Acute toxicity and structure-activity relationships of chlorophenols in fish

The 2.5-h LC50 values (C) of chlorophenols in goldfish, Carassius auratus were determined at pH 7.0, and taking the effect of dissociation into account, each of the values was divided into the concentrations of both undissociated form (Cn) and dissociated form (Ci). The increase of the chlorine atom number in chlorophenols enhanced the toxicity to fish, whereas in the chlorophenols having the same number of chlorine atoms, the toxicity decreased in the order of non-, mono- and di-ortho-chlorophenols. The log 1/C values were closely correlated with the log Pow values (r = 0.948). A good linear correlation (r = 0.943) was also observed between log 1/Cn and log Pow, whereas the log 1/Ci was not correlated with the log Pow (r = 0.186). These results suggested that the toxicity is enhanced by the enhanced lipophilic property with increasing number of chlorine atoms, and the undissociated form plays an important role in the transfer of chlorophenols from media to the site of action. A good linear correlation was observed between log 1/C and ΔpKa (pKa of phenol − pKa of each chlorophenol) in three groups of non-, mono- and di-ortho-chlorophenols in parallel. This result suggested that the enhanced toxicity with increasing number of chlorine atoms is attirubted to not only the increased lipophilic property as described above but also the reduced electron density of the OH group, whereas in chlorophenols having the same number of chlorine atoms, the reduced toxicity in the order of non-, mono- and di-ortho-chlorophenols is attributed to the reduction of reactivity of the OH group owing to the formation of intramolecular hydrogen bond between the OH group and the chlorine atom substituted at the ortho-position.