Variability in biological monitoring of solvent exposure. I. Development of a population physiological model.

Droz, Pierre‐Olivier; Wu, M M; Cumberland, William G.; Berode, M.

doi:10.1136/oem.46.7.447

Cited by 34 publications

(31 citation statements)

References 32 publications

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“…The solvents studied were perchloroethylene (PCE; Dallas et al 1994a, b;Gearhart et al 1993), styrene (Andersen and Ramsey 1983;Csanady et al 1994;Filser et al 1993;LoÈ f and Johanson 1993;Paterson and Mackay 1986;Perbellini et al 1988;Ramsey and Andersen 1984), and toluene (Droz et al 1989;Purcell et al 1990;Tardif et al 1993a, b), which have been widely used in industry and for which PB-PK models have been reported by several authors.…”

Section: Methodsmentioning

confidence: 99%

“…The exact structure of the model is therefore not critical. We used a PB-PK model that had been presented and used several times as the basic model in this study (Droz et al 1989;Droz 1996, 1997). It was written with BASIC and consisted of seven compartments representing di erent tissues.…”

Section: Methodsmentioning

confidence: 99%

“…Physiological parameters for the basic model of this study were calculated by equations (Droz et al 1989;Jang and Droz 1996) and are shown in the ®rst column of Table 1. The cardiac output and alveolar ventilation for a 50-W work load were 10.47 and 16.29 l/ min, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The tissue-gas partition coe cient of the fat compartment for perchloroethylene is 3020 in one model (Dallas et al 1994a), corresponding to 2-fold the values of 1450±1455 used in other models (Droz et al 1989;Gearhart et al 1993). For toluene, there is no big difference among the authors.…”

Section: Methodsmentioning

confidence: 99%

“…Some studies have pointed out the importance of di erences in input parameters in PB-PK model uncertainties (Hattis et al 1990(Hattis et al , 1993. The variability of PB-PK models and the sensitivity of model predictions to variability in the input parameters have also been investigated by many authors (Bois et al 1990;Clewell et al 1994;Droz et al 1989;Farrar et al 1989;Hetrick et al 1991;Spear and Bois 1994).…”

Section: Introductionmentioning

confidence: 99%

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Uncertainties in physiologically based pharmacokinetic models caused by several input parameters

Jang¹,

Droz²,

Chung³

1999

International Archives of Occupational and Environmental Health

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Objective: One of the problems in the application of physiologically based pharmacokinetic (PB-PK) models is that authors often use di erent input parameters, with unknown in¯uence on the results. Di erences in the simulation results obtained with various sets of parameters are examined herein. Method: Chemicals considered were perchloroethylene, toluene, and styrene. Simulations of alveolar concentrations, blood concentrations, and urinary metabolite excretions were performed for the three solvents. The input parameters discussed herein are physiological values, metabolic constants, and partition coe cients. The inuence of metabolic constants and partition coe cients is studied by comparison of models against one another. Results: Metabolic parameters such as V max and K m varied considerably between authors. Tissue-gas partition coe cients, especially for the fat compartment, also di ered according to the authors. Such di erences in input parameter values proved to have a large in¯uence on PB-PK model results and, therefore, increased their uncertainties. Uncertainties were much more signi®cant in urinary metabolite concentration than in alveolar and blood concentration for chemicals that are poorly metabolized. On the other hand, uncertainties were more signi®cant in alveolar and blood concentrations than in urinary metabolite excretions for chemicals that are well metabolized. Conclusion: Careful attention is necessary in the selection and/or citation of values from published data. The validity of PB-PK models should be simultaneously con®rmed with both the blood and/or alveolar concentration and urinary metabolite concentrations.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Uncertainties in physiologically based pharmacokinetic models caused by several input parameters

Jang¹,

Droz²,

Chung³

1999

International Archives of Occupational and Environmental Health

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Estimation of absorption of aromatic hydrocarbons diffusing from interior materials in automobile cabins by inhalation toxicokinetic analysis in rats

Yoshida

2010

J of Applied Toxicology

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Aromatic hydrocarbons, as well as aliphatic hydrocarbons, diffusing from interior materials in automotive cabins are the most common compounds contributing to interior air pollution. In this study, the amounts of seven selected aromatic hydrocarbons absorbed by a car driver were estimated by evaluating their inhalation toxicokinetics in rats. Measured amounts of these substances were injected into a closed chamber system containing a rat, and the concentration changes in the chamber were examined. The toxicokinetics of the substances were evaluated on the basis of the concentration-time course using a nonlinear compartment model. The amounts absorbed in humans at actual concentrations in automobile cabins without ventilation were extrapolated from the results obtained from rats. The absorbed amounts estimated for a driver during a 2 h drive were as follows (per 60 kg of human body weight): 30 microg for toluene (interior median concentration, 40 microg m(-3) in our previous study), 10 microg for ethylbenzene (12 microg m(-3)), 6 microg for o-xylene (10 microg m(-3)), 8 microg for m-xylene (11 microg m(-3)), 9 microg for p-xylene (11 microg m(-3)), 11 microg for styrene (11 microg m(-3)) and 27 microg for 1,2,4-trimethylbenzene (24 microg m(-3)). Similarly, in a cabin where air pollution was marked, the absorbed amount of styrene (654 microg for 2 h in a cabin with an interior maximum concentration of 675 microg m(-3)) was estimated to be much higher than those of other substances. This amount (654 microg) was approximately 1.5 times the tolerable daily intake of styrene (7.7 microg kg(-1) per day) recommended by the World Health Organization.

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A Physiologically Based Pharmacokinetic (PB-PK) Model for 1,2-Dichlorobenzene Linked to Two Possible Parameters of Toxicity

Hissink

Ommen

Krüse

et al. 1997

Toxicology and Applied Pharmacology

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Variability in biological monitoring of solvent exposure. I. Development of a population physiological model.

Cited by 34 publications

References 32 publications

Uncertainties in physiologically based pharmacokinetic models caused by several input parameters

Uncertainties in physiologically based pharmacokinetic models caused by several input parameters

Estimation of absorption of aromatic hydrocarbons diffusing from interior materials in automobile cabins by inhalation toxicokinetic analysis in rats

A Physiologically Based Pharmacokinetic (PB-PK) Model for 1,2-Dichlorobenzene Linked to Two Possible Parameters of Toxicity

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