Handbook of Solvents - George Wypych - ChemTech - Ventech!

1090 Myrto Petreas
of time after exposure. One study involved single exposures, whereas in others at least some
of the subjects participated more than once.
In one of the first chamber studies, nine male volunteers were exposed to 100-200 ppm
of PERC for 80 to 180 minutes. Concentrations of PERC in exhaled air were measured over
time. 54 The authors demonstrated that exposures of similar duration resulted in similar decay
curves of PERC concentrations in breath after exposure. In addition, the data showed
that the length of time that PERC was measurable in exhaled air was proportional to both the
concentration and the duration of the exposure.
The same group 55 exposed sixteen males to single and repeated concentrations of 100
ppm PERC for periods of 7 hrs/day over a 5-day workweek. Alveolar air samples were collected
over a period of up to 300 hours post-exposure. The authors observed higher alveolar
air concentration in subjects with greater body mass. They recommended measurement of
PERC in alveolar air 2-16 hours post-exposure to assess the average exposure.
Six healthy males were exposed to 72 and 144 ppm, as well as 142 ppm with 2 half
hours of 100 W of exercise. 51 Uptake of PERC was calculated from the minute volume and
the concentration of PERC in breath. PERC was measured in breath and blood and TCA
was measured in blood and urine. During the first hour of exposure the uptake was higher by
25% than during the last hour and retention decreased with time and with exercise. The
mean ratio of the concentration of PERC in venous blood and the concentration of PERC in
mixed exhaled air was 23. Assuming a mix-exhaled air to end-exhaled air ratio of 0.71, they
estimated a blood/air partition coefficient of 16. After 20 hours from the end of exposure the
half-life was estimated to be 12-16 hours, after 50 hours the half-life was estimated to be
30-40 hours and after 100 hours it was estimated at approximately 55 hours. The authors estimated
that 80-100% of PERC was excreted unchanged through the lung, and about 2%
was excreted as TCA in the urine.
Simple and multiple linear regression analyses were applied to the data collected
above to predict the best estimator of exposure to PERC. 56,57 PERC in blood was the best
predictor followed by PERC in exhaled air. TCA per gram of creatinine in urine was the
least reliable predictor.
Twenty four subjects were exposed to 100, 150 and 200 ppm of PERC for 1 to 8
hours. 52 The concentration of PERC in alveolar air decreased rapidly during the first hours
of the post-exposure period, but 2 weeks were required for complete elimination following
an exposure of 100 ppm for 8 hours. The authors were the first to demonstrate that the rate of
rise and of decay of the alveolar concentration with respect to time was independent of the
level of the inspired concentration during exposure.
The experimental data from the above study were used in a pharmacokinetic model 58
that divided the body into four tissue compartments: the Vessel Rich Group (VRG), the
Muscle Group (MG), the Fat Group (FG) and the Vessel Poor Group (VPG). No metabolic
pathway was considered. After 20 hours from the end of the exposure the concentration of
PERC in alveolar air was related to release from the FG with an approximate half-life of
71.5 hours. The model predicted small differences in alveolar concentrations due to differences
in body weight, height and fat tissue. The authors provided a nomogram to predict
mean exposure given the exposure duration (0-8 hrs), time since end of exposure (0-8 hrs)
and post-exposure measurement of the alveolar air concentration.
A perfusion-limited, four compartment model was used to simulate the effect of several
confounding factors on the levels of several contaminants in the breath, including
PERC. 6 The model, which considered metabolic clearance, consisted of a pulmonary compartment,
a vessel-rich group, a group of low-perfused tissues containing muscles and skin,
and a group of poorly perfused fatty tissues. The authors predicted that intra-day fluctuations
in exposure would have a large effect on breath sampled just after the shift, but that the