An Approach to Allergic Contact Sensitization Risk Assessment of New Chemicals and Product Ingredients

Gerberick, Frank; Robinson, Michael K.; Stotts, J. A.

doi:10.1097/01634989-199312000-00001

Cited by 24 publications

(11 citation statements)

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“…Sensitization rates of contact allergens are dependent not only on the inherent sensitizing capacity of the chemical, but also on the dose and type of exposure (17), the amount of allergen per unit area surface of skin (18), the vehicle (19) and the condition of the skin (20). An approach to allergic contact sensitization risk assessment has been published (21).…”

Section: Discussionmentioning

confidence: 99%

Monitoring levels of preservative sensitivity in Europe

et al. 2002

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A 10-year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5-chloro-2-methyl-4-isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re-evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave-on products.

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Section: Discussionmentioning

confidence: 99%

Monitoring levels of preservative sensitivity in Europe

et al. 2002

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“…Risk assessment combines an appreciation of inherent hazards with an understanding of anticipated conditions of exposure to provide an estimate of the likelihood that human health will be affected adversely. Approaches to skin sensitization risk assessment, including the contribution of LLNA data to the risk assessment process, have been considered thoroughly elsewhere (96, 106–112), and a detailed commentary is outwith the scope of this article. The important point to make, however, is that the availability now of information on relative potency based on EC3 values has transformed, and improved considerably, approaches to skin sensitization risk assessment.…”

Section: Llna Data and Risk Assessmentmentioning

confidence: 99%

The local lymph node assay: past, present and future

et al. 2002

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The local lymph node assay (LLNA) was developed originally as a method for the identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. The assay is based on an understanding that the acquisition of contact sensitization is associated with, and dependent upon, the stimulation by chemical allergens of lymphocyte proliferative responses in skin-draining lymph nodes. Those chemicals that provoke a defined level of lymph node cell (LNC) proliferation (a 3-fold or greater increase compared with concurrent vehicle controls) are classified as skin sensitizers. Following its original inception and development, the LLNA was the subject of both national and international interlaboratory collaborative trials, and of very detailed comparisons with other test methods and with human skin sensitization data. The assay has now been validated fully as a stand-alone test for the purposes of hazard identification. In recent years, there has been a growing interest also in the use of the LLNA to assess the potency of contact allergens and in risk assessment. There is reason to believe that the extent of skin sensitization achieved is associated with the vigour of LNC proliferation induced in draining nodes. Given this relationship, the relative potency of skin sensitizing chemicals is measured in the LLNA by derivation of an EC3 value, this being the concentration of chemical required to provoke a 3-fold increase in the proliferation of LNC compared with controls. Experience to date indicates that relative potency as determined using this approach correlates closely with what is known of the activity of skin sensitizing chemicals in humans. In this article, we review the development, evaluation and validation of the LLNA for the purposes of hazard identification, and the more recent application of the method for evaluation of potency in the context of risk assessment. In addition, we consider what new applications and modifications are currently being investigated.Key words: allergic contact dermatitis; hazard identification; local lymph node assay; lymphocyte proliferation, potency assessment; risk assessment; skin sensitization. C Blackwell Munksgaard, 2002. C Blackwell Munksgaard, 2002. Accepted for publication 28 October 2002Skin sensitization resulting in allergic contact dermatitis is an important occupational disease, and certainly the most common manifestation of chemical allergy in humans. There is a need therefore to identify the hazards and risks of allergic contact dermatitis that may be associated with exposure to chemicals at work, at home and in the environment. Conventionally, toxicological assessments of this kind are conducted (conceptually at least) in 2 phases, wherein potential hazards are first identified and then the likelihood of those hazards translating into human health risks is assessed. The latter risk assessments are predicated upon consideration of the nature of the hazard (of particular importance being an appreciation of potency) and the likel...

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“…Based on human patch test data (in water), the threshold for skin sensitization by MCI/MI is approximately 2 mg/cm 2 , with approximately 1 mg/ cm 2 defined as a no-effect level (12). The weighting factors used to determine a safety factor for MCI/ MI in a shampoo are shown in Table 5.…”

Section: Exposure-based Risk Assessmentmentioning

confidence: 99%

“…The skin sensitization testing and risk assessment process for new ingredients and products generally follows a stepwise approach that may involve analytical assessments, preclinical skin sensitization testing, clinical testing, and benchmarking of resulting data against similar ingredients and product types. The details of these various elements and the overall process have been reviewed previously (1)(2)(3)(4)(5). Case studies of its application have also been described relevant to specific ingredients and product types (1,(6)(7)(8).…”

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The importance of exposure estimation in the assessment of skin sensitization risk

et al. 2000

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The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study.

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An Approach to Allergic Contact Sensitization Risk Assessment of New Chemicals and Product Ingredients

Cited by 24 publications

References 0 publications

Monitoring levels of preservative sensitivity in Europe

Monitoring levels of preservative sensitivity in Europe

The local lymph node assay: past, present and future

The importance of exposure estimation in the assessment of skin sensitization risk

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