Value of the cutaneous basophil hypersensitivity (CBH) response for distinguishing weak contact sensitization from irritation reactions in the guinea pig.
Numerous studies of the histology of allergic contact dermatitis reactions to potent allergens in guinea pigs and humans have indicated that there is significant tissue infiltration with basophilic leukocytes. In this study we determined whether this histologic finding could be of value in distinguishing weak sensitization reactions from primary irritation, thereby aiding in the predictive identification of weak or moderate contact allergens. Guinea pigs were sensitized by the Buehler test method. Skin reactions were graded 24, 48, and 72 h post-challenge with duplicate patch sites biopsied at the 24- or 72-h grading timepoints. The biopsies were fixed, embedded in glycol methacrylate, thin sectioned, and Giemsa stained. The number of basophils per 400 leukocytes were counted along the upper dermis just below the dermal/epidermal junction. Challenge patch sites from animals sensitized to a relatively low dose of the strong contact allergen, oxazolone, were compared with patch sites from animals challenged only with a strong irritant, sodium lauryl sulfate (SLS). Compared to normal skin (7.5 +/- 1.0 basophils/400 leukocytes +/- SEM) only the oxazolone patch sites showed significant basophil infiltration (36.8 +/- 6.5), despite the fact that the skin reactions to the low oxazolone challenge dose were relatively weak. SLS patch sites showed no basophil infiltration above normal skin levels (4.8 +/- 0.9). Subsequent blinded studies compared weak/moderate presumptive sensitization reactions (as defined by accepted visual skin grading criteria) to various chemicals (citronellal, vanillin, cinnamic aldehyde, and ethylenediamine) to primary irritation reactions to the same chemicals. In each case, low-challenge-dose sensitization sites on previously treated (induced) animals showed mean basophil infiltration (range, 11.9-69.2 basophils/400 leukocytes) significantly greater than higher-dose irritant reactions (range, 1.6-13.3). The range for normal skin was 0.2-10.2 and the range for strong patch reactions to higher concentrations of oxazolone was 59.8-209.3. These data strongly indicate that light-microscopic quantitation of the CBH response can be used to distinguish relatively weak to moderate contact sensitization reactions from primary irritation reactions to the same chemicals.
Robinson
M K
MK
Human and Environmental Safety Division, Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45239.
Fletcher
E R
ER
Johnson
G R
GR
Wyder
W E
WE
Maurer
J K
JK
D000818:Animals; D001491:Basophils / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000008:administration & dosage; D005260:Female; D006168:Guinea Pigs; D007958:Leukocyte Count; D008297:Male; D010081:Oxazolone / Q000009:adverse effects; D012882:Skin Tests
D005029:Ethylenediamines; D010081:Oxazolone; C031234:ethylenediamine