PMID- 8685908
OWN - NLM
STAT- MEDLINE
DCOM- 19960821
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 139
IP  - 1
DP  - 1996 Jul
TI  - Interindividual differences in 2H8-toluene toxicokinetics assessed by 
      semiempirical physiologically based model.
PG  - 49-61
AB  - Recent applications of physiologically band toxicokinetic (PBTK) models have used 
      animal to human scaling, the hypothetical average man, and Monte Carlo techniques 
      to estimate human exposure to toxicants. Our study built a PBTK model suitable 
      for person-specific dosimetry. Individual measurements of age, ventilation rate, 
      blood/air partition coefficient, body weight, and adipose tissue fraction were 
      made on 26 male subjects exposed to 50 ppm 2H8-toluene and 50 ppm toluene for 2 
      hr at rest, with collection of venous blood samples for 120 hr postexposure. 
      Fitted lung metabolism was a novel feature of the PBTK model, used to explain a 
      systemic clearance of 2H8-toluene well in excess of hepatic blood flow. A 10-fold 
      interindividual range in venous concentrations was found. Subject-specific 
      modeling explained 91% of the observed data variability, compared to 53% using 
      literature values for model parameters. Body weight, adipose tissue fraction, and 
      blood/air partition coefficient were correlated with terminal half-life, 
      steady-state volume of distribution, and terminal volume of distribution. Lung 
      metabolism was correlated with systemic clearance and terminal half-life. 
      Interindividual differences in lung metabolism resulted in divergent predicted 
      fractions of 2H8-toluene in the body at 2 and 100 hr. An increased adipose 
      fraction led to lower blood concentrations up to 8 hr postexposure, and 
      simulations showed that at 98 hr, adipose tissue contained 97-99% of 2H8-toluene 
      in the body. Use of subject-specific model parameters greatly improved model fit 
      and demonstrated interindividual differences in toxicokinetics.
FAU - Pierce, C H
AU  - Pierce CH
AD  - Department of Environmental Health, University of Washington, Seattle 98195, USA.
FAU - Dills, R L
AU  - Dills RL
FAU - Morgan, M S
AU  - Morgan MS
FAU - Nothstein, G L
AU  - Nothstein GL
FAU - Shen, D D
AU  - Shen DD
FAU - Kalman, D A
AU  - Kalman DA
LA  - eng
GR  - ES 04696/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 3FPU23BG52 (Toluene)
SB  - IM
CIN - Toxicol Appl Pharmacol. 1997 Oct;146(2):328-9. PMID: 9346872
MH  - Absorption
MH  - Adipose Tissue/blood supply/metabolism
MH  - Adult
MH  - Aging/metabolism/physiology
MH  - Blood-Air Barrier/physiology
MH  - Body Weight/physiology
MH  - Computer Simulation
MH  - Environmental Exposure
MH  - Humans
MH  - Isotope Labeling
MH  - Linear Models
MH  - Liver/metabolism
MH  - Liver Circulation
MH  - Lung/metabolism
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Toluene/*pharmacokinetics/toxicity
MH  - Ventilation-Perfusion Ratio/physiology
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - S0041008X96901428 [pii]
AID - 10.1006/taap.1996.0142 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1996 Jul;139(1):49-61. doi: 10.1006/taap.1996.0142.