Disease relevance of Ethylhexanol

• Taken together, these data indicate that ethylhexanol toxicity is dependent on oxygen tension in isolated sublobular regions of the liver lobule, and therefore it is unlikely that drug delivery can explain the selective injury to periportal regions in studies with the perfused liver [1].
• Therefore, the purpose of this study was to investigate the influence of several hepatotoxic chemicals (allyl alcohol, ethylhexanol, and menadione) and hypoxia on phagocytic activity of Kupffer cells in perfused rat liver [2].
• Previous studies have shown that ethylhexanol (2-EH) and its oxidation products, but not n-hexanol, produce hepatomegaly, peroxisomal proliferation and hypotriglyceridaemia [3].
• Di(2-ethylhexyl)phthalate and 33 other phthalates, ethylhexanol derivatives, and related chemicals were tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 without metabolic activation and in the presence of rat and hamster liver S-9 metabolic activation systems [4].
• The results of this investigation indicate that DEHP, MEHP, and EH, at these dose levels, did not induce detectable chromosomal aberrations after oral administration [5].

Psychiatry related information on Ethylhexanol

• A series of contrastive experiments have illustrated that 2-ethylhexanol, PEG 400, KOH, and reaction time play an important role in the synthesis of the nanobundles [6].

High impact information on Ethylhexanol

• Other agents that increase NADH (xylitol and 2-ethyl-1-hexanol) also potentiated the stimulation of oxygen uptake due to menadione bisulfite, suggesting that ethanol was working by increasing the NADH redox state [7].
• The main metabolites of DEHP, mono(2-ethylhexyl)phthalate and 2-ethyl-1-hexanol, also caused an induction of levels of P450 4A1, lauric acid omega-hydroxylase activities and the activity of peroxisomal palmitoyl-CoA oxidase [8].
• Based on these data it is concluded that 2-ethylhexanol inhibits beta-oxidation of fatty acids in mitochondria but not in peroxisomes [9].
• This phenomenon apparently can be explained by a direct effect of ethylhexanol on mitochondria in upstream regions since active state 3 rates of respiration were inhibited by ethylhexanol in isolated mitochondria [10].
• O2-dependent hepatotoxicity due to ethylhexanol in the perfused rat liver: mitochondria as a site of action [10].

Chemical compound and disease context of Ethylhexanol

• Studies concerning the toxicity of DEHP in haemodialysis patients and other highly exposed groups should therefore include 4-heptanone together with DEHP and its primary metabolites mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol [11].
• Both the 2-ethylhexanol and 2-ethylhexanoic acid were shown to be toxic and their presence explained the increase of toxicity as the fermentations proceeded [12].

Biological context of Ethylhexanol

• In vitro promoting activity of DEHP and its hydrolysis products, mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol (EH), was studied by using promotable mouse epidermis-derived JB6 cells [13].
• In contrast, weak peroxisome proliferators and tumor promoters, di(ethylhexyl)phthalate and 2-ethylhexanol, did not affect ketogenesis, oxygen consumption, or protein kinase C at similar concentrations [14].
• These results indicate that active site mutations of P450cam can alter catalysis of 2-ethylhexanol [15].
• Indoor air pollution by 2-ethyl-1-hexanol in non-domestic buildings in Nagoya, Japan [16].
• 2-Ethylhexanol uncouples oxidative phosphorylation in rat liver mitochondria [17].

Anatomical context of Ethylhexanol

• These metabolites, together with MEHP and 2-ethylhexanol, were added to primary rat hepatocyte cultures and the effect on peroxisomal enzyme activity was determined [18].
• Therefore, we hypothesize that ethylhexanol initially uncouples oxidative phosphorylation leading to diminished ATP synthesis and collapse of ion gradients across the mitochondrial membrane [17].
• Emissions related to degradation of DEHP due to dampness in the floor, indicated by increased 2-ethyl-1-hexanol in the air, seem to increase both the secretion of lysozyme from the nasal mucosa and the occurrence of ocular and nasal symptoms [19].
• Of the 50 metaphase bone marrow cells examined from each animal, no significant increase in chromatid and chromosome breaks or structural rearrangements were noted for DEHP, MEHP, and EH [5].
• Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were tested for genetic activity in both the Salmonella/mammalian microsome mutagenicity (Ames) assay and the L5178Y TK+/- mouse lymphoma cell mutagenicity assay [20].

Associations of Ethylhexanol with other chemical compounds

• Under in vitro conditions, DEHP produced no effect on the activity of aminopyrine N-demethylase or aniline hydroxylase, while mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol (2-EH) significantly inhibited their activity at concentrations ranging from 2.5 to 15.0 mM [21].
• Although 2-ethylhexanol has been shown to induce peroxisome proliferation, it appears to be less active in this respect than the monoester of DEHP [22].
• OBJECTIVES: To evaluate the degree of exposure to and the fate of di(2-ethylhexyl)phthalate (DEHP) and its major derivatives mono(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH), and phthalic acid (PA) in patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) during a 4-hour dwell period [23].
• It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EHXO), which in turn is metabolized to 2-ethylhexanoic acid (2-EHXA), the proximate teratogen [24].
• Significant increases in linalool, nerol, furanoid cis-linalool oxide, 4-methyl-1-pentanol, 6-methyl-hept-5-en-2-ol and 2-ethylhexanol were detected in transgenic plants when compared with wild-type controls [25].

Gene context of Ethylhexanol

• 4. Ethylhexanol was a competitive inhibitor of yeast alcohol dehydrogenase, but a good substrate for horse alcohol dehydrogenase [26].
• 2-Ethylhexanol was less potent as an inducer of carnitine acetyltransferase than MEHP and the linear alcohols had no effect on this enzyme [27].
• The larger molecular weight representative of each series (i.e., 2-ethyl-1-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances [28].

Analytical, diagnostic and therapeutic context of Ethylhexanol

• 1. 2-Ethylhexanol was efficiently absorbed following oral administration to rats [26].
• Three possible metabolites (aniline, 2-ethyl-1-hexanol, and 1-amino-2-hexene) were observed during this investigation as a result of gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry [29].
• Perfusion with a higher, hepatotoxic dose of ethylhexanol (3 mM) led to a transient increase in oxygen uptake followed by a rapid inhibition of respiration of over 50% in 10 min [17].
• Mechanical ventilation was effective in the temporary reduction of indoor 2-ethyl-1-hexanol level [16].

References