A method to quantitatively assess
dermal exposure to volatile organic
compounds
Matteo Creta1, Katrien Poels1, Laurens Thoelen1, Karine Vranckx1, Peter Collaerts1,
Fleur Jansen2, Michel Vangeel2, Lode Godderis1,3, Radu-Corneliu Duca1, and Jeroen
A.J. Vanoirbeek1
1 Centre for Environment and Health, Department of Public Health and Primary Care, KU
Leuven, Kapucijnenvoer 35 - 6th floor box 7001, 3000 , Leuven, Belgium;
2 Janssen Pharmaceutical NV, EHS Janssen
Campus Belgium, Janssen Pharmaceuticalaan 3, B-2440 Geel, Belgium;
3 Idewe, External Service for Prevention and Protection at Work, Interleuvenlaan 58, 3001
Heverlee, Belgium
Exposure assessment: Inhalation vs. dermal exposure
• Inhalation:
= traditionally perceived as the most
important exposure pathway
o Included in basic risk assessment
o Occupational Exposure Limits (OELs)
o Validated sampling and analytical methods
o Respiratory protection: well-established
• Dermal:
= often perceived to be a secondary
exposure pathway
o Considered during basic risk assessment
o (D)OELs not available
o No validated analytical methods
o Dermal protection: less well-established
o No standardized evaluation for PPE efficiency
Goal of the study
To develop and validate a robust and sensitive methodology for the
assessment of dermal exposure on the work floor:
• Volatile organic compounds (VOCs)
- The European Union defines a VOC as "any organic compound having an initial boiling point less
than or equal to 250 °C (482 °F) measured at a standard atmospheric pressure of 101.3 kPa."
- Dermal and respiratory irritants;
- Headaches, loss of coordination and nausea;
- Damage to the liver, kidney and central nervous system.
www.who.int/ipcs/publications/ehc/ehc_242.pdf
Selection of the monitoring tool
Analytical method development
• Permea-TecTM patch = glove permeation indicator
Activated charcoal
cloth (ACC)Qualitative
colorimetric
evaluation
Can we use this qualitative indicator patch for
quantitative assessment of dermal exposure to VOCs ?
• The colorimetric
indicator is removed
• Analyse the resulting
solution
• The activated charcoal
layer is detached
• The charcoal is placed
in a 5mL glass vial
• The vial is filled with
extraction solvent (CS2)
• The vials are shaken for 30
minutes
Analytical method development
To develop a suitable method for quantitative analysis of dermal patches for 181 different VOCs, we
relied on the existing method for air samples (on activated charcoal; analyzed by GC-FID)
Analytical method development
Simultaneous injection on 2 capillary columns with different stationary phase (apolar and polar column)
VOC-analysis with gas chromatography (GC-FID)
• identification based on set of two retention-times (RT)
• identical RT on column 1 ? => separation on column 2
• separation of 181 VOCs
Analytical method development
Desorption efficiency from patch
Compound specific extraction recoveries or “desorption efficiencies” for VOCs
upon CS2 extraction
Desorption Efficiency for 3 different concentrations (0.001%, 0.005%, 0.01%)
“Phase Equilibrium method”
185 VOCs, divided over 10 standard solutions
0.001 %
0.005 %
0.01 %
Standard solution+patch
Standard solution
Compounds Conc. levels (% v/v) DE test
185 VOCs, divided over 10
standard solutions
0.001 %, 0.005 %, 0.01 % (per
standard solution)
+ patch (n=3)
- patch (n=1)
Desorption efficiency from patch
Group 1
Non-polar VOCs:
• DEs around 100%
• Conc. Independent
• Low RSD
Group 2
Polar VOCs:
• DEs 20-90%
• Conc. dependent
• High RSD
Desorption efficiency from patch
Group 2Group 1.
.
.
Hypothesis (based on existing VOC air method)
Polar compounds (e.g. 1-Methyl-2-pyrrolidone) :
DE not quantitative, conc. dependent (Dubinin
isotherm)
Isotherm allows accurate
quantification of polar
compounds on charcoal
patch
Desorption efficiency for polar compounds
Compounds Conc. levels (% v/v) DE test
Polar VOCs :
• DEs 20-90%
• Conc. Dependent
14 concentrations
(0.0005 % => 1 %)
(per compound)
+ patch (n=3)
- patch (n=1)
Compound solution
Compound+patch
0.0005 % 1 %
0,00
0,10
0,20
0,30
0,40
0,50
0,60
0,70
0,80
0,90
0,000 2,000 4,000 6,000 8,000 10,000 12,000
De
sorp
tio
n E
ffic
ien
cy
Concentration (mg/mL)
1-Methyl-2-pyrrolidone
0
0,2
0,4
0,6
0,8
1
1,2
0,0000 2,0000 4,0000 6,0000 8,0000 10,0000
De
sorp
tio
n E
ffic
ien
cy
Concentration (mg/mL)
Acrylonitrile
Desorption efficiency for polar compounds
(polar) VOCs with constant DE (70-90%)
Acrylonitrile, 2-Butanol,...
(polar) VOCs with concentration-dependent DE
1-Methoxy-2-propanol, 1-Methyl-2-pyrrolidone,...
Conclusion – VOCs on patch
The 181 VOCs can be classified into 3 different groups :
o (apolar) VOCs with constant DE near 100% (160 VOCs)
• Toluene, m-Xylene,…
o (polar) VOCs with constant DE (70-90%) (19 VOCs)
• 2-Butanol,...
o (polar) VOCs with concentration-dependent DE (6 VOCs)
• 1-Methoxy-2-propanol, 1-Methyl-2-pyrrolidone,...
Time 0timescale
24 h
48 h
1 week
1 month
Temperature: 25°C, 4°C, -20°C, -80°C
VOCs mixture:(spiked on ACC patches)
Benzene
Trichloroethylene
Tetrachloroethylene
m-Xylene
Mesitylene
1,2,3-tri-Methylbenzene
Isophorone
1,2,3,5-tetra-Methylbenzene
n-Pentane
1,1-Dichloroethane
Acetone
2-Methoxyethanol
1-Methoxy-2-propanol
Toluene
gamma-Buttyrolactone
1-Methyl-2-pyrrolidone
Ethylene glycol monohexylether
Sample stability on the dermal patch
Sample stability on the dermal patch
Benzene
Mesitylene
n-Pentane
1-Methoxy-2-propanol
Ethylene glycol monohexylether
Trichloroethylene
1,2,3-tri-Methylbenzene
1,1-Dichloroethane
Toluene
Tetrachloroethylene
Isophorone
Acetone
gamma-Buttyrolactone
m-Xylene
1,2,3,5-tetra-Methylbenzene
2-Methoxyethanol
1-Methyl-2-pyrrolidone
Sample stability on the dermal patch
Benzene
Mesitylene
n-Pentane
1-Methoxy-2-propanol
Ethylene glycol monohexylether
Trichloroethylene
1,2,3-tri-Methylbenzene
1,1-Dichloroethane
Toluene
Tetrachloroethylene
Isophorone
Acetone
gamma-Buttyrolactone
m-Xylene
1,2,3,5-tetra-Methylbenzene
2-Methoxyethanol
1-Methyl-2-pyrrolidone
Sample stability on the dermal patch
Benzene
Mesitylene
n-Pentane
1-Methoxy-2-propanol
Ethylene glycol monohexylether
Trichloroethylene
1,2,3-tri-Methylbenzene
1,1-Dichloroethane
Toluene
Tetrachloroethylene
Isophorone
Acetone
gamma-Buttyrolactone
m-Xylene
1,2,3,5-tetra-Methylbenzene
2-Methoxyethanol
1-Methyl-2-pyrrolidone
Sample stability on the dermal patch
Benzene
Mesitylene
n-Pentane
1-Methoxy-2-propanol
Ethylene glycol monohexylether
Trichloroethylene
1,2,3-tri-Methylbenzene
1,1-Dichloroethane
Toluene
Tetrachloroethylene
Isophorone
Acetone
gamma-Buttyrolactone
m-Xylene
1,2,3,5-tetra-Methylbenzene
2-Methoxyethanol
1-Methyl-2-pyrrolidone
Conclusion: sample stability on the patch
• Ideally patches should be analyzed within the first 2 days after
sampling
• Up to 7 days storage at -20°C or -80°C is recommended
• For longer periods (30 days or more) the patches should be stored at
-80°C and special attention should be given to compounds having a
low boiling temperature
Dermal patch sampling in simulated environment
VOCs Mixture :(spiked in Petri dish)
Benzene,
Trichloroethylene,
Toluene,
Tetrachloroethylene,
m-Xylene,
Mesitylene,
1,2,3-tri-Methylbenzene,
Isophorone,
1,2,3,5-tetra-Methylbenzene,
n-Pentane,
1,1-Dichloroethane.
Dermal patch
3M passive
monitors
Spiked Volume(VOCs mixture) µg/cm2 µg/m3
1µL 1.68 618.8
1.35 679.9
1.85 740.9
3µL 4.76 2328.9
4.21 2360.6
4.18 2588.6
5µL 8.59 4191.9
7.00 3783.5
9.88 3732.0
10µL 14.35 6686.4
10.12 5594.9
11.91 6644.3
50µL 58.32 36970.0
75.24 41567.0
68.24 31429.0
100µL 86.79 57840.0
91.35 72745.0
120.62 78638.0
250µL 260.56 174950.0
262.65 201891.0
280.59 209915.0
500µL 388.50 289329.0
345.97 228387.6
325.59 200185.0
R² = 0.9883
0
50000
100000
150000
200000
250000
300000
350000
0 50 100 150 200 250 300 350 400 450
Air
co
nce
ntr
atio
n (μ
g/m
3)
Patch concentration (μg/cm2)
Benzene
Dermal patch sampling in simulated environment
• The quantity of VOCs found on ACC patches reflects well the variation of
air concentration
• The results of this exposure test can be further used to consider the
contribution of vapors to dermal exposure or to determine the
contribution due to splashing or droplets
• Good linearity: 0.7731 < R2 < 0.9986
Conclusion: Dermal patch sampling in simulated environment
181 VOCs
Hydrocarbons Halogenated compounds
Compound (CAS-number) Compound (CAS-number) Compound (CAS-number) Compound (CAS-number)
n-Pentane (109-66-0) 2,5-di-Methylhexane (592-13-2) n-Propylbenzene (103-65-1) Methylene chloride (75-09-2)
2-Methylbutane (78-78-4) 2,2,5-tri-Methylhexane (3522-94-9) Cumene (98-82-8) Chloroform (67-66-3)
n-Hexane (110-54-3) 2-Methylheptane (592-27-8) alpha-Methylstyrene (98-83-9) Tetrachloromethane (56-23-5)
2,3-Dimethylbutane (79-29-8) 3-Methylheptane (589-81-1) n-Butylbenzene (104-51-8) 1,1-Dichloroethane (75-34-3)
2-Methylpentane (107-83-5) 4-Methylheptane (589-53-7) iso-Butylbenzene (538-93-2) 1,2-Dichloroethane (107-06-2)
3-Methylpentane (96-14-0) n-Nonane (111-84-2) sec-Butylbenzene (135-98-8) 1,1,1-Trichloroethane (71-55-6)
Cyclopentane (287-92-3) n-Decane (124-18-5) tert-Butylbenzene (98-06-6) 1,1,2-Trichloroethane (79-00-5)
Methylcyclopentane (96-37-7) n-Undecane (1120-21-4) m-Xylene (108-38-3) 1,1,2,2,-Tetrachloroethane (79-34-5)
Cyclohexane (110-82-7) n-Dodecane (112-40-3) p-Xylene (106-42-3) Pentachloroethane (76-01-7)
Cyclohexene (110-83-8) n-Tridecane (629-50-5) o-Xylene (95-47-6) Trichloroethylene (79-01-6)
n-Heptane (142-82-5) n-Tetradecane (629-59-4) 2-Ethyltoluene (611-14-3) Tetrachloroethylene (127-18-4)
2,2,3-tri-Methylbutane (464-06-2) n-Pentadecane (629-62-9) 3-Ethyltoluene (620-14-4) iso-Propylchloride (75-29-6)
2,2-di-Methylpentane (590-35-2) n-Hexadecane (544-76-3) 4-Ethyltoluene (622-96-8) 1,2,3-Trichloropropane (96-18-4)
2,3-di-Methylpentane (565-59-3) Limonene (5989-27-5) p-Cymene (99-87-6) 1-Bromo-3-chloropropane (109-70-6)
2,4-di-Methylpentane (108-08-7) cis-Decalin (493-01-6) 4-tert-Butyltoluene (98-51-1) mono-Chlorobenzene (108-90-7)
2-Methylhexane (591-76-4) trans-Decalin (493-02-7) 1,3-di-iso-Propylbenzene (99-62-7) Benzylchloride (100-44-7)
3-Methylhexane (589-34-4) Benzene (71-43-2) 1,4-di-iso-Propylbenzene (100-18-5) Benzylidenechloride (98-87-3)
Methylcyclohexane (108-87-2) Toluene (108-88-3) Mesitylene (108-67-8) trans-1,2-Dichloroethene (156-60-5)
n-Octane (111-65-9) Ethylbenzene (100-41-4) 1,2,3-tri-Methylbenzene (526-73-8) cis-1,2-Dichloroethene (156-59-2)
iso-Octane (540-84-1) 1,2-Diethylbenzene (135-01-3) 1,2,4-tri-Methylbenzene (95-63-6) p-Dichlorobenzene (106-46-7)
2,3,4-tri-Methylpentane (565-75-3) 1,3-Diethylbenzene (141-93-5) 1,2,3,4-tetra-Methylbenzene (488-23-3) o-Dichlorobenzene (95-50-1)
2,3-di-Methylhexane (584-94-1) Styrene (100-42-5) 1,2,3,5-tetra-Methylbenzene (527-53-7) m-Dichlorobenzene (541-73-1)
3,4-di-Methylhexane (583-48-2) Naphthalene (91-20-3) Tetralin (119-64-2) 1,2,3-Trichlorobenzene (87-61-6)
Methyliodide (74-88-4)
Esters Ketones Glycol ethers and derivatives
Compound (CAS-number) Compound (CAS-number) Compound (CAS-number) Compound (CAS-number)
Methyl formate (107-31-3) iso-Butyl methacrylate (97-86-9) Acetone (67-64-1) Ethylene glycol monomethyl ether (2-Methoxyethanol) (109-86-4)
Ethyl formate (109-94-4) Dimethyl succinate (106-65-0) Methyl ethyl ketone (78-93-3) Ethylene glycol monoethyl ether (2-Ethoxyethanol) (110-80-5)
n-Propyl formate (110-74-7) Dimethyl glutarate (1119-40-0) Methyl n-butyl ketone (591-78-6) Ethylene glycol mono-iso-propyl ether (iso-Propoxyethanol) (109-59-1)
Methyl acetate (79-20-9) Dimethyl adipate (627-93-0) Methyl iso-butyl ketone (108-10-1) Ethylene glycol monopropyl ether (2-Propoxyethanol) (2807-30-9)
Ethyl acetate (141-78-6) Alcohols Methyl iso-amyl ketone (110-12-3) Ethylene glycol monobutyl ether (2-Butoxyethanol) (111-76-2)
Vinyl acetate (108-05-4) Methanol (67-56-1) Ethyl n-pentyl ketone (106-68-3) Ethylene glycol dimethyl ether (Dimethylglycol) (100-71-4)
n-Propyl acetate (109-60-4) Ethanol (64-17-5) di-n-Propyl ketone (123-19-3) Ethylene glycol diethyl ether (Diethylglycol) (629-14-1)
iso-Propyl acetate (108-21-4) n-Propanol (71-23-8) di-iso-Propyl ketone (565-80-0) Ethylene glycol monomethyl ether acetate (Methyl glycol acetate) (110-49-6)
n-Butyl acetate (123-86-4) iso-Propanol (67-63-0) di-iso-Butyl ketone (108-83-8) Ethylene glycol monoethyl ether acetate (Ethyl glycol acetate) (111-15-9)
iso-Butyl acetate (110-19-0) 1-Butanol (71-36-3) Cyclohexanone (108-94-1) Ethylene glycol monobutyl ether acetate (Butyl glycol acetate) (112-07-2)
tert-Butyl acetate (540-88-5) 2-Butanol (78-92-2) Isophorone (78-59-1) Ethylene glycol acetate (542-59-6)
n-Amyl acetate (628-63-7) iso-Butanol (78-83-1) Mesityloxide (141-79-7) Ethylene glycol diacetate (111-55-7)
iso-Amyl acetate (123-92-2) tert-Butanol (75-65-0) Diacetone alcohol (123-42-2) Diethylene glycol diethyl ether (Diethyl diglycol) (112-36-7)
Benzyl acetate (140-11-4) 3-Pentanol (584-02-1) Acetophenone (98-86-2) Propylene glycol monomethyl ether (1-Methoxy-2-propanol) (107-98-2)
Ethyl propionate (105-37-3) iso-Amyl alcohol (123-51-3) 1-Methyl-2-pyrrolidone (872-50-4) Propylene glycol monoethyl ether (1-Ethoxy-2-propanol) (1569-02-4)
n-Propyl propionate (106-36-5) tert-Amyl alcohol (75-85-4) Cyclopentanone (120-92-3) Propylene glycol monomethyl ether acetate (1-Methoxy-2-propanol acetate) (108-65-6)
Methyl Butyrate (623-42-7) Cyclohexanol (108-93-0) 2-Methyl cyclohexanone (583-60-8) Propylene glycol monoethyl ether acetate (1-Ethoxy-2-propanol acetate) (98516-30-4)
Ethyl butyrate (105-54-4) Methyl iso-butylcarbinol (108-11-2) 3-Methyl cyclohexanone (591-24-2)
Methyl acrylate (96-33-3) Benzyl alcohol (100-51-6) 4-Methyl cyclohexanone (589-92-4)
Ethyl acrylate (140-88-5) Allyl alcohol (107-18-6) Miscellaneous :
Butyl acrylate (141-32-2) Ethers Tetrahydrofuran (109-99-9)
Methyl methacrylate (80-62-6) Diethyl ether (60-29-7) 1,4-Dioxane (123-91-1)
Ethyl methacrylate (97-63-2) di-iso-Propyl ether (108-20-3) Acetonitrile (75-05-8)
Butyl methacrylate (97-88-1) tert-Butyl methyl ether (1634-04-4) Acrylonitrile (107-13-1)
gamma-Butyrolactone (96-48-0)
1,2-Dibromoethane (106-93-4)
181 VOCs
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/29028249
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