Impact of human variability on the biological monitoring of exposure to toluene: I. Physiologically based toxicokinetic modelling.

Using an approach involving physiologically based toxicokinetic (PBTK) modelling and Monte Carlo simulation (MCS), we investigated the impact of the biological variability affecting the parameters (e.g. physiological, physicochemical, biochemical) which determine toluene (TOL) kinetics on two exposure indicators (EIs): urinary excretion of o-cresol (o-CR), measured at the end of an 8 h exposure at 50 ppm, and unchanged TOL in blood (B-TOL) sampled prior to the last shift of a 5 day workweek. Population variance was described by assuming normal, or lognormal, distribution of parameter values and assigning to each one+/-2 S.D. (or+/-2 G.S.D.). PBTK-MCS (n=1000) resulted in a geometric mean (G.M.) of 0.635 mmol/mol creatinine for urinary o-CR, upper and lower limits (95%) ranging from 0.23 to 1.75, whereas, the GM for B-TOL was 120.6 microg/l (95% limits: 64.5-225.7). Overall, the results showed that this approach facilitates the prediction of the range of BEI values that could be anticipated to occur in a group of workers exposed to a chemical.

[1]  Pierre O. Droz,et al.  Simulation of Toluene in Venous Blood with a Physiologically Based Pharmacokinetic Model: Its Application to Biological Exposure Index Development , 1996 .

[2]  P. Droz,et al.  Ethnic differences in biological monitoring of several organic solvents. I. Human exposure experiment , 1997, International archives of occupational and environmental health.

[3]  M E Andersen,et al.  A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. , 1984, Toxicology and applied pharmacology.

[4]  R. Tardif,et al.  Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air , 1995, International archives of occupational and environmental health.

[5]  R. S. Thomas,et al.  Variability in biological exposure indices using physiologically based pharmacokinetic modeling and Monte Carlo simulation. , 1996, American Industrial Hygiene Association journal.

[6]  J. Brodeur,et al.  Assessment of Occupational Health Risk From Multiple Exposure: Review of Industrial Solvent Interaction and Implication for Biological Monitoring of Exposure , 1992, Toxicology and industrial health.

[7]  P O Droz,et al.  Variability in biological monitoring of organic solvent exposure. II. Application of a population physiological model. , 1989, British journal of industrial medicine.

[8]  R Tardif,et al.  Physiologically based pharmacokinetic modeling of a ternary mixture of alkyl benzenes in rats and humans. , 1997, Toxicology and applied pharmacology.

[9]  A Sato,et al.  Partition coefficients of some aromatic hydrocarbons and ketones in water, blood and oil. , 1979, British journal of industrial medicine.

[10]  M E Andersen,et al.  Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. , 1989, Toxicology and applied pharmacology.

[11]  R. Tardif,et al.  Impact of human variability on the biological monitoring of exposure to toluene, phenol, lead, and mercury: II. Compartmental based toxicokinetic modelling. , 2002, Toxicology letters.

[12]  T. Simon.  Combining physiologically based pharmacokinetic modeling with Monte Carlo simulation to derive an acute inhalation guidance value for trichloroethylene. , 1997, Regulatory toxicology and pharmacology : RTP.

[13]  D J Paustenbach,et al.  Proposed occupational exposure limits for select ethylene glycol ethers using PBPK models and Monte Carlo simulations. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[14]  M. Andersen,et al.  Sensitivity Analysis and the Design of Gas Uptake Inhalation Studies , 1995 .

[15]  Christopher J. Portier,et al.  Variability of safe dose estimates when using complicated models of the carcinogenic process. A case study: methylene chloride. , 1989 .

[16]  G. Csanády,et al.  The relevance of physical activity for the kinetics of inhaled gaseous substances , 2000, Archives of Toxicology.

[17]  C H Pierce,et al.  Interindividual differences in 2H8-toluene toxicokinetics assessed by semiempirical physiologically based model. , 1996, Toxicology and applied pharmacology.

[18]  G. Johanson,et al.  Toxicokinetics of organic solvents: a review of modifying factors. , 1998, Critical reviews in toxicology.

[19]  R. Tardif,et al.  o-cresol: a good indicator of exposure to low levels of toluene. , 1999, Applied occupational and environmental hygiene.

[20]  R S Yang,et al.  Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using advanced continuous simulation language (ACSL): a computational method. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.