An overall evaluation of the concept and organisation of the.doc

Expert evaluation of the activities ofNational Allergy Research Centrefor chemical substances in consumer productsprepared for:Chemicals DivisionNational Environmental Protection AgencyFile no. M: 7041-004Ref: LFH/12by:Ian R. White, Chairman of the Scientific Committee for Cosmetic and Non-Food Products at the European Commission (DG SANCO ; Consumer safety and health protection) and Chairman of The Contact Dermatitis Clinic, at St. Thomas Hospital, London, UK.Magnus Bruze, Prof. Dept. of Occupational and Environmental Dermatology, Malmö University Hospital, SwedenEva Millquist, Ass. Prof. Asthma and Allergy Research Group, Department of Respiratory Medicine and Allergy, Sahlgrenska University Hospital, Göteborg, Sweden. 29 January 2004Executive summaryThe concept of the National Allergy Research Centre is, we believe unique in Europe. In the short time since its foundation, the National Allergy Research Centre has established it self as an institution of excellence. Its design and organisation optimises the conditions required for effective flow of information and for actions to be instigated to advise authorities and protect the consumer.As a result of the close co-operation between the hospital and office-based centres, detailed standard operating procedures are being developed. This will broaden the availability of quality evaluations within the Danish healthcare system. This model of co-operation and collaboration between the two divisions of healthcare provision is also unique.Up until the present time, the Centre has produced some 30 scientific papers that have been published or have been accepted for publication. This is an impressive output considering the short time that the Centre has been active. The lists of authors highlights the excellence of co-operation that the Centre has with colleagues within Denmark and internationally. The papers are relevant to the aims of the Centre and the investigations described are central to discussion and regulation to reduce allergy in the consumer. It is known that data from the Centre has been used regularly by the European Commissions advisory services to provide recommendations for protecting the consumer. We are not aware of any other organisation having facilitated health protection of the consumer in European in a similar way.We strongly support the activities and structure of the National Centre for Allergy. It has undertaken essential work with relatively limited resources and its impact on allergy prevention, control and understanding is impressive and must be continued. Increased funding is highly recommended. Evaluation1. An overall evaluation of the concept and organisation of the Centre, in relation to fulfilling the aims and performing the tasksThe National Allergy Research Centre was established in 2001 and is funded by the Environmental Protection Agency. The prime aim of the Centre is described as being the prevention of contact allergy caused by chemical substances. Specifically, it is contact allergy caused by non-occupational exposure to these chemical substances, i.e., from consumer products, which is being assessed. However, the individual is exposed to the same or similar chemical substances from a variety of exposure situations, including occupational. In due course, these other situations need to be evaluated within the framework of identifying the relevance, exposure characteristics and the impact on the disease processes of allergy caused by the chemical agents. Data on the prevalence of contact hypersensitivity must be considered together with data on exposure to the allergens being evaluated. This information includes types of products, frequency of use and the concentration of the chemical agent within the product types. This should not be divorced from considering exposure from non-consumer products.A diversion from the main aim of the Centre has been investigation of bronchial reactivity caused by the irritant effects of fragrance substances. This diversion is justified by considering the possible relationship with such hyper-reactivity with cutaneous contact allergy and eczematous processes including hand dermatitis.Immediate hypersensitivity reactions, (type 1 reactions) are not currently being investigated at the Centre. This is a wise decision at this juncture; allocation of resources here would have a deleterious impact on the ability to investigate the prime goal.The concept of the National Allergy Research Centre is, we believe unique in Europe. Denmark does have a strong tradition in cutaneous allergy that has been nurtured over many decades at the Gentofte Hospital and other institutions. It is apparent that the Centre has built upon this tradition and the legacies of previous activities are clearly enshrined within the organisation of the National Allergy Research Centre. In the short time since its foundation, the National Allergy Research Centre has established it self as an institution of excellence. The geographical proximity between the Centre and active clinical units is pivotal to success. A creative atmosphere, so essential for research, has been successfully fostered by this close working relationship. This is of benefit both to the consumer (patient) and to the researcher. The hub and spoke organisation enables centres and individuals with expertise to co-operate closely with the Centre. This design and organisation optimises the conditions required for effective flow of information and for actions to be instigated to advise authorities and protect the consumer.2. The value of the surveillance systems in relation to monitoring contact allergy and improving quality of the medical services The provision of dermatological care in Denmark has some differences compared to other European countries. The result of this is that much of the diagnostic patch test investigations undertaken in Denmark are performed by office-based practitioners rather than within the hospital system. The patch test data generated within hospitals such as the Gentofte Hospital and Odense Hospital is known for its quality. A frequent criticism of the collection and evaluation of data generated from within the office-based setting is that the quality of the data may be variable. However, many of the office-based dermatologists in Denmark have had specific training in the techniques of diagnostic patch testing and the interpretation of the results, and are active members of the Danish Contact Dermatitis Group. As a result of the close co-operation between the hospital and office-based centres, detailed standard operating procedures are being developed. This will broaden the availability of quality evaluations within the Danish healthcare system.Presently, the contact allergy data generated from the hospitals is being compared with that from the competent office-based practitioners. It is possible that the data from the office practitioners will provide a better indicator (representation) of the background and importance of contact allergy and contact allergens in the Danish population as a whole. This model of co-operation and collaboration between the two divisions of healthcare provision is unique. The concept of the allergen bank, where unusual/rare contact allergens are appropriately prepared for use in diagnostic patch test and are provided to dermatologists to investigate their patients, is also a unique facility. Of importance is the requirement that the results of the investigations with these substances are reported back. This permits surveillance of the importance of unusual contact allergens in the community.Tele-dermatology has been widely explored in recent years. The usefulness of tele-dermatology is questionable and we understand that further work on it will be explored outside the frame of National Allergy Research Centre.3. Quantity and quality of the scientific production in relation to the aims of the Centre and resources allocatedUp until the present time, the Centre has produced some 30 papers that have been published or have been accepted for publication. This is impressive output considering the short time that the Centre has been active. The lists of authors highlights the excellence of co-operation that the Centre has with colleagues within Denmark and internationally. Table. Scientific publications from the National Allergy Research CentreProjectsScientific Papers Published Accepted SubmittedIn preparationTeledermatology1Chrome and leather products11Preservatives432Combination effects11Allergy, fragrances and mucosal symptoms11Genome1Hair dyes211Plant allergy and cosmetics1Fragrance allergy1011Miscellaneous311The papers consist of some reviews relevant to allergy in the consumer, but most of the papers relate to specific research initiatives. The quality of the papers is excellent and it is clear that innovation is thoroughly established. The papers are relevant to the aims of the Centre and the investigations described are central to discussion and regulation to reduce allergy in the consumer. All this is remarkable considering the relatively limited resources that have been allocated for work that is so important for consumer safety and health protection.It is known that the data from the Centre has been used regularly by the European Commissions advisory services to provide recommendations for protecting the consumer. We are not aware of any other organisation having facilitated health protection of the consumer in European in a similar way.4. Relevance of the results of the investigations in relation to regulations and potential preventative measures.Chrome/leather. One comprehensive review and a paper accepted for publication have been produced. The data demonstrate that the chrome released from tanned leather products is now an important cause of contact allergy and that the relative importance of trivalent chrome has hitherto been underestimated. The data indicate that fuller consideration of trivalent chrome bioavailability must be considered as part of any regulatory response to protect the consumer.Contact allergy and preservatives. Preservatives are a very important cause of contact allergy. Presently, the preservative methyldibromo glutaronitrile is recognised as causing an unacceptable level of disease in the consumer. This is because of the widespread use of the preservative in many product types and the concentrations of the preservatives that hitherto have been permitted in cosmetic products. The Centre has collaborated nationally and internationally within Europe to collect data on the prevalence and relevance of this allergen. As a result of the information provided, the European regulatory authorities have recommended that this preservative should no longer be used in leave-on cosmetic products. Industry has suggested that a safe level of use in leave-on products may be determined. However, data from the Centre demonstrates that methyldibromo glutaronitrile remains an important allergen even at levels of 50ppm. Regarding safe levels of uses for rinse off cosmetic products, there have been preliminary results showing that elicitation is equally rapid from multiple applications with a low concentration of the preservative as with a single application with a higher concentration. There is clear demonstration that even the current permitted level of 1000ppm in rinse-off cosmetic products is not safe; the regulatory authorities may use this data to further protect the consumer. Additionally, there has been clear demonstration that when methydibromo glutaronitrile is applied to the skin in combination with an irritant substance (such as a detergent) there is an increased clinical response by a factor of 6.4. This is important information as many of the rinse-off products that are currently preserved with methyldibromo glutaronitrile are detergent based. Experience with methyldibromo glutaronitrile has resulted in the development of a model for determining the importance of combination effects resulting from exposure to an allergen and an irritant at the same time.We are pleased to observe that within framework of the assessment of preservatives, the Centre has two publications concerning rare/unusual allergens from occupational exposure but one of these is widely used in consumer products.Mucosal symptoms and consumer products. Associations between skin reactivity, (contact allergy and eczema) and sensitivity of the mucosal surfaces to perfumes have been elucidated. The knowledge of such interplay is new and has never been reported before. The main association is with hand eczema and not to atopy itself. It is believed that the lack of association with atopy indicates that IgE mechanisms do not play a mayor role in the development of these symptoms. However, fragrance products causing airways symptoms affect a large proportion of the population. Potential mechanisms are being explored and this may led to the development of preventive measures. The Centre has developed an innovative system for double blind experimentation of the effects of fragrance materials on the conjunctival surface. This could be useful in mapping mucosal reactions towards different chemicals. In the long run it may be a valuable tool in all kinds of eye provocations, including allergens.Genome. Leading-edge initiatives in looking for genetic markers/genetic susceptibility for the development of contact allergy are being explored. Mapping of gene expression in chrome sensitive patients compared to non-allergic individuals is being performed. Investigation of the possible association between certain genetic markers and the individuals ability to produce allergic contact reactions is being undertaken. There is an ongoing analysis of 22 000 genes.Work in this field may elucidate markers to assess the risk of development of allergic contact dermatitis and the development of new diagnostic tools. Further work may explore possible associations between up-regulation of certain genes and the importance of this in the developments of other disease types such as auto-immunity and malignancy.These studies are fundamental in providing better understanding of the mechanisms underlying susceptibility to the development to contact allergy.Allergy and hair dyes. Hair dye allergy is an important problem to the European consumer. Up to 2% of the patch tested population with eczema may have hair dye allergy. Many permanent hair dye chemicals are known to be allergens and some of them are potent allergens. We understand that industry considers there to be no alternative systems of dying hair