145

Ann. occup. Hyg., Vol. 47, No. 2, pp. 145150, 2003

Crown Copyright 2003. Reproduced with the permission of the Controller
of Her Majestys Stationery Office. Published by Oxford University Press
DOI: 10.1093/annhyg/meg016
Factors Affecting the Extent of Dermal Absorption of
Solvent Vapours: A Human Volunteer Study
K. JONES
1
*, J. COCKER
1
, L. J. DODD
1
and I. FRASER
2
*Author to whom correspondence should be addressed.
Tel: 0114-289-2774; fax: 0114 289 2768; e-mail:
katherine.jones@hsl.gov.uk
1
Health & Safety Laboratory, Broad Lane, Sheffield S3 7HQ;
2
Health & Safety Executive, Bootle,
Liverpool L20 3QZ, UK
Received 15 August 2002; in final form 6 November 2002
Objectives: We have previously reported that solvent vapours can be absorbed through the skin
and that the extent varies markedly and depends on the chemical. For some chemicals, the
extent of absorption is significant, e.g. for 1-methoxy-2-propanol dermal absorption accounts
for up to 14% of the total absorbed dose after 8 h exposure at the OES. We have conducted a
second study using 2-butoxyethanol to investigate the influence of temperature, humidity and
clothing on the dermal absorption of vapours. As for the first study, the extent of dermal
absorption was determined by biological monitoring to measure the resultant body burden of
the chemical.
Methods: Four volunteers were exposed on nine occasions. For eight of these exposures they
wore air-fed half-masks to supply clean air for the inhalation route. The baseline conditions
(one whole body and one skin only exposure) were 25C, 40% relative humidity with volun-
teers wearing shorts and T-shirt. For each subsequent exposure, a single parameter was
changed: humidity (60%, 65%), temperature (20C, 30C) or clothing (minimal and overalls).
Finally, a industrial scenario was conducted where volunteers wore overalls over their shorts
and T-shirts and environmental conditions reflected high temperature and high humidity
(30C, 60%), such as might be encountered in a tank-cleaning operation or similar.
Results: Results show that baseline dermal absorption of 2-butoxyethanol vapour was, on
average, 11% of the total absorbed dose. Higher temperature (30C, mean 14%, P = 0.03) and
greater humidity (65% RH, mean 13%, P = 0.1) increased dermal absorption. The wearing of
whole-body overalls did not attenuate absorption (mean 10%). By combining several factors
together in the industrial scenario, dermal absorption of vapours was significantly increased
with a mean of 39% of the total absorbed dose.
Conclusions: The work has shown that dermal absorption of vapours can be significant and
that environmental conditions may affect the absorption. Some types of protective clothing may
not be suitable to reduce absorption. The possibility of dermal absorption of vapours should be
considered particularly for workers in high vapour concentration conditions where control of
exposure relies on respiratory protection.
Keywords: 2-butoxyethanol; solvent vapours; dermal absorption; temperature; humidity; clothing
INTRODUCTION
Although skin absorption of organic solvents in the
liquid phase is well recognized, fewer data on absorp-
tion of solvent vapours through the skin are available.
We have previously published a study (Brooke et al.,
1998) investigating the extent of dermal absorption
of vapours for a range of organic solvents. This study
showed that the extent of skin absorption can vary
widely and depends on the chemical. For some chem-
icals, the extent of absorption was significant, e.g. for
1-methoxy-2-propanol (a glycol ether) dermal absorp-
tion accounts for up to 14% of the total absorbed
dose. Other authors (Johanson and Boman, 1991;
Corley et al., 1997; Kezic et al., 1997) have also
studied the dermal absorption of glycol ether
vapours. Johanson and Boman (1991) estimated
(from a whole body exposure) that up to 75% of body
burden for butoxyethanol could be due to dermal
aborption of vapours. This estimate was disputed by

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146 K. Jones et al.
Corley et al. (1997) who estimated (using PBPK
modelling from a single arm exposure) the dermal
absorption contribution to be 1527% depending on
environmental conditions. Kezic et al. (1997) also
used an arm exposure (forearm) to assess the dermal
absorption of methoxy- and ethoxyethanol vapour.
They estimated that 4055% of the body burden
could be due to dermal absorption of vapours at very
high vapour concentrations (1000 and 1250 p.p.m.
versus UK exposure limits of 5 and 10 p.p.m.). Mraz
and Nohova (1992) investigated the dermal absorp-
tion of N,N-dimethylformamide vapours and showed
that this could account for 1336% of the body
burden. They observed that temperature and humid-
ity strongy influenced the extent of absorption.
Studies have shown that temperature, humidity and
occlusion all have an influence on the extent of skin
hydration and permeability (Wiechers, 1989; Vana-
koski et al., 1996; Boman and Maibach, 2000). Vana-
koski et al. (1996) suggested that high temperature
(82C in a sauna) increased skin absorption through
enhanced skin blood flow. Schafer et al. (2002)
studied the effects of occlusion and environmental
conditions on the forearms of volunteers. Lower
temperatures and humidity (20C and 30%, respect-
ively) had little impact on skin surface water loss or
the relative humidity in the microclimate between the
skin and the occlusive article but did reduce skin
hydration. Higher temperatures and humidity (30C
and 75%, respectively) increased both the relative
humidity of the microclimate and skin hydration. In
addition, the use of a vapour-impermeable occlusion
reduced skin surface water loss. Meuling et al. (1997)
studied the dermal absorption of the pesticide
propoxur at 30C under various humidities (50, 70 or
90%). The percentage body burden attributable to
dermal absorption increased from 13% (at 50% rela-
tive humidity) to 63% (at 90% RH), indicating that
skin moisture is important in dermal absorption of
propoxur.
Despite studies showing that temperature, humidity
and occlusion influence dermal absorption and that
higher temperatures and humidities can dramatically
increase the penetration of liquids through the skin,
there has been little work on the effect of such factors
on the dermal absorption of vapours. Dermal absorp-
tion of vapours can be significant although there are
some conflicting data. Johanson and Boman (1991)
reported 75% dermal absorption for 2-butoxyethanol
whereas Corley et al. (1997) estimated a maximum of
only 27% under various environmental scenarios.
The study reported here has investigated the effects
of temperature, humidity and clothing on the whole
body dermal absorption of 2-butoxyethanol in order
to clarify some of the data and determine the potential
consequences of dermal absorption of vapours to
workers.
The study reported here was conducted in a similar
manner to our previous study (Brooke et al., 1998) of
whole body absorption of chemical vapours under a
series of controlled environmental conditions.
MATERIALS AND METHODS
Volunteers
The experimental protocol was approved by the
Health & Safety Executive Research Ethics Committee
and all volunteers provided written informed consent
before participating in the study. Four volunteers (2
male, 2 female, aged 2833) took part in the study
and were exposed on nine separate occasions, each
occasion separated by at least 3 weeks. All the volun-
teers were in good health at the time of the study, did
not suffer from respiratory disease and were not on
medication. A medical assessment was made imme-
diately before the start of each experiment by a
medical supervisor to ensure that each volunteer was
fit to participate in the study. The medical supervisor
was present throughout the exposure period and
assessed each volunteer afterwards to ensure they
were fit for discharge. All volunteers were asked to
refrain from taking alcohol for 12 h before and after
exposure.
Exposure protocol
In total there were nine exposure sessions, two of
which were conducted under baseline conditions. All
exposures were 50 p.p.m. 2-butoxyethanol for 2 h
(8 h TWA OES 25 p.p.m.). Exposures were performed
in the Health & Safety Laboratory Controlled
Atmosphere Facility, a purpose-built room of 8 m
3
volume. Experimental atmospheres were generated
by introducing 2-butoxyethanol vapour into the room
by purging solvent-filled bubblers with compressed
air. The atmospheric concentration within the chamber
was then monitored continuously by two independ-
ently calibrated Miran infra-red spectrophotometers.
One infra-red spectrophotometer was calibrated by
an internal closed-loop system and the other by a
dynamically generated standard atmosphere (MDHS3)
(HSE, 1990).
Under the baseline conditions, volunteers were
exposed at rest whole body and skin only on two
separate occasions. The baseline conditions were
25C, 40% relative humidity with volunteers wearing
shorts and T-shirt. For skin only exposure, the
volunteers wore air-fed half-masks (clean air at a
flow rate of 80100 l/min) so that the inhalation route
was excluded as a source of uptake. Inward leakage
into the masks was assessed using the methods
described in EN140 (1989) and was confirmed to be
<0.02% for all volunteers. For the whole body
exposures no masks were used and thus uptake was
via inhalation, ingestion and dermal routes. In this
way, by comparing the differences in measures of

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Dermal absorption of solvent vapours 147
body burden between the two exposure conditions,
the contribution via dermal absorption could be
assessed. For the subsequent exposures, volunteers
also wore air-fed half-masks and a single parameter
was changed: humidity (60% or 65%), temperature
(20C or 30C) and clothing: either minimal (shorts
only for male volunteers, shorts and bra-top for female
volunteers) or overalls (all-in-one boiler suits, Tyvek
Pro-Tech Chemical Protective Clothing conforming
to CE 0120). Finally, a industrial scenario was
conducted where volunteers wore Tyvek overalls
over their shorts and T-shirts and environmental
conditions reflecting high temperature and high
humidity (30C, 60%), such as might be encountered
in a tank-cleaning operation or similar.
Biological monitoring
2-Butoxyacetic acid is the major urinary metabolite
of 2-butoxyethanol in humans. Rettenmeier et al.
(1993) reported that up to 64% of the total 2-butoxy-
acetic acid formed could be excreted as a glutamine
conjugate. This was confirmed by Sakai et al. (1994),
who stated that total 2-butoxyacetic acid gave a
better correlation with 2-butoxyethanol exposure
than free 2-butoxyacetic acid. The use of total 2-
butoxyacetic acid is preferred as it compensates for
individual differences in the glutamine conjugation
pathway. The use of total butoxyacetic acid in urine
has been used in this study to assess the absorbed
body burden after exposures to 2-butxoyethanol
vapour.
For all exposures, volunteers provided urine
samples before and after each exposure (0, 4, 6, 8, 10,
12, 22, 26, 30 and 34 h). Urine volume was recorded
and samples stored at 20C until used for analysis.
At the end of the exposure period for skin only
exposures, volunteers took a final breath of solvent-
free air via the mask and were asked to hold their
breath prior to leaving the chamber in order to reduce
the potential for inhalation. Clothing was then
changed to ensure that uptake from contaminated
clothing was unlikely.
All urine samples were analysed in duplicate for total
2-butoxyacetic acid using the following procedure.
An aliquot of sample (50 l) was hydrolysed with
50 l concentrated hydrochloric acid at 90C for 1 h
in sealed tubes. After cooling, 1 ml acetone was
added along with internal standard (propoxyacetic
acid), anhydrous potassium carbonate and penta-
fluorobenzyl bromide (50 l). Samples were then
capped and derivatized at 90C for 1 h. After cooling,
an aliquot was transferred to GC vials prior to analysis.
Analysis was by GC-MS (HP 5973, Agilent) with
negative ion chemical ionisation using methane as
reagent gas. Aliquots (1 l) were injected splitless
(30 s) at 350C into a ZB-1 column, 30 m 0.32 mm
i.d., 1 m film (Phenomenex). The oven programme
was 100C (held for 1 min), then ramped at 10C/min
to 200C then ramped at 20C/min to 220C where it
was again held for 1 min. The ions monitored were
m/z 117 for propoxyacetic acid (internal standard)
and m/z 131 for 2-butoxyacetic acid.
Physiological monitoring
To record any physiological changes in the volun-
teers (altered breathing or pulse rate) under the
different conditions, physiological monitoring equip-
ment (MP100, BioPac Systems Inc.) was used. The
parameters monitored were breathing rate, pulse rate,
skin surface temperature and skin resistance (a
measure of perspiration).
Calculations and statistics
Urinary elimination is expressed as the cumulative
total analyte excreted over the post-exposure collec-
tion period, calculated by summing the products of
the analyte concentration and urine volume for the
individual time points. The results obtained for skin
only exposure are expressed as a percentage of the
whole body measurement (inhalation and dermal
exposure) in order to obtain an estimate of the uptake
via the dermal route. In making these comparisons it
is assumed that following uptake into the body the
distribution, metabolism and excretion of these
substances is identical under both sets of exposure
conditions.
Each volunteer acted as their own control, i.e. their
dermal absorption body burden for each exposure is
compared to their own body burden for the whole
body exposure. Any differences in the percentage
dermal absorption under different scenarios was
assessed using the paired t-test; however, it should be
borne in mind that there were only four volunteers
when assessing the statistical significances found.
RESULTS
The actual environmental conditions for each
exposure are given in Table 1. All exposures were
within 5% of the target concentration. All tempera-
tures were within 4% of the target value with a
coefficient of variation of <2%. The humidity was
slightly more difficult to control, however, all humid-
ities were within 5% of the target value with a coeffi-
cient of variation of <14%.
Figure 1 shows the mean and range of estimates of
the dermal absorption contribution to total body
burden under the different environmental conditions.
The mean baseline (25C, 40% RH) percentage
dermal absorption was 11% (range 914 %) of the
whole body burden. Low temperature did not
significantly affect the percentage dermal absorption.
In the high temperature study, the percentage dermal
absorption was significantly increased (P = 0.03)
with a mean of 14% (range 1215%). Increasing the
humidity increased the percentage dermal absorption

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148 K. Jones et al.
although not significantly. Clothing had little effect
on the percentage dermal absorption. The overalls did
not attenuate absorption significantly, with a mean
percentage absorption of 10%. In the industrial
scenario (30C, 60% RH and overalls), skin absorp-
tion as a percentage of the whole body burden was
significantly increased (P < 0.005) when compared to
the baseline dermal study and when compared to any
single parameter change (e.g. high temperature alone,
minimal clothing alone). Under these conditions, skin
absorption could account for up to 42% of the total
body burden (mean 39%).
No significant differences (P > 0.05) in any of the
physiological parameters were seen between the
studies. However, it should be borne in mind that the
skin temperature and resistance measurements were
taken on the back of the hand and on the middle two
fingers, respectively. In the high temperature, high
humidity, overalls and industrial scenario studies, the
skin temperature and sweatiness on other parts of the
body are likely to have been increased.
DISCUSSION
These studies have shown that under normal
conditions (25C, 40% RH) skin absorption of 2-
butoxyethanol vapours contributes a mean of 11%
(range 914%) of total body burden. This is higher
Table 1. Environmental conditions for each 2h exposure period
a
Values are mean (SD).
b
Only mean values available for the high temperature exposure period.
Exposure Concentration of BE
(p.p.m.)
Temperature (C) Relative humidity (%) Clothing
Whole body 49.0 (1.5)
a
24.6 (0.3) 42.1 (1.1) Shorts and T-shirt
Skin only
Baseline 49.0 (1.5) 24.7 (0.4) 41.6 (5.5) Shorts and T-shirt
Low temperature 47.7 (2.9) 20.7 (0.3) 40.7 (3.2) Shorts and T-shirt
High temperature
b
49 30 40 Shorts and T-shirt
High humidity 48.6 (1.9) 24.7 (0.5) 58.5 (6.9) Shorts and T-shirt
Higher humidity 49.0 (0.9) 24.9 (0.5) 65.4 (3.0) Shorts and T-shirt
Minimal clothing 47.8 (1.8) 25.2 (0.4) 37.7 (4.4) Shorts only
Overalls 49.4 (0.9) 25.1 (0.6) 36.6 (5.2) Overalls
Industrial scenario 49.6 (0.8) 29.8 (0.6) 58.1 (5.1) Overalls
Fig. 1. Effect of environmental conditions on dermal absorption (% mean with range, N = 4). *Statistically significant
(P < 0.005).

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Dermal absorption of solvent vapours 149
than found for 1-methoxy-2-propanol (mean 4%
from urine analysis, although the maximum seen in
blood and breath was 14% for one volunteer each) in
the previous study which suggests that 2-butoxyeth-
anol vapour is more readily absorbed through the
skin than 1-methoxy-2-propanol vapour.
The studies have shown that both increased
temperature and increased humidity increase the
percentage dermal absorption and this is statistically
significant for increased temperature (P = 0.03,
30C). This is likely to be due to increased surface
blood flow (as reported, for example, by Vanakoski
et al., 1996), increased skin hydration (as observed
by Schafer et al., 2002) and perspiration [aiding
dissolution of 2-butoxyethanol, forming a solution on
the surface of the skin which may increase the
apparent permeability coefficient (Wilkinson and
Williams, 2002)] and opening of skin pores under
conditions of increased temperature and/or humidity.
The studies showed that clothing had a minimal
effect on the dermal contribution to total body burden
with neither minimal clothing nor overalls having a
significant effect on the amount absorbed through the
skin. This could be because the rate of gas exchange
through the clothing exceeds the absorption rate of 2-
butoxyethanol through the skin.
Combining high temperature, high humidity and
the wearing of overalls had a significant impact on
the percentage dermal absorption, resulting in a mean
dermal contribution to total body burden of 39%
(range 3342%). This may be due to the overalls
generating a micro-climate next to the skin (as
observed by Schafer et al., 2002) where the environ-
ment is significantly hotter and more humid than the
ambient environment.
Our study shows good agreement with the PBPK
estimations of Corley et al. (1997) under baseline
conditions (our study: 25C, 40% RH, mean absorp-
tion 11%; Corley et al.: 23C, 29% RH, predicted
absorption 15%). However, under conditions of
higher temperature and humidity (33C, 71% RH),
Corley et al. (1997) estimated the dermal absorption
of vapours to be 27% of total body burden, assuming
that 100% of the skin was exposed. This is substan-
tially lower than our observed values of 3742%,
even though we used a lower temperature and
humidity. This is likely to be due to the microclimate
induced by the wearing of overalls which increases
the dermal absorption of vapours. Corley et al.
(1997) also reduced their estimate to 8% when
assuming only the head and arms were exposed (25%
of the no clothing scenario). Our study shows that
some types of clothing (such as studied here) are
unlikely to attenuate exposure by such an extent and
that certain clothing may exacerbate absorption.
The combination of conditions in the industrial
scenario has illustrated that, for 2-butoxyethanol,
conditions of high temperature and high humidity
may lead to significant body burden via the dermal
route. In addition, and as our study shows, the use of
some types of overalls will not attenuate this body
burden and may in fact increase the amount absorbed
through the skin. In environments of high vapour
concentration, where reliance is on the use of
personal and respiratory protective equipment, it is
possible that a worker could receive a significant
exposure of which they are unaware.
AcknowledgementsThe authors would like to thank Dr D.
Fishwick, Dr C. Barber and Dr J.A. Burton for providing
medical cover throughout the exposure periods and pre- and
post-exposure medical check ups of the volunteers. The authors
would also like to thank Mike Clayton, HSL for conducting the
inward leak testing of the air-fed masks and the volunteers for
participating. This work was funded by the Health & Safety
Executive, UK.
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