http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–9 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.966109
REVIEW ARTICLE
Shaving effects on percutaneous penetration: clinical implications Muhammad Hamza1, Hassaan Tohid2, and Howard Maibach1 Department of Dermatology, University of California San Francisco, San Francisco, USA and 2Sindh Medical College, Dow University of Health Sciences, Karachi, Pakistan
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Abstract
Keywords
Context: Human/animal shaving biology. Objective: To assess the effect of shaving on percutaneous penetration and skin function. Methods: We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc. Result: Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence. Conclusion: Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.
Blade and absorption, dyes and skin permeation, hair removal, razor and shave, shave and absorption, stratum corneum and axillary shaving
Introduction 1,2
Shaving is an art involving robust hair removal . Men usually shave their beards, mustache, chest, head, axilla and pubic area while women shave axilla, pubic area, arms, legs and occasionally the chest. Shaving has become a trademark of beauty in women and a sign of attraction in men, which is the reason it is attributed as a cosmetic modification. However, shaving is also performed on religious, cultural, hygienic as well as personal grounds. Stratum corneum is a main rate-limiting barrier to percutaneous penetration3 and a main layer damaged by shaving3,4. Shaving is often accompanied by visible and/or sensory irritation3. This irritation may be due to cuts and nicks which can impair the natural barrier to the irritants5,6. Percutaneous penetration and its effects on shaving is a topic which has not been studied in depth. We conducted this overview to ascertain the relation between percutaneous penetration and shaving, and effect of shaving on stratum corneum.
Methods We screened 500+research articles in databases, e.g. Pub MED, Scopus, Google Scholar, Cochrane library and pertinent journals of which 17 were deemed relevant.
Address for correspondence: Dr. Howard Maibach, University of California, School of Medicine, 90 Medical Center Way, San Francisco, CA 94143-0989, USA. Tel: 707-999-1268. Fax: 415-6739693. E-mail: [email protected]
History Received 24 July 2014 Revised 1 September 2014 Accepted 12 September 2014 Published online 30 October 2014
Search terms included but not limited to hair removal, adverse effects of shaving, after-shave and penetration/ absorption, blade and penetration, razor and shave, razor and absorption, razor and minor injuries, dermatitis and shaving, allergy and shaving, skin damage and shaving, stratum corneum and shaving, shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc. Data from relevant articles was studied, compared and organized to draw a conclusion regarding the effects of shaving on percutaneous penetration.
Results and discussion The biological effects of shaving are incompletely studied. Female axillary shaving has not been studied in depth, although it is a common practice worldwide. Physical effects on the stratum corneum and physiological effects on the epidermis and dermis are encountered due to shaving. For example, 20% of the material removed in male facial shaving comprises skin (and remaining hair)1. Two processes could influence barrier properties following shaving (i) Increased epidermal hyper proliferation that occurs after chronic shaving7,8 and (ii) Direct physical damage to the stratum corneum by scratching/friction which also has been shown at the raised perifollicular areas8. Marti et al.4 utilized image analysis of the stratum corneum surface both pre- and post-shaving which revealed
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Figure 1. The irritation potential range of antiperspirant aerosol bases under patch 47 h, both in pre-shaved and unshaven control skin. Adapted from Marti4.
distinct opaque lines because of uplifting skin flakes with a corresponding significant increase (statistically) in the scaliness parameter from 0.48 to 0.61 demonstrating immediate damage to cornified layer. These have been interpreted as uplifted skin flakes, likely to promote ingress of potentially irritating ingredients. Direct damage to the stratum corneum was supported by the observation that dry shaving perturbed barrier function in the upper layers of stratum corneum as shown with a lower Colorimetric Index of Mildness (CIM) value. Physical damage to the stratum corneum was reflected in a significant increase in dry skin. Marti et al. studied axillary shaving involving two groups. The first shaved one axilla daily (1/day) while group 2 comprised of shaving the other axilla once weekly (1/7 days). By visual assessment, irritation was significantly elevated in the first group. However, determination of the barrier function by CSM and analysis of stratum corneum lipid composition indicated only a limited effect of increased shaving on stratum corneum parameters. They assessed the role of shaving on antiperspirant use. An extension of the antiperspirant patch test was employed. Preshaving of the volar forearm followed by the standard 47 h patch test revealed that compared to unshaved skin, the antiperspirant irritancy increased significantly (biologically) (Figure 1). Although damage to the stratum corneum was detected, major effect of shaving appeared to be on skin irritancy. Hence, they investigated the effect of shaving on a proinflammatory stimulus using histamine iontophoresis in conjunction with dry shaving. An area of the forearm was lightly dry shaved five times with a disposable razor. Histamine iontophoresis was performed immediately after shaving. There were two control sites adjacent to the shaved sites. Itch perception increased significantly at the shaved sites as compared to the control sites (Figure 2). They concluded that damage to the surface barrier properties allows increased entry of irritant molecules and gentle shaving is capable of having profound effects on
inflammatory response of the epidermis and the structure of the stratum corneum. Lucova et al.9 studied the damage to the skin barrier due to shaving in relation to permeation of chemicals and also assessed dermal absorption values of two dyes, namely, Brilliant Blue and Patent Blue through skin as compared to intact skin. They used pig skin from the back of the pig’s ears, which contains no adipose tissue. They showed the shaving process manifested in a noticeable permeation of both dyes from three dosing model products (after-shave, facial cleanser and O/W emulsion) into deeper compartments of the diffusion system as demonstrated in Tables 1 and 2. Lucova et al. observed that vehicles influence permeation of absorption of dyes and the greatest amount of both dyes penetrated into the epidermis from ethanol-based aftershave. Their findings were consistent with the renowned skinpenetration-enhancing effect of ethanol-water solvent system7,8,10. The study suggested shaving caused only a slight decrease in thickness of full-thickness pig-ear skin (FTS) approx. 1%, but significant increase in transdermal electrical conductivity (TEC) values (3.5- to 5.7-fold) compared to intact FTS and shaven skin showed permeation higher than intact FTS. Lucova et al. concluded the normal process of shaving markedly enhances the potential for systemic availability of both dyes from hydrophilic vehicles. This finding was of concern with respect to the frequency of skin treatment after shaving with cosmetic products containing dyes that people use for long periods. Turner et al.6 and others assessed the impact of shaving on underarm skin in which the thickness of the axillary vault and fossa were measured using Optical Coherence Tomography (OCT) and the response of the axilla to histamine iontophoresis was also investigated. Additionally they investigated the impact of an antiperspirant roll-on formulation on irritation and self-perceived sensory properties of the axilla. The study involved 16 subjects; measurements were taken from the shaved and unshaved areas and showed an increased
Shaving effects on percutaneous penetration
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DOI: 10.3109/15569527.2014.966109
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Figure 2. The effect of shaving on histamine-induced itch. Histamine iontophoresis was performed on untreated control site (control 1), followed by pre-shaved site (shave) and then by untreated control site (control 2). Perceived itch was determined using a VAS scale. Adapted from Marti4.
Table 1. The amounts of test compounds detected in a given compartment (epidermis) of the in vitro diffusion system after 24-h exposure of ex vivo full-thickness pig-ear skin (FTS) to Brilliant Blue FCF. Membrane.
Intact FTS Shaven FTS
Compartment of diffusion system
After-shave ethanol-based BB
Facial cleanser ethanol-free BB
O/W emulsion BB
W/O emulsion BB
Epidermis Epidermis
65 ± 8 89 ± 17
56 ± 13 110 ± 12
14 ± 3 18 ± 3
13 ± 2 23 ± 6
Note the penetration increases with shaving. Adapted from Lucova9. Table 2. The amounts of test compounds detected in a given compartment (epidermis) of the in vitro diffusion system after 24-h exposure of ex vivo full-thickness pig-ear skin (FTS) to Patent Blue V and demonstration of increased penetration post-shaving.
Membrane Intact FTS Shaven FTS
Compartment of diffusion system
After-shave ethanol-based PB
Facial cleanser ethanol-free PB
O/W emulsion PB
W/O emulsion PB
Epidermis Epidermis
82 ± 4 105 ± 30
79 ± 13 99 ± 32
44 ± 13 48 ± 14
40 ± 8 40 ± 5
Adapted from Lucova9.
epidermal thickness of shaved areas, which could be due to chronic hyper proliferation and local thickening to facilitate repair of the barrier and protection from subsequent shaving events. They further performed histamine iontophoresis in the vault and fossa of both axilla of the nine volunteers who were asked to shave both axilla 2 d prior to the study. One axilla was shaved immediately prior to iontophoresis. Histamine iontophoresis in both vault and axilla resulted in an increase in both wheal and flare in the shaved axilla as compared to the unshaved control. This supported the previous studies which show that the shaving of axillary skin can damage the epidermal barrier4 while shaved skin has demonstrated to respond to increased itch and erythema following iontophoretic delivery of histamine3. They also performed a randomized control study of 30 female volunteers. In the test phase, subjects were given two-coded antiperspirant roll-on formulations labeled for right and left underarm. Test phase consisted of 2/week underarm shaving and exaggerated product use and irritation
assessed by an expert assessor 3/week. In the provocation phase, daily underarm shaving along with exaggerated application (4 times daily) of a control antiperspirant roll-on was performed. Results showed a decrease in irritation due to the roll-on used in the test phase compared to the control rollon formulation used in the provocation phase. Turner et al. concluded that axillary shaving results in removal of skin and increased potential for irritation and itch. Moreover, axillary vault showed a greater thickening in the epidermis than the unshaved area of the fossa. The response to histamine iontophoresis in the shaved axilla was greater than that of the unshaved which supported the fact that shaving causes damage to epidermal barrier. Banerjee and Ritschel11 studied transdermal permeation of vasopressin using female Sprague–Dawley rats. Effect of shaving was studied by shaving rat skin one day before the study with an electric shaver after preliminary clipping of hair before excision. Skin was allowed to heal for 24 h. This was compared to Flynn’s study12 of stripping the skin 25 times
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Figure 3. The Cyclosporin A serum concentration in murine blood as a function of time after an epicutaneous administration of flexible vehicles under normal skin and shaved skin. Serum concentration increases significantly after epicutaneous application of flexible vesicles post-shaving compared to normal skin. Adapted from Guo14.
Figure 4. No difference between shaved and unshaved ventral forearm skin in vivo in the percutaneous absorption of testosterone in rhesus monkey utilizing the urinary excretion method. Adapted from Wester15.
with cellophane tape to remove the stratum corneum. Vasopressin solution was used to study the effect of shaving on its permeation. Flux was increased 5-fold due to shaving and the lag time of vasopressin was reduced significantly in comparison to light clipping. Stripping (25 times) resulted in the removal of stratum corneum and showed a marked increase in vasopressin permeation. This shows skin is partially damaged and demonstrates the stratum corneum is one of the main barriers to permeation of vasopressin. The results are consistent with that of Bruger and Flexner13, which demonstrated an increase in insulin permeation due to shaving.
Guo et al.14 examined Cyclosporin A using Kunming mice (kept under normal laboratory conditions). The hair of test mice was trimmed short with a pair of scissors. To destroy the integrity of stratum corneum, the other group of mice was shaved with scrapper. Application area on the abdominal skin was 2 2 cm. Flexible and conventional vesicles were administered respectively and left to dry out. Results of the in vivo study demonstrated that with the application of flexible vesicles on unshaven skin, serum drug concentration of 53.4 ± 9 ng/ml was detected after 2 h of permeation and amounted to 154 ± 27 ng/ml 6 h later. Whereas, after the stratum corneum of mouse skin was destroyed post-shaving, a large amount of drug into blood was
Marti et al. / Effect of shaving on axillary Stratum corneum.
Lucova et al.9/Absorption of triphenyl-methane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life
2
4
Study
1
S. #
Case-control study.
Study design
6-month old pigs
30 Humans
No. of subjects
Table 3. The contents of the various studies mentioned in the text.
1. 2 groups studied for 4 weeks. Group 1: shaved axilla once a week. Group 2: shaved axilla once a day 7days/week) All participants used a roll-on antiperspirant 4 times daily. 2. Antiperspirant patch test: Pre-shaving of the volar forearm followed by the standard 47- hr patch test was compared to unshaven skin. 3. Histamine iontophoresis was performed after shaving an area of the forearm five times. In addition, the two adjacent sites were tested as control sites: Control 1: prior to shaving. Control 2: after iontophoresis at the shaved site. Ears and tongues of pigs prepared according to OECD TG 428. The fullthickness skin membrane (FTS) obtained from the upper half part of the pig-ear’s back, which contains no adipose tissue. To mimic the in-use conditions when cosmetics are applied to human skin slightly damaged mechanically, hair follicles of every second FTS were shaved. Wet intact FTS membrane was traveled with a manual razor (Wilkinson Sword Extra II, Solingen, Germany) twice in the opposite direction of hair growth, and once in the direction of growth. The pressure exerted on FTS was similar to shaving. 250 ng/cm2 of BB and 2500 ng/cm2 of CAF or 250 ng/cm2 of PB and 2500 ng/ cm2 of CAF were applied in one dose. Diffusion was carried out during nonoccluded 24-h exposure (an infinite dose) to simulate typical consumer usage of leave-on cosmetics. After the experiment, in order to remove a residual dose, the surface of FTS was carefully rinsed three times with 1 mL of appropriate solvent (distilled water for after-shave and facial cleanser, isopropanol for O/W emulsion and diethyl ether for W/O emulsion).
Method
The highest amounts of both dyes penetrated into the epidermis from ethanol-based after-shave; for example 4.0 and 2.6 times higher for BB and PB, respectively than from W/O emulsion. Shaving caused only a slight decrease in thickness of FTS (approx. 1%) but significant increase in the TEC values (between 3.5 and 5.7-fold) compared to intact FTS. Subsequently, diffusion studies through shaven skin showed permeation values higher roughly 1.2-fold for after-shave, 1.3-fold for facial cleanser, 1.1-fold for O/W emulsion and 1.8-fold for W/O emulsion as through intact FTS
3. Itch perception and histamine-induced neurogenic flare significantly increased at the shaved site.
2. The antiperspirant irritancy increased significantly.
1. Dry shaving immediately perturbed barrier function in the upper layers of the stratum corneum as observed with a lowered CIM value.
Results
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(continued )
Chemicals used: Triphenyl-methane dyes Brilliant Blue and Patent Blue and caffeine. Conclusion: The normal process of shaving significantly increases the potential of systemic availability of both dyes from hydrophilic vehicles. This finding is worrisome, taking into account the frequency of skin treatment after shaving and depilation with cosmetic products containing the dyes, perhaps during the long years of life.
Chemicals used: antiperspirant roll-on.
Comments
DOI: 10.3109/15569527.2014.966109
Shaving effects on percutaneous penetration 5
Study design
Randomized trial
Clinical trial
Study
Turner6/Impact of shaving and antiperspirant use on the axillary vault
Banerjee and Ritchel11/ Transdermal permeation of vasopressin. I. Influence of pH, concentration, shaving and surfactant on in vitro permeation
3
4
S. #
Female SpragueDawley rats (Harlan) of 10-20 weeks of age
9 participants (8 females and 1 male)
No. of subjects Experimental design Three series of in vitro diffusion experiments were carried out; first through intact FTS and second through shaven FTS (a dose: the model cosmetic product); third through FTL (a dose: the salivary solution), all separately for BB and PB dye. Subjects were asked to shave both axillae 2 days prior to the study and apply no underarm product on the day of the study. One axilla (randomized to left or right) was shaved immediately prior to iontophoresis in both vault and fossa. Sterile solution of 1% histamine dihydrochloride in a 2.5% methyl cellulose hydrogel was delivered into the skin using an electric current supplied by an iontophoresis controller (Moor Instruments Ltd, Axminster, U.K.). Blood flow was measured using a dualchamber laser Doppler flow monitor (Moor Instruments Ltd). Baseline flux (blood flow) measurements were monitored for 1 min, followed by a 50 mA electric current for 10 s, followed by a further monitoring for 5 min. On removal of the chambers, transparent film was placed over the area and the size of wheal and flare were recorded. Female Sprague-Dawley rats (Harlan) of 10-20 weeks of age were sacrificed by overdose ether inhalation. The skins, excised after light clipping of the hair on the back with electric clippers (Oster), were cleaned of subcutaneous tissue and fat. The skin was mounted on diffusion cells and used within an hour. Binding study: Full-thickness excised rat skin was used. Epidermis was separated from dermis by a previously reported method. The sorption isotherm was determined by equilibration of a measured weight of epidermis with 1 ml known concentration of radio-labeled vasopressin solution in a shaker-bath for 3 h at 30 C. After
Method
Table 3. Continued
Shaving increased the flux (about 5 times) and decreased the lag time of vasopressin significantly when compared to light clipping. Stripping (25 times), which removes the stratum corneum showed dramatic increase in VP skin permeation.
Histamine iontophoresis of the axillary vault and fossa resulted in an increase in both flare and wheal in the shaved axilla when compared with the respective unshaved control. Results provide evidence of this increased sensitivity to histamine in shaved skin. However, the flare in the fossa was significantly greater than that observed in the vault (p50.05), when both of these sites were shaved (wheal was also greater, although not significantly).
Results
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This shows that shaving damages the skin partially and gives evidence to the fact that the stratum corneum is the main barrier to permeation of vasopressin.
Conclusion: response to histamine iontophoresis in the shaved axilla was greater than that of the unshaved (both flare and wheal), providing a further example of the potential for shaving to damage the epidermal barrier. Histamine response in the vault of the shaved axilla was less than that in the shaved fossa, which is proposed to be due to the thicker epidermis in the vault affording some degree of protection from the shaving process.
Comments
6 M. Hamza et al. Cutan Ocul Toxicol, Early Online: 1–9
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Wester and Maibach15/ Percutaneous Absorption in the Rhesus Monkey Compared to Man
Clinical Trial
Female rhesus monkeys used
equilibration, the epidermis was digested with TS-1 tissue solubilizer (Research Products International) and analyzed by scintillation counting. Duplicate samples were also taken from the aqueous phase and analyzed. The effect of shaving was studied by shaving rat skin one day before the study with a Remington Super Mesh Electric Shaver (Model SM-100, Remington Products Inc.) after preliminary clipping of the hair. The skin was allowed to heal for 24 h (although no visible damage was observed), and excised. This was compared to stripping, where the skin was stripped 25 times with cellophane tape (Scotch Brand, 3 M) to remove stratum corneum (Flynn et al.18). Concentrations of vasopressin solution in the donor phase were 46.8 g/ml (4/Ci/ml) for clipped and shaved skin and 49.5/zg/ml (4 tCi/ml) for stripped skin Female rhesus monkeys (Macaca mulattu), trained for metabolic studies, were used. For iv administration a saline solution of the compounds was slowly given in the cephalic vein. The amount given was the same as was topically applied, averaging approximately 5 PCi. Urine was then collected in a metabolism cage. For topical application the monkeys were placed in a metabolic chair for the first 24 hr of the study. The hands of the monkey were secured to the sides of the chair to avoid its wiping off the applied compound. This was done by wrapping shaved wrists with adhesive tape, reinforced with a second layer of filament tape (Scotch brand). By using adhesive tape the hands were secured but blood circulation was not interfered with. Testosterone and hydrocortisone were applied to the skin in acetone, and benzoic acid applied in methanol. The application dose of 0.25 ml was applied with a pipette on to a premarked area and the solvent quickly evaporated by gentle blowing. Because of variations in the specific activity it The ventral forearm of the rhesus monkey is not very hairy. The effect of shaving the topical application site was tested by lightly depilating the area with an electric razor. The data shows that there was no difference between shaved and unshaved skin in the percutaneous absorption of testosterone. Application to the shaved area was easier and so electric razor-dipilated skin was use.
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(continued )
DOI: 10.3109/15569527.2014.966109
Shaving effects on percutaneous penetration 7
6
S. #
Guo14/Lecithin vesicular carriers for transdermal delivery of cyclosporin A (October 1999)
Study
Clinical trial
Study design
Kunming mice
No. of subjects was necessary to vary the total area of application. However, the quantity of compound applied was always 4 pug/ cm*. For the next 24 hr, urine was collected in a container below the metabolism chair. Then the site of application was washed with soap and water and the monkey returned to a metabolism cage to continue the urine collection. Kunming mice, 3–4 weeks old, weighed 18–22 g, were kept under normal laboratory conditions. The hair of test mice was carefully trimmed short with a pair of scissors. To destroy the integrity of stratum corneum, the other group of mice was shaved with scraper. The application area on the abdominal skin was limited to 2 cm2. Flexible Vesicles and conventional vesicles were respectively administered and left to dry out. Mice were respectively sacrificed after 1, 2,4,6,8 and 12 h of application. Serum conc. Followed the same procedure of extraction was detected by HPLC.
Method
Table 3. Continued
In vivo study showed that with the application of flexible vesicles, serum drug concentration of 53.4399. 24 ng/ ml was detected after 2 h of permeation and amounted to 154.37927.15 ng/ml 6 h later (Figure 3). When the stratum corneum of mouse skin has been destroyed by shaving, flexible vesicles transferred large amount of drug into blood, up to 187.32953.21 ng/ml after 1 h of application and amounted to 364.51954.06 ng/ml 4 h later. Conventional vesicles failed to deliver measurable amount of drug into the blood under normal skin condition.
Results
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Comments
8 M. Hamza et al. Cutan Ocul Toxicol, Early Online: 1–9
Shaving effects on percutaneous penetration
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DOI: 10.3109/15569527.2014.966109
transferred by flexible vesicles, up to 187.3 ± 53 ng/ml after 1 h of application and amounted to 364.5 ± 54 ng/ml 4 h later (Figure 3). This indicates shaving has a profound effect on the permeation of Cyclosporin A. Lastly, Wester and Maibach15 used female rhesus monkeys trained for metabolic studies. For IV administration a saline solution of the compounds was slowly given in the cephalic vein. Amount given was the same as was topically applied. Urine was then collected in a metabolism cage. For topical application the monkeys were placed in a metabolic chair for the first 24 h. Hands of the monkey were secured to the sides of the chair to avoid its wiping off the applied compound. Testosterone and hydrocortisone were applied to the skin. Effect of shaving the topical application site of the ventral forearm of rhesus monkey was tested by lightly depilating the area with an electric razor. Results showed there was no difference between electric razor shaved and unshaved skin in the percutaneous absorption of testosterone (Figure 4). Table 3 summarizes the contents of the various studies discussed above.
Conclusion Shaving is ubiquitous, millions of people shave every day. Many of the areas that are shaved have additional chemical exposure e.g. (i) Disinfectants and antiseptics on operating tables. (ii) After-shave tonic, lotions and balms. (iii) Moisturizers. Therefore, it is highly relevant to investigate the systemic and chemical effects of the various chemicals that come in contact with the shaven areas. Shaving also destroys barrier integrity of stratum corneum, which adds to increased penetration. It has an exaggerated response to itch perception and erythema. This article summarizes the minimal experimental data available. Hence, it surpasses a simple interpretation. For example, in the histamine iontophoresis study conducted by Marti et al., a standard 47 h patch test showed that antiperspirant irritancy increased post shaving as compared to unshaved skin suggesting that shaving alters rapid penetration possibly through shunts. The experiment performed by Lucova et al. also showed a statistically significant increase in permeation of the dye Brilliant Blue (ethanol-based aftershave) from 65 ± 8 to 89 ± 17 and the dye Patent Blue (ethanol-based aftershave) from 82 ± 4 to 105 ± 30 compared from intact to shaven FTS (full thickness skin), respectively. Whereas Wester’s urinary excretion experiment does not demonstrate any increase in penetration following shaving. Therefore, this effect could be a species/compoundspecific as human, rat and pig skin has increased permeability for various substances post-shaving whereas rhesus monkey skin exhibits no such effect of testosterone in Wester’s experiment.
9
Intuitively, we suspect that any possible increase in penetration from shaving would be obtained in long term rather than acute effects; for instance, we know of no database demonstrating acute toxicity following shaving. Using current knowledge about percutaneous penetration, this is a vastly underserved area which will benefit by further research and re-evaluation of different methods of shaving, e.g. clippers/electric shavers versus razor blades, examining chemicals of various physiochemical properties, species, shaving and pre- and post-shave methods as well as anatomic sites, which in the end, will permit a general predictive theory and pertinent interventions and risk assessment.
Declaration of interest There is no conflict of interest to declare.
References 1. Elden HR. Advances in understanding mechanisms of shaving. Cosmet Toiletries 1985;100:1. 2. Zupkosky PJ, Coffindaffer TW, Kaczvinsky JR, et al. Hydration and skin condition in context of shaving. Int J Cosmetic Sci 2012; p 2620. 3. Holbrook AK, Odland FG. Regional differences in the thickness (cell layers) of the human stratum corneum: an ultrastructural analysis. J Investig Dermatol 1974;62:415–422. 4. Marti VPJ, Lee RS, Moore AE, et al. Effect of shaving on axillary stratum corneum. Int J Cosmetic Sci 2003;25:193–198. 5. Marti V, Brennan G, Clarke P, et al. Assessing the irritation potential of anti-perspirants. J Invest Dermatol 2001;117:961. 6. Turner GA, Moore AE, Marti VPJ, et al. Impact of shaving and antiperspirant use on the axillary vault. Int J Cosmetic Sci 2007; 29:31–38. 7. Kavaliunas DR, Nact S, Bogardus RE. Men’s skin care needs. Cosmet Toiletries 1985;100:29–32. 8. Bhaktaviziam C, Mescon H, Matoltsy AG. Study of skin and shaving. Arch Dermatol 1963;88:242–247. 9. Lucova M, Hojerova J, Pazourekova S, Klimova Z. Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products. Food Chem Toxicol 2013;52:19–27. 10. Krishnaiah YS, Bhaskar P, Satyanarayana V. Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin. Pharm Dev Technol 2004;9: 63–74. 11. Banerjee PS, Ritschel WA. Transdermal permeation of vasopressin. I. Influence of pH, concentration, shaving and surfactant on in vitro permeation. Int J Pharm 1989;49:189–197. 12. Flynn GL, Du¨rrheim H, Higuchi WI. Permeation of hairless mouse skin II. Membrane sectioning techniques and influence on alkanol permeabilities. J Pharm Sci 1981;70:52–56. 13. Bruger M, Flexner J. Integrity of the skin in relation to cutaneous absorption of insulin. Proc Soc Exp Biol Med 1936;35:429–432. 14. Guo J, Ping Q, Sun G, Jiao C. Lecithin vesicular carriers for transdermal delivery of cyclosporin A. Int J Pharm 2000;194: 201–207. 15. Wester RC, Maibach HI. Percutaneous absorption in the rhesus monkey compared to man. Toxicol Appl Pharmacol 1975;32: 394–398.
REVIEW ARTICLE
Shaving effects on percutaneous penetration: clinical implications Muhammad Hamza1, Hassaan Tohid2, and Howard Maibach1 Department of Dermatology, University of California San Francisco, San Francisco, USA and 2Sindh Medical College, Dow University of Health Sciences, Karachi, Pakistan
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1
Abstract
Keywords
Context: Human/animal shaving biology. Objective: To assess the effect of shaving on percutaneous penetration and skin function. Methods: We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc. Result: Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence. Conclusion: Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.
Blade and absorption, dyes and skin permeation, hair removal, razor and shave, shave and absorption, stratum corneum and axillary shaving
Introduction 1,2
Shaving is an art involving robust hair removal . Men usually shave their beards, mustache, chest, head, axilla and pubic area while women shave axilla, pubic area, arms, legs and occasionally the chest. Shaving has become a trademark of beauty in women and a sign of attraction in men, which is the reason it is attributed as a cosmetic modification. However, shaving is also performed on religious, cultural, hygienic as well as personal grounds. Stratum corneum is a main rate-limiting barrier to percutaneous penetration3 and a main layer damaged by shaving3,4. Shaving is often accompanied by visible and/or sensory irritation3. This irritation may be due to cuts and nicks which can impair the natural barrier to the irritants5,6. Percutaneous penetration and its effects on shaving is a topic which has not been studied in depth. We conducted this overview to ascertain the relation between percutaneous penetration and shaving, and effect of shaving on stratum corneum.
Methods We screened 500+research articles in databases, e.g. Pub MED, Scopus, Google Scholar, Cochrane library and pertinent journals of which 17 were deemed relevant.
Address for correspondence: Dr. Howard Maibach, University of California, School of Medicine, 90 Medical Center Way, San Francisco, CA 94143-0989, USA. Tel: 707-999-1268. Fax: 415-6739693. E-mail: [email protected]
History Received 24 July 2014 Revised 1 September 2014 Accepted 12 September 2014 Published online 30 October 2014
Search terms included but not limited to hair removal, adverse effects of shaving, after-shave and penetration/ absorption, blade and penetration, razor and shave, razor and absorption, razor and minor injuries, dermatitis and shaving, allergy and shaving, skin damage and shaving, stratum corneum and shaving, shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc. Data from relevant articles was studied, compared and organized to draw a conclusion regarding the effects of shaving on percutaneous penetration.
Results and discussion The biological effects of shaving are incompletely studied. Female axillary shaving has not been studied in depth, although it is a common practice worldwide. Physical effects on the stratum corneum and physiological effects on the epidermis and dermis are encountered due to shaving. For example, 20% of the material removed in male facial shaving comprises skin (and remaining hair)1. Two processes could influence barrier properties following shaving (i) Increased epidermal hyper proliferation that occurs after chronic shaving7,8 and (ii) Direct physical damage to the stratum corneum by scratching/friction which also has been shown at the raised perifollicular areas8. Marti et al.4 utilized image analysis of the stratum corneum surface both pre- and post-shaving which revealed
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Figure 1. The irritation potential range of antiperspirant aerosol bases under patch 47 h, both in pre-shaved and unshaven control skin. Adapted from Marti4.
distinct opaque lines because of uplifting skin flakes with a corresponding significant increase (statistically) in the scaliness parameter from 0.48 to 0.61 demonstrating immediate damage to cornified layer. These have been interpreted as uplifted skin flakes, likely to promote ingress of potentially irritating ingredients. Direct damage to the stratum corneum was supported by the observation that dry shaving perturbed barrier function in the upper layers of stratum corneum as shown with a lower Colorimetric Index of Mildness (CIM) value. Physical damage to the stratum corneum was reflected in a significant increase in dry skin. Marti et al. studied axillary shaving involving two groups. The first shaved one axilla daily (1/day) while group 2 comprised of shaving the other axilla once weekly (1/7 days). By visual assessment, irritation was significantly elevated in the first group. However, determination of the barrier function by CSM and analysis of stratum corneum lipid composition indicated only a limited effect of increased shaving on stratum corneum parameters. They assessed the role of shaving on antiperspirant use. An extension of the antiperspirant patch test was employed. Preshaving of the volar forearm followed by the standard 47 h patch test revealed that compared to unshaved skin, the antiperspirant irritancy increased significantly (biologically) (Figure 1). Although damage to the stratum corneum was detected, major effect of shaving appeared to be on skin irritancy. Hence, they investigated the effect of shaving on a proinflammatory stimulus using histamine iontophoresis in conjunction with dry shaving. An area of the forearm was lightly dry shaved five times with a disposable razor. Histamine iontophoresis was performed immediately after shaving. There were two control sites adjacent to the shaved sites. Itch perception increased significantly at the shaved sites as compared to the control sites (Figure 2). They concluded that damage to the surface barrier properties allows increased entry of irritant molecules and gentle shaving is capable of having profound effects on
inflammatory response of the epidermis and the structure of the stratum corneum. Lucova et al.9 studied the damage to the skin barrier due to shaving in relation to permeation of chemicals and also assessed dermal absorption values of two dyes, namely, Brilliant Blue and Patent Blue through skin as compared to intact skin. They used pig skin from the back of the pig’s ears, which contains no adipose tissue. They showed the shaving process manifested in a noticeable permeation of both dyes from three dosing model products (after-shave, facial cleanser and O/W emulsion) into deeper compartments of the diffusion system as demonstrated in Tables 1 and 2. Lucova et al. observed that vehicles influence permeation of absorption of dyes and the greatest amount of both dyes penetrated into the epidermis from ethanol-based aftershave. Their findings were consistent with the renowned skinpenetration-enhancing effect of ethanol-water solvent system7,8,10. The study suggested shaving caused only a slight decrease in thickness of full-thickness pig-ear skin (FTS) approx. 1%, but significant increase in transdermal electrical conductivity (TEC) values (3.5- to 5.7-fold) compared to intact FTS and shaven skin showed permeation higher than intact FTS. Lucova et al. concluded the normal process of shaving markedly enhances the potential for systemic availability of both dyes from hydrophilic vehicles. This finding was of concern with respect to the frequency of skin treatment after shaving with cosmetic products containing dyes that people use for long periods. Turner et al.6 and others assessed the impact of shaving on underarm skin in which the thickness of the axillary vault and fossa were measured using Optical Coherence Tomography (OCT) and the response of the axilla to histamine iontophoresis was also investigated. Additionally they investigated the impact of an antiperspirant roll-on formulation on irritation and self-perceived sensory properties of the axilla. The study involved 16 subjects; measurements were taken from the shaved and unshaved areas and showed an increased
Shaving effects on percutaneous penetration
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DOI: 10.3109/15569527.2014.966109
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Figure 2. The effect of shaving on histamine-induced itch. Histamine iontophoresis was performed on untreated control site (control 1), followed by pre-shaved site (shave) and then by untreated control site (control 2). Perceived itch was determined using a VAS scale. Adapted from Marti4.
Table 1. The amounts of test compounds detected in a given compartment (epidermis) of the in vitro diffusion system after 24-h exposure of ex vivo full-thickness pig-ear skin (FTS) to Brilliant Blue FCF. Membrane.
Intact FTS Shaven FTS
Compartment of diffusion system
After-shave ethanol-based BB
Facial cleanser ethanol-free BB
O/W emulsion BB
W/O emulsion BB
Epidermis Epidermis
65 ± 8 89 ± 17
56 ± 13 110 ± 12
14 ± 3 18 ± 3
13 ± 2 23 ± 6
Note the penetration increases with shaving. Adapted from Lucova9. Table 2. The amounts of test compounds detected in a given compartment (epidermis) of the in vitro diffusion system after 24-h exposure of ex vivo full-thickness pig-ear skin (FTS) to Patent Blue V and demonstration of increased penetration post-shaving.
Membrane Intact FTS Shaven FTS
Compartment of diffusion system
After-shave ethanol-based PB
Facial cleanser ethanol-free PB
O/W emulsion PB
W/O emulsion PB
Epidermis Epidermis
82 ± 4 105 ± 30
79 ± 13 99 ± 32
44 ± 13 48 ± 14
40 ± 8 40 ± 5
Adapted from Lucova9.
epidermal thickness of shaved areas, which could be due to chronic hyper proliferation and local thickening to facilitate repair of the barrier and protection from subsequent shaving events. They further performed histamine iontophoresis in the vault and fossa of both axilla of the nine volunteers who were asked to shave both axilla 2 d prior to the study. One axilla was shaved immediately prior to iontophoresis. Histamine iontophoresis in both vault and axilla resulted in an increase in both wheal and flare in the shaved axilla as compared to the unshaved control. This supported the previous studies which show that the shaving of axillary skin can damage the epidermal barrier4 while shaved skin has demonstrated to respond to increased itch and erythema following iontophoretic delivery of histamine3. They also performed a randomized control study of 30 female volunteers. In the test phase, subjects were given two-coded antiperspirant roll-on formulations labeled for right and left underarm. Test phase consisted of 2/week underarm shaving and exaggerated product use and irritation
assessed by an expert assessor 3/week. In the provocation phase, daily underarm shaving along with exaggerated application (4 times daily) of a control antiperspirant roll-on was performed. Results showed a decrease in irritation due to the roll-on used in the test phase compared to the control rollon formulation used in the provocation phase. Turner et al. concluded that axillary shaving results in removal of skin and increased potential for irritation and itch. Moreover, axillary vault showed a greater thickening in the epidermis than the unshaved area of the fossa. The response to histamine iontophoresis in the shaved axilla was greater than that of the unshaved which supported the fact that shaving causes damage to epidermal barrier. Banerjee and Ritschel11 studied transdermal permeation of vasopressin using female Sprague–Dawley rats. Effect of shaving was studied by shaving rat skin one day before the study with an electric shaver after preliminary clipping of hair before excision. Skin was allowed to heal for 24 h. This was compared to Flynn’s study12 of stripping the skin 25 times
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Figure 3. The Cyclosporin A serum concentration in murine blood as a function of time after an epicutaneous administration of flexible vehicles under normal skin and shaved skin. Serum concentration increases significantly after epicutaneous application of flexible vesicles post-shaving compared to normal skin. Adapted from Guo14.
Figure 4. No difference between shaved and unshaved ventral forearm skin in vivo in the percutaneous absorption of testosterone in rhesus monkey utilizing the urinary excretion method. Adapted from Wester15.
with cellophane tape to remove the stratum corneum. Vasopressin solution was used to study the effect of shaving on its permeation. Flux was increased 5-fold due to shaving and the lag time of vasopressin was reduced significantly in comparison to light clipping. Stripping (25 times) resulted in the removal of stratum corneum and showed a marked increase in vasopressin permeation. This shows skin is partially damaged and demonstrates the stratum corneum is one of the main barriers to permeation of vasopressin. The results are consistent with that of Bruger and Flexner13, which demonstrated an increase in insulin permeation due to shaving.
Guo et al.14 examined Cyclosporin A using Kunming mice (kept under normal laboratory conditions). The hair of test mice was trimmed short with a pair of scissors. To destroy the integrity of stratum corneum, the other group of mice was shaved with scrapper. Application area on the abdominal skin was 2 2 cm. Flexible and conventional vesicles were administered respectively and left to dry out. Results of the in vivo study demonstrated that with the application of flexible vesicles on unshaven skin, serum drug concentration of 53.4 ± 9 ng/ml was detected after 2 h of permeation and amounted to 154 ± 27 ng/ml 6 h later. Whereas, after the stratum corneum of mouse skin was destroyed post-shaving, a large amount of drug into blood was
Marti et al. / Effect of shaving on axillary Stratum corneum.
Lucova et al.9/Absorption of triphenyl-methane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life
2
4
Study
1
S. #
Case-control study.
Study design
6-month old pigs
30 Humans
No. of subjects
Table 3. The contents of the various studies mentioned in the text.
1. 2 groups studied for 4 weeks. Group 1: shaved axilla once a week. Group 2: shaved axilla once a day 7days/week) All participants used a roll-on antiperspirant 4 times daily. 2. Antiperspirant patch test: Pre-shaving of the volar forearm followed by the standard 47- hr patch test was compared to unshaven skin. 3. Histamine iontophoresis was performed after shaving an area of the forearm five times. In addition, the two adjacent sites were tested as control sites: Control 1: prior to shaving. Control 2: after iontophoresis at the shaved site. Ears and tongues of pigs prepared according to OECD TG 428. The fullthickness skin membrane (FTS) obtained from the upper half part of the pig-ear’s back, which contains no adipose tissue. To mimic the in-use conditions when cosmetics are applied to human skin slightly damaged mechanically, hair follicles of every second FTS were shaved. Wet intact FTS membrane was traveled with a manual razor (Wilkinson Sword Extra II, Solingen, Germany) twice in the opposite direction of hair growth, and once in the direction of growth. The pressure exerted on FTS was similar to shaving. 250 ng/cm2 of BB and 2500 ng/cm2 of CAF or 250 ng/cm2 of PB and 2500 ng/ cm2 of CAF were applied in one dose. Diffusion was carried out during nonoccluded 24-h exposure (an infinite dose) to simulate typical consumer usage of leave-on cosmetics. After the experiment, in order to remove a residual dose, the surface of FTS was carefully rinsed three times with 1 mL of appropriate solvent (distilled water for after-shave and facial cleanser, isopropanol for O/W emulsion and diethyl ether for W/O emulsion).
Method
The highest amounts of both dyes penetrated into the epidermis from ethanol-based after-shave; for example 4.0 and 2.6 times higher for BB and PB, respectively than from W/O emulsion. Shaving caused only a slight decrease in thickness of FTS (approx. 1%) but significant increase in the TEC values (between 3.5 and 5.7-fold) compared to intact FTS. Subsequently, diffusion studies through shaven skin showed permeation values higher roughly 1.2-fold for after-shave, 1.3-fold for facial cleanser, 1.1-fold for O/W emulsion and 1.8-fold for W/O emulsion as through intact FTS
3. Itch perception and histamine-induced neurogenic flare significantly increased at the shaved site.
2. The antiperspirant irritancy increased significantly.
1. Dry shaving immediately perturbed barrier function in the upper layers of the stratum corneum as observed with a lowered CIM value.
Results
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(continued )
Chemicals used: Triphenyl-methane dyes Brilliant Blue and Patent Blue and caffeine. Conclusion: The normal process of shaving significantly increases the potential of systemic availability of both dyes from hydrophilic vehicles. This finding is worrisome, taking into account the frequency of skin treatment after shaving and depilation with cosmetic products containing the dyes, perhaps during the long years of life.
Chemicals used: antiperspirant roll-on.
Comments
DOI: 10.3109/15569527.2014.966109
Shaving effects on percutaneous penetration 5
Study design
Randomized trial
Clinical trial
Study
Turner6/Impact of shaving and antiperspirant use on the axillary vault
Banerjee and Ritchel11/ Transdermal permeation of vasopressin. I. Influence of pH, concentration, shaving and surfactant on in vitro permeation
3
4
S. #
Female SpragueDawley rats (Harlan) of 10-20 weeks of age
9 participants (8 females and 1 male)
No. of subjects Experimental design Three series of in vitro diffusion experiments were carried out; first through intact FTS and second through shaven FTS (a dose: the model cosmetic product); third through FTL (a dose: the salivary solution), all separately for BB and PB dye. Subjects were asked to shave both axillae 2 days prior to the study and apply no underarm product on the day of the study. One axilla (randomized to left or right) was shaved immediately prior to iontophoresis in both vault and fossa. Sterile solution of 1% histamine dihydrochloride in a 2.5% methyl cellulose hydrogel was delivered into the skin using an electric current supplied by an iontophoresis controller (Moor Instruments Ltd, Axminster, U.K.). Blood flow was measured using a dualchamber laser Doppler flow monitor (Moor Instruments Ltd). Baseline flux (blood flow) measurements were monitored for 1 min, followed by a 50 mA electric current for 10 s, followed by a further monitoring for 5 min. On removal of the chambers, transparent film was placed over the area and the size of wheal and flare were recorded. Female Sprague-Dawley rats (Harlan) of 10-20 weeks of age were sacrificed by overdose ether inhalation. The skins, excised after light clipping of the hair on the back with electric clippers (Oster), were cleaned of subcutaneous tissue and fat. The skin was mounted on diffusion cells and used within an hour. Binding study: Full-thickness excised rat skin was used. Epidermis was separated from dermis by a previously reported method. The sorption isotherm was determined by equilibration of a measured weight of epidermis with 1 ml known concentration of radio-labeled vasopressin solution in a shaker-bath for 3 h at 30 C. After
Method
Table 3. Continued
Shaving increased the flux (about 5 times) and decreased the lag time of vasopressin significantly when compared to light clipping. Stripping (25 times), which removes the stratum corneum showed dramatic increase in VP skin permeation.
Histamine iontophoresis of the axillary vault and fossa resulted in an increase in both flare and wheal in the shaved axilla when compared with the respective unshaved control. Results provide evidence of this increased sensitivity to histamine in shaved skin. However, the flare in the fossa was significantly greater than that observed in the vault (p50.05), when both of these sites were shaved (wheal was also greater, although not significantly).
Results
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This shows that shaving damages the skin partially and gives evidence to the fact that the stratum corneum is the main barrier to permeation of vasopressin.
Conclusion: response to histamine iontophoresis in the shaved axilla was greater than that of the unshaved (both flare and wheal), providing a further example of the potential for shaving to damage the epidermal barrier. Histamine response in the vault of the shaved axilla was less than that in the shaved fossa, which is proposed to be due to the thicker epidermis in the vault affording some degree of protection from the shaving process.
Comments
6 M. Hamza et al. Cutan Ocul Toxicol, Early Online: 1–9
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Wester and Maibach15/ Percutaneous Absorption in the Rhesus Monkey Compared to Man
Clinical Trial
Female rhesus monkeys used
equilibration, the epidermis was digested with TS-1 tissue solubilizer (Research Products International) and analyzed by scintillation counting. Duplicate samples were also taken from the aqueous phase and analyzed. The effect of shaving was studied by shaving rat skin one day before the study with a Remington Super Mesh Electric Shaver (Model SM-100, Remington Products Inc.) after preliminary clipping of the hair. The skin was allowed to heal for 24 h (although no visible damage was observed), and excised. This was compared to stripping, where the skin was stripped 25 times with cellophane tape (Scotch Brand, 3 M) to remove stratum corneum (Flynn et al.18). Concentrations of vasopressin solution in the donor phase were 46.8 g/ml (4/Ci/ml) for clipped and shaved skin and 49.5/zg/ml (4 tCi/ml) for stripped skin Female rhesus monkeys (Macaca mulattu), trained for metabolic studies, were used. For iv administration a saline solution of the compounds was slowly given in the cephalic vein. The amount given was the same as was topically applied, averaging approximately 5 PCi. Urine was then collected in a metabolism cage. For topical application the monkeys were placed in a metabolic chair for the first 24 hr of the study. The hands of the monkey were secured to the sides of the chair to avoid its wiping off the applied compound. This was done by wrapping shaved wrists with adhesive tape, reinforced with a second layer of filament tape (Scotch brand). By using adhesive tape the hands were secured but blood circulation was not interfered with. Testosterone and hydrocortisone were applied to the skin in acetone, and benzoic acid applied in methanol. The application dose of 0.25 ml was applied with a pipette on to a premarked area and the solvent quickly evaporated by gentle blowing. Because of variations in the specific activity it The ventral forearm of the rhesus monkey is not very hairy. The effect of shaving the topical application site was tested by lightly depilating the area with an electric razor. The data shows that there was no difference between shaved and unshaved skin in the percutaneous absorption of testosterone. Application to the shaved area was easier and so electric razor-dipilated skin was use.
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(continued )
DOI: 10.3109/15569527.2014.966109
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S. #
Guo14/Lecithin vesicular carriers for transdermal delivery of cyclosporin A (October 1999)
Study
Clinical trial
Study design
Kunming mice
No. of subjects was necessary to vary the total area of application. However, the quantity of compound applied was always 4 pug/ cm*. For the next 24 hr, urine was collected in a container below the metabolism chair. Then the site of application was washed with soap and water and the monkey returned to a metabolism cage to continue the urine collection. Kunming mice, 3–4 weeks old, weighed 18–22 g, were kept under normal laboratory conditions. The hair of test mice was carefully trimmed short with a pair of scissors. To destroy the integrity of stratum corneum, the other group of mice was shaved with scraper. The application area on the abdominal skin was limited to 2 cm2. Flexible Vesicles and conventional vesicles were respectively administered and left to dry out. Mice were respectively sacrificed after 1, 2,4,6,8 and 12 h of application. Serum conc. Followed the same procedure of extraction was detected by HPLC.
Method
Table 3. Continued
In vivo study showed that with the application of flexible vesicles, serum drug concentration of 53.4399. 24 ng/ ml was detected after 2 h of permeation and amounted to 154.37927.15 ng/ml 6 h later (Figure 3). When the stratum corneum of mouse skin has been destroyed by shaving, flexible vesicles transferred large amount of drug into blood, up to 187.32953.21 ng/ml after 1 h of application and amounted to 364.51954.06 ng/ml 4 h later. Conventional vesicles failed to deliver measurable amount of drug into the blood under normal skin condition.
Results
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Comments
8 M. Hamza et al. Cutan Ocul Toxicol, Early Online: 1–9
Shaving effects on percutaneous penetration
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DOI: 10.3109/15569527.2014.966109
transferred by flexible vesicles, up to 187.3 ± 53 ng/ml after 1 h of application and amounted to 364.5 ± 54 ng/ml 4 h later (Figure 3). This indicates shaving has a profound effect on the permeation of Cyclosporin A. Lastly, Wester and Maibach15 used female rhesus monkeys trained for metabolic studies. For IV administration a saline solution of the compounds was slowly given in the cephalic vein. Amount given was the same as was topically applied. Urine was then collected in a metabolism cage. For topical application the monkeys were placed in a metabolic chair for the first 24 h. Hands of the monkey were secured to the sides of the chair to avoid its wiping off the applied compound. Testosterone and hydrocortisone were applied to the skin. Effect of shaving the topical application site of the ventral forearm of rhesus monkey was tested by lightly depilating the area with an electric razor. Results showed there was no difference between electric razor shaved and unshaved skin in the percutaneous absorption of testosterone (Figure 4). Table 3 summarizes the contents of the various studies discussed above.
Conclusion Shaving is ubiquitous, millions of people shave every day. Many of the areas that are shaved have additional chemical exposure e.g. (i) Disinfectants and antiseptics on operating tables. (ii) After-shave tonic, lotions and balms. (iii) Moisturizers. Therefore, it is highly relevant to investigate the systemic and chemical effects of the various chemicals that come in contact with the shaven areas. Shaving also destroys barrier integrity of stratum corneum, which adds to increased penetration. It has an exaggerated response to itch perception and erythema. This article summarizes the minimal experimental data available. Hence, it surpasses a simple interpretation. For example, in the histamine iontophoresis study conducted by Marti et al., a standard 47 h patch test showed that antiperspirant irritancy increased post shaving as compared to unshaved skin suggesting that shaving alters rapid penetration possibly through shunts. The experiment performed by Lucova et al. also showed a statistically significant increase in permeation of the dye Brilliant Blue (ethanol-based aftershave) from 65 ± 8 to 89 ± 17 and the dye Patent Blue (ethanol-based aftershave) from 82 ± 4 to 105 ± 30 compared from intact to shaven FTS (full thickness skin), respectively. Whereas Wester’s urinary excretion experiment does not demonstrate any increase in penetration following shaving. Therefore, this effect could be a species/compoundspecific as human, rat and pig skin has increased permeability for various substances post-shaving whereas rhesus monkey skin exhibits no such effect of testosterone in Wester’s experiment.
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Intuitively, we suspect that any possible increase in penetration from shaving would be obtained in long term rather than acute effects; for instance, we know of no database demonstrating acute toxicity following shaving. Using current knowledge about percutaneous penetration, this is a vastly underserved area which will benefit by further research and re-evaluation of different methods of shaving, e.g. clippers/electric shavers versus razor blades, examining chemicals of various physiochemical properties, species, shaving and pre- and post-shave methods as well as anatomic sites, which in the end, will permit a general predictive theory and pertinent interventions and risk assessment.
Declaration of interest There is no conflict of interest to declare.
References 1. Elden HR. Advances in understanding mechanisms of shaving. Cosmet Toiletries 1985;100:1. 2. Zupkosky PJ, Coffindaffer TW, Kaczvinsky JR, et al. Hydration and skin condition in context of shaving. Int J Cosmetic Sci 2012; p 2620. 3. Holbrook AK, Odland FG. Regional differences in the thickness (cell layers) of the human stratum corneum: an ultrastructural analysis. J Investig Dermatol 1974;62:415–422. 4. Marti VPJ, Lee RS, Moore AE, et al. Effect of shaving on axillary stratum corneum. Int J Cosmetic Sci 2003;25:193–198. 5. Marti V, Brennan G, Clarke P, et al. Assessing the irritation potential of anti-perspirants. J Invest Dermatol 2001;117:961. 6. Turner GA, Moore AE, Marti VPJ, et al. Impact of shaving and antiperspirant use on the axillary vault. Int J Cosmetic Sci 2007; 29:31–38. 7. Kavaliunas DR, Nact S, Bogardus RE. Men’s skin care needs. Cosmet Toiletries 1985;100:29–32. 8. Bhaktaviziam C, Mescon H, Matoltsy AG. Study of skin and shaving. Arch Dermatol 1963;88:242–247. 9. Lucova M, Hojerova J, Pazourekova S, Klimova Z. Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products. Food Chem Toxicol 2013;52:19–27. 10. Krishnaiah YS, Bhaskar P, Satyanarayana V. Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin. Pharm Dev Technol 2004;9: 63–74. 11. Banerjee PS, Ritschel WA. Transdermal permeation of vasopressin. I. Influence of pH, concentration, shaving and surfactant on in vitro permeation. Int J Pharm 1989;49:189–197. 12. Flynn GL, Du¨rrheim H, Higuchi WI. Permeation of hairless mouse skin II. Membrane sectioning techniques and influence on alkanol permeabilities. J Pharm Sci 1981;70:52–56. 13. Bruger M, Flexner J. Integrity of the skin in relation to cutaneous absorption of insulin. Proc Soc Exp Biol Med 1936;35:429–432. 14. Guo J, Ping Q, Sun G, Jiao C. Lecithin vesicular carriers for transdermal delivery of cyclosporin A. Int J Pharm 2000;194: 201–207. 15. Wester RC, Maibach HI. Percutaneous absorption in the rhesus monkey compared to man. Toxicol Appl Pharmacol 1975;32: 394–398.
