j.1600-0536.2002.470504.x

7/28/2019 j.1600-0536.2002.470504.x

1/7

Contact Dermatitis 2002, 47, 272278 Copyright C Blackwell Munksgaard 2002

Printed in Denmark . All rights reserved

ISSN 0105-1873

Review Article

Ethnicity as a possible endogenous factor in irritantcontact dermatitis: comparing the irritant responseamong Caucasians, blacks, and Asians

S. P. M H. I. M

University of California, San Francisco, California, USA

Irritant contact dermatitis (ICD) is a common dermatological diagnosis in which endogenous andexogenous factors have been implicated. This review explores ethnicity as a possible endogenousfactor. While there is a clinical consensus that blacks are less reactive and Asians are more reactive

than Caucasians, the data supporting this hypothesis rarely reaches statistical significance. Thestudies reviewed do not provide sufficient evidence to determine that race is a predisposing factorto the degree of irritation in ICD. We conclude that race could be a factor in ICD, which haspractical consequences regarding topical product testing requirements, an ever-expanding globalmarket, occupational risk assessment, and the clinical thinking about ICD. Pitfalls in definingdifferences are discussed.

Key words: endogenous factors; ethnicity; irritant contact dermatitis; irritation; man, race. CBlackwell Munksgaard, 2002.

Accepted for publication 18 October 2002

Irritant contact dermatitis (ICD) is a common andpotentially serious dermatological disorder (13).It is also the second most common occupationalillness (4). Because contact dermatitis can developinto chronic skin disease, understanding the under-lying factors of its aetiology is clinically important.

This condition is divided into several forms de-pending on the nature of exposure and the result-ing clinical presentation. Two common entities areacute and cumulative contact dermatitis. Acutecontact dermatitis presents the classic symptoms

of irritation such as localized and superficial ery-thema, oedema, and chemosis. It occurs as a resultof single exposure to an acute irritant (5). Cumula-tive irritant contact dermatitis presents similarsymptoms, but occurs when exposure to a less po-tent irritant is persistent or repeated until signsand symptoms develop over weeks, years, or dec-ades.

The ability of the offending irritant to causecontact dermatitis depends on both the natureof the irritant agent and the initial skin con-dition. The severity of symptoms depends onexogenous and endogenous factors (68). Exoge-

nous factors include the irritants chemical andphysical properties, and the vehicle and frequencyof application. Endogenous factors have beenspeculated to be age, sex, pre-existing skin dis-eases, skin sensitivity, genetic background, and the subject of this reviewrace (6), or, in todaysparlance, ethnicity.

Ethnic differences in skin physiology and patho-physiology exist (911), and so whether ethnicityis, in fact, an endogenous factor affecting ICD isan important question in dermatotoxicology. Eth-

nic predisposition to ICD has been studied bycomparing the irritant responses of blacks and As-ians to those of Caucasians as a benchmark. Wereview these studies to evaluate if ethnic differencesin susceptibility to ICD do exist.

The answer to the question of ethnicity as a fac-tor in ICD has clinical and practical researchconsequences. Pre-market testing of topical prod-ucts (soaps, detergents, perfumes, and cosmetics),risk assessment for occupational hazards, and sub-ject-inclusion requirements for product safetystudies require knowledge about ethnic differencesin irritation (12).

7/28/2019 j.1600-0536.2002.470504.x

2/7

273ETHNICITY AND IRRITANT CONTACT DERMATITIS

Black versusCaucasian irritation response

Using erythema as the parameter to quantify irri-tation, early studies note that blacks display lessredness than Caucasians. In a hallmark paper,Marshall et al. (13) showed that while 59% of Cau-

casians exhibit acute irritant contact dermatitis asdefined by erythema from 1% dichlorethylsulfide(DCES), only 15% of blacks do. Later, Weigandand Mershon (14) performed a 24-h patch testusing ortho-chlorobenzylidene malononitrile as anirritant, which confirmed that blacks are less sus-ceptible than Caucasians to ICD as defined by ery-thema. Further studies, also using erythema as ameasure of irritation, showed that blacks are lessreactive than Caucasians to irritants(160m/L and1280m/L methacoline) (15, 16).

Weigand and Gaylor (17) showed that if the stra-tum corneum of black and Caucasian subjects is

removed, there is no significant difference in irri-tation as measured by erythema between the twogroups. They conclude that there might be struc-tural differences in the stratum corneum that pro-vide more protection from chemical irritation toblack skin than Caucasian skin. Indeed, while thestratum corneum thickness is the same in bothraces (18), the stratum corneum of black skin hasmore cellular layers and stronger cells (12), morecasual lipids (19), increased desquamation (20), de-creased ceramides (21), and higher electrical re-sistance (22) than Caucasian skin. Some of theseanatomical and physiological differences of the

stratum corneum could be used to explain the ob-served reduced irritation in black skin as measuredby erythema (3).

It is difficult, however, to conclude that blacksare less susceptible to cutaneous irritation basedonly on studies using visual scoring. Erythema isnotoriously difficult to measure in darker skin.Perhaps the difference in skin irritation betweenthe two test groups is simply a result of the diffi-culty of assessing erythema in black subjects.

To understand this issue better it is necessary toanalyse studies that use alternative accurate detec-

tion methods (23) to assess the level of inducedcutaneous irritation. Berardesca et al. (24) per-formed such a study to determine the differencein irritation between young Caucasian and youngblack skin. They applied 0.5% and 2.0% sodiumlauryl sulfate (SLS) to untreated, pre-occluded,and predelipidized skin. Then they quantified theresulting level of irritation using objective tech-niques: laser Doppler velocimetry (LDV), transepi-dermal water loss (TEWL), and water content ofthe stratum corneum (WC). They found no stat-istical difference in irritation between the twogroups as measured by LDV and WC, but they did

find a statistical difference in the TEWL results ofthe pre-occluded test with 0.5% SLS. In that test,blacks had higher TEWL levels than Caucasians,suggesting that in the pre-occluded state blacks aremore susceptible to irritation than Caucasians.The finding of this study contradicts the hypoth-

esis that blacks are less reactive than Caucasians.Similarly Gean et al. (25) found no statisticallysignificant difference in the maximum LDV re-sponse between black and Caucasian subjectgroups when they challenged skin with topicalmethyl nicotinate (0.1M, 0.3 M, and 1.0 M).Further, unlike the earlier studies, they found nodifference in the blood flow and erythema re-sponses between the two groups.

Guy et al. (26) supports the results finding thatLDV measurements of induced blood flow afterapplication of 100-m methyl nicotinate reveal nosignificant differences between black and Cauca-

sian subject groups; however, a significant differ-ence was found using photoplethysmography(PPG). Caucasians had a greater PPG value thanblacks, suggesting that Caucasians may be moresusceptible to irritation. The authors did not ex-plain why blood flow measurements using PPGshowed a statistically significant difference betweenthe groups when LDV did not.

Berardesca et al. (27) also found decreased reac-tivity in blood vessels in the black test group thanthe Caucasian test group. They measured the post-occlusive cutaneous reactive hyperaemia tempor-ary increase in blood flow after vascular oc-

clusion after an application of a potent corticos-teriod, and measured vasoconstriction using LDV;the black subject group had several significantlydifferent parameters of the hyperaemic reaction.They found a decreased area under the LDV curveresponse, a decreased LDV peak response, and adecreased decay slope after peak blood flow, show-ing that blacks have a decreased level of irritation-induced reactivity of blood vessels. These resultsare consistent with their previous work.

In conclusion, older studies using erythema asthe only indicator for irritation show that blacks

have less-irritable skin than Caucasians, but morerecent studies using objective bioengineering tech-niques suggest that the eye may have misled us toan incorrect interpretation. Findings that do anddo not show statistically significant differences inthe irritation response between blacks and Caucas-ians are summarized in Tables 1 and 2.

Asian versusCaucasian irritation response

An early study comparing Caucasian and Japanesesusceptibility to cutaneous irritation was done byRapaport (28). He performed a standard 21-day

7/28/2019 j.1600-0536.2002.470504.x

3/7

274 MODJTAHEDI AND MAIBACH

Table1. Findings that show a statistically significant difference in the irritation response between blacks and Caucasians

Interference End-point Comment Reference

1% Dichlorethylsulfide Erythema Untreated Marshall et al. (13)Ortho-chorobenzylidene Erythema Untreated Weigand et al. (14)100m methyl nicotinate PPG Untreated Guy et al. (26)0.05% clobetasol LDV Pre-occluded Berardesca et al. (27)0.52.0% SLS TEWL Pre-occluded Berardesca et al. (24)

Table2. Findings that do not show a statistically significant difference in the irritation response between blacks and Caucasians

Interference End-point Comment Reference

0.52.0% SLS LDV and WC Untreated, pre-occluded, Berardesca et al. (24)and pre-delipidized

100m methyl nicotinate LDV Untreated Guy et al. (26)0.1 , 0.3 , and 1.0 methyl nicotninate LDV and Erythema Untreated Gean et al. (25)

patch test protocol on Caucasian and Japanese fe-males in the Los Angeles area in which 15 irritants

(different types or concentrations of cleansers,sunscreen, and SLS) were tested. The results werereported according to the cumulative readings ofall subjects in an ethnicity group for each irritant.Japanese women had higher cumulative irritationscores for 13 of the 15 irritants tested; he inter-preted these findings to confirm the common im-pression that Japanese are more sensitive to irri-tants than Caucasians. Also, this sensitivity was in-dependent of the concentration or exact chemicalformulation of the substance tested, suggestingthat Japanese are in general more sensitive thanCaucasians.

While these findings are important, it is difficultto interpret this data. First, as also noted byRobinson (12), Rapaport provides little experi-mental detail and data. For example, while thestudy required 21 separate days of irritation read-ings, only the end cumulative irritation scores arereported. If he had reported daily irritation read-ings, we would have been able to note the timepattern of response. Further, no statistical testswere conducted to ascertain if the differences be-tween the Japanese and Caucasian subjects werestatistically significant. Note, too, that the cumula-

tive irritation test score does not distinguish be-tween the intensity of a subjects response and thenumber of subjects responding. Thus it is possible,for example, for a few extremely sensitive Japanesesubjects to inflate the overall irritation score.Therefore, at the minimum, it would be helpful toprovide standard deviations to rule out such prob-lems.

At first seemingly surprising, Basketter et al.(29) found that Germans are more sensitive thanChinese subjects. Subjects in Germany, China, andthe United Kingdom were exposed to varying con-centrations (0.1%-20%) of sodium dodecyl sulfate

(SDS) for 4 h on the upper outer arm, and theresulting doseresponse irritation was measured

based on erythema. They concluded that Germanstend to be more sensitive than Chinese subjects,and the Chinese subjects slightly more sensitivethan the British subjects. This conclusion runscontrary popular belief and to the Rapaport study,which indicated that Asians are more likely to de-velop irritant contact dermatitis than Caucasians.

There are, however, inherent flaws in this study,some of which the authors acknowledged. Firstand foremost, this study does not control the vari-ables of time and location. The German and Chi-nese studies were performed over 36weeks in thewinter, while the UK study was spread over 15

months. Also, in particular, German winters arecolder and drier than Chinese winters, and Chinesewinters tend to be colder than English winters.These variables will distort the results in a predict-able way if we assume that an individual becomesmore sensitive to irritant contact dermatitis in col-der and drier climates (2). We would then expect,based on climatic conditions, that the Germansubjects would be more reactive than the Chinesesubjects, and the Chinese subjects more reactivethan those from the UK. As these are the actualresults, we cannot necessarily contribute the differ-

ences in irritant response to ethnicity, as it is poss-ible that the differences are due to weather con-ditions. Also, they mention that 15% of the UKvolunteers were black. While they account for thisby showing that the black irritant response wassimilar to the overall UK group response, it isscientifically problematic to mix racial groups in astudy testing for racial differences. Furthermore,they supplied no statistical tests for their con-clusion that Germans are slightly more sensitivethan the other ethnic groups. To shed more lighton the results, we conducted simple binomial testsof the differences in the percentage response of the

7/28/2019 j.1600-0536.2002.470504.x

4/7


Table3. Statistical analysis of the Basketter et al. (29) study

0.1% SDS 0.25% SDS 0.5% SDS 1.0% SDS 2.5% SDS 5.0% SDS 10% SDS 20% SDS

Germany 0.03 0.09 0.23 0.50 0.65 0.72 0.76 NDChina 0 0 0.01 0.21 0.45 0.61 0.79 0.90UK 0.01 0.01 0.06 0.15 0.33 0.41 0.49 0.76N 100 100 100 100 100 100 100 100Z (Germany-China) 1.75 3.07* 4.79* 4.29* 2.84* 1.65 0.51 NA

Z (UK-China) 1.00 1.00 1.92 1.10 1.74 2.83* 4.42* 2.64*Z (UK- Germany) 1.01 2.60* 3.41* 5.28* 4.53* 4.42* 3.94* NA

The numbers in the first three rows are the decimal value of the percentage of the group that developed a positive irritant reactionat a specific SDS concentration. The numbers in the last three rows are the Z-values. We applied the binomial test to ascertain thedifferences in the percentage response of the subject groups: Z (r1 r2)/[2r(1r)/100]

50, where r1 and r2 are the ratios for the twoethnic groups and r is the weighted average. As the sample sizes for different groups are equal, r becomes the simple average. Anasterisk indicates that the ratios are significant at the 5% level. Note that all the UKGermany differences, except one, are statisti-cally significant; however, more than half of the UKChina and almost half of GermanyChina differences are not statisticallysignificant. This indicates a larger statistically significant difference between the two Caucasian groups that between the Caucasianand Asian groups.

subject groups. Using the resulting statistics, wefound a larger statistically significant difference be-

tween the two predominantly Caucasian groupsthan between each of the Caucasian and the Chi-nese groups (Table3). These results indicate thatrace may not be the predominant factor affectingsusceptibility to ICD in this study; other uncon-trolled variables may dominate the results.

Variables such as time and location were elimin-ated by the Goh and Chia (30) study that testedthe susceptibility to acute irritant contact derma-titis in Chinese, Malaysian, and Indian subjects.These subjects were exposed to 2% SLS in the rightscapular region, and resulting irritation measuredusing transepidermal water loss (TEWL). This

technique is an objective way to indirectly quantifyirritation the higher the TEWL value, the greaterthe implicit irritation. There was no significant dif-ference in the TEWL level of irritant skin in a 3-way statistical test of the three racial groups. Therewas a significant difference, however, between theTEWL values of Chinese and Malaysian subjectssuch that Chinese subjects were more susceptibleto contact dermatitis. While this test does not con-tribute to the discussion of the difference in predis-position of irritation in Caucasian versus Asianskin, it does add to the overall question of whether

race can be a predisposition to irritant contact der-matitis.Foy et al. (31) clearly added to our knowledge

of the difference in the acute and cumulative irri-tation response in Japanese and Caucasian femaleskin. They reduced some variables that compro-mised other studies; location, time, season, andscorer were the same for both study populations.11 different materials were tested in the acute test;they were applied to the upper arms for 24h, andirritation was measured based on erythema. Thecumulative test consisted of testing 5 irritants usinga 4-exposure cumulative patch protocol.

In the acute test, while there is a slight tendencyto greater susceptibility to irritation among Ja-

panese subjects, only 4 out of the 11 irritantscaused a significant difference in reactivity betweenthe two groupsthese were the most-concentratedirritants used. This shows that perhaps for more-concentrated irritants there is indeed a statisticaldifference in the acute contact dermatitis response;of course, this study needs to be interpreted in con-text with others to follow. For the cumulative studythe skin irritation scores between the two testgroups are close but the Japanese tended to haveslightly higher numbers. The differences, however,only reached statistical significance in two in-stances. and as the authors noted, it is difficult to

interpret the importance of those two instances,since the statistically significant differences are notmaintained at later points in the timeline. It is safeto conclude therefore that while the acute irritantresponse to highly concentrated irritants was sig-nificantly different between the Japanese and Cau-casian subjects, the cumulative irritant responserarely reaches a statistical difference.

Studies that include both acute and cumulativeirritant tests, like the one above, are more informa-tive than single tests since they give a more com-plete view of differences in skin irritation between

groups. Robinson (32) conducted a series ofstudies that tested racial differences in acute andcumulative skin irritation responses between Cau-casian and Asian populations. In the first acutetests, Caucasian and Japanese groups were ex-posed on the upper outer arm to 5 irritants underocclusion for up to 4 h. The resulting erythema wasscored on an arbitrary visual scale. The resultswere represented as the cumulative percent inci-dence of positive test reactions to the different irri-tants.

It is curious to note that while Japanese subjectstend to be more susceptible to acute irritation than

7/28/2019 j.1600-0536.2002.470504.x

5/7


Caucasians, no one irritant nor one test timecaused a significant response difference betweenthe two groups; rather, the significant differenceswere scattered across 5 different test materials andtime points. The acute irritation response data wasthen reanalysed in terms of possible differences in

temporal response. It was shown that Japanesesubjects generally react faster than their Caucasiancounterparts, as indicated by their shorter TR50values (the time it takes for the cumulative irri-tation score to reach 50%). While this result is in-teresting, and adds the new dimension of temporaldifferences in reactivity between the two groups,hard data was not given and statistical analysis wasnot conducted to see if this temporal pattern dif-ference is indeed statistically significant.

The cumulative irritation test was conductedconcurrently and on the same Japanese and Cau-casian subjects. Four concentrations of SDS

(0.025%, 0.05%. 0.1%, and 0.3%) were applied onthe subjects upper backs for 24 h for a total of 14days. The resulting skin grades were summed forall subjects for all test days. For the two lower SDSconcentrations the Japanese subjects reacted onlyslightly more than the Caucasian subjectsbutonly the difference in skin grades for 0.025% SDSreached statistical significance. When this data wasanalysed in terms of temporal response, the twolowest concentrations the Japanese reacted onlyslightly faster than their Caucasian counterparts.Whether the difference in reaction time is statisti-cally significant in not known.

In the same study, Robinson then applied boththe acute and cumulative irritation protocols tocompare three new subject groups Chinese, Ja-panese, and Caucasian to each other. The cumu-lative irritation study found no statistically sig-nificant differences between the different groups.In the acute test, he found that, in most cases, theChinese subjects were more reactive to irritantsthan Caucasians, but that in only one case was thisdifference significant, and he states that most likelythis was an anomaly. There was no discernible dif-ference between the Japanese and Chinese groups.

and surprisingly, when the Japanese subjects wereagain compared to the Caucasian subjects as theywere in the beginning of his study, the resultsshowed no significant difference between the twogroups.

While Robinsons first 2-way irritation responsecomparison test between Japanese and Caucasiansubjects did show some statistical differences, thefact that they could not be confirmed in the secondhalf of the study emphasizes the difficulty in ob-taining repeatable results in this type of study. Forone thing, in the statistical sense Robinsonssample sizes (approximately 20 people) were small,

combined with the variability between human skinwithin an ethnic group, this makes it difficult tomake concrete conclusions. His study showed,however, that there were essentially no significantdifferences between the Asian and Caucasiangroups, at least none that could be repeated.

Robinson et al. (33) had similar results. Usingthe 4-h occlusion patch method, they comparedthe relative acute skin reactivity of Asian and Cau-casian subjects using the irritation temporal re-sponse to measure the difference in reactivity be-tween the test groups. They tested 5 chemicals, in-cluding 20% SDS and 100% decanol. Unlike thepreviously described study, they failed to find astatistical difference between the reactivity tomultiple irritants between the two groups, even atthe 4-h mark. Then they did something new: theyseparated the racial subpopulations into sensitiveand normal groups to test any differences in per-

cent cumulative scores and temporal responseswithin these new groups but across race (i.e. theycompared sensitive Asians to sensitive Caucasi-ans). There were no statistically significant differ-ences between subjects of the same skin type indifferent racial groups. This further contradicts thehypothesis that Asians are more reactive to irri-tants than Caucasians.

Recently, Robinson (34) compiled 5years of hisprevious data and compared the acute reactivitydifferences between Caucasian and Asian (com-bined Japanese and Chinese) subgroups using the4-h human patch method. The data was repre-

sented in terms of the time it took subjects to havea positive response to the irritant chemical. Again,as in most experiments, Asians displayed a greaterirritation response score than Caucasians. Notethat while these results of this study are probablymore representative of the population at large be-cause of the relatively large sample size (200 plus),the data from this study was compiled from 3 dif-ferent testing centres over 5 years. This could havepotentially added uncontrolled and unaccounted-for variables.

In support of the long-held belief that Asians

are more susceptible to irritant contact dermatitis,several studies do indeed demonstrate this ten-dency (31, 33, 34). Rarely, however, is this trendstatistically significant, and even more rarely canthe statistical significance be repeated in an an-other study. Therefore, it can be concluded fromthese studies that there is no fundamental differ-ence between Asian and Caucasian cutaneous irri-tant reactivity, the overall irritant response and thetime to reach that response is similar in both sub-groups.

However, the lack of comparable studies, smallsample sizes, external variability, and intravari-

7/28/2019 j.1600-0536.2002.470504.x

6/7


Table4. Potent factors that might influence refinement of inter-pretation in future investigations

Experimental designBaseline versus stress test differencesAnatomic siteOpen versus occluded irritant stressesEthnic groups in the same versus varying geographyComparable climatic conditionsPresentation of hard data and statistical analysis

ability within the subgroups make it difficult tocompletely dismiss Rapaports original findingsthat Asians are more reactive than Caucasians. Forexample, different studies apply the irritant testmaterial on different parts of the body, whichmight have different reaction responses. Thismakes it difficult to compare the results of onestudy to another, and therefore raises the question

of whether a more solid trend among studieswould exist if the irritants were applied to the sameanatomical site. Some potent factors that might in-fluence refinement of interpretation in future in-vestigations are listed in Table4. For the timebeing, however, in terms of topical product safety,risk assessment for occupational hazards, and glo-bal product marketing it would be practical to as-sume that few statistically significant difference be-tween Asian and Caucasian cutaneous reactivityexists.

ConclusionThe studies reviewed demonstrate that there islittle evidence of statistically significant differencesin the irritant response between Caucasian, blackand Asian groups. We can see no consensus onwhether race is indeed an endogenous factor inICD. Intuitively, we suspect that ethnic differencesexist in skin function and may have evolved as havehair and other differences. Basically, the studiessuggesting differences in skin (24, 26) are stressin nature (pre-occluded). Presumably new insightsinto physiology, pharmacology, and toxicology

may clarify this situation.Also it is possible that the well-known divergentresponse to irritants is due to intra-individual vari-ations in the skin irritation response (3537). Thisis a relatively new idea, and therefore furtherstudies need to be conducted in this area beforea definitive statement can be made linking intra-individual variation to ethnic differences in the in-tensity of an irritation response.

We reviewed PubMed, MD Consult, the Melvylcatalogue in the CDL-Hosted Database, Yahoo,Google, and our library files from 1967 to June2002.

References

1. Hjorth N. Fregert. Contact dermatitis. In: Rook, A Wilkin-son, D S Ebling, F J G, eds. Textbook of Dermatology,Chapter 4. Oxford: Blackwell 1968.

2. Malten K E. Thoughts on irritant dermatitis. Contact Der-matitis 1981: 7: 238247.

3. Lammintausta K, Maibach H I. Irritant contact dermatitis.In: Dermatology, 3rd edn (Samuel L M, Harry J H, eds).Philadelphia: W.B. Saunders Co, Harcourt Brace, Jovanov-inch Inc 1992, 425432.

4. NORA. Allergic and Irritant Dermatitis 11 June, 1999.Center for Disease Control 9 April 2002, http://www.cdc.goc/niosh/nrderm.html.

5. Wilkinson J D, Rycroft R J G. Contact dermatitis. In: Text-book of Dermatology, Vol. 1, 4th edn (Rook A, WilkinsonD S, Ebling F J G, eds) Oxford: Blackwell, 1986: 435532.

6. Lammintausta K, Maibach H I. Exogenous and endoge-nous factors in skin irritation. Int J Dermatol 1988: 27:213222.

7. Mathias C G T, Maibach H I. Dermatoxicology mono-graphs I. Cutaneous irritation: factors influencing the re-sponse to irritants. Clin Toxicolocy 1978: 13: 333346.

8. Wilheim K P, Maibach H. Factors predisposing cutaneousirritation. Dermatologic Clinics 1990: 8: 1722.9. Berardesca E, Maibach H. Racial differences in skin patho-

physiology. J Am Acad Dermatol 1996: 34: 667672.10. Berardesca E, de Rigal J, Leveque J L, Maibach H I. In

vivo biophysical characterization of skin physiological dif-ferences in races. Dermatologica 1991: 182: 8993.

11. Benardesca E, Maibach H I. Contact dermatitis in blacks.Dermatologic Clinics 1988: 6: 363368.

12. Robinson M K. Population differences in skin structureand physiology and the susceptibility to irritant and allergiccontact dermatitis: implications for skin safety testing andrisk assessment. Contact Dermatitis 1999: 41: 6579.

13. Marshal E K, Lynch V, Smith H W. On dichlorethylsulphi-de (mustard gas) II. Variations in susceptibility of the skinto dichlorethylsulphide. J Pharmacol Exp Therap 1919: 12:

291301.14. Weigand D A, Mershon M M. The cutaneous irritant reac-

tion to agent O-chlorobenzylidene (CS). Edgewood ArsenalTechnical Report, MD, EB-TR-4332, February 1970.

15. Anderson K E, Maibach H I. Black and white human skindifferences. J Am Acad Dermatol 1976: 1: 276282.

16. Buckley C E III, Lee K L, Burdick D S. Methacholine in-duced cutaneous flare response. bivariate analysis of re-sponsiveness and sensitivity. J Allergy Clin Immunol 1982:69: 2534.

17. Weigand D A, Gaylor J R. Irritant reaction in Negro andCaucasian skin. South Med J1974: 67: 548551.

18. Thomson M L. Relative efficiency of pigment and hornylayer thickness in protecting the skin of Europeans andAfricans against solar ultraviolet radiation. J Physiol(Lond) 1955: 127: 236238.

19. Rienerston R P, Wheatley V R. Studies on the chemicalcomposition of human epidermal lipids. J Invest Dermatol1959: 32: 4951.

20. Corcuff P, Lotte C, Rougier A et al. Racial differences incorneocytes. Acta Derm Venereol (Stockh) 1991: 71: 146148.

21. Sugino K, Imokawa G, Maibach H. Ethnic difference ofstratum corneum lipid in relation to stratum corneum func-tion [Abstract]. J Invest Dermatol 1993: 100: 597.

22. Johnson L C, Corah N L. Racial differences in skin re-sistance. Science 1963: 139: 766769.

23. Flusher J W, Kuss O, Diepgen T et al. Testing for irritationwith a multifactorial approach: comparison of eight non-invasive measuring techniques of five different irritationtypes. Br J Dermatol 2001: 145: 696703.

7/28/2019 j.1600-0536.2002.470504.x

7/7


24. Berardesca E, Maibach H I. Racial difference in sodiumlauryl sulphate induced cutaneous irritation: black andwhite. Contact Dermatitis 1988: 18: 6570.

25. Gean C J, Tur E, Maibach H I, Guy Rh. Cutaneous re-sponses to topical methyl nicotinate in black, oriental, andCaucasian subjects. Arch Dermatol Res 1989: 281: 9598.

26. Guy Rh, Tur E, Bjerke S, Maibach H I. Are there age andracial differences to methyl nicotinate-induced vasodilation

in human skin? J Am Acad Dermatol 1985: 12: 10011006.27. Berardesca E, Maibach H I. Cutaneous reactive hyper-

aemia: racial differences induced by corticoid application.Br J Dermatol 1989: 120: 787794.

28. Rapaport M. Patch testing in Japanese subjects. ContactDermatitis 1984: 11: 9397.

29. Basketter D A, Griffith H A, Wang X A, Wilhelm K P,McFadden J. Individual, ethnic and seasonal variability inirritant susceptibility of skin: the implications for a predic-tive human patch test. Contact Dermatitis 1996: 35: 208213.

30. Goh C L, Chia S E. Skin irritability to sodium lauryl sul-phateas measured by skin water lossby sex and race.Clin Exp Dermatol 1988: 13: 1619.

31. Foy V, Weinkauf R, Whittle E, Basketter D A. Ethnic vari-

ation in the skin irritation response. Contact Dermatitis2001: 45: 346349.32. Robinson M K. Racial differences in acute and cumulative

skin irritation responses between Caucasian and Asianpopulations. Contact Dermatitis 2000: 42: 134143.

33. Robinson M K, Perkins M A, Basketter D A. Applicationof a 4-h human test patch method for comparative andinvestigative assessment of skin irritation. Contact Derma-titis 1998: 38: 194202.

34. Robinson M K. Population differences in acute skin irri-tation responses. Contact Dermatitis 2002: 46: 8692.

35. Robinson M K. Intra-individual variations in acute andcumulative skin irritation responses. Contact Dermatitis

2001: 45: 7583.36. Judge M R, Griffith H A, Basketter D A, White I R,

Rycroft R J G, McFadden J P. Variations in response ofhuman skin to irritant challenge. Contact Dermatitis 1996:34: 115117.

37. McFadden J P, Wakelin Sh, Basketter D A. Acute irritationthresholds in subjects with type Itype VI skin. ContactDermatitis 1998: 38: 147149.

Address:Howard I. MaibachSchool of MedicineDepartment of Dermatology90 Medical Center WaySurge 110

San FranciscoCalifornia 941430989USAFax: 415 7535304e-mail: himjlm/itsa.ucsf.edu

j.1600-0536.2002.470504.x

Documents