Development of a physiologically based pharmacokinetic model for chloroform

Corley, Richard A.; Mendrala, Alan L.; Smith, F.A.; Staats, D.A.; Gargas, Michael L.; Conolly, Rory B.; Andersen, Melvin E.; Reitz, Richard H.

doi:10.1016/0041-008x(90)90324-n

Cited by 175 publications

(84 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Partition coefficient values of DCP and TCP were determined using the vial-equilibration method (Gargas et al, 1989;Vinegar et al, 1994). A literature value was used for chloroform (Corley et al, 1990). Human blood samples were collected from Subject A to determine the blood/air partition coefficient.…”

Section: Blood/air Partition Coefficientmentioning

confidence: 99%

Human respiratory uptake of chloroform and haloketones during showering

Weisel

2004

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

Inhalation is an important exposure route for volatile water contaminants, including disinfection by-products (DBPs). A controlled human study was conducted on six subjects to determine the respiratory uptake of haloketones (HKs) and chloroform, a reference compound, during showering. Breath and air concentrations of the DBPs were measured using gas chromatography and electron capture detector during and following the inhalation exposures. A lower percentage of the HKs (10%) is released from shower water to air than that of chloroform (56%) under the experiment conditions due to the lower volatility of the HKs. Breath concentrations of the DBPs were elevated during the inhalation exposure, while breath concentrations decreased rapidly after the exposure. Approximately 85-90% of the inhaled HKs were absorbed, whereas only 70% of the inhaled chloroform was absorbed for the experiment conditions used. The respiratory uptake of the DBPs was estimated using a linear one-compartment model coupled with a plug flow stream model for the shower system. The internal dose of chloroform normalized to its water concentration was approximately four times that of the HKs after a 30-min inhalation exposure. Approximately 0.3-0.4% of the absorbed HKs and 2-9% of the absorbed chloroform were expired through lung excretion after the 30-min exposure. The inhalation exposure from a typical 10-15 min shower contributes significantly to the total dose for chloroform in chlorinated drinking water but only to a moderate extent for HKs.

show abstract

Section: Blood/air Partition Coefficientmentioning

confidence: 99%

Human respiratory uptake of chloroform and haloketones during showering

Weisel

2004

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

show abstract

“…Physiologically based pharmacokinetic (PBPK) models give information about the absorption, elimination and distribution of a pollutant in an organism by integrating physiology of the organism and biochemistry of the specific pollutant (Clewell and Clewell, 2008;Reddy et al, 2005). Traditionally, these models were used to describe the kinetics of chemicals in rodents (Corley et al, 1990;Reitz et al, 1988). Recently, the bioaccumulation of environmental pollutants, such as polychlorinated biphenyls (PCBs) in wildlife and humans has Toxicology and Applied Pharmacology 256 (2011) 136-145 received increasing attention (Hickie et al, 1999;Maruyama and Aoki, 2006;Redding et al, 2008;Sonne et al, 2009;Verner et al, 2008;Weijs et al, 2010b).…”

Section: Introductionmentioning

confidence: 99%

A non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in protected marine mammals: PBPK modeling in harbor porpoises

Weijs

Yang

Das

et al. 2011

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically, these models provide a new, non-destructive tool that enables the integration of biomonitoring activities and in vitro studies. The goals of the present study were firstly to develop PBPK models for several environmental relevant PCB congeners in harbor porpoises (Phocoena phocoena), a species that is sensitive to pollution because of its limited metabolic capacity for pollutant transformation. These models were tested using tissue data of porpoises from the Black Sea. Secondly, the predictive power of the models was investigated for time trends in the PCB concentrations in North Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess metabolic capacities of harbor porpoises for the investigated PCBs. In general, results show that parameter values from other species (rodents, humans) are not always suitable in marine mammal models, most probably due to differences in physiology and exposure. The PCB 149 levels decrease the fastest in male harbor porpoises from the North Sea in a time period of 18 years, whereas the PCB 101 levels decrease the slowest. According to the models, metabolic breakdown of PCB 118 is probably of lesser importance compared to other elimination pathways. For PCB 101 and 149 however, the presence of their metabolites can be attributed to bioaccumulation of metabolites from the prey and to metabolic breakdown of the parent compounds in the harbor porpoises.

show abstract

“…The main target organs were generally the kidney and liver. Corley et al ( 1990 ) developed a PBPK model for chloroform and obtained information on the various parameters such as blood:air ( 7.4) , fat:blood (37.7 ), slowly perfused tissue:blood (1.6 ), rapidly perfused tissue:blood ( 2.3 ) partition coefficients, maximum rate of metabolism (307.0 mg /h) and Michaelis ± Menten constant for metabolism (0.448 mg /l ), which were later used by other studies. Blancato and Chiu ( 1993 ) applied PBPK modelling to examine the biologically effective dose resulting from exposure to chloroform in water.…”

Section: Physiologically Based Pharmacokinetic Modelingmentioning

confidence: 99%

“…Physiologically based pharmacokinetic (PBPK ) models have been used to model the relative uptake from various exposure routes and the distribution of chloroform in the body (Corley et al, 1990;Blancato and Chiu, 1993;Chinery and Gleason, 1993;McKone, 1993;Georgopoulos et al, 1994;Smith and Evans, 1995 ) . The main target organs were generally the kidney and liver.…”

Section: Physiologically Based Pharmacokinetic Modelingmentioning

confidence: 99%

Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies

Nieuwenhuijsen

Toledano²,

Elliott³

2000

J Expo Sci Environ Epidemiol

163

View full text Add to dashboard Cite

We have reviewed the relevant issues in the exposure assessment of disinfection by -products ( DBPs ) of chlorination for epidemiological and health risk assessment. Various DBPs can be detected in drinking water and swimming pools, and the reported levels show a considerable range, but were generally below the current health standard for total trihalomethanes ( TTHMs ) ( 100 g / l ) . Relatively little information is available on the correlation between the various DBPs in drinking water and in swimming pools. Chloroform was generally, but not always, the most predominant DBP. In epidemiological studies, TTHM levels have been used as an indicator for total DBP load, even though TTHM levels do not always correlate well with individual DPBs. Factors such as residence time, temperature, pH, organic content, including humic and fulvic acid and bromide levels affect the composition and levels of DBPs. Although there are biomarkers of DBPs, mainly for chloroform and more recently for the other volatile trihalomethanes ( THMs ) and the nonvolatile haloacetic acids ( HAAs ) such as trichloroacetic acid ( TCAA ) and dichloroacetic acid ( DCAA ) , they have not been used in epidemiological studies. The THMs have been measured in exhaled breath and serum, while the HAAs have been measured in urine. These biomarkers have been useful to estimate the actual uptake of the DBPs and the relative contribution of various exposure routes. Physiologically based pharmacokinetic ( PBPK ) models exist for, e.g. chloroform, but their main target organs are the kidney and liver and they have not been used in epidemiological studies. Tap water ingestion, showering, bathing, swimming, boiling water and dishwashing are all activities that have been associated with the uptake of DBPs, and considerable variation in these activities has been observed between people. No studies have reported on the correlation between human uptake of DBPs and water -zone mean estimates, but various studies found a good correlation between THM concentrations in exhaled breath and THM concentrations in water during showering and swimming. In general exposure assessment in epidemiological studies has been limited which complicates the interpretation. These findings have implications for epidemiological studies, particularly with reference to Berkson and classical error type models, study power, attenuation and precision of health -risk estimates and study efficiency. Recommendations are made for further areas of study.

show abstract

Development of a physiologically based pharmacokinetic model for chloroform

Cited by 175 publications

References 25 publications

Human respiratory uptake of chloroform and haloketones during showering

Human respiratory uptake of chloroform and haloketones during showering

A non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in protected marine mammals: PBPK modeling in harbor porpoises

Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies

Contact Info

Product

Resources

About