Assessment of the percutaneous absorption of trichloroethylene in rats andhumans using MS/MS real-time breath analysis and physiologically based pharmacokinetic modeling
Ts. Poet et al., Assessment of the percutaneous absorption of trichloroethylene in rats andhumans using MS/MS real-time breath analysis and physiologically based pharmacokinetic modeling, TOXICOL SCI, 56(1), 2000, pp. 61-72
The development and validation of noninvasive techniques for estimating the
dermal bioavailability of solvents in contaminated soil and water can faci
litate the overall understanding of human health risk. To assess the dermal
bioavailability of trichloroethylene (TCE), exhaled breath was monitored i
n real time using an ion trap mass spectrometer (MS/MS) to track the uptake
and elimination of TCE from dermal exposures in rats and humans. A physiol
ogically based pharmacokinetic (PBPK) model was used to estimate total bioa
vailability, Male F344 rats were exposed to TCE in water or soil under occl
uded or nonoccluded conditions by applying a patch to a clipper-shaved area
of the back. Rats were placed in off-gassing chambers and chamber air TCE
concentration was quantified for 3-5 h postdosing using the MS/MS, Human vo
lunteers were exposed either by whole-hand immersion or by attaching patche
s containing TCE in soil or water on each forearm. Volunteers were provided
breathing air via a face mask to eliminate inhalation exposure, and exhale
d breath was analyzed using the MS/MS, The total TCE absorbed and the derma
l permeability coefficient (K-p) were estimated for each individual by opti
mization of the PBPK model to the exhaled breath data and the changing medi
a and/or dermal patch concentrations. Rat skin was significantly more perme
able than human skin. Estimates for K-p in a water matrix were 0.31 +/- 0.0
1 cm/h and 0.015 +/- 0.003 cm/h in rats and humans, respectively. K-P estim
ates were more than three times higher from water than soil matrices in bot
h species. K-P values calculated using the standard Fick's Law equation wer
e strongly affected by exposure length and volatilization of TCE, In compar
ison, K-P values estimated using noninvasive real-time breath analysis coup
led with the PBPK model were consistent, regardless of volatilization, expo
sure concentration, or duration.