I R White

The University of Manchester, Manchester, ENG, United Kingdom

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Publications (205)620.68 Total impact

  • [Show abstract] [Hide abstract]
    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; · 2.93 Impact Factor
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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;
  • Contact Dermatitis 07/2014; 71(1):62-4. · 2.93 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; · 2.93 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). · 2.93 Impact Factor
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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; · 2.93 Impact Factor
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    Contact Dermatitis 05/2014; 70(5). · 2.93 Impact Factor
  • Wisam Alwan, Ian R. White, Piu Banerjee
    Contact Dermatitis 05/2014; 70(5). · 2.93 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; · 2.93 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; · 2.93 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. · 2.93 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; · 2.93 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. · 2.93 Impact Factor
  • Contact Dermatitis 07/2013; 69(1):53-5. · 2.93 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. · 2.93 Impact Factor
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    ABSTRACT: Background. Dimethylfumarate (DMF) was the cause of a major outbreak of allergic contact dermatitis as a consequence of its use as an antifungal agent in leather products, particularly in furniture, with what became known as 'toxic sofa dermatitis'. Objectives. To determine whether the frequency and severity of reactions to DMF arose as a function of its intrinsic potency and/or the nature and extent of exposure. Methods. The intrinsic potency of DMF was measured with the standard local lymph node assay (LLNA), with determination of an EC3 value, which is the threshold in the LLNA and serves as an indicator of relative skin-sensitizing potency in humans. Results. The EC3 value for DMF was 0.35% when tested in dimethylformamide as a vehicle, indicating that DMF is a strong, but not an extreme, skin sensitizer in this mouse model. Conclusions. DMF appears to have a sensitizing potency in the mouse that is very similar to that of formaldehyde, which is also a strong human skin sensitizer. However, the frequency and intensity of allergic contact dermatitis reactions to DMF suggest that it was the prolonged, repeated and occlusive exposure to this chemical over large skin areas, combined with the strong sensitizing potency, that generated the 'perfect storm' conditions that caused the DMF epidemic.
    Contact Dermatitis 04/2013; · 2.93 Impact Factor
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    ABSTRACT: Background. Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R-limonene has previously been patch tested in multicentre studies, giving 2-3% positive patch test reactions in consecutive patients. Objectives. To investigate whether oxidized R-limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim-OOHs), could be a useful tool for the detection of contact allergy in an international setting. Methods. Oxidized R-limonene 3.0% (Lim-OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. Results. Overall, 5.2% (range 2.3-12.1%) of the patients showed a positive patch test reaction to oxidized R-limonene. Doubtful reactions were found in 7.0% of the patients (range 0-24%). Few irritant reactions were seen. Conclusions. Oxidized R-limonene at 3.0% pet. with a specified content of Lim-OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R-limonene would not be informed of their fragrance allergy if this specific test had not been performed.
    Contact Dermatitis 04/2013; 68(4):214-223. · 2.93 Impact Factor
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    ABSTRACT: Background.The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. Objectives.To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co-reactivity with quaternium-15. Materials and methods.In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm(2) ) and 1.0% (wt/vol) (0.30 mg/cm(2) ) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. Results.Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium-15-positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. Conclusion.On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.
    Contact Dermatitis 01/2013; 68(1):50-53. · 2.93 Impact Factor
  • Contact Dermatitis 01/2013; 68(1):1-2. · 2.93 Impact Factor
  • Contact Dermatitis 12/2012; 67(6):375-376. · 2.93 Impact Factor

Publication Stats

3k Citations
620.68 Total Impact Points

Institutions

  • 2013
    • The University of Manchester
      • Faculty of Life Sciences
      Manchester, ENG, United Kingdom
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
    • Karolinska Institutet
      • Institute of Environmental Medicine - IMM
      Stockholm, Stockholm, Sweden
  • 2009–2013
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2012
    • Liverpool John Moores University
      • School of Pharmacy and Biomolecular Sciences
      Liverpool, ENG, United Kingdom
  • 2009–2012
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom
  • 2010
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 2009–2010
    • Videncenter for Allergi
      København, Capital Region, Denmark
  • 2003–2009
    • University of Copenhagen
      • Department of International Health, Immunology and Microbiology
      Copenhagen, Capital Region, Denmark
  • 2002–2007
    • Unilever
      Londinium, England, United Kingdom
  • 2002–2005
    • Klinikum Dortmund gGmbH
      Dortmund, North Rhine-Westphalia, Germany
  • 1999–2005
    • Malmö University
      Malmö, Skåne, Sweden
    • University of Strasbourg
      Strasburg, Alsace, France
    • Universität Witten/Herdecke
      • Chair of Dermatology
      Witten, North Rhine-Westphalia, Germany
  • 2004
    • Aichi Medical University
      • Department of Dermatology
      Japan
  • 2001
    • University of Southern Denmark
      Odense, South Denmark, Denmark
  • 1998
    • Copenhagen University Hospital Gentofte
      • Department of Dermato-Allergology
      Hellebæk, Capital Region, Denmark
  • 1995
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 1990
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Occupational Dermatology
      Amsterdam, North Holland, Netherlands
    • Universität Heidelberg
      • University Hospital of Dermatology
      Heidelberg, Baden-Wuerttemberg, Germany