Studies on the mechanism of toxicity of chlorophenols found in fish through quantitative structure-activity relationships

the mechanism of the toxicity of chlorophenols in fish was investigated through the relation between the toxicity in vivo and each of Pow, and ΔpKa (pKa of phenol—pKa of each chlorophenol). The acute toxicity of chlorophenols in goldfish, Carassius auratus, was evaluated as 5-h LC50 in media (W) and 5-h LC50, in vivo (V). The 1/W value steeply increased with increasing number of chlorine atoms, while the 1/V value gradually increased. The log 1/V was linearly correlated with log Pow (r = 0.914). A linear correlation of r = 0.805 was observed between log 1/V and ΔpKa Taking the effect of dissociation into account, each of the V values was divided into the concentrations of undissociated form (Va) and dissociated form (Vi). In grouping chlorophenols on the basis of the position of chlorine atoms substituted, a good linear relationship was observed between log 1/Vn and ΔpKa. The parallel linear relationships showed that the suppressed magnitude of the interaction between the undissociated chlorophenols and the site of action increases in the order of 4-CP < 3-CP < 3,5-DCP < 2-CP < 2,4-DCP < 2,3-DCP 2,5-DCP < 2,4,5-TCP < 2,6-DCP 2,4,6-TCP 2,3,4,6-TCP PCP, i.e. the suppressed magnitude increased with the closing of the chlorine atom position to the OH group. From these results, it was concluded that chlorophenols are transferred from media to the site of action in fish mainly by the passive diffusion of their undissociated forms through various biological membranes, and that the OH group of their undissociated forms interacts with the site, resulting in the occurrence of the toxicity in fish.