Structure-toxicity relationship of ethylene glycol ethers

Abstract

The ultimate purpose of the present study was to evaluate correlations between acute in vivo and in vitro toxicity and log P (P is n-octanol-water partition coefficient). The in vitro toxicity to cloned cells (neuroblastoma N18TG-2 and glioma C6) in culture (ED₅₀) and the in vivo toxicity to mice (LD₅₀) of ethylene glycol ethers were studied in terms of the structure-activity relationship. The test ethers showed a wide range of ED₅₀ values in both cells. LD₅₀ was determined under two conditions: LD₅₀-cont. was estimated in mice pretreated with olive oil and LD₅₀-CCl₄ in CCl₄-pretreated mice. Multiple regression analyses revealed a significant correlation between log 1/LD₅₀ and log P as follows: log (1/LD₅₀−cont.) = − 0.120 (log P)²+0.4871og P−1.182, and log (1/LD₅₀-CCl₄) = −0.128 (log P)²+0.5661og P−1.157. There was no significant correlation either between ED₅₀ and LD₅₀ or between ED₅₀ for N18TG-2 and ED₅₀ for C6. The results suggest that metabolic activation might not occur during acute toxicity from the ethers, and that hydrophobicity, expressed as log P, plays an important role in acute toxicity.