The authors report here on the relationships of the acute toxicities to Photobacterium phosphoreum of 1,4-di-substituted benzenes with their pctanol/water partition coefficients and with the toxicities of the corresponding mono-substituted benzene derivatives and also identify the types of derivatives for which such toxicities can or cannot safely be predicted. "Outliers" to the previously established quantitative structure-activity relationships (QSARs) are identified, and reasons for their aberrant behavior are discussed in terms of specific substituent groups and their electronic effects on the basic molecule and on the other substituents present, as measured by the substituent-induced chemical shifts of carbon-13 (¹³C) nuclear magnetic resonance data of the substituent-bearing carbon atoms of the benzene ring. With the combination of these parameters, the toxicity of highly toxic compounds can be predicted within an error of approximately 0.35 logarithmic toxicity units over more than four orders of magnitude. Nitrobenzene derivatives require the use of a parameter for the charge buildup on the oxygen atoms of the nitro group.