Variability in biological exposure indices using physiologically based pharmacokinetic modeling and Monte Carlo simulation

Thomas, RS; Bigelow, PL; Keefe, TJ; Yang, RS

HERO ID

819742

Reference Type

Journal Article

Year

1996

Language

English

PMID

8588550

HERO ID 819742
In Press No
Year 1996
Title Variability in biological exposure indices using physiologically based pharmacokinetic modeling and Monte Carlo simulation
Authors Thomas, RS; Bigelow, PL; Keefe, TJ; Yang, RS
Journal American Industrial Hygiene Association Journal
Volume 57
Issue 1
Page Numbers 23-32
Abstract By using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation, the interindividual variability in the concentrations of chemicals in a worker's exhaled breath and urine were estimated and compared with existing biological exposure indices (BEIs). The PBPK model simulated an exposure regimen similar to a typical workday, while exposure concentrations were set to equal the ambient threshold limit values (TLVs) of six industrial solvents (benzene, chloroform, carbon tetrachloride, methylene chloride, methyl chloroform, and trichloroethylene). Based on model predictions incorporating interindividual variability, the percentage of population protected was derived using TLVs as the basis for worker protection. Results showed that current BEIs may not protect the majority or all of the workers in an occupational setting. For instance, current end-expired air indices for benzene and methyl chloroform protect 95% and less than 10% of the worker population, respectively. Urinary metabolite concentrations for benzene, methyl chloroform, and trichloroethylene were also estimated. The current BEI recommendation for phenol metabolite concentration at the end-of-shift sampling interval was estimated to protect 68% of the worker population, while trichloroacetic acid (TCAA) and trichloroethanol (TCOH) concentrations for methyl chloroform exposure were estimated to protect 54% and 97%, respectively. The recommended concentration of TCAA in urine as a determinant of trichloroethylene exposure protects an estimated 84% of the workers. Although many of the existing BEIs considered appear to protect a majority of the worker population, an inconsistent proportion of the population is protected. The information presented in this study may provide a new approach for administrative decisions establishing BEIs and allow uniform application of biological monitoring among different chemicals.
Doi 10.1080/15428119691015188
Pmid 8588550
Wosid WOS:A1996TQ04900004
Url https://search.proquest.com/docview/77961364?accountid=171501
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword Humans; Models, Biological; Monte Carlo Method; Occupational Exposure/statistics & numerical data; Pharmacokinetics
Is Qa No