Preservatives and skin sensitisation quantitative risk assessment: risk benefit considerations. Dermatitis

Unilever, Colworth House, Sharnbrook, Bedfordshire, UK.
Dermatitis (Impact Factor: 1.63). 01/2008; 19(1):20-7. DOI: 10.2310/6620.2008.07018
Source: PubMed


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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    • "As indicated earlier, potency alone does not make a skin sensitiser an SVHC candidate, any more than does the dissociation between the inducing exposures and the ultimate expression of skin disease (which is a property that all sensitisers, from the very weakest to the most potent, share in common). Importantly, it is possible to identify safe levels of exposure to formaldehyde with respect to the acquisition of skin sensitisation, and thereby assess and manage the risk (Basketter et al., 2008 "
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    ABSTRACT: The identification, characterisation, risk assessment and risk management of materials that cause allergic sensitisation is an important requirement for human health protection. It has been proposed that for some chemical and protein allergens, and in particular for those that cause sensitisation of the respiratory tract (associated with occupational asthma), it may be appropriate to regard them as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). We have argued previously that categorisation of sensitising agents as SVHC should be used only in exceptional circumstances. In the present article, the subject of SVHC is addressed from another perspective. Here the information that would be required to provide a compelling case for categorisation of a skin sensitising substance as a SVHC is considered. Three skin sensitising chemicals have been identified to serve as working examples. These are chromate, a potent contact allergen, and the skin sensitisers formaldehyde and isoeugenol. The key criterion influencing the decision regarding a skin sensitiser being categorized as SVHC is the extent to which impacts on the quality of life are reversible. Consequently, SVHC categorisation for skin sensitising chemicals should be used only in exceptional circumstances.
    Regulatory Toxicology and Pharmacology 01/2014; · 2.03 Impact Factor
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    • "In this approach EC3 values are used as a point-of-departure to calculate levels below which no sensitization will occur, called the NESIL (No Expected Sensitization Induction Level). Different safety factors are then applied to calculate safe exposure levels (Robinson et al., 2000; Api et al., 2008; Basketter et al., 2008). In the future, such quantitative approaches might be used to determine concentration limits that are safe for consumers, rather than the current concentration limits that are arbitrary chosen. "
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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. DOI:10.1016/j.tox.2012.05.002 · 3.62 Impact Factor
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    • "This range suggests that the risk to induce fragrance allergy as a result of wearing clothes that have been machine washed with laundry products is extremely low. More recently, Basketter et al. (2008) undertook a retrospective QRA on four different preservatives (formaldehyde, MCI/MI, imidazolidinyl urea and 3-iodo-2-propynyl butyl carbamate) in five product types (shampoo, face cream, non-aerosol deodorant, body lotion and lipstick). This analysis illustrated that, for certain preservative/product type combinations, actual exposure through product use resulted in an AEL/CEL value 61). "
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    ABSTRACT: Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for classification and labelling. Second, is there any reason to revise the recommendation of a previous ECETOC Task Force regarding specific EC3 values used for sub-categorisation of substances based upon potency? Third, what recommendations can be made regarding classification and labelling of preparations under GHS? Finally, consider how to integrate LLNA data into risk assessment and provide a rationale for using concentration responses and corresponding no-effect concentrations. Although skin sensitising chemicals having high EC3 values may represent only relatively low risks to humans, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling. The conclusion drawn from reviewing the use of distinct categories for characterising contact allergens was that the most appropriate, science-based classification of contact allergens according to potency is one in which four sub-categories are identified: 'extreme', 'strong', 'moderate' and 'weak'. Since draining lymph node cell proliferation is related causally and quantitatively to potency, LLNA EC3 values are recommended for determination of a no expected sensitisation induction level that represents the first step in quantitative risk assessment.
    Regulatory Toxicology and Pharmacology 10/2009; 56(1):54-66. DOI:10.1016/j.yrtph.2009.08.016 · 2.03 Impact Factor
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