I R White

Guy's and St Thomas' NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (210)788.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In view of the current and unprecedented increase in contact allergy to methylisothiazolinone (MI), we characterized and evaluated two recent epidemics of contact allergy to preservatives used in cosmetic products to address failures in risk assessment and risk management. To evaluate temporal trends of preservative contact allergy. The study population included consecutive patch tested eczema patients seen at a university hospital between 1985 and 2013. A total of 23 138 patients were investigated for a contact allergy. The overall prevalence of contact allergy to at least one preservative increased significantly over the study period, from 6.7% in 1985 to 11.8% in 2013 (p < 0.001). Importantly, the preservatives methyldibromo glutaronitrile and MI rapidly resulted in high sensitization prevalence rates, which reached epidemic proportions. Although the proportion of patients with current clinical disease attributable to methyldibromo glutaronitrile contact allergy decreased significantly following the ban on its use in cosmetic products (p < 0.001), the sudden and high proportion of current sensitization to MI requires immediate attention (p < 0.001). The introduction of new preservatives in Europe with inadequate pre-market risk assessment has rapidly increased the overall burden of cutaneous disease caused by preservatives. We suggest that the cosmetic industry has a responsibility to react faster and replace troublesome preservatives when a preservative contact allergy epidemic is recognized, but the European Commission has the ultimate responsibility for failures in risk management after new, major sensitizing preservatives are introduced onto the market. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Contact Dermatitis 07/2015; 73(3). DOI:10.1111/cod.12446 · 3.75 Impact Factor
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    ABSTRACT: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Contact Dermatitis 07/2015; 73(4). DOI:10.1111/cod.12432 · 3.75 Impact Factor
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    ABSTRACT: Many key ingredients of hair cosmetics (in particular, dyes, bleaches, and hair-styling agents) are potent (strong to extreme) contact allergens. Some heterogeneity is apparent from published results concerning the range of allergens for which patch testing is important. The objective of the present review was to collect information on the current practice of using 'hair cosmetic series', and discuss this against the background of evidence concerning consumer/professional exposure and regulatory aspects to finally derive a recommendation for a 'European hair cosmetic series'. The methods involved (i) a survey targeting all members of the COST action 'StanDerm' (TD1206) consortium, (ii) analysis of data in the database of the European Surveillance System on Contact Allergies (ESSCA), and (iii) literature review. Information from 19 European countries was available, partly from national networks, and partly from one or several departments of dermatology or, occasionally, occupational medicine. Apart from some substances being tested only in single departments, a broad overlap regarding 'important' allergens was evident. Some of the substances are no longer permitted for use in cosmetics (Annex II of the Cosmetics Regulation). An up-to-date 'European hair cosmetics series', as recommended in the present article, should (i) include broadly used and/or potent contact allergens, (ii) eliminate substances of only historical concern, and (iii) be continually updated as new evidence emerges. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Contact Dermatitis 06/2015; 393(2). DOI:10.1111/cod.12424 · 3.75 Impact Factor
  • Wisam Alwan · Piu Banerjee · Ian R White ·

    Contact Dermatitis 12/2014; 71(6):376. DOI:10.1111/cod.12306 · 3.75 Impact Factor
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    ABSTRACT: Background In view of the current epidemic of contact allergy to methylisothiazolinone (MI), it is important to clarify the extent of use of MI and related isothiazolinones in paints currently available for the consumer and worker in Europe.Objectives To elucidate the use and concentrations of MI, methylchloroisothiazolinone (MCI) and benzisothiazolinone (BIT) in paints on the European retail market.Methods Wall paints (n = 71) were randomly purchased in retail outlets in five European countries. The paints were quantitatively analysed for their contents of MI, MCI and BIT by high-performance liquid chromatography coupled to tandem mass spectrometry.ResultsMI was found in 93.0% (n = 66) of the paints, with concentrations ranging from 0.7 to 180.9 ppm, MCI in 23.9% (n = 17), ranging from 0.26 to 11.4 ppm, and BIT in 95.8% (n = 68), ranging from 0.1 to 462.5 ppm. High concentrations of MI were found in paints from all five countries. Paints purchased in Denmark and Sweden contained especially high concentrations of BIT.Conclusion The use of MI across European countries is extensive. In view of the ongoing epidemic of MI contact allergy, an evaluation of the safety of MI in paints is needed.
    Contact Dermatitis 12/2014; 72(3). DOI:10.1111/cod.12322 · 3.75 Impact Factor
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    ABSTRACT: BackgroundR-Limonene is a common fragrance terpene found in domestic and industrial products. R-Limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a recent multicentre study, 5.2% (range 2.3–12.1%) of 2900 patients showed a positive patch test reaction to oxidized R-limonene.Objective To study the exposure to limonene among consecutive dermatitis patients reacting to oxidized R-limonene in an international setting, and to assess the relevance of the exposure for the patients' dermatitis.Methods Oxidized R-limonene 3.0% (containing limonene hydroperoxides at 0.33%) in petrolatum was tested in 2900 consecutive dermatitis patients in Australia, Denmark, the United Kingdom, Singapore, Spain, and Sweden. A questionnaire assessing exposure to limonene-containing products was completed.ResultsOverall, exposure to products containing limonene was found and assessed as being probably relevant for the patients' dermatitis in 36% of the limonene-allergic patients. In Barcelona and Copenhagen, > 70% of the patients were judged to have had an exposure to limonene assessed as relevant.Conclusions Oxidized R-limonene is a common fragrance allergen, and limonene was frequently found in the labelling on the patients' products, and assessed as relevant for the patients' dermatitis. A large number of domestic and occupational sources for contact with R-limonene were identified.
    Contact Dermatitis 08/2014; 71(5). DOI:10.1111/cod.12285 · 3.75 Impact Factor
  • David Basketter · Ian R White · John P McFadden · Ian Kimber ·
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    ABSTRACT: Abstract Background: Hexyl cinnamal (HCA) is a widely used fragrance chemical, the low skin-sensitizing potency of which has made it a common choice for the use as a positive control for predictive toxicology assays. However, HCA is commonly negative in current candidate in vitro alternatives test methods. Objective: To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing. Methods: Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed. Results: The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures. Conclusions: Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control.
    Cutaneous and Ocular Toxicology 07/2014; 34(3):1-5. DOI:10.3109/15569527.2014.933973 · 1.12 Impact Factor
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    ABSTRACT: Background Ingredient labels on products used by consumers and workers every day, such as food, cosmetics, and detergents, can be difficult to read and understand.Objective To assess whether typographical design and ordering of ingredients can improve the readability of product ingredient labels.Methods The study subjects (n = 16) had to search for two target ingredients in 30 cosmetic product labels and three alternative formats of each. Outcome measures were completion time (reading speed), recognition rate, eye movements, task load and subjective rating when the reading of ingredient labels was assessed by video recording, an eye tracking device, and questionnaires.ResultsThe completion time was significantly lower (p < 0.001) when subjects were reading all alternative formats than when they were reading the original. The recognition rate was generally high, and improved slightly with the alternative formats. The eye movement measures confirmed that the alternative formats were easier to read than the original product labels. Mental and physical demand and effort were significantly lower (p < 0.036) and experience rating was higher (p < 0.042) for the alternative formats. There were also differences between the alternative formats.Conclusions Simple adjustments in the design of product ingredient labels would significantly improve their readability, benefiting the many allergic individuals and others in their daily struggle to avoid harmful or unwanted exposure.
    Contact Dermatitis 07/2014; 71(4). DOI:10.1111/cod.12274 · 3.75 Impact Factor
  • Adil Sheraz · Mark J Simms · Ian R White · Jonathan M L White ·

    Contact Dermatitis 07/2014; 71(1):62-4. DOI:10.1111/cod.12197 · 3.75 Impact Factor
  • Bjorn R. Thomas · Ian R. White · John P. McFadden · Piu Banerjee ·
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    ABSTRACT: Background Hair dye exposure is the most common cause of sensitization to p-phenylenediamine (PPD). Cross-reactions with structurally related allergens occur.Objectives It is suggested that a stronger patch test reaction (3+ rather than 1+) to PPD (usually tested as 1% petrolatum) is associated with an increased propensity for cross-reactions. In this article we will demonstrate this association.Methods Of 230 patients with allergic reactions to PPD on patch testing identified during 2007–2012 from clinical records, notes for 221 were available for review. Data were collected regarding age, sex, and grade of reaction [International Contact Dermatitis Research Group (ICDRG) criteria] to PPD. Cross-reactions with the following allergens, found in our baseline series, were recorded: Disperse Yellow 3, N-isopropyl-N′-phenyl-p-phenylenediamine (IPPD), and caine mix. Having excluded 23 doubtful reactions, the reactions from 198 patients were further considered.ResultsOf the patients, 75.3% (n = 149) were female, and the mean age was 48.6 years (12–82 years). Of the patients allergic to PPD, 16.6% (n = 33) showed cross-reactions with one or more related allergens. Cross-reactions were seen in 16% with a grade of 1+, 14.5% with a grade of 2+, 28.6% with a grade of 3+ when PPD was tested 1% pet., and 50.0% when PPD was tested at 0.1–0.001%, arbitrarily considered to be 4+ (p = 0.02; Cramér's V = 0.23).Conclusion An increasing likelihood of reactions to Disperse Yellow 3, IPPD or caine mix was seen with increasing strength of patch test reaction to PPD. The clinical relevance of these cross-reactions is unclear.
    Contact Dermatitis 05/2014; 71(2). DOI:10.1111/cod.12255 · 3.75 Impact Factor
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    ABSTRACT: Background Negative patch test results with fragrance allergy markers in the European baseline series do not always predict a negative reaction to individual fragrance substances.Objectives To determine the frequencies of positive test reactions to the 26 fragrance substances for which labelling is mandatory in the EU, and how effectively reactions to fragrance markers in the baseline series predict positive reactions to the fragrance substances that are labelled.Methods The records of 1951 eczema patients, routinely tested with the labelled fragrance substances and with an extended European baseline series in 2011 and 2012, were retrospectively reviewed.ResultsTwo hundred and eighty-one (14.4%) (71.2% females) reacted to one or more allergens from the labelled-fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were cinnamyl alcohol (48; 2.46%), Evernia furfuracea (44; 2.26%), and isoeugenol (40; 2.05%). Of the 203 patients who reacted to any of the 26 fragrances in the labelled-fragrance substance series, only 117 (57.6%) also reacted to a fragrance marker in the baseline series. One hundred and seven (52.7%) reacted to either fragrance mix I or fragrance mix II, 28 (13.8%) reacted to Myroxylon pereirae, and 13 (6.4%) reacted to hydroxyisohexyl 3-cyclohexene carboxaldehyde.Conclusions These findings confirm that the standard fragrance markers fail to identify patients with contact allergies to the 26 fragrances.
    Contact Dermatitis 05/2014; 70(5). DOI:10.1111/cod.12171 · 3.75 Impact Factor
  • Wisam Alwan · Ian R. White · Piu Banerjee ·

    Contact Dermatitis 05/2014; 70(5). DOI:10.1111/cod.12219 · 3.75 Impact Factor
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    Contact Dermatitis 05/2014; 70(5). DOI:10.1111/cod.12220 · 3.75 Impact Factor
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    ABSTRACT: Background Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the active ingredients in commonly used preservative systems (e.g. Kathon CG®). MCI/MI is present in the European baseline patch test series at 100 ppm aq. Since 1986, 200 ppm (dose 0.006 mg/cm2) has been used in Sweden without causing skin irritation. Centres in Spain, the United Kingdom and Ireland have also used 200 ppm in their baseline series.Objectives To find the optimal patch test concentration for MCI/MI.Materials and methodsMCI/MI 100 ppm aq. and MCI/MI 200 ppm aq. were simultaneously patch tested in 3300 consecutively tested dermatitis patients at eight European patch test clinics and one US patch test clinic. With the Finn Chambers® technique (diameter 8 mm), 15 µl was micropipetted on to the filter paper in the chamber. The corresponding volume for Van der Bend® chambers was 20 µl, and that for IQ Chambers® was 25 µl.ResultsContact allergy to MCI/MI at 100 and 200 ppm was found in 1.2% and 2.1% of patients, respectively (p < 0.001).ConclusionsMCI/MI 200 ppm aq. (dose 0.006 mg/cm2) diagnoses significantly more contact allergy than the presently used concentration of 100 ppm (dose 0.003 mg/cm2), without resulting in more adverse reactions. MCI/MI at 200 ppm should therefore be considered for inclusion in the European baseline test series.
    Contact Dermatitis 04/2014; 71(1). DOI:10.1111/cod.12241 · 3.75 Impact Factor
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    ABSTRACT: Experimental and clinical studies have shown that fragrance substances act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohapten and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.
    Contact Dermatitis 09/2013; 69(6). DOI:10.1111/cod.12127 · 3.75 Impact Factor
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    ABSTRACT: The ability to be sensitized to experimental contact allergens declines significantly with increasing age, from as early as age 40 years. In contrast, the rate of contact allergy to chemical allergens (haptens) in cosmetic products significantly increases with age. This has been explained previously on the basis of greater cumulative exposure in the older age groups. However, outbreaks of contact allergy to preservatives in cosmetic products recorded soon after their introduction to the market have also shown a significantly higher rate among older adult age groups. This association with increasing age cannot be readily explained by exposure history or pattern, and is not compatible with a sensitizing/stimulatory reaction that degrades with age as the sole immune response. From this, the existence of a second, tolerizing/regulatory arm to the immune response to cutaneous haptens that possibly becomes less effective with age at a higher rate than the sensitizing/stimulatory arm can be inferred. This reinforces the view that current clinical and experimental observations of allergic contact dermatitis are best explained by an immune system with the functional ability to produce both sensitizing/stimulatory and tolerizing/regulatory responses.
    Contact Dermatitis 09/2013; 69(3):129-37. DOI:10.1111/cod.12100 · 3.75 Impact Factor
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    ABSTRACT: Contact allergy to fragrances is still relatively common, affecting ∼ 16% of patients patch tested for suspected allergic contact dermatitis, considering all current screening allergens. The objective of the review is to systematically retrieve, evaluate and classify evidence on contact allergy to fragrances, in order to arrive at recommendations for targeting of primary and secondary prevention. Besides published evidence on contact allergy in humans, animal data (local lymph node assay), annual use volumes and structure-activity relationships (SARs) were considered for an algorithmic categorization of substances as contact allergens. A total of 54 individual chemicals and 28 natural extracts (essential oils) can be categorized as established contact allergens in humans, including all 26 substances previously identified as contact allergens (SCCNFP/0017/98). Twelve of the 54 individual chemicals are considered to be of special concern, owing to the high absolute number of reported cases of contact allergy (> 100). Additionally, 18 single substances and one natural mixture are categorized as established contact allergens in animals. SARs, combined with limited human evidence, contributed to the categorization of a further 26 substances as likely contact allergens. In conclusion, the presence of 127 single fragrance substances and natural mixtures should, owing to their skin sensitizing properties, be disclosed, for example on the label. As an additional preventive measure, the maximum use concentration of 11 substances of special concern should be limited to 100 ppm. The substance hydroxyisohexyl 3-cyclohexene carboxaldehyde and the two ingredients chloroatranol and atranol in the natural extracts Evernia prunastri and Evernia furfuracea should not be present in cosmetic products.
    Contact Dermatitis 07/2013; 69(4). DOI:10.1111/cod.12117 · 3.75 Impact Factor

  • Contact Dermatitis 07/2013; 69(1):53-5. DOI:10.1111/cod.12093 · 3.75 Impact Factor
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    ABSTRACT: p-Phenylenediamine (PPD) is the primary patch test screening agent for hair dye contact allergy, and approximately 100 different hair dye chemicals are allowed. To examine whether PPD is an optimal screening agent for diagnosing hair dye allergy or whether other clinically important sensitizers exist. Two thousand nine hundred and thirty-nine consecutive patients in 12 dermatology clinics were patch tested with five hair dyes available from patch test suppliers. Furthermore, 22 frequently used hair dye ingredients not available from patch test suppliers were tested in subgroups of ∼ 500 patients each. A positive reaction to PPD was found in 4.5% of patients, and 2.8% reacted to toluene-2,5-diamine (PTD), 1.8% to p-aminophenol, 1% to m-aminophenol, and 0.1% to resorcinol; all together, 5.3% (n = 156). Dying hair was the most frequently reported cause of the allergy (55.4%); so-called 'temporary henna' tattoos were the cause in 8.5% of the cases. p-Methylaminophenol gave a reaction in 20 patients (2.2%), 3 of them with clinical relevance, and no co-reaction with the above five well-known hair dyes. Hair dyes are the prime cause of PPD allergy. PPD identifies the majority of positive reactions to PTD, p-aminophenol and m-aminophenol, but not all, which justifies additional testing with hair dye ingredients from the used product.
    Contact Dermatitis 07/2013; 69(1):32-9. DOI:10.1111/cod.12077 · 3.75 Impact Factor
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    ABSTRACT: Nickel-plated steel coins have recently been introduced in the United Kingdom. To compare the performance and allergy risk of the new nickel-plated coins (five and ten pence) with those of the cupro-nickel coins being replaced. Coin handling studies with assessment of skin exposure and metal release in artificial sweat were performed. Six volunteers participated. The amount of nickel deposited onto skin during the handling of nickel-plated coins for 1 hr was 7.5 µg/cm(2) , four times higher than that from cupro-nickel coins. The nickel content in the oxidized surface of nickel-plated coins was higher, explaining the higher skin dose. Initial nickel release rates were 10-27 times higher than 1-week rates, emphasizing that brief and repeated contact results in significant nickel exposure. Nickel-plated coins deposit higher levels of nickel onto skin than cupro-nickel coins, and hence pose an increased allergy risk. One-week release in artificial sweat is not suitable for determining the risk of handling items with high nickel release that come into short, repeated contact with the skin. The nickel skin dose is recommended for risk assessment. UK citizens are now, because of this change in coinage, unnecessarily exposed to higher levels of nickel on the skin. This is of public health concern.
    Contact Dermatitis 06/2013; 68(6):323-30. DOI:10.1111/cod.12092 · 3.75 Impact Factor

Publication Stats

5k Citations
788.82 Total Impact Points


  • 2009-2013
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2012
    • Bundesinstitut für Risikobewertung
      Berlín, Berlin, Germany
  • 2003
    • St. John's Hospital
      Springfield, Illinois, United States
  • 1999-2003
    • Malmö University
      Malmö, Skåne, Sweden
  • 2001
    • University of Southern Denmark
      Odense, South Denmark, Denmark
  • 1995
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 1992
    • IT University of Copenhagen
      København, Capital Region, Denmark