Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
3070746
Reference Type
Journal Article
Title
Phthalate metabolism and kinetics in an in vitro model of testis development
Author(s)
Harris, S; Wegner, S; Hong, SW; Faustman, EM
Year
2016
Is Peer Reviewed?
Yes
Journal
Toxicology In Vitro
ISSN:
0887-2333
EISSN:
1879-3177
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Location
OXFORD
Volume
32
Issue
Elsevier
Page Numbers
123-131
Language
English
PMID
26689326
DOI
10.1016/j.tiv.2015.12.002
Web of Science Id
WOS:000372760900014
URL
https://linkinghub.elsevier.com/retrieve/pii/S0887233315300254
Exit
Abstract
We have developed an in vitro model of testis development (3D-TCS) using rat testicular cells overlaid with extracellular matrix. One barrier preventing utilization of in vitro models in toxicity testing is the absence of metabolic capability. Another challenge is lack of kinetic data for compounds in vitro. We characterized metabolic capabilities and investigated the kinetics of phthalate male reproductive toxicants in the 3D-TCS. Cells were treated with three phthalate diesters for 2, 8 and 24h. Parent compounds and metabolites were measured in cell culture media and cell lysate via mass spectrometry. Levels of monoester metabolites were used as an indication of metabolism of phthalates via lipase activity. Metabolites were detected in all treated cell media and cell lysate samples, with levels ranging from <0.5-14.7% of initial mass of parent compound. Phthalates partitioned between media and lysate in a manner consistent with each compound's degree of lipophilicity. UDGPT activity was detected in DBP and DEP treated samples. 3D-TCS microarray data indicated gene expression for lipases and CYPP450s. Results indicate that the 3D-TCS is a metabolically active co-culture and that physiochemical properties can provide information about the kinetics of compounds in the 3D-TCS, improving our ability to interpret results from the model.
Keywords
Phthalate esters; Reproductive toxicity; in vitro models; Testes; Metabolism; Organotypic
Tags
IRIS
•
Dibutyl Phthalate (DBP)
Database Searches
Litsearch Jan 2016 - July 2016
Pubmed
WOS
LitSearch Jul 2016 - Jan 2017
Prior search overlap
PubMed
WoS
Studies with Supporting Data
Mechanistic and genotoxicity studies
Studies with Health Effects Data
Animal toxicology studies
Litsearch June 2015 - Jan 2016
Pubmed
•
Diethyl phthalate (DEP)
Database searches
Jan 2016 update
Pubmed
Jun 2016 update
Pubmed
Web of Science
Jan 2017 update
Prior search overlap
Web of Science
Jan 2020 update
PubMed
Web of Science
Studies with Supporting Data
Toxicokinetics
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity