Reference

Further studies on ketone neurotoxicity and interactions

Further studies on ketone neurotoxicity and interactions. O'Donoghue, John L.; Krasavage, Walter J.; DiVincenzo, George D.; Katz, Gary V. (Health, Saf. Hum. Factors Lab., Eastman Kodak Co., Rochester, NY 14650, USA). Toxicol. Appl. Pharmacol., 72(2), 201-9 (English) 1984. CODEN: TXAPA9. ISSN: 0041-008X. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Section cross-reference(s): 17, 62 Et n-Bu ketone (EBK) [106-35-4] given by gavage at 2 g/kg/day, 5 days/wk for 14 wk produced a typical central-peripheral distal axonopathy characterized by giant axonal swelling and neurofilamentous hyperplasia. This dose approximates the single dose LD50 (2.76 g/kg) of EBK detd. by Smyth et al., 1949. Large multiple doses (1.5 g/kg/day, 5 days/wk, 14 wk) of Me Et ketone (MEK) [78-93-3] given by gavage potentiated EBK neurotoxicity but 5-methyl-2-octanone [58654-67-4] did not, MEK modestly increased the urinary excretion of 2 neurotoxic g-diketones, 2,5-heptanedione [1703-51-1] and 2,5-hexanedione [110-13-4], when MEK was given by gavage with EBK. When rats were exposed to EBK (700 ppm) and MEK (700 or 1400 ppm) in combination by inhalation exposure, serum 2,5-heptanedione levels were increased ~2.5-fold.There are some commonly used reagents with their cas registry numbers 58654-67-4 and 110-13-4 in this article. This effect was absent at MEK levels of 700 ppm. The serum from rats exposed to EBK or EBK/MEK combinations did not contain 2,5-hexanedione. The toxicity of EBK appears to involve the metab. of EBK to 2 neurotoxic g-diketones, 2,5-heptanedione and 2,5-hexanedione. Combined EBK/MEK exposure modestly increased g-diketone levels in the serum and urine suggesting that MEK potentiates EBK neurotoxicity by stimulating the metab. of EBK to neurotoxic metabolites. The magnitude of the doses used in the present study to produce neurotoxicity and the absence of neurotoxicity in previous subchronic studies suggest that the neurotoxic hazard of EBK is low. .

Metabolism of branched medium chain length fatty acid

Metabolism of branched medium chain length fatty acid. 11. b-Oxidation of sodium dipropylacetate in rats. Matsumoto, Isamu; Kuhara, Tomiko; Yoshino, Makoto (Sch. Med., Kurume Univ., Kurume, Japan). Biomed. Mass Spectrom., 3(5), 235-40 (English) 1976. CODEN: BMSYAL. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Section cross-reference(s): 13 Urine exts. from rats treated with sodium dipropylacetate (I) [1069-66-5] were examd. by gas chromatog.-mass spectrometry for catabolic intermediates. Unmetabolized I, succinic acid [110-15-6], EtCH(OH)CHPrCO2H (II) [58888-84-9], MeCH(OH)CH2CHPrCO2H [60113-82-8], EtCOCHPrCO2H (III) [60113-81-7], HO(CH2)3CHPrCO2H [53660-23-4], adipic acid [124-04-9], 2-propylglutaric acid [32806-62-5], dipropylacetic acid glucuronide [60113-83-9], EtCO2H [79-09-4], and BuCOEt [106-35-4] were identified in the urine. Admin. of I with isoleucine to rats resulted in the disappearance of III and a large decrease in the amt. of II from the urine, indicating that b-oxidn. was involved in the metabolism of I together with glucuronide conjugation and w-oxidn.