REAL-TIME MEASUREMENTS OF VOC EXPOSURE AND HEART RATE VARIABILITY IN INDOOR AND OUTDOOR ENVIRONMENTS

Abstract

While various VOCs are known to show neurotoxic effects, the detailed mechanisms of VOCs on autonomic nervous system have not been fully understood partly because objective and quantitative measures to indicate neural abnormalities are still under development. Nevertheless, heart rate variability (HRV) has been recently proposed as an indicative measure of the autonomic defect. In this study, we used HRV as an indicative measure of the autonomic defect to relate their values to the personal concentrations of VOCs measured by a real-time VOC monitor. The measurements were conducted to 7 healthy subjects for 24 hours. The results showed HF powers were decreased for 6 subjects when the TVOC concentration changes were high, indicating the suppression of parasympathetic nervous induced by the exposure to VOCs. The present study indicated these real-time monitoring was useful to characterize the trends of VOC exposures and their effects on autonomic nervous system. Application of the present method is expected to lead to diagnosis and cure for the patients such as MCS and sick building syndrome in the future.

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REAL-TIME MEASUREMENTS OF VOC EXPOSURE AND HEART
RATE VARIABILITY IN INDOOR AND OUTDOOR ENVIRONMENTS

Atsushi Mizukoshi1†, Kazukiyo Kumagai1, Naomichi Yamamoto2, Miyuki Noguchi1,
Kazuhiro Yoshiuchi4, Hiroaki Kumano4, Yukio Yanagisawa1

1 Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan
2 Department of Nursing, The School of Health Sciences, Tokai University, Kanagawa, Japan
3Japan Society for the Promotion of Science (JSPS), Tokyo, Japan
4 Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

ABSTRACT
While various VOCs are known to show neurotoxic effects, the detailed mechanisms of VOCs on
autonomic nervous system have not been fully understood partly because objective and quantitative
measures to indicate neural abnormalities are still under development. Nevertheless, heart rate
variability (HRV) has been recently proposed as an indicative measure of the autonomic defect. In this
study, we used HRV as an indicative measure of the autonomic defect to relate their values to the
personal concentrations of VOCs measured by a real-time VOC monitor. The measurements were
conducted to 7 healthy subjects for 24 hours. The results showed HF powers were decreased for 6
subjects when the TVOC concentration changes were high, indicating the suppression of
parasympathetic nervous induced by the exposure to VOCs. The present study indicated these
real-time monitoring was useful to characterize the trends of VOC exposures and their effects on
autonomic nervous system. Application of the present method is expected to lead to diagnosis and cure
for the patients such as MCS and sick building syndrome in the future.

KEYWORDS
real-time assessment, VOCs, heart rate variability (HRV), Holter monitor

INTRODUCTION
Volatile organic compounds (VOCs) are of great concern because of their wide-range health impacts
(Cooke 1991, Jones 1999). In particular, it has been suggested that VOCs are the responsible
compounds for sick-building syndrome and multiple chemical syndrome (MCS). Although these
symptoms are suspected to be developed by frequent and/or continuous exposures to low
concentrations of VOCs (Cullen 1987), the detailed mechanisms have not been fully understood.
Various VOCs are known to show neurotoxic effects and cause clinical symptoms of fatigue, headache,
giddiness, nausea, a coma, melancholy and so on (Cooke 1991). To clarify the relationship between
the neurotoxic effects and the daily life VOC exposures, simultaneous measurements of both VOC
exposures and nervous system are essential. Recently the real-time monitor for total VOCs (TVOCs) in
a general environmental level has been developed (Coy et al 2000). Meantime, the effects on
autonomic nervous system are known to be estimated by the measurements of heart rate variability
(HRV) by the Holter monitor. Indeed, HRV has been measured to evaluate health effects by various
environmental pollutants. For example, HRV parameters such as %RR50, SD, LF and HF of asthmatic
children were lower than normal children even in the normal condition without an asthma attack
(Kazuma et al. 1997). It was clarified the increase of PM2.5 mass concentrations were related to the
decrease in low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) of HRV in the
elderly (Liao et al. 1999). To date, however, no research has been conducted using the real-time
measurements of VOC exposure and HRV. Therefore, the objective of this study is to conduct real-time

† Corresponding Author: Tel: +81-4-7136-4712, Fax: +81-4-7136-4712
E-mail address: atsushi_mizukoshi@yy.k.u-tokyo.ac.jp

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measurements of the VOC exposure and HRV by using the real-time VOC monitor and the Holter
monitor, respectively, to elucidate their relationship. In this study, the measurements were conducted
for 7 healthy subjects to demonstrate the usability of the present methodology.

METHOD
Study design
This study was designed to continuously and simultaneously monitor changes in TVOC concentrations
and HRV in daily life for 7 health subjects. The measurements were conducted from December 2006 to
January 2007. The subjects included 4 adult males and 3 adult females recruited from the laboratory
and the public. The ages of the subjects ranged from 22 to 54. The subjects were requested to carry
the Holter monitor and TVOC monitor for 24 hours from 8:00am and record Time-activity patterns.

HRV monitoring
HRV was measured by continuous electrocardiographic (ECG) monitoring using the Holter monitor
(FM-150 FUKUDA DENSHI Japan). In the analysis, intervals between the R waves of ECG (RR
intervals) were used. HF (High frequency, 0.15-0.4 Hz) and LF (Low frequency, LF, 0.04-0.15 Hz)
power were calculated for each 10 sec interval by Gabor wavelet transform (Fluclet WT Dainippon
Sumitomo Phrma Japan) and averaged in 5 min interval. While HF was used as an indicator of
parasympathetic nervous function, the ratio of LF to HF was used as an indicator of sympathetic
nervous function (Task Force of The European Society of Cardiology and The North American Society
of Pacing and Electrophysiology 1996).

TVOC monitoring
Exposure concentrations of TVOCs were measured by a portable real-time monitor using photon
ionization detection (PID) (ppbRAE RAE systems USA). TVOC concentrations were calculated as
toluene equivalent concentrations for each 5 min interval. Furthermore, the maximum and minimum
TVOC concentrations in 5 min were also measured and TVOC concentration changes in 5 min (Δ
TVOC, µg/m3) were calculated by subtracting minimum concentration from maximum concentration. Δ
TVOC was used as an indicator of the amount of maximum concentration change in 5 min.

Time-activity pattern
Time-activity patterns in each 5 min interval were recorded by the subjects. The subjects were
requested to select kinds of activities and microenvironments from the following items. The kinds of the
activities included exercise, eating, sleeping and the other. The kinds of the microenvironments
included home, office, other indoor and outdoor.

RESULTS ANALYSIS AND DISCUSSION
Time series data
An example of the time series data is shown in Fig.1. In the figure, the TVOC concentration change was
notably large (mean±SD, 354±349, range 63-1447 µg/m3). According to time-activity pattern, the peaks
at 8:40 and 21:05 were speculated to be outdoor sources and the peaks at 18:00 and 21:50 were
speculated to be indoor sources from meals. From the time series of HRV parameters, the HF
decreased during exercise and increased during eating and sleeping. Therefore to exclude the
confounding effects by the abovementioned tendencies, we used the HRV data excluding the time for
exercise, eating and sleeping.

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Summary statistics
Exposure
TVOCs and HRV parameters for
all subjects are summarized in
Table 1. This result indicates that
the exposure concentrations differ
by each microenvironment. This is
considered to be due to the
difference of VOC compositions in
each microenvironment (Saarela
2003). Inter-individual variation in
concentration at office was low
values since 6 subjects stayed at
same building.

Bivariate analysis
The Spearman rank correlations were calculated to assess the correlations between TVOC exposures
and HRV parameters. Table 2 shows the correlations for all subjects. The significant negative
correlations between ΔTVOC and HF were observed in 6 out of 7 subjects, while 2 out of 7 cases
were negatively significant between TVOC concentrations and HF. Based on these results, it seems
that HF decreases with change of TVOC concentrations rather than concentrations of TVOCs. The
significant negative correlations were observed between ΔTVOC and LF/HF in 4 subjects, indicating
concentrations of
Fig.1. Time series of TVOC concentration and HRV for a subject
0
500
1000
1500
8:00
10:0012:0014:0016:0018:0020:0022:00
0:002:004:006:008:00
TVOC concentration (µg/m3)
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
Log10 HF (msec2), Log10 LF/HF
Exercise EatingSleeping TVOCHF LF/HF
Table 1. Summary of TVOC exposure concentration and HRV
Na
Mean±SDb
CVc
TVOC exposure concentration (µg/m3)
Total7 175±12873
Home7 327±26581
Office6 93±3133
Other indoor6 219±77 35
Outdoor6164±7143
HRV
HF (msec2)
787.7±87.6100
LF/HF ratio711.0±10.797
a Sample size
b Standard deviation
c Coefficient of variance
Table 2. Correlation between TVOC exposure and HRV
+-
TVOC vs HF-0.24 **-0.05-0.090.11-0.37 **-0.070.0102
∆TVOC vs HF-0.22 **-0.67 ** -0.33 **-0.04 -0.32 **-0.26 ** -0.25 **06
TVOC vs LF/HF 0.26 **0.16-0.06 0.120.00-0.05-0.1410
∆TVOC vs LF/HF0.16 *0.34 **0.09 0.15 0.17 *-0.25 ** 0.43 **41
* Spearman rank correlation, p<0.05 + Positive correlation
* Spearman rank correlation, p<0.01 - Negative correlation
Number of significant
correlation
efg
Subject
abcd

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the changes of TVOC concentrations were associated with the decrease of the activity of
parasympathetic nervous and enhancement of the activity of the sympathetic nervous system.
Since compositions of VOCs differ with microenvironments, the health effects may also differ. To adjust
such differences, the correlations between TVOC exposures and HRV parameters were investigated in
each microenvironment. Table 3 shows the number of significant correlations between TVOC and HRV
in each environment (p＜0.05). The result indicates the significant negative correlations were observed
in indoor environments such as home, office and other indoor between ΔTVOC concentration and HF.
Therefore in this case, indoor VOCs may have influence on the autonomic nervous system more than
outdoor.

CONCLUSIONS
In this study, real-time measurements of VOC exposure and HRV in daily life were conducted and the
relationships between the TVOC exposures and their effects were investigated. For 6 out of 7 subjects,
the HF powers characterized by the Holter monitor were decreased when the TVOC concentration
changes were large, indicating the suppression of parasympathetic nervous because of exposures to
VOCs. Although the measurements were conducted for healthy subjects in this study, the
measurements are expected for the patients such as MCS and sick building syndrome. Application of
the present measurement methodology is expected to lead to diagnosis and cure for such adverse
health symptoms in the future.

ACKNOWLEDGEMENTS
We are grateful to all the subjects for their cooperation. This study was supported by Health Labour
Sciences Research Grant and Grant-in-Aid for Scientific Research (A).

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Table 3. Number of significant correlation between TVOC exposure and HRV
+-+-+-+-
TVOC vs HF00140100
∆TVOC vs HF04030211
TVOC vs LF/HF11200101
∆TVOC vs LF/HF10100000
+ Positive correlation - Negative correlation
Outdoor Home OfficeOther indoor