A quantitative comparison of induction and challenge concentrations inducing a 50% positive response in three skin sensitization tests; the guinea pig maximization test, adjuvant and patch test and Buehler test.
The sensitivities of three skin sensitization tests such as the Guinea pig maximization test (GPMT), Adjuvant and patch test (APT) and Buehler test (BT), were quantitatively compared with reference to induction and challenge concentrations. Four chemical which had different physico-chemical properties (octanol-water partition coefficient (logP) and reactivity with NH2-group) were used in order to clarify the effect of the physico-chemical properties of chemicals on the sensitivity of the different methods. The induction concentrations inducing a 50% positive response (IC50) demonstrated extreme variation with the three methods. For example, the BT/GPMT ratio of IC50 values for 2,4-dinitrochlorobenzene was 33, whereas that for maleic anhydride was 300,000. The results were thought to be caused by difference properties such as the logP and reactivity of chemicals. This correlation was confirmed by using 2-dodecen-1-yl succinic anhydride, which had the same reactivity but higher logP than that of maleic anhydride. On the other hand, the challenge concentrations inducing 50% positive responses (CC50) were less affected by the methods and the BT/GPMT ratios for CC50 values were all within a 10-fold range. These results suggest that the sensitivity might be strongly different with reference to induction concentration, but not challenge concentration among the three methods.
Nakamura
Y
Y
Sumitomo Chemical Co., Ltd., Environmental Health Science Laboratory, Osaka, Japan.
Higaki
T
T
Kato
H
H
Kishida
F
F
Kogiso
S
S
Isobe
N
N
Kaneko
H
H
D000276:Adjuvants, Immunologic; D000818:Animals; D004137:Dinitrochlorobenzene / Q000633:toxicity; D006168:Guinea Pigs; D007114:Immunization / Q000379:methods*; D007509:Irritants / Q000633:toxicity; D008299:Maleic Anhydrides / Q000633:toxicity; D010328:Patch Tests; D012882:Skin Tests / Q000379:methods*; D013387:Succinic Anhydrides / Q000633:toxicity
D000276:Adjuvants, Immunologic; D004137:Dinitrochlorobenzene; D007509:Irritants; D008299:Maleic Anhydrides; D013387:Succinic Anhydrides; C031801:succinic anhydride