A quantitative method for assessing the sensitizing potency of low molecular weight chemicals using a local lymph node assay: employment of a regression method that includes determination of the uncertainty margins.
Risk assessment of sensitizing chemicals requires, besides hazard identification, the assessment of potency. To examine the sensitizing capacity of low molecular weight chemicals, a murine local lymph node assay (LLNA) was used. The sensitizing capacity of known allergens was quantified by dose-response modeling. At a stimulatory index (SI) of 3, the corresponding estimated concentration was calculated (EC(3)), together with a confidence interval to take account of the quality of the particular data set. We tested ten allergens (ethyl-p-aminobenzoate (benzocaine), diethylamine (DEA), 2,4-dinitrochlorobenzene (DNCB), 2-mercaptobenzothiazole (MBT), 4-ethoxymethylene 2-phenyl oxazol-5-one (oxazolone), phthalic anhydride (PA), toluene diisocyanate (TDI), trimellitic anhydride (TMA), tetramethylthiuramdisulfide (TMTD) and zincdimethyldithiocarbamate (ZDMC)). Oxazolone showed the strongest sensitizing potency followed in this order by DNCB, TDI, TMA, PA, TMTD, ZDMC, MBT, benzocaine and DEA. The approach performed in this study is a way to accurately assess the potency of sensitizing chemicals and thus a possibility for classification.
van Och
F M
FM
National Institute of Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.h.van.loveren@rivm.nl
Slob
W
W
de Jong
W H
WH
Vandebriel
R J
RJ
van Loveren
H
H
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001566:Benzocaine / Q000276:immunology; D052160:Benzothiazoles; D003877:Dermatitis, Contact / Q000276:immunology*; D004048:Diethylamines / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016014:Linear Models; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000276:immunology; D010796:Phthalic Anhydrides / Q000276:immunology; D012044:Regression Analysis; D012588:Scintillation Counting; D013047:Specific Pathogen-Free Organisms; D013844:Thiazoles / Q000276:immunology; D013893:Thiram / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology; D015039:Ziram / Q000276:immunology
D000485:Allergens; D052160:Benzothiazoles; D004048:Diethylamines; D004137:Dinitrochlorobenzene; D010796:Phthalic Anhydrides; D013844:Thiazoles; D013893:Thiram; D010081:Oxazolone; D014051:Toluene 2,4-Diisocyanate; C005563:captax; D015039:Ziram; C015559:trimellitic anhydride; C034281:diethylamine; D001566:Benzocaine; C043103:phthalic anhydride