Disease relevance of NSC 10980

• Recently, we have shown that butoxyacetic acid (BAA) is the proximate hemolytic agent and that inhibition of alcohol or aldehyde dehydrogenases protected rats against BE-induced hemolytic anemia [1].
• When 2-butoxyethanol (2-BE) is administered to rats, hemolysis occurs as the active metabolite butoxyacetic acid (BAA) is formed [2].
• BE and its oxidation products, butoxyacetaldehyde (BAL) and butoxyacetic acid (BAA), are mainly associated with haemolytic toxicity [3].
• Neurotoxicity, acidosis, and butoxyacetic acid persisted after hemodialysis [4].
• 2-Butoxyacetic acid was incubated with red blood cells from healthy young and older individuals and with red blood cells from patients with hereditary spherocytosis and sickle cell disease [5].

High impact information on NSC 10980

• No increase in DNA damage was observed following 2-butoxyethanol (1-10mM), 2-butoxyacetaldehyde (0.1-1.0mM), or 2-butoxyacetic acid (1-10mM) in endothelial cells after 2, 4, or 24 h of exposure [6].
• 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 [6].
• 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 [6].
• The present study used Syrian Hamster Embryo (SHE) cell transformation, a surrogate in vitro model for carcinogenesis in vivo, to examine whether 2-butoxyethanol, 2-butoxyacetic acid, or iron (ferrous sulfate) produced cell transformation [7].
• In vitro sub-hemolytic effects of butoxyacetic acid on human and rat erythrocytes [2].

Biological context of NSC 10980

• A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid [8].
• Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans [8].
• It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data [8].
• In conclusion, we propose that total butoxyacetic acid (after acid hydrolysis) in urine is the biomarker of choice for monitoring exposure to 2-butoxyethanol [9].
• No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume [10].

Anatomical context of NSC 10980

• Further, in vitro incubation of blood obtained from BE-pretreated/recovered with the hematotoxic metabolite of BE, 2-butoxyacetic acid (BAA), revealed that erythrocytes obtained from these rats were significantly less sensitive to BAA than those obtained from normal rats [11].

Associations of NSC 10980 with other chemical compounds

• HPLC analysis of the urinary metabolites of BE in adult and young rats showed that the ratio of butoxyacetic acid (BAA)/BE-glucuronide + BE - sulfate (previously thought to reflect an activation/detoxification index of BE; see text) was significantly higher in older rats [12].
• A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans [8].
• The method developed in this study provides a procedure for the simultaneous urinalysis of methoxyacetic acid (MAA), ethoxyacetic acid (EAA), butoxyacetic acid (BAA), oxalic acid (OA), 2-methoxypropionic acid (2-MPA) and 2-ethoxypropionic acid (2-EPA) [13].
• 2-[(2H(9))Butoxy]acetic acid and 2-(3-methylbutoxy)acetic acid were synthesized, mixed with 2-butoxyacetic acid, and separated by capillary gas chromatography on a fused-silica column with a length of 50 m, inside diameter of 0.200 mm, and a "free fatty acid phase" wall coating of 0.3 microm film [14].

Analytical, diagnostic and therapeutic context of NSC 10980

• Qualitative and quantitative HPLC analysis of the urinary and biliary metabolites of BE revealed that the major urinary metabolite, butoxyacetic acid (BAA), accounted for more than 75% of the radioactivity excreted in the urine [15].
• Urine was collected for 24 h and analyzed for the metabolite butoxyacetic acid, also by gas chromatography [16].
• New methods for determination of 2-butoxyethanol, butoxyacetaldehyde and butoxyacetic acid in aqueous systems, with special reference to cell culture conditions [3].
• Free and total urinary 2-butoxyacetic acid following dermal and inhalation exposure to 2-butoxyethanol in human volunteers [17].

References