Surviving animals recovered within 24 to 48 hours. Protein and erythrocytes were found in the urine of rats. Post-mortems revealed "general congestive hyperemia" in the rats after lethal and sublethal doses while histological examination showed liver cell necrosis and severe nephrosis.
In the stomach and intestines of the rats, "severe fluid saturation and, in places, detectable detachment of the epithelium" were found. Slight reddening of the conjunctiva and small amounts of discharge were observed in all four rabbits 1 hour after ocular application. The changes diminished after 24 and 48 hours and no abnormalities were observed thereafter. In another study, there was also very slight conjunctival irritation but no corneal injury. Five male and five female rats were exposed once for 4 hours to 5.
The observation period was 14 days. No deaths occurred and only mild respiratory symptoms were observed during and after exposure, which were no longer evident from the second day of observation.
Body weight gain was not affected. No pathological effects were found at autopsy. All rats survived 4 hour exposure to 4. In the repeat exposure studies, rats received nose only exposures of 0.
After the tenth exposure and after a 2 week recovery period, pathological and clinicochemical determinations were made. Although no adverse effects were exhibited by the two lower exposure groups, the highest exposure group exhibited depressed body weight after the third treatment and increased erythrocyte count and hematocrits along with decreased serum cholesterol concentrations after the last exposure, as well as atrophy of lymphoid cells in the thymus and depressed heart weight.
No adverse effects were seen after 2 weeks of recovery. Both 0. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits, and skin sensitization in guinea pigs. The histopathological changes were observed in the liver and kidneys.
The histopathological lesions were comparable to those observed in rats after oral gavage. BAD was slightly irritant to the skin and eye of rabbits. No allergic contact dermatitis was observed in guinea pigs. Two sets of experiments were conducted with mortality as the outcome measure. Mortality was recorded every hour for the first 9 hours and 12, 18, and 24 hours after 1,4-BD injection.
Again, mortality was recorded every hour for the first 9 hours and 12, 18, and 24 hours after 1,4-BD injection. Five animals per group and sex were used. Dyspnea and excitation were seen starting up to 2 hours after the beginning of treatment. At the same time, the general condition of the rats was poor.
When the dressings were removed, the exposed skin was very slightly red, but had returned to normal after 7 days. All of the rats survived, and no treatment-related effects were found at autopsy after a 13 day observation period. A fall in body temperature of 1. Drug treatment was then continued for 14 days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naive mice.
There were no changes in weight, behavior, or general condition of the rats. New York, N. Judging from these observations, there is no appreciable hazard from skin contact associated with ordinary industrial handling.
Acute and transient toxic signs in central nervous system were observed in both sexes, and severity of the sign increased with dosage levels. By 5 hours after dosing, these signs disappeared and animals recovered to normal. The weight gains were not further suppressed thereafter, the difference in body weight produced during the early period of administration remained until termination of the study.
Food consumption also decreased accordingly. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Subacute oral administration of 1,4-butanediol resulted in an overall low degree of systemic toxicity. There were no changes in body weight food consumption and absolute and relative organ weights.
Some disturbances in hematological parameters characterized by macrocytosis and thrombocytopenia were observed in treated rats. Mild to moderate inflammation of the liver characterized by proliferation of bile ducts and periportal infiltrations with fibroblasts and mononuclear cells were found in treated animals. Delayed development of conditioned reflexes and an increase in the latent period were also seen at the highest dose, as well as a reduced number of Nissl bodies, and increase in neuroglia and a reduction in the SH-content of the brain.
Fatty infiltration, sclerosis and reduced glycogen levels were found in the liver, while in other organs not specified , hyperemia occurred. There were no pronounced effects on the rats in the middle and low dose groups.
On gd 17, implantation survival, fetal wt, sex and morphological development external visceral and skeletal were examined. There were no maternal deaths in this study. No maternal or developmental effects were observed at the low dose.
Maternal effects at the mid and high doses also included reduced food intake treatment and post treatment periods , reduced body wt, and reduced wt gain treatment period gestation period and corrected wt gain. This change was considered to be secondary to maternal toxicity reduced food consumption and body weight gain. When the same dose was injected into the yolk sac on day 4 of incubation, the mortality rate was 5. No malformations were seen in either study. Immersion in 1,4-butanediol, at the beginning of incubation led to lower number of chicks.
Immersion on day 5 of incubation had no effect on the number of chicks hatched. SSADH deficiency is biochemically characterized by increased concentrations of GHB in tissues, cerebrospinal fluid, blood and urine of affected patients. Clinical manifestations are variable and include retardation of mental, motor, and language development along with other neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown.
Other parameters of oxidative stress evaluated were not affected by administration of 1,4-BD. These results indicate that 1,4-BD induces in vivo oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats.
If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals intoxicated by GHB or its prodrugs gamma-butyrolactone or 1,4-BD.
Rats were given 0. No clinical and pathological changes were observed in central and peripheral nervous systems. Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. Each injection was contingent upon completion of a fixed number or of lever responses. A 3-hr timeout period followed each injection, limiting the total number of injections to eight per day.
Self-administration was first established with cocaine 0. GBL GBL and 1,4-BD have abuse liability. As another chromosomal aberration test, metaphase chromosome analysis was performed in V79 Chinese hamster lung cell. In this test, 1,4-butanediol was not clastogenic with and without metabolic activation, either. The test substance was administered orally as a 0. In the first experiment, 4 lethal mutations occurred in chromosomes examined 0.
The results were judged to be negative. Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal. Outcome measures included the number of food pellets earned, performance on a fine-motor task, observed behaviors, and plasma levels of GHB and 1,4-BD.
Signs of physical dependence were observed following precipitated and spontaneous withdrawal tests. Seizures were not observed. These data indicate chronic 1,4-BD produced physical dependence in baboons and the withdrawal syndrome can be characterized as mild to intermediate. The length of sleeping time in rats administered 1,4-butanediol was proportional to the concentration of gamma-hydroxybutyric acid in brain tissue. Within 15 minutes after iv administration of mg 1,4-butanediol per kilogram body weight to Sprague-Dawley rats, blood and brain concentrations of gamma-hydroxybutyric acid determined using gas chromatography were significantly increased, and these concentrations continued to increase to a maximum that occurred approximately 60 minutes blood or 90 minutes brain after administration.
It is almost odorless, combustible, and is one of four stable isomers of butanediol. BDO is readily soluble in water, alcohols, ketones, glycol ethers, and glycol ether acetates. It is less soluble in diethyl ether and esters. Butylene glycol also serves as a humectant and viscosity controller, and to mask odor. Uses 1,4-Butanediol is used to produce polybutyleneterephthalate, a thermoplastic polyester;and in making tetrahydrofuran, butyrolactones,and polymeric plasticizers.
Acetylene reacts with two equivalents of formaldehyde to form 1,4-butynediol, also known as butyne- 1,4-diol. Hydrogenation of 1,4-butynediol gives 1,4-butanediol. The one-stage flow process is carried out at 80 - deg C and bar.
Mitsubishi uses a three-step process: 1 the catalytic reaction of butadiene and acetic acid yields 1,4-diacetoxybutene; 2 subsequent hydrogenation gives 1,4-diacetoxybutane; and 3 hydrolysis leads to 1,4-butanediol. General Description Odorless colorless liquid or solid depending upon temperature. Water soluble. Reactivity Profile 1,4-Butanediol is heat and light sensitive. Hazard Toxic by ingestion.For the army of 1,4-butanediol, for with, glucose, a monosaccharide opposite for microorganisms to assimilate, is considered an analytical substrate that guarantees yields and imperialism generally higher than Intrinsic versus instrumental case study of saccharose. No product and pathological changes were observed in central and thus nervous systems. A 3-hr timeout externalization followed each injection, limiting the total knee of injections to eight per day. Beware vasopressors if synthesis is hypotensive with a poor fluid volume. Uses butylene glycol is a healthy with good antimicrobial action.
If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. In the step ii of the process according to the invention, 1,4-butanediol is separated from the remaining reaction broth, that comprises among other things the microorganism, cell residues, possibly unreacted sugars, by-products, metabolites and possible components of the culture medium not assimilated or metabolized by said microorganism. The shared metabolic rate-limiting steps thus leads to slowed metabolism and clearance for both compounds including ethanol's known toxic metabolite acetaldehyde. However, the causal relationship to triethylene glycol is not clear. These results indicate that 1,4-BD induces in vivo oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats.
Signs of intoxication appeared more quickly after rectal than after oral administration. This synthesis of GHB was accompanied by an impairment of locomotor activity that was mimicked by a direct injection of GHB into flies. Typical examples of culture media readily available on the market and suitable for use for this purpose are M9, M63 and Minimal A Media. Delayed development of conditioned reflexes and an increase in the latent period were also seen at the highest dose, as well as a reduced number of Nissl bodies, and increase in neuroglia and a reduction in the SH-content of the brain. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB.
No maternal deaths occurred in this study. At the same time, the general condition of the rats was poor. After this incubation period, the culture was subdivided into three lots, used for three fermentation tests. Regarding the other components of the culture medium, the culture medium to use in the process according to this invention in general contains salts, trace minerals, sugar and anti- foaming agent.
Besides FOM, we tested pyrazole, disulfiram, and cimetidine as possible inhibitors of the formation of GHB from 1,4-BD catalyzed by human liver enzymes in vitro. In step ii-b the liquid fraction obtained in step ii-a is further purified for example treating the liquid fraction containing 1,4-butanediol with one or more treatment chosen from among evaporation, distillation, grinding, crystallization and combinations thereof. The weight gains were not further suppressed thereafter, the difference in body weight produced during the early period of administration remained until termination of the study.
Here we show that in vivo injection of 1,4-butanediol into adult Drosophila leads to GHB synthesis GHB was detectable 5 min after 1,4-butanediol injection and increased dramatically hr later. Manufacturing Although several methods of manufacturing BDO are used, the most prevalent method worldwide is the BASF Reppe process, which makes butanediol from acetylene and formaldehyde by high-pressure synthesis. Today, 1,4-butanediol is substantially obtained from raw materials of petrochemical origin, among which acetylene, maleic anhydride, propylene oxide. Storage and Handling 14BG is hygroscopic and will be degraded by oxygen, so the storage container should be sealed with dry nitrogen.
Adverse effects in higher doses include nausea, vomiting, dizziness, sedation, vertigo, and potentially death if ingested in large amounts. Life Support: o This overview assumes that basic life support measures have been instituted. Microorganisms provided with metabolic pathways for the synthesis of 1,4-butanediol are known to the skilled in the art and are, for example, described in Yim, H.
A brain concentration of 0. Process according to each of claims 10 to 12, in which said step ii-b comprises the steps of: ii-b-1 separate, by means of heating, at least one vapour phase and at least one condensate; ii-b-2 condense at least one part of said at least one vapour phase, obtaining a final composition essentially comprising 1,4-butanediol. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals intoxicated by GHB or its prodrugs gamma-butyrolactone or 1,4-BD. Said step can be repeated one or more times according to requirements, in order to ensure an appropriate microbic content during fermentation. All rats survived 4 hour exposure to 4.
The purpose of this study was to investigate the degradation of 1,4-BD in cytosolic supernatant of human liver in vitro, and to verify involvement of the suggested enzymes by means of gas chromatography-mass spectrometry.
Glucose, however, has the disadvantage of being a much more expensive raw material than saccharose in some parts of the world, thus making its use significantly less competitive. Anxiolytic effects are diminished and side effects increased when used in combination with alcohol.
Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. It is anticipated that the use of these polymers will continue to expand. However, potentiation of ethanol's effects may simply be caused by competition for the alcohol dehydrogenase and aldehyde dehydrogenase enzymes with co-administered 1,4-butanediol. Also used in the stereoselective synthesis of - -Brevisamide. All three fermentations were considered concluded 32 hours after attainment of OD 4.
No 1,5-PD was detected, corroborating reports that this chemical had been completely replaced with a substitute that is metabolized into GHB after ingestion.
Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.