Orotic acid

156.09600

156.10

200-619-8

61H4T033E5

758903|9791

DTXSID0025814

Crystals

29335990

103.02000

-1.4

Orotic acid appears as white crystals or crystalline powder. (NTP, 1992)

1.642 g/cm3

345-346 °C

656.9ºC at 760 mmHg

351.1ºC

1.705

H2O: Slightly soluble

Keep in a cool, dry, dark location in a tightly sealed container or cylinder. Keep away from incompatible materials, ignition so

1X10-8 mm Hg at 25 deg C (est)

pic-esc 1 g/L ZAPOAK12,583,72

Henry's Law constant = 8.1X10-15 atm-cu m/mol at 25 °C (est)

pKa1 = 2.07; pKa2 = 9.45

138.85 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]|181.87 Ų [M+Na]+ [CCS Type: DT, Method: stepped-field]|125.2 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|121.7 Ų [M-H]-

Hydroxyl radical reaction rate constant = 8.9X10-12 cu cm/molec-sec at 25 °C (est)

Slightly soluble in water.

Acids, Carboxylic

Carboxylic acids, such as OROTIC ACID, donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Carboxylic acids with six or fewer carbon atoms are freely or moderately soluble in water; those with more than six carbons are slightly soluble in water. Soluble carboxylic acid dissociate to an extent in water to yield hydrogen ions. The pH of solutions of carboxylic acids is therefore less than 7.0. Many insoluble carboxylic acids react rapidly with aqueous solutions containing a chemical base and dissolve as the neutralization generates a soluble salt. Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt. Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry. Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in it to corrode or dissolve iron, steel, and aluminum parts and containers. Carboxylic acids, like other acids, react with cyanide salts to generate gaseous hydrogen cyanide. The reaction is slower for dry, solid carboxylic acids. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.

NONH for all modes of transport

3

R22; R36/37/38

S22-S26-S36/37/39

RM3180000

Xn

Stable. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Warning|H315 (95.74%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 49 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (91.24%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, and P362|Aggregated GHS information provided by 339 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 59 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this chemical at ambient temperatures, and keep it away from oxidizing materials. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

In rats treated with phenobarbital for 3 days and simultaneously fed a semisynthetic diet containing 1.0% orotic acid, the extent of the increases in liver microsomal phosphatidylcholine, phosphatidylethanolamine, total RNA, total protein, and cytochrome P-450 were significantly greater than they were in rats treated identically with phenobarbital but without dietary orotic acid. This is attributed primarily to the stimulation of hepatic phosphatidylcholine synthesis by dietary orotic acid. In the absence of phenobarbital, orotic acid was shown to cause some increase in liver smooth endoplasmic reticulum components, but not cytochrome P-450. Orotic acid also decreased the activity of microsomal phosphatidylethanolamine N-methyltransferase, which may have contributed to the increase in the microsomal content of phosphatidylethanolamine. The hypothesis is advanced that phospholipid availability is a limiting factor in the hepatic response to phenobarbital. When more phospholipid is available to provide the structural framework for biogenesis of endoplasmic reticulum, all of the hepatic actions of phenobarbital, including induction of cytochrome P-450, are amplified.

LD50 Mouse iv 770 mg/kg|LD50 Mouse ip 841 mg/kg|LD50 Mouse oral 2 g/kg

Orotic acid occurs in cow's milk and has also been isolated from certain strains of molds (Neurospora).

Orotic acid's production and use in biochemical research, particularly in the synthesis of nucleic acids(1) and its proposed use as a feed supplement for calves(2), 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 10(SRC), determined from a log Kow of -0.83(2) and a regression-derived equation(3), indicates that orotic acid is expected to have very high mobility in soil(SRC). Volatilization from moist soil surfaces is not an important environmental fate process because orotic acid will exist in ionized form, based on pKa values of 2.07 and 9.45(4), and ionized species do not volatilize(SRC). Volatilization from dry soil surfaces is not expected to occur based on an estimated vapor pressure of 1X10-8 mm Hg determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of -0.83(2) and a regression derived equation(3), indicates that orotic acid is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not an important environmental fate process because orotic acid will exist in ionized form based on pKa values of 2.07 and 9.45(4), and ionized species do not volatilize(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Orotic acid may undergo direct photolysis in sunlit surface waters since it absorbs light greater than 290 nm(7), but the rate of this reaction is not known(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), orotic acid, which has an estimated vapor pressure of 1X10-8 mm Hg at 25 °C(2), is expected to exist in the particulate phase in the ambient atmosphere. Particulate-phase orotic acid may be removed from the air by wet and dry deposition(SRC). Orotic acid may undergo direct photolysis in the environment since it absorbs light greater than 290 nm(3); however, the rate of this reaction is unknown(SRC).

Orotic acid may undergo direct photolysis in the environment since it absorbs light greater than 290 nm(1); however, the rate of photolysis is unknown(SRC). pKa values of 2.07 and 9.45(2), indicate that orotic acid will exist in ionized form in water(SRC).

An estimated BCF of 3 was calculated for orotic acid(SRC), using a log Kow of -0.83(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of orotic acid is estimated as 10(SRC), using a log Kow of -0.83(1) and a regression-derived equation(2). According to a classification scheme(2), this estimated Koc value suggests that orotic acid is expected to have high mobility in soil(SRC).

pKa values of 2.07 and 9.45(1), indicate that orotic acid will exist in various ionized forms at pH range 5-9 in water and moist soil surfaces. Volatilization from water and moist soil surfaces will not be an important environmental fate process since ionized species do not volatilize(SRC). Volatilization from dry soil surfaces is not expected to occur based on an estimated vapor pressure of 1X10-8 mm Hg determined from a fragment constant method(2).

Occupational exposure to orotic acid may occur through inhalation and dermal contact with this compound at workplaces where orotic acid is produced or used. (SRC)

Uricosuric|This study deals with the potential therapeutic effect of orotic acid (OA) and Mg Orotate (MgO) on myocardial degeneration and the development of congestive heart failure in cardiomyopathic (CM) hamsters of the UM-X7.1 line. Two major age groups (group I, < 30 days and group II, > 180 days old) were used in these experiments, which lasted 30 and 50 days, respectively; the orotic salts were incorporated (10%) into Purina Lab Chow given ad libitum. Macroscopic and microscopic assessment of pathologic changes together with ECG recordings revealed that MgO treatment significantly reduces myocardial damage, especially the severity of calcific changes. ECG recordings clearly demonstrated a significant shortening of QTc and PR intervals, resulting in partial electrical stabilization of failing hearts, with a significant delay in systemic congestive changes. The prevention of heart lesions was less evident in animals receiving OA, but both preparations proved to be equally efficient in prolonging survival of the CM hamsters.|... Three studies were performed: (1) The time course of changes in tissue and plasma concentrations of pyrimidine compounds was examined in unoperated rats after the administration of 100 mg/kg OA. (2) Rats were given OA (30 mg/kg/d) for 2 days after experimental infarction, and tissue and plasma pyrimidine concentrations were examined; the hearts were removed for perfusion in the isolated working rat heart model (37 degrees C), subjected to 30 minutes of global ischemia, and recovery of function was assessed. AN content was assessed in the noninfarcted myocardium before and after ischemia. Isolated hearts were subjected to 30 minutes of hypoxic perfusion and the effect of adding 17 microM uridine to the perfusate was examined. Study 1 showed that OA administration produced an increase in hepatic uridine and cytidine, followed by increased plasma uridine and cytidine (cytidine, +55%, P < 0.001; uridine, +124%, P = 0.011). Myocardial uracil nucleotides increased temporarily after 4 hours (+21%, P < 0.01). In infarcted hearts after 2 days of OA administration, there were no significant changes in myocardial uracil or cytosine nucleotides or total RNA. Infarction significantly reduced functional recovery after global ischemia (sham = 62%; infarct = 26% of preischemic level; P < 0.05). OA improved the recovery of preischemic function by 133% (P < 0.05) in infarcted, but not sham-operated, hearts. Preischemic ATP and total adenine nucleotides (TAN) were decreased in the surviving myocardium of infarcted hearts (ATP reduced from 21.7 +/- 0.8 to 14.7 +/- 0.7 mumol/g dry wt, P < 0.001; TAN decreased from 30.3 +/- 0.8 to 22.4 +/- 1.1 mumol/g dry wt, P < 0.001). OA treatment prevented these reductions. Study 3 showed that uridine improved myocardial ATP and TAN levels, and decreased purine loss in hypoxic hearts. The increased AN levels were accompanied by evidence of enhancement of anerobic glycolysis.

[14C]Orotic acid was rapidly distributed in blood after both i.p. and s.c. injection but was not completely absorbed from the peritoneal cavity until 20 min after injection. S.c. injection should be an acceptable alternative to i.p. injection although the incorporation into the liver acid soluble- and RNA-fractions was somewhat delayed after the s.c. injection.

... The aim of this work was to investigate whether orotate is differently metabolized in gut and in liver thus explaining the lack of effect on the intestinal lipoproteins secretion. Multienzyme complex (complex U) was found in appreciable amounts in rat, mouse and rabbit livers; the intestinal mucosa of the two last species contains a much lower level of multienzyme complex whereas in rat intestine its activity cannot be detected. Indeed, radioactive aspartate and orotate were not incorporated into intestinal cells RNA. The absence of orotate metabolisation by lack of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase activity in rat intestine would explain why this organ, in contrast to the liver, is protected against disturbances of nucleotide metabolism and lipoproteins secretion induced by orotic-acid-supplemented diets.

SYMPTOMS: This compound may cause irritation. ACUTE/CHRONIC HAZARDS: This compound may cause irritation. When heated to decomposition it may emit toxic fumes of carbon monoxide, carbon dioxide and NOx. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Acid, Orotic

4-Pyrimidinecarboxylic acid, 1,2,3,6-tetrahydro-2,6-dioxo-: ACTIVE|Classified as a vitamin (vitamin B13)

Cosmetics -> Emulsifying; Surfactant