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 investigate d through the relation between the toxicity in vivo and each of P-ow, and Delta pK(a) (pK(a) of phenol - pK(a) of each chlorophenol). The ac ute toxicity of chlorophenols in goldfish, Carassius auratus, was eval uated as 5-h LC(50) in media (W) and 5-h LC(50) in vivo (V). The 1/W v alue steeply increased with increasing number of chlorine atoms, while the 1/V value gradually increased. The log 1/V was linearly correlate d with log P-ow (r = 0.914). A linear correlation of r = 0.805 was obs erved between log 1/V and Delta pK(a). Taking the effect of dissociati on into account, each of the V values was divided into the concentrati ons of undissociated form (V-n) and dissociated form (V-i). In groupin g chlorophenols on the basis of the position of chlorine atoms substit uted, a good linear relationship was observed between log 1/V-n and De lta pK(a) in each group in parallel. On the other hand, such a relatio nship was not observed between log 1/V-n and Delta pK(a). The parallel linear relationships showed that the suppressed magnitude of the inte raction 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 is-approximately-equal-to 2,5-DCP < 2,4,5-TCP < 2,6-DCP is-appro ximately-equal-to 2,4,6-TCP is-approximately-equal-to 2,3,4,6-TCP is-a pproximately-equal-to PCP, i.e. the suppressed magnitude increased wit h the closing of the chlorine atom position to the OH group. From thes e results, it was concluded that chlorophenols are transferred from me dia to the site of action in fish mainly by the passive diffusion of t heir undissociated forms through various biological membranes, and tha t the OH group of their undissociated forms interacts with the site, r esulting in the occurrence of the toxicity in fish.