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Article

Skin decontamination: principles


and perspectives

Toxicology and Industrial Health


29(10) 955968
The Author(s) 2012
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DOI: 10.1177/0748233712448112
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Heidi P Chan, Hongbo Zhai, Xiaoying Hui and


Howard I Maibach

Abstract
Skin decontamination is the primary intervention needed in chemical, biological and radiological exposures,
involving immediate removal of the contaminant from the skin performed in the most efficient way. The most
readily available decontamination system on a practical basis is washing with soap and water or water only.
Timely use of flushing with copious amounts of water may physically remove the contaminant. However, this
traditional method may not be completely effective, and contaminants left on the skin after traditional washing
procedures can have toxic consequences. This article focuses on the principles and practices of skin
decontamination.
Keywords
Skin decontamination, chemical alteration/deactivation, wash-in effect, chemical warfare agents, tape stripping

Introduction
Human skin presents a partially effective barrier for
protection against potentially toxic chemicals, mainly
attributed to its stratum corneum (SC)the uppermost and nonviable layers of the epidermis (Dreher
et al., 2005; Lee and Korzun, 2008). Its thickness varies in different body locations (Lee and Korzun, 2008)
and correspondingly correlates with the rates of penetration and absorption of chemicals (Maibach et al.,
1971). Thus, a rate-limiting step for the penetration
of most substances is diffusion through the SC
(Dreher et al., 2005; Lee and Korzun, 2008).
The most readily available decontamination system on a practical basis is washing with soap and
water or water only (Moore and Mettler, 1980; Wester, 1995; Zhai et al., 2007). Timely use of flushing
with copious amounts of water may physically
remove the contaminants (Hurst, 1997; Levitin
et al., 2003). The mechanisms of action of water
decontamination include: (i) dilution of the chemical
agent; (ii) rinsing off the chemical substance; (iii)
decreasing the rate of chemical reaction; (iv) decreasing the tissue metabolism, hence minimizing inflammatory reaction; (v) decreasing the hygroscopic
effects of the chemicals responsible for its production
and (vi) restoring the skins normal pH in acid and
alkali burns (Hall and Maibach, 2006). However, this

traditional method may not be completely effective,


and contaminants left on the skin after traditional
washing procedures can have toxic consequences
(Wester and Maibach, 2002).
Skin decontamination is the primary intervention
needed in chemical, biological and radiological
exposures (Houston and Hendrickson, 2005), involving immediate removal of the contaminant from the
skin (Hurst, 1997; Loke et al., 1999), which is performed in the most efficient wayphysical
removal of the contaminant (Hurst, 1997), solvating or emulsifying the contaminant in a liquid vehicle, transferring contaminant to another media
through absorption/adsorption of the chemical,
through chemical alteration of the contaminant and
rubbing materials to dislodge the contaminant (friction) (Boeniger, 2005).

Department of Dermatology, University of California, San


Francisco, CA, USA
Corresponding author:
Heidi P Chan, Department of Dermatology, Surge Building Room
110, 90 Medical Center Way, University of California, San
Francisco, CA 94143-0989, USA.
Email: heidichan0220@yahoo.com

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956

Toxicology and Industrial Health 29(10)

Classification and mechanisms of skin


cleansing/decontaminating products
Physical removal
Physical removal of the contaminant involves immediate elimination or eradication of the contaminant,
performed by scraping the contaminant with a wooden stick (e.g. tongue depressor or popsicle stick),
flushing/flooding the contaminant with copious water
or removal of contaminated clothing (Houston and
Hendrickson, 2005; Hurst, 1997; Levitin et al., 2003).
Once the contaminated clothing is removed, it should
be labeled with a patient/worker identifier, sealed in
plastic bags and stored to prevent evaporation or aerolization of the agent (Houston and Hendrickson, 2005).

Solvation or emulsification
Solvation refers to the interaction of a solute and a
solvent, while emulsification refers to combining two
immiscible liquids, that is, oil and water. Surfactants
(derived from the word surface-active-agent) are
aqueous-based skin cleansers possessing the ability
to dissolve or emulsify contaminants from skin (Boeniger, 2005). Surfactants are amphiphilic compounds,
that is, they bear hydrophilic and lipophilic moieties,
and act by reducing boundary layers or surface tension between two phases (Boeniger, 2005; Merianos,
2001). Surface tension of the liquid is the molecular
force of the air, preventing the liquid to expand its surface area; while interfacial tension is the tension that
occurs between two immiscible liquids (Merianos,
2001). Molecular or electrostatic forces are responsible for surface and interfacial tensions (Merianos,
2001). Surfactants also have the tendency to produce
micelles, which help reduce the free energy of the system by decreasing the hydrophobic surface area
exposed to water (Boeniger, 2005).
One major type of surfactant is soapa cleansing
agent produced by saponificaton (neutralization of
fatty acids such as vegetable oil or tallow) of alkaline
salts (such as sodium hydroxide or potassium hydroxide) (Boeniger, 2005; Merianos, 2001). Examples
of salts of fatty acids are lauric, oleic and stearic fatty
acids (Boeniger, 2005; Merianos, 2001). Surfactants
produced from petroleum are called detergents (Boeniger, 2005; Merianos, 2001), and these were developed in response to the shortage of animal and
vegetable fats used to make soap during World Wars
I and II (Houston and Hendrickson, 2005). Synthetic
detergents are called syndets (Ananthapadmanabhan

et al., 2004; Boeniger, 2005; Merianos, 2001). An


example of syndets is sodium lauryl sulfate (SLS).
Surfactants may be classified as: (i) anionic or
negatively charged; (ii) cationic or positively
charged; (iii) noncharged or uncharged and (iv) zwitterionic, having both positive and negative charges in
the same molecule (Merianos, 2001). Amphoteric surfactants can only be one of the four classes of surfactants and are pH dependent (Merianos, 2001).
Soap is an anionic surfactant most commonly used
by the consumers as well as the pharmaceutical industries, as these surfactants have the ability to dissolve
compounds (Merianos, 2001). However, the pharmaceutical industries mostly prefer the nonionic group,
such as the polyoxethylene sorbitan fatty acid esters,
because this class has low toxicity, good compatibility and excellent stability in biological systems
(Merianos, 2001).
The nitrogen atom is the source of the positive
charge of the cationic compounds (Merianos, 2001),
and the quaternary ammonium compounds (e.g. benzalkonium chloride) are the most popular group of
this class (Boeniger, 2005), as they are hydrolytically
stable and posses good germicidal ability, making them
generally more expensive than others (Merianos,
2001).
The zwitterionic surfactants, like betaine, imidazoline and amine oxide, are characterized as having
excellent dermatological properties, more so because
they may exhibit minimal eye irritation and are often
used in shampoos and other cosmetic products
(Merianos, 2001).

Chemical alteration/deactivation
Chemical alteration/deactivation, the process of
detoxification or neutralization of chemical toxicity
(Houston and Hendrickson, 2005), is an important
type of skin decontamination used by the military to
combat chemical warfare agents (CWAs) (Hurst,
1997). Hydrolysis and oxidative chlorination are the
examples of chemical alterations that have been
extensively studied (Houston and Hendrickson,
2005). Hydrolysis involves the addition of acidic or
alkaline solutions and are effective in deactivating
nerve agents (Houston and Hendrickson, 2005) such
as the CWA VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methyl-phosphonothionate) (Chilcott et al.,
2005). On the other hand, oxidative chlorination
involves the addition of dilute (0.5%) hypochlorite
solution for decontaminating the CWA sulfur mustard

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Chan et al.

957

(35SM) (Chilcott et al., 2001; Houston and Hendrickson, 2005; Hurst, 1997).
Chemical alteration is also exemplified in the management of chemical burns (Hall and Maibach, 2006;
Yasuda et al., 1999). Hydrofluoric acid is a common
ingredient of commercial and household rust and
scale removers, and in high concentrations (40
70%), it may cause severe burns, penetrating deeply,
resulting to massive tissue necrosis (Hall and Maibach, 2006; Yasuda et al., 1999). Calcium gluconate
chelates fluoride ions and has been found effective
in managing hydrofluoric acid burns (Hall and Maibach, 2006; Yasuda et al., 1999). Despite early water
decontamination followed by repeated topical or parenteral administration of calcium gluconate, hydrofluoric acid burns often cannot be prevented (Hall
and Maibach, 2006).

Absorption and adsorption


Absorption refers to the assimilation or taking of
molecules of one substance directly to another (Boeniger, 2005). On the other hand, adsorption, also
known as dry decontamination (Houston and
Hendrickson, 2005), denotes the use of a solid substance for adherence of another substance (Adsorption, 2009). Examples of absorbing materials are
cellulose (paper) towels and cotton rags; whereas, dry
powders such as powdered soap or detergents, earth
and flour are used for adsorption (Boeniger, 2005).
The M291 decontamination kit is a current battlefield method used by the military when exposed to
CWAs (Boeniger, 2005; Houston and Hendrickson,
2005; Hurst, 1997; Levitin et al., 2003), and utilizes
two mechanisms of decontamination: adsorption and
chemical alteration. This wallet-like kit carries six
individual packs sufficient for three skin decontaminating procedures (Hurst, 1997). Each packet contains
a nonwoven fiber fill laminated pad impregnated with
carbonaceous powder, polymeric polystyrene and an
ion-exchange resin (Ambergard, Rohm & Haas
Co., Philadelphia, Pennsylvania) (Hurst, 1997).
In Chilcott et al.s in vitro study on human and pig
skin epidermal membranes, the methods of adsorption
and chemical alteration were used for the decontamination of the CWA 35SM, similarly, utilizing the ionexchange resin Ambergard, comparing it with two
adsorbent materials Fullers earth (FE) and BDH
Laboratory spillage granules (BDH Laboratory, Dorset, UK) (Chilcott et al., 2001). The decontaminants
were ranked based on their percentage E values (i.e.

percentage of the total amount of 35SM penetrated


between control and decontamination) and revealed:
FE >> Ambergard > BDH granules for human skin;
while for pig-ear skin, Ambergard > FE >> BDH
granules. The effectiveness of FE in human skin
agrees with a previous in vivo human volunteer study
(Chilcott et al., 2001).

Friction
The physical process of two objects in contact and
rubbing against each other in opposite directions is
called friction (Boeniger, 2005). In skin decontamination, friction removes materials by dislodging the contaminantlike rubbing the hands while washing,
using pretreated or untreated towels in wiping and
using soaps with beads, termed abrasives (Boeniger,
2005). However, the use of harsh abrasives may
roughen the skin making decontamination difficult
or it may damage the skin barrier promoting chemical
penetration instead (Merrick et al., 1982; Moody
and Maibach, 2006). In one study, the dermabrasive
(Dome Acne Skin Cleanser, manufacturer not mentioned) was found effective in removing the radioactive isotope chromium (51Cr) when compared with
soap and water, a liquid detergent (Radiacwash1,
Atom Products Corporation) and a detergent foam
(Count-Off, NEN Research Products, Boston, Massachusetts, USA) in eight hospital workers hands, as
this dermabrasive had the least residual activity of
51
Cr after 1, 2, 3 and 4 min washing time (Table 1)
(Merrick et al., 1982).

Factors that influence the effectiveness


of decontaminants
The effectiveness of decontaminants is influenced by:
(i) chemical properties of the contaminant; (ii)
amount of contaminant on the skin; (iii) timing of
decontamination; (iv) duration of decontamination,
(Boeniger, 2005) and (v) the anatomical site (Lee and
Korzun, 2008).

Chemical nature of the contaminant and


decontaminant
A rate-limiting step in dermal penetration/absorption
is the partitioning of chemical into SC (i.e. partitioning in a skin reservoir) (Bos and Meinardi, 2000);
while the rate of dermal penetration/absorption (flux)
depends on octanol/water solubility and molecular
weight (MW) (Dellarco et al., 2000; Vanbever

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958
Table 1. Residual percentage of

Toxicology and Industrial Health 29(10)


32

Cr activity (eight subjects).a


Washing time (minutes)

Washing solutions
Dermabrasive cleanserb
Detergent foamc
Liquid detergentd
Soap and water

9.4 + 4.3
10.4 + 10.1
19.6 + 10.1
21.7 + 12.6

5.9 + 2.7
7.0 + 3.1
12.9 + 7.0
17.0 + 11.9

4.6 + 2.0
5.6 + 2.6
10.4 + 5.9
14.0 + 9.2

4.0 + 1.7
4.8 + 2.2
8.5 + 4.9
12.1 + 8.4

Adapted from Merrick et al., 1982.


Dome Acne Skin Cleanser.
c
N.E.N. Count-Off.
d
Radiacwash diluted 1:40.
b

et al., 1997; Van Der Merwe and Riviere, 2005).


These variables (solubility and MW) partially predict
which chemicals are likely to promote dermal penetration of the contaminant.
Solubility of a compound in lipophilic and aqueous
phases may be expressed by reporting its octanol and
water concentration when mixed together with equal
amounts of these solvents, and the log of the ratio is
the partition coefficient (PC; log Po/w) (Boeniger,
2005).
Lipophilic compounds tend to penetrate the skin
more readily than hydrophilic compounds, and tend
to partition into the intercellular lipid matrix (Dellarco et al., 2000; Van Der Merwe and Riviere,
2005); while hydrophilic compounds are less able
to penetrate the skin, and tend to partition into the corneocytes proteins (Dellarco et al., 2000).
The MW of a compound, expressed in Daltons
(Da) (Bos and Meinardi, 2000), also has a similar
relationship in terms of penetration. Generally, low
MW (LMW) compounds, such as the solvents acetone
(58.079 Da) (Acetone, 2011) and ethanol (46.068 Da)
(Ethanol, 2011), more readily penetrate the skin;
while high MW (HMW) compounds (350500 Da),
such as hydrocortisone (362.4599 Da) (Hydrocortisone, 2011), are minimally absorbed (Dellarco et al.,
2000).
Alternatively, macromolecules, compounds with
HMW (>500 Da), such as peptides, are composed of
hundreds of amino acids covalently linked into polypeptide chains (Tanford, 1994), may be delivered in two
ways. First, macromolecules could enhance penetration
through electroporation-assisted transport created by
high-voltage pulses (Vanbever et al., 1997). Suggested
mechanistic explanation for this occurrence is that high
electrically charged macromolecules such as the DNA
can be electrophoretically driven into and trapped

within electropores; thus, temporarily widening the


pores and hinder their closing by electrical repulsion and
steric effects (Vanbever et al., 1997, Weaver, 1995).
Second, macromolecules are utilized as transdermal
transport facilitators, where the presence of macromolecules at the skin surface facilitates the passage of a
chemical or drug (Wester et al., 2002). This may be
explained by the presence of macromolecules at the skin
surface interphase with drug to alter the initial phase of
percutaneous absorption, that is, partitioning to the SC
(Wester et al., 2002).
Two macromolecular polymers (a lipophilic polymer with a MW of 2081 and a hydrophilic polymer
with a MW of 2565) were designed to hold drugs and
cosmetics to the skin surface thereby changing initial
chemical and skin partitioning of a model compound
(estradiol) were investigated using powdered human
SC (PHSC) (Wester et al., 2002). A 30-min preincubation with agitation of three concentrations of each
polymer (1, 5 and 10% w/v in ethanol) and the PHSC
were performed. After centrifugation to remove excess
water, the PHSC was washed twice with 50% ethanol
and once with 100% water. The resulting dry PHSC was
incubated for 2 h. This procedure was performed with
each polymer concentration. The formula used to calculate PC is
PCPHSC=water

dpm PHSC=mg PHSC


dpmi  dpm PHSC=mg water

where dpmi is initial concentration of estradiol in


water. There was no statistically significant effect
on estradiols PC, when it was increased to 100 
(0.028  2.8 mg/mL), when the incubation time was
increased to from 0 to 24 h or when PHSC was delipidized. The hydrophilic polymer (MW: 2565) showed
a significant polymer concentration-dependent increase
(p < 0.01) in log PC for estradiol concentrations.

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Chan et al.

959

Table 2. Percentage doses of [14C] MDI recovered from skin washes.a


Percentage dose recovered [14C] MDI, (mean + SD)
Washing solutions
Water
5% Soap
50% Soap
PG
PG-C
Corn oil

5 min
60.0
71.2
67.3
88.9
85.3
95.1

+
+
+
+
+
+

11.1
5.2
9.6
13.5
9.5
9.0

1h
56.7 +
51.1 +
68.6 +
86 +
67.7 +
77.2 +

4h
10.1
14.1
16
14.1
24.6
24.2

40.2 +
46.1 +
54.4 +
78.9 +
73.7 +
73.2 +

8h
8.9
8.2
5.2
16.4
3.0
17.4

29.2
36.6
45.7
71.6
77.9
86.2

+ 9.7
+ 12.8
+ 6.6
+ 19.7
+ 20.6
+ 10.0

MDI: methylene bisphenylene isocyanate; PG: propylene glycol; PG-C: propylene glycol-based cleanser.
a
Adapted from Wester et al., 1998

The old adage like dissolves like principle suggests that oil-based cleansers remove lipophilic contaminants better, and aqueous cleansers are better in
washing water soluble contaminants. This principle
was illustrated in Wester et al.s in vivo investigation
of methylene bisphenylene isocyanate (MDI) in adult
rhesus monkeys (Wester et al., 1999). The abdominal
skin was marked with twenty-four 1-cm2 sites, and
aliquots (2 mL) of [14C]-MDI were applied on each
site and left unoccluded. The treated sites were
washed five times (for each of the six washing solutions) at designated time periods (5 min, 1 h, 4 h and
8 h). At the end of the 8th hour, percentage dose of
[14C]-MDI recovered were higher for the corn oil
(86.2), propylene glycol-based cleanser (PG-C)
(77.9) and propylene glycol (71.6) versus 50% soap
(45.7), 5% soap (36.6) and water (29.2). MDI was
removed more effectively by propylene glycol, PGC and corn oil when compared with 5% and 50% soap
concentrations and water only, as MDI was partly oil
miscible (Table 2). This study also illustrated the
importance of timing of decontamination in decontamination effectiveness (see below).
Zhai et al. observed the effect of osmotic pressure
(i.e. the pressure exerted by the flow of water through
a semipermeable membrane separating two solutions
with different concentrations of solute (Osmotic
pressure, 2009)) of saline solutions (hypertonic and
isotonic) and compared it with tap water, for decontaminating glyphosate utilizing human skin in vitro
(Zhai et al., 2008). Each human cadaver skin was dosed
with approximately 375 mg of [14C]-glyphosate and
exposed at different times (1, 3 and 30 min). Afterward, the surface of each skin was washed thrice with
4 mL of each of the decontamination solutions. Two
tape-strippings were performed for each skin. The
wash solutions, tape discs, strippings, receptor fluid
and the remainder of the skin were liquid scintillation

analyzer counted to determine the amount of glyphosate. The total mass balance for each group ranged
from 94.8 to 102.4%. There were no statistical differences (p > 0.05) among the groups. Difference in the
osmotic pressures of the saline solutions did not affect
the water solubility of glyphosate.

Initial amount of contaminant on the skins


surface
Intuitively, the greater the initial amount of the chemical on skins surface, the longer will be the decontamination time for the skin. To determine the initial
amount of contaminant is to define the initial surface
load of the chemical to skin, and one of the methods
of quantifying is tape-stripping (Nylander-French,
2000).
Horizontal sectioning of the SC through tapestripping has become a popular method of investigation (Escobar-Chavez et al., 2008). Tape-stripping is
a minimally invasive technique used to measure the
SC mass, barrier function, drug reservoir and percutaneous penetration (Bashir et al., 2001). NylanderFrench used this method to define the amount of
tripropylene glycol diacrylate (TPGDA) and UVresin that penetrated the skin from the five sites on the
hands and forearms in 10 healthy human volunteers
(Nylander-French, 2000). Only two tape strips were
used for each site and were removed 2 min after each
tape application. The second tape served to remove
residual chemical left. Gas chromatography was utilized to measure the total dermal TPGDA and UVresin exposure. The average total recoveries were 102
and 113% for TPGDA and UV-resin, respectively, from
the consecutive tape-strippingsaverage recovery
from the first tape-stripping was 94% for TPGDA and
89% for UV-resin; while the average recovery from the
second tape-stripping were 6 and 21% for TPGDA and

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960

Toxicology and Industrial Health 29(10)

Table 3. The effects of washing pesticides with soap and water and rubbing alcohol.a
Percentage penetration (minute/s and hours)
Min
Soap and water

Dose (mg/cm2)

2,4-D
2,4-D
Azodrin
Baygon
Ethion
Guthion
Lindane
Malathion
Malathion
Malathion
Parathion
Parathion
Parathion
Parathion
Parathion
Rubbing alcohol
Parathion
Malathion
a

Site

4
40
4
4
4
4
4
4
40
400
4
40
400
4
4

arm
arm
arm
Arm
arm
arm
arm
arm
arm
arm
arm
arm
arm
forehead
palm

0.5

4
4

arm
arm

1.2

1.7
1.3

2.8

8.4
6.2

Hours

15

30

0.7
0.7
2.3
4.7
1.6

1.8

1.2

3.7

4.5

4.7

11.8

3.7
2.8
8.6
15.5
2.9

1.8
4.3
4.7
1.4
6.7
3.1
2.2
7.1
13.6

4.2
4.5

3.9
6.1

6.7
8.3

8.2
17.7

2.0
8.4

12.2
13.3

10.5
11.7

20.1
9.4

7.0
5.8

5.1
12.1
6.8
4.7
8.0
6.9
27.7
7.7

24
5.8

11.3

14.7
19.6
3.3
9.3
6.8

15.8

8.6
9.5
36.3
11.8

10.3
16.8

Adapted from Feldmann and Maibach, 1974a.

UV-resin, respectively. It was necessary to compute for the recoveries for each site since both the
total recoveries were greater than the calculated
amount. In general, recoveries for the first tapestripping were 1015% higher and for the second
tape-stripping recovery was 1015% lower for
TPGDA than the UV-resin. The excess calculated
amounts recovered from the second tape-stripping
represented the chemicals absorbed by the upper
levels of the epidermis, as suggested by
the investigator. It was recommended that the
tape-stripping method is more apt for assessing
exposure to chemicals with low volatility and does
not quickly penetrate through the epidermis.
A theoretical prediction of the amount of chemicals likely to penetrate in a 4-day-period was proposed by Rougier et al. (1987) using the
mathematical equation: y 1.83x  0.52, where
x is the amount of the chemical absorbed on the
surface of the SC after 30 min. This equation was
correlated with a curve established in humans
exposed to increasing doses of benzoic acid over
a 30-min period. The findings of this study suggest
that 30 min is the maximum time window of
chemical penetration that will predict the chemicals 4-day total absorption.

Timing of decontamination
In theory, the longer the duration of contact of the
contaminant on the skin, the more likely the chemical
will be absorbed (Boeniger, 2005; Wester et al.,
1999).
The Report to the Federal Working Group on
Pest Management from the Task Group on Occupational Exposure to Pesticides (1974) comprises two
variables affecting skin decontaminationthe
duration of time between application of chemical
and washing (1, 5, 15 and 30 min and 1, 2, 4, 8 and
24 h, respectively) and the anatomic site (Table 2)
(Feldmann and Maibach, 1974a). At 4 mg/cm2 concentration of azodrin on the forearm, there was
14% penetration if the site were not washed for
24 h. This amount of penetration decreased to 8%
when washed at the fourth hour (Table 3). Similarly, with the pesticide ethion, at 4 mg/cm2 concentration on the forearm, there was 3.3%
penetration if the site were not washed for 24 h.
This amount of penetration decreased to 2.9%
when washed at the fourth hour.
This is similarly exemplified by Wester et al.s MDI
study illustrating the significance of the time element
aside from the proper choice of decontaminating

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Chan et al.

961

solutions (oil based vs. water based cleansers) (Wester


et al., 1999). Table 1 shows the percentage dose of
[14C]-MDI recovered after 5 min, 1 h, 4 h and 8 h. After
the fourth hour washing, there was a noticeable decline
of [14C]-MDI recovery by the aqueous solutions: water
(40.2), 5% soap (46.1) and 50% soap (54.4) when compared with the oil-based cleansers: propylene glycol
(78.9), PG-C (73.7) and corn oil (73.2); and even
greater decline by the aqueous solutions after the
eighth hour by water (29.2), 5% soap (36.6) and 50%
soap (45.7) when compared with propylene glycol
(71.6), PG-C (77.9) and corn oil (86.2). The investigators observed that it is better to wash the skin as soon as
decontamination occurs.

Anatomical site
The thickness of the SC varies in different parts of the
bodythe palm is seven times thicker than that of the
eyelid (Lee and Korzun, 2008); the face, head, scalp
and neck absorb two to six times more than the forearm (Feldmann and Maibach, 1974b). Feldmann and
Maibach documented the regional variation of percutaneous absorption of parathion and found that the
scrotum had the greatest absorption, followed by the
head and neck and the least was the ball of the foot
(Feldmann and Maibach, 1974b).
The anatomic site was also a variable affecting the
percutaneous penetration of pesticides in the Report
to the Federal Working Group on Pest Management
from the Task Group on Occupational Exposure to Pesticides (1974) (Feldmann and Maibach, 1974a). There
was greater penetration of 4 mg/cm2 parathion when
applied on the forehead (36.3%), when compared with
that applied on the palm (11.8%), when washed after
24 h (Table 3) (Feldmann and Maibach, 1974a).

Duration of decontamination
The time allocated for washing contaminants affects
decontamination efficiency (Boeniger, 2005, Merrick
et al., 1982). This was illustrated by Merrick et al.s
study comparing four decontamination methods
soap and water, a liquid detergent (Radiacwash), a
detergent foam (Count-Off) and a dermabrasive
(Dome Acne Skin Cleanser, manufacturer not mentioned) in 21 hospital workers hands for the radiotracers 99Tc (15 subjects), 123I (eight subjects) and 51Cr
(eight subjects) in different duration of washing times
(1, 2, 3 and 4 min) (Merrick et al., 1982). Results are
recorded in Tables 1, 4 and 5. In all cases,

improvement in the degree of decontamination was


observed with increased washing time.

Other relevant matters


The wash-in effect
Moody and Maibach (2006) neologized the term
wash-in (W-I) effect to refer to the phenomenon of
solvents enhancing the penetration of chemicals
rather than washing them off, as was illustrated by
Loke et al.s in vitro study, where the decontaminating surfactants and saline solutions turned out to be
penetration enhancers of the nerve agent diethylmalonate (Loke et al., 1999). Hydration of the SC is
believed by the investigators to open up the compact
nature of the SC by increasing the layer of immobilized water on the outer surface of the keratinocytes.
Aside from skin hydration, they further suggested
other possible explanations: (i) the effects of the surfactant on skin barrier integrity (i.e. resulting from
delipidation, membrane irritation or skin irritation);
(ii) friction (e.g. using cotton swab dipped in the
decontaminating solution for washing the SC); (iii)
acid/base reactions and (iv) artifact effects.

In vivo, in vitro and animal models for skin


decontamination studies
A pig skin has long been considered to closely
resemble the human skin (Simon and Maibach,
2000). Comparison of human and porcine skins for
percutaneous penetration and absorption studies
may be influenced by the anatomical site, age and
sex (in humans) (Simon and Maibach, 2000). Skins
from both the porcine and man have spare hair
coats, thick epidermis, well-differentiated layers
of the skin as well as epidermaldermal junction,
except for the skin vasculature (rich in man; poor
in pig) and sweat glands (mostly eccrine in
humans, while pigs only have apocrine glands)
(Simon and Maibach, 2000). Some compounds
(such as acetyl salicylic acid, benzoic acid and progesterone) have similar penetration in human and
pig skin. However, the findings of Chilcott et al.s
in vitro study found that both mammalian species
differed in 35SM penetrationthe pig-ear epidermal membrane was more permeable to 35SM than
the human epidermal membrane (as indicated by
their Kp values) (Chilcott et al., 2001).
Alternatively, regulatory agencies recommend rat
skin for toxicological research (OECD, 2004; US

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962

Toxicology and Industrial Health 29(10)

Table 4. Residual percentage of

99

Tc activity (15 subjects).a


Washing time (seconds) (mean + SD)

Washing solutions

30

Dermabrasive cleanserb
Detergent foamc
Liquid detergentd
Soap and water

4.8
11.0
13.5
6.8

+
+
+
+

60
2.2
4.8
4.7
2.6

1.7
8.0
5.8
2.7

90

+ 0.9
+ 3.26
+ 3.0
+ 1.6

1.1
6.7
3.4
1.7

+
+
+
+

0.6
2.7
2.3
1.4

120

150

5.4 + 1.7
3.1 + 1.6

4.7 + 1.7
2.4 + 1.4

Adapted from Merrick et al., 1982.


Dome Acne Skin Cleanser.
c
N.E.N. Count-Off.
d
Radiacwash diluted 1:40.
b

Table 5. Residual percentage of

123

I activity (eight subjects).


Washing time (seconds) (mean + SD)

Washing solutions

30
b

Dermabrasive cleanser
Detergent foamc
Liquid detergentd
Povidone-iodine
Soap and water

2.1 +
2.7 +
7.2 +
1.6 +
21.7 +

60
1.2
1.8
5.1
0.5
12.6

1.0
1.3
3.8
0.7
17.0

+
+
+
+
+

0.4
0.7
2.7
0.2
11.9

90

120

0.7 + 0.2
0.5 + 0.5
2.87 + 2.0
0.5 + 0.2
14.0 + 9.2

0.5 + 0.1
0.7 + 0.5
2.4 + 1.8
12.1 + 8.4

Adapted from Merrick et al., 1982.


Dome Acne Skin Cleanser.
c
N.E.N. Count-Off.
d
Radiacwash diluted 1:40.
b

EPA, 1998). Korinth et al. (2007) described the discrepancies between different rat models for percutaneous penetration of 2-butoxyethanol (BE) and
toluene, by comparing in vivo microdialysis experiments and in vitro diffusion cell experiments in 10
male Wister (haired) and 10 Lewis (hairless) rats.
In the in vivo microdialysis experiments, the penetrated amount was 1.4 greater for the hairless
mouse (p < 0.01) than the haired mouse for BE. The
inverse was true for toluene (1.9 greater in the
haired rat, p < 0.001 vs. the hairless rats); both BEs
and toluenes fluxes were in pseudo-steady states,
and the lag times were similar values. On the other
hand, in the in vitro diffusion cell experiments, the
penetrated amounts of BE and toluene were uniformly higher (significant for toluene, p < 0.02) in
the hairless rat as well as both the fluxes and lag
times (significant for BE, p < 0.02). Hence, the in
vivo microdialysis method may be superior to the
in vitro diffusion cell method to describe percutaneous penetration kinetics. The comparability of the
data was affected by different rat strains as well as
the experimental methods.

Dorandeu et al. (2010) developed a less costly cutaneous challenge model for screening studies in CWA
skin decontamination and protection, the euthymic hairless mouse Crl: SKH-1 (hr/hr) BR (SKH-1), as using
porcine and human skins are expensive. The SKH-1
mice were anesthetized prior to liquid VX serial dilution
applications, and neat liquid application or saturated
vapor (using vapor cups) exposure of SM was carried
out. To measure the severity and poisoning of the organophosphate VX, plasma and white blood cholinesterase (ChE) were performed. On the other hand, visual
grading and histological studies, individually and combined, were used to measure the vesicant property of
SM. To measure SMs immunosuppressive effects,
bone marrow (BM) and spleen cells suspensions assays
were extracted. VX inhibition tended to be higher at
300 min compared with 120 min, and a significant difference (p 0.05) was obtained for 0.7 and 1.4 mg.
Similarly, higher exposures of SM obtained by increasing the contact time with vapors (8, 16 or 32 min)
induced more severe lesions. Even if the SKH-1 mice
showed a good health status, they still exhibited severe
BM depression 3 days following liquid SM challenge.

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Chan et al.

963

Table 6. Protocols used to test the decontamination systems on SKH-1 mice skin 5 min after exposure to VX and SMa
CWA

Number of
animals

Type of decontamination
systems

Time of decontamination
(min)
Parameters evaluated

VX (50 mg/kg)

10

Control

T5

Measure of plastic
cholinesterase activities:
T 30 min, T 2 h,
T 4 h, T 24 h, T 15 d

SM (2 mL)

10
10
7
8
8
10

Fullers earth
Sponge
Sponge-RSDL 10
Sponge-RSDL 20
Sponge-RSDL 50
Control

T5

Observations and evaluation


of skin erythemas:
T 30 min, T 2 h,
T 4 h, T 24 h, T 48 h,
T 72 h. Measurements of
skin injuries and histological
analysis: T 72 h.

10
10
7
10
10

Fullers earth
Sponge
Sponge-RSDL 10
Sponge-RSDL 20
Sponge-RSDL 50

CWA: chemical warfare agent; RSDL: reactive skin decontamination lotion (Milpharm, Paris, France); T: time; SM: sulfur mustard; VX:
(O-ethyl-S-[2-(diisopropylamino)ethyl] methyl-phosphonothionate).
a
Adapted from Taysse et al., 2011.

To further stress that the SKH-1 mice model be


the first steps in in vivo screening for topical skin
protectants and decontaminants, the investigators
performed an accompanying study with its main
objective was to asses two decontaminating systems: FE and Canadian reactive skin decontamination lotion (RSDL; Milpharm, Paris, France)
against VX and SM (Taysse et al., 2011). In previous studies, FE and RSDL were found to be effective decontaminants, the former being an adsorbent
while the latter served as both skin protectant and
decontaminant. The Canadian RSDL comprises a
barrier cream and skin decontaminant. Neat SM
of 2 mL or a dose of 50 mg/kg of VX was delivered,
as this was the dose that showed in the previous
study that induced skin injuries by SM and inhibition of ChE by VX. Positive-control mice were
challenged but not decontaminated. Evaluations of
both the CWAs were same as with the previous
study. Table 6 lists the experimental protocols used
to test the decontamination systems on the SKH-1
mice skin 5 min after VX or SM exposures. FE
showed a significant difference between the

treatment groups of VX-induced ChE inhibition


(F 19.55; p < 0.0001) and that a beneficial effect
was only observed with FE (p < 0.001). Unexpectedly, ChE inhibition was worsened by the sponge
alone in comparison with the control groups. Moreover, the sponge RSDL 10, RSDL 20 and RSDL
50 could not significantly reduce VX-induced ChE
inhibition. Alternatively, the Canadian sponge
RSDL 10 and RSDL 50 significantly decreased
erythema at 1, 4 and 24 h after exposure of SM.
Although not statistically significant, a decreasing
eschar formation trend at 72 h was observed for
FE and sponge RSDL. Histologically, although
basal cell necrosis reduction intensity was observed
in all treatment comparisons, only sponge RSDL
50 versus sponge RSDL 50 was statistically significant (F 4.86; p < 0.001). Investigators surmised that the SKH-1 mouse is a suitable model
to quickly perform an initial screening of decontaminants that is less costly. Careful evaluation of
difference between species and decontamination
protocols is paramount in doing skin decontamination studies (Taysse et al., 2011).

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964

Toxicology and Industrial Health 29(10)

Models for assessment predictions and


estimates (EASE and DREAM models)
Estimation and assessment exposure (EASE)
model
The European directives and regulations (Commission Directive 93/67EEC and Commission Regulation
(EC) 1499/94) required that all existing and new substances in the occupational industry undergo risk
assessment (Tickner et al., 2005). The UK Health and
Safety Executive (HSE) and the Health and Safety
Laboratory (HSL) developed the EASE model (a
computer-based software) for inhalational and dermal
exposures, the main data source of which is the HSEs
National Exposure Database (NEDB) supported by
expert discussion and judgment. The inhalational
model estimated chemical exposure in three parameters: (i) physical properties (liquid high/
medium/low vapor pressures; solid finely divided
or granular); (ii) toxicological properties (very toxic/
toxic/harmful or irritant or low toxicity) and (iii) containment (fully contained plant or small quantities
with good local exhaust ventilation (LEV) or large
quantities with LEV or large evaporation areas with
no containment or LEV or spray application). Its most
important limitation is the fact that the NEDB data
itself is not wholly comprehensive and was not
obtained from randomly selected occupational settings. Similarly, the EASE dermal exposure estimates
are performed using modified versions of the latter
two parameters because of the lack of data. The
NEDB did not have any existing data on dermal exposure at that time (1990s), and the little data that the
EASE utilized were mostly from information regarding pesticide exposure. The US Environmental Protection Agency (EPA) provided some information
that allowed a simple dermal exposure method to be
developed.

Dermal assessment estimate (DREAM) model


Van Wendel de Joode et al. (2005) explored the accuracy of the DREAM model, a semiquantitative
method, by comparing it with two tested quantitative
methods (surrogate skin pad and video imaging technique for assessing dermal exposure (VITAE)), for
the dermal and inhalational exposure to semisynthetic
metal working fluids in a cross-sectional study design.
The study was performed in four metal working
machining departments of a truck manufacturing
plant, estimating dermal and inhalation exposures in

36 of 80 machine operators. The surrogate skin


method utilizes alpha-cellulose pads placed between
two circular Fixomul stretch bandage plasters, with
a circular opening of 2.5 cm in diameter in the upper
plastic layer. These pads are placed on one hand, one
wrist and neck. After exposure, a small punched-out
segment of the pad is immediately processed and
stored in a freezer until analyzed. On the other hand,
the VITAE method is based on the fluorescent detection of the tracer on the part of the skin to be assessed.
Finally, the DREAM method, designed for epidemiological and occupational surveys, is comprised of two
parts: (i) a multiple choice questionnaire (about the
dermal route/dermal covering and protection/physical
and chemical characteristics of the contaminant/exposure duration) and (ii) mathematical evaluation of the
answers (with the appointed numerical values) to the
said questionnaire. This model estimates the amount
of chemical on the clothing layer and the skin. For
skin exposures, the Spearman correlation coefficients
for individual observations ranged from 0.19 to 0.82.
DREAM estimates for exposure levels on the hands
and forearms showed a fixed effect between and
within surveys, explaining mainly between-task variance. In general, exposure levels on the clothing
layer were only predicted in a meaningful way by
detailed DREAM estimates, which comprised
detailed information on the concentration of the
chemical in the formulation to which the exposure
occurred.

Effects of cleansers and


decontaminants on the skin
Most skin cleansing products have long been identified to cause skin irritation (Ananthapadmanabhan
et al., 2004). Ananthapadmanabhan et al. (2004)
explained how harsh surfactants damage skin in several ways. The interaction of skin cleanser surfactants
with the SC is with its proteins and lipids. Cleanser
surfactant can bind to the SC proteins causing transient swelling and hyperhydration while washing.
Swelling may facilitate surfactant penetration, including other surfactant ingredients, leading into the
deeper layers and possibly triggering biochemical
pathway processes such as skin irritation and itching.
When the water evaporates, usually deswelling
occurs. On the other hand, the interaction of skin
cleansers with SC lipids, although extensively studied, has not yet provided a sound explanation. It was
suggested that surfactants above their critical micelle

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Chan et al.

965

concentration solubilize lipids in surfactant micelles


causing SC delipidation. The role of the pH on surfactants was described. Generally, surfactants with high
pH damage the skin. The ideal pH for the surfactant
should resemble the pH of normal skin, that is, pH
5.56.5. The clinical manifestations due to surfactant
damage are (i) after wash tightness (perceivable tightening of skin); (ii) skin dryness, scaling and roughness and (iii) skin irritation (explained above).

lower skin hydration and TEWL were observed in


using the detergent alone. These findings show that
(i) alcohol-based disinfectants are less irritating to
skin; (ii) there was no summation of irritating effects
of a common detergent and propanolol and (iii) the
combination of washing and disinfection has rather
a proactive aspect than washing alone.
Using emollients or skin cleansers formulated with
emollients is helpful in lowering the irritant effects of
surfactants (Boeniger, 2005).

Irritant contact dermatitis


Irritant contact dermatitis is the most common type of
skin disease caused by surfactants, especially when
used cumulatively (Ananthapadmanabhan et al.,
2004). The biological response of (normal) human
skin to alcohol-based disinfectants and detergents
(SLS 0.5%, propanolol-based hand disinfectant
(Sterillium1 hand rub, BODE Chemie, Hamburg,
Germany), Sterilliums propanolol mixture (2propanolol 45% w/w and 1-propanolol 30% w/w) and
distilled water) was investigated utilizing noninvasive
diagnostic tools (transepidermal water loss (TEWL;
Tewameter TM 210, Courage and Khazaka, Cologne,
Germany; marker for barrier disruption); laserDoppler flowmetry (PERIFLUX 5010; marker for
cutaneous blood flow); corneometry (Corneometer
CM 820, Courage and Khazaka, Acaderm, Menlo
Park, California, USA) and marker for skin hydration)
in a repetitive design on the forearms of 45 healthy
human volunteers (Slotosch et al., 2007). Patch testing of the detergent (SLS) only, propanolol only and
combination was utilized to reproduce irritancy, while
the wash test was used to provoke and reproduce
cumulative irritancy. In the wash test, the subjects
were divided into three groups (A, B and C), where
each group was assigned a certain surfactant treatments on each forearm (A: SLS hand rub (forearm
one) and hand rub (forearm two); B: SLS hand rub
(forearm one) and SLS (forearm two); C: hand rub
(forearm one) and tap water (forearm two)). In the
patch test, there was significantly higher blood flow
(p < 0.001) and TEWL (p < 0.001) using the detergent
than using alcohol-based preparations, while there
was a lower blood flow (p < 0.001) and lower TEWL
(p < 0.001) in the combination of detergent and
alcohol-based cleansers. The results for the wash test
were (i) no significant differences in the blood flow
and skin hydration between water versus hand rub
(p 0.513); (ii) a higher skin hydration was observed
in the combination of SLS hand rub and (iii) a

Allergic contact dermatitis


Hypersensitivity from surfactants may occur under
the following conditions: (i) concomitant exposure
of irritants and allergens (Cumberbatch et al., 1993);
(ii) production of allergens through auto-oxidation
(Bergh et al., 1998); (iii) when some ingredients of
surfactants are not pure; (iv) the active ingredient of the
surfactant is an allergen (Li, 2008); (v) allergy from the
coloring and fragrance of the surfactant (Heydorn et
al., 2003) and (vi) allergy from the preservatives of
surfactants ( Flyvholm and Menne, 1992).
SLS was found to augment the skin sensitizing
potential of subirritant concentrations of 2,4dinitrochlorobenzene (DNCB) via an increase in the
number of immunostimulatory dendritic cells (DCs)
reaching the draining nodes, in vitroan important
early event in the induction phase of skin sensitization
(Cumberbatch et al., 1993). The frequency of DC in
draining nodes was measured following topical application of 10% SLS, DNCB or both. Skin administration to 0.1% of DNCB resulted to a moderate increase
in the number of lymph node DC. When the concentration of SLS was increased to 10%, there was an
increased in number of DC. The same was true for the
10% SLS and 0.1% DNCB mixture.
The allergenic activity of an air-oxidized nonionic
surfactant, penta-ethylene glycol mono-n-dodecyl
ether (C12E5), was investigated in guinea pigs using
a modified cumulative contact enhancement test
(CCET) protocol (Karlberg et al., 2003). C12E5 was
stored for 10 months for oxidation, and then was
administered to guinea pigs grouped into four, for
auto-oxidation. C12E5 containing 20% oxidation
products were found to be sensitizing.
Cocamidopropyl betaine is an example of an
amphoteric surfactant commonly used in shampoos,
liquid soaps, and so on, and has been identified as a
common cosmetic allergen for many years (Li,
2008). Most skin care formulators add fragrances to

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966

Toxicology and Industrial Health 29(10)

mask the unpleasant odor of their products (Boeniger,


2005). Benzyl salicylate is an example of a fragrance
used in surfactants that was implicated to cause
allergy (Bury, 1986). Formaldehyde and formaldehyde releasers (e.g. quaternium-15) are preservatives
used in skin cleansing products (Boeniger, 2005). The
EEC directive 76/768/EEC (European Economic
Committee) mandates European manufacturers to
keep the levels of formaldehyde, formaldehyde releasers and other chemicals at a low concentration
(0.8%) to minimize the potential of these chemicals
to cause allergy (Mowad, 2000).

Essential qualities of skin


decontaminants
The desirable traits of a good contaminant are (i) it
effectively removes the contaminant of interest; (ii)
it is readily available; (iii) it acts rapidly; (iv) it does
not enhance percutaneous penetration/absorption of
the contaminant (the wash-in effect); (v) it is readily
removed without leaving an objectionable residue;
(vi) it does not damage the skin; (vii) it is easily disposed of and (ix) it is affordable (Boeniger, 2005;
Hurst, 1997). All of these qualities will depend on the
proper choice of the type of decontamination method.
Usually, more than one method is requiredfor
example, physical removal of clothing, flushing with
water and chemical alteration are the methods often
performed in laboratory chemical spillage (Hall and
Maibach, 2006). The availability of the decontaminant may affect the immediate or rapid removal of the
contaminant (Lee and Korzun, 2008).
In the formulation of skin cleansers as well as
industrial decontaminants, the manufacturers are
aware of the abovementioned qualities (Boeniger,
2005). In the United States, the Food and Drug
Administration (FDA) oversees the safety and efficacy of the food and drug products (Boeniger,
2005). The skin cleansers are under the category of
cosmetics and are mandated by the Food, Drug and
Cosmetic Act (Boeniger, 2005). On the other hand,
the Cosmetic Ingredient Review (CIR) Expert Panel,
composed of independent scientific experts, was
established in 1976 by the Cosmetics, Toiletry, and
Fragrance Association (CFTA; now Personal Care
Product Council) (Boeniger, 2005). The CIR reviews
and issues report on the toxicity and safety of cosmetic ingredients. If a certain active ingredient has not
been reviewed by the CIR, manufacturers must label
their products with Warning: The safety of this

product has not been determined, to avoid misleading


the consumers (Boeniger, 2005).
Conflict of interest
The authors declared no conflicts of interest.

Funding
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.

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