Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 64-18-6 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Formic acid
  • HYDROGEN CARBOXYLIC ACID

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: ...Workers exposed to formic /acid/ ... in a textile plant complained of nausea. Air tests in the area revealed concentrations ... averaging 15 ppm. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 279]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Ingestions of less than 10 grams by children have led to superficial oropharyngeal burns with the children recovering. In adults, ingestions exceeding about 50 grams were generally fatal with lesser doses resulting in superficial oropharyngeal burns, hematemesis, hepatotoxicity, ulcerations and perforation of the gastrointestinal tract. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Twelve farmers exposed to formic acid for eight hours in silage making were examined for effects on calcium excretion and renal ammoniagenesis. Eight of the subjects were exposed below 9 mg/cu m (MAK value) and four were exposed at or above this level. Exposure was associated with increased renal ammoniagenesis and urinary calcium excretion at 30 hours post exposure. It was speculated that these biochemical effects could be explained by the interaction of formic acid with the oxidative metabolism of renal tubular cells. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • BIOMONITORING: After the inhalation of methanol (40-160 ppm) and formic acid (2-5.5 ppm), 10 employees in the formic acid filling plant and in the production of urea formaldehyde resin showed formic acid concentrations of 21.2-118 mg/g creatinine in the urine 16 hr after exposure. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Signs and symptoms from accidental or intentional overdoses (50 g or more) are salivation, vomiting, a burning sensation in the mouth and pharynx, and severe pain. Circulatory collapse may follow, causing death. Ingestion of; or skin contact with, smaller quantities of formic acid may produce ulceration of membranes. Contact with eyes may cause permanent scarring of the cornea. Dilute solutions (eg, 10%) appear to be noncorrosive. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.698]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Intentional ingestion (overdoses) are reported to produce salivation, vomiting (which maybe bloody), a burning sensation in the mouth and pharynx, diarrhea, and severe pain. Circulatory collapse may follow, causing death. ... Formic acid ingestions are unique in their ability to cause death after a prolonged course of classical acid-induced gastrointestinal damage. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Chronic absorption has been reported to cause albuminuria, hematuria. [The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 605]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Principal hazard is that of severe primary damage to skin, eye or mucosal surface. Sensitization is rare, but may occur in person previously sensitized to formaldehyde. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 44]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Lacrimation, increased nasal discharge, cough, throat discomfort, erythema, and blistering may occur depending upon solution concentrations. [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 466]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Extensive exposure can result in depressive effects to the central nervous system (CNS), like visual and mental disturbances. After oral intake... severe acidosis... and nephropathy may occur. [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 200]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Swallowing formic acid has caused a number of cases of severe poisoning and death. The symptoms... include salivation, vomiting, burning sensation in the mouth, bloody vomiting, diarrhea, and pain. In severe poisoning, shock may occur. Later breathing difficulties may develop. Kidney damage may also be present. [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 466]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Symptomatology (after ingestion or skin contact): Corrosion of mucous membranes of mouth, throat and esophagus, with ... pain and dysphagia. Necrotic areas are at first grayish white but soon acquire a blackish discoloration (yellow in case of nitric acid) and sometimes shrunk or wrinkled texture. Epigastric pain ... may be associated with nausea and vomiting of mucoid and coffee-ground material. ... Intense thirst. Ulceration of all membranes and tissues ... Circulatory collapse with clammy skin, weak and rapid pulse, shallow respiration and scanty urine. ... Shock is often ... cause of death. Asphyxial death due to glottic edema. Late esophageal, gastric and pyloric structures and stenosis, which may require ... surgical repair, should be anticipated. ...Permanent scars may ... appear in cornea, skin and oropharynx. Uncorrected circulatory collapse of several hr ... may lead to renal failure and ischemic lesions in liver and heart. /Acids/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-10]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Formic acid produced by bees, wasps, and ants will cause tissue irritation upon contact or injection. [Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 558]**PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Accidental or intentional overdoses (50 g or more) are reported to produce salivation, vomiting, a burning sensation in the mouth and pharynx, diarrhea, and severe pain. Circulatory collapse may follow, causing death. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 1]**PEER REVIEWED**
  • CASE REPORTS: ...A drop of reaction mixture composed of 0.8 mL 90% formic acid and 0.2 mL 30% hydrogen peroxide /was/ splashed in one eye /of a patient/. The eye was quickly irrigated with water, but an area of swelling of epithelium and anterior stroma of cornea and cells and flare in anterior chamber were observable half an hr later. However, in 12 hr the aqueous and cornea had become clear except for an area of loss of epithelium, and in 36-60 hr recovery was complete. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 447]**PEER REVIEWED**
  • CASE REPORTS: A worker who had suffered splashes of hot formic acid to his face developed marked dyspnea with difficulty in swallowing, inability to speak, and died 6 hours later. [American Conference of Governmental Industrial Hygienists. Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH. 2001., p. 1]**PEER REVIEWED**
  • CASE REPORTS: 45 cases of ingestion of formic acid were described. Abdominal pain, vomiting, hematemesis, dysphagia, dyspnea, burns in the gastrointestinal tract with subsequent strictures, coagulation disorders, pneumonia, acute kidney failure and hepatic dysfunction occurred. After ingestion of 45-200 g formic acid, 9 of 16 patients died after perforations in the gastrointestinal tract and 5 died of acute kidney failure. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: One death is reported after ingestion of formic acid (approx. 200 mL of an approx. 50% solution). The blood level is 348 ug/mL formic acid approximately 2 hr after ingestion. Hematemesis, cyanosis, burns in the gastrointestinal tract, shock, metabolic acidosis and hemolysis occurred. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: Ingestion of over 60 g of formic acid by an adult is potentially fatal. A case of a 36-year-old woman with a history of depression who ingested 110 g of formic acid is reported. She survived a complicated intensive care hospitalization following usage of intravenous folinic acid, urinary alkalinization, intravenous furosemide and supportive care. It is suggested to minimize formate toxicity by enhancing hepatic formate degradation via the folinic acid "one carbon pool" and by enhanced renal elimination of formate. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: Systemic toxicity developed in a 3-year-old girl burned by formic acid over 35% of her total body surface area. The patient presented with profound metabolic acidosis and a serum formate level of 400 mg/mL, the highest reported in the literature for poisoning by any route. The patient was successfully treated with hemodialysis, IV bicarbonate, and supportive measures. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: A case in which a patient sustained an inhalation injury as a result of aerosolized formic acid is reported. The patient sustained a partial thickness burn to the face from a chemical spray; however, as a result of aerosolization, he also inhaled formic acid. This resulted in a reversible pulmonary chemical injury. Inhalation of formic acid results in a reactive airway dysfunction syndrome, a common response to inhalation of an occupational irritant. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: A fatality caused by ingestion of a decalcifying agent containing formic acid is reported. Quantitative analysis of formic acid in the form of its methyl ester was performed in different body fluids and organ samples using head-space gas chromatography with flame ionization detection. The blood taken at the time of admission to hospital had a concentration of 370.3 ug/mL, which declined to 13.9 ug/mL after 6.5 hr of hemodialysis. Post-mortem concentrations were 855.4 ug/mL (heart blood), 2,712 ug/mL (gastric contents), 1128 ug/mL (hemorrhagic fluid from abdominal cavity), 3,051 ug/mL (bile), 2,664 ug/mL (contents of small intestine), 442.7 ug/g (liver) and 542.3 ug/g (kidney). The most important morphological findings for differentiating between oral and respiratory ingestion were ulceration of the oropharynx and the esophagus as well as extensive necrotic lesions in the stomach and the duodenum without perforation. Death was caused by massive acidosis, hemolysis, bleeding complications, hepatic and renal failure. Toxicological and morphological findings revealed that a considerable amount of formic acid had been ingested orally with a suicidal intention. [Westphal F et al; Int J Legal Med 114 (3): 181-185 (2001) ]**PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: In a human case of formaldehyde poisoning, toxic concentrations of formate (7-8 mm) were detected within 30 min of ingestion, confirming rapid metabolism of formaldehyde to formate in humans. [WHO; Environ Health Criteria 196: Methanol p.62 (1997). Available from: http://www.inchem.org/documents/ehc/ehc/ehc196.htm as of July 14, 2005. ]**PEER REVIEWED**
  • CASE REPORTS: Two patients were studied who presented with methanol poisoning. Formate accumulation was marked with initial blood levels ranging from 11.1-26.0 meq/L. Decrease in blood bicarbonate concentration of similar magnitude coincided with the increase in formate accumulation. Accumulation of formic acid thus plays a major part in the acidosis observed in human subjects poisoned with methanol. [McMartin KE et al; Am J Med 68 (3): 414-8 (1980) ]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: In a ... rabbit, pure liquid formic acid applied with a brush to part of cornea ... /caused/ immediate local opacity. This began to clear ... in 5 days, but by that time there was hypopyon, posterior subcapsular lens opacity, absence of portions of corneal endothelium, infiltration, and growth of new blood vessels at the limbus. The iris was also infiltrated and hyperemic. In another rabbit a five minute application of formic acid diluted to 10% also caused dense white local opacity, and at 5 days the reaction in the cornea was similar to that of the eye exposed to concentrated acid, but hypopyon was absent. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 446]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In sheep formic acid given orally (150 mg/kg) was without adverse effect, except for some indication of anorexia. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.694]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: About 50 mg/kg in 10% aqueous solution given orally to dogs or 6 mg/kg given subcutaneously to rabbits produced methemoglobinemia which lasted about 10 days. This slow disappearance may be due to the inhibition of catalase by formic acid. 4.6 mg/kg intravenously given to 6 dogs produced no ill effect and 13.8 mg/kg only slight hypertension. [JECFA; FAO Nutrition Meetings Rpt Ser No. 38A: Specifications for Identity and Purity and Toxicological Evaluation of Some Antimicrobials and Antioxidants- Formic Acid (1965). Available from: http://www.inchem.org/documents/jecfa/jecmono/v38aje03.htm as of July 13, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Wistar rats were exposed by inhalation to 20 ppm formic acid for 3-8 days for 6 hr daily./ No clinical symptoms. On the 3rd day of exposure, the glutathione concentration was reduced in the liver and kidneys and increased in the brain as compared with the control. The cerebral and acid proteinase activity was increased at the end of the test. The hepatic superoxide dismutase activity was below the control level whereas the activity of the ethoxycoumarin deethylase was increased. The activities of cytochrome P450 and ethoxycoumarin deethylase were reduced in the kidneys. No relation of the changes to the duration of exposure /was determined/. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In guinea pigs, formic acid vapor (0.3 to 42 ppm for 1 hr) is a... potent irritant... . [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 694]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Intravenous doses of 0.46 to 1.25 mg/kg caused central nervous system depression, vasoconstiction, and diuresis in rabbits; larger doses (approximately 4 g/kg) produced convulsions and death in rabbits and methemoglobinemia in dogs. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.694]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: A feeding study using pigs was conducted with duration of approximately 90-days examining the effect of feeding K-diformate (30% potassium, 35.4 % formic acid and 34.6% formates) at 0, 0.6 or 1.2% of the diet to growing-finishing pigs. The K-diformate has previously been shown to be an effective growth promoter in diets of both weaning pigs and growing-finishing pigs. K-diformate, added on top of the basal diet, significantly increased the growth rate of the pigs. There were no adverse effects on the health status of pigs fed K-diformate and an examination of the stomachs at necropsy revealed no effect on stomach keratinization or ulceration. Additional studies revealed that feeding 1.2% K-diformate to pigs decreases the coliform bacteria level in the gastrointestinal tract. The presumed mechanism of action was reportedly partially explained by reduction of the population of gut coliform bacteria leading to reduced metabolic needs of gut bacteria and improved availability of dietary nutrients for the animal. /Potassium diformate/ [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In young rats administered formic acid in the diet (0.5 or 1.0%) or drinking water (0.5 or 1.0%) for 6 wk the body weight gain and the size of most organs were reduced. Rats receiving 8 to 360 mg/kg formic acid in drinking water for 2 to 27 wk showed no adverse effects other than a reduced rate of body weight gain (and feed intake) at the highest dose level. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.694]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Exposure of 3 month old male Wistar rats to 20 ppm formic acid vapor for 3 wk (5 days/wk; 6 hr daily) resulted in an increase in brain lysosomal acid proteinase and succinate dehydrogenase and decrease in glutathione peroxidase and 2',3'-cyclic nucleotide 3'-phosphohydrolase. [Savolainen H, Zitting A; Acta Pharmacol Toxicol 47 (3): 239-40 (1980) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In /a/ two week study, Fischer 344/N rats and B6C3F1 mice (5/sex/exposure level) were exposed to atmospheres containing 0, 31, 62.5, 125, 250, or 500 ppm formic acid. Deaths occurred in both species at 500 ppm and in one female mouse at 250 ppm. No effects were noted in blood chemistries or urinalysis parameters. Effects upon histological examination of the respiratory tract included squamous metaplasia, necrosis, and inflammation. These lesions were dose-related. In /a/ 13 week inhalation study, the same species (10/sex/exposure level) were exposed to formic acid concentrations of 0, 8, 16, 31, 64, or 128 ppm. One mouse of each sex, but no rats, died from the high exposure groups (dose related). Microscopic lesions that occurred only in the high exposure group consisted of squamous metaplasia of the respiratory epithelia and degeneration of the olfactory epithelia. The no observed adverse effect level was 32 ppm from irritation of the respiratory tract epithelium but no evidence of systemic toxicity. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 694]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: /Fisher 344 rats (male and female) were exposed by inhalation to formic acid (approximately 95% and 5% water) 5 days per week, 6 hours a day fo 13 weeks at concentrations 0.015; 0.030; 0.061; 0.122; 0.244 mg/L (8, 16, 32, 64, 128 ppm)/. All animals used survived. The body weight of the males of the 32 ppm group was slightly but significantly increased at the end of the study. The body weight gains of the males of the 16, 32 and 64 ppm groups were also significantly increased. No definitely substance-related clinical signs of toxicity were observed during the study. The hematologic changes observed were all slight: At the end of the study, the number of neutrophils was significantly but not dose-dependently reduced in animals of both sexes in all dose groups. Other hematologic changes were rather of an incidental nature and not relevant. Furthermore, few and slight changes of the biochemical serum parameters were observed. No unusual gross lesions were observed. The absolute liver weights were significantly increased in the males of all exposure groups, and the relative liver weights were significantly increased in the three highest dose groups only. The absolute and relative lung weights were significantly reduced in the females of all exposure groups. In the males, the relative lung weights were significantly reduced in all exposure groups, and the absolute lung weights were significantly reduced in the two highest dose groups only. Most of the histopathologic changes at the respiratory and olfactory nasal epithelia were restricted to the highest dose group. The respiratory epithelium mainly showed slight squamous epithelial metaplasias, and the olfactory epithelium showed minimal to slight degenerative changes. In the 32 and 64 ppm groups, a minimal degeneration of the olfactory epithelium was observed in one male in each case. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ...The developmental effects of sodium (Na) formate and formic acid /were evaluated/ in rodent whole embryo culture (WEC). Day 9 rat embryos were cultured for 24 or 48 hours and day 8 mouse embryos were cultured for 24 hours in the presence of Na-formate or formic acid. Rat and mouse embryos exposed to either agent for 24 hours exhibited a trend toward reduced growth and development and the number of abnormalities increased at the higher concentrations. Rat embryos exposed for 48 hours to either Na-formate or formic acid showed a trend toward reduced growth and development with increasing concentration. Embryo lethality and incidence of abnormal embryos were also increased at the higher concentrations. The anomalies observed in both species after exposure to either compound were primarily open anterior and posterior neuropore with less frequent incidence of rotational defects, tail anomalies, enlarged pericardium and delayed heart development. [Andrews JE et al; Teratology 51 (4): 243-51 (1995) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ... In vitro assays indicated that formic acid can cause toxicity when embryos were incubated with either sodium formate or formic acid but are inadequate to determine whether formic acid can cause developmental toxicity in vivo. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 698]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Sprague-Dawley rat embryo cultures (9th day of gestation) were treated with sodium formate or formic acid at concentrations of 200, 400, 800, 1200, 1600, 2000 ug/mL (sodium formate) or 140, 270, 540, 810, 1080 ug/mL (formic acid). The pH of the medium was no longer corrected after addition of the test substance. Both after 24- and after 48-h incubation with sodium formate, there was a significant and concentration-dependent reduction of the developmental parameters yolk sac diameter (YSD), crown-rump length (CRL), head length (HL), somite number (SN) and developmental score (DEVSC). Embryolethality was significantly increased only in the highest concentration after 48-h incubation. The number of anomalies (mainly CNS: open anterior and posterior neuropores and erratic neurorrhaphy) was significantly increased at 1.6 and 2.0 mg/mL after 24 h and at 0.8 and 2.0 mg/mL after 48-h incubation. The protein and DNA levels showed a significant and concentration-dependent reduction. Incubations with formic acid also showed a significant and concentration-dependent reduction of YSD, CRL, HL, SN and DEVSC after 24-h incubation and of CRL, HL, SOM and DEVSC after 48 h. Embryolethality was significantly increased in the highest concentration after 24 h and in the two highest concentrations after 48 h. Protein and DNA concentrations showed significant and concentration dependent decreases in both cases. The number of anomalies (open anterior and posterior neuropores, rotatory defects and enlarged maxillary process) showed a significant increase only at 0.81 mg/mL after 48-h incubation. To sum up, concentration-dependent embryotoxic and dysmorphic changes were detected in the culture both using formate and formic acid in this test system. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: In a 13 wk inhalation study, there were no effects on sperm motility, density, and testicular or epididymal weights in rats and mice. No changes were found to develop in the estrous cycle. [Sheftel, V.O.; Indirect Food Additives and Polymers. Migration and Toxicology. Lewis Publishers, Boca Raton, FL. 2000., p. 914]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: One hundred microL of... 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. ... Animals that received... 1% formate showed nearly normal optical media and fundi. ... Eyes that received... 1% formate appeared histologically normal. [Hayasaka Y et al; Pharmacol Toxicol. 89 (2): 74-78 ]**PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Formic acid has been reported to be mutagenic in Escherichia coli and Drosophila germ cells, but did not affect DNA transformation in Bacillus subtilis at concentrations up to 0.46%. [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. 4908]**PEER REVIEWED**
  • GENOTOXICITY: A cytogenetic assay using CHO-K1 cells produced ambiguous results for chromosome aberrations. Unbuffered or unneutralized formic acid was clastogenic at pH values around 6.0 (10-14 mM) and cytotoxic at and below pH 5.7 (12-16 mM). Clastogenicity is stopped by neutralization with sodium hydroxide or by increasing the buffer concentrations in the incubation medium. The /investigators/ concluded from this that it is not the substance as such that induces chromosome damage but that the damage is due to the acid pH of the incubation medium as a nonspecific effect. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: Two sister chromatid exchange assays have been conducted using formic acid. Both produced negative results. One utilized Chinese hamster V79 cells at formic acid concentrations of 0.4, 0.6, 1.0 and 2.0 mM with and without an activation system. The second utilized human lymphocytes at a formic acid concentration from 29 - 460 ug/mL (0.63 - 10 mM) with an activation system. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: An E. coli reverse mutation assay without activation produced slightly positive results. ... The number of bacteria was varied while the test substance concentration remained at almost the same level. The survival rate was reduced with a decrease in the bacterial count (from 100% at 1.5 x 10+9 bacteria up to 2.8% at 2.6 x 10+7). In parallel, the number of mutations was reduced with an increase in the survival rate. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: Formic acid was reported to be negative in a SOS chromotest. The test was conducted with and without an activation system and used 3-5 concentrations at up to 100 mM. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: A Drosophila SLRL test was performed using oral (feed) or inhalation exposure. The mutation result was positive after inhalation exposure and administration via the diet with mutation rates of 1.31 and 1.11% as compared with the control limit of 0.15% in each case. If the pH was buffered to 7.5 in the feeding study, there was no increased mutation rate. The positive effect was likely due to the pH of the acid form used in the testing. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: Formic acid (approximately 95% and 5% water) was negative for genetic activity in the Ames assay using Salmonella typhimurium TA97, TA98, TA100, TA1535 at concentrations of 10, 33, 100, 333, 1000, 3333 ug/plate with and without metabolic activation. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: ...Catalase and glutathione were analyzed in the two retinal cell lines to determine whether differences in these antioxidant systems contributed to cell-type-specific differences in cytotoxicity. Cells were exposed to formic acid (pH 6.8) in the culture medium in the presence or absence of a catalase activity inhibitor, 3-amino-1,2,4-triazole (AT), or a glutathione synthesis inhibitor, buthionine L-sulfoximine (BSO). Catalase protein, catalase enzyme activity, glutathione, glutathione peroxidase activity, cellular ATP, and cytotoxicity were analyzed. Compared to ARPE-19, 661W cells show lower antioxidant levels: 50% less glutathione, glutathione peroxidase and catalase protein, and 90% less catalase enzyme activity. In both cell types, formic acid treatment produced decreases in glutathione and glutathione peroxidase, and glutathione synthesis inhibition with BSO produced greater ATP depletion and cytotoxicity than formic acid treatment alone. In contrast, formate exposure produced decreases in catalase protein and activity in 661W cells, but increases in activity in ARPE-19. Treatment with the catalase inhibitor AT increased the formate sensitivity only of the ARPE-19 cells. ARPE-19 cells, therefore, may be less susceptible to formate toxicity due to higher levels of antioxidants, especially catalase, which increases on formate treatment and which has a significant cytoprotective effect for the RPE cell line. [Treichel J et al; Toxicol Sci 82 (1): 183-192 (2004) ]**PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE IN VITRO TESTS: ...The effects of formate exposure on the two retinal cell types were analyzed ...in vitro using photoreceptor (661W) and RPE (ARPE-19) cell lines. Cells were exposed for time courses from minutes to days to sodium formate at pH 7.4 or to formic acid at pH 6.8, to simulate the metabolic acidosis that accompanies methanol poisoning. Formate accumulation, cellular ATP, cytotoxicity (lactate dehydrogenase (LDH) release) and cell phenotype were analyzed. Formate accumulated with a similar biphasic pattern in both cell types, and to similar levels whether delivered as sodium formate or as formic acid. ATP changes with sodium formate treatment differed between cell types with only 661W cells showing a rapid (within minutes), transient ATP increase. The subsequent ATP decrease was earlier in 661W cells (6 hr) than the ATP decrease in ARPE-19 cells (24 hr), and although both cell types showed evidence of cytotoxicity, the effects were greater for 661W cells. Both cell types showed enhanced morphologic and biochemical changes with formic acid treatment including earlier and/or greater effects on ATP depletion and cytotoxicity; again effects were more pronounced in 661W cells. [Treichel J et al; Neurotoxicology 24 (6): 825-834 (2003) ]**PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE IN VITRO TESTS: ...Forelimb buds were excised from GD-11 mouse embryos and cultured for six days in 1, 3, 4, or 6 mg formate/mL culture medium (CM). Limb buds exposed to 3 and 4 mg formate/mL CM showed significant structural differences in the radius, ulna, and proximal phalanges. Exposures to 3, 4, and 6 mg formate/mL CM resulted in the absence of distal phalanges. Concentrations of 6 mg formate/mL CM were dysmorphogenic, causing a significant increase in missing proximal phalanges and abnormal half moon shaping of the radius and ulna. Only the 4 mg formate/mL CM group had an effect on the metatarsals causing elongation. There were no significant developmental effects on the humerus or scapula at any of the formate concentrations. The 1 mg/mL CM concentration of formate showed no significant adverse effects on overall limb bud development. Protein, but not DNA, was significantly decreased in a concentration dependent manner at concentrations greater than or equal to 3 mg formate/mL CM. [Nichols H et al; Teratology 53 (2): 118-119 (1996) ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: ... Formic acid administration in unspecified quantity to rabbits and dogs produced the same histopathology in retina and optic nerve as did methyl alcohol. Presumably, acidosis was induced by formic acid in these experiments in which the eyes were found to be injured, whereas acidosis would not be produced by feeding neutral formates. ... In ... a series of studies in dogs, /investigators/ ... concluded that metabolism of methanol to formic acid could produce generalized acidosis. Futhermore, they postulated that as tissue pH was lowered in acidosis, toxicity attributable to /formic acid/ ... increased, owing to greater proportion being present as formic acid and smaller proportion as relatively innocuous formate ion. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 446]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Dog oral 4000 mg/kg /Sodium formate/ [JECFA; FAO Nutrition Meetings Rpt Ser No. 38A: Specifications for Identity and Purity and Toxicological Evaluation of Some Antimicrobials and Antioxidants- Formic Acid (1965). Available from: http://www.inchem.org/documents/jecfa/jecmono/v38aje03.htm as of July 13, 2005. ]**PEER REVIEWED**
  • LD50 Dog iv 3000 mg/kg /Sodium formate/ [JECFA; FAO Nutrition Meetings Rpt Ser No. 38A: Specifications for Identity and Purity and Toxicological Evaluation of Some Antimicrobials and Antioxidants- Formic Acid (1965). Available from: http://www.inchem.org/documents/jecfa/jecmono/v38aje03.htm as of July 13, 2005. ]**PEER REVIEWED**
  • LC50 Mouse inhalation 6200 mg/cu m /15 min [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1690]**PEER REVIEWED**
  • LD50 Mouse oral 700 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1690]**PEER REVIEWED**
  • LD50 Mouse iv 142 mg/kg [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.695]**PEER REVIEWED**
  • LD50 Mouse ip 940 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1690]**PEER REVIEWED**
  • LD50 Rat oral 730 mg/kg bw [European Chemicals Bureau; IUCLID Dataset, Formic acid (64-18-6) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of July 14, 2005. ]**PEER REVIEWED**
  • LC50 Rat inhalation 15 g/cu m/15 min [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1690]**PEER REVIEWED**
  • LC50 Rat inhalation 7.4 mg/L/4 hr [European Chemicals Bureau; IUCLID Dataset, Formic acid (64-18-6) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of July 14, 2005. ]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Formic acid is absorbed from the gastrointestinal tract, via the lungs and the intact skin. The absorbed substance is degraded to carbon dioxide (CO2) and water and is partially excreted unchanged in the urine. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • Some formic acid may be excreted unchanged, the amt depending on the species, dose, and route of admin. [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. 4908]**PEER REVIEWED**
  • During hemodialysis in a methanol poisoned patient, formate elimination followed first order kinetics with a plasma half-life of 165 min. The mean dialyzer (1.6 at 59 mL) clearance of formate was 148 mL/min at a blood flow of 215 mL/min. Distribution volume was 0.5 L/kg. Formate is more effectively removed by hemodialysis than methanol. /Formate/ [Jacobsen D et al; Acta Med Scand 214 (5): 409-12 (1983) ]**PEER REVIEWED**
  • Male New Zealand rabbits given 300 mg/kg 14C-formate excreted approximately 40% of the dose in the urine within 40 hr, about 70% of which was identified as formate and the rest as bicarbonate. After repeated intravenous dosing with 100 mg/kg of buffered formic acid daily for 4 days, adult male rabbits were injected on the fifth day with 14C-formic acid and were euthanized 1, 2, or 20 hr after the last injection. The highest formic acid concentrations were found 1 hr after the fifth dose. Total formic acid and concentrations were always higher than those measured radiometrically. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.697]**PEER REVIEWED**
  • The urine specimens of 12 male farmers who were exposed to formic acid in a concentration of 0.0073+/-0.0022 mg/L were examined. Immediately after exposure, the excretion of formic acid was not increased as compared with the control group. After 15 and 30 hours, however, there were substantial and significantly increased concentrations of formic acid in the urine of the persons exposed. Excretion showed a linear dependence on the exposure concentration. The pH in the urine was unchanged, but the ammonium and calcium excretion was significantly increased 30 hours after exposure. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • The objective is to describe the kinetics of formate, the main toxic metabolite of methanol, in a series of consecutive patients treated in the same intensive care unit for severe methanol poisoning. The charts of the patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration >50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate <15 mmol/L, arterial pH <7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in three cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.80+/-0.78 h, which was statistically different from the values observed before or in the absence of dialysis (6.04+/-3.26 hr, P=0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 176+/-43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. [Hantson P et al; Hum Exp Toxicol 24 (2): 55-59 (2005) ]**PEER REVIEWED**

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Metabolism/Metabolites

  • Formate is a normal constituent of intermediary metabolism ... /of formic acid/. Formate is metabolized in the rat primarily via the one carbon pool, but in some circumstances the catalase-peroxidative pathway may serve as an alternative route of oxidation. Oxidation occurs in a variety of organs and tissues, including liver, lung, and erythrocytes, the end products being carbon dioxide and water. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5 p.697]**PEER REVIEWED**
  • Enzyme pathways involved in detoxification of hydrogen peroxide, formaldehyde, and formic acid, which are produced as a consequence of oxidative demethylation by the cytochrome P-450 system, were examined in isolated hepatocytes from phenobarbital pretreated rats. The formaldehyde produced during oxidative demethylation in isolated hepatocytes is rapidly oxidized to formic acid. Depletion of cellular reduced glutathione by pretreatment of rats with diethylmaleate decreases the rate of formic acid production, and therefore, it appears that formaldehyde produced by oxidative demethylation is oxidized by formaldehyde dehydrogenase, an enzyme which requires but does not consume reduced glutathione. Because of the rapid nonenzymatic reaction of formaldehyde with reduced glutathione, this enzyme system may be viewed as essential to prevent the loss of reduced glutathione due to S-hydroxymethylglutathione formation. Reduced glutathione concentration in isolated hepatocytes decreased rapidly following addition of substrates undergoing oxidative demethylation. Addition of other cytochrome P-450 substrates which do not undergo demethylation did not result in such a dramatic oxidation of reduced glutathione. Formic acid, produced during oxidative demethylation acts as a substrate for the peroxidatic mode of catalase, but also binds to catalase as an anionic ligand. This binding decreases the catalase concentration detectable by cyanide titration and therefore appears to inhibit the catalytic reaction mode. [Jones DP et al; J Biol Chem 253 (17): 6031-7 (1978) ]**PEER REVIEWED**
  • The major part of the absorbed formic acid is metabolized in the liver, but partially also in the intestinal mucosa, lungs, kidneys and spleen. Formic acid is oxidized in relation to folate and according to a catalase-peroxidative mechanism. Formic acid is metabolized into CO2 considerably more slowly in primates than in rats. The species sensitivity to methanol intoxication (metabolic acidosis caused by formic acid) is possibly dependent on the tetrahydrofolate concentration. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • The dose-dependent elimination of formate was investigated in the rat using both in vitro and in vivo systems. The in situ perfused liver was used to define the kinetics of hepatic metabolism and obtain initial in vitro estimates of the hepatic metabolism parameters. Formate was eliminated from the perfused rat liver following the Michaelis-Menten kinetics. Estimates of the Michaelis-Menten parameters obtained from the perfused liver studies were used in a two-compartment pharmacokinetic model of the dose-dependent elimination of formate in vivo. A good fit of the model to the observed in vivo data was obtained. Initial estimates of the Michaelis-Menten parameters, Vmax and Km, obtained from the perfused liver model, were within 40% of the final fitted values of these parameters in the in vivo model. [EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Formates (December 2001) as of July 12, 2005. ]**PEER REVIEWED**
  • Formic acid was excreted in the urine of rabbits during inhalation of methyl alcohol ... . [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. 4535]**PEER REVIEWED**
  • The elimination of formaldehyde in many species including primates is extremely rapid with a half-life of approximately 1 min. ...Equimolar infusions of formaldehyde, formic acid and sodium formate in dogs /were found to/ produced equivalent peak concentrations of formic acid, indicating that formaldehyde was rapidly metabolized to formic acid. ...Formate is oxidized to CO2 in vivo in mammalian species primarily by a tetrahydrofolate-dependent pathway. Formate enters this pathway by combining with tetrahydrofolate (H4folate) to form 10-formyl-H4folate in a reaction catalysed by formyl-tetrahydrofolate synthetase. 10-Formyl-H4folate may then be further oxidized to CO2 and H4folate by formyl-H4folate dehydrogenase. ...An inverse correlation /was found/ between plasma concentrations of folate in different animal species and the half-life of exogenously administered formate, suggesting that folates are involved in formate metabolism. Formate metabolism in rats and monkeys has been shown to be mediated by the folate-dependent pathway. Inhibition of catalase with aminotriazole had no effect on formate oxidation, whereas folate-deficiency markedly reduced formate oxidation in both species. Tetrahydrofolate is derived from folic acid in the diet and is the major determinant of the rate of formate metabolism. [WHO; Environ Health Criteria 196: Methanol p.62 (1997). Available from: http://www.inchem.org/documents/ehc/ehc/ehc196.htm as of July 14, 2005. ]**PEER REVIEWED**
  • The folate-mediated oxidation of formate proceeds about twice as slowly in non-human primates and humans as in rats. This explains the susceptibility of primates to the accumulation of formate, which is seen to occur at doses of methanol greater than 0.5 g/kg. [WHO; Environ Health Criteria 196: Methanol p.10 (1997). Available from: http://www.inchem.org/documents/ehc/ehc/ehc196.htm as of July 14, 2005. ]**PEER REVIEWED**
  • Normal (CB6-F1) and NEUT2 heterozygous and homozygous mice had essentially identical LD(50) values for methanol, 6.08, 6.00, and 6.03 g/kg, respectively. Normal mice oxidized low doses of [(14)C]sodium formate (ip 5 mg/kg) to (14)CO(2) at approximately twice the rate of homozygous NEUT2 mice, indicating the presence of another formate-oxidizing system in addition to FDH. Treatment of mice with the catalase inhibitor, 3-aminotriazole (1 g/kg ip) had no effect on the rate of formate oxidation, indicating that at low concentrations formate was not oxidized peroxidatively by catalase. High doses of [(14)C]sodium formate (ip 100 mg/kg) were oxidized to (14)CO(2) at identical rates in normal and NEUT2 homozygous mice. Pretreatment with 3-aminotriazole (1 g/kg ip) in this instance resulted in a 40 and 50% decrease in formate oxidation to CO(2) in both normal and homozygous NEUT2 mice, respectively. These results indicate that mice are able to oxidize formate to CO(2) by at least three different routes: (1) folate-dependent via FDH at low levels of formate; (2) peroxidation by catalase at high levels of formate; and (3) by an unknown route(s) which appears to function at both low and high levels of formate. [Cook R et al; Arch Biochem Biophys 393 (2): 192-198 ]**PEER REVIEWED**
  • Formic acid is an intermediary human metabolite that is immediately transformed to formate. [Malorny G; Z Ernaehrungswiss 9: 340-8 (1969) ]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008