| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 92.6% (188 of 203) of all reports.Not ClassifiedAggregated GHS information provided per 203 reports by companies from 7 notifications to the ECHA C&L Inventory. |
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| Regulatorische Informationen | Chemical: L-Glutamic acid, N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-Regulation (EC) No 178/2002 (amended)REACH registered substance: Folic acid (EC: 200-419-0).beta.-D-ribo-2-Heptulopyranose, 2,7-anhydro-1,4-dideoxy-3-O-methyl-5-O-(phenylmethyl)-: Does not have an individual approval but may be used under an appropriate group standard.beta.-D-Allopyranose, 1,6-anhydro-2,3-di-O-methyl-4-O-(phenylmethyl)-: Does not have an individual approval but may be used under an appropriate group standardFolic acid: Does not have an individual approval but may be used under an appropriate group standard |
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| Weitere Sicherheitsinformationen | Evaluation - Chemicals that are unlikely to require further regulation to manage risks to environment |
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| Brandgefahren | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
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| Gesundheitsgefahren | SYMPTOMS: Symptoms of exposure to this compound include anorexia, nausea, abdominal distension, flatulence, altered sleep and dream patterns, malaise, irritability, hypersensitivity and fever. It may also cause allergic sensitization. |
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| Gefahrenübersicht | Rare allergic reactions after IV injection reported[Olson, p. 557] May cause allergic sensitization[NTP] May cause irritation[Sigma-Aldrich MSDS] |
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| FDA-Anforderungen | Folic acid (CAS Reg. No. 59-30-3), also known as folacin or folate, may be safely used in food as a nutrient in accordance with the following prescribed conditions: (a) Folic acid is the chemical N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid. (b) Folic acid meets the specifications of the "Food Chemicals Codex," 4th ed. (1996), pp. 157-158, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. ... (c) Folic acid may be added to foods subject to a standard of identity established under section 401 of the Federal Food, Drug, and Cosmetic Act (the act) when the standard of identity specifically provides for the addition of folic acid. (d) Folic acid may be added, at levels not to exceed 400 micrograms (ug) per serving, to breakfast cereals, as defined under §170.3(n)(4) of this chapter, and to corn grits at a level such that each pound of corn grits contains not more than 1.0 milligram of folic acid. (e) Folic acid may be added to infant formula in accordance with section 412(i)(1) of the act or with regulations issued under section 412(i)(2) of the act which are codified in §107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive nutritional requirements of the disease or condition for which the food is formulated. (g) Folic acid may be added to food for special dietary use at levels not to exceed the amount necessary to meet the special dietary needs for which the food is formulated. (h) Folic acid may be added to foods represented as meal-replacement products, in amounts not to exceed: (1) Four hundred ug per serving if the food is a meal-replacement that is represented for use once per dayor (2) Two hundred ug per serving if the food is a meal-replacement that is represented for use more than once per day.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Folic acid is included in weight control drug products. |
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| Reaktive Gruppe | Acids, Carboxylic |
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| Special Reports | AnonMaternal and Infant Folate Status Relationships Nutr Rev 48 (3): 157-9 (1990). A population based case control study was conducted to test the hypothesis that the risk of the occurrence of neural tube defects in infants with no other birth defects (isolated neural tube defects) is associated inversely with the maternal dietary intake of free and/or total folate in early pregnancy. Information was collected from the mothers of 77 case subjects with isolated neural tube defects who were born in Western Australia from 1982 to 1984, from the mothers of 77 control subjects with birth defects other than neural tube defects (control group 1) and from the mothers of 154 control subjects with no birth defects (control group 2). Crude and adjusted odds ratios showed a protective effect of an increasing intake of free folate in the first six weeks of pregnancy. These findings support the hypothesis that the dietary intake of folate in early pregnancy protects against the occurrence of isolated neural tube defects in infants. Measures of postpartum dietary folate and of postpartum serum and red cell folate levels showed no association with the occurrence of neural tube defects in infants.Young SN, Ghadirian AMFolic Acid and Psychopathology Prog Neuropsychopharmacol Biol Psychiatry 13 (6): 841-63 (1989).Butterworth CE Jr, Tamura TFolic Acid Safety and Toxicity: A Brief ReviewAm J Clin Nutr 50 (2): 353-8 (1989). Oral folic acid (pteroylglutamic acid) is generally regarded as not toxic for normal humans but it may cause neurological injury when given to patients with undiagnosed pernicious anemia. The vitamin should be given with caution to drug-treated epileptic patients because seizure control may be affected. Some studies suggest that folic acid supplements interfere with intestinal zinc absorption in humans and animals but others do not confirm such an effect. The weight of current evidence favors the view that daily supplements of 5-15 mg folic acid do not have significant adverse effects on zinc nutriture in healthy nonpregnant subjects. Because antifolate medications are now being used to treat a wide range of malignant and nonmalignant disorders, further investigation is needed concerning folate metabolism and the safety of supplements in patients with these disorders. |
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| FIFRA-Anforderungen | Folic acid is exempted from the requirement of a tolerance when used as a synergist (maximum of 0.5% of formulation) in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. |
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| Reactivity Profile | Acid solutions of FOLIC ACID are sensitive to heat, but towards neutrality, stability progressively increases. Solutions are inactivated by ultraviolet light and alkaline solutions are sensitive to oxidation. It is also inactivated by light. This chemical is incompatible with oxidizing agents, reducing agents and heavy metal ions. (NTP, 1992) |
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| Air and Water Reactions | Insoluble in water. Aqueous solutions have pHs of 4.0-4.8. |
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| Hazard Classes and Categories | Not Classified |
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| Brandbekämpfung | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
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| Erste Hilfe | 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. |
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| Lagerbedingungen | Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. |
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| Freisetung ohne Brand | SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with 5% acetic acid, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% acetic acid to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% acetic acid followed by washing 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. |
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| Entsorgungsverfahren | 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 qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations. |
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| Allowable Tolerances | Folic acid is exempted from the requirement of a tolerance when used as a synergist (maximum of 0.5% of formulation) in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. |
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| Personal Protective Equipment (PPE) | 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) |
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| Körperbelastung | Folic acid is considered a member of the vitamin B complex and it is a natural component of the liver and kidney(1). The level of folic acid in human milk is 0.0020 mg/L(2).FOLIC ACID IS EXCRETED IN HUMAN MILK. /FROM TABLE/ |
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| Wechselwirkungen | The use of high dose folic acid concomitantly with pyrimethamine to prevent bone marrow depression may cause a pharmacodynamic antagonism of the antiparasitic effect of pyrimethamine.Nonsteroidal antiinflammatory drugs (NSAIDS), including ibuprofen, indomethacin, naproxen, mefenamic acid, piroxicam, and sulindac taken at high therapeutic dosages may exert antifolate activity.Folic acid supplementation in mice was found to augment the therapeutic activity and ameliorate the adverse reactions of the ... antifolate cancer chemotherapeutic agent lometrexol.The /daily/ use of folic acid ... was found to enhance the antidepressant action of fluoxetine ...For more Interactions (Complete) data for FOLIC ACID (17 total), please visit the HSDB record page. |
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| Hepatotoxicity | Neither normal nor excessively high intakes of folate are associated with liver injury or liver test abnormalities. In long term clinical trials, serum enzyme and bilirubin elevations were no more frequent with folic acid therapy than with placebo. Use of high doses of folic acid (up to 15 mg daily) has not been associated with appreciable adverse reactions, ALT elevations or hepatotoxicity. |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a water solubility of 1.6 mg/L(2) and a regression-derived equation(3), indicates that folic acid is expected to have slight mobility in soil(SRC). The estimated pKa values of the two carboxylic acid moieties of folic acid are 3.5 and 4.3(4) indicating that this compound will primarily exist as an anion in the environment(5). Volatilization of folic acid from moist soil surfaces is not an important fate process(SRC) because anions do not volatilize. Folic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.2X10-20 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation is not expected to be an important environmental fate process in soil as indicated by a low BOD/COD ratio obtained using a sewage inoculum test(7).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a water solubility of 1.6 mg/L(2) and a regression-derived equation(3), indicates that folic acid is expected to adsorb to suspended solids and sediment(SRC). The estimated pKa values of the carboxylic acid moieties of folic acid are 3.5 and 4.3(3), indicating that this compound will primarily exist in anion form in the environment(4). Volatilization from water surfaces does not occur since anions do not volatilize. According to a classification scheme(5), an estimated BCF of 3.2(SRC), from its water solubility(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegadation is not expected to be an important environmental fate process in water as indicated by a low BOD/COD ratio obtained using a sewage inoculum test(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), folic acid, which has an estimated vapor pressure of 6.2X10-10 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 folic acid may be removed from the air by wet and dry deposition(SRC). Folic acid absorbs UV light >290 nm(3)therefore folic acid may be susceptible to photolysis although the rate is not known. |
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| Lebensmitteluntersuchungswerte | Folic acid is considered a member of the vitamin B complex and it is a natural component of liver, mushrooms, spinach, fresh fruit, and yeast(1). In Total Diet Studies conducted by the US Food and Drug Administration from the years 1987 to 1993, folic acid was tested for during 1991 through 1993results were not published in this particular study(2).Folic acid food sources include beans and legumes, citrus fruits and juices, wheat bran and other whole grains, dark green leafy vegetables, poultry, pork, shellfish, and liver(1). Many foods are now fortified with folic acid to help prevent neural tube birth defects such as spina bifida(1). |
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| Unerwünschte Wirkungen | For the general population, a diet that contains a daily amount of folic acid below the established upper intake level of 1000 mcg has not been demonstrated to result conclusively in any adverse health outcomes. The U.S. National Toxicology Program (NTP) examined areas of previous concern, including cognition (relating to vitamin B12 deficiency), cancer, diabetes- and thyroid-related disorders, and hypersensitivity-related outcomes. |
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| Expositionspfade | Intravenous, Oral |
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| Milk Concentrations | FOLIC ACID IS EXCRETED IN HUMAN MILK. /FROM TABLE/Levels of folic acid in cows milk, goats milk, sheeps milk, mares milk, and human milk are 0.0023 mg/L, 0.0024 mg/L, 0.0024, 0.0012, and 0.0020 mg/L, respectively(2). |
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| Toxizitätsübersicht | IDENTIFICATION: Folic acid is an antianaemic vitamin. Origin of the substance: Folic acid was isolated from green leafy vegetables, liver, yeast and fruits. Synthetic folic acid is commercially available. Yellow to orange brown crystalline powder which is odorless. Readily soluble in alkali, hydroxides and carbonates. Insoluble in alcohol, acetone, chloroform and ether. Solutions are inactivated by ultraviolet light. Alkaline solutions are sensitive to oxidation and acid solutions are sensitive to heat. Indications: For the prevention and treatment of vitamin B deficiency. For the treatment of megaloblastic anemia and macrocytic anemia due to folic acid deficiency. Folic acid supplements may be required in low birth weight infants, infants breastfed by folic acid deficient mothers, or those with prolonged diarrhea and infection. Other conditions which may increase folic acid requirements include alcoholism, hepatic disease, hemolytic anemia, lactation, oral contraceptive use and pregnancy. It has been given to pregnant mothers to reduce the risk of birth defects. HUMAN EXPOSURE: Main risks and target organs: Folic acid is relatively non-toxic. However, there have been reports of reactions to parenteral injections. Allergic reactions to folic acid have been rarely reported. Summary of clinical effects: Severe allergic reactions are characterized by hypotension, shock, bronchospasm, nausea, vomiting, rash, erythema. Itching may also occur. Adverse gastrointestinal and central nervous system effects have been reported. Treatment with folic acid is usually well tolerated except for rare reports of allergic reactions. Bioavailability: Folic acid is rapidly absorbed from gastrointestinal tract following oral administration. Peak folate activity in blood is 30 to 60 minutes after oral administration. Contraindications: It should be given with caution to patients with abnormal renal function. It is also contra-indicated in patients who show hypersensitivity reactions to folic acid. Caution is advised in patients who may have folate dependent tumours. Folic acid should never be given alone or in conjunction with inadequate amounts of Vitamin B12 for the treatment of undiagnosed megaloblastic anaemia. Although folic acid may produce a haematopoietic response in patients with megaloblastic anaemia due to Vitamin B12, it fails to prevent the onset of subacute combined degeneration of the cord. Absorption by route of exposure: Oral: Folic acid is rapidly absorbed from the proximal part of the gastrointestinal tract following oral administration. It is mainly absorbed in the proximal portion of the small intestine. The naturally occurring folate polyglutamate is enzymatically hydrolyzed to monoglutamate forms in the gastrointestinal tract prior to absorption. The peak folate activity in blood after oral administration is within 30 to 60 minutes. Enterohepatic circulation of folate has been demonstrated. Distribution by route of exposure: Tetrahydrofolic acid and its derivatives are distributed in all body tissues. The liver contains half of the total body stores of folate and is the principal storage site. Metabolism: Folic acid once absorbed is acted upon by hepatic dihydrofolate reductase to convert to its metabolically active form which is tetrahydrofolic acid. Following absorption, folic acid is largely reduced and methylated in the liver to N-5 methyltetrahydrofolic acid, which is the main transporting and storage form of folate in the body. Larger doses may escape metabolism by the liver and appear in the blood mainly as folic acid. Elimination by route of exposure: Oral: Following oral administration of single doses of folic acid in health adults, only a trace amount of the drug appears in urine. Following administration of large doses, the renal tubular reabsorption maximum is exceeded and excess folate is excreted unchanged in urine. Small amounts of orally administered folic acid have been recovered from feces. Pharmacodynamics: Folic acid is transformed into different coenzymes that are responsible for various reactions of intracellular metabolism mainly conversion of homocysteine to methionine, conversion of serine to glycine, synthesis of thymidylate, histidine metabolism, synthesis of purines and utilization or generation of formate. In man, nucleoprotein synthesis and the maintenance of normal erythropoiesis requires exogenous folate. Folic acid is the precursor of tetrahydrofolic acid which is active and acts as a co-factor for 1-carbon transfer reactions in the biosynthesis of purines and thymidylates of nucleic acids. Adults: There is little data available on folic acid toxicity in humans. A case of two patients who showed exacerbation of psychotic behavior during treatment with folic acid has been reported. Cytomorphological effects of folic acid were studied using in-vitro establishment human oral epithelium. A concentration twice that used clinically did not induce marked cytotoxic reaction in cultured cells. The most pronounced changes were cultures which showed degenerating cells showing edema, increased translucency of the cytoplasm, flattened cells and atypical filaments. Interactions: Folic acid therapy may increase phenytoin metabolism in folate deficient patients resulting in decreased phenytoin serum concentration. It has also been reported that concurrent administration of folic acid and chloramphenicol in folate deficient patients may result in antagonism of the hematopoietic response to folic acid. The use of ethotoin or mephenytoin concurrently with folic acid may decrease the effects of hydantoins by increasing hydantoin metabolism. Trimethoprim acts as a folate antagonist by inhibiting dihydrofolate reductase, so in patients receiving this drug leucovorin calcium must be given instead of folic acid. Folic acid may also interfere with the effects of pyrimethamine. Aminopterin (4 aminofolic acid) and methotrexate (4 amino- 10 methylfolic acid) antagonizes reduction of folic acid to tetrahydrofolic acid. Methotrexate continues to be used as an antineoplastic drug whose activity may be dependent on blocking certain syntheses, of purines, in which folic acid is required, thereby depriving neoplastic cells of compounds essential for their proliferation. Calcium leucovorin is used therapeutically as a potent antidote for the toxic effects of folic acid antagonists used as antineoplastic agents. Methotrexate or pyrimethamine or triamterene also acts as folate antagonist by inhibiting dihydrofolic reductase. Analgesics, anticonvulsants, antimalarials and corticosteroids may cause folic acid deficiency. Main adverse effects: Allergic reactions to folic acid have been rarely reported including erythema, rash, itching, general malaise and bronchospasm. Adverse gastrointestinal and central nervous system effects have been reported in patients receiving 15 mg of folic acid daily for one month. ANIMAL/PLANT STUDIES: Mode of action: Folic acid is relatively non-toxic. Toxicity studies in mice showed that folic acid could cause convulsions, ataxia and weakness. Histopathological studies in some strains of mice showed that toxic doses may also cause acute renal tubular necrosis. A possible relationship between folic acid neurotoxicity and cholinergic receptors in the pyriform cortex and amygdala has been shown.Like other water-soluble vitamins, folic acid does not have significant storage in the bodyhence toxicity is not a common concern. However, infrequent neurologic side effects have been noted in the context of folate supplementation in individuals with pernicious anemia.Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase. |
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| Plant Concentrations | Folic acid is considered a member of the vitamin B complex and it is a natural component of mushrooms, spinach, fresh fruit, and yeast(1). |
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| Animal Concentrations | Folic acid is considered a member of the vitamin B complex and it is a natural constituent of liver and kidney(1). |
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| Soil Adsorption/Mobility | The Koc of folic acid is estimated as 3,400(SRC), using a water solubility of 1.6 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that folic acid is expected to have slight mobility in soil. The estimated pKas of the carboxylic acid moieties of folic acid are 3.5 and 4.5(4), indicating that this compound will primarily exist as an anion and generally do not absorb more strongly to organic carbon and clay than their neutral species(5). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(6,7), suggesting that mobility may be much lower in some soils(SRC). |
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