Rubratoxin B

518.51000

518.51

244-582-6

CRYSTALIZES FROM DIETHYL ETHER AS ROSETTES OF NEEDLES; FROM BENZENE & ETHYL ACETATE AS LONG LATHES; HEXAGONAL PLATES FROM AMYL ACETATE|Crystalline

173.73000

0.69740

1.45g/cm3

168-170 °C (decomp)

807.4ºC at 760mmHg

271.8ºC

1.608

PARTIALLY SOL IN WATER, FAIRLY SOL IN ALC & ESTERS & VERY SOL IN ACETONE /RUBRATOXINS/|INSOL IN OILS OR CHLOROFORM /RUBRATOXINS/

0-6ºC

0mmHg at 25°C

PKA= 4.69

Very soluble in acetone, moderately soluble in alcohol and esters and only sparingly soluble in water; completely insoluble in non-polar solvents /Rubratoxins/|Infra-red spectra reveal strong absorption in the carbonyl region... strong absorption at about 3500 cm-1 /Rubratoxins/|THE ONLY DIFFERENCE BETWEEN THE RUBRATOXINS IS THAT ONE OF THE ANHYDRIDE GROUPS OF RUBRATOXIN B IS REDUCED TO THE LACTOL IN THE A TOXIN

III

6.1(b)

UN 2811

R22

GX9275000

Xn

STABLE AT ROOM TEMP /RUBRATOXINS/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

THE FORMATION, CHEMICAL AND PHYSICAL PROPERTIES, ANALYSIS, AND BIOLOGICAL ACTIVITY OF RUBRATOXINS A AND B ARE REVIEWED WITH 43 REFERENCES.[NEWBERNE PM; PENICILLIUM RUBRUM- RUBRATOXINS; MYCOTOXINS: 163 (1974)]|A REVIEW WITH 12 REFERENCES. THE TOXICITY AND TERATOGENICITY OF RUBRATOXINS A AND B ARE DISCUSSED.[WILSON BJ, HARBISON RD; RUBRATOXINS; J AMER VET MED ASS 163(11) 1274 (1973)]

EVIDENCE OF POTENTIATION OF THE LETHAL ACTION OF RUBRATOXIN B, BUT NOT THE CARCINOGENIC ACTION OF AFLATOXIN B1, WAS FOUND IN RATS TREATED WITH RUBRATOXIN B (25 MG/KG, 3 TIMES/WK FOR 5 WK) & FED OVER THE SAME PERIOD A DIET CONTAINING 0.1 PPM AFLATOXIN B1.|IN SIMULTANEOUS DOSING EXPT /WITH SPRAGUE-DAWLEY RATS/, THE NEONATE LD50 VALUE OF OCHRATOXIN A IN THE PRESENCE OF 5 MG/KG RUBRATOXIN B WAS REDUCED 16-FOLD BELOW THE LD50 VALUE OF OCHRATOXIN A ALONE. THE NEONATE LD50 OF RUBRATOXIN B WAS DECR 4-FOLD IN THE PRESENCE OF OCHRATOXIN. IN EXPT WHEN RUBRATOXIN B WAS ADMIN ON DAY ONE & AFLATOXIN B1 ON DAY 15, DECR WT GAINS WERE MEDIATED BY BOTH AGENTS RATHER THAN BY EITHER AGENT ALONE. A SYNERGISTIC RESPONSE, HOWEVER, WAS NOT DEMONSTRATED WHEN AFLATOXIN B1 WAS GIVEN ON DAY 1 OR IN EXPT USING OCHRATOXIN FOLLOWED BY RUBRATOXIN.|USING PROPYLENE GLYCOL AS THE SOLVENT, THE ACUTE IP LD50 IN MALE MICE WAS EST AT 1.42 MG/KG. PRETREATMENT WITH SC PELLETS OF PENTOBARBITAL REDUCED TOXICITY APPROX 42% WHILE CASTRATION OR PRETREATMENT WITH SKF-525A INCR TOXICITY 20% & 60%, RESPECTIVELY. RUBRATOXIN B POTENTIATED PENTOBARBITAL-INDUCED /SRP: CNS DEPRESSION/ & ENHANCED PENTOBARBITAL HYPOTHERMIA. /IN ANOTHER EXPT/...PRETREATMENT WITH PENTOBARBITAL REDUCED TOXICITY APPROX 20% WHILE SKF-525A PRETREATMENT INCR TOXICITY NEARLY 50%. DIETHYL MALEATE PRETREATMENT ALSO DEMONSTRATED ENHANCED TOXICITY, SUGGESTING A PROTECTIVE ACTION OF GLUTATHIONE. THESE DATA SUGGEST THAT INCR MIXED FUNCTION OXIDASE ACTIVITY IS ASSOC WITH DECR RUBRATOXIN B TOXICITY, FURTHER IMPLYING THAT RUBRATOXIN B & NOT A METABOLITE IS THE ACTIVE FORM.|THE EFFECTS OF RUBRATOXIN ALONE IN COMBINATION WITH AFLATOXIN GIVEN ORALLY TO GUINEA PIGS...FOR 3 WK PRODUCED MORTALITY HIGHER THAN PRODUCED BY RUBRATOXIN ALONE.|For more Interactions (Complete) data for RUBRATOXIN B (10 total), please visit the HSDB record page.

LD50 Mongolian gerbils ip 2.0 (2.26-1.77) mg/kg|LD50 Syrian golden hamsters ip 0.4 (0.2-0.8) mg/kg|LD50 RATS ORAL 400 MG/KG, WT 60 G, MALES, IN DIMETHYL SULFOXIDE|LD50 RATS INTRAPERITONEAL 350 UG/KG (95% CONFIDENCE LIMIT 280-450 UG/KG), WT 59 G, FEMALES, IN DIMETHYL SULFOXIDE|For more Non-Human Toxicity Values (Complete) data for RUBRATOXIN B (24 total), please visit the HSDB record page.

RUBRATOXINS A & B ARE HEPATOTOXIC METABOLITES PRODUCED BY THE MOLDS PENICILLIUM RUBRUM & P PURPUROGENUM. THESE MOLDS OFTEN GROW IN FEEDSTUFFS ALONG WITH ASPERGILLUS SP; RUBRATOXINS & AFLATOXINS MAY COEXIST IN THE GRAIN OR FEED PRODUCT. THIS MEANS THAT AFLATOXICOSIS MAY BE COMPLICATED BY RUBRATOXINS & THAT THE CONDITIONS FAVORING AFLATOXIN PRODUCTION IN STORED FEEDS CAN ALSO FAVOR RUBRATOXIN.

EXCRETION PATTERNS OF (14)C DERIVED FROM RADIOLABELED RUBRATOXIN B...IN MICE & RATS...EXCRETED 40-50% OF THE ADMIN RADIOACTIVITY DURING THE INITIAL 24 HR. A MAJOR EXCRETORY ROUTE WAS RESP CO2 WHICH ACCOUNTED FOR 30% OF THE ADMIN (14)C IN MICE & 35% IN RATS. 6 TO 9% WAS EXCRETED IN THE URINE; LESS RADIOACTIVITY WAS PRESENT IN FECES. RADIOACTIVITY DERIVED FROM RUBRATOXIN WAS PRESENT AT MAX LEVELS IN LIVER & KIDNEYS ONE HR AFTER ADMIN; SMALLER AMT WERE FOUND IN OTHER ORGANS. THE CONCN OF RADIOACTIVITY WAS GREATEST IN LIVER TISSUE.|EXCRETION PATTERNS OF (14)C DERIVED FROM RADIOLABELED RUBRATOXIN B...IN MICE & RATS. ...ALL DETECTABLE RADIOACTIVITY PRESENT IN THE LIVER 1/2 HR AFTER INJECTION WAS IN THE MICROSOMAL SUPERNATANT FLUID. WITHIN THE FIRST 2 HR, INCR AMT OF RADIOACTIVITY WERE FOUND IN THE MITOCHONDRIA WITH A CONCOMITANT DECR IN THE MICROSOMAL SUPERNATANT FLUID. AT 24 HR, THE MITOCHONDRIAL FRACTION CONTAINED APPROX 14% OF THE LIVER RADIOACTIVITY WITH 80% REMAINING IN THE SOL FRACTION. THE MICROSOMAL FRACTION CONTAINED 4 TO 10% OF THE LIVER RADIOACTIVITY DURING THE 24-HR PERIOD.|EXCRETION, TISSUE CONCN IN KIDNEY & LIVER, & PHARMACOKINETIC PARAMETERS ESTIMATED FROM PLASMA BLOOD CONCN WERE DETERMINED FOR RATS GIVEN A SINGLE IP DOSE OF (14)C-RUBRATOXIN B (0.05 MG DISSOLVED IN PROPYLENE GLYCOL). BY 7 DAYS, 80% OF ADMIN RADIOACTIVITY WAS EXCRETED INTO THE URINE (41.7%) & FECES (38.7%). URINARY EXCRETION WAS PRIMARILY AS THE PARENT COMPOUND, ACCOUNTING FOR 75% OF RADIOACTIVITY EXCRETED BY 7 DAYS. ELIMINATION OF RADIOACTIVITY FROM KIDNEYS WAS MONOPHASIC WITH T/2 OF 97.35 HR. ELIMINATION OF RADIOACTIVITY FROM LIVER WAS BIPHASIC, WITH T/2 OF 13.66 HR FOR THE SLOW PHASE. ELIMINATION OF RUBRATOXIN B & (14)C-RUBRATOXIN B-DERIVED RADIOACTIVITY (RADIOACTIVITY DERIVED FROM BOTH THE PARENT COMPOUND & METABOLITES) FROM PLASMA WAS BIPHASIC. THE RAPID PHASES OF ELIMINATION HAD T/2 OF 2.57 & 1.08 HR, & SLOW PHASES HAD T/2 OF 60.80 & 100.46 HR FOR RUBRATOXIN B & (14)C-RUBRATOXIN B-DERIVED RADIOACTIVITY RESPECTIVELY. THE LONG PLASMA T/2 IS SUGGESTIVE OF ENTEROHEPATIC CIRCULATION. THE CONCN OF RADIOACTIVITY WAS GREATEST AT 1 HR IN LIVER & 2 HR IN PLASMA. EXCEPT FOR THE FIRST FEW HR FOLLOWING INJECTION, THE CONCN OF RADIOACTIVITY IN LIVER NEVER EXCEEDED SIGNIFICANTLY THAT IN THE PLASMA, SUGGESTING A PASSIVE ABSORPTION PROCESS.

AS WELL AS SERVING TO COMPLETE THE OXIDATION OF GLUCOSE TO CO2 & WATER, THE TRICARBOXYLIC ACID CYCLE ALSO PROVIDES INTERMEDIATES FOR THE BIOSYNTHESIS OF SOME SECONDARY METABOLITES, INCL THE RUBRATOXINS... THE FIRST STEP INVOLVES CONDENSATION OF DECANOIC ACID WITH OXALOACETIC ACID IN A MANNER ANALOGOUS TO THE FORMATION OF CITRIC ACID. SUBSEQUENT DEHYDRATION, DECARBOXYLATION & OXIDATION LEAD TO AN INTERMEDIATE ANHYDRIDE WHICH DIMERIZES TO FORM, AFTER FURTHER OXIDATION, RUBRATOXIN A. AT WHAT STAGE THE OXYGEN FUNCTIONS ARE INTRODUCED IS NOT CLEAR, &, IN PARTICULAR, SUCH A HYPOTHESIS WOULD MEAN THAT THE CARBOXYL GROUP OF THE ALPHA,BETA-UNSATURATED GAMMA-LACTONE WOULD BE DERIVED FROM THE METHYL CARBON OF ACETATE. /RUBRATOXINS/|THE LIVER METABOLIZES RUBRATOXINS. THERE ARE A NUMBER OF METABOLITES. IN RATS, GLUCURONIDE & SULFATE CONJUGATES ARE EXCRETED IN BILE, APPARENTLY HYDROLYZED IN THE INTESTINE, & THE PARENT TOXIN MAY BE RESORBED IN AN ENTEROHEPATIC CYCLE. UNKNOWN METABOLITES ARE ALSO FORMED. /RUBRATOXINS/

... THE RAPID PHASES OF ELIMINATION HAD T/2 OF 2.57 & 1.08 HR, & SLOW PHASES HAD T/2 OF 60.80 & 100.46 HR FOR RUBRATOXIN B & (14)C-RUBRATOXIN B-DERIVED RADIOACTIVITY RESPECTIVELY

/SRP:/ Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison 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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

rubratoxin

HEATING AT 85-100 °C FOR 2 HR MAY DESTROY OR ALTER THE B TOXIN IN FEEDSTUFFS.|(14)C-RUBRATOXIN B WAS PRODUCED BY CULTURING PENICILLIUM RUBRUM STOLL FOR 13 DAYS AT 22 °C IN MEDIUM CONTAINING (14)C-GLUCOSE. THE MOST EFFICIENT INCORPORATION OF GLUCOSE INTO RUBRATOXIN B OCCURRED WHEN RAULIN-THOM MEDIUM ENRICHED WITH 2.5% MALT EXTRACT WAS SUPPLEMENTED WITH 2.5% ADDED GLUCOSE.

FACTORS THAT AFFECT RECOVERY OF RUBRATOXIN B FROM MIXED FEED WERE STUDIED. RESULTS SHOWED THAT STORAGE TEMPERATURE, FEED MOISTURE CONTENT & ATMOSPHERE HAD A MARKED EFFECT ON THE DETERIORATION RATE OF RUBRATOXIN B AS MEASURED BY ITS RECOVERY FROM MIXED FEED. HIGH-PRESSURE LIQUID CHROMATOGRAPHY ASSAY SYSTEM PROVIDES EXCELLENT RESOLUTION & DETECTED AS LITTLE AS 5 NG RUBRATOXIN B.|TLC DATA: ADSORBENT: SILICA GEL HF254; SOLVENT GLACIAL ACETIC ACID-METHANOL-CHLOROFORM, 2:20:80 VOL/VOL/VOL; DETECTION: A DARK SPOT AGAINST A GREEN FLUORESCENT BACKGROUND WHEN EXAMINED UNDER SHORTWAVE UV LIGHT; HAYES AW, WILSON BJ; APPL MICROBIOL 16: 1163 (1968).|RUBRATOXINS A AND B WERE RESOLVED AS SHARP PEAKS IN THE ORDER A-B BY REVERSED-PHASE HIGH PRESSURE LIQUID CHROMATOGRAPHY ON A SMALL-PARTICLE (10 MUM) COLUMN IN 3 MINUTES BY AN ACETONITRILE-WATER-ETHYL ACETATE ELUTION SOLVENT (11:9.9:3), WITH DETECTION BY UV ABSORBANCE AT 254 NM.