ICCVAM Evaluation of the Murine Local Lymph Node Assay

Sailstad, Denise M.; Hattan, David G.; Hill, Richard N.; Stokes, William S.

doi:10.1006/rtph.2001.1496

Cited by 107 publications

(27 citation statements)

References 16 publications

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“…The animal test best suited for providing dose-response information is the local lymph node assay (LLNA) in mice (Dean et al, 2001;Haneke et al, 2001;Kimber et al, 2002;OECD, 2002;Sailstad et al, 2001). In the LLNA, the test substance is applied onto the mouse ear on three consecutive days.…”

Section: Parameter Explanationmentioning

confidence: 99%

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%

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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“…In recent years, three kinds of murine local lymph node assays (LLNAs) for skin sensitization have been developed. After thorough evaluation and reviews, these tests were adopted by The Organisation for Economic Co-operation and Development (OECD) as stand-alone skin sensitizing tests: Test Guideline (TG) 429, TG442A, and TG442B (Kimber et al, 1986;Basketter et al, 1996;Gerberich et al, 2000;Dean et al, 2001;Haneke et al, 2001;Takeyoshi et al, 2001;Sailstad et al, 2001;OECD TG No. 429, 2002, 2010bYamashita et al, 2005;Idehara et al, 2008;Omori et al, 2008;ICCVAM, 2010;OECD TG No.…”

Section: Introductionmentioning

confidence: 99%

Further development of LLNA:DAE method as stand-alone skin-sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals

Yamashita

Shinoda²,

Hagiwara³

et al. 2015

J. Toxicol. Sci.

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-To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elicitation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnamic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

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“…In more recent years, due to the absence of clear rules and guidances, the qualification of a biomarker was mostly accepted based on consensus among scientists, as well as between scientists and regulatory agencies. These biomarkers were mostly context independent, this means that their application was discussed for more general testing strategies, such as preclinical toxicology [42,43]. Current regulatory guidances are focused on contextspecific qualifications assuming that most markers will be developed in association with a drug development program and, accordingly, to study and monitor the effects of specific drugs [42].…”

Section: Qualificationmentioning

confidence: 99%