The murine local lymph node assay: Regulatory and potency considerations under REACH

McGarry, Helen F.

doi:10.1016/j.tox.2007.06.002

Cited by 45 publications

(13 citation statements)

References 112 publications

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“…For the LLNA and LLNA:DA, some skin irritants showed false positive results and/or borderline positive results due to non-specific proliferation (Monelius et al, 1998;McGarry, 2007;Idehara et al, 2008;ICCVAM, 2010). Furthermore, Kreiling et al (2008) reported that several unsaturated compounds that were LLNA-positive showed negative results in the guinea pig maximization test (Magnusson and Kligman, 1969;Kreiling et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…These LLNAs evaluated the skin-sensitizing potential of chemicals at the induction phase. It was known that some skin irritants gave false positive results (Montelius et al, 1998;McGarry, 2007). This potential for misclassification was especially apparent when the borderline positive criterion was defined in the LLNA method modified by Daicel based on ATP content (LLNA:DA) was adopted as TG442A by the OECD.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…The broad range of LLNA EC3 values and human DSA 05 values shown in Table 3 are due in part to the different vehicles used in the different studies. The vehicle effect is thought to differ due to the following two reasons: 1) the vehicle will influence the ability of the test substance to traverse the stratum corneum and reach the viable epidermis and 2) the vehicle will influence the efficiency of Langerhans cell migration from the skin Lea et al, 1999;McGarry, 2007;Wright et al, 2001). The former of these two points is of particular relevance to the EE assay described in this manuscript.…”

Section: Discussionmentioning

confidence: 99%

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

Gibbs¹,

Corsini

Spiekstra³

et al. 2013

Toxicology and Applied Pharmacology

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“…After the formal validation of the assay, some groups thought that it may be too sensitive and/or prone to false positives [53,54] . This topic has been extensively discussed in the literature [41,[54][55][56][57] . It is a fact that any toxicology assay has both false positives and false negatives, and the LLNA is no exception.…”

Section: Guinea Pig Modelsmentioning

confidence: 99%

Skin Irritation and Sensitization: Mechanisms and New Approaches for Risk Assessment

Basketter

Darlenski

Fluhr

2008

Skin Pharmacol Physiol

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Allergic contact dermatitis (ACD) is a common skin disease with a significant social and economic impact. In contrast to irritation, skin sensitization is a response of the adaptive immune system, in which there is a delayed T-cell-mediated allergic response to chemically modified skin proteins. The chemicals that can covalently modify the skin proteins and trigger an allergic reaction are referred to as haptens or sensitizers. Attempts have been made in many countries to reduce the problems of ACD by the implementation of legislations related to skin-sensitizing chemicals, as well as by the early detection and risk assessment of substances with sensitizing properties. For many years, the simple identification of sensitizing chemicals was performed in guinea pig tests. A murine test, the local lymph node assay (LLNA), has been validated as a replacement for the guinea pig tests. Despite the recent introduction of in vitro methods for the identification of sensitizing chemicals, the LLNA results (when coupled with good exposure data) can be used as the starting point for a quantitative risk assessment. The quantitative risk assessment is aimed to identify the safe use thresholds for any potential skin sensitizer.

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The murine local lymph node assay: Regulatory and potency considerations under REACH

Cited by 45 publications

References 112 publications

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

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

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

Skin Irritation and Sensitization: Mechanisms and New Approaches for Risk Assessment

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