POTENCY RANKING OF METHEMOGLOBIN-FORMING AGENTS

This study represents the first systematic attempt to rank methemoglob in-forming agents. It is a quantitative potency ranking study utilizin g linear regression analysis of dose-response data for comparative pur poses. Six agents that are direct-acting and eight that require bioact ivation were tested for their ability to induce methemoglobin formatio n in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected t o induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l(-1) of the agent . The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to leas t potent inducers of the bioactivated agents are: alpha-naphthol > p-n itroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = anilin e > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discus sed and issues of interindividual variation and agent-specific sensiti vities are addressed.