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HSDB Env. Health & Toxicology TOXNET HSDB

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Human Health Effects:


Human Toxicity Excerpts:
AGED AQ SOLN OF EITHER SUBSTANCE /MALEIC ACID OR MALEIC ANHYDRIDE/ EXHIBIT EQUAL TOXICITY OWING TO CONVERSION OF THE ANHYDRIDE TO ACID BY REACTION WITH WATER.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 574] **PEER REVIEWED**

Toxic by ingestion.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 724] **PEER REVIEWED**


Skin, Eye and Respiratory Irritations:
Dust: Irritating to eyes, nose and throat. ... Solid: Irritating to skin and eyes.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Probable Routes of Human Exposure:
The general population is exposed to maleic acid in aerosols from auto exhaust. Occupational exposure would be via dermal contact and inhalation of aerosols containing maleic acid. (SRC)
**PEER REVIEWED**

17,037 Workers are potentially exposed to maleic acid based on statistical estimates derived from the NIOSH survey conducted in 1972-1974 in the USA(1). 8,733 workers are potentially exposed to maleic acid based on statistical estimates derived from the NIOSH survey conducted in 1981-1983 in the USA(2).
[(1) NIOSH; National Occupational Health Survey (1975) (2) NIOSH; National Occupational Exposure Survey (1985)] **PEER REVIEWED**


Emergency Medical Treatment:


Emergency Medical Treatment:

MALEIC ACID CASRN: 110-16-7

EMT Copyright Disclaimer:

The information contained in the Truven Health Analytics Inc. products is intended as an educational aid only. All treatments or procedures are intended to serve as an information resource for physicians or other competent healthcare professionals performing the consultation or evaluation of patients and must be interpreted in view of all attendant circumstances, indications and contraindications. The use of the Truven Health Analytics Inc. products is at your sole risk. These products are provided "as is" and "as available" for use, without warranties of any kind, either express or implied. Truven Health Analytics Inc. makes no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the productsAdditionally, Truven Health ANALYTICS INC. makes no representation or warranties as to the opinions or other service or data you may access, download or use as a result of use of the Truven Health ANALYTICS INC. products. All implied warranties of merchantability and fitness for a particular purpose or use are hereby excluded. Truven Health Analytics Inc. does not assume any responsibility or risk for your use of the Truven Health Analytics Inc. products. The following Overview, *** GENERAL OR UNKNOWN CHEMICAL ***, is relevant for this HSDB record chemical.

Life Support:

o   This overview assumes that basic life support measures       have been instituted.

Clinical Effects:

0.2.1 SUMMARY OF EXPOSURE   0.2.1.1 ACUTE EXPOSURE     A)  A SPECIFIC REVIEW on the clinical effects and treatment         of individuals exposed to this agent HAS NOT YET BEEN         PREPARED. The following pertains to the GENERAL         EVALUATION and TREATMENT of individuals exposed to         potentially toxic chemicals.     B)  GENERAL EVALUATION -      1)  Exposed individuals should have a careful, thorough          medical history and physical examination performed,          looking for any abnormalities. Exposure to chemicals          with a strong odor often results in such nonspecific          symptoms as headache, dizziness, weakness, and nausea.     C)  IRRITATION -      1)  Many chemicals cause irritation of the eyes, skin, and          respiratory tract. In severe cases respiratory tract          irritation can progress to ARDS/acute lung injury,          which may be delayed in onset for up to 24 to 72 hours          in some cases.      2)  Irritation or burns of the esophagus or          gastrointestinal tract are also possible if caustic or          irritant chemicals are ingested.     D)  HYPERSENSITIVITY -      1)  A number of chemical agents produce an allergic          hypersensitivity dermatitis or asthma with          bronchospasm and wheezing with chronic exposure.

Laboratory:

A)  A number of chemicals produce abnormalities of the       hematopoietic system, liver, and kidneys. Monitoring       complete blood count, urinalysis, and liver and kidney       function tests is suggested for patients with significant       exposure.   B)  If respiratory tract irritation or respiratory depression       is evident, monitor arterial blood gases, chest x-ray,       and pulmonary function tests.

Treatment Overview:

0.4.2 ORAL EXPOSURE    A)  GASTRIC LAVAGE     1)  Significant esophageal or gastrointestinal tract         irritation or burns may occur following ingestion. The         possible benefit of early removal of some ingested         material by cautious gastric lavage must be weighed         against potential complications of bleeding or         perforation.     2)  GASTRIC LAVAGE: Consider after ingestion of a         potentially life-threatening amount of poison if it can         be performed soon after ingestion (generally within 1         hour). Protect airway by placement in the head down         left lateral decubitus position or by endotracheal         intubation. Control any seizures first.      a)  CONTRAINDICATIONS: Loss of airway protective reflexes          or decreased level of consciousness in unintubated          patients; following ingestion of corrosives;          hydrocarbons (high aspiration potential); patients at          risk of hemorrhage or gastrointestinal perforation;          and trivial or non-toxic ingestion.    B)  ACTIVATED CHARCOAL     1)  Activated charcoal binds most toxic agents and can         decrease their systemic absorption if administered soon         after ingestion. In general, metals and acids are         poorly bound and patients ingesting these materials         will not likely benefit from activated charcoal         administration.      a)  Activated charcoal should not be given to patients          ingesting strong acidic or basic caustic chemicals.          Activated charcoal is also of unproven value in          patients ingesting irritant chemicals, where it may          obscure endoscopic findings when the procedure is          justified.     2)  ACTIVATED CHARCOAL: Administer charcoal as a slurry         (240 mL water/30 g charcoal). Usual dose: 25 to 100 g         in adults/adolescents, 25 to 50 g in children (1 to 12         years), and 1 g/kg in infants less than 1 year old.    C)  DILUTION -     1)  Immediate dilution with milk or water may be of benefit         in caustic or irritant chemical ingestions.     2)  DILUTION: Immediately dilute with 4 to 8 ounces (120 to         240 mL) of water or milk (not to exceed 4 ounces/120 mL         in a child).    D)  IRRITATION -     1)  Observe patients with ingestion carefully for the         possible development of esophageal or gastrointestinal         tract irritation or burns. If signs or symptoms of         esophageal irritation or burns are present, consider         endoscopy to determine the extent of injury.    E)  OBSERVATION CRITERIA -     1)  Carefully observe patients with ingestion exposure for         the development of any systemic signs or symptoms and         administer symptomatic treatment as necessary.     2)  Patients symptomatic following exposure should be         observed in a controlled setting until all signs and         symptoms have fully resolved.  0.4.3 INHALATION EXPOSURE    A)  DECONTAMINATION -     1)  INHALATION: Move patient to fresh air. Monitor for         respiratory distress. If cough or difficulty breathing         develops, evaluate for respiratory tract irritation,         bronchitis, or pneumonitis. Administer oxygen and         assist ventilation as required. Treat bronchospasm with         inhaled beta2 agonist and oral or parenteral         corticosteroids.    B)  IRRITATION -     1)  Respiratory tract irritation, if severe, can progress         to pulmonary edema which may be delayed in onset up to         24 to 72 hours after exposure in some cases.    C)  ACUTE LUNG INJURY -     1)  ACUTE LUNG INJURY: Maintain ventilation and oxygenation         and evaluate with frequent arterial blood gas or pulse         oximetry monitoring. Early use of PEEP and mechanical         ventilation may be needed.    D)  BRONCHOSPASM -     1)  If bronchospasm and wheezing occur, consider treatment         with inhaled sympathomimetic agents.    E)  OBSERVATION CRITERIA -     1)  Carefully observe patients with inhalation exposure for         the development of any systemic signs or symptoms and         administer symptomatic treatment as necessary.     2)  Patients symptomatic following exposure should be         observed in a controlled setting until all signs and         symptoms have fully resolved.  0.4.4 EYE EXPOSURE    A)  DECONTAMINATION: Irrigate exposed eyes with copious        amounts of room temperature water for at least 15        minutes. If irritation, pain, swelling, lacrimation, or        photophobia persist, the patient should be seen in a        health care facility.  0.4.5 DERMAL EXPOSURE    A)  OVERVIEW     1)  DERMAL DECONTAMINATION -      a)  DECONTAMINATION: Remove contaminated clothing and wash          exposed area thoroughly with soap and water. A          physician may need to examine the area if irritation          or pain persists.     2)  PESTICIDES -      a)  DECONTAMINATION: Remove contaminated clothing and          jewelry. Wash the skin, including hair and nails,          vigorously; do repeated soap washings. Discard          contaminated clothing.     3)  IRRITATION -      a)  Treat dermal irritation or burns with standard topical          therapy. Patients developing dermal hypersensitivity          reactions may require treatment with systemic or          topical corticosteroids or antihistamines.     4)  DERMAL ABSORPTION -      a)  Some chemicals can produce systemic poisoning by          absorption through intact skin. Carefully observe          patients with dermal exposure for the development of          any systemic signs or symptoms and administer          symptomatic treatment as necessary.

Range of Toxicity:

A)  No specific range of toxicity can be established for the       broad field of chemicals in general.

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2013; CCIS Volume 157, edition expires Aug, 2013. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2013; CCIS Volume 157, edition expires Aug, 2013.] **PEER REVIEWED**


Animal Toxicity Studies:


Non-Human Toxicity Excerpts:
IN CHRONIC FEEDING STUDIES WITH RATS SOME TOXIC EFFECTS WERE NOTED AT CONCN AS LOW AS 0.5%. THE DIFFERENCES FROM CONTROLS WERE NOT MARKED AND THE PATHOLOGY WAS NONSPECIFIC. DAILY DOSES OF 0.5 TO 2.0 MG/RAT INJECTED SUBCUTANEOUSLY IN SESAME OIL FOR 60 DAYS WERE TOLERATED, WHEREAS 5 TO 10 MG/RAT PRODUCED DEATH, RETARDED GROWTH AND PATCHY HAIR DISTRIBUTION.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4969] **PEER REVIEWED**

ON RABBIT EYES 10% MALEIC ACID IN WATER AT PH 1 APPLIED FOR THIRTY SECONDS CAUSES PERMANENT OPACITY & VASCULARIZATION. A 1% SOLN APPLIED FOR 2 MINUTES CAUSES CLOUDINESS OF CORNEA, BUT NO INJURY REMAINS THE NEXT DAY. A 5% SOLN HAS SIMILAR BUT MORE INTENSE EFFECT, WITH RECOVERY DELAYED 6-7 DAYS.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 574] **PEER REVIEWED**

ADMIN OF MALEIC ACID (WHICH GIVES RISE TO RENAL TUBULAR TRANSPORT DEFECTS) TO RATS CAUSED INCREASED URINARY EXCRETION OF S-(1,2-DICARBOXYETHYL)CYSTEINE & INCREASED BINDING OF MALEIC ACID TO TISSUE PROTEINS.
[SHIMOMURA M; PHYSIOL CHEM PHYS 9 (6): 539-42 (1977)] **PEER REVIEWED** PubMed Abstract

... 400 MG/KG BY INTRAPERITONEAL INJECTION MARKEDLY DECREASED BLOOD SUGAR LEVELS IN FASTED RATS, CAUSING A SIMULTANEOUS INCREASE IN PLASMA FREE FATTY ACIDS AND ACETOACETATE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4969] **PEER REVIEWED**

A 1 HR INHALATION EXPOSURE OF SIX RATS TO 0.72 MG/L, PRODUCED GENERALIZED INACTIVITY, HYPERPNEA, AND SEDATION WITHIN 15 MIN OF EXPOSURE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4969] **PEER REVIEWED**

MALEIC ACID PRODUCES IN RATS A CONDITION ANALOGOUS TO THE HUMAN FANCONI SYNDROME, CHARACTERIZED BY INCREASED URINARY ELIMINATION OF GLUCOSE, AMINO ACIDS, AND OTHER BIOCHEMICALS, AND RESULTING FROM IMPAIRED TUBULAR REABSORPTION OF THESE MATERIALS. ULTRASTRUCTURAL CHANGES OCCUR AT CONCENTRATIONS AS LOW AS 1.5 MMOL MALEIC ACID.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4971] **PEER REVIEWED**

The effects of maleic hydrazide & its conversion or decomposition products, maleic acid diamide, succinic acid, maleic acid, lactic acid, & hydrazine on chromosomal aberrations in Vicia faba roots tips were evaluated. All maleic hydrazide products, except hydrazine, were nonclastogenic with aberration yields ranging from 0.01 to 0.02 aberrations/cell. Controls treated with water had 0.01 aberrations/cell.
[Heindorff K et al; Mutat Res 140 (2-3): 123-6 (1984)] **PEER REVIEWED** PubMed Abstract

When tested using Salmonella typhimurium TA100, maleic acid was not mutagenic when reacted with chlorine in aqueous solution. In a 50/50 by vol methanol/water solution it was substantially mutagenic, and reacted with chlorine with a peak at 3 equivalents per mole.
[Nazar MA et al; Mutat Res 89: 45-55 (1981)] **PEER REVIEWED** PubMed Abstract

Admin of maleic acid to rats is used as an exptl model of Fanconi's syndrome. To determine the site & extent of morphologic injury within the kidney after maleic acid admin, the renal tissue was examined using light, transmission electron, & scanning electron microscopy. Evidence of injury was observed only in cells of the late pars convoluta & the pars recta in the medullary rays of the cortex & in the outer strip of the medulla. Injury was apparent immediately after maleic acid admin & progressed to extensive necrosis by 24 hr after 200 or 400 mg/kg dose. Results provide evidence that maleic acid produces tubular injury & necrosis only in the proximal tubules, primarily in the medullary rays, & outer strip of the mudulla, & not in the distal tubules.
[Verani RR et al; Lab Invest 46 (1): 79-88 (1982)] **PEER REVIEWED** PubMed Abstract

IN DOGS THE INTRAVENOUS ADMINISTRATION OF MALEIC ACID (50 MG/KG) INCREASED SODIUM, POTASSIUM, AND PHOSPHATE EXCRETION.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4971] **PEER REVIEWED**

During the acute renal tubular dysfunction of Fanconi syndrome and type two renal tubular acidosis (FS/RTA2) induced by maleic acid in the unanesthetized dog, /the following was observed/: 1) 30 minutes after the onset of FS/RTA2, the urinary excretion of lysosomal enzymes, N-acetyl-beta-glucosaminidase, beta-glucuronidase (beta-gluc) and beta-galactosidase (beta-glac), increased simultaneously with the anticipated increase in renal clearance of lysozyme; 2) the severities of all these hyperenzymurias increased rapidly, progressisvely, and in parallel, all reaching a peak some 60 to 80 minute after their onset; 3) thereafter, while the FS/RTA2 continued undiminished in severity, the severity of the hyperenzymurias decreased rapidly, greatly, progressively, and in parallel; and 4) sodium phosphate loading strikingly attenuated the FS/RTA2 and the hyperenzymurias.
[Al-Bander HA et al; Kidney Int 30 (6): 804-12 (1986)] **PEER REVIEWED** PubMed Abstract

Maleic acid was administered iv both alone and after initating iv administered neutral sodium phosphate, sodium sulfate, or sodium choride to 10 unanesthetized trained female dogs undergoing water diuresis. /The following observations were noted:/ 1) Administration of maleic acid alone predictably induced dose-dependent increments in urine flow and in renal clearance of HCO3-, Na+, K+, and alpha-aminonitrogen and a pronounced increase in the renal clearance and excretion of citrate. 2) Prior phosphate loading, which increased the plasma concentration of phosphate from 2.5 + or - 0.20 to 11.3 + or - 2 mg/dl: a) attenuated the increment in renal clearance of HCO3 by one-half even though the filtered load of bicarbonate was higher by 37%, owing to the higher values of both GFR and plasma bicarbonate concentration that obtained with phosphate loading; b) prevented the increment in renal clearance and exretion ofalpha-aminonitrogen; c) significantly attenuated the increments in urine flow and renal clearance of K+; but d) did not affect the increment in renal clearance and excretion of citrate.
[Al-Bander H et al; Am J Physiol 248 (4): 513-21 (1985)] **PEER REVIEWED**

Single oral administration of pravadoline maleate (WIN 48098-6), the maleic acid salt of WIN 48098, induced acute tubular necrosis in male and female beagle dogs at dosages > or = 40 mg/kg (WIN 48098 base (31 mg/kg) and maleic acid (9 mg/kg)). Subsequent oral studies were conducted with equimolar dosages of maleic acid and WIN 48098-7, the ethanesulfonate salt of WIN 48098, to determine the nephrotoxic moiety of WIN 48098-6. Acute tubular necrosis was observed for dogs given only maleic acid at single oral dosages > or = 9 mg/kg. This result provided evidence that maleic acid was responsible for the nephrotoxicity observed in dogs given single oral dosages of WIN 48098-6. The induction of maleic acid related nephrotoxicity in dogs may confound the interpretation of toxicologic studies of maleic acid salts of basic pharmaceutics, if the dosage of test article results in the delivery of dosages of maleic acid > or = 9 mg/kg. Furthermore, the results of these studies underscore the importance of establishing maximum no observed effect dosages and target organ toxicity profiles for acids and bases that are commonly used in the development of salts of pharmaceutics.
[Everett RM et al; Fundam Appl Toxicol 21 (1): 59-65 (1993)] **PEER REVIEWED** PubMed Abstract

The potential for maleic acid to influence revertant rates in Ames Salmonella plate incorporation mutagenicity assays was assessed. Maleic acid, its acid salt monosodium maleate, and its neutral salt disodium maleate hydrate were examined at toxicity limited dose levels with the routine Salmonella tester strains (TA-1535), (TA-1537), (TA-1538), (TA-98), and (TA-100). Metabolic activatio was provided by adding rat liver microsomal enzymes supplemented with cofactors. Revertant colonies were quantitated after 2 days of incubation. The normal salt of maleic acid did not influence top agar pH; the acid salt progressively lowered pH to 5.8; and maleic acid itself depressed pH to as low as 2.4. Maleic acid proved nonmutagenic despite the noted depression of top agar pH in accordance with the degree of protonation of the polybasic acid. It was concluded that the butenedioic moiety and potential oxidative metabolites of maleic acid are not mutagenic to the tested Salmonella strains; activity detected by the assay with maleate salt compounds could be attributed to the base moiety rather than maleate or pH depression per se.
[Lake RS et al; Mut Res Lett 207 (1): 1-5 (1988)] **PEER REVIEWED**

IN RENAL CORTEX SLICES OF THE RAT, MALEATE HAD NO EFFECT ON THE RATE OF DISAPPEARANCE OF GLUTATHIONE (GSH) BETWEEN 10 AND 60 MIN OF INCUBATION, BUT GSH LEVELS IN MALEATE-TREATED SLICES DROPPED TO LOWER LEVELS THAN CONTROL SLICES AT 90 AND 120 MIN. /MALEATE/
[RICHARDSON RJ ET AL; DEPARTMENT OF PHYSIOLOGY, SCHOOL OF PUBLIC HEALTH, HARVARD UNIVERSITY, 665 HUNTINGTON AVENUE, BOSTON, MA 02115] **PEER REVIEWED**

Maleate stimulates glutamine uptake, ammonia production & glutamate production while inhibiting gluconeogenesis by renal cortical slices from control & acidotic rats. Uptake of (14)C glutamine by luminal brush border vesicles is stimulated by maleate in the absence of sodium. /Maleate/
[McFarlane-Anderson N, Alleyne GAO; Biochem Med 25 (2): 149-59 (1981)] **PEER REVIEWED** PubMed Abstract

Nephrotoxic acute renal failure was induced in rats by ip admin of maleate. Maleate enhanced the formation of free radicals & peroxides, which presumably overload the cell's natural elimination mechanisms for these highly reactive intermediates. In addition, a reduction in activities of superoxide dismutase, catalase, & glutathione-peroxidase was found. Acute renal failure, enhanced lipid peroxidation in kidney homogenates in vitro was observed. Maleate may react with free SH-groups & lead to a depletion of glutathione in tubular cells. Renal cortical contents of reduced & oxidized glutathione were drastically diminished. Alterations in membrane integrity, possibly caused by peroxidative processes, can be considered the cause of the disturbances in renal function observed during the initiation phase of maleate induced acute renal failure. /Maleate/
[Gstraunthaler G et al; Biochem Pharmacol 32 (19): 2969-72 (1983)] **PEER REVIEWED** PubMed Abstract

The mechanism of tubular acidification was studied in proximal tubular acidification defect induced in rats by acute parenteral infusion of maleate (200 mg/kg), which causes diuresis & bicarbonaturia. Results show that maleate affects both proximal Na+ & H+ transport; this effect may be ascribed to impairment of sodium-dependent transport systems in the brush-border membrane. /Maleate/
[Reboucas NA et al; Pflugers Arch 401 (3): 266-71 (1984)] **PEER REVIEWED** PubMed Abstract

The effects of maleate on the physical state of isolated brush border & basolateral membranes from dog kidney cortex were studied by fluorescence polarization & ESR methods. Results indicate that maleic acid nephropathy is not due to a direct effect of maleate on tubular membranes per se. /Maleate/
[Le Grimellec C et al; Life Sci 30 (13): 1107-11 (1982)] **PEER REVIEWED** PubMed Abstract

Micropuncture & clearance studies were performed to assess reabsorptive function in the proximal & distal nephron of rats with experimental Fanconi's syndrome induced by maleic acid. These studies suggest that maleic acid inhibits reabsorption at a distal nephron site or sites as well as in the proximal tubule.
[Brewer ED et al; Am J Physiol 245 (3): F339-44 (1983)] **PEER REVIEWED**


Non-Human Toxicity Values:
LD50 Rat oral 708 mg/kg
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 786 (1981)] **PEER REVIEWED**

LD50 Mouse oral 2400 mg/kg
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 786 (1981)] **PEER REVIEWED**

LD50 Rabbit dermal 1560 mg/kg
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 786 (1981)] **PEER REVIEWED**


Ecotoxicity Values:
TLm Mosquito fish 240 ppm/24-48 hr fresh water /Conditions of bioassay not specified/
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**

TLm Fathead minnow 5 ppm/96 hr fresh water /Conditions of bioassay not specified/
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Metabolism/Pharmacokinetics:


Mechanism of Action:
... MAY ENHANCE ANAPHYLACTIC HISTAMINE RELEASE FROM GUINEA PIG LUNG BY ITS METABOLIC UTILIZATION IN THE TRICARBOXYLIC ACID CYCLE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4971] **PEER REVIEWED**

Administration of heavy metals or maleic acid induces a condition resembling the Fanconi syndrome. Transport of aspartate is now shown to be similarly inhibited by maleic acid and cephaloridin. Maleic acid exerts an apparent uncompetitive effect within minutes of injection, the inhibition cannot simply reflect characteristics of regenerating epithelium. The mechanism of the aminoaciduric action of maleic acid remains unclear but cannot, under present conditions, involve back leakage of amino acids into tubular urine.
[Foulkes EC; Toxicol Appl Pharmacol 71 (3): 445-50 (1983)] **PEER REVIEWED** PubMed Abstract


Interactions:
The admin of maleic acid (100 mg/kg) to rats which were infused with acetoacetic acid (200 mM at 0.1 ml/min) did not induce phosphaturia or calciuria, whereas maleic acid given alone was phosphaturic & calciuric. There was a significant decrease of the phosphate & calcium excretion in maleic acid-treated rats after the iv injection of 150 pg 1,25-dihydroxyvitamin D3 in comparison with the control group.
[Angielski S et al; Calcium Phosphate Transp Biomembr (Int Workshop): 231-5 (1981)] **PEER REVIEWED**

Groups of male and female Sprague Dawley rats (n = 4 to 8 for each sex) were admin either maleic acid (150 mg/kg, sc), dichloromaleic acid (100, 200, 300, or 400 mg/kg, ip) or their combination. Urine was collected at 24 hr intervals. In both males and females, dose dependent declines in food and water consumption as well as body wt and urine flow were observed at 24 hr post-treatment with maleic acid, dichloromaleic acid, or dichloromaleic acid + maleic acid. Sc administration of maleic acid at a dose of 150 mg/kg had no effect on several parameters of renal function in either sex at 24 hr and only modest effects at 48 hr. Maleic acid alone had no effect on renal organic ion accumulation in either sex. The combination of maleic acid + dichloromaleic acid caused a depression of tetraethylammonium accumulation in renal slices from females. Also changes in urinary glucose excretion and blood urea nitrogen, although additive in the male following coexposure, appeared synergistic or potentiated in the female. For females, maleic maleic alone produced a greater response in urinary glucose than control, and the combination resulted in a significantly exaggerated response at 24 hr. There were not significant alterations in urinary glucose in the male at 24 hr after any dosages. Both p-aminohippurate and lactate stimulated p-aminohippurate transport were impaired in the female with either dichloromaleic acid or dichloromaleic acid + maleic acid and to a significantly greater extent than in the male. Triethanolamine accumulation in the female declined significantly when exposed to dichloromaleic acid + maleic acid, an effect not observed in the male.
[Christenson WR et al; Toxicology 56 (3): 229-38 (1989)] **PEER REVIEWED** PubMed Abstract


Pharmacology:


Interactions:
The admin of maleic acid (100 mg/kg) to rats which were infused with acetoacetic acid (200 mM at 0.1 ml/min) did not induce phosphaturia or calciuria, whereas maleic acid given alone was phosphaturic & calciuric. There was a significant decrease of the phosphate & calcium excretion in maleic acid-treated rats after the iv injection of 150 pg 1,25-dihydroxyvitamin D3 in comparison with the control group.
[Angielski S et al; Calcium Phosphate Transp Biomembr (Int Workshop): 231-5 (1981)] **PEER REVIEWED**

Groups of male and female Sprague Dawley rats (n = 4 to 8 for each sex) were admin either maleic acid (150 mg/kg, sc), dichloromaleic acid (100, 200, 300, or 400 mg/kg, ip) or their combination. Urine was collected at 24 hr intervals. In both males and females, dose dependent declines in food and water consumption as well as body wt and urine flow were observed at 24 hr post-treatment with maleic acid, dichloromaleic acid, or dichloromaleic acid + maleic acid. Sc administration of maleic acid at a dose of 150 mg/kg had no effect on several parameters of renal function in either sex at 24 hr and only modest effects at 48 hr. Maleic acid alone had no effect on renal organic ion accumulation in either sex. The combination of maleic acid + dichloromaleic acid caused a depression of tetraethylammonium accumulation in renal slices from females. Also changes in urinary glucose excretion and blood urea nitrogen, although additive in the male following coexposure, appeared synergistic or potentiated in the female. For females, maleic maleic alone produced a greater response in urinary glucose than control, and the combination resulted in a significantly exaggerated response at 24 hr. There were not significant alterations in urinary glucose in the male at 24 hr after any dosages. Both p-aminohippurate and lactate stimulated p-aminohippurate transport were impaired in the female with either dichloromaleic acid or dichloromaleic acid + maleic acid and to a significantly greater extent than in the male. Triethanolamine accumulation in the female declined significantly when exposed to dichloromaleic acid + maleic acid, an effect not observed in the male.
[Christenson WR et al; Toxicology 56 (3): 229-38 (1989)] **PEER REVIEWED** PubMed Abstract


Environmental Fate & Exposure:


Environmental Fate/Exposure Summary:
Maleic acid may be released into waste water during its production and use in the manufacture of polymer products. Maleic acid is also released into the atmosphere from motor exhaust and is a constituent of aerosols in urban air. If released on land, maleic acid will leach into the ground and probably biodegrade. If released into water, maleic acid will also probably biodegrade. Adsorption to sediment, bioconcentration in aquatic organisms, and volatilization should not be significant. It will be primarily associated with aerosols in the atmosphere and be subject to gravitational settling and degradation by reaction with ozone and photochemically produced hydroxyl radicals (vapor phase half-life 1.1 hr). The general population is exposed to maleic acid in areas with heavy traffic since it is found in aerosols from auto exhaust. Occupational exposure would be via dermal contact and inhalation of aerosols containing maleic acid. (SRC)
**PEER REVIEWED**


Probable Routes of Human Exposure:
The general population is exposed to maleic acid in aerosols from auto exhaust. Occupational exposure would be via dermal contact and inhalation of aerosols containing maleic acid. (SRC)
**PEER REVIEWED**

17,037 Workers are potentially exposed to maleic acid based on statistical estimates derived from the NIOSH survey conducted in 1972-1974 in the USA(1). 8,733 workers are potentially exposed to maleic acid based on statistical estimates derived from the NIOSH survey conducted in 1981-1983 in the USA(2).
[(1) NIOSH; National Occupational Health Survey (1975) (2) NIOSH; National Occupational Exposure Survey (1985)] **PEER REVIEWED**


Artificial Pollution Sources:
Maleic acid may be released into waste water during its production and use in the manufacture of alkyd and other resins(1), organic synthesis, dyeing and finishing of textiles, as a preservative for fats and oils(2) and as a by product of phthalic anhydride production(4). Motor exhaust is an important primary source in urban areas(3).
[(1) Kuney JH; Chemcyclopedia Amer Chem Soc Washington,DC p. 87 (1987) (2) Hawley GG; Condensed Chem Dictionary 10th ed. NY: Von Nostrand Reinhold pp. 638 (1981) (3) Kawamura K, Kaplan IR; Environ Sci Technol 21: 105-10 (1987) (4) Bemis AG et al; In: Kirk-Othmer Encyclopedia Chemical Technology 3rd ed. 17: 732-77 (1982)] **PEER REVIEWED**

Maleic anhydride released into water will hydrolyze rapidly (half-life 0.37 min)to maleic acid.
**PEER REVIEWED**


Environmental Fate:
TERRESTRIAL FATE: If released on land, maleic acid will leach into the ground and probably biodegrade. While maleic acid is readily biodegraded, no degradability data were found for soil systems. (SRC)
**PEER REVIEWED**

AQUATIC FATE: If released into water, maleic acid will probably biodegrade based on the results of screening studies. No biodegradability studies were found in environmental waters. Adsorption to sediment and volatilization should not be significant. (SRC)
**PEER REVIEWED**

ATMOSPHERIC FATE: Due to its polar nature, maleic acid released into the atmosphere will be primarily associated with aerosols. It will be subject to gravitational settling and also degrade by reaction with ozone and photochemically produced hydroxyl radicals (half-life 1.1 hr). (SRC)
**PEER REVIEWED**


Environmental Abiotic Degradation:
Maleic acid has pKa's of 1.83 and 6.07(1) and will therefore exist largely in the dissociated form in the environment and form salts with cations. The vapor should react with ozone and photochemically produced hydroxyl radicals in the atmosphere by addition to the double bond with a resulting estimated vapor phase half-life of 1.1 hr(2). When adsorbed on silica gel and irradiated with light >290 nm for 17 hr, 17% of the maleic acid is mineralized(3).
[(1) Weast RC; Handbook of Chemistry and Physics (1972) (2) GEMS; Graphical Exposure Modeling System. FAP. Fate of Atmos Pollut (1986) (3) Freitag D, et al; Ecotox Environ Safety 6: 60-81 (1982)] **PEER REVIEWED**


Environmental Bioconcentration:
The BCF of maleic acid in fish (golden ide) was <10 after 3 days of exposure while that in algae (Chorella fusca) was 11 after 24 hr(1). The BCF calculated from the water solubility (788 g/l) using a recommended regression equation is 3(2), which indicates the bioconcentration should not be an important process.
[(1) Freitag D, et al; Ecotox Environ Safety 6: 60-81 (1982) (2) Geyer H, et al; Chemosphere 10: 1307-13 (1981)] **PEER REVIEWED**


Soil Adsorption/Mobility:
Maleic acid is extremely soluble in water (788 g/l(1)) and therefore would not adsorb appreciably to soil(2).
[(1) Geyer H, et al; Chemosphere 10:1307-13 (1981) (2) Lyman WJ et al; Handbook of Chem Property Estimation Methods. Environ Behavior of Organic Compounds. McGraw-Hill NY pp.4-1 to 4-33 (1982)] **PEER REVIEWED**


Volatilization from Water/Soil:
Maleic acid is a solid that melts at 130 deg C(1) and is extremely soluble in water (788 g/l(2)). Therefore, volatilization from water should not be a significant transport process(3).
[(1) Daubert TE, Danner RP; Data Compilation Tables Of Properties Of Pure Compounds American Institute Of Chemical Engineers pp.450 (1985) (2) Geyer H, et al; Chemosphere 10: 1307-13 (1981) (3) Lyman WJ et al; Handbook of Chem Property Estimation Methods. Environ Behavior of Organic Compounds. McGraw-Hill NY pp.15-1 to 15-33 (1982)] **PEER REVIEWED**


Effluent Concentrations:
Motor exhaust of two automobiles contained 2.66 and 25.5 ug/cu m of maleic acid(2).
[(1) Kawamura K, Kaplan IR; Environ Sci Technol 21: 105-10 (1987)] **PEER REVIEWED**


Sediment/Soil Concentrations:
Soil samples taken at the Univ. of California, Los Angeles campus contained ND and 270 ppb of maleic acid, whereas bog sediment samples from the Sierra Nevada foothills contained 930 ppb(1).
[(1) Kawamura K, Kaplan IR; Environ Sci Technol 21: 105-10 (1987)] **PEER REVIEWED**


Atmospheric Concentrations:
The concn of maleic acid in aerosol samples from West Los Angeles and Los Angeles were 9-204 and 64-95 ng/cu m, respectively(1). Dust samples from these areas contained 6.4 and 2.4 ppm of maleic acid, respectively(1).
[(1) Kawamura K, Kaplan IR; Environ Sci Technol 21: 105-10 (1987)] **PEER REVIEWED**


Environmental Standards & Regulations:


FIFRA Requirements:
Maleic acid and maleic anhydride are exempted from the requirement of a tolerance when used as a stabilizer for pesticide formulations applied to apples with a minimum pre-harvest interval of 21 days.
[40 CFR 180.1001(d) (7/1/91)] **PEER REVIEWED**


CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
[40 CFR 302.4 (7/1/91)] **PEER REVIEWED**


Atmospheric Standards:
This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Maleic acid is produced, as an intermediate or a final product, by process units covered under this subpart.
[40 CFR 60.489 (7/1/91)] **PEER REVIEWED**


Clean Water Act Requirements:
Designated as a hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges of this substance.
[40 CFR 116.4 (7/1/91)] **QC REVIEWED**


FDA Requirements:
Maleic acid is an indirect food additive for use only as a component of adhesives.
[21 CFR 175.105 (4/1/91)] **PEER REVIEWED**


Allowable Tolerances:
Maleic acid and maleic anhydride are exempted from the requirement of a tolerance when used as a stabilizer for pesticide formulations applied to apples with a minimum pre-harvest interval of 21 days.
[40 CFR 180.1001(d) (7/1/91)] **PEER REVIEWED**


Chemical/Physical Properties:


Molecular Formula:
C4-H4-O4
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**


Molecular Weight:
116.07
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**


Color/Form:
MONOCLINIC PRISMS FROM WATER
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-311] **PEER REVIEWED**

WHITE CRYSTALS FROM WATER, ALCOHOL & BENZENE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**

Colorless crystals
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 724] **PEER REVIEWED**


Odor:
FAINT ACIDULOUS ODOR
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**


Taste:
CHARACTERISTIC REPULSIVE, ASTRINGENT TASTE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**


Boiling Point:
135 DEG C (DECOMP)
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4969] **PEER REVIEWED**


Melting Point:
138-139 DEG C CRYSTALS FROM WATER; 130-131 DEG C CRYSTALS FROM ALC & BENZENE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**


Corrosivity:
May corrode metals when wet.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Density/Specific Gravity:
1.590 @ 20 DEG C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-311] **PEER REVIEWED**


Dissociation Constants:
pKa = 1.83
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 76th ed. Boca Raton, FL: CRC Press Inc., 1995-1996., p. 8-46] **QC REVIEWED**


Heat of Combustion:
-323.89 Kg cal/g mol wt @ 25 deg C
[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 67th ed. Boca Raton, FL: CRC Press, Inc., 1986-87., p. D-275] **PEER REVIEWED**


Octanol/Water Partition Coefficient:
log Kow= -0.48
[Sangster J; LOGKOW Databank. Sangster Res Lab Montreal Quebec, Canada (1994)] **QC REVIEWED**


Solubilities:
FREELY SOL IN ALCOHOL; SOL IN ACETONE, GLACIAL ACETIC ACID; SLIGHTLY SOL IN ETHER; PRACTICALLY INSOL IN BENZENE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**

INSOL IN CHLOROFORM; SOL IN CONCENTRATED SULFURIC ACID
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-365] **PEER REVIEWED**

788 g/l water at 25 deg C, 3926 g/l water at 97.5 deg C
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 803] **PEER REVIEWED**

79.000 lb/100 lb water at 77 deg F
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**

Solubility (g/100 g) @ 25 deg C: benzene 0.024, chloroform 0.11, carbon tetrachloride 0.002, diethyl ether 7.57.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 772 (1981)] **PEER REVIEWED**

Solubility (g/100 g): acetone 38.6 (@ 20 deg C), methanol 41.0 (@ 22.5 deg C), ethanol 30.2 (@ 0 deg C) & 34.4 (@ 22.5 deg C), 1-propanol 20.0 (@ 0 deg C) & 24.3 (@ 22.5 deg C), 2-butenenitrile 4.38 (@ 50 deg C)
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 772 (1981)] **PEER REVIEWED**

water solubility = 441,000 mg/l @ 25 deg C
[Yalkowsky SH, Dannenfelser RM; The AQUASOL dATAbASE of Aqueous Solubility. Fifth Ed, Tucson, AZ: Univ Az, College of Pharmacy (1992)] **QC REVIEWED**


Spectral Properties:
MAX ABSORPTION (WATER): 210 NM (LOG E= 4.14); SADTLER REFERENCE NUMBER: 6253 (IR PRISM)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-365] **PEER REVIEWED**

IR: 15240 (Sadtler Research Laboratories IR Grating Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 819] **PEER REVIEWED**

UV: 6-18 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 819] **PEER REVIEWED**

NMR: 4532 (Sadtler Research Laboratories Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 819] **PEER REVIEWED**

MASS: 465 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 819] **PEER REVIEWED**


Vapor Density:
4.0 (AIR= 1)
[Sax, N.I. Dangerous Properties of Industrial Materials. 5th ed. New York: Van Nostrand Rheinhold, 1979., p. 784] **PEER REVIEWED**


Vapor Pressure:
3.59X10-5 mm Hg @ 25 deg C (extrapolated)
[Yaws CL; Handbook of Vapor Pressure. Volume 1 - C1 to C4 Compounds. Gulf Publishing Co: Houston, TX (1994)] **QC REVIEWED**


Other Chemical/Physical Properties:
CONVERTED IN PART INTO THE MUCH HIGHER-MELTING FUMARIC ACID (MP: 287 DEG C) WHEN HEATED TO A TEMP SLIGHTLY ABOVE THE MP.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**

Heat of combustion: 1356.3 kJ/mol (crystal)
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 5-83] **PEER REVIEWED**

Heat of combustion: -2,800 cal/g = -117x10+5 J/kg
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Chemical Safety & Handling:


DOT Emergency Guidelines:
/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Substance will react with water (some violently) releasing flammable, toxic or corrosive gases and runoff. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapors may travel to source of ignition and flash back. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated or if contaminated with water.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Health: TOXIC; inhalation, ingestion or contact (skin, eyes) with vapors, dusts or substance may cause severe injury, burns or death. Contact with molten substance may cause severe burns to skin and eyes. Reaction with water or moist air will release toxic, corrosive or flammable gases. Reaction with water may generate much heat which will increase the concentration of fumes in the air. Fire will produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Public Safety: CALL Emergency Response Telephone Number ... . As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Fire: Note: Most foams will react with the material and release corrosive/toxic gases. Small fires: CO2, dry chemical, dry sand, alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. ... Move containers from fire area if you can do it without risk. Use water spray or fog; do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Spill or Leak: ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). All equipment used when handling the product must be grounded. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. A vapor suppressing foam may be used to reduce vapors. ... DO NOT GET WATER on spilled substance or inside containers. Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact spilled material. Prevent entry into waterways, sewers, basements or confined areas. Small spills: Cover with DRY earth, DRY sand, or other non-combustible material followed with plastic sheet to minimize spreading or contact with rain. Use clean non-sparking tools to collect material and place it into loosely covered plastic containers for later disposal.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**

/GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ First Aid: Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004] **QC REVIEWED**


Skin, Eye and Respiratory Irritations:
Dust: Irritating to eyes, nose and throat. ... Solid: Irritating to skin and eyes.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Fire Potential:
It is combustible though it may take some effort to ignite.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**


Fire Fighting Procedures:
If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Solid streams of water may be ineffective. Use "alcohol" foam, carbon dioxide or dry chemical.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**


Firefighting Hazards:
Irritating smoke containing maleic anhydride may form in fire.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Hazardous Decomposition:
When heated to decomp it emits acrid smoke and fumes.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 551] **PEER REVIEWED**


Protective Equipment & Clothing:
/NIOSH certified respirator/; goggles or face shield; protective gloves.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**

Compatible protective equipment construction materials include: natural rubber, neoprene, nitrile rubber, nitrile rubber/polyvinyl chloride, polyethylene, polyurethane, polyvinyl chloride, and viton.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**


Preventive Measures:
SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
**PEER REVIEWED**

Local exhaust.
[Handling Chemicals Safety 1980; 2nd Ed, Dutch Association of Safety Experts, the Dutch Chemical Industry Association and the Dutch Institute] **PEER REVIEWED**

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**

Personnel protection: Avoid breathing vapors or dust. Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**


Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
[49 CFR 171.2 (7/1/96)] **QC REVIEWED**

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.
[IATA. Dangerous Goods Regulations. 38th ed. Montreal, Canada and Geneva, Switzerland: International Air Transport Association, Dangerous Goods Board, January, 1997., p. 172] **QC REVIEWED**

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.
[IMDG; International Maritime Dangerous Goods Code; International Maritime Organization p.8182 (1988)] **QC REVIEWED**


Storage Conditions:
Storage temp: ambient
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**

Protect containers against physical damage. Store in a cool, dry, well-ventilated location, away from any areas where the fire hazard may be extremely potential. Outdoor or detached storage is preferred.
[ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1982., p. 310] **PEER REVIEWED**


Cleanup Methods:
Environmental considerations: Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Cover solids wil a plastic sheet to prevent dissolving in rain or fire fighting water.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**

Environmental considerations: Water spill: If dissolved, in region of 10 ppm or greater concentration, apply activated carbon at 10 times the spilled amount. Use mechanical dredges or lifts to remove immobilized masses of pollutants and precipitates.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1992., p. 592] **PEER REVIEWED**


Occupational Exposure Standards:


Manufacturing/Use Information:


Major Uses:
CHEM INT FOR COMONOMERS IN ADHESIVES, FUMARIC ACID, ALKYD RESINS, & SYNTHETIC OILS
[SRI] **PEER REVIEWED**

MFR ARTIFICIAL RESINS; TO RETARD RANCIDITY OF FATS & OILS IN 1:10,000 (THESE ARE SAID TO KEEP 3 TIMES LONGER THAN THOSE WITHOUT THE ACID); DYEING & FINISHING WOOL, COTTON, & SILK; PREPARING THE MALEATE SALTS OF ANTIHISTAMINES & SIMILAR DRUGS
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**

IN ORG SYNTHESES OF MALIC, SUCCINIC, ASPARTIC, TARTARIC, PROPIONIC, LACTIC, MALONIC, ACRYLIC, & HYDROACRYLIC ACIDS
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 45] **PEER REVIEWED**

IN PREPN OF ERGOMETRINE MALEATE INJECTION
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1227] **PEER REVIEWED**

IN REABSORPTIVE PATHWAY STUDIES FOR AMINO ACIDS & GLUCOSE IN PROXIMAL TUBULE
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 243] **PEER REVIEWED**

Manufacture of alkyd and polyester resins; surface coatings; lubricant additives; plasticizers; copolymers; and agricultural chemicals.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V14 770 (1981)] **PEER REVIEWED**


Manufacturers:
New Hampshire Oak, Hq, Liberty Lane, Hampton, NH 03842, (603) 926-5911; General Chemical Corp, 90 E Halsey Rd, PO Box 393, Parsippany, NJ 07054-0393; Production site: Claymont, DE 19703
[SRI. 1992 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1992., p. 741] **PEER REVIEWED**

Schweizerhall Inc, Hq, 10 Corporate Place South, Piscataway, NJ 08854, (908) 981-8200, (800) 243-6564; Production site: Piscataway, NJ 08854
[SRI. 1992 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1992., p. 741] **PEER REVIEWED**

Haarman Reimer Corp, 70 Diamond Rd, Springfield, NJ 07081, (201) 467-5600; Food Ingredients Div, 1127 Myrtle St, Elkhart, IN 46515
[United States International Trade Commission. Synthetic Organic Chemicals-United States Production and Sales, 1991. USITC Publication 2607, February 1993. Washington, DC: United States Trade Commission, 1993., p. 15-21] **PEER REVIEWED**


Methods of Manufacturing:
... BY THE CATALYTIC OXIDATION OF BENZENE OVER VANADIUM PENTOXIDE.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 895] **PEER REVIEWED**

Vapor-phase oxidation of n-butane or n-butylene in air over a solid catalyst.
[KIRK-OTHMER CONDENSED ENCYC CHEM TECH 1985 p.724] **PEER REVIEWED**

Resorcinol reacts with hydrogen peroxide in the presence of tungstic oxide.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V13 42 (1981)] **PEER REVIEWED**


General Manufacturing Information:
By-product from manufacture of phthalic anhydride from naphthalene with special recovery conditions.
[Hawley, G.G. The Condensed Chemical Dictionary. 10th ed. New York: Van Nostrand Reinhold Co., 1981., p. 638] **PEER REVIEWED**


Formulations/Preparations:
Grades of purity: Reagent; Technical
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


U. S. Production:
(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS
[SRI] **PEER REVIEWED**

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS
[SRI] **PEER REVIEWED**


U. S. Imports:
(1983) 1.00X10+7 g
[USITC. IMPORTS OF BENZENOID CHEM & PROD 1983 p.21] **PEER REVIEWED**


U. S. Exports:
(1984) 7.08X10+8 g
[BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1984 p.2-79] **PEER REVIEWED**


Laboratory Methods:


Analytic Laboratory Methods:
MALEIC ACID /WAS/ DETECTED IN AIR BY GC METHYLATION WITH BORON TRIFLUORIDE.
[WATHNE BM; ANALYST (LONDON) 105 (1249): 400-3 (1980)] **PEER REVIEWED**

Maleic acid and timolol in mixtures & formulations containing timolol maleate were determined by HPLC. The eluate was monitored at 235 nm for 5 min & then at 294 nm. The detection limit was approx 500 pg, and accuracy was greater than 98%.
[Mazzo DJ; J Chromatogr 299 (2): 503-7 (1984)] **PEER REVIEWED** PubMed Abstract

An ion chromatographic system was developed for routine measurement of carboxylic acids with carbon numbers up to C8 in precipitation samples. The system combines online sample preconcentration on a low capacity anion exchange resin with separation by ion exclusion and subsequent detection by UV absorption. Maleate anions, however, are hidden under the large peak of the strong mineral acids. Using mixtures of carboxylic acids likely to occur in the atmosphere, maleic acid was found to have a retention time of 12.0 min.
[Elbert W et al; Int J Environ Anal Chem 35 (3): 149-59 (1989)] **PEER REVIEWED**


Special References:


Special Reports:
Dangerous Prop Ind Mater Rep 7 (1): 61-5 (1987). A review of safety and the health hazards of maleic acid.


Synonyms and Identifiers:


Synonyms:
BUTENEDIOIC ACID
**PEER REVIEWED**

CIS-BUTENEDIOIC ACID
**PEER REVIEWED**

(Z)-Butenedioic acid
**PEER REVIEWED**

2-BUTENEDIOIC ACID, (Z)-
**PEER REVIEWED**

CIS-1,2-ETHYLENEDICARBOXYLIC ACID
**PEER REVIEWED**

1,2-ETHYLENEDICARBOXYLIC ACID, (Z)
**PEER REVIEWED**

MALEINIC ACID
**PEER REVIEWED**

MALENIC ACID
**PEER REVIEWED**

Toxilic acid
**PEER REVIEWED**


Formulations/Preparations:
Grades of purity: Reagent; Technical
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.] **PEER REVIEWED**


Shipping Name/ Number DOT/UN/NA/IMO:
NA 2215; MALEIC ANHYDRIDE

UN 2215; Maleic acid

IMO 8.0; Maleic Acid, maleic anhydride


Standard Transportation Number:
49 411 55; Maleic acid


Administrative Information:


Hazardous Substances Databank Number: 666

Last Revision Date: 20030305

Last Review Date: Reviewed by SRP on 3/2/1994

Update History:
Complete Update on 03/05/2003, 2 fields added/edited/deleted.
Field Update on 02/14/2003, 1 field added/edited/deleted.
Field Update on 11/08/2002, 1 field added/edited/deleted.
Field Update on 10/31/2002, 1 field added/edited/deleted.
Field Update on 08/06/2002, 1 field added/edited/deleted.
Field Update on 01/14/2002, 1 field added/edited/deleted.
Field Update on 08/08/2001, 1 field added/edited/deleted.
Field Update on 05/15/2001, 1 field added/edited/deleted.
Complete Update on 06/12/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 11/18/1999, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 02/27/1998, 1 field added/edited/deleted.
Complete Update on 10/17/1997, 1 field added/edited/deleted.
Complete Update on 07/08/1997, 4 fields added/edited/deleted.
Complete Update on 04/01/1997, 2 fields added/edited/deleted.
Complete Update on 01/24/1997, 1 field added/edited/deleted.
Complete Update on 05/10/1996, 1 field added/edited/deleted.
Complete Update on 01/19/1996, 1 field added/edited/deleted.
Complete Update on 12/22/1994, 1 field added/edited/deleted.
Complete Update on 05/18/1994, 51 fields added/edited/deleted.
Field Update on 05/05/1994, 1 field added/edited/deleted.
Field Update on 03/18/1994, 1 field added/edited/deleted.
Field update on 12/14/1992, 1 field added/edited/deleted.
Field update on 03/06/1990, 1 field added/edited/deleted.
Complete Update on 02/23/1990, 3 fields added/edited/deleted.
Complete Update on 09/14/1989, 2 fields added/edited/deleted.
Complete Update on 04/13/1989, 1 field added/edited/deleted.
Complete Update on 09/02/1988, 63 fields added/edited/deleted.
Complete Update on 11/08/1985