NDLI: Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

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Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

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Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hou, Fenxia Xing, Caihong Li, Bin Cheng, Juan Chen, Wei Zhang, Man
Description	Author Affiliation: Hou F ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address: houfenxia66@163.com.); Xing C ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.); Li B ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.); Cheng J ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.); Chen W ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.); Zhang M ( Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.)
Abstract	INTRODUCTION: Allergic contact dermatitis (ACD) is a skin disease characterized by eczema and itching. A considerable proportion of chemicals induce ACD in humans. More than 10,000 substances should be tested for skin sensitization potential under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for sensitization testing by REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred mouse strain recommended in the regulatory guidelines. However, the availability of CBA/JN mouse in China is only limited to a few animal suppliers, which makes the mouse difficult to obtain. BALB/c mouse, which is widely commercially available, is considered for alternative use but it can only be used in the assay after it has been evaluated by formal validation study. Thus, a validation study was conducted in our laboratory to determine if BALB/c mouse could also be used in the LLNA:BrdU-ELISA. METHODS: Forty-three test substances including 32 LLNA sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration used were the same as that used in the formal validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Female BALB/c mice of 8-10 weeks old were randomly allocated to groups (four mice per group). The test substance (25 µl) or the vehicle alone was applied to the dorsum of both ears daily for 3 consecutive days. A single intraperitoneal injection of 0.5 ml of BrdU (10mg/ml) solution was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, weighed and stored at -20°C until BrdU-ELISA was conducted. RESULTS: This validation study for the LLNA:BrdU-ELISA using BALB/c mouse correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The accuracy, sensitivity, specificity, false positive rate, false negative rate, positive predictivity values and negative predictivity values in this study, which could indicate the performance of the LLNA:BrdU-ELISA using BALB/c mouse, were not different statistically from that of the validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. DISCUSSION: This validation study indicates that BALB/c mouse could be used alternatively in the LLNA:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.
File Format	HTM / HTML
ISSN	10568719
Volume Number	72
e-ISSN	1873488X
Journal	Journal of Pharmacological and Toxicological Methods
Language	English
Publisher	Elsevier
Publisher Date	2015-03-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Discipline Pharmacology Allergens Toxicity Bromodeoxyuridine Metabolism Dermatitis, Allergic Contact Local Lymph Node Assay Animals Enzyme-linked Immunosorbent Assay Female Lymph Nodes Cytology Mice Mice, Inbred Balb C Mice, Inbred Cba Predictive Value Of Tests Sensitivity And Specificity Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Toxicology Pharmacology

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Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

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Ethosome formulations of known contact allergens can increase their sensitizing capacity.

Comparison of BALB/c and CBA/J mice for the local lymph node assay using bromodeoxyuridine with flow cytometry (LLNA: BrdU-FCM).

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The regulatory use of the Local Lymph Node Assay for the notification of new chemicals in Europe.

Immunophenotyping does not improve predictivity of the local lymph node assay in mice.

Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

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