PMID- 30027468
OWN - NLM
STAT- MEDLINE
DCOM- 20191114
LR  - 20191114
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 92
IP  - 9
DP  - 2018 Sep
TI  - Human metabolism and kinetics of tri-(2-ethylhexyl) trimellitate (TEHTM) after 
      oral administration.
PG  - 2793-2807
LID - 10.1007/s00204-018-2264-2 [doi]
AB  - Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for PVC material and is 
      used for medical devices as an alternative to di-(2-ethylhexyl) phthalate. As 
      plasticizers are known to migrate easily into contact liquids, exposure of 
      patients to TEHTM is highly probable. In the present study, human metabolism 
      pathways of TEHTM and its elimination kinetics were investigated. For that 
      purpose, four healthy volunteers were orally exposed to a single dose of TEHTM. 
      TEHTM and its postulated primary metabolites were investigated in blood samples 
      (up to 48 h after exposure), and in urine samples (collected until 72 h after 
      exposure) using liquid chromatography tandem mass spectrometry (LC-MS/MS). TEHTM 
      was found to be regioselectively hydrolyzed to its diesters di-2-(ethylhexyl) 
      trimellitates (1,2-DEHTM, 2,4-DEHTM) with maximum blood concentrations at 3-h 
      post-exposure, and to its monoester isomers mono-2-(ethylhexyl) trimellitates 
      (1-MEHTM, 2-MEHTM) with peak blood concentrations 5-h post-exposure. For the 
      elimination of investigated urinary metabolites, biphasic elimination kinetics 
      was observed. The most dominant urinary biomarker was found to be 2-MEHTM 
      (2-mono-(2-ethylhexyl) trimellitate), followed by several specific secondary 
      metabolites. All in all, approximately 5.8% of the orally administered dose was 
      recovered in urine over a period of 72 h, indicating a comparatively low 
      resorption rate of TEHTM in humans in combination with an apparently rather slow 
      metabolism and excretion rate. In fact, TEHTM and selected metabolites were still 
      detectable in blood and urine 48-h and 72-h post-exposure, respectively. This 
      study is the first to elucidate TEHTM metabolism pathways in humans and to 
      identify metabolites of TEHTM in blood and urine by usage of especially designed 
      human biomonitoring methods. Powerful tools for exposure monitoring and risk 
      assessment of TEHTM are therewith available for future research.
FAU - Hollerer, Christine
AU  - Hollerer C
AD  - Institute and Outpatient Clinic of Occupational, Social and Environmental 
      Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 
      91054, Erlangen, Germany.
FAU - Becker, Gunther
AU  - Becker G
AD  - OXEA GmbH, Rheinpromenade 4a, 40789, Monheim, Germany.
FAU - Goen, Thomas
AU  - Goen T
AD  - Institute and Outpatient Clinic of Occupational, Social and Environmental 
      Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 
      91054, Erlangen, Germany.
FAU - Eckert, Elisabeth
AU  - Eckert E
AUID- ORCID: 0000-0002-6037-9556
AD  - Institute and Outpatient Clinic of Occupational, Social and Environmental 
      Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 
      91054, Erlangen, Germany. elisabeth.eckert@fau.de.
LA  - eng
PT  - Journal Article
DEP - 20180719
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Benzoates)
RN  - 0 (Plasticizers)
RN  - 3319-31-1 (tri-(2-ethylhexyl)trimellitate)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Benzoates/administration & dosage/blood/*pharmacokinetics/urine
MH  - Chromatography, Liquid/methods
MH  - Diethylhexyl Phthalate/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Kidney/drug effects/metabolism
MH  - Kinetics
MH  - Male
MH  - Middle Aged
MH  - Plasticizers/pharmacokinetics
MH  - Tandem Mass Spectrometry/methods
OTO - NOTNLM
OT  - Biomonitoring
OT  - Elimination kinetics
OT  - Human metabolism
OT  - Plasticizers
OT  - Tri-(2-ethylhexyl) trimellitate
EDAT- 2018/07/22 06:00
MHDA- 2019/11/15 06:00
CRDT- 2018/07/21 06:00
PHST- 2018/05/25 00:00 [received]
PHST- 2018/07/12 00:00 [accepted]
PHST- 2018/07/22 06:00 [pubmed]
PHST- 2019/11/15 06:00 [medline]
PHST- 2018/07/21 06:00 [entrez]
AID - 10.1007/s00204-018-2264-2 [pii]
AID - 10.1007/s00204-018-2264-2 [doi]
PST - ppublish
SO  - Arch Toxicol. 2018 Sep;92(9):2793-2807. doi: 10.1007/s00204-018-2264-2. Epub 2018 
      Jul 19.