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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 28 (2003), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prospective identification of potential contact allergens and their subsequent safety assessment are pivotal in successful management of this risk to human health. Although much can be learned from the chemical and physical properties of a substance, the definitive information in respect of sensitizing hazard/risk derives from an assessment of the integrated response of the immune system. In recent years, the focus for such assessments has begun to switch from the guinea pig to the mouse, notably to the local lymph node assay (LLNA). In this paper, the current value of the LLNA for hazard identification is reviewed and its regulatory status defined. Once a potential contact allergen has been identified, however, the vital clue to accurate safety evaluation is the assessment of the potency of the allergen. How this can be achieved using the LLNA and employed in safety evaluation is discussed in detail, together with practical suggestions for the deployment of such processes in regulatory toxicology.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 27 (2002), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Irritant contact dermatitis is the clinical result of sufficient inflammation arising from release of pro-inflammatory cytokines from skin cells (principally keratinocytes) in response to (usually) chemical stimuli. Different clinical forms may arise. The three main pathophysiological changes seen are skin barrier disruption, epidermal cellular changes and cytokine release. An important role of irritancy in allergic contact dermatitis (ACD) comes from earlier animal and human studies. Evidence is outlined which is consistent with a ‘danger model’ of ACD rather than one based on a traditional ‘self–nonself’ immune model. In such a model an antigenic signal will produce sensitization only in the presence of a danger signal; in the absence of a danger signal tolerance will occur. We propose that the danger signal in ACD is cytokine release from nonimmune skin cells (principally keratinocytes) and that both the antigenic and ‘danger’ signals arises from the hapten.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 40 (1999), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A formalized, standardized and effective mechanism for the identification of substances which possess significant skin sensitization potential is a necessary first step in the process of limiting the incidence of allergic contact dermatitis. Strategies to achieve such hazard identification are unified throughout the European Union and also have been publicised by the World Health Organization. Global harmonization of these and other approaches (e.g., in the USA) is being driven by the Organization for Economic Cooperation and Development. In this paper, the benefits and limitations of these classification systems are reviewed. A common element of all the systems is that they seek to distinguish important contact allergens from chemicals which are infrequent sensitizers. The European criteria are legal requirements in the EU member states and formal classification as a skin sensitizer leads to mandatory labelling. The most notable omission from current and proposed classification criteria relates to the relative potency of a classified skin sensitizer and the exposure dose. Such information is necessary for proper risk assessment and management measures to be implemented.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 39 (1998), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To study the length of exposure time required to elicit para-phenylenediamine (PPD) allergic reactions, patients known to be allergic to PPD were recruited and patch tested. A group of 7 patients were patch tested with 1% PPD in pet. for 15 min, 30 min and for 120 min. The remaining 9 patients were patch tested with 1%, 0.3%, 0.1% and 0.01% PPD for 15 min, 30 min and for 120 min each. With exposure for 120 min, 11 of 16 subjects reacted to 1% PPD and 2 of 9 reacted to 0.01%. With exposure of 15 min, 6 of 16 reacted to 1% PPD and 0 of 9 reacted to 0.01% PPD. This study showed marked inter-individual variability in eliciting a reaction to the PPD molecule on patch testing, with regard to both the exposure time and the concentration required.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 38 (1998), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study compares the cutaneous reactivity between the hand and the back for 7 female patients with active hand eczema, who were found to be nickel-sensitive on routine patch testing with the European standard series. Patients were patch tested to a dilution series of nickel sulfate on the back in order to determine the threshold concentration for elicitation of allergic contact dermatitis, and based upon this result a lower concentration of nickel was then used for patch tests on the hand. We found that in the majority of patients (6/7) the cutaneous responsiveness of the hand was not increased compared with that of the back. However, the hand of 1 patient was more sensitive to nickel and patch testing was accompanied with a flare of her eczema, which suggests that cutaneous hyperreactivity may be important in individual patients with hand eczema.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 41 (1999), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cocamidopropyl betaine (CAPB) has been identified as a cause of contact allergy in personal care products. Furthermore, it has been suggested that chemicals responsible are impurities, especially dimethylaminopropylamine (DMAPA). However, skin contact concentrations with these impurities, especially DMAPA. are very low. The aim of the study was to analyse whether subjects with previous positive patch tests to CAPB would react in provocative use tests of a product containing CAPB. 10 individuals with a clinical history of contact allergy to CAPB (by positive patch test and history) took part in a ROAT which used a CAPB-based shower gel at 25% (DMAPA concentration 〈 1 ppm). None of the subjects showed positive allergic reactions. 1 of the test subjects did experience a flare of atopic dermatitis at the treatment site. Later, all 10 subjects were patch tested to 3 different concentrations of CAPB and DMAPA (0.1%, 0.3%, 1%) to verify the threshold that was capable of inducing a positive test reaction. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions. Only 1 of the subjects showed an allergic reaction to DMAPA. Finally, in uncontrolled use testing with the shower gel, none of the test subjects reported any adverse skin reactions. Thus, the study confirmed that CAPB-sensitive individuals can use a CAPB-based rinse-off product without the risk of experiencing an allergic reaction to CAPB.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 38 (1998), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Adverse skin reactions cover many types of response: toxic, irritant, allergic, urticarial, sensory, etc. The relationships between an individual's tendency to develop different types of skin response are not well-described. We examined whether those who perceive stinging might be more likely to experience urticarial, sensory and irritation reactions in skin. A panel of 86 volunteers was tested with 10% lactic acid in the nasolabial fold to assess their ability to perceive stinging. At the same time, their capacity to develop non-immunologic contact urticaria was evaluated using chemicals of different structural type and urticant ability: methyl nicotinate, benzoic acid, cinnamic acid, cinnamaldehyde and dimethyl sulfoxide (DMSO). DMSO was also used to assess sensory effects and skin irritation. 44 were classed as “stingers” and 42 as “non-stingers”. The pattern of urticant reactivity in the stingers and non-stingers was essentially the same, with neat DMSO generating the strongest reactions in both groups. Sensory reactions to DMSO (stinging, itching, tingling or burning) were similar in stingers and non-stingers; although the former may have reacted more quickly, a smaller proportion reacted (64% versus 76%). The skin irritation response to DMSO was also identical in stingers and non-stingers and the intensity of the urticant response in an individual did not correlate with the intensity of their subsequent irritant reaction. In conclusion, this study demonstrated that an individual's ability to perceive skin stinging does not give a general indication of their susceptibility to other types of non-immunologic skin response. Indeed, there appeared to be little evidence of correlations between any of the skin effects studied.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 41 (1999), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The biological activity of skin-sensitizing chemicals is related to their ability to react, either directly or after metabolic activation, with appropriate skin proteins. For direct acting electrophilic compounds, this ability can be modelled, using the RAI (relative alkylation index) approach, by a combination of electrophilicity and hydrophobicity parameters. Several structure-activity relationships based on this approach have been reported, but most of them cover guinea pig sensitization test data on what chemists would classify as relatively soft electrophilic chemicals. In the present work, an electrophilicity parameter based on Taft substituent constants is derived for hard electrophiles having a reactive carbonyl group, and is used to calculate RAI values for the analyis of sensitization test data obtained in the murine local lymph node assay (LLNA) for a series of α,β-diketones. The sensitization potential of these reactive hard electrophilic carbonyl compounds in the LLNA shows a good correlation with the RAI. Overall, the findings reaffirm our view that physical organic chemistry is the key to understanding why some chemicals sensitize more strongly than others, while some do not sensitize at all, and provide further evidence of the value of the LLNA for SAR studies.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Contact dermatitis 45 (2001), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, α-amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 38 (1998), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Predictive testing of chemicals to assess their acute skin irritation potential is an important part of the assessment of their toxicological profile. It is possible, where safety and ethical considerations can be met, to do this work in groups of human volunteers. Previously, the relative responsiveness of atopics and non-atopics has been evaluated. The results showed that atopics (defined broadly by high IgE reactivity) were a little more susceptible to skin irritation, but not significantly so. In the present work, the relative reactivity of a skin atopic group versus a non-atopic group was examined in more detail. Sodium lauryl sulfate (SLS) was applied at a range of concentrations and exposure times, such that a fairly constant degree of skin irritation was produced. At various time points, the irritation response was measured by visual assessment, chromametry, laser Doppler flowmetry and transepidermal water loss. Using all of the methods of assessment, the reactions in atopics were similar to or a little less than those seen in non-atopics. The conclusion is that atopics and non-atopics will give similar results in a predictive human test for acute skin irritation. Furthermore, the pattern of response obtained from short duration exposure should be predictive of that following longer durations of (single) exposure.
    Type of Medium: Electronic Resource
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