(2E,4Z,6R,8Z,10E,14E,17S,18E,20Z)-20-(Carboxymethyl)-6-methoxy-2,5,17-trimethyl-2,4,8,10,14,18,20-docosaheptaenedioic acid

486.6

486.60

231-791-2

L7V4I673D2

White amorphous solid

121.13000

5.88560

1.114±0.06 g/cm3(Predicted)

50-60°

715.1±60.0 °C(Predicted)

231ºC

1.545

In water, 0.002 mg/L at 25 °C (est)

−20°C

3.9X10-15 mm Hg at 25 °C (est)

LD50 i.v. in mice: 1.41 mg/kg (Lijmbach)

D25 +162.5°

pKa 1 = 3.94; pKa 2 = 4.48; pKa 3 = 4.99 (est)

NONH for all modes of transport

Stable under recommended storage conditions.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. For personal protection see section Environmental precautions: No special environmental precautions required. Methods and materials for containment and cleaning up: Keep in suitable, closed containers for disposal

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|Appropriate engineering controls: General industrial hygiene practice.|ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. For personal protection see section Environmental precautions: No special environmental precautions required.

IDENTIFICATION AND USE: Bongkrekic acid (BA) is a white amorphous solid. BA is known to be produced by the bacterium Burkholderia gladioli pv. cocovenenans. It is used as a tool in biochemical research. HUMAN STUDIES: In a rural town in Mozambique, >230 persons became sick and 75 died of an illness linked to drinking pombe, a traditional alcoholic beverage. Toxic levels of BA were detected in the suspect pombe but not the control pombe. Burkholderia gladioli pathovar cocovenenans, the bacteria that produces BA, was detected in the flour used to make the pombe. BA is an inhibitor of adenine nucleotide translocase (ANT). Since inhibition of ANT is connected to the inhibition of cytochrome c release from mitochondria, which then results in the suppression of apoptosis, it has been used as a tool for the mechanistic investigation of apoptosis. BA has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. ANIMAL STUDIES: BA, a potent inhibitor of the mitochondrial ATP/ADP translocase, inhibits glucose-induced electrical activity in the pancreatic beta-cell through the stimulation of ATP-sensitive potassium channel (K-ATP-channel) activity.

The in vitro effect of bongkrekic acid on stem bromelain, papain and ficin was studied. The hydrolysis of casein by these enzymes was inhibited by bongkrekic acid, but the inhibition was always incomplete even with a large excess of the effector. Using a fully activated specimen of stem bromelain, purified on an organomercurial agarose affinity column, the inhibition by bongkrekic acid was not stoichiometric. The SH group of cysteine remained intact after incubation with an excess of bongkrekic acid at 24 degrees C for 20 min. However, partial inhibition of stem bromelain by bongkrekic acid was reversed by incubation at 37 degrees C for 5 min with 5 mM cysteine or 2-mercaptoethanol. Ethylene glycol and glycerol had no such restorative effect. These results indicate that molecules of bongkrekic acid are non-covalently bound to a thiol protease, only partially and reversibly shielding its essential SH group.

LD50 Mice iv 1.4 mg/kg|LD50 Mice oral 3.16 mg/kg /Purified Flavotoxin A/

Bongkrekic acid is an antibiotic produced by the bacterium Burkholderia gladioli otherwise known as Pseudomonas cocovenenans(1,2).

Bongkrekic acid's production and use as a laboratory chemical for the synthesis of substances(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of >5000(SRC), determined from a structure estimation method(2), indicates that bongkrekic acid is expected to be immobile in soil(SRC). The estimated pKa values of bongkrekic acid are 3.94, 4.48 and 4.99(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Bongkrekic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2018).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of >5000(SRC), determined from a structure estimation method(2), indicates that bongkrekic acid is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 3.94, 4.48 and 4.99(3), indicate bongkrekic acid will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 1.8(SRC), from an estimated log Kow of 7.06(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2018).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bongkrekic acid, which has an estimated vapor pressure of 3.9X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase bongkrekic acid may be removed from the air by wet and dry deposition(SRC). Bongkrekic acid contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Bongkrekic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Bongkrekic acid contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 1.8 was calculated in fish for bongkrekic acid(SRC), using an log Kow of 7.06(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bongkrekic acid can be estimated to be >5000(SRC). According to a classification scheme(2), this estimated Koc value suggests that bongkrekic acid is expected to be immobile in soil. The estimated pKa values of bongkrekic acid are 3.94, 4.48 and 4.99(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

Estimated pKa values of 3.94, 4.48 and 4.99(1) indicate bongkrekic acid will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Bongkrekic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-15 mm Hg(SRC), determined from a fragment constant method(2).

Bongkrekic acid has been isolated as one of the toxins in Pseudomonas cocovenenans which has been found on the coconut food product bongkrek in Indonesia; this was related to outbreaks of fatal food poisonings(1). In 2015, bongkrekic acid, and its structural isomer isobongkrekic acid, were detected at potentially fatal levels in a traditional homebrew African beer called pombe; the microorganisms (Burkholderia gladioli pv. cocovenenans) that produced the toxin were isolated from corn flour at the brewer's home, the starting ingredient for the pombe(2).

Occupational exposure to bongkrekic acid may occur through dermal contact with this compound at workplaces where bongkrekic acid is produced or used. Use and limited monitoring data indicate that the general population is not likely to be exposed to bongkrekic acid; exposure may occur via ingestion of food or beverages contaminated with bongkrekic acid. (SRC)

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Bongkrekic acid (BKA) is an inhibitor of adenine nucleotide translocase (ANT). Since inhibition of ANT is connected to the inhibition of cytochrome c release from mitochondria, which then results in the suppression of apoptosis, it has been used as a tool for the mechanistic investigation of apoptosis. BKA consists of a long carbon chain with two asymmetric centers, a nonconjugated olefin, two conjugated dienes, three methyl groups, a methoxyl group, and three carboxylic acids. This complicated chemical structure has caused difficulties in synthesis, supply, and biochemical mechanistic investigations.|Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/CASE REPORTS/ In January 2015, 75 people died and 177 were hospitalized in the Mozambique village of Chitima after attending a funeral. The deaths were linked to the consumption of a traditional African beverage called pombe. Samples of the suspect pombe were subjected to myriad analyses and compared to a control sample. Ultimately, non-targeted liquid chromatography-mass spectrometry screening revealed the presence of the potent toxin bongkrekic acid, and its structural isomer, isobongkrekic acid. Quantitative analysis found potentially fatal levels of these toxins in the suspect pombe samples. Bongkrekic acid is known to be produced by the bacterium Burkholderia gladioli pv. cocovenenans. This bacterium could not be isolated from the suspect pombe, but bacteria identified as B. gladioli were isolated from corn flour, a starting ingredient in the production of pombe, obtained from the brewer's home. When the bacteria were co-plated with the fungus Rhizopus oryzae, which was also isolated from the corn flour, synergistic production of bongkrekic acid was observed. The results suggest a mechanism for bongkrekic acid intoxication, a phenomenon previously thought to be restricted to specific regions of Indonesia and China.|/CASE REPORTS/ BACKGROUND: On 9 January 2015, in a rural town in Mozambique, >230 persons became sick and 75 died of an illness linked to drinking pombe, a traditional alcoholic beverage. METHODS: An investigation was conducted to identify case patients and determine the cause of the outbreak. A case patient was defined as any resident of Chitima who developed any new or unexplained neurologic, gastrointestinal, or cardiovascular symptom from 9 January at 6:00 am through 12 January at 11:59 pm. We conducted medical record reviews, healthcare worker and community surveys, anthropologic and toxicologic investigations of local medicinal plants and commercial pesticides, and laboratory testing of the suspect and control pombe. RESULTS: We identified 234 case patients; 75 (32%) died and 159 recovered. Overall, 61% of case patients were female (n = 142), and ages ranged from 1 to 87 years (median, 30 years). Signs and symptoms included abdominal pain, diarrhea, vomiting, and generalized malaise. Death was preceded by psychomotor agitation and abnormal posturing. The median interval from pombe consumption to symptom onset was 16 hours. Toxic levels of bongkrekic acid (BA) were detected in the suspect pombe but not the control pombe. Burkholderia gladioli pathovar cocovenenans, the bacteria that produces BA, was detected in the flour used to make the pombe. CONCLUSIONS: We report for the first time an outbreak of a highly lethal illness linked to BA, a deadly food-borne toxin in Africa. Given that no previous outbreaks have been recognized outside Asia, our investigation suggests that BA might be an unrecognized cause of toxic outbreaks globally.|/ALTERNATIVE and IN VITRO TESTS/ BACKGROUND/AIM: An in vitro cell model of long-term estrogen-deprived MCF-7 (LTED) cells has been utilized to analyze the re-growth mechanisms of breast cancers treated with blockers for estrogen receptor a (ERa) signaling. Bongkrekic acid (BKA) is a natural toxin isolated from coconut tempeh contaminated with the bacterium Burkholderia cocovenans. MATERIALS AND METHODS: LTED cells, MCF-7 cells and MDA-MB-231 cells were employed in the study. After treatment with BKA (chemically synthesized; purity: >98%), several biochemical analyses were carried out. RESULTS: LTED cells were categorized into an oxidative phenotype. When LTED cells were treated with BKA, lactate dehydrogenase A (LDH-A)/pyruvate dehydrogenase kinase 4 (PDK4) were down-regulated, thereby prompting the aggressive use of glucose via mitochondrial oxidative phosphorylation and induction of cell death responses. These effects of BKA were not observed in the other breast cancer cells analyzed. CONCLUSION: We suggest the potential of BKA as an experimental tool for the analysis of cancer biology in LTED cells.|/ALTERNATIVE and IN VITRO TESTS/ Bongkrekic acid (BKA) is an inhibitor of adenine nucleotide translocase (ANT). Since inhibition of ANT is connected to the inhibition of cytochrome c release from mitochondria, which then results in the suppression of apoptosis, it has been used as a tool for the mechanistic investigation of apoptosis. BKA consists of a long carbon chain with two asymmetric centers, a nonconjugated olefin, two conjugated dienes, three methyl groups, a methoxyl group, and three carboxylic acids. This complicated chemical structure has caused difficulties in synthesis, supply, and biochemical mechanistic investigations. In this study, we designed and synthesized more simple tricarboxylic acids that were inspired by the molecular structure of BKA. Their cytotoxicity and apoptosis-preventing activity in HeLa cells and the effect on the mitochondrial inner membrane potential in HL-60 cells were then evaluated. All tested tricarboxylic acid derivatives including BKA showed little toxicity against HeLa cells. BKA and two of the synthesized derivatives significantly suppressed staurosporine (STS)-induced reductions in cell viability. Furthermore, STS-induced /mitochondrial potential/ collapse was significantly restored by pretreatment with BKA and a tricarboxylic acid derivative. Other derivatives, in which one of three carboxylic acids was esterified, exhibited potent toxicity, especially a derivative bearing a carbon chain of the same length as that of BKA. In conclusion, we have developed a new ... compound as an apoptosis inhibitor bearing three carboxylic acids connected with the proper length of a long carbon chain.|For more Human Toxicity Excerpts (Complete) data for Bongkrekic acid (7 total), please visit the HSDB record page.

Bongkrekate

An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of mitochondrial ADP, ATP translocases. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.|Natural product; Anti-Bacterial Agent; Anti-Infective Agent; Drug/Therapeutic Agent|Tempe bongkrek is an Indonesian food made by fermentation of coconut presscake or coconut milk residue Rhizopus oligosporus. Consumption of tempe bongkrek is associated with a food-borne human intoxication and significant numbers of deaths annually. The bacterium Burkholderia cocovenenans, which is the causative organism, produces two toxins, toxoflavin and bongkrekic acid (also commonly referred to as bongkrek acid). The reasons why these poisonings occur only in a very limited number of foods and only in isolated regions of the world are unclear. Our preliminary experiments in defined media and coconut investigated several compositional and environmental factors and suggested that lipid type and/or concentration were important. The effect of lipid concentration and fatty acid type on the production of bongkrekic acid by B. cocovenenans was examined by adding different amounts of coconut fat or individual free fatty acids to defatted and sterilized Rich Coconut Media (dRCM). The dRCM with added lipid was inoculated with B. cocovenenans, incubated at 30 degrees C for 5 days and the amount of bongkrekic acid formed quantified by HPLC. Coconut fat concentrations of 10% (dry basis) or less did not result in detectable amounts of bongkrekic acid even though the B. cocovenenans grew to high levels. Forty and 50% coconut fat resulted in as much as 1.4 mg/g bonkrekic acid (dry weight) at the same level of growth. Of eight saturated fatty acids tested, only lauric (12:0), myristic (14:0), and palmitic (16:0) acids stimulated the production of detectable amounts of toxin. When four 18-carbon free fatty acids with different degrees of saturation were compared, significant amounts of bongkrekic acid (2.62 mg/g dry weight) were produced only with oleic acid (18:1). These data indicate that the concentration and type of lipid in the substrate is critical for bongkrekic acid formation. This may explain why bongkrekic acid intoxication is limited to certain foods. Outbreaks associated with foods containing less than 20% fat may be a result of toxoflavin formation and not bongkrekic acid formation.|One of two toxic antibiotic principles produced by Pseudomonas cocovenenans on partially defatted coconut; the other being toxoflavin, q.v. Name derived from "bongkrek", a molded coconut product from Indonesia which becomes highly poisonous when P. cocovenenans outgrows the mold.

Flavotoxin A was isolated from Pseudomonas cocovenenans subsp. farinofermentans culture in semisolid potato-dextrose-agar medium, which was isolated from fermented corn meal that had caused food poisoning outbreaks in China. The isolation, purification, and chemical structure of this toxin were studied. The NMR spectra, the UV spectra, and molar extinction coefficients, and the mass spectra of Flavotoxin A are in good agreement with those reported for bongkrekic acid. Therefore, Flavotoxin A and bongkrekic acid are the same organic chemical compound; the molecular formula is C28H38O7. The oral LD50 of the purified Flavotoxin A in mice was 3.16 mg/kg (1.53-6.15 mg/kg). The existence of bongkrekic acid in toxic fermented corn samples collected during food poisoning outbreaks was also confirmed. It is concluded that bongkrekic acid has played an important role in the outbreaks of fermented corn poisoning.