Structure-toxicity Relationship of Ethylene Glycol Ethers

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1992 Jan 1

PMID 1610300

Authors

H Tanii

S Saito

K Hashimoto

Affiliations

Soon will be listed here.

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.

References

Hardin B, Eisenmann C . Relative potency of four ethylene glycol ethers for induction of paw malformations in the CD-1 mouse. Teratology. 1987; 35(3):321-8. DOI: 10.1002/tera.1420350306. View

Tanii H, Tsuji H, Hashimoto K . Structure-toxicity relationship of monoketones. Toxicol Lett. 1986; 30(1):13-7. DOI: 10.1016/0378-4274(86)90173-6. View

Tanii H, Hashimoto K . Structure-toxicity relationship of acrylates and methacrylates. Toxicol Lett. 1982; 11(1-2):125-9. DOI: 10.1016/0378-4274(82)90116-3. View

Nagano K, Nakayama E, KOYANO M, Oobayashi H, Adachi H, Yamada T . [Testicular atrophy of mice induced by ethylene glycol mono alkyl ethers (author's transl)]. Sangyo Igaku. 1979; 21(1):29-35. DOI: 10.1539/joh1959.21.29. View

Hjelle J, Grubbs J, Beer D, Petersen D . Time course of the carbon tetrachloride-induced decrease in mitochondrial aldehyde dehydrogenase activity. Toxicol Appl Pharmacol. 1983; 67(2):159-65. DOI: 10.1016/0041-008x(83)90220-x. View

Nelson B, Setzer J, Brightwell W, Mathinos P, Kuczuk M, Weaver T . Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats. Environ Health Perspect. 1984; 57:261-71. PMC: 1568279. DOI: 10.1289/ehp.8457261. View

Head B, Moody D, Woo C, SMUCKLER E . Alterations of specific forms of cytochrome P-450 in rat liver during acute carbon tetrachloride intoxication. Toxicol Appl Pharmacol. 1981; 61(2):286-95. DOI: 10.1016/0041-008x(81)90419-1. View

Fander U, Haas W, KRONER H . The damage of the hepatic mixed functional oxygenase system by CCl4: significance of incorporation of 14CCl4 metabolites in vivo. Exp Mol Pathol. 1982; 36(1):34-43. DOI: 10.1016/0014-4800(82)90077-6. View

Moss E, Thomas L, Cook M, Walters D, Foster P, Creasy D . The role of metabolism in 2-methoxyethanol-induced testicular toxicity. Toxicol Appl Pharmacol. 1985; 79(3):480-9. DOI: 10.1016/0041-008x(85)90145-0. View

10.

Tanii H, Hashimoto K . Inhibition of brain enolases by acrylamide and its related compounds in vitro, and the structure-activity relationship. Experientia. 1984; 40(9):971-2. DOI: 10.1007/BF01946464. View

11.

Ghanayem B, Burka L, Matthews H . Structure-activity relationships for the in vitro hematotoxicity of N-alkoxyacetic acids, the toxic metabolites of glycol ethers. Chem Biol Interact. 1989; 70(3-4):339-52. DOI: 10.1016/0009-2797(89)90054-9. View

12.

Tanii H, Hashimoto K . Studies on the mechanism of acute toxicity of nitriles in mice. Arch Toxicol. 1984; 55(1):47-54. DOI: 10.1007/BF00316585. View

13.

Miller R, Carreon R, Young J, McKenna M . Toxicity of methoxyacetic acid in rats. Fundam Appl Toxicol. 1982; 2(4):158-60. DOI: 10.1016/s0272-0590(82)80039-0. View