The effect of altering area of application and dose per unit area on sensitization by DNCB

White, S.I.; Friedmann, Peter S.; Moss, Celia; Simpson, Judy M.

doi:10.1111/j.1365-2133.1986.tb06646.x

Cited by 89 publications

(39 citation statements)

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“…Several experimental investigations, especially with DNCB in human subjects, revealed that the induction of skin sensitization is dependent on the dose of the test chemical per skin area (Friedmann, 1990;White et al, 1986). Therefore, it has been widely recommended that sensitization thresholds obtained in LLNA, HRIPT or HMT should be expressed as the area dose (Boukhman and Maibach, 2001;Robinson et al, 2000;Roggeband et al, 2001).…”

Section: Parameter Explanationmentioning

confidence: 99%

“…From research done during the last 15 years, e.g., using experimental human sensitization to 2,4-dinitrochlorobenzene (DNCB) (Friedmann et al, 1983;White et al, 1986;reviewed in Friedmann, 1990), we know today that skin sensitization as well as allergy elicitation only occur above threshold doses and follow predictable dose-response relationships (Basketter, 1998;Boukhman and Maibach, 2001;Kimber et al, 1999Kimber et al, , 2002Marzulli and Maibach, 1974;Roggeband et al, 2001;Scott et al, 2002;Van Och et al, 2001). It has become clear that skin sensitization is not different from other toxicological effects in this respect.…”

Section: Introductionmentioning

confidence: 96%

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Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data

Griem

Goebel

Scheffler

2003

Regulatory Toxicology and Pharmacology

117

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Section: Parameter Explanationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data

Griem

Goebel

Scheffler

2003

Regulatory Toxicology and Pharmacology

117

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“…Using DNCB (dinitrochlorobenzene) as a model contact allergen, it was found that the dose per unit area of allergen was the critical parameter for whether sensitization occurred (27). The data demonstrated a threshold for the induction of clinically relevant sensitization to occur.…”

Section: Contact Sensitization: Observations On Exposurementioning

confidence: 99%

Contact allergy, irritancy and ‘danger’

2000

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Conventional models of the immune response are based on distinguishing self and non-self. However, we consider that the more recently proposed 'danger' model may be an illuminating alternative for studying allergic contact dermatitis. In this model, an antigenic signal on its own would tend to produce tolerance. In contrast, in the presence of a 'danger' signal, which, in the case of allergic contact dermatitis, we suggest is usually cutaneous irritancy, the immune system would become activated, leading first to the induction of sensitization and then subsequently to the elicitation of a contact hypersensitivity response. In most cases, both the antigenic signal and irritant signal will come from the hapten, although, e.g., in an occupational setting, traumiterative dermatitis would be the source of the 'danger' signal. Typically, the irritant signal tends to be more concentration-dependent and thus is the overriding factor in the determination of the effective sensitizing and eliciting concentrations of the hapten. A further prediction of this hypothesis is that successful experiments demonstrating low-dose tolerance with contact allergens may be explained by the loss of the irritant effect at lower dilutions, whilst an antigenic stimulus remains present.

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“…The assumption from this is that, in any given test system, an equal % exposure will lead to a similar incidence and/or severity of sensitization. However, in a series of elegant human skin sensitization studies, Friedmann and his colleagues proved that it is not the % (weight/volume) of material applied that is critical, but the total dose/area of exposed skin (11,26,(30)(31)(32)(33). They used a potent contact allergen, dinitrochlorobenzene (DNCB), and repeatedly exposed subjects to varying doses per unit area of skin to observe the incidence of sensitization upon challenge.…”

Section: Importance Of Dose/unit Area In the Skin Sensitization Processmentioning

confidence: 99%

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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The effect of altering area of application and dose per unit area on sensitization by DNCB

Cited by 89 publications

References 0 publications

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data

Contact allergy, irritancy and ‘danger’

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

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