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Genotoxicity of 1-propanol. Is there a problem?

: Licht, O.; Gerdes, H.; Ziemann, C.; Bitsch, A.; Mangelsdorf, I.

Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie -DGPT-:
51st Annual Meeting 2010. Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie. Abstracts : 23 - 25 March 2010, Mainz, Germany
Berlin: Springer, 2010 (Naunyn-Schmiedeberg's Archives of Pharmacology 381.2010, Supplement 1)
ISSN: 0028-1298
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <51, 2010, Mainz>
Fraunhofer ITEM ()

1-Propanol is currently being assessed both under the Biocidal Products Directive 98/8/EC (BPD) and regulation EC 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). The EU Risk assessment report concluded based on the available information that for 1-propanol there is no relevant concern with respect to mutagenicity. The substance demonstrated no genotoxic potential in vitro. However, reliable data on in vivo genotoxicity are not available, but were deemed not to be necessary, because of the negative outcome of the in vitro tests.During the new assessment of 1-propanol, metabolism was taken into account and the question arose, if under in vitro conditions possible genotoxic effects of the metabolite propionaldehyde could be missed. 1-Propanol is metabolised rapidly via propionaldehyde to propionic acid. As an aldehyde, propionaldehyde is able to interact with the DNA and can cause DNA-protein crosslinks. However, in vitro genotoxicity of propionaldehyde occurred only at un-physiologically high concentrations and was less pronounced, compared to other aldehydes. In addition, no or only equivocal effects were observed in vivo in the bone marrow micronucleus assay with mice after oral or i.p. administration, even at toxic levels. However, in the in vivo micronucleus test, the liver as major metabolising organ and other organs being the site of first contact have not been analysed. Therefore, the database on genotoxicity with emphasize on the intermediate propionaldehyde gave rise to further discussions. For clarification purposes, it has been requested to perform an in vivo comet assay with the target organs: stomach, liver and blood. The test should help to assess possible genotoxic effects on human health. On the other hand animal welfare considerations have also to be addressed adequately, leading to a conflicting situation.To encourage further discussions on data requirements for risk assessment under current regulations, the available genotoxicity data for the active substance 1-propanol and its metabolites will be presented. Finally, the test strategy will be discussed towards its impact on registration both under BPD and REACH.