Preservatives and skin sensitization quantitative risk assessment.
ABSTRACT Preservatives are an unfortunately common cause of allergic contact dermatitis (ACD). Often, this is in association with exposure to cosmetics or medicaments. Recently, a quantitative risk assessment (QRA) approach to the quantitation of safe exposure levels for sensitizers has been promulgated as a more effective tool for the identification of acceptable levels of potential sensitizers in consumer products.
To assess this QRA approach, which facilitates the prediction of acceptable exposure levels to skin sensitizers in consumer products, levels that are normally below the threshold for the induction of skin sensitization.
Retrospective QRA analysis on four preservatives in five consumer product types.
The analysis shows that functional levels of preservatives may be somewhat above an ideal exposure level for some product types, an outcome that is consistent with the clinical picture.
QRA represents a new tool that in the future should be used in combination with the assessment of microbiologic protection needs of specific product types to limit the problem of preservative ACD.
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ABSTRACT: Abstract: Xerosis is one of the most common problems of patients with atopic eczema, it is also relatively common in allergic and irritant contact eczema. Moreover, patients with atopic diathesis in a broad sense complain more often of dry skin. As a rule, these patients are administered with emollient preparations that moisturize, soften and smoothen the skin, as well as keep water in the epidermis, supplement lipids of skin's upper layers and protect from external harmful agents. However, emollients just as most other cosmetics, may contain "problematic" ingredients, including sensitizers. The objective of this study was to analyse compositions of emollients available from pharmacies, with the focus on the occurrence of active substances, as well as of ingredients whose use in cosmetics is either subject to restrictions or banned. Material and methods: Emollients offered by Internet pharmacies were analyzed with special attention paid to occurrence of active and "problematic" ingredients as defined by the European directives. Results: We identified 177 cosmetics that contained in total 522 different ingredients, including 181 active substances and 49 "problematic" ingredients (mainly preservatives and fragrances). The active ingredients that were most frequently used in the emollients were liquid paraffin (46%), triglycerides of caprylic and capric acid (33%), cetearyl alcohol and allatoin (each 27%). Methylparaben (38%), phenoxyethanol (36%) and propylparaben (33%) were the most common "problematic" ingredients of the emollients. Conclusions: The vast majority of emollients available from pharmacies contain ingredients with sensitizing potential that are subject to restrictions of use in cosmetics on account of the risk to human health. Lack of correlation between the numbers of active and "problematic" ingredients occurring in the analysed products indicates on the possibility of creating safer emollients while maintaining effectiveness. Key words: emollients, active ingredients, "problematic" ingredients, consumer safety, contact allergy.Alergia Astma Immunologia 01/2012; 17(3):147-153.
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ABSTRACT: The concept that thresholds exist for the induction of allergic contact dermatitis by chemicals with skin sensitizing properties has been used for a quantitative risk assessment approach. In this approach the potency of skin sensitizers as determined in the Local Lymph Node Assay is used to calculate the threshold for induction of sensitization. These are then used to estimate safe exposure levels for consumers. Whether these exposure levels will protect subjects that are already sensitized is unknown. The elicitation of allergic contact dermatitis supposedly occurs above a certain threshold as well and this threshold is most likely lower than that for the induction. It is unclear if induction thresholds can be extrapolated to elicitation thresholds. The aim of this study was to assess the potency of sensitizers with different sensitizing potencies in the elicitation phase in a mouse model for elicitation. Mice were sensitized by topical application on days 0 and 7 using equipotent concentrations of oxazolone, 2,4-dinitrochlorobenzene (DNCB) and eugenol to ensure that the sensitization strength would not influence the elicitation potency. Mice were challenged on day 21 by topical application on the ears in a dose-dependent manner and dose-response data were used to calculate the elicitation potency. Unexpectedly, sensitizers with different sensitizing potencies induced not the same dose-response curves in sensitized mice. The most potent sensitizer in the elicitation phase was oxazolone, followed by DNCB and eugenol. Similar to the induction phase, under equipotent sensitization conditions strong sensitizers such as oxazolone and DNCB elicit allergic reactions at lower concentrations than weak sensitizers such as eugenol. Our results indicate that elicitation thresholds cannot be readily deduced from sensitization thresholds.Toxicology 05/2012; 299(1):20-4. · 4.02 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