Gutenberg Open Science: Enigmatic mechanism of the N-vinylpyrrolidone hepatocarcinogenicity in the rat

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7660

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DC Field	Value	Language
dc.contributor.author	Oesch, Franz	-
dc.contributor.author	Fruth, Daniela	-
dc.contributor.author	Hengstler, Jan G.	-
dc.contributor.author	Fabian, Eric	-
dc.contributor.author	Berger, Franz Ingo	-
dc.contributor.author	Landsiedel, Robert	-
dc.date.accessioned	2022-09-01T09:46:06Z	-
dc.date.available	2022-09-01T09:46:06Z	-
dc.date.issued	2021	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7674	-
dc.description.abstract	N-vinyl pyrrolidone (NVP) is produced up to several thousand tons per year as starting material for the production of polymers to be used in pharmaceutics, cosmetics and food technology. Upon inhalation NVP was carcinogenic in the rat, liver tumor formation is starting already at the rather low concentration of 5 ppm. Hence, differentiation whether NVP is a genotoxic carcinogen (presumed to generally have no dose threshold for the carcinogenic activity) or a non-genotoxic carcinogen (with a potentially definable threshold) is highly important. In the present study, therefore, the existing genotoxicity investigations on NVP (all showing consistently negative results) were extended and complemented with investigations on possible alternative mechanisms, which also all proved negative. All tests were performed in the same species (rat) using the same route of exposure (inhalation) and the same doses of NVP (5, 10 and 20 ppm) as had been used in the positive carcinogenicity test. Specifically, the tests included an ex vivo Comet assay (so far not available) and an ex vivo micronucleus test (in contrast to the already available micronucleus test in mice here in the same species and by the same route of application as in the bioassay which had shown the carcinogenicity), tests on oxidative stress (non-protein-bound sulfhydryls and glutathione recycling test), mechanisms mediated by hepatic receptors, the activation of which had been shown earlier to lead to carcinogenicity in some instances (Ah receptor, CAR, PXR, PPARα). No indications were obtained for any of the investigated mechanisms to be responsible for or to contribute to the observed carcinogenicity of NVP. The most important of these exclusions is genotoxicity. Thus, NVP can rightfully be regarded and treated as a non-genotoxic carcinogen and threshold approaches to the assessment of this chemical are supported. However, the mechanism underlying the carcinogenicity of NVP in rats remains unclear.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Enigmatic mechanism of the N-vinylpyrrolidone hepatocarcinogenicity in the rat	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7660	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Archives of toxicology	de
jgu.journal.volume	95	de
jgu.pages.start	3717	de
jgu.pages.end	3744	de
jgu.publisher.year	2021	-
jgu.publisher.name	Springer	de
jgu.publisher.place	Berlin u.a.	de
jgu.publisher.issn	1432-0738	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1007/s00204-021-03151-8	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	JGU-Publikationen

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