This document summarizes a study that investigated using blood and exhaled air samples to monitor human exposure to hydrofluorocarbons (HFCs). The study exposed subjects to four common HFCs (HFC152a, HFC143a, HFC134a, HFC245fa) and measured levels in blood and exhaled air over time. A physiologically-based pharmacokinetic model was developed and fit the experimental data well. The study concluded that sampling blood or exhaled air is suitable for monitoring HFC exposure in humans, but samples should not be taken immediately after exposure when levels drop rapidly.

1. Blood and exhaled air can be used for
biomonitoring of hydrofluorocarbons in
humans
Lena Ernstgård
Work environment toxicology, Institute of Environmental Medicine
Karolinska Institutet, Sweden

2. Introduction
Various hydrofluorocarbons (HFCs) have replaced the ozone-depleting
chlorofluorocarbons and hydrochlorofluorocarbons in refrigeration and
air-conditioning applications.
Colorless gases with faint, ethereal smell and are low-or non-flammable
at atmospheric pressure and room temperature.
Four studied HFCs; 1,1-Difluoroethane (HFC152a), 1,1,1trifluoroethane (HFC143a), 1,1,1,2-tetrafluoroethane (HFC134a), and
1,1,1,3,3-pentafluoropropane (HFC245fa).

3. Aim
The main objective of this study was to investigate the
possibility to use blood and exhaled air for exposure
biomonitoring of HFCs.
Exposure to HFCs, e.g. during installation or repair of refrigeration
or air-condition systems, occur as short peaks and probably locally
distributed. Air monitoring in the breathing zone, may be
misleading. In such cases, biological exposure monitoring may be
advantageous as it more closely reflects the internal exposure.

4. Method
Exposures for 2 h at 50 W exercise.
HFC152a (0, 500, and 1000 ppm)
HFC143a (500 ppm)
HFC134a (500 ppm)
HFC245fa (0, 100, and 300 ppm)
Sample collection 0-22 h postexposure:
Capillary blood
Exhaled air
Urine
Temperature 18°C and humidity 30%
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5. Methods
Analysis of HFC in capillary blood, urine and exhaled air.
By gas-chromatography
The observed time courses in blood and exhaled air were described
with a physiologically-based pharmacokinetic (PBPK) model.
One model for all four HFC
In additional PBPK simulations, the experimental 2-h exposures were
extended to 8-h exposures to better capture occupational conditions.
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6. Partition coefficients
Blood/air, and tissue/blood coefficients are essential to characterize the
uptake and disposition of volatile substances.
Experimental data on human blood:air, olive oil:air and water:air
partition coefficients of all four HFCs and HFC125a (1,1,1,2,2pentafluoroethane).
Ernstgård L, Lind B, Andersen ME, Johanson G. Liquid-air partition coefficients of 1,1-difluoroethane
(HFC152a), 1,1,1-trifluoroethane (HFC143a), 1,1,1,2-tetrafluoroethane (HFC134a), 1,1,1,2,2pentafluoroethane (HFC125) and 1,1,1,3,3-pentafluoropropane (HFC245fa). J Appl Toxicol. 2010
Jan;30(1):59-62.
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7. PBPK model
The PBPK parameters (compartmental
volumes and blood flows and cardiac output)
were calculated for each individual by
allometric scaling based on body weight and
height.
Individually measured pulmonary ventilation
rates, and chamber air concentrations.
The parameters were also scaled to a 50-W
workload or to rest.
Sensitivity analyses showed that the blood:air
partition coefficient is the most sensitive
parameter.

8. Results
µM
Blood.
HFC152a (1000 ppm)
100
HFC143a (500 ppm)
HFC134a (500 ppm)
10
HFC245fa (300 ppm)
1
Exposure
0.1
0
60
120
180
Time (min)
240
300
360
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9. Conc, µM
100
Conc, µM
100
B. 300 ppm HFC245fa
A. 1000 ppm HFC152a
10
10
1
1
0.1
0.1
0.01
0.01
0
60
120
180
Time, min
240
300
0
360
60
120
180
240
300
360
Time, min
Conc, µM
Conc, µM
100
100
D. 500 ppm HFC134a
C. 500 ppm HFC143a
10
10
1
1
0.1
0.1
0.01
0
60
120
180
240
300
360
0.01
0
Time, min
Conc, µM
60
120
180
240
300
360
Time, min
100
E. 500 ppm HFC125a
10
1
0.1
0.01
0
60
120
180
240
Time, min
300
360
9

10. Conc, µM
HFC152a
HFC245a
HFC134a
HFC143a
HFC125a
Blood
10
Conc, µM
Blood
10
1
1
0.1
0.1
8,0
Time, h
8,5
0.01
0
2
4
6
Time, h
8
10
12
Exhaled air
10
Exhaled air
Conc, µM
Conc, µM
10
1
1
0.1
0.1
8,0
Time, h
8,5
0.01
0
2
4
6
Time, h
8
10
12
10

11. HFC152a
HFC143a
HFC134a
HFC245fa
HFC125a
Concentration in blood (µM)
Immediately after exposure
11.7
2.3
4.8
7.7
1.4
30 min after exposure
3.8
0.61
1.4
2.4
0.33
0.0073
0.019
0.019
0.13
0.036
Next morning
Concentration in exhaled air (µM)
Immediately after exposure
3.8
1.1
2.1
3.0
0.65
30 min after exposure
1.2
0.28
0.59
0.87
0.16
0.0023
0.0089
0.0077
0.049
0.017
Next morning
Half-time in blood (min)
Immediately after exposure
1.3
4.0
2.1
1.8
6.4
30 min after exposure
44
165
85
68
265
Next morning
129
223
220
443
317
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12. Conclusion
The experimental data as well as PBPK simulations
suggest that sampling of blood or exhaled air is
appropriate.
However, sampling should not be carried out
immediately after shift, as the levels in blood and
exhaled air drop rapidly during the first minutes postexposure where after the decline is considerably
slower.

13. Read more ….
Ernstgård L, Sjögren B, Gunnare S, Johanson G. Blood and exhaled air can be used
for biomonitoring of hydrofluorocarbon exposure. Submitted to Toxicol Lett.
Ernstgård L, Sjögren B, Dekant W, Schmidt T, Johanson G. Uptake and disposition of 1,1difluoroethane (HFC-152a) in humans. Toxicol Lett. 2012 Feb 25;209(1):21-9.
Ernstgård L, Andersen M, Dekant W, Sjögren B, Johanson G. Experimental exposure to 1,1,1,3,3Pentafluoropropane (HFC-245fa): Uptake and disposition in humans. Toxicol Sci. 2010
Feb;113(2):326-36.
Gunnare S, Ernstgård L, Sjögren B, Johanson G. Experimental exposure to 1,1,1-trifluoroethane
(HFC-143a): uptake, disposition and acute effects in male volunteers.
Toxicol Lett. 2007 Aug;172(3):120-30
Gunnare S, Ernstgård L, Sjögren B, Johanson G. Toxicokinetics of 1,1,1,2-tetrafluoroethane
(HFC-134a) in male volunteers after experimental exposure. Toxicol Lett. 2006 Nov 1;167(1):5465.

14. Co workers
Bengt Sjögren
Sara Gunnare
Gunnar Johanson
Thank you for your attention!
Lena Ernstgård
14 oktober 2013
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