PMID- 17638682
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20121115
IS  - 1232-1087 (Print)
IS  - 1232-1087 (Linking)
VI  - 20
IP  - 2
DP  - 2007
TI  - Physiologically-based toxicokinetic modeling of durene 
      (1,2,3,5-tetramethylbenzene) and isodurene (1,2,4,5-tetramethylbenzene) in 
      humans.
PG  - 155-65
AB  - OBJECTIVES: Physiologically-based toxicokinetic (PB-TK) models are developed to 
      simulate absorption, distribution and excretion of xenobiotics. PB-TK models 
      consist of several groups of compartments, where tissues are grouped together 
      according to physiological parameters (tissue blood flows, tissue group volumes) 
      and physicochemical properties (partition coefficients, metabolic constants). 
      Tetramethylbenzene (TETMB), a mixture of its three isomers: prenitene 
      (1,2,3,4-TETMB), isodurene (1,2,3,5-TETMB), and durene (1,2,4,5-TETMB) is an 
      essential component of numerous commercial preparations of organic solvents. The 
      aim of the study was to develop the PB-TK model for two TETMB isomers, durene and 
      isodurene, in humans. MATERIALS AND METHODS: The assumed PB-TK model groups 
      organs and tissues into five physiological compartments: fat tissue, muscles, 
      organs, liver, and brain. The brain has been considered as a separate compartment 
      due to the potential neurotoxicity of TETMB. Water/air, oil/air and blood/air 
      partition coefficients for durene and isodurene were measured in vitro. 
      Tissue/air partition coefficients were calculated from values of olive/air and 
      water/air partition coefficients and the average fat and water content in 
      different tissues. Tissue/blood partition coefficients were calculated as a 
      tissue/air quotient and the blood/air partition coefficient measured in vitro. 
      The Michaelis-Menten constant (KM) values and maximum metabolism rate constant 
      (VMAX) for selected metabolites of durene and isodurene were obtained in vitro 
      using microsomal fraction of the human liver. RESULTS: The developed model was 
      validated against experimental data obtained earlier as a result of an 8-h 
      exposure of volunteers to durene and isodurene vapors of 10 and 25 mg/m3. The 
      prediction of both TETMB isomers concentration in blood as well as of the 
      elimination rates of 2,4,5-TMBA and 2,3,5-TMBA were close to the results of 
      experimental exposures. CONCLUSIONS: Simulations of one working week inhalation 
      exposure to aromatic hydrocarbons indicate that the elaborated PB-TK model may be 
      used to predict the chemical distribution in different body compartments, based 
      on physicochemical properties.
FAU - Jalowiecki, Piotr
AU  - Jalowiecki P
AD  - Department of Biological Monitoring, Nofer Institute of Occupational Medicine, 
      Lodz, Poland. pjalowiecki@mors.sggw.waw.pl
FAU - Janasik, Beata
AU  - Janasik B
LA  - eng
PT  - Journal Article
PL  - Poland
TA  - Int J Occup Med Environ Health
JT  - International journal of occupational medicine and environmental health
JID - 9437093
RN  - 0 (Benzene Derivatives)
RN  - 0 (Hydrocarbons, Aromatic)
RN  - 0 (Solvents)
RN  - 0 (Xenobiotics)
RN  - 0JBI5Y5A5Z (isodurene)
RN  - 181426CFYB (durene)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Benzene Derivatives/*metabolism/toxicity
MH  - Chromatography, Gas
MH  - Humans
MH  - Hydrocarbons, Aromatic/metabolism/toxicity
MH  - Male
MH  - *Metabolic Networks and Pathways
MH  - Models, Biological
MH  - Models, Molecular
MH  - Poland
MH  - Solvents/metabolism/toxicity
MH  - Toxicity Tests/methods
MH  - Xenobiotics/classification/*metabolism/toxicity
EDAT- 2007/07/20 09:00
MHDA- 2007/11/14 09:00
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
AID - 329L705542XM1714 [pii]
AID - 10.2478/v10001-007-0012-6 [doi]
PST - ppublish
SO  - Int J Occup Med Environ Health. 2007;20(2):155-65. doi: 
      10.2478/v10001-007-0012-6.