Dichloroacetic Acid

Other Classes -> Organic Acids

Corrosives

Pharmaceuticals -> Metabolite of Chloral hydrate

Pharmaceuticals -> Listed in ZINC15

Pesticide -> EPA IRIS

Environmental transformation -> Pesticide transformation products (metabolite, successor)

log Kow = 0.92

0.92

0.92

1.563 at 68 °F (NTP, 1992) - Denser than water; will sink

1.5634 g/cu cm at 20 °C

Relative density (water = 1): 1.56

1.563

1.5634 @ 20°C

Liquid

Colorless liquid

Colorless crystalline solid melting at 49 °C

greater than or equal to 100 mg/mL at 59 °F (NTP, 1992)

Miscible with water

Miscible with ethanol, diethyl ether; soluble in acetone; slightly soluble in carbon tetrachloride

Solubility in water: miscible

Highly corrosive liquid that gives off acidic vapors.

Corrosive to metals and tissues

greater than 235 °F (NTP, 1992)

113 °C (235 °F) - closed cup

>235 °F

Danger

H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

P260, P264, P273, P280, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P321, P363, P391, P405, and P501 (click each P-code to see the statement)

Danger

H290 (26%): May be corrosive to metals [Warning Corrosive to Metals]

P203, P234, P260, P262, P263, P264, P264+P265, P270, P273, P280, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P319, P321, P361+P364, P363, P390, P391, P405, P406, and P501 (click each P-code to see the statement)

Chemical: Acetic acid, 2,2-dichloro-

Hazard Traits - Carcinogenicity; Developmental Toxicity; Neurotoxicity; Reproductive Toxicity

Status: Active Update: 16-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/24275

Dichloroacetic acid: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· Combustible material: may burn but does not ignite readily.

Not combustible. Gives off irritating or toxic fumes (or gases) in a fire.

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· TOXIC and/or CORROSIVE; inhalation, ingestion or skin contact with material may cause severe injury or death.

Critical Effects include upper respiratory tract; CNS; male reproductive effects; developmental toxicity; and cancer. [ACGIH] Corrosive to eyes, skin, and respiratory tract; Inhalation of high concentrations can cause pulmonary edema; [CHEMINFO]

WHO/International Programme on Chemical Safety; Environmental Health Criteria 216, Disinfectants and Disinfectant By-Products (1999). The Environmental Health Criteria (EHC) documents produced by the International Programme on Chemical Safety include an assessment of the effects on the environment and on human health of exposure to a chemical or combination of chemicals, or physical or biological agents. They also provide guidelines for setting exposure limits.[Available from, as of June 5, 2018: http://www.inchem.org/documents/ehc/ehc/ehc216.htm]

U.S. EPA; Toxicological Review of Dichloroacetic Acid (CAS No. 79-43-6) In Support of Summary Information on the Integrated Risk Information System EPA 635/R-03/007192 pp. (August 2003) presents background and justification for the hazard and dose-response assessment smmaries in IRIS.[Available from, as of June 5, 2018: http://www.epa.gov/iris/]

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

In case of fire in the surroundings, use appropriate extinguishing media.

Fresh air, rest. Half-upright position. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Refer for medical attention .

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

General First Aid:

· Wear positive pressure self-contained breathing apparatus (SCBA).

0.2 [ppm]

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use dry chemical, carbon dioxide, or alcohol or foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.). 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.

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature 2-8 °C. Handle and store under inert gas.

Store separately in a corrosive-resistant location. Prior to working with DCA you should be trained on its proper handling and storage. Store in tightly closed containers in a cool, well-ventilated area away from incompatible materials ... . Metal containers involving the transfer of this chemical should be grounded and bonded. Where possible, automatically pump liquid from drums or other storage containers to process containers. Drums must be equipped with self-closing valves, pressure vacuum bungs, and flame arresters. Use only non-sparking tools and equipment, especially when opening and closing containers of this chemical. Sources of ignition, such as smoking and open flames, are prohibited where this chemical is used, handled, or stored in a manner that could create a potential fire or explosion hazard. Wherever this chemical is used, handled, manufactured, or stored, use explosion-proof electrical equipment and fittings.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

Evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Ventilate area of spill or leak. Absorb liquids in vermiculite, dry sand, earth, peat, carbon, or a similar material and deposit in sealed containers. Keep this chemical out of a confined space, such as a sewer, because of the possibility of an explosion, unless the sewer is designed to prevent the buildup of explosive concentrations. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... Summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Dichloroacetic acid (8 total), please visit the HSDB record page.

In this study, groups of B6C3F1 male mice were treated with dichloroacetate (DCA), trichloroacetate (TCA), and mixtures of the compounds (Mix I, II, and III) daily by gavage, for 13 weeks. The tested doses were 7.5, 15, and 30 mg DCA/kg/day and 12.5, 25, and 50 mg TCA/kg/day. The DCA: TCA ratios in Mix I, II, and III were 7.5:12.5, 15:25, and 30:50 mg/kg/day, respectively. Peritoneal lavage cells were collected at the end of the treatment period and assayed for the biomarkers of phagocytic activation, including superoxide anion and tumor necrosis factor-alpha production, and myeloperoxidase activity. The mixtures produced nonlinear effects on the biomarkers of phagocytic activation, with Mix I and II effects were found to be additive, but Mix III effects were found to be less than additive. /Dichloroacetate/

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro. /Dichloroacetate/

The unique metabolic profile of cancer (aerobic glycolysis) is an attractive therapeutic target for cancer. Dichloroacetate(DCA), an inhibitor of pyruvate dehydrogenase kinase, has been shown to reverse glycolytic phenotype and induce mitochondrion-dependent apoptosis. In the present study, we investigated the effects of S6 kinase 1 (S6K1) inhibition on DCA-induced cell death and the underlying mechanisms in breast cancer cells. Cell death was evaluated by annexin V and PI staining. The synergistic effects of DCA and PF4708671 were assessed by isobologram analysis. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein levels were measured by RT-PCR and Western blot analysis, respectively. PF4708671, a selective inhibitor of S6K1, and knockdown of S6K1 with specific siRNA enhanced DCA-induced cell death. Interestingly, a combination of DCA/PF4708671 markedly reduced protein expression of a glycolytic enzyme, hexokinase 2 (HK2). Suppression of HK2 activity using specific siRNA and 2-deoxyglucose (2-DG) further enhanced cell sensitivity to DCA/PF4708671. Overexpression of Myc-tagged HK2 rescued cell death induced by DCA/PF4708671. Based on these findings, we propose that inhibition of S6K1, in combination with the glycolytic inhibitor, DCA, provides effective cancer therapy. /Dichloroacetate/

The unique metabolism of breast cancer cells provides interest in exploiting this phenomenon therapeutically. Metformin, a promising breast cancer therapeutic, targets complex I of the electron transport chain leading to an accumulation of reactive oxygen species (ROS) that eventually lead to cell death. Inhibition of complex I leads to lactate production, a metabolic byproduct already highly produced by reprogrammed cancer cells and associated with a poor prognosis. While metformin remains a promising cancer therapeutic, we sought a complementary agent to increase apoptotic promoting effects of metformin while attenuating lactate production possibly leading to greatly improved efficacy. Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism. Our purpose was to examine the synergy and mechanisms by which these two drugs kill breast cancer cells. Cell lines were subjected to the indicated treatments and analyzed for cell death and various aspects of metabolism. Cell death and ROS production were analyzed using flow cytometry, Western blot analysis, and cell counting methods. Images of cells were taken with phase contrast microscopy or confocal microscopy. Metabolism of cells was analyzed using the Seahorse XF24 analyzer, lactate assays, and pH analysis. We show that when DCA and metformin are used in combination, synergistic induction of apoptosis of breast cancer cells occurs. Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production. We demonstrate that DCA and metformin combine to synergistically induce caspase-dependent apoptosis involving oxidative damage with simultaneous attenuation of metformin promoted lactate production. Innovative combinations such as metformin and DCA show promise in expanding breast cancer therapies. /Dichloroacetate/

For more Interactions (Complete) data for Dichloroacetic acid (22 total), please visit the HSDB record page.

Multiple independent studies demonstrate that DCA has the ability to alter normal carbohydrate metabolism. Dichloroacetic acid treatment results in a significant reduction in plasma levels of glucose, pyruvate, and lactate. Another consistent finding in DCA ingestion studies is a dose-related increase in liver size, generally accompanied (or caused) by an increase in glycogen deposition in the liver. There is an extensive and consistent data base demonstrating the reproductive toxicity of DCA in males and females. Neurologic symptoms and morphologic changes in the nervous system have been reported in humans, dogs, and rats. (L2086)

EC50; Species: Xenopus laevis (African clawed frog) embryo; Conditions: freshwater, renewal, 23 °C, pH 7.0; Concentration: 3560000 ug/L for 96 hr (95% confidence interval: 2400000-4680000 ug/L); Effect: increased malformation, teratogenic measurements /formulated product/

LC50; Species: Xenopus laevis (African clawed frog) embryo; Conditions: freshwater, renewal, 23 °C, pH 7.0; Concentration: 4060000 ug/L for 96 hr (95% confidence interval: 3900000-5600000 ug/L) /Formulated product/

LC50; Species: Nitocra spinipes (Harpacticoid copepod) adult, length 0.6-0.9 mm; Conditions: saltwater, static, 21 °C, pH 7.8, salinity 7 ppt, alkalinity 75 mg/L CaCO3, dissolved oxygen >5 mg/L; Concentration: 23000 ug/L for 96 hr (95% confidence interval: 21000-25000 ug/L) /95% purity/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2(SRC), determined from a structure estimation method(2), indicates that dichloroacetic acid is expected to have very high mobility in soil(SRC). A pKa of 1.26(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Dichloroacetic acid has a vapor pressure of 0.179 mm Hg(5) and exists as a liquid under environmental conditions: therefore, dichloroacetic acid may volatilize from dry soil(SRC). Utilizing the Japanese MITI test, 97% of the Theoretical BOD was reached in 2 weeks(6) indicating that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2(SRC), determined from a structure estimation method(2), indicates that dichloroacetic acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 1.26(3) indicates dichloroacetic acid will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 0.92(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation of 14 and 8% for river water and seawater, respectively, after 3 days incubation(6) suggests that biodegradation may be an important fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dichloroacetic acid, which has a vapor pressure of 0.179 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dichloroacetic acid is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 22 days(SRC), calculated from its rate constant of 7.3X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Dichloroacetic acid does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

The substance can be absorbed into the body by inhalation of its aerosol and through the skin.

Ingestion

IDENTIFICATION AND USE: Dichloroacetic acid (DCA) is a colorless liquid. Dichloroacetic acid, particularly in the form of its esters, is an intermediate in organic synthesis, used in the production of glyoxylic acid, dialkoxy and diaroxy acids, and sulfonamides and in the preparation of iron chelates in the agricultural sector. It is also used as an analytical reagent in fiber manufacture (polyethylene terephthalate) and as a medicinal disinfectant (substitute for formalin). DCA is a cauterizing agent and is used in medical practice as dichloroacetate on calluses, hard and soft corns, xanthoma palpebrarum, seborrhoeic keratoses, in-grown nails, cysts and benign erosion of the cervix. DCA is a nonproprietary drug used for treatment of inherited mitochondrial diseases. It was discovered in 2007 that dichloroacetate sodium (the sodium salt of DCA) promotes human cancer cell death by a novel mechanism. Soon after this discovery, physicians began using it off-label for cancer treatment. Dichloroacetate inhibits pyruvate dehydrogenase kinase, an enzyme that promotes pyruvate entry into mitochondria. HUMAN STUDIES: Drowsiness is a fairly frequent side effect of DCA and has been observed in healthy volunteers, adults with type I diabetes and patients with lactic acidosis. A patient with homozygous familial hypercholesterolemia who received single doses of 50 mg/kg bw DCA daily for four months developed reversible peripheral neuropathy characterized by loss of reflexes and muscle weakness. The effect subsided several weeks after cessation of administration of DCA. Preclinical evidence suggests that dichloroacetate can reverse the "Warburg effect" and inhibit growth in cancer models. The "Warburg effect," also termed aerobic glycolysis, describes the increased reliance of cancer cells on glycolysis for ATP production, even in the presence of oxygen. Consequently, there is continued interest in inhibitors of glycolysis as cancer therapeutics. One example is dichloroacetate, a pyruvate mimetic that stimulates oxidative phosphorylation through inhibition of pyruvate dehydrogenase kinase. ANIMAL STUDIES: DCA induced severe injury when applied to eyes of rabbits. Exposure of male and female rats to DCA at target doses of 10-600 mg/kg body weight per day in the drinking water for 14 days resulted in reduced weight gain only in the group given the highest dose. Treatment also increased urinary excretion of ammonia and changed the activities of enzymes of ammoniagenesis, indicating renal compensation for an acid load. Ocular toxicity was observed in beagle dogs that were treated for 13 weeks with an approximate dose of 1100 mg/kg body weight DCA in the drinking water. No similar organ specific effect has been seen in other studies or in other species. Induction of peroxisome proliferation has been repeatedly associated with the chronic toxicity and carcinogenicity of DCA to the liver. It can induce peroxisome proliferation in the livers of both mice and rats, as indicated by increased activities of palmitoyl coenzyme A oxidase and carnitine acetyl transferase, the appearance of a peroxisome proliferation associated protein and increased volume-density of peroxisomes after exposure to DCA for 14 days. In eight studies, DCA salt administered in the drinking water to male and/or female mice increased the incidences of hepatocellular adenomas and/or carcinomas. Following oral administration of DCA in the drinking-water to male rats, an increased incidence of hepatocellular carcinomas was found at a dose that decreased body weight and an increase in the combined incidence of adenomas and carcinomas was found at a lower dose. When administered in the drinking-water, DCA promoted hepatocellular carcinomas in carcinogen-initiated male and female mice in three studies. DCA and its metabolites accumulate in rat fetuses after treatment of the dam. Maternal doses of 140-2400 mg/kg bw per day on days 6-15 of gestation altered development of the heart and major vessels and less frequently, the kidneys and the orbits of the eyes, as reported in some studies. DNA strand breaks were not induced in mammalian cells in vitro in the absence of an exogenous metabolic activation system, but contradictory results were obtained in vivo. No effect was seen in either mouse or rat hepatic cells after single or repeated dosing, and no effects were observed in epithelial cells from spleen, stomach or duodenum after a single dose. Dichloroacetic acid did not induce differential toxicity in DNA repair-deficient strains of Salmonella typhimurium but did induce prophage in Escherichia coli in one study. It was mutagenic to Salmonella typhimurium TA100 and TA98 in single studies. Most of the mutations in 400 revertants of DCA-treated Salmonella typhimurium TA100 cultures were GA AT transitions. ECOTOXICITY STUDIES: DCA is a common contaminant of aquatic ecosystems. A study to investigate potential phytotoxic effects was conducted on rooted and floating macrophytes (Myriophyllum spicatum, M. sibiricum, and Lemna gibba). The most sensitive plant endpoints were wet mass and plant length.

The dichloroacetate ion stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting the enzyme pyruvate dehydrogenase kinase. Thus, it decreases lactate production by shifting the metabolism of pyruvate from fermentation towards oxidation in the mitochondria. (Wikipedia)

/AQUATIC SPECIES/ ...The kinetics and effects of dichloroacetic acid (DCA) in rainbow trout /were examined/. Branchial uptake was measured in fish confined to respirometer-metabolism chambers. Branchial uptake efficiency was <5%, suggesting passive diffusion through aqueous channels in the gill epithelium. DCA concentrations in tissues following prolonged (72, 168, or 336 hr) waterborne exposures were expressed as tissue:plasma concentration ratios. Concentration ratios for the kidney and muscle at 168 and 336 hr were consistent with the suggestion that DCA distributes primarily to tissue water. Reduced concentration ratios for the liver, particularly at 72 hr, indicated that DCA was highly metabolized by this tissue. Routes and rates of elimination were characterized by injecting chambered animals with a high (5.0 mg/kg) or low (50 ug/kg) bolus dose. DCA was rapidly cleared by naive animals resulting in elimination half-lives (t(1/2)) of less than 4 hr. Waterborne pre-treatment of fish with DCA increased the persistence of a subsequently injected dose. In high dose animals, pre-treatment caused a 4-fold decrease in whole-body clearance (CL(B)) and corresponding increases in the area under the plasma concentration-time curve (extrapolated to infinity; AUC(0-->infinity)) and t(1/2). Qualitatively similar results were obtained in low dose fish, although the magnitude of the pre-treatment effect (approximately 2.5-fold) was reduced. Renal and branchial clearance contributed little (combined, <3% of CL(B)) to the elimination of DCA. Biliary elimination of DCA was also negligible. The steady-state volume of distribution (V(SS)) did not vary among treatment groups and was consistent with results of the tissue distribution study. DCA had no apparent effects on respiratory physiology or acid-base balance; however, the concentration of blood lactate declined progressively during continuous waterborne exposures. A transient effect on blood lactate was also observed in bolus injection experiments. The results of this study suggest that clearance of DCA is due almost entirely to metabolism. The pathway responsible for this activity exhibits characteristics in common with those of mammalian glutathione S-transferase zeta (GSTzeta), including non-linear kinetics and apparent suicide inactivation by DCA. Observed effects on blood lactate are probably due to the inhibition of pyruvate dehydrogenase kinase in aerobic tissues and may require the participation of a monocarboxylase transport protein to move DCA across cell membranes.

/OTHER TERRESTRIAL SPECIES/ Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, ...cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 ug/mL) /are evaluated/ using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 hr to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. ...Locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps /were also examined/ at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. ...Mild OS and induction of antioxidant defense system in 20.0 ug/mL DCA-exposed organism after 24 hr. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA.

/FIELD STUDIES/ Dichloroacetic acid (DCA), a haloacetic acid, is a common contaminant of aquatic ecosystems. A study to investigate potential phytotoxic effects on rooted and floating macrophytes (Myriophyllum spicatum, M. sibiricum, and Lemna gibba) was conducted. Replicate 12,000 L outdoor microcosms (n = 3) were treated with 3, 10, 30, and 100 mg/L of DCA that had been neutralized to the sodium salt, plus controls. Plants were sampled regularly over 21 days and assessed for a variety of endpoints including plant growth, root growth, number of nodes, wet and dry mass, chlorophyll-a, chlorophyll-b, carotenoids, and citrate levels. EC10, EC25, and EC50 values were calculated for each endpoint that exhibited a concentration-response. Overall, M. sibiricum was slightly more sensitive than M. spicatum to DCA exposure. The most sensitive plant endpoints were wet mass and plant length. Pigments showed no response with exposure to DCA. The probability of current concentrations of DCA in Canadian lake water and Swiss river waters exceeding thresholds of toxicity derived from single species effect measure distributions (EC10s) is << 0.01%... Currently, environmental levels of DCA do not pose a risk to these plants.

Pine needles taken from trees surrounding a pulp and paper mill in western Finland contained 0-3.80 ng/g fresh weight dichloroacetic acid, while pine needles taken from areas surrounding a metal reclamation plant in southern Finland contained 0.65-2.55 ng/g fresh weight dichloroacetic acid(1). Mean concentrations of <2, <2, 2, 2 and 12 ng/g wet weight were reported in conifer needle samples from Chilo, Banff Natl Park, Canada, Gulephy Ontario, Canada, Malwai and Lancaster UK, respectively, sampled 1999-2000(2).

The maximum contaminant level for haloacetic acids (five) (HAA5) is 0.060 mg/L. /Haloacetic acids (five) (HAA5) mean the sum of the concentrations in milligrams per liter of the haloacetic acid compounds (monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid), rounded to two significant figures after addition./

Both dichloroacetate (DCA) and metformin (Met) have shown promising antitumor efficacy by regulating cancer cell metabolism. However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages will improve their therapeutic effects. In the present study, we found that DCA and Met synergistically inhibited the growth and enhanced the apoptosis of ovarian cancer cells. Interestingly, we for the first time revealed that Met sensitized DCA via dramatically attenuating DCA-induced Mcl-1 protein and protective autophagy, while DCA sensitized Met through markedly alleviating Met-induced excessive lactate accumulation and glucose consumption. The in vivo experiments in nude mice also showed that DCA and Met synergistically suppressed the growth of xenograft ovarian tumors. These results may pave a way for developing novel strategies for the treatment of ovarian cancer based on the combined use of DCA and Met. /Dichloroacetate/

Dichloroacetate (DCA) promotes pyruvate entry into the Krebs cycle by inhibiting pyruvate dehydrogenase (PDH) kinase and thereby maintaining PDH in the active dephosphorylated state. DCA has recently gained attention as a potential metabolic-targeting therapy for heart failure but the molecular basis of the therapeutic effect of DCA in the heart remains a mystery. Once-daily oral administration of DCA alleviates pressure overload-induced left ventricular remodeling. We examined changes in the metabolic fate of pyruvate carbon (derived from glucose) entering the Krebs cycle by metabolic interventions of DCA. (13)C6-glucose pathway tracing analysis revealed that instead of being completely oxidized in the mitochondria for ATP production, DCA-mediated PDH dephosphorylation results in an increased acetyl-CoA pool both in control and pressure-overloaded hearts. DCA induces hyperacetylation of histone H3K9 and H4 in a dose-dependent manner in parallel to the dephosphorylation of PDH in cultured cardiomyocytes. DCA administration increases histone H3K9 acetylation in in vivo mouse heart. Interestingly, DCA-dependent histone acetylation was associated with an up-regulation of 2.3% of genes (545 out of 23,474 examined). Gene ontology analysis revealed that these genes are highly enriched in transcription-related categories. This evidence suggests that sustained activation of PDH by DCA results in an overproduction of acetyl-CoA, which exceeds oxidation in the Krebs cycle and results in histone acetylation. We propose that DCA-mediated PDH activation has the potential to induce epigenetic remodeling in the heart, which, at least in part, forms the molecular basis for the therapeutic effect of DCA in the heart. /Dichloroacetate/

Short-term treatment (11 days) of mice with dichloroacetate produced hypomethylation of DNA in liver, but this effect disappeared with longer-term treatment (44 weeks). However, the extent of methylation at 5-methylcytosine sites in DNA of liver tumors was reduced by chronic treatment (44 weeks) with dichloroacetic acid, but returned to normal if treatment was suspended 1 week prior to sacrifice. Hypomethylation of DNA and of the specific proto-oncogenes c-jun and c-myc was associated with an increase in their expression in dichloroacetate-promoted tumors when compared with surrounding nontumorous liver. The hypomethylation was reversed by prior administration of methionine, suggesting that dichloroacetate acts by depleting the availability of S-adenosyl-methionine for methylation. It appears that hypomethylation of promoter region for the c-myc gene occurs in several tissues (liver, kidney and bladder) in mice and precedes cell replication within these tissues; dichloroacetate prevents the methylation of hemimethylated sites in newly synthesized strands of DNA.

Pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase (PDH) activity and thus promotes energetic switch from mitochondrial glucose oxidation to cytoplasmic glycolysis in cancerous cells (a phenomenon known as the 'Warburg effect') for their energy need, which facilitates the cancer progression by resisting induction of apoptosis and promoting tumor metastasis. Thus, in the present investigation, we explored the molecular mechanisms of the tumoricidal action of dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, on cells of a murine T cell lymphoma, designated as Dalton's lymphoma (DL). In vitro treatment of tumor cells with DCA inhibited their survival accompanied by a modulation of the biophysical composition of tumor-conditioned medium with respect to pH, glucose and lactate. DCA treatment also altered expression of HIF1-alpha and pH regulators: VATPase and MCT1 and production of cytokines: IL-10, IL-6 and IFN-gamma. Moreover, we also observed an alteration in the expression of other apoptosis and cell survival regulatory molecules: PUMA, GLUT1, Bcl2, p53, CAD, caspase-3 and HSP70. The study discusses the role of novel molecular mechanisms underlying DCA-dependent inhibition of tumor cell survival. This study shows for the first time that DCA-dependent alteration of tumor cell survival involves altered pH homeostasis and glucose metabolism. Thus, these findings will provide a new insight for therapeutic applications of DCA as a novel antineoplastic agent against T cell lymphoma. /Dichloroacetate/

Spontaneous apoptosis in hepatocytes of male B6C3F1 mice that received dichloroacetic acid (DCA) in their drinking water for 5-30 days (28-58 days of life) was examined as part of ongoing studies to determine the molecular basis of the hepatocarcinogenicity of this nongenotoxic water chlorination by-product. DCA at 0.5 and 5.0 g/liter, significantly reduced apoptosis relative to untreated controls in a dose dependent fashion. Regression analysis indicated that apoptosis declined over the 30-day period in the livers of control, age paired animals receiving no drug. Animals receiving low dose DCA exhibited a similar, although quantitatively depressed, trend line, whereas animals receiving high-dose DCA showed maximal depression of apoptosis at 5 days, which was sustained throughout the course of the 30 day period. These studies suggest that DCA has the ability to down regulate apoptosis in murine liver. When taken together with previous data demonstrating DCA dependent decrease in labeling index in these same livers, these data further support the hypothesis that the carcinogenic mechanism of DCA may involve suppression of the ability of the liver to remove initiated cells by apoptosis rather than by induction of selective proliferation of initiated cells.

The pharmacokinetics of dichloroacetic acid was studied in 111 patients (66 men, 56.0 +/- 18.4 years old) with lactic acidosis, who received dichloroacetic acid (50 mg/kg bw) by intravenous perfusion over 30 min, then a second perfusion of 50 mg/kg bw 2 hr after the beginning of the first. ... In the two-compartment model, the plasma half-life and plasma clearance were 18.15 +/- 3.12 hr (mean +/- standard error (SE)) and 0.041 L/kg/hr, respectively, after the first treatment, whereas the two values were 68.30 +/- 14.50 hr (mean +/- SE) and 0.017 L/kg/hr, respectively, after the second treatment. Plasma clearance of dichloroacetic acid tended to decrease as either the number of compartments or the number of treatments increased. The prolonged half-life and decreased plasma clearance indicate that repeated administration of dichloroacetic acid impairs its metabolism

Dichloroacetic acid was given intravenously (50 mg/kg bw) or orally (50 mg/kg bw or 50 mg/kg bw plus 50 mg thiamine (vitamin B1) to healthy human volunteers (eight men and four women, aged 18 to 45 years), and a range of pharmacokinetic parameters were measured. On average, there was no evidence of an effect of vitamin B1 on the kinetics of dichloroacetic acetic. The average plasma half-life was 2.7 +/- 0.4 hr ... . There was no difference in the ... elimination half-life between men and women. ... The elimination half-life was markedly prolonged after a second dose of dichloroacetic acid.

The pharmacokinetics of dichloroacetic acid was studied in rats and dogs. Three male Sprague-Dawley rats and two male beagle dogs were given 100 mg/kg bw dichloroacetic acid intravenously; the average plasma elimination half-life was 2.97 hr (range, 2.1-4.4 hr) in rats and 20.8 hr (range, 17.1-24.6 hr) in dogs; ... .

Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. ... We studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. ... According to the best-fit model, bioavailability of oral TCE was approximately 74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 hr, 0.081 mL/hr; TCA: 12 hr, 3.80 mL/hr; DCVG: 1.4 hr, 16.8 mL/hr; DCVC: 1.2 hr, 176 mL/hr. ...

For more Biological Half-Life (Complete) data for Dichloroacetic acid (11 total), please visit the HSDB record page.

Dichloroacetate (DCA) inhibits its own metabolism and is converted to glyoxylate by glutathione S-transferase zeta (GSTz). GSTz is identical to maleylacetoacetate isomerase, an enzyme of tyrosine catabolism that converts maleylacetoacetate (MAA) to fumarylacetoacetate and maleylacetone (MA) to fumarylacetone. MAA and MA are alkylating agents. Rats treated with DCA for up to five days had markedly decreased hepatic GSTz activity and increased urinary excretion of MA. When dialyzed cytosol obtained from human liver was incubated with DCA, GSTz activity was unaffected. In contrast, DCA incubation inhibited enzyme activity in dialyzed hepatic cytosol from rats. Incubation of either rat or human hepatic cytosol with MA led to a dose dependent inhibition of GSTz. These data indicate that humans or rodents exposed to DCA may accumulate MA and/or MAA which inhibit(s) GSTz and, consequently, DCA biotransformation. Moreover, DCA-induced inhibition of tyrosine catabolism may account for the toxicity of this xenobiotic in humans and other species.

... Glutathione transferase zeta (GSTZ1-1) catalyzes the biotransformation of a range of alpha-haloalkanoates and the cis-trans isomerization of maleylacetoacetate. ... The purpose of this study was to examine the GSTZ1-1-catalyzed bioactivation of dichloroacetic acid (DCA), including the reaction of DCA-derived glyoxylate with amino acid nucleophiles and the characterization of the structures and kinetics of adduct formation by LC/MS. The binding of (1-(14)C)DCA-derived label to bovine serum albumin required both GSTZ1-1 and GSH, whereas the binding to dialyzed rat liver cytosolic protein was increased in the presence of GSH. Studies with model peptides (antiflammin-2 and IL-8 inhibitor) indicated that glyoxylate, rather than S-(alpha-chlorocarboxymethyl)glutathione, was the reactive species that modified amino acid nucleophiles. Both addition (+74 Da) and addition-elimination (+56 Da) adducts of glyoxylic acid were observed. Addition adducts (+74 Da) could not be characterized completely by mass spectrometry, whereas addition-elimination adducts (+56 Da) were characterized as 2-carboxy-4-imidazolidinones. 2-Carboxy-4-imidazolidinones were formed by the rapid equilibrium reaction of glyoxylate with the N-terminal amino group of antiflammin-2 to give an intermediate carbinolamine (K(eq) = 0.63 mM(-1)), which slowly eliminated water to give an intermediate imine (k(2) = 0.067 hour(-1)), which rapidly cyclized to give the 2-carboxy-4-imidazolidinone. Glucose 6-phosphate dehydrogenase was inactivated partially by glyoxylate when reactants were reduced with sodium borodeuteride, which may indicate that glyoxylate reacts with selective lysine epsilon-amino groups. The results of the present study demonstrate that GSTZ1-1 catalyzes the bioactivation of DCA to the reactive metabolite glyoxylate. The reaction of glyoxylate with cellular macromolecules may be associated with the multiorgan toxicity of DCA.

Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. Recently, we developed a new analytical method for simultaneous assessment of these TCE metabolites in small-volume biological samples. Since important gaps remain in our understanding of the pharmacokinetics of TCE and its metabolites, we studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic concentration-time data, we constructed multi-compartment models to explore the kinetic properties of the formation and disposition of TCE metabolites, as well as the source of DCA formation. We conclude that TCE-oxide is the most likely source of DCA. According to the best-fit model, bioavailability of oral TCE was approximately 74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 hr, 0.081 mL/hr; TCA: 12 hr, 3.80 mL/hr; DCVG: 1.4 hr, 16.8 mL/hr; DCVC: 1.2 hr, 176 mL/hr. In B6C3F1 mice, oxidative metabolites are formed in much greater quantities (approximately 3600 fold difference) than glutathione-conjugative metabolites. In addition, DCA is produced to a very limited extent relative to TCA, while most of DCVG is converted into DCVC. These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment.

Dichloroacetate (DCA) is a potential environmental hazard and an investigational drug. Repeated doses of DCA result in reduced drug clearance, probably through inhibition of glutathione transferase zeta1 (GSTZ1), a cytosolic enzyme that converts DCA to glyoxylate. DCA is known to be taken up by mitochondria, where it inhibits pyruvate dehydrogenase kinase, its major pharmacodynamic target. We tested the hypothesis that the mitochondrion was also a site of DCA biotransformation. Immunoreactive GSTZ1 was detected in liver mitochondria from humans and rats, and its identity was confirmed by liquid chromatography/tandem mass spectrometry analysis of the tryptic peptides. Study of rat submitochondrial fractions revealed GSTZ1 to be localized in the mitochondrial matrix. The specific activity of GSTZ1-catalyzed dechlorination of DCA was 2.5- to 3-fold higher in cytosol than in whole mitochondria and was directly proportional to GSTZ1 protein expression in the two compartments. Rat mitochondrial GSTZ1 had a 2.5-fold higher (App)K(m) for glutathione than cytosolic GSTZ1, whereas the (App)K(m) values for DCA were identical. Rats administered DCA at a dose of 500 mg/kg/day for 8 weeks showed reduced hepatic GSTZ1 activity and expression of approximately 10% of control levels in both cytosol and mitochondria. We conclude that the mitochondrion is a novel site of DCA biotransformation catalyzed by GSTZ1, an enzyme colocalized in cytosol and mitochondrial matrix. /Dichloroacetate/

For more Metabolism/Metabolites (Complete) data for Dichloroacetic acid (22 total), please visit the HSDB record page.

Dichloroacetic acid is metabolized in the liver by oxidative dechlorination to yield glyoxylate, which can enter intermediary metabolism and either be oxidized to oxalate and excreted, converted to carbon dioxide, and/or incorporated into amino acids or other cellular molecules. (L2086)

We characterized the pharmacokinetics and dynamics of dichloroacetate (DCA), an investigational drug for mitochondrial diseases, pulmonary arterial hypertension, and cancer. Adult Beagle dogs were orally administered 6.25 mg/kg q12h DCA for 4 weeks. Plasma kinetics was determined after 1, 14, and 28 days. The activity and expression of glutathione transferase zeta 1 (GSTZ1), which biotransforms DCA to glyoxylate, were determined from liver biopsies at baseline and after 27 days. Dogs demonstrate much slower clearance and greater inhibition of DCA metabolism and GSTZ1 activity and expression than rodents and most humans. Indeed, the plasma kinetics of DCA in dogs is similar to humans with GSTZ1 polymorphisms that confer exceptionally slow plasma clearance. Dogs may be a useful model to further investigate the toxicokinetics and therapeutic potential of DCA. /Dichloroacetate/

... The kinetics and biotransformation of dichloroacetate (DCA) and its effects on tyrosine metabolism /were measured/ in nine patients treated for 6 months with 25 mg/kg/day and in rats treated for 5 days with 50 mg/kg/day. ... The activity and expression of hepatic GSTz1/MAAI /was also measured/. Chronic administration of DCA causes a striking age-dependent decrease in its plasma clearance and an increase in its plasma half-life in patients and rats. Urinary excretion of unchanged DCA in rats increases with age, whereas oxalate, an end product of DCA metabolism, shows the opposite trend. Low concentrations of monochloroacetate (MCA), which is known to be neurotoxic, increase as a function of age in the urine of dosed rats. MCA was detectable in plasma only of older animals. Hepatic GSTz1/MAAI-specific activity was inhibited equally by DCA treatment among all age groups, whereas plasma and urinary levels of maleylacetone, a natural substrate for this enzyme, increased with age. We conclude that age is an important variable in the in vivo metabolism and elimination of DCA and that it may account, in part, for the neurotoxicity of this compound in humans and other species. /Dichloroacetate/

... Seven subjects with cirrhosis and six healthy volunteers received a 5-hour primed constant infusion of 6,6-2H2-glucose. After a 2-hour basal period, subjects received intravenous dichloroacetate, 35 mg/kg, over 30 minutes. Dichloroacetate pharmacokinetics were compared by the mixed-effects population-based technique. Glucose production was calculated by means of isotope dilution. ... Peak plasma dichloroacetate concentration in subjects with cirrhosis did not differ from that in control subjects, but typical dichloroacetate clearance was only 36% of that in control subjects (P <0 .001). Dichloroacetate decreased plasma lactate concentration by approximately 50% (P < 0.001), glucose production by 7% to 9% (P < 0.05), and plasma glucose concentration by 9% to 14% (P < 0.05) in both subjects with cirrhosis and control subjects. Dichloroacetate-induced decreases in plasma lactate and glucose concentrations and in glucose production in subjects with cirrhosis did not differ from those in control subjects. ... Plasma dichloroacetate clearance is markedly decreased in patients with cirrhosis, likely because of compromised hepatic function. Subjects with cirrhosis exhibit neither exaggerated inhibition of glucose production nor increased risk of hypoglycemia as a result of acute dichloroacetate-induced hypolactatemia. /Dichloroacetate/

The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 hr after oral gavage of 282 mg/kg of 1- or 2-(14)C-DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA. DCA was absorbed quickly, and the major route of disposition was through exhalation of carbon dioxide and elimination in the urine. The dispositions of 1- and 2-DCA at 282 mg/kg were similar. With 2-DCA, the disposition differed with dose in that the percentage of the dose expired as carbon dioxide decreased from 34.4% (28.2 mg/kg) to 25.0% (282 mg/kg), while the percentage of the radioactivity excreted in the urine increased from 12.7 to 35.2%. This percentage increase in the urinary excretion was mostly attributable to the presence of unmetabolized DCA, which comprised more than 20% at the higher dose and less than 1% at the lower dose. The major urinary metabolites were glycolic acid, glyoxylic acid, and oxalic acid. DCA and its metabolites accumulated in the tissues and were eliminated slowly. After 48 hr, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2-DCA and 282 mg/kg of 1-DCA, respectively. Of the organs examined, the liver (4.9-7.9% of dose) and muscle (4.5-9.9%) contained the most radioactivity, followed by skin (3.3-4.5%), blood (1.4-2.6%), and intestines (1.0-1.7%). ...

For more Absorption, Distribution and Excretion (Complete) data for Dichloroacetic acid (17 total), please visit the HSDB record page.

Used as an intermediate to make other chemicals, a test reagent for fiber analysis, a disinfectant, and a medication; [CHEMINFO]

Using Disinfectants or Biocides [Category: Clean]

Intermediate, pharmaceuticals, medicine.

... Used as a test reagent for analytical measurements during fiber manufacture [poly(ethylene terephthalate)] and as a medicinal disinfectant (substitute for formalin). ... Used as a deblocking agent in the solid-phase synthesis of oligonucleotides. ... Dichloroacetic acid, particularly in the form of its esters, is an important intermediate in organic synthesis. It is a reactive starting material for the production of glyoxylic acid, dialkoxy and diaroxy acids, and sulfonamides.

... Used in the synthesis of chloramphenicol and allantoin. Dichloroacetic acid has virucidal and fungicidal activity. It was found to be active against several staphylococci.

Dichloroacetic acid, particularly in the form of its esters, is an intermediate in organic synthesis, used in the production of glyoxylic acid, dialkoxy and diaroxy acids, and sulfonamides and in the preparation of iron chelates in the agricultural sector. It is also used as an analytical reagent in fiber manufacture (polyethylene terephthalate) and as a medicinal disinfectant (substitute for formalin).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#6395]

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Dichloroacetic acid:

The most cost-effective production method is the hydrolysis of dichloroacetyl chloride. Moreover, 98% dichloroacetic acid can be obtained in 90% yield by hydrolysis of pentachloroethane with 88-99% sulfuric acid or by oxidation of 1,1-dichloroacetone with nitric acid and air. Extremely pure dichloroacetic acid can be produced by hydrolysis of the methyl ester, which is readily available by esterification of crude dichloroacetic acid. ... Dichloroacetic acid and ethyl dichloroacetate can be obtained by catalytic dechlorination of trichloroacetic acid or ethyl trichloroacetate with hydrogen over a palladium catalyst.

It has been manufactured by the chlorination of acetic and chloroacetic acids, reduction of trichloroacetic acid, hydrolysis of pentachloroethane, and hydrolysis of dichloroacetyl chloride. Due to similar boiling points, the separation of dichloroacetic acid from chloroacetic acid is not practical by conventional distillation. However, this separation has been accomplished by the addition of azeotropeforming hydrocarbons such as bromobenzene or by distillation of the methyl or ethyl ester.

Derivation: Chlorination of acetic acid in presence of iodine.

Cosmetics product ingredient: Dichloroacetic acid

Information on 4 consumer products that contain Dichloroacetic acid in the following categories is provided:

Acetic acid, 2,2-dichloro-: ACTIVE

Haloacetic acids (five) (HAA5) mean the sum of the concentrations in milligrams per liter of the haloacetic acid compounds (monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid), rounded to two significant figures after addition. /Haloacetic Acids (five) (HAA5)/

Dichloroacetic acid was reported to be first synthesized in 1864 by the further chlorination of monochloroacetic acid with chlorine. Haloacetic acids were first detected in 1983 as disinfection by-products in chlorinated drinking-waters, 9 years after the discovery of trihalomethanes in chlorinated waters.