Effects of ethylene glycol and metabolites on in vitro development of rat embryos during organogenesis.
The aim of this study was to investigate in vitro the relative impact of ethylene glycol, a major industrial chemical, and its individual metabolites on the embryonic development of rats. Rat whole embryos were exposed for 48 h (day 9.5-11.5 of gestation) to ethylene glycol (EG) and its metabolites glycolaldehyde (GAl), glycolic acid (GA), glyoxylic acid (GXA), glyoxale (GXAl) and oxalic acid (OXA) at increasing concentrations. Embryotoxic concentrations were achieved within the following range: ethylene glycol (100-200 mM), glycolic acid (3 mM), glyoxal (6 mM), oxalic acid (1-3 mM), glyoxylic acid (0.3-1 mM), glycolaldehyde (0.1-0.2 mM). The pattern of dysmorphogenesis with all compounds including EG showed a general embryotoxicity with diffusely distributed cell necroses with no specific target tissues selectively affected. The results obtained in this study emphasize the hypothesis that the metabolites and not ethylene glycol itself are responsible for the embryotoxicity of ethylene glycol in rats.
Klug
S
S
Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Garystrasse 5, 14195, Berlin, Germany. stephan.klug@medizin.fu-berlin.de
Merker
H J
HJ
Jäckh
R
R
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D000826:Animal Testing Alternatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D019855:Ethylene Glycol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D006016:Glycolates / Q000633:toxicity; D006037:Glyoxal / Q000633:toxicity; D006038:Glyoxylates / Q000633:toxicity; D009924:Organ Culture Techniques; D019815:Oxalic Acid / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000378:metabolism / Q000633:toxicity*
D006016:Glycolates; D006038:Glyoxylates; D013723:Teratogens; C031149:glycolic acid; D006037:Glyoxal; D019815:Oxalic Acid; D019855:Ethylene Glycol; D000079:Acetaldehyde; C031150:glyoxylic acid; C010972:glycolaldehyde