Dose-response relationship in skin sensitization.
The dose-response relationship (challenge phase) of the skin sensitization response was investigated in previously sensitized Hartley guinea pigs. Larger numbers of animals were used per group at the lower doses so that statistically significant observations could be made. Model compounds known to be skin sensitizers were used: a strong sensitizer, dinitrochlorobenzene (DNCB), and a weaker sensitizer, p-phenylenediamine (PPDA). A gradation in response to changing DNCB doses was easily observed by using either the open epicutaneous test (OET) or the Buehler occlusive patch test. The Buehler test was used to study the dose-response relationship of DNCB sensitization. The sensitivity of the OET and Buehler test was judged not adequate to measure the dose response for PPDA, because at high doses a high incidence of responders was not obtained. Therefore, the maximization test was used to evaluate PPDA. Similar, non-linear dose-response curves were obtained with each compound. The higher doses produced a somewhat linear relationship, but at lower doses the curves flattened out and more slowly approached a zero response. Thus, for potent sensitizers, concentrations found in exposure situations might be in the linear portion of the dose-response curve. For weak responders, use concentrations might be in the shallow portion of the curve, where reactions would be underestimated if a linear dose-response curve were assumed.
Bronaugh
R L
RL
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204.
Roberts
C D
CD
McCoy
J L
JL
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007428:Intradermal Tests; D008297:Male; D010328:Patch Tests; D010655:Phenylenediamines / Q000633:toxicity*; D012867:Skin / Q000187:drug effects*; D013194:Staining and Labeling
D004137:Dinitrochlorobenzene; D010655:Phenylenediamines; C029728:4-phenylenediamine