Metabolism / Metabolites
Butanediol is metabolized by the liver... beta-hydroxybutyric acid /a main metabolite/ is further metabolized in the tricarboxylic acid cycle to carbon dioxide, which accounts for about 90% of the dose administered. In other studies... in which rats were fed 1,3-butanediol for 3 to 7 weeks, it was found that the blood level of beta-hydroxybutyrate, was also higher than normal.
R- and S-1,3-butylene glycol are taken up by the isolated liver of fed or starved rats at the same rate. R-1,3-butylene glycol is mainly transformed to the physiological ketone bodies R-3-hydroxybutyrate and acetoacetate. Only 29-38&% of the S-enantiomer are converted into physiological ketone bodies. The S-enantiomer is further metabolised to S-3-hydroxybutyrate (not a natural compound), lipids and carbon dioxide. Based on these results it can be concluded that the test item is metabolised via physiological pathways, suggesting that it has a low potential to accumulate.

Toxicity Summary
IDENTIFICATION AND USE: 1,3-Butanediol is an odorless, colorless, viscous liquid with a sweet flavor and bitter aftertaste. It is used as an intermediate in manufacture of polyester plasticizers; humectant for cellophane, tobacco; and in the cosmetic and pharmaceutical industry as a glycerin substitute.1,3-Butanediol also has some mold inhibiting action. It is not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: 1,3-Butanediol is not irritating to human skin or mucous membranes. When applied to the human eye it causes immediate severe stinging, but irrigation with water brings rapid complete relief. ANIMAL STUDIES: Eye irritation occurred in one individual, although its irritant potency in rabbits appeared low. It was of low acute oral toxicity to rodents. No treatment-related effects on mortality, body weight gain, organ weights, hematology, histopathology or neoplastic changes were observed in rats fed 1,3-butanediol in the diet at 1, 3 or 10% (~ 643, 1960 or 6230 mg/kg-bw/day for males or ~ 844, 2330 or 7300 mg/kg-bw/day for females) for two years. Feeding studies in which 1,3-butylene glycol replaced carbohydrate as an energy source found central nervous system effects in rats, dogs and calves. 1,3-Butanediol decreased glucose and increased beta-hydroxybutyrate in lactating goats fed 1,3-butanediol in their diets.1,3-Butylene glycol was fetotoxic when fed to rats during pregnancy, and a multigeneration feeding study in rats gave some indication of reduced male fertility. No genotoxic activity (dominant lethality or chromosomal damage) was seen in rats treated orally.

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Interactions
1,3-Butanediol and phlorhizin were used to induce ketonemia and hypoglycemia in steers. Oral administration of butanediol increased blood beta-hydroxybutyrate (BHB) and plasma nonesterified fatty acids (NEFA) and decreased serum glucose. Subcutaneous injections of phlorhizin, given in addition to butanediol orally, further increased NEFA and BHB concentrations and decreased glucose. Dietary niacin supplementation of steers given phlorhizin and butanediol caused serum glucose concentration to increase and blood BHB and plasma NEFA concentrations to decrease.
Evidence previously reported suggest that 1,3-butanediol (BD) enhances the hepatotoxic effect of a single small dose of carbon tetrachloride (CCl4) in a dose-related manner. The present study provides additional information concerning the quantitative relationship between the severity of the ketotic state produced by BD and the magnitude of the potentiation observed and emphasizes the use of ketone bodies (KB) to predict the potential hazard of the BD-CCl4 interaction. Liver damage was modulated in male Sprague-Dawley rats by varying the concentration of the BD solutions ingested prior to a CCl4 challenge (0.1 ml/kg, i.p.). These data were compared to ketone bodies in plasma, hepatic tissue and urine. BD produced a dose-dependent metabolic ketosis observable at dosages between 1.1 and 9.9 g/kg per day given for 7 days. Plasma and liver data correlated well together. Concomitantly, potentiation of the CCl4-induced liver injury was also dose-related for the same dosage range; the minimum effective dosage of BD for potentiation was estimated as 1.1 g/kg per day. The linear correlations between hepatic or plasma KB values and the indices of hepatic dysfunction (ALT, OCT) were highly significant. Using a semiquantitative method, a correlation was also found for the urinary KB data. These results suggest that plasma KB concentrations might be useful for predicting possible potentiation of the hepatonecrotic effect of CCl4 by BD.
For 28 days, four steers received l,3-butanediol, which causes ketonemia, and phlorizin, which causes glucosuria. Steers also were fasted for 9 days. Effects of treatments on concentrations of metabolites in blood and liver and on kinetics of glucose metabolism were determined. Treatments were: control, control with dietary butanediol plus injected phlorizin, and fasting. Fasting caused hypoinsulinemia and decreased liver glycogen by 60%. Butanediol plus phlorizin and fasting caused 18% and 19% decreases of plasma glucose and 2.5- and 6-fold increses of free fatty acid concentrations in blood plasma. Glucose irreversible loss averaged 371, 541, and 182 g/day during control, butanediol plus phlorizin treatment, and fasting. Butanediol plus phlorizin increased-liver ketone body concentrations, caused glucosuria, ketonuria, and ketonemia, but did not affect insulin, glucagon, or growth hormone concentrations in plasma or triglyceride and glycogen contents in liver. Steers given butane plus phlorizin did not show all the usual signs of lactation ketosis, but the treatment still offers promise for studying causes and effects of ketosis.
Rats maintained on 1,3-butanediol exhibit potentiated cholestatic responses to taurolithocholate or manganese-bilirubin injections; with alpha-naphthylisothiocyanate, the hyperbilirubinemia is enhanced but not the depression in bile flow.

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Non-Human Toxicity Values
LD50 Rat oral 22800 mg/kg.
LD50 Mice sc 16.5 mL/kg
LD50 Rat sc 20.1 mL/kg
LD50 Guinea pig oral 11 g/kg
For more Non-Human Toxicity Values (Complete) data for 1,3-BUTANEDIOL (6 total), please visit the HSDB record page.

[1]. Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study. J Cereb Blood Flow Metab. 1987 Dec;7(6):794-800.

[2]. Nutritional and metabolic studies in humans with 1,3-butanediol. Fed Proc. 1975 Nov;34(12):2171-6.

Butane-1,3-diol is a butanediol compound having two hydroxy groups in the 1- and 3-positions. It is a butanediol and a glycol.
1,3-Butanediol is found in pepper (c. annuum). 1,3-Butanediol is a solvent for flavouring agents 1,3-Butanediol is an organic chemical, an alcohol. It is commonly used as a solvent for food flavouring agents and is a co-monomer used in certain polyurethane and polyester resins. It is one of four stable isomers of butanediol. In biology, 1,3-butanediol is used as a hypoglycaemic agent. 1,3-Butanediol belongs to the family of Secondary Alcohols. These are compounds containing a secondary alcohol functional group, with the general structure HOC(R)(R') (R,R'=alkyl, aryl).
See also: Avobenzone; butylene glycol (component of) ... View More ...

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Therapeutic Uses
/EXP THER/ This study examined the effect of 1,3-butanediol on the selective loss of CA1 pyramidal neurons following a short period of near-complete forebrain ischemia. Injection of 55 mmol 1,3-butanediol/kg body weight at 24 h of recirculation and again at 36 hr following 10 min of forebrain ischemia markedly reduced damage to CA1 neurons examined at 72 hr of recirculation compared with that in saline-treated rats. Comparable treatment with ethanol did not cause significant protection. Neuronal loss was also not reduced by 1,3-butanediol treatment when the ischemic period was extended to 15 min or by single treatments at 24 hr or 36 hr following 10 min of ischemia. However, a single treatment 5 min after reversal of 10 min of ischemia was effective in ameliorating cell loss. The difference in effectiveness of 1,3-butanediol following 10 min and 15 min of ischemia is consistent with a number of previous studies, indicating that the processes leading to loss of CA1 neurons are modified when the ischemic period is extended. Previous findings that 1,3-butanediol reduced damage in other ischemia-susceptible neuronal subpopulations but not in CA1 neurons most likely reflected the longer period of ischemia which was used. The results of the present investigation demonstrate that administration of 1,3-butanediol offers a novel approach for interfering with post-ischemic loss of CA1 neurons following a brief ischemic period which is effective even when initiated after prolonged recirculation periods.
/EXP THER/ The biochemical effect of S-1,3-butanediol on streptozotocin induced diabetic rats was studied. Rats were made diabetic by the intraperitoneal injection of 40 mg/kg body weight streptozotocin in sodium citrate buffer. A dosage of 25 mmol/kg body weight of S-1,3-butanediol was injected intraperitoneally for treatment. The streptozotocin induced diabetic rats showed a marked increase in blood glucose level, and significant increase in the level of cholesterol, triglycerides and free fatty acids. The glycogen levels in liver and kidney were greatly decreased in diabetic rats. Treatment with butanediol normalized the glucose and glycogen level but had no significant effect on protein and lipid levels.
/EXP THER/ We previously showed that intrastriatal administration of aminooxyacetic acid (AOAA) produces striatal lesions by a secondary excitotoxic mechanism associated with impairment of oxidative phosphorylation. In the present study, we show that and the specific complex I inhibitor rotenone produces a similar neurochemical profile in the striatum, consistent with an effect of AOAA on energy metabolism. Lesions produced by AOAA were dose-dependently blocked by MK-801, with complete protection against GABA and substance P depletions at a dose of 3 mg/kg. AOAA lesions were significantly attenuated by pretreatment with either 1,3-butanediol or coenzyme Q10, two compounds which are thought to improve energy metabolism. These results provide further evidence that AOAA produces striatal excitotoxic lesions as a consequence of energy depletion and they suggest therapeutic strategies which may be useful in neurodegenerative diseases.
/EXP THER/ In order to assess the therapeutic value of 1,3 butanediol in ethylene glycol toxicosis, mixed-bred dogs were given an oral dose of commercial antifreeze at 6 mL/kg of body weight (0 hour) and treated (IV) 7 times at 6-hour intervals with 5.5 mL/kg of body weight 1,3 butanediol solution (20% in physiological saline solution) beginning at 8, 12, and 21 hours. Serum glycolic acid concentration was quantitated by high-pressure liquid chromatography. Three dogs that were given ethylene glycol, but no 1,3 butanediol treatment, died with elevated serum glycolic acid concentrations. Five dogs were given ethylene glycol and 1,3 butanediol treatment. Of 2 dogs treated at 8 hours, 1 survived and 1 died at 39 hours; 1 treated at 12 hours and 1 treated at 21 hours survived; 1 dog died soon (27 hours) after treatment was initiated at 21 hours. Four of the 5 dogs had dramatically decreased serum glycolic acid concentrations after 1,3 butanediol treatment, indicating its effectiveness in inhibiting alcohol dehydrogenase-dependent glycolic acid formation in vivo.
/EXP THER/ Pre-partum feeding of 1,3-butanediol to sows has been shown to improve the metabolic status and survival rate of neonatal pigs. To evaluate the efficacy of short-term, pre-partum feeding of 1,3-butanediol on pig and sow productivity on a large scale and low concentration was the focus of the research. The secondary objective was to determine if pre-partum feeding of 1,3-butanediol had any effect on survival rate and weight gain of lesser body weight pigs, sow body weight and subsequent sow reproductive performance. In a large commercial unit, 2537 sows were fed one of two pre-partum diets (0% or 4.55% 1,3-butanediol) on Day 108+/-3 of pregnancy. 1,3-butanediol provided 8% of the total metabolizable energy. Pigs born live in those litters were equalized by cross-fostering among sows receiving the same pre-partum diet. Pigs were weaned from the sows at 16+/-3 days post-partum and return of sows to estrus and conception rates were determined. Pre-partum feeding of 1,3-butanediol reduced (P=0.01) pre-weaning pig mortalities from 1.44 to 1.24 pigs per litter. The reduction in pig mortality was independent of length of 1,3-butanediol feeding (4 to 11 days). In a subset of 750 litters, four lesser birth-weight pigs from each litter were tagged and monitored to determine the effect of 1,3-butanediol on survival rates and pre-weaning weight gain of pigs with the greatest mortality risk. 1,3-butanediol reduced (P=0.01) pre-weaning mortality of these low birth weight pigs by 5.27%. Based on these data, short-term pre-partum feeding of 1,3-butanediol effectively improves pre-weaning pig productivity at a lower concentration than previously reported.

C4H10O2

90.12

90.068

107-88-0

(R)-(-)-1,3-Butanediol;6290-03-5

7896

Viscous liquid
Pure compound is colorless

1.0±0.1 g/cm3

207.0±0.0 °C at 760 mmHg

-54ºC

121.1±0.0 °C

0.1±0.8 mmHg at 25°C

1.438

-0.69

2

2

2

6

28.7

0

O([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O[H]

PUPZLCDOIYMWBV-UHFFFAOYSA-N

InChI=1S/C4H10O2/c1-4(6)2-3-5/h4-6H,2-3H2,1H3

butane-1,3-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ≥ 500 mg/mL (5548.16 mM)
DMSO: 100 mg/mL (1109.63 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (27.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (27.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 1.72 mg/mL (19.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.2 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)