PMID- 15840426 OWN - NLM STAT- MEDLINE DCOM- 20050601 LR - 20141120 IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 210 IP - 2-3 DP - 2005 Jun 1 TI - Urinary metabolites of di-n-octyl phthalate in rats. PG - 123-33 AB - Di-n-octyl phthalate (DnOP) is a plasticizer used in polyvinyl chloride plastics, cellulose esters, and polystyrene resins. The metabolism of DnOP results in the hydrolysis of one ester linkage to produce mono-n-octyl phthalate (MnOP), which subsequently metabolizes to form oxidative metabolites. We investigated the toxicokinetics of DnOP in adult female Sprague-Dawley rats by monitoring the excretion of DnOP metabolites in urine after oral administration of DnOP (300 mg/kg). By using authentic standards, the presence of urinary phthalic acid (PA), MnOP, and the major DnOP metabolite, mono-(3-carboxypropyl) phthalate (MCPP) was clearly established. Furthermore, we identified five additional urinary DnOP oxidative metabolites based on their chromatographic behavior and mass spectrometric fragmentation pattern. These DnOP oxidative metabolites, are postulated to be mono-carboxymethyl phthalate (MCMP), mono-(5-carboxy-n-pentyl) phthalate (MCPeP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), and isomers of mono-hydroxy-n-octyl phthalate (MHOP) (e.g., mono-(7-hydroxy-n-octyl) phthalate) and of mono-oxo-n-octyl phthalate (MOOP) (e.g., mono-(7-oxo-n-octyl) phthalate). The urinary excretion of DnOP metabolites followed a biphasic excretion pattern. The metabolite levels decreased significantly after the first day of DnOP administration although MCPP, MCHpP, MHOP, and MOOP were detectable after 4 days. We also studied the in vitro metabolism of DnOP and MnOP by rat liver microsomes. DnOP produced MnOP, MHOP, and PA in vitro whereas, MnOP produced MHOP and PA in vitro at detectable levels. FAU - Silva, Manori J AU - Silva MJ AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Mailstop F17, 4770 Buford Hwy NE, Atlanta, GA 30341, USA. zca2@cdc.gov FAU - Kato, Kayoko AU - Kato K FAU - Gray, Earl L AU - Gray EL FAU - Wolf, Cynthia AU - Wolf C FAU - Needham, Larry L AU - Needham LL FAU - Calafat, Antonia M AU - Calafat AM LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Phthalic Acids) RN - 0 (Plasticizers) RN - 8X3RJ0527W (di-n-octyl phthalate) SB - IM MH - Administration, Oral MH - Animals MH - Female MH - Inactivation, Metabolic MH - Mass Spectrometry MH - Microsomes, Liver/*metabolism MH - Oxidation-Reduction MH - Phthalic Acids/metabolism/*urine MH - Plasticizers/*pharmacokinetics MH - Rats MH - Rats, Sprague-Dawley EDAT- 2005/04/21 09:00 MHDA- 2005/06/02 09:00 CRDT- 2005/04/21 09:00 PHST- 2004/10/29 00:00 [received] PHST- 2005/01/20 00:00 [revised] PHST- 2005/01/21 00:00 [accepted] PHST- 2005/04/21 09:00 [pubmed] PHST- 2005/06/02 09:00 [medline] PHST- 2005/04/21 09:00 [entrez] AID - S0300-483X(05)00071-5 [pii] AID - 10.1016/j.tox.2005.01.012 [doi] PST - ppublish SO - Toxicology. 2005 Jun 1;210(2-3):123-33. doi: 10.1016/j.tox.2005.01.012.