Disease relevance of Ethylene glycol butyl ether

• Acute exposure to 2-butoxyethanol (BE) causes dose- and age-dependent hemolytic anemia in rats [1].
• 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration [2].
• Additional studies examined the involvement of hemolysis and macrophage activation in 2-butoxyethanol carcinogenesis [3].
• Exposure of rats to 2-butoxyethanol (BE) has been associated with hemolytic anemia, disseminated thrombosis, and infarction in multiple organs including bone [4].
• Mechanisms of 2-butoxyethanol-induced hemangiosarcomas [3].

High impact information on Ethylene glycol butyl ether

• The U.S. National Toxicology Program (NTP) has completed 2-yr inhalation exposures in rats and mice with 2-butoxyethanol (BE) [5].
• Alteration in methyl-methanesulfonate-induced poly(ADP-ribosyl)ation by 2-butoxyethanol in Syrian hamster embryo cells [6].
• Effects of dose, age, inhibition of metabolism and elimination on the toxicokinetics of 2-butoxyethanol and its metabolites [1].
• Hemolyzed RBCs also activated macrophages, as evidenced by increased tumor necrosis factor (TNF) alpha, while neither 2-butoxyethanol nor butoxyacetic acid increased TNF-alpha from macrophages [3].
• 2-Butoxyethanol is metabolized to 2-butoxyacetaldehyde and 2-butoxyacetic acid, and although the aldehyde metabolite is short lived, the potential exists for this metabolite to cause DNA damage [3].

Chemical compound and disease context of Ethylene glycol butyl ether

• Recent work in this laboratory indicated that 2-butoxyethanol (BE) causes acute hemolytic anemia in rats, and activation of BE to butoxyacetic acid (BAA), presumably through the intermediate 2-butoxyacetaldehyde (BAL), is a prerequisite for development of hematotoxicity [7].
• Eruptive cherry angiomas and irritant symptoms after one acute exposure to the glycol ether solvent 2-butoxyethanol [8].
• For tissue processed at low temperatures into GMA, using ethanol dehydration, the following compounds were as satisfactory as 2-butoxyethanol whilst being less toxic: 2-isopropoxyethanol, 2-(2-methoxyethoxy)ethanol, 2-(2-ethoxyethoxy)ethanol, 2-(n-butoxyethoxy)ethanol [9].
• Three compounds (2-butoxyethanol, p-nitroaniline, and para-chloroaniline) were associated with a relatively high incidence of Kupffer cell pigmentation consisting of hemosiderin in both sexes; only the male mice developed a relatively low incidence of treatment-related hemangiosarcoma [10].

Biological context of Ethylene glycol butyl ether

• This toxic effect, coupled with the observation that continued treatment with 2-butoxyethanol results in hemosiderin deposition in the liver, has led to our hypothesis that liver carcinogenicity by 2-butoxyethnaol is mediated via oxidative stress (iron catalyzed) and Kupffer cell activation [11].
• An increase in hemolysis (measured by a decrease in hematocrit and increase in relative spleen weight) was observed in 2-butoxyethanol-treated rats and mice in a dose-dependent manner [12].
• These data demonstrate that 2-butoxyethanol and related metabolites do not directly cause DNA damage [3].
• No apparent differences in apoptosis and mitosis in the liver were observed in mouse and rat liver between 2-butoxyethanol treatment groups and untreated controls [12].
• Chronic inhalation studies with 2-butoxyethanol (BE) conducted by the National Toxicology Program identified the forestomach and liver of B6C3F1 mice as target organs for tumorigenicity (NTP, 2000) [13].

Anatomical context of Ethylene glycol butyl ether

• Butoxyethanol (BE) causes anemia and lowered hematocrits in rats due to direct hemolysis of red blood cells [14].
• These results suggest that DNA synthesis, possibly from oxidative stress or Kupffer cell activation, occurs selectively in the mouse liver, primarily in endothelial cells (a target of 2-butoxyethanol neoplasia), following exposure to 2-butoxyethanol [12].
• Hepatic effects of 2-butoxyethanol in rodents [12].
• An increase in the percentage of iron-stained Kupffer cells was observed following treatment with 450 and 900 mg/kg of 2-butoxyethanol in mice and 225 and 450 mg/kg of 2-butoxyethanol in rats [12].
• 2-Butoxyethanol has been examined for genotoxic activity in a range of in vitro and in vivo assays, including the mouse bone marrow micronucleus assay [15].

Associations of Ethylene glycol butyl ether with other chemical compounds

• The present study examined whether 2-butoxyethanol and its metabolites, 2-butoxyacetaldehyde and 2-butoxyacetic acid, damaged mouse endothelial cell DNA using the comet assay [3].
• Mutagenicity and cytotoxicity of 2-butoxyethanol and its metabolite, 2-butoxyacetaldehyde, in Chinese hamster ovary (CHO-AS52) cells [16].
• Rat spleen and thymus tissues were fixed by immersion in fixatives containing different concentrations of paraformaldehyde, washed in sucrose phosphate buffer, dehydrated in acetone, infiltrated in a glycol methacrylate mixture in which the commonly used softener 2-butoxyethanol was replaced by butaandiol monoacrylate, and embedded [17].
• Although CVds and CSVd could not be detected in NA-PEX by RT-PCR, they were detected after further purification: differential precipitation with 2-butoxyethanol and HCl treatment followed by ethanol-precipitation [18].
• Toxicokinetics of inhaled 2-butoxyethanol (ethylene glycol monobutyl ether) in man [19].

Gene context of Ethylene glycol butyl ether

• Ocular expression of vascular cell adhesion molecule (VCAM-1) in 2-butoxyethanol-induced hemolysis and thrombosis in female rats [20].
• Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases [21].
• 2-Butoxyacetic acid was more potent than 2-butoxyethanol, the NOEL for the former being 50 mg/kg and for the latter, 150 mg/kg [22].
• Our working hypothesis is that the mode of action of butoxyethanol-induced mouse liver hemangiosarcomas and hepatic neoplasia involves the metabolism of 2-butoxyethanol to butoxyacetic acid which results in the induction of RBC hemolysis [23].
• Urinary BAA excretion of 75 mmol/mol creatinine in postshift urine corresponded to an 8-h 2-butoxyethanol and 2-butoxyethylacetate exposure of 5 cm3/m3 [24].

Analytical, diagnostic and therapeutic context of Ethylene glycol butyl ether

• These collected considerations indicate that 2-butoxyethanol is unlikely to be a genotoxic carcinogen to rodents, a prediction that supplements seventeen published predictions of the outcome of the ongoing NTP rodent carcinogenicity bioassays [15].
• Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol [25].
• Hemodialysis following butoxyethanol ingestion [26].
• Arterialized capillary blood samples were collected from the other hand before, during, and up to 4 h after the exposure and analyzed for butoxyethanol by gas chromatography [27].
• Human repeated insult patch test of 2-butoxyethanol [28].

References