Physicochemical Properties
| Molecular Formula | C2H2BR2O2 |
| Molecular Weight | 217.84 |
| Exact Mass | 215.842 |
| CAS # | 631-64-1 |
| PubChem CID | 12433 |
| Appearance | Hygroscopic crystals |
| Density | 2.382 g/mL at 25ºC(lit.) |
| Boiling Point | 128-130ºC16 mm Hg(lit.) |
| Melting Point | 32-38ºC(lit.) |
| Flash Point | >230 °F |
| Index of Refraction | 1.598 |
| LogP | 1.186 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 6 |
| Complexity | 60.6 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(C(=O)O)(Br)Br |
| InChi Key | SIEILFNCEFEENQ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C2H2Br2O2/c3-1(4)2(5)6/h1H,(H,5,6) |
| Chemical Name | 2,2-dibromoacetic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Thymocyte proliferation is significantly reduced in vitro when exposed to DBAA (5–40 μM)[1]. Cell cycle arrest was induced by DBAA treatment (5–40 μM) for a 24-hour period. Thymocytes treated with varying concentrations of DBAA exhibited a minimum 40% increase in the G0 /G1 phase and a 50% decrease in the S phase, according to the data[1]. For a 24-hour period, DBAA (5–40 μM) increases the expression of Fas/FasL and decreases the expression of Bcl-2[1]. |
| ln Vivo | Based on a higher frequency of malignant mesothelioma in male rats, there is some indication that dibromoacetic acid has carcinogenic potential. The elevated rates of mononuclear cell leukemia observed in male rats could potentially be linked to exposure to dibromoacetic acid [2]. Dibromoacetic acid activity in female rats is based on a positive trend and higher frequency of mononuclear cell leukemia [2]. Based on elevated occurrences of hepatocellular neoplasms and hepatoblastoma (in males only), dibromoacetic acid is clearly carcinogenic in both male and female mice. Male mice also had higher rates of lung neoplasms, which were thought to be associated to exposure[2]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: Thymocytes from BALB/c mice Tested Concentrations: 0, 5, 10, 20, and 40 μM Incubation Duration: 6, 12, 24, 48, and 72 hrs (hours) Experimental Results: Led to a Dramatically diminished cell proliferative response to T-cell mitogen for 6 hr or longer. At 6 hr, significant inhibition was observed only at 40 μM, and significant inhibition was observed for all concentrations at 24, 48, and 72 hr. Western Blot Analysis[1] Cell Types: Thymocytes Tested Concentrations: 0, 5, 10, 20, and 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: The expression of Fas/FasL increased Dramatically from 10 μM, and the expression of Bcl-2 diminished at all concentration. |
| Animal Protocol |
Animal/Disease Models: Male and female F344/N rats and B6C3F1 mice[2] Doses: Groups of five male and five female rats/mice were exposed to 0, 125, 250, 500, 1,000, or 2,000 mg/L Dibromoacetic acid in drinking water for 2 weeks Groups of 10 male and 10 female rats /mice were exposed to 0, 125, 250, 500, 1,000, or 2,000 mg/L Dibromoacetic acid in drinking water for 3 months Groups of 50 male and 50 female rats/mice were exposed to drinking water containing 0, 50, 500, and 1,000 mg/L Dibromoacetic acid for 2 years Route of Administration: Exposed to Dibromoacetic acid (greater than 99% pure) in drinking water for 2 weeks, 3 months, or 2 years. Experimental Results: Exposure to Dibromoacetic acid for 2 years caused increased incidences of cystic degeneration of the liver in male rats, increased incidences of alveolar epithelial hyperplasia and nephropathy in female rats, and increased incidences of splenic hematopoiesis in male mice. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Dibromoacetic acid (DBA) ... /was/ provided in drinking water in range-finding reproductive/developmental toxicity studies (rats) ... Studies included absorption and biodisposition of DBA ... including passage into placentas, amniotic fluid, fetuses ... or milk ... . The DBA ... range-finding reproductive/developmental toxicity studies each included 50 Sprague-Dawley rats/sex/group. DBA (0, 125, 250, 500, or 1000 ppm) ... was provided in drinking water 14 days premating through gestation and lactation (63 to 70 days). ... Satellite groups (6 male, 17 female rats/group/study ... were used for bioanalytical sampling. Rats ... had exposure-related reduced water consumption caused by apparent taste aversion to DBA ..., especially in the parental animals at the two highest exposure levels (500 and 1000 ppm DBA ... . Female rats consumed slightly higher mg/kg/day doses of DBA than male rats, especially during gestation and lactation; weanling rats consumed the highest mg/kg/day doses. DBA produced detectable and quantifiable concentrations in plasma, placentas, amniotic fluid, and milk. Plasma samples confirmed that rats drink predominately during the dark; this drinking pattern, not accumulation, produced detectable plasma concentrations for 18 to 24 hours/day... Dibromoacetate was measured in the testicular interstitial fluid of male Sprague-Dawley rats given five daily gavage doses of 250 mg dibromoacetate/kg body weight ... . The level of dibromoacetate in testicular fluid peaked at 79 ug/mL (approximately 370 uM) 30 minutes after the last dose, and the half-life was approximately 1.5 hours. Dibromoacetate was administered to Sprague-Dawley rats in drinking water at concentrations ranging from 125 to 1,000 ppm (mg/L) with exposures beginning 14 days before cohabitation and continuing through gestation and lactation ... Quantifiable levels of dibromoacetate were measured in parental and fetal plasma, placental tissue, amniotic fluid, and milk. Thus, dibromoacetate crosses the placenta and is taken up by fetal tissue. The oral bioavailability of dibromoacetate was reported to be 30% in male F344/N rats ... . The lower bioavailability of dibromoacetate compared to dichloroacetate is due to greater first-pass metabolism of dibromoacetate in the liver. Biological Half-Life Dibromoacetate was measured in the testicular interstitial fluid of male Sprague-Dawley rats given five daily gavage doses of 250 mg dibromoacetate/kg body weight ... . The half-life was approximately 1.5 hours. |
| Toxicity/Toxicokinetics |
Interactions The disinfection by-product dibromoacetic acid (DBA) has been found in female rats to increase circulating concentrations of both estradiol (E2) and estrone (E1). This effect is apparently due, at least in part, to a suppression in hepatic catabolism. The present study investigated whether DBA, by increasing sex steroid levels, is able either to augment the hypothalamic up-regulation involved in triggering a luteinizing hormone (LH) surge, or to affect the ability of the neurotoxicant sodium dimethyldithiocarbamate (DMDC) to block the surge. Sprague-Dawley rats were gavaged for 14 days with DBA (0-150 mg/kg) and ovariectomized on dosing day 11, and at the same time implanted with an estradiol capsule to generate daily LH surges. An injection of 0.1 mM/kg DMDC was administered at 13:00 hr on day 14 and blood was sampled over the afternoon. DBA induced a dose-related increase in total estrogens. For identified surges, areas under the LH curve partitioned into two groups, comprising the two lower (0 and 37.5 mg/kg DBA) and the two higher (75 and 150 mg/kg) treatment groups. Consequently, low and high DBA groups were compared and found to be significantly different. At 150 mg DBA/0.1 mM DMDC, the timing of an identifiable LH peak was comparable to non-DMDC females, unlike the 37.5mg DBA/0.1 mM DMDC group in which the appearance of peak concentrations was delayed. A significant effect with DBA treatment alone was not present. Results indicated that this exposure to DBA induced a dose-related increase in total estrogen concentrations that paralleled a diminished DMDC blockade of the LH surge. The effect appeared to be attributable to an augmentation in the estrogen-associated up-regulation in brain mechanisms stimulating the surge. Chlorination of drinking water generates disinfection by-products (DBPs) , which have been shown to disrupt spermatogenesis in rodents at high doses, suggesting that DBPs could pose a reproductive risk to men. ... A cohort study /was conducted/ to evaluate semen quality in men with well-characterized exposures to DBPs. ... The results of the present study do not support an association between exposure to DBPs at levels approaching regulatory limits and adverse sperm outcomes, although /there was/ an association between total organohalides and sperm concentration. ... The lone association of total organohalide exposure with sperm concentration may lend support to findings that have suggested that total organohalide is a stronger risk factor for adverse pregnancy outcomes than any of the regulated DBP groups or species and that the toxicity of total organohalides is greater than that of the individual or subclasses of DBPs. ... /Disinfection by-products/ Non-Human Toxicity Values LD50 Rat oral 1737 mg/kg |
| References |
[1]. Shu-Ying Gao, et al. Dibromoacetic Acid Induces Thymocyte Apoptosis by Blocking Cell Cycle Progression, Increasing Intracellular Calcium, and the Fas/FasL Pathway in Vitro.Toxicol Pathol. 2016 Jan;44(1):88-97. [2]. National Toxicology Program. Toxicology and carcinogenesis studies of dibromoacetic acid (Cas No. 631-64-1) in F344/N rats and B6C3F1 mice (drinking water studies). Natl Toxicol Program Tech Rep Ser. 2007 Apr;(537):1-320. |
| Additional Infomation |
Dibromoacetic Acid can cause cancer according to The National Toxicology Program. Dibromoacetic acid is a monocarboxylic acid that is acetic acid in which two of the methyl hydrogens are replaced by bromo groups. It has a role as a marine metabolite, an apoptosis inducer and a geroprotector. It is a monocarboxylic acid and a 2-bromocarboxylic acid. It is functionally related to an acetic acid. Dibromoacetic acid has been reported in Asparagopsis taxiformis with data available. Mechanism of Action ... The ability of dibromoacetic acid (DBA) to cause DNA hypomethylation, glycogen accumulation, and peroxisome proliferation /was examined/ ... Female B6C3F1 mice and male Fischer 344 rats were administered 0, 1,000, and 2,000 mg/L DBA in drinking water. The animals were euthanized after 2, 4, 7, and 28 days of exposure. Dibromoacetic acid caused a dose-dependent and time-dependent decrease of 20% to 46% in the 5-methylcytosine content of DNA. Hypomethylation of the c-myc gene was observed in mice after 7 days of DBA exposure. Methylation of 24 CpG sites in the insulin-like growth factor 2 (IGF-II) gene was reduced from 80.2% +/- 9.2% to 18.8% +/- 12.9% by 2,000 mg/l DBA for 28 days. mRNA expression of the c-myc and IGF-II genes in mouse liver was increased by DBA. A dose-dependent increase in the mRNA expression of the c-myc gene was also observed in rats. In both mice and rats, DBA caused dose-dependent accumulation of glycogen and an increase of peroxisomal lauroyl-CoA oxidase activity. Hence, DBA, like dichloroacetic acid and trichloroacetic acid, induced hypomethylation of DNA and of the c-myc and IGF-II genes, increased mRNA expression of both genes, and caused peroxisome proliferation. Again like DCA, DBA also induced glycogen accumulation. These results indicate that DBA shares biochemical and molecular activities in common with dichloroacetic acid and/or trichloroacetic acid, suggesting that it might also be a liver carcinogen. Haloacetic acids (HAs) are embryotoxic contaminants commonly found in drinking water. The mechanism of HA embryotoxicity ... may be mediated in part by protein kinase C (PKC) inhibition. This study was conducted to evaluate the pathogenesis of HA embryotoxicity, and to compare these data with those from specific (Bis I) and non-specific (staurosporine) inhibitors of PKC. Embryos were incubated for varying times with several HAs, Bis I, staurosporine, or Bis V (a negative control). Cell cycle analysis was performed by flow cytometry following nuclear staining with propidium iodide; apoptosis was evaluated by fluorescence microscopy following LysoTracker staining. At concentrations producing 100% embryotoxicity with no embryolethality, only staurosporine perturbed the cell cycle. However, flow cytometry revealed accumulation of sub-G1 events (an apoptotic indicator) across time with bromochloroacetic acid, dichloroacetic acid, and staurosporine, but not dibromoacetic acid, Bis I, or Bis V. Sub-G1 events were particularly prominent in the head region, and remained at control levels in the heart. LysoTracker staining confirmed a similar pattern of apoptosis in the intact embryo; BCA and DCA produced intense staining in the prosencephalon, with virtually no staining in the heart. These data indicate that while cell-cycle perturbation may not mediate the pathogenesis of HA embryotoxicity, these agents do induce embryonic apoptosis. In addition, the lack of Bis I-induced apoptosis indicates that PKC inhibition is unlikely to be the sole mediator of HA embryotoxicity. The mechanisms associated with the carcinogenic effects of HAAs include those identified for DCA and TCA. It is apparent that more than one mechanism is responsible for the effects of this class and that the importance of these mechanisms to the activity of individual members of the class varies. In part, these differences in mechanism can be related to the differences in tumor phenotypes that are induced. One phenotype seems to be associated with prior characterizations of tumors induced by peroxisome proliferators and is induced by TCA. The second phenotype involves glycogen-poor tumors that stain heavily with antibodies to c-Jun and c-Fos. This phenotype is produced by DCA. These effects are probably produced by selection of lesions with differing defects in cell signalling pathways that control the processes of cell division and cell death. The brominated HAAs are about 10-fold more potent than their chlorinated analogues in their ability to induce point mutations. This does not establish that they are inducing cancer by mutagenic mechanisms in vivo, but this activity will have to be taken into account as data on their carcinogenic activity become more complete. The HAAs vary widely in their ability to induce oxidative stress and to elevate the 8-OH-dG content of nuclear DNA of the liver. This property becomes increasingly apparent with the brominated compounds. It is notable that the brominated analogues are not more potent inducers of hepatic tumors than the corresponding chlorinated HAAs. Therefore, it is doubtful that this mechanism is the most important determinant of this effect. |
Solubility Data
| Solubility (In Vitro) | DMSO : 100 mg/mL (459.05 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (11.48 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5905 mL | 22.9526 mL | 45.9053 mL | |
| 5 mM | 0.9181 mL | 4.5905 mL | 9.1811 mL | |
| 10 mM | 0.4591 mL | 2.2953 mL | 4.5905 mL |