A retrospective analysis of the two-generation study, author response to letter to the editor

摘要

It is with great interest that we have read the letter by Ruden and Hansson commenting on our recent publication . We welcome their appreciation of the importance of our contribution as well as their careful assessment of our analysis. In the following we would like to take the opportunity to reiterate the aim and design of our study and to respond to the analysis given by Ruden and Hansson.The aim of our study was to review past practice with the rat two-generation reproductive toxicity study. Therefore, as our main source of information we took existing risk assessment reports and relied on the conclusions emerging from those reports. Lists of classified substances were taken from the Annex 1 of the EU Classification and Labeling Directive (http://ecb.jrc.it/esis/index.php?PGM=cla ) and from the Proposition 65 of the State of California Environmental Protection Agency (http://www.oehha.ca.gov/prop65.html ). Given that we aimed to review historic assessments it was on purpose that we did not perform our own data analysis. On this basis we collected all good quality two-generation studies that could be identified for classified substances, and subsequently we added a series of acceptable two-generation studies performed with non-classified substances. For classified substances, only in absence of publicly available data and/or guideline compliant studies, we included two-generation studies that deviated from the OECD guideline and/or we referred to confidential data. Given this historic database, our own data assessment was limited to a comparison of the effects found in the P versus F1 adults, and in the F1 versus F2 offspring within each study.