A method to quantitatively assess dermal exposure to ... · A method to quantitatively assess dermal exposure to volatile organic compounds Matteo Creta 1, Katrien Poels , Laurens

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.

https://en.wikipedia.org/wiki/European_Union

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


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)


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


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)


Group 1

Non-polar VOCs:

• DEs around 100%

• Conc. Independent

• Low RSD

Group 2

Polar VOCs:

• DEs 20-90%

• Conc. dependent

• High RSD


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


Ethylene glycol monohexylether

Sample stability on the dermal patch


Benzene

Mesitylene

n-Pentane



Trichloroethylene


1,1-Dichloroethane

Toluene

Tetrachloroethylene

Isophorone

Acetone


m-Xylene


2-Methoxyethanol



Benzene

Mesitylene

n-Pentane



Trichloroethylene


1,1-Dichloroethane

Toluene

Tetrachloroethylene

Isophorone

Acetone


m-Xylene


2-Methoxyethanol



Benzene

Mesitylene

n-Pentane



Trichloroethylene


1,1-Dichloroethane

Toluene

Tetrachloroethylene

Isophorone

Acetone


m-Xylene


2-Methoxyethanol



Benzene

Mesitylene

n-Pentane



Trichloroethylene


1,1-Dichloroethane

Toluene

Tetrachloroethylene

Isophorone

Acetone


m-Xylene


2-Methoxyethanol


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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A method to quantitatively assess dermal exposure to ... · A method to quantitatively assess dermal exposure to volatile organic compounds Matteo Creta 1, Katrien Poels , Laurens