Toxicological investigation of di(2-ethylhexyl)phthalate in rats. The determination of a no-observed-effect-level

2.50
Hdl Handle:
http://hdl.handle.net/10029/256070
Title:
Toxicological investigation of di(2-ethylhexyl)phthalate in rats. The determination of a no-observed-effect-level
Authors:
Jansen EHJM; van den Ham WA; Dormans JAMA; van Apeldoorn ME; van Leeuwen FXR
Other Titles:
[Toxicologisch onderzoek van di(2-ethylhexyl)ftalaat in ratten. De bepaling van het niveau waarop geen effect wordt waargenomen.]
Abstract:
Two animal experiments are described in which male rats have been exposed to di(2-ethylhexyl)phthalate (DEHP) for 2 and 4 weeks. Besides morphometric analysis using both light and electron microscopy, a number of enzyme parameters in liver homogenates have been determined which have a relation with the proliferation of peroxisomes in hepatocytes, such as palmitoyl coenzyme-A oxidase (PCO), enoyl coenzyme-A hydratase (ECH), carnitine acetyl transferase (CAT), catalase (cat) and lauric acid hydroxylase (LAH). Glutamate dehydrogenase (GIDH) was measured as a control enzyme for mitochondria. For all enzymes, except GIDH, a dose-response relationship was observed. There were not many differences between the results of the parameters examined in the 2 and 4 weeks exposed animals. In the 2 weeks exposure experiment, the enzyme parameters appeared to be slightly more sensitive. Therefore the parameters from this experiment were taken for determination of the doses-without-effect (DWE). Also the morphometric analysis has been performed on the 2 weeks-experiment. Although CAT turned out the most sensitive parameter, this enzyme activity was not considered in the establishment of an overall no-observed-effect-level since it is not specific for peroxisome proliferation. The second most sensitive parameters were the morphometric analysis and the induction of LAH and ECH activity (DWE = 5 mg/kg b.w./day) followed by PCO (DWE = 18 mg/kg b.w./day). Catalase activity was not a very sensitive parameter (52 mg/kg b.w./day). An overall no-observed-effect-level for DEHP was established as 5 mg/kg b.w./day, based on the parameters mentioned for peroxisome proliferation.<br>
Publisher:
Rijksinstituut voor Volksgezondheid en Milieu RIVM
Issue Date:
31-Dec-1992
Additional Links:
http://www.rivm.nl/bibliotheek/rapporten/618902007.html
Type:
Onderzoeksrapport
Language:
en
Sponsors:
HIGB
Appears in Collections:
RIVM official reports

Full metadata record

DC FieldValue Language
dc.contributor.authorJansen EHJM-
dc.contributor.authorvan den Ham WA-
dc.contributor.authorDormans JAMA-
dc.contributor.authorvan Apeldoorn ME-
dc.contributor.authorvan Leeuwen FXR-
dc.date.accessioned2014-01-17T13:39:31-
dc.date.issued1992-12-31-
dc.identifier618902007-
dc.description.abstractTwo animal experiments are described in which male rats have been exposed to di(2-ethylhexyl)phthalate (DEHP) for 2 and 4 weeks. Besides morphometric analysis using both light and electron microscopy, a number of enzyme parameters in liver homogenates have been determined which have a relation with the proliferation of peroxisomes in hepatocytes, such as palmitoyl coenzyme-A oxidase (PCO), enoyl coenzyme-A hydratase (ECH), carnitine acetyl transferase (CAT), catalase (cat) and lauric acid hydroxylase (LAH). Glutamate dehydrogenase (GIDH) was measured as a control enzyme for mitochondria. For all enzymes, except GIDH, a dose-response relationship was observed. There were not many differences between the results of the parameters examined in the 2 and 4 weeks exposed animals. In the 2 weeks exposure experiment, the enzyme parameters appeared to be slightly more sensitive. Therefore the parameters from this experiment were taken for determination of the doses-without-effect (DWE). Also the morphometric analysis has been performed on the 2 weeks-experiment. Although CAT turned out the most sensitive parameter, this enzyme activity was not considered in the establishment of an overall no-observed-effect-level since it is not specific for peroxisome proliferation. The second most sensitive parameters were the morphometric analysis and the induction of LAH and ECH activity (DWE = 5 mg/kg b.w./day) followed by PCO (DWE = 18 mg/kg b.w./day). Catalase activity was not a very sensitive parameter (52 mg/kg b.w./day). An overall no-observed-effect-level for DEHP was established as 5 mg/kg b.w./day, based on the parameters mentioned for peroxisome proliferation.<br>en
dc.description.sponsorshipHIGB-
dc.format.extent28 p-
dc.language.isoen-
dc.publisherRijksinstituut voor Volksgezondheid en Milieu RIVM-
dc.relation.ispartofRIVM Rapport 618902007-
dc.relation.urlhttp://www.rivm.nl/bibliotheek/rapporten/618902007.html-
dc.subject07nl
dc.subjectdehpnl
dc.subjecttoxicititeitnl
dc.subjecttoxiciteitstestennl
dc.subjecteffectennl
dc.subjectdiermodelnl
dc.subjectdiethylhexyl phthalateen
dc.subjecttoxicity testingen
dc.subjecthealth effectsen
dc.subjectanimal modelsen
dc.subjectdose-response relationshipen
dc.subjectno effect levelen
dc.subjectperoxisoomproliferatieen
dc.titleToxicological investigation of di(2-ethylhexyl)phthalate in rats. The determination of a no-observed-effect-levelen
dc.title.alternative[Toxicologisch onderzoek van di(2-ethylhexyl)ftalaat in ratten. De bepaling van het niveau waarop geen effect wordt waargenomen.]nl
dc.typeOnderzoeksrapport-
dc.date.updated2014-01-17T12:41:48Z-
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