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Received: 10 January 2018 | Revised: 11 June 2018 | Accepted: 17 July 2018

DOI: 10.1111/jocd.12758

ORIGINAL CONTRIBUTION

Effects of four soaps on skin trans‐epidermal water loss and


erythema index

Zeynab Khosrowpour PharmD1 | Saman Ahmad Nasrollahi PharmD , PhD2 |


2 2 2
Azin Ayatollahi MD | Aniseh Samadi MD | Alireza Firooz MD

1
Department of Clinical Pharmacy, Faculty
of Pharmacy, Pharmaceutical Sciences Summary
Branch, Islamic Azad University, Tehran, Background: Various tests have been carried out to determine the irritant potential
Iran
2 of soaps/cleansers.
Pharmaceutical, Cosmeceutical and
Hygienic Evaluation Lab, Center for Objectives: This study was carried out to compare the effects of four different soap
Research & Training in Skin Diseases &
formulations on biophysical parameters of the skin, including trans‐epidermal water
Leprosy, Tehran University of Medical
Sciences, Tehran, Iran loss (TEWL) and erythema index.
Methods: Four different soap formulations (creamy, glycerin containing, syndet, and
Correspondence
Alireza Firooz, Center for Research & traditional alkaline soaps) were studied. Twenty healthy volunteers were enrolled and
Training in Skin Diseases & Leprosy, Tehran
8% solutions (W/V) of the soaps made with distilled water, 20% sodium dodecyl sulfate
University of Medical Sciences, Tehran, Iran.
Email: firozali@tums.ac.ir (positive control) and water (negative control) were applied to their volar forearms as a
single dose patch test. The patches remained on the sites for 4 hours. The skin TEWL
and erythema index were measured before applying the patches and 24 and 72 hours
after removal of them using TEWAmeter and Mexameter probes, respectively.
Results: Alkaline and creamy soaps caused a significant increase in TEWL 24 hours
after patch removal. However, 72 hours after patch removal, this increase was sig-
nificant only in case of alkaline soap (P‐value = 0.002). A decreasing trend in skin
erythema was observed 24 and 72 hours after application of syndent, glycerin, and
creamy soaps. In case of creamy soap, this decrease was significant 72 hours after
patch removal (P‐value = 0.006).
Conclusion: Traditional alkaline soap increased TEWL and skin erythema, which are
signs of prolonged damage to the skin barrier. However, the effects of other formu-
lations were transient, and TEWL returned to baseline at 72 hours. Creamy soap
even showed a relative protective effect (decrease in erythema index compared to
baseline), probably due to the lanolin content of the formulation.

KEYWORDS
patch test, skin irritation, soaps

1 | INTRODUCTION quite frequently can cause dryness and irritation of the skin.1,2
Traditional soaps are often highly alkaline with an anionic surfac-
Soap is probably the oldest skin cleanser. Soap is obtained from
tant and therefore inexpensive. Often in these soaps, natural oils
the saponification of oils and fats by alkali from many years ago. It
like tallow and coconut oil are used and final pH is between 9
is the prototype anionic surfactant used in skin cleansers and plays
and 10.3
a prominent role in the personal cleansing market. However, soap

J Cosmet Dermatol. 2018;1–5. wileyonlinelibrary.com/journal/jocd © 2018 Wiley Periodicals, Inc. | 1


2 | KHOSROWPOUR ET AL.

Glycerin soap is a kind of moisturizing soap. It contains humec- Training in Skin Diseases and Leprosy, Tehran University of Medical
tant—glycerin—to counter the drying effects of soap. The unique Sciences (TUMS).
quality of this soap allows it to be used for different types of skin.
Glycerin soap can be used for the most sensitive skin, such as
2.2 | Subjects
eczema or psoriasis.4,5
Creamy soap has the same base of alkaline soaps and is mostly In this pilot study, 20 healthy volunteers, between the age of 18 and
alkaline. A series of self‐emulsion compounds (emollients) are added 50 years, without past or present history of skin diseases were
to these soaps to reduce the damage caused by alkaline soaps. These enrolled. They had healthy forearm skin and should have not used
ingredients reduce trans‐epidermal water loss (TEWL) and increase antihistamines and oral corticosteroids in the week before the start
the amount of water present in the horny layer of the skin.4–7 of the study. The participants accepted not to use cosmetics and
The word “syndet” is derived from “synthetic” and “detergent.” any other topical agents in test sites 7 days before the start and dur-
Often the term “soap free” or “soap without soap” is used for syn- ing the study.
det. Syndets have a nonsoap synthetic surfactant such as fatty acid Individuals were excluded if they were pregnant, lactating, cur-
isothiocyanates, sulfosuccinic acid esters as their principal ingredient, rently receiving any systemic or topical medications, had a heavy hair
and they have a different formulation and chemistry than traditional density on their arms, had any soap allergy history or had a past his-
soap based on natural oils. These synthetic surfactants make syndet tory of acne, eczema and psoriasis.
the most neutral person cleaning soap, have a neutral or slightly Participants were not allowed to wash their test sites within
acidic pH and are less irritating to skin. The relatively high free fatty attaching and after removing the patches for 72 hours. The study
acid content of synthetic detergent bars provides a moisturizing ben- was performed during the summer time (July to September 2016).
efit that helps to maintain skin hydration.1,4,8 Written informed consent was obtained from all participants and the
Soaps and most surfactants cause irritant skin reactions. For this study protocol was reviewed and approved by the Ethics Committee
reason, the effects of surfactants on the skin have been extensively of TUMS (acceptance code: IR.TUMS.VCR.REC1395.625).
studied under in vitro and in vivo conditions.9,10 It was shown that
skin cleansers induced biochemical changes in the skin when applied
2.3 | Products
topically.11 After the introduction of the soap chamber test by
Frosch and Kingman in 1979, many other tests were considered to Four commercially available soap bars were used in this study. The
evaluate the irritation potential of various soaps. It is proposed that products were traditional alkaline soap bar, glycerin soap bar, creamy
a 4‐hour patch test represents a direct method for assessment of soap bar, and syndet bar (Table 1).
the skin irritation potential of detergent formulations like soaps.
The aim of this study was to compare the effects of four soaps
2.4 | Patch test procedures
in Iran’s market on skin trans‐epidermal water loss (TEWL) and ery-
thema index after 4‐hours patch test. All bar soaps were chopped down. About 8% solution (W/V) of the
soaps was made in distilled water. We used 20% sodium dodecyl
sulfate (SDS) as a positive control and distilled water as a negative
2 | METHODS
control. SDS (20%) is a model irritant that gives rational, but not
extreme, levels of irritation. Approximately 30 µL of each four soap
2.1 | Setting
solutions and two controls were applied on Finn chambers (Smart-
This study was carried out in the Pharmaceutical, Cosmeceutical and practice, Phoenix, AZ) with a micropipette, and the patches were
Hygienic Evaluation Lab (DermaLab) of Centre for Research and sealed for 4 hours on right forearm of volunteers.

T A B L E 1 Characteristics of four commercially available soap bars


Soap type Ingredients pH pH analysis method
Syndet Sodium cocoyl isethionate, disodium lauryl sulfosuccinate, cetearyl alcohol, 5.5 The pH of 8% aqueous solutions of all soaps was
stearic acid, glycerin, zea mays (corn starch), hydrogenated castor oil, measured by 827 pH laboratory, Metrohm AG,
sodium trideceth sulfate, cocamide MEA, paraffin liquid, cocamidopropyl Swiss.
betaine, almond oil, jojoba oil, bicarbonate sodium, deionized water
Glycerin Sodium palmitate, sodium palm kernelate, propylene glycol, sodium palm 10.13
soap kernel acid, glycerin, fragrance, color
Creamy Tallow, coconut fatty acid, sodium hydroxide, lanolin, EDTA, fragrance, 10.27
soap color, and preservatives
Traditional Sodium tallowate/sodium palmate, sodium cocoate/sodium palm 10.48
alkaline kernelate, TiO2, magnesium sulfate 7H2O, sodium silicate, paraffin,
soap EDTA, color, fragrance, and water
KHOSROWPOUR ET AL. | 3

No significant changes in the erythema index were observed


2.5 | Measurements
after 24 hours in any of four soaps (Figure 3). After 72 hours, there
Skin erythema and TEWL were measured before the intervention was only significant reduction in erythema from 218.34 ± 74.29 to
(baseline), 24 and 72 hours after removing the patches. The room 184.01 ± 57.11 in creamy soap (P‐value = 0.006).
temperature was set to 19‐21°C and the humidity level between
35% and 50 %. All the measurements were taken using probes of
4 | DISCUSSION
TEWAmeter TM 300 and Mexameter MX 18 (Courage & Khazaka
electronic GmbH, Cologne, Germany). This study we showed that four different soaps caused an increase
TEWAmeter probe measures the density gradient of the water in TEWL 24 hours after a 4‐hour patch test model, which was statis-
evaporation from the skin. It has two pairs of sensors (temperature tically significant for traditional alkaline and creamy soaps compared
and relative humidity). A microprocessor analyses the values and to the baseline, which is an indication of acute injury to the epider-
−1 −2
express the evaporation rate in g h m . For the Mexameter mal barrier. The human 4‐hour patch test provides a novel method
probe, the measurement is based on absorption/reflection. Specific for the testing of acutely irritating chemicals in human volunteers.12
wavelengths are used for measuring the erythema index by corre- The validity of this method for chemical irritancy prediction, as well
sponding them to the spectral absorption peak of hemoglobin. The as its adherence to high ethical standards, has been described by
experimental procedure is summarized in Figure 1. Robinson et al. in 2001.13 Various parameters (visual aspects and
skin biophysical indexes) have been used to evaluate the irritation
level of cleansers on the skin. Among them, TEWL and erythema are
2.6 | Statistical analysis
mostly used.14
Statistical analysis was carried out using SPSS (Version 18.0; Interna- TEWL has played an important role in assessing the skin’s barrier
tional Business Machines crop (IBM), North Castle, NY, USA). Descrip- function.15 Several studies have used TEWL to monitor stratum cor-
tive statistics (mean, standard deviation, and percentages) were neum (SC) damages resulting from exposure to surfactants and have
performed and statistical differences were tested between the differ- reported that TEWL had good correlation with subjective assess-
ent visits, using Paired‐Sample T Test. Significance was set as P < 0.01. ment of irritancy.16 Grunewald et al.17 confirmed that TEWL and
hydration measurements can discover chronic skin damage at an ear-
lier time. Tupker et al. have used only TEWL as an indicator for the
3 | RESULTS
damage to the skin caused by surfactants. They concluded that it is
Twenty volunteers (4 males, 16 females) participated in this study. possible to rank the detergents according to their irritation potential
The age of the volunteers ranged between 18 and 50 (mean age of by using TEWL.18 Subjective evaluation of irritation caused by a vari-
34.5 ± 8.66) years. The site of positive control (20% SDS) demon- ety of toilet soaps correlated well with increased TEWL.
strated varying degrees of erythema. There were no sores at the site In our study, the baseline values of TEWL and erythema
of application of positive control, although induration was observed observed at the anterolateral surface of the forearm can be consid-
in one volunteer. ered as normal values and are in agreement with previously pub-
As depicted in Figure 2, generally there was an increase in TEWL lished data.19
in all soaps. Twenty‐four hours after removing the patch, traditional Although in this study, all four different soaps increased TEWL
alkaline soap and creamy soap showed significant increase in TEWL 24 hours after path rest application, this change was significant only
from 10.35 ± 5.03 to 13.30 ± 3.90 g h−1 m−2 (P‐value = 0.001) and for traditional alkaline and creamy soaps. Seventy‐two hours after
from 10.93 ± 1.79 to 13.66 ± 3.27 g h−1 m−2 (P‐value = 0.0009), the exposure, only the traditional alkaline soap had significantly high
respectively. After 72 hours, the TEWL of the traditional alkaline TEWL, which indicates that this soap is more irritant than other
soap still remained significantly higher (14.58 ± 5.25) than the base- ones. The main components of traditional alkaline soap and creamy
line (P‐value = 0.002). one are NaOH and anionic surfactants, which both are known to be

24 hr. after 72 hr. after


removing removing
Exposure 4 hr. patches patches
Times (h)

Initial
measurement Second Third
measurement measurement
TEWL, Erythema
TEWL, Erythema TEWL, Erythema

FIGURE 1 Experimental procedure. Measurement schedule of erythema and TEWL after single exposure to soaps
4 | KHOSROWPOUR ET AL.

*
30 *
before
25

TEWL(g/h.m2)
after 24 Hour
20
* *
* after 72 Hour
15

10

0
SDS 20% syndet pH=5.5 glycerin soap creamy soap alkaline soap H2O
*: significant @ P< 0.01

FIGURE 2 Comparison of TEWL after 4‐h patch test of four different soaps

300 before

250 * after 24 Hour


Erythema level (AU)

after 72 Hour
200

150

100

50

0
SDS 20% syndet pH=5.5 glycerin soap creamy soap alkaline soap H2O

*: significant @ P< 0.01

FIGURE 3 Comparison of erythema index after 4‐h patch test of four different soaps

irritants to the skin. They degrease the SC from functional lipids Yamamoto et al.23 showed that erythema index could be used in a
such as ceramides and cholesterol. Also, the surfactants bind to the variety of dermatological studies, such as patch test, UV‐irradiation
SC proteins and cause temporary swelling of cells along with hyper test, quantitative evaluation of blood volume in granulation tissue in
hydration. After washing, deswelling occurs leading to the develop- chronic skin ulcer, and quantitative evaluation of treatments for vas-
ment of empty spaces between the cells, leading to, an increase in cular or pigmented skin lesions. Paye et al.24 made a comparison
TEWL of the skin.20 between a soap, a syndet, and a face cleanser and stated that soap
Angelova‐Fischer et al.21 confirmed that exposure to alkaline causes more skin irritancy and dryness with the highest TEWL and
agents such as NaOH will lead to an increase in the skin pH, and this erythema.
event will alter the activity of the enzymes involved in the degrada- Erythema was the second parameter that we measured in this
tion of filaggrin. Filaggrin is necessary for proper SC hydration, and study. The erythema index was reduced significantly 72 hours after
its degradation decreases the levels of natural moisturizing factors the patch test with creamy soap, which could be due to the pres-
(NMF), which leads to dry skin. Glycerin and creamy soaps also have ence of lanolin as an emollient agent in the formulation of this
the same anionic surfactants and soda, but adding glycerin as a soap.7,25 This trend was also noticed for syndent and glycerin soaps,
humectant or lanolin as an emollient reduces TEWL and diminishes although not statistically significant.
5
adverse reactions of NaOH and anionic surfactants. In the case of In the case of traditional alkaline soap (unlike the others), ery-
creamy soap, lanolin as an emollient ingredient neutralized some thema index, 24 and 72 hours after exposure, continued to increase,
harmful effects and made creamy soap softer than traditional alka- although this increase was not statistically significant.
line one. Therefore, the TEWL returned to baseline after 72 hours.
The syndet bar with its synthetic surfactants has neutral or slightly
5 | CONCLUSION
acidic pH. So the cell swelling and skin irritation and dryness are
much less with syndet bar.20 In this study, syndet bar did not induce In conclusion, 4‐hour patch test demonstrated that traditional alka-
significant changes in TEWL. line soap (containing plenty of anionic surfactant and NaOH) causes
Erythema in the skin occurs when skin is exposed to irritants the highest increase in TEWL and erythema than other soaps. This
such as chemical substances, cleansers, allergens, or UV. Erythema probably indicates that epidermal damage caused by alkaline soap is
and melanin are useful indicators of integrity of the skin barrier.22 more severe than the other types of soaps, and skin requires more
KHOSROWPOUR ET AL. | 5

time to repair itself. Acidic pH of syndet makes it less damaging than 12. Basketter DA, Whittle E, Griffiths HA, York M. The identification
alkaline soap. Also glycerin and creamy soaps have additives like and classification of skin irritation hazard by human patch test. Food
Chem Toxicol. 1994b;32:769‐775.
emollients and humectants, which diminish the destructive effect of
13. Robinson MK, McFadden JP, Basketter DA. Validity and ethics of
alkaline‐base of these soaps. So we suggested to choose routine the human 4‐h patch test as an alternative method to assess acute
soaps for daily consumption by the following order: glycerin soap, skin irritation potential. Contact Dermatitis. 2001;45:1‐12.
syndent, creamy soap, and traditional alkaline soap. 14. Tupker RA, Bunte EE, Fidler V, Wiechers JW, Coenraads PJ. Irritancy
ranking of anionic detergents using one‐time occlusive, repeated
occlusive and repeated open tests. Contact Dermatitis. 1999;40:316‐
ACKNOWLEDGMENT 322.
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This study was supported by research grant number 95‐03‐34‐ human skin. In: Maibach HI, Lowe N, eds. Modelsin Dermatology, Vol.
I. Basel, Switzerland: Karger, S. Karger; 1985:246‐257.
32801 from Center for Research and Training in Skin Diseases and
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Leprosy, Tehran University of Medical Sciences. soap and synthetic detergents as measured by skin water loss. Der-
marolvgicn. 1982;164:314‐321.
17. Grunewald AM, Gloor M, Gehring W, Kleesz P. Damage to the skin
ORCID by repetitive washing. Contact Dermatitis. 1995;32:225‐232.
18. Tupker RA, Pinnagoda J, CoenraadsPJ, NaterJP. The influence of
Zeynab Khosrowpour http://orcid.org/0000-0002-0781-8900
repeated exposure to surfactants on the human skin as determined
Saman Ahmad Nasrollahi http://orcid.org/0000-0002-7384-6686 by transepidermal water loss and visual scoring. Contact Dermatitis.
Aniseh Samadi http://orcid.org/0000-0002-0134-429X 1989;20:108‐114.
Alireza Firooz http://orcid.org/0000-0001-7274-4840 19. Firooz A, Sadr B, Babakoohi S, et al. Variation of biophysical parame-
ters of the skin with age, gender, and body region. Sci World J.
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