1 of the ACuteTox project. Toxicol. In Vitro 27, 1377–1394 (epub 2012 November 21). Prieto, P., Kinsner-Ovaskainen, A., Stanzel, S., Albella, B., Artursson, P., Campillo, N., Cecchelli, R., Cerrato, L., Díaz, L., Di Consiglio, E., Guerra, A., Gombau, L., Herrera, G., Honegger, P., Landry, C., O’Connor, J.E., Páez, J.A., Quintas, G., Svensson, R., Turco, L., Zurich, M.G., Zurbano, M.J., Kopp-Schneider, A., 2013. The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox. Toxicol. In Vitro 27, 1357–1376 (epub 2012 August 16).
⇑
Pilar Prieto Agnieszka Kinsner-Ovaskainen Institute for Health and Consumer Protection (IHCP), Joint Research Centre, European Commission, Via E. Fermi 2749, 21027 Ispra, VA, Italy ⇑ Corresponding author. Tel.: +39 0332 78 5534; fax: +39 0332 78 6297. E-mail address: [email protected] (P. Prieto) Available online 9 December 2014
