Application of a weight of evidence approach to assessing discordant sensitisation datasets: Implications for REACH

Basketter, David A.; Ball, Nicholas; Cagen, Stuart Z.; Carrillo, Juan-Carlos; Certa, Hans; Eigler, Dorothea; Garcia, Christine; Esch, Harald L.; Graham, Cynthia; Haux, Carl; Kreiling, Reinhard; Mehling, Annette

doi:10.1016/j.yrtph.2009.06.005

Cited by 46 publications

(21 citation statements)

References 38 publications

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“…These LLNA methods have several advantages over the GPMT/BA, including generation of quantitative data, a reduction in test time, a reduction in the required number of animals, and an improvement in animal welfare (Haneke et al, 2001;Basketter et al, 1996). Thus, the LLNA became the method of first choice (Grindon et al, 2008;Basketter et al, 2009). However, these LLNA methods have given falsepositive results for some skin irritants.…”

Section: Introductionmentioning

confidence: 99%

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing

Yamashita

Shinoda²,

Hagiwara³

et al. 2014

J. Toxicol. Sci.

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-We developed a new local lymph node assay (LLNA) that includes the elicitation phase termed LLNA:DAE for discrimination of borderline-positive chemicals as classified by the LLNA modified by Daicel based on ATP content (LLNA:DA) and for cross-sensitization testing. Although the LLNA:DA method could help identify skin sensitizers, some skin irritants classified as non-sensitizers by the LLNA were classified as borderline positive. In addition, the evaluation for the cross-sensitization potential between chemicals was impossible. In the LLNA:DAE procedure, test group of mice received four applications of chemicals on the dorsum of the right ear for induction and one application on the dorsum of the left ear for elicitation. Control group of mice received one chemical application on the dorsum of the left ear. We evaluated the sensitizing potential by comparing the weights of the lymph nodes from the left ears between the two groups. The results of using the LLNA:DAE method to examine 24 chemicals, which contained borderline-positive chemicals, were consistent with those from the LLNA method, except for nickel chloride (NiCl 2 ). Two chemical pairs, 2,4-dinitrochlorobenzene (DNCB) with 2,4-dinitrofluorobenzene (DNFB) and hydroquinone (HQ) with p-benzoquinone (p-BQ), showed clear cross-sensitization with each other, while another chemical pair, DNFB with hexylcinnamic aldehyde (HCA) did not. Taken together, our results suggest that the LLNA:DAE method is useful for discriminating borderline-positive chemicals and for determining chemical cross-sensitization.

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Section: Introductionmentioning

confidence: 99%

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing

Yamashita

Shinoda²,

Hagiwara³

et al. 2014

J. Toxicol. Sci.

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“…Detailed discussion of this topic, with several examples, has been published elsewhere. [44][45][46][47] Clinical data on skin sensitization…”

Section: Skin Sensitization Hazard Identification and Characterizationmentioning

confidence: 99%

Skin sensitization

et al. 2015

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Skin sensitization associated with allergic contact dermatitis is a common health problem and is an important consideration for toxicologists in safety assessment. Historically, in vivo predictive tests have been used with good success to identify substances that have the potential to induce skin sensitization, and these tests formed the basis of safety evaluation. These original tests are now being replaced gradually either by in vitro assays or by further refinements of in vivo methods such as the local lymph node assay. Human data have also been available to inform classification decisions for some substances and have been used by risk managers to introduce measures for exposure reduction. However, humans encounter hazards in the context of exposure rather than in the form of intrinsic hazards per se, and so in this article, we have examined critically the extent to which human data have been used to refine classification decisions and safety evaluations. We have also evaluated information on the burden of human allergic skin disease and used this to address the question of whether, and to what extent, the identification and evaluation of skin sensitization hazards has led to an improvement of public and/or occupational health.

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“…3 H]-thymidine to monitor proliferation labeling leads to the generation of radioactive biologic wastes (and, accordingly, the need for dedicated 'hot' housing of the hosts and special handling/disposal of all lab/animal wastes) and the possibility of false positive results caused by non-specific cell activation due to inflammatory processes in the skin (irritation) (Takeyoshi et al, 2001;Basketter et al, 2009). In this study, we aimed to investigate the following non-radioactive endpoints of LLNA: 5-bromo-2′-deoxyuridine (BrdU) incorporation ex vivo and in vivo, as well as the formation/release of IL-2, IFNγ, IL-4, and IL-5 by isolated lymph node cells.…”

Section: Research Articlementioning

confidence: 99%

Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

Ülker

Atak

Ateş

et al. 2011

Journal of Immunotoxicology

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Application of a weight of evidence approach to assessing discordant sensitisation datasets: Implications for REACH

Cited by 46 publications

References 38 publications

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing

Skin sensitization

Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

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