General Description
A colorless crystalline solid. The primary hazard is the threat to the environment. Immediate steps should be taken to limit spread to the environment. Combustible, though may be difficult to ignite. Used to make paints and plastics, in food processing and preservation, and for other uses.
Reactivity Profile
FUMARIC ACID(110-17-8) is a carboxylic acid. Carboxylic acids 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 FUMARIC ACID(110-17-8) 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. Partial carbonization and formation of maleic anhydride occur at 446° F (open vessel).
Air & Water Reactions
Slightly soluble in water.
Health Hazard
Inhalation of dust may cause respiratory irritation. Compound is non-toxic when ingested. Prolonged contact with eyes or skin may cause irritation.
Potential Exposure
Fumaric acid is used in production of
resins, polyesters, plasticizers, and alkyl surface coatings; as
a food additive; as an antioxidant in resins; to make dyes.
First aid
If this chemical gets into the eyes, remove any
contact lenses at once and irrigate immediately for at least
15 minutes, occasionally lifting upper and lower lids. Seek
medical attention immediately. If this chemical contacts the
skin, remove contaminated clothing and wash immediately
with soap and water. Seek medical attention immediately.
If this chemical has been inhaled, remove from exposure,
begin rescue breathing (using universal precautions, includ ing resuscitation mask) if breathing has stopped and CPR if
heart action has stopped. Transfer promptly to a medical
facility. When this chemical has been swallowed, get medi cal attention. Give large quantities of water and induce
vomiting. Do not make an unconscious person vomit.
Incompatibilities
Dust cloud from powder or granular
form mixed with air can explode. Incompatible with oxidi zers (chlorates, nitrates, peroxides, permanganates, perchlo rates, chlorine, bromine, fluorine, etc.); contact may cause
fires or explosions. Keep away from alkaline materials,
strong bases, strong acids, oxoacids, epoxides, sulfuric
acid, caustics, ammonia, amines, isocyanates, alkylene oxi des; epichlorohydrin. Decomposes above 350℃ forming
toxic fumes of maleic anhydride.
Waste Disposal
Use a licensed professional
waste disposal service to dispose of this material. Dissolve
or mix the material with a combustible solvent and burn in
a chemical incinerator equipped with an afterburner and
scrubber. All federal, state, and local environmental regula tions must be observed.
Occurrence
Reported found in several plants, Fumaria offcinalis L , Boletus scaber Boll and lean raw fsh
Definition
butenedioic acid: Either oftwo isomers with the formulaHCOOHC:CHCOOH. Both compoundscan be regarded as derivativesof ethene in which a hydrogenatom on each carbon has been replacedby a –COOH group. The compoundsshow cis–trans isomerism.The trans form is fumaric acid (r.d.1.64; sublimes at 165°C) and the cisform is maleic acid (r.d. 1.59; m.p.139–140°C). Both are colourless crystallinecompounds used in makingsynthetic resins. The cis form israther less stable than the trans formand converts to the trans form at120°C. Unlike the trans form it caneliminate water on heating to form acyclic anhydride containing a–CO.O.CO– group (maleic anhydride).Fumaric acid is an intermediate inthe Krebs cycle.
Definition
ChEBI: A butenedioic acid in which the C2C double bond has E geometry. It is an intermediate metabolite in the citric acid cycle.
Definition
Either of two isomers. Transbutenedioic
acid (fumaric acid) is a crystalline
compound found in certain plants. Cisbutenedioic
acid (maleic acid) is used in the
manufacture of synthetic resins. It can be
converted into the trans isomer by heating
at 120°C.
Preparation
By the action of certain fungi (Rhizopus nigricans) on glucose; by oxidation of furfural with sodium chlorate in the pres- ence of vanadium pentoxide.
Production Methods
Commercially, fumaric acid may be prepared from glucose by the
action of fungi such as Rhizopus nigricans, as a by-product in the
manufacture of maleic and phthalic anhydrides, and by the
isomerization of maleic acid using heat or a catalyst.
On the laboratory scale, fumaric acid can be prepared by the
oxidation of furfural with sodium chlorate in the presence of
vanadium pentoxide.
Biotechnological Production
Currently, fumaric acid is mainly manufactured by chemical synthesis via the
precursor maleic acid, which is produced using either benzene or n-butane via
catalytic oxidation. However, there are enzymatic and fermentative
production routes for fumaric acid. Prior to the advent of inexpensive petroleumbased
chemistry, fumaric acid was produced commercially by fermentation using
organisms of the genus Rhizopus with an annual production of 4,000 metric tons
. Product concentrations from 30 to 130 g.L-1 with yields from 0.3 to 1.0 g
of fumaric acid per gram of glucose and productivities of 0.46–2.0 g.L-1.h-1 have
been reported growing on glucose .
In recent years, new approaches using metabolic engineering have been studied.
For example, fumaric acid concentrations of 28.2 g.L-1 with a productivity of
0.448 g.L-1.h-1 have been reached in fed-batch cultivation of a genetic modified
E. coli . To achieve this result, eight modifications have been implemented.
Fumaric acid could be alternatively synthesized by an enzymatic process
starting from maleic acid as in the chemical synthesis. By whole-cell biocatalysis
of the Pseudomonas alcaligenes strain XD-1, a yield of 0.698 g of fumaric acid per
gram of maleic acid and a production rate of 6.98 g.L-1.h-1 have been reached
. The process has been optimized. The formation of the byproduct malic acid
was avoided due to an inactivation of fumarase by a heat treatment of the cells
beforehand. Finally, a yield of 0.95 g fumaric acid per gram maleic acid and a
production rate of 14.25 g.L-1.h-1 have been observed.
Flammability and Explosibility
Nonflammable
Pharmaceutical Applications
Fumaric acid is used primarily in liquid pharmaceutical preparations
as an acidulant and flavoring agent. Fumaric acid may be
included as the acid part of effervescent tablet formulations,
although this use is limited as the compound has an extremely
low solubility in water. It is also used as a chelating agent which
exhibits synergism when used in combination with other true
antioxidants.
In the design of novel pelletized formulations manufactured by
extrusion–spheronization, fumaric acid was used to aid spheronization,
favoring the production of fine pellets. It has also been
investigated as an alternative filler to lactose in pellets.
Fumaric acid has been investigated as a lubricant for effervescent
tablets, and copolymers of fumaric acid and sebacic acid have
been investigated as bioadhesive microspheres.It has been used in
film-coated pellet formulations as an acidifying agent and also to
increase drug solubility.
Fumaric acid is also used as a food additive at concentrations up
to 3600 ppm, and as a therapeutic agent in the treatment of
psoriasis and other skin disorders.
Safety
Fumaric acid is used in oral pharmaceutical formulations and food
products, and is generally regarded as a relatively nontoxic and
nonirritant material. However, acute renal failure and other adverse
reactions have occurred following the topical and systemic
therapeutic use of fumaric acid and fumaric acid derivatives in the
treatment of psoriasis or other skin disorders. Other adverse
effects of oral therapy have included disturbances of liver function,
gastrointestinal effects, and flushing.
The WHO has stated that the establishment of an estimated
acceptable daily intake of fumaric acid or its salts was unnecessary
since it is a normal constituent of body tissues.
LD50 (mouse, IP): 0.1 g/kg
LD50 (rat, oral): 9.3 g/kg
Carcinogenicity
No evidence of carcinogenicity
was found in several chronic studies with rats in
which fumaric acid was added to the diet at concentrations
up to 1.5%. As for dermal application, Swiss
mice were treated topically twice weekly with a 1% solution in acetone (volume not specified). Moderate focal
hyperplasia was found in the treated group, but no tumors
developed.
The inhibitory effect of fumaric acid on hepatocarcinogenesis
was examined in male IBR mice fed 0.035% thioacetamide
in the diet for 40 weeks and then fed a basal diet for
48 weeks. The inhibitory effect of 1% fumaric acid in the
basal diet on thioacetamide carcinogenesis was so marked
that no hepatic carcinomas were found in any of the 15 animals
fed fumaric acid in combination with thioacetamide
. Similar inhibitory effects of fumaric acid on
forestomach and lung carcinogenesis in mice (that resulted
from exposure to potassium naphthyridine-3-carboxylate)
have been identified.
storage
Fumaric acid is stable although it is subject to degradation by both
aerobic and anaerobic microorganisms. When heated in sealed
vessels with water at 150–170°C it forms DL-malic acid.
The bulk material should be stored in a well-closed container in a
cool, dry place.
Purification Methods
Crystallise it from hot M HCl or water and dry it at 100o. [Beilstein 2 IV 2202.]
Regulatory Status
GRAS listed. Accepted for use as a food additive in Europe.
Included in the FDA Inactive Ingredients Database (oral capsules,
suspensions, syrups, extended release and sustained action chewable
tablets). Included in the Canadian List of Acceptable Nonmedicinal
Ingredients.