Screening Petrochemicals for Contact Hypersensitivity Potential: A Comparison of the Murine Local Lymph Node Assay with Guinea Pig and Human Test Data

EDWARDS, D. A.; SORANNO, T. M.; AMORUSO, M. A.; House, Robert V.; TUMMEY, A. C.; Trimmer, Gary W.; Thomas, Peter T.; Ribeiro, P. L.

doi:10.1093/toxsci/23.2.179

Cited by 6 publications

(7 citation statements)

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“…but not in an aqueous solution. Using EDA (as dihydrochloride), no sensitizing effect was obvious either in water or in acetone/olive oil (49,50).…”

Section: Experimental Studies In Animals Monoethanolamine: In a Maximmentioning

confidence: 99%

Skin sensitizing properties of the ethanolamines mono‐, di‐, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK*) and review of the literature

et al. 2009

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Numerous publications address the skin sensitizing potential of the short chain alkanolamines triethanolamine (TEA), diethanolamine (DEA), monoethanolamine (MEA), which are not skin sensitizing according to animal studies. Regarding TEA, we analysed patch test data of 85 098 patients who had been tested with TEA 2.5% petrolatum by Information Network of Departments of Dermatology (IVDK) to identify particular exposures possibly associated with an elevated risk of sensitization. Altogether, 323 patients (0.4%) tested positive. The profile of patch test reactions indicates a slightly irritant potential rather than a true allergic response in many cases. Although used widely, no exposure associated with an increased risk of TEA sensitization was identified. Therefore, the risk of sensitization to TEA seems to be very low. MEA and DEA were patch tested in a much more aimed fashion in 9602 and 8791 patients, respectively when prevalence of contact allergy was 3.8% and 1.8%. MEA is the prominent allergen in metalworkers with exposure to water-based metalworking fluids (wbMWFs); DEA is probably used in cutting fluids less frequently nowadays. Chronic damage to the skin barrier resulting from wbMWF, the alkalinity of ethanolamines (increasing from TEA to MEA), and other cofactors may contribute to a notable sensitization risk.

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“…but not in an aqueous solution. Using EDA (as dihydrochloride), no sensitizing effect was obvious either in water or in acetone/olive oil (49,50).…”

Section: Experimental Studies In Animals Monoethanolamine: In a Maximmentioning

confidence: 99%

Skin sensitizing properties of the ethanolamines mono‐, di‐, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK*) and review of the literature

et al. 2009

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“…Included among these are the use of an alternative isotope, changes to the duration of exposure and/or the analysis of lymph nodes isolated from individual mice (rather than pooled for each experimental group). 34,36,[50][51][52] Results deriving from recent international inter-laboratory evaluation and validation studies of the LLNA indicate that the method is sufficiently robust to accommodate conservative procedural modifications such as these without loss of performance or variation in the data obtained. [12][13][14][15][16] Some attempts have been made to develop supplementary or alternative endpoints for the LLNA that it is claimed might permit a more exacting discrimination between contact allergens and skin irritants.…”

Section: Procedural Modifications Alternative Endpoints and Related mentioning

confidence: 99%

Local lymph node assay: use in hazard and risk assessment

1999

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The murine local lymph node assay (LLNA) was developed as an alternative method for the identification of chemicals that have the ability to cause skin sensitization and allergic contact dermatitis. The assay now has been evaluated extensively in the context of both national and international inter‐laboratory collaborative trials and has been the subject of detailed comparisons with guinea pig test methods and human skin sensitization data. On the basis of these evaluations the LLNA has been endorsed recently by the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) as a stand‐alone method for skin sensitization testing. The assay offers a number of important benefits compared with conventional guinea pig test methods, among these being provision of an objective and quantitative endpoint. Moreover, the LLNA provides advantages in the context of animal welfare; compared with guinea pig tests, fewer animals are required and these animals are subject to less trauma. It is important now that the validation status of the LLNA is recognized and the method applied widely so that these advantages may be realized. Hazard identification represents only the first step in the risk assessment process. A full toxicological evaluation of skin sensitization activity requires an understanding of relative potency. Guinea pig methods do not lend themselves readily to assessment of potency, and interest recently has focused on the utility of the LLNA for this purpose. Contained within this review article are brief descriptions of the history of the LLNA and the immunobiological basis for the method, together with detailed accounts of the conduct and interpretation of the assay. Procedural modifications to, and alternative endpoints for, the LLNA are considered also. Finally, the current regulatory status of the LLNA is summarized and the application of the method for the purposes of defining relative potency and developing risk assessments is reviewed. Copyright © 1999 John Wiley & Sons, Ltd.

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“…In studies that investigated the correlation between GPMT and LLNA results, where both were conducted in parallel, it was shown that the LLNA assay was capable of detecting chemicals that exhibited a strong sensitization potential in the GPMT. The moderate sensitizers were generally positive or gave equivocal results in the LLNA, whereas the weak sensitizers were not detected (5,7).…”

Section: Discussionmentioning

confidence: 95%

“…In addition, this test causes less animal distress than guinea-pig tests and is of shorter duration. Since its original development, the LLNA has been the subject of extensive comparisons with guinea-pig tests (3)(4)(5)(6) and/or with human data (7)(8)(9)(10). Although comparisons of LLNA data with the results of guinea-pig tests have been presented for various classes of materials, including process intermediates, comparisons of animal with human data have not been reported for process intermediates.…”

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confidence: 99%

Use of the local lymph node assay in the evaluation of the sensitizing potential of pharmaceutical process intermediates

et al. 2003

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The murine local lymph node assay (LLNA) has recently been developed to determine the contact sensitization potential of chemicals. Since its original development, the LLNA results have been the subject of extensive comparisons with guinea pig and human data. The investigations described here were designed to explore the ability of the LLNA to identify accurately, pharmaceutical process intermediates (PIs) known to cause contact allergy in humans. To that end, 16 PIs previously tested in the guinea-pig maximization test (GPMT) were tested in the LLNA. Another PI known to be a contact sensitizer in humans was tested only in the LLNA. Cases of contact sensitization in humans were reported only for PIs that were extreme sensitizers in the GPMT and had low EC3 values (concentration of the test substance required to generate a threefold increase in lymph node cell proliferation) in the LLNA. These data provide additional evidence that the LLNA is able to discriminate skin sensitizers from chemicals that do not possess a significant skin sensitization potential and is thus a useful method for hazard identification. In addition, this method also offers important animal welfare benefits and may also be useful for risk assessment purposes.

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Screening Petrochemicals for Contact Hypersensitivity Potential: A Comparison of the Murine Local Lymph Node Assay with Guinea Pig and Human Test Data

Cited by 6 publications

References 0 publications

Skin sensitizing properties of the ethanolamines mono‐, di‐, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK*) and review of the literature

Skin sensitizing properties of the ethanolamines mono‐, di‐, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK*) and review of the literature

Local lymph node assay: use in hazard and risk assessment

Use of the local lymph node assay in the evaluation of the sensitizing potential of pharmaceutical process intermediates

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