EPA Science Inventory

URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS

Citation:

SILVA, M. J., K. KATO, L. E. GRAY, C. J. WOLF, L. L. NEEDHAM, AND A. M. CALAFAT. URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 210(2-3):123-133, (2005).

Description:

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.

Purpose/Objective:

To study the excretion toxicokinetics of the Di-n-octyl phthalate metabolites in urine

URLs/Downloads:

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 02/24/2005
Completion Date: 12/31/2005
Record Last Revised: 08/22/2007
Record Created: 10/06/2006
Record Released: 10/06/2006
OMB Category: Other
Record ID: 159723

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

REPRODUCTIVE TOXICOLOGY DIVISION

ENDOCRINOLOGY BRANCH