title: 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+0.487log P-1.182, and log (1/LD50-CCl4) = -0.128 (log P)2+0.566log 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.
authors.affiliation: Department of Hygiene, School of Medicine, Kanazawa University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanii
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005026:Ethylene Glycols / Q000633:toxicity*; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D006899:Mixed Function Oxygenases / Q000378:metabolism; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D005026:Ethylene Glycols; D006899:Mixed Function Oxygenases