Pergamon
PII: S0003^*878(98)00004-0
Ann oecup Hyg, Vol 42, No 3. pp 201-207. 1998
© 1998 British Occupational Hygiene Society
Published by Ebevier Science Ltd AU rights reserved
Printed in Great Britain
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SoipDnffltte nm ASir toy Ttoermmal BesoirpltidDini G a s
ClhirdDiimatogirapIhy-Mass Spectfrromnieitiry
EMMA SCOBBIE* and JOHN A. GROVES
Health and Safety Laboratory, Broad Lane, Sheffield S3 1HQ, U.K.
A method for measuring dimethyl sulphate (DIMS) and diethyl sulphate (DES) in air was evaluated,
both in the laboratory and in the workplace. The method involved sampling onto sorbent tubes
containing Tenax TA, followed by thermal desorption and analysis by Gas ChromatographyMass Spectrometry. It was shown to be effective at measuring DMS and DES over the range 0.1
to 2 times the British occupational exposure limit of 0.05 ppm for 8 hours. © 1998 British
Occupational Hygiene Society. Published by Elsevier Science Ltd.
INTRODUCTION
The main purpose of this work was to validate a
method for the measurement of dimethyl sulphate and
diethyl sulphate in air to allow assessment against the
British occupational exposure limit. This limit is a
Maximum Exposure Limit (MEL) of 0.05 ppm
(0.26 mg/m3 for DMS and 0.32 mg/m3 for DES)
related to an 8 hour time weighted average (TWA)
reference period (HSE, 1997).
DMS is used as a methylating agent in organic
syntheses and the production of Pharmaceuticals, and
as a quaternizing agent in dyestuffs manufacture. DES
is used as an ethylating agent in the dyestuffs and
Pharmaceuticals industries.
Both the liquid and vapour forms of these dialkyl
sulphates are harmful to the skin, eyes and mucous
membranes (World Health Organisation, 1989).
There are no warning properties (no smell or initial
irritation) and the symptoms are delayed by a few
hours. Under the EU Dangerous Substances Directive
67/548/EEC as amended and adapted to technical
progress (HSE, 1994-1997), they are classified as category 2 carcinogens (may cause cancer). DES is also
classified as a category 2 mutagen (may cause heritable
genetic damage).
Although several possible methods may be found
in the literature (Royal Society of Chemistry, 1989;
Dueblin and Thoene, 1988; Ellgehausen el al., 1991;
Fukui et al, 1991; Gilland and Bright, 1986; Hansen
el at., 1986; Keller, 1974; NIOSH, 1994; Sidhu, 1981;
Vanisha-Das et al., 1994; Williams, 1982), there is
currently no HSE validated method for measuring
Received 19 August 1997; in final form 18 November 1997.
•Author to whom correspondence should be addressed.
201
DMS and DES. This paper describes the validation
of such a method according to CEN requirements
(British Standards Institution, 1994).
EXPERIMENTAL DETAILS
Materials
Pure dimethyl sulphate (99% + ) and diethyl sulphate (99%+) were obtained from Fisher Scientific
UK. Perkin Elmer thermal desorption tubes were used
(available from SKC Ltd.), packed with 200 mg Tenax
TA, particle size 0.18-0.25 mm, 60-80 mesh (SKC
Ltd). The Tenax tubes were reconditioned before use
by heating slowly under inert carrier gas to 250°C and
maintaining that temperature for 10 minutes.
Sampling details
Samples were collected onto Tenax TA tubes using
personal sampling pumps (Gillian Gil-Air) at a flow
rate of 200 ml/min. The flow rates were checked before
and after sampling. Tenax TA was chosen because this
adsorbent has previously been suggested as a suitable
adsorbent for analysis of dialkyl sulphates (Dueblin
and Thoene, 1988).
Analytical method
Thermal desorption of the sample tubes was carried
out using a Perkin-Elmer Automatic Thermal Desorption System ATD 400 (Perkin-Elmer Ltd). This apparatus contained a mechanism for holding the tubes
to be desorbed while they were heated and purged
simultaneously with inert carrier gas. The desorbed
sample, contained in the purge gas, was routed to
the gas chromatograph (Hewlett Packard 5890) via
a heated transfer line. The ATD 400 also included
202
E. Scobbie and J A. Groves
Table 1. Analytical conditions for the measurement of DMS and DES
Desorption conditions
Desorb temp
Desorb time
Transfer line
Typical split ratio
250°C
5 min
200°C
100 1
Cold trap low
Cold trap high
Trap hold time
-30 G C
250°C
10mm
Gas chromatograph conditions
Column dimensions
Phase/thickness
Carrier gas/pressure
Initial oven temperature (7",)
Time at 7",
Oven ramp 1
60 m x 0.25 mm
BP-l;0.25/jm
Helium; 20psi
35°C
Omin
5°Cmin-'
Oven temperature 2 (T2)
Time at 7",
Oven ramp 2
Oven temperature 3 (7"3)
Time at 7"3
Total run time
I2O°C
Omin
20°Cmin-'
200°C
Orrun
21 min
Mass Spectrometry parameters (Selected Ion Monitoring)
DMS ions (0-14 min)
66,95,96, 125
Dwell time
DES ions (14-21 min)
59,99, 111, 125, 130
automatic sample tube loading, leak-testing, and a
cold trap containing Tenax TA in the transfer line to
concentrate the desorbed sample.
The gas chromatograph was connected to a Hewlett
Packard 5970 Series Mass Selective Detector (MSD)
The analytical conditions are detailed in Table 1.
Although the MSD was chosen for this development
work, a Flame Ionisation Detector (FID) may be used
as an alternative.
50 ms
Table 2 Amount of alkyl sulphate in terms of the exposure
limit (0 05ppm)—for a sample taken at 200ml/min for 8
hours
/ig on sample tube
DMS
DES
0.1 x exposure limit
1 x exposure limit
2 x exposure limit
2.5
25
50
3.1
31
61
METHOD TESTS AND RESULTS
Calibration
The exposure limit for DMS and DES is 0.05 ppm
(0.26 mg/m3 and 0.32 mg/m3 respectively) over 8
hours. A suitable analytical method must be able to
measure 0.1 to 2 times the exposure limit to satisfy the
requirements of the CEN protocol. The analytical
method must therefore be able to measure the range
2.4 fig to 61 fig to cover the 8 hour limit, assuming a
sampling flow rate of 200ml/min.
A linear response was observed for DMS and DES
concentrations of between 1.5 ng and 100 ng reaching
the detector. Using a 1% split on the ATD (i.e. 1%
reaching the detector), this range is equivalent to
0.15 ng to 10/xg per sample and using a 0.1 % split on
the ATD (i.e. 0.1% reaching the detector), the range
is 1.5/ig to 100/ig per sample. At least six calibration
standard solutions were prepared in diethyl ether.
Tenax tubes were spiked with 5 or 10/il of the calibration solution of the appropriate dialkyl sulphate
to obtain tubes in the range 150 ng to 100 ng (to cover
the range 0.1 to 2 times the exposure limit, 0.05 ppm,
for 8 hour samples taken at aflowrate of 200 ml/min).
The limit of quantification (defined as the concentration which gives a signal to noise ratio of 10:1)
was 1 ppb for a 15 minute sample collected at
200 ml/min.
Determination of sampling efficiency
The sampling efficiency was determined by measuring the breakthrough of the analyte through the
sampler. Six tubes, each with a back-up, were spiked
with a solution of 10 000 ng analyte in ether and air
drawn through at 200 ml/min for 8 hours (Table 2
shows the amount of alkyl sulphate expressed in terms
of the exposure limit). The front and back-up tubes
were then analysed and the breakthrough calculated
as;
breakthrough (%)
peak area counts from the back-up tube
peak area counts from front and back-up tubes
xlOO
The results in Table 3 show that very little breakthrough occurred onto the back-up tube and therefore
the sampling efficiency of the Tenax tube sampler is
effectively 100% for DMS and DES. (In this and
subsequent tables, the relative standard deviations of
repeat determinations are shown as plus or minus %
values.)
Table 3. Sampling efficiency
Mean peak area (counts)
Front tube
Back-up tube
DMS
DES
76704772 ± 2 %
65775679 ± 3 %
53046
0
Mean %
breakthrough
0.07%
0 00%
Determination of dimethyl sulphate and diethyl sulphate in air
203
Table 4. Desorption efficiency
Amount on tube
DMS
DES
150ng
lOOOOng
150ng
10000 ng
Mean peak area (counts)
1st Desorption
2nd Desorption
139887+14%
77824072 ± 3 %
195134 ± 7 %
66564037 ± 2 %
Determination of desorption efficiency
The desorption efficiency was tested at 2 different
levels by spiking tubes and thermally desorbing each
tube twice to see if any analyte remained after the first
desorption. The desorption efficiency was calculated
as:
% Desorption
efficiency
0
2324
0
8917
100.00
100.00
100.00
99.99
Table 6. Storage
Mean mass on tube (ng)
0 days storage
14 days storage
DMS
DES
3660 ± 5 %
3643 ± 4 %
3538 ± 1 %
3531+7%
desorption efficiency
peak area counts from first desorption
peak area counts from first + second desorption
x 100
Table 4 shows that little DMS and DES remain
on the Tenax tubes after a single desorption i.e. the
desorption efficiency is effectively 100%. (Relative
standard deviations shown as plus or minus % values.)
The effect of humidity on desorption efficiency
Nine Tenax tubes were spiked with approximately
lOOOng analyte. Six of the tubes were then used to
sample two atmospheres of clean air at relative
humidities of 0 and 80% (temperature = 20°C). Standard atmosphere apparatus was used for this experiment, in which temperature and humidity could be
accurately controlled and monitored. The sampling
rate was 200ml/min over a sampling period of at least
5 hours. The remaining three tubes were left capped
and placed in a plastic bag and left without any air
drawn through them for comparison (controls). After
sampling, all the Tenax tubes were analysed.
The results in Table 5 show that the peak areas at
0% RH and 80% RH do not differ significantly from
the control which suggests that the desorption
efficiency is not significantly affected by humidities up
to 80% RH. (Relative standard deviations shown as
plus or minus % values.)
The effect of storage
This test was intended to establish how long samplers which have been exposed may be stored before
analysis. 12 tubes were spiked with approximately
4000 ng dialkyl sulphate in ether. Six were analysed
immediately and six were stored at room temperature
and analysed after 2 weeks.
The results are shown in Table 6. The means of the
two sets of data (0 and 14 days storage) differ by 3 % .
Therefore samples may be stored at room temperature
for up to 14 days.
The effect of exposure to zero concentration
This test was designed to assess the effect of situations in which exposure is early in the sampling
period, followed by a period of drawing clean air
through the tube before the end of sampling.
Twelve Tenax tubes were spiked with lOOOOng
DMS and clean lab air drawn through at 200ml/min
for 8 hours.
The results (Table 7) show that the peak areas did
not alter significantly by drawing clean air through
the samplers; therefore exposure to a period of zero
concentration after sampling does not affect the result
obtained
Table 7. Zero concentration
Mean peak area (counts)
01 Air
901 Air
DMS
DES
76704772 ± 2 %
65775679 ± 3 %
77824072± 3%
66564037 ± 2 %
Table 5. The effect of humidity on desorption efficiency
Control
DMS
DES
Mean peak area (counts)
0% RH
80% RH
8180579 ± 6%
894O597±7%
8985781 ± 9 %
9141942±3%
8847055±9%
8764325±10%
% of control
0% RH 80% RH
110
102
108
98
204
E Scobbie and J. A. Groves
Comparison between spiking from solution and sampling of vapour
This test is designed to compare the results of samples spiked with a solution of dimethyl sulphate or
diethyl sulphate with samples spiked with DMS or
DES in vapour form, in order to demonstrate the
validity of tests involving liquid spiked Tenax tubes.
Table 9. Solution vs vapour spike (glass tube method)
Mean peak area (counts)
Solution spike Vapour spike
(S)
(A)
DES (lab air)
8354030±9%
A/S%
8194132±17% 98%
Tedlar bag atmosphere. A 12 litre Tedlar bag was
used to generate a simple static atmosphere. Due to Tenax tube in vapour form. This method of vapour
the low exposure limit and carcinogenic nature of generation may be more effective than the tedlar bag
these species, it was not considered appropriate to atmosphere as there is less opportunity for loss of
attempt to set up dynamic atmospheres when a sim- analyte, for example by sticking to the walls of the
pler approach could be adopted. 6 litres of air was tedlar bag. Tenax tubes were also spiked with an equiinitially drawn into the bag at a flow rate of 1 1/min. valent amount of analyte solution in ether.
Table 9 shows that in this experiment the peak areas
10 /i\ of a 400ng//il solution in ether was injected into
the bag through a septum and a further 6 litres of air for the vapour spike are similar to those from the
was then drawn into the bag. Thus the concentration solution spike. Therefore Tenax tubes may be effectively spiked with DES in the vapour phase by drawing
of the resulting atmosphere was 4000 ng in 12 litres.
3 litre samples were taken from the bag (at air over a droplet of DES in ether in a glass tube. (As
200ml/min for 15mins) so that each sample should in the other tables, the relative standard deviations of
contain 1000 ng. Tenax tubes were also spiked directly repeat determinations are shown as plus or minus
with 2.5/il of the same solution i.e. also lOOOng per percent % values.)
tube.
Table 8 shows that samples taken from an atmoOVERALL UNCERTAINTY
sphere of DMS gave a similar result to those spiked
The overall uncertainty for a measuring procedure
directly with a DMS solution A static atmosphere
may therefore be prepared by evaporating a solution is defined in BS EN 482 (British Standards Institution,
of DMS in ether in a tedlar bag and diluting as 1994) as 'the quantity used to characterise as a whole
the uncertainty of the result given by a measuring
required with air.
However, for DES the results of the samples taken procedure', and is quoted as a percentage combining
from the atmosphere were only about half the results bias and precision using the following equation.
of the samples spiked directly from solution. This
\S-xn
Overall uncertainty =
x 100
may be due to poor vaporisation of diethyl sulphate
(unlikely in such a dilute solution in ether), DES sticking to the walls of the tedlar bag or some unknown where
behaviour of DES in air. An alternative method of
x is the mean value of results of a number n of
generating DES vapour was tried in an attempt to
repeated measurements;
resolve this.
-Y^ is the t r u e o r accepted reference value of concentration,
Glass tube. An alternative method of generating
j is the standard deviation of measurements.
dialkyl sulphate vapour was earned out. Tenax tubes
An additional 5% is usually allowed for the variawere connected to sampling pumps as usual and a
glass tube was connected to the front of each Tenax bility of the pump flow rate. The performance requiretube. 10 fi\ of an alkyl sulphate standard solution in ments quoted in BS EN 482 (British Standards Instiether was then introduced into the glass tube and tution, 1994) for overall uncertainty are ^ 5 0 % for
laboratory air was drawn through each of the tubes samples in the range 0.1 to 0.5LV and ^ 3 0 % for
for 2 hours at lOOml/min. The intention was that the samples in the range 0.5 to 2.0LV (LV = Limit Value).
air passing through the glass tube would vaporise the
The bias in these determinations is effectively zero,
droplet and the analyte would be sampled onto the and the results in the tables show that the overall
uncertainty is well within the EN 482 specifications,
even if the variability of the pump is allowed for.
Table 8. Solution vs vapour spike
Field trials
Mean peak area (counts)
Three separate field trials were carried out at a
Solution spike Vapour spike
location where the dialkyl sulphates are used in dye
A/S%
(S)
M)
menufactunng. A teflon sampling chamber was used
DMS (dry air)
3209409±4% 3I08350± 10% 97%
which enabled the collection of 12 identical samples
DMS (lab air)
3017741 + 18% 2764831 ± 6 % 92%
for comparison.
DES (dry air)
3205329 ± 1 % 1609132 ± 2 % 50%
Samples were taken at various different points in
DES (lab air)
3203032±4% 1857662±7% 58%
the process involving the use of DMS or DES;
Determination of dimethyl sulphate and diethyl sulphate in air
(i) Samples were collected during addition of
DMS by gravity from measure vessel to reactor
vessel ('enclosed' system). Twelve samples were
taken at 200 ml/min during the entire period of
DMS addition (270 minutes).
(ii) DMS samples were collected during adjustment of pH of mixture in reactor vessel at
the end of the reaction period. Twelve samples
were taken above the open lid of the reactor
vessel during this procedure (42mins at
200 ml/min).
(iii) Samples were collected during drum addition
of DES to reactor vessel (5 mins), stirring (2
hours), a further drum addition (5 mins) and
stirring (2 hours). Twelve samples were taken
at 200 ml/min throughout this entire period
(255 minutes).
ms
Example GC-MS chromatograms are shown in Figs
1 and 2.
The primary aim of the field trials was to study the
effect of any interferences which may be present in
the workplace. Possible interferents were identified by
taking separate samples and analysing by GC-MS in
scan mode. For the processes involving DMS these
included dichorobenzene (major component), N-ethyl
ethanamine, acetic acid, benzene, toluene, dimethyl
benzene and phenol. For the process involving DES
these included toluene, dimethyl benzene (major components) and chlorobenzene, benzene, tetrachloroethene, ethyl benzene, styrene, methoxybenzene, benzaldehyde and methyl ethyl benzene.
Prior to analysis half of the sample tubes were
spiked with a known amount of dialkyl sulphate in
the lab and the remaining tubes were left unspiked.
Fig. 1. GC-MS trace for DMS, A, standard; B, sample; C, blank
E. Scobbie and J. A Groves
Abundance
TIC: 1766A.D
A
200000 150000 100000 50000 0rime — >
Abundance
200000 -
5.00
10. 00
TIC: SAMP7.D
15.00
20.00
B
150000 100000 50000 *
Time—>
Abundance
200000
5.00
10. 00
I
15.00
20.00
15.00
20.00
TIC: BLNK3.D
C
150000 100000
50000 -
Time—>
5.00
10. 00
Fig 2. GC-MS trace for DES. A. standard, B, sample; C. blank
Six clean Tenax tubes were also spiked with the same
known amount of dialkyl sulphate. By comparing the
results of the analysis of the three sets of six tubes it
was then possible to determine whether any species
present in the workplace environment interfered with
the method. If an interferent was present which
reacted with the dialkyl sulphate on the tube, then the
spiked sample tubes (Table 10, column C) would give
a smaller peak than would be expected, i.e. a smaller
peak than obtained by summing the peak areas for
the sample tubes and the spiked clean tubes (Table 10,
columns A + B).
Table 10 indicates that for the DMS sampling visits,
the spiked sample tubes gave a DMS concentration
which did not differ significantly from the expected
result obtained by summing columns A + B. Thus any
other species present in the workplace atmosphere did
not appear to interfere with the technique. For the
DES visit, the spiked sample tubes gave a DES concentration 19% higher than the expected result
obtained by summing columns A + B. An interferent
would be expected to cause a decrease rather than an
increase in the size of the analyte peak of the spiked
sample and the difference observed is most likely to
be due to experimental variation.
CONCLUSIONS
Sampling onto Tenax tubes and analysis by thermal
desorption GC-MS has been shown to offer an effective means of monitoring airborne dimethyl and
diethyl sulphate in air and has sufficient sensitivity to
cover the range 0.1 to 2 times the 15 minute and
8 hour exposure limit. The sampling efficiency and
Determination of dimethyl sulphate and diethyl sulphate in air
207
Table 10. Field trials
(0 DMS
(ii) DMS
(iii) DES
Air samples
(A)
Mean mass detected (ng)
Spiked unexposed tubes
(B)
Spiked air samples
(Q
C/(A + B)
821 ±12% (/i = 6)
418± 13% (n = 4)
2070±!4%(n = 3)
922±10%(n = 6)
965 ± 9% (n = 5)
854±7%(n = 6)
1825± 13% (n = 6)
1519±7%(n = 5)
3474±5% (n = 4)
105
110
119
desorption efficiency of the method are 100% for
DMS and DES, and the method is effective in the
range 0 to 80% RH. Exposure to clean air after
exposure to the dialkyl sulphates does not affect the
result obtained and the samples may be stored for 2
weeks at room temperature prior to analysis.
Acknowledgements—The authors would like to thank the
staff at the sampling sites for their help and co-operation,
and also the Health Directorate of the Health and Safety
Executive for sponsoring the study.
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