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].

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 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.

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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/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.

Absorption, Distribution and Excretion
In the preliminary reproductive/developmental toxicity studies (rats), dibromoacetic acid (DBA) was added to drinking water. The studies included the absorption and biodistribution of DBA, including its entry into the placenta, amniotic fluid, fetus, or breast milk. Each group in the preliminary reproductive/developmental toxicity studies of DBA consisted of 50 Sprague-Dawley rats (per sex per group). DBA (0, 125, 250, 500, or 1000 ppm) was added to drinking water from 14 days prior to mating until gestation and lactation (63 to 70 days). …Satellite groups (6 male rats and 17 female rats per group per study)…were used for bioanalytical sampling. Rats…drank less water due to a marked taste aversion to DBA, especially in parent animals at the two highest exposure levels (500 and 1000 ppm DBA). DBA intake (mg/kg/day) was slightly higher in female rats than in male rats, especially during pregnancy and lactation; the highest intake (mg/kg/day) was observed in weaned rats. DBA reached detectable and quantifiable concentrations in plasma, placenta, amniotic fluid, and milk. Plasma samples confirmed that rats primarily drank water in the dark; this drinking pattern, rather than accumulation, resulted in sustained DBA concentrations in plasma for 18 to 24 hours…
DBA concentrations were determined in the testicular interstitial fluid of male Sprague-Dawley rats that received 250 mg/kg body weight of DBA via gavage for five consecutive days. Body weight… The concentration of dibromoacetic acid in the testicular fluid peaked at 79 μg/mL (approximately 370 μM) 30 minutes after the last administration, with a half-life of approximately 1.5 hours.
Dibromoacetic acid (DIA) was added to the drinking water of Sprague-Dawley rats at concentrations ranging from 125 to 1000 ppm (mg/L), starting 14 days before cohabitation and continuing into pregnancy and lactation… Quantifiable amounts of DIA were detected in parental and fetal plasma, placental tissue, amniotic fluid, and breast milk. Therefore, DIA can cross the placenta and be absorbed by fetal tissues.
The oral bioavailability of DIA in male F344/N rats has been reported to be 30%… Compared to dichloroacetic acid, the lower bioavailability of DIA is due to its… first-pass metabolism in the liver.
Biological half-life

The DIA content in the testicular interstitial fluid of male Sprague-Dawley rats administered 250 mg/kg body weight of DIA by gavage for five consecutive days was measured… The half-life was approximately 1.5 hours.

Interactions
Studies have found that the disinfection byproduct dibromoacetic acid (DBA) increases the concentrations of circulating estradiol (E2) and estrone (E1) in female rats. This effect is clearly at least partly due to the inhibition of hepatic catabolism. This study aimed to investigate whether DBA could enhance hypothalamic upregulation to trigger a luteinizing hormone (LH) surge by increasing sex hormone levels, or affect the ability of the neurotoxin sodium dimethyl dithiocarbamate (DMDC) to block LH surges. Sprague-Dawley rats were administered DBA (0–150 mg/kg) by gavage for 14 consecutive days, and ovariectomy was performed on day 11, with estradiol capsules implanted to induce daily LH surges. 0.1 mM/kg DMDC was injected at 13:00 on day 14, and blood samples were collected that afternoon. DBA induced a dose-dependent increase in total estrogen levels. For the identified LH peak, the area under the LH curve was divided into two groups, corresponding to two low-dose groups (0 and 37.5 mg/kg DBA) and two high-dose groups (75 and 150 mg/kg DBA). Therefore, comparisons were made between the low-dose and high-dose groups, revealing significant differences between them. In the 150 mg DBA/0.1 mM DMDC group, the time to identifiable LH peak was comparable to that of female mice not treated with DMDC, while the time to peak was delayed in the 37.5 mg DBA/0.1 mM DMDC group. No significant effect was observed with DBA treatment alone. These results indicate that exposure to DBA leads to a dose-dependent increase in total estrogen concentration, while the blocking effect of DMDC on the LH peak is weakened. This effect appears to be attributed to enhanced upregulation of estrogen-related brain mechanisms, thereby stimulating LH peak production. Chlorination of drinking water produces disinfection byproducts (DBPs), and studies have shown that high doses of DBPs disrupt spermatogenesis in rodents, suggesting that DBPs may pose a risk to male reproduction. ...A cohort study aimed to assess semen quality in men with defined DBP exposure. ...The results of this study do not support an association between DBP exposure levels near regulatory limits and poor sperm outcomes, although an association was found between total organohalides and sperm concentration. ...The only association between total organohalides exposure and sperm concentration may support the following findings: total organohalides are more likely to cause poor pregnancy outcomes than any regulated disinfection byproduct (DBP) class or type, and the toxicity of total organohalides is greater than that of individual or subclasses of disinfection byproducts. .../Disinfection Byproducts/

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Non-human Toxicity Values
Oral LD50 in rats: 1737 mg/kg

[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.

According to data from the National Toxicology Program (NTP), dibromoacetic acid (DBA) may be carcinogenic. DBA is a monocarboxylic acid formed when two methyl hydrogen atoms in the acetic acid molecule are replaced by bromine atoms. It is a marine metabolite that induces apoptosis and delays aging. It is a monocarboxylic acid and also a 2-bromocarboxylic acid. Its function is related to acetic acid. DBA has been reported in Asparagopsis taxiformis, and relevant data are available. Mechanism of Action…The ability of dibromoacetic acid (DBA) to induce DNA hypomethylation, glycogen accumulation, and peroxisome proliferation was investigated… Female B6C3F1 mice and male Fischer 344 rats were given DBA solutions at concentrations of 0, 1000, and 2000 mg/L, respectively. Animals were euthanized after 2, 4, 7, and 28 days of exposure. DBA resulted in a dose- and time-dependent decrease in the content of 5-methylcytosine in DNA of 20% to 46%. Hypomethylation of the c-myc gene was observed in mice after 7 days of exposure to dibromoacetic acid (DBA). The methylation level of 24 CpG sites in the insulin-like growth factor 2 (IGF-II) gene decreased from 80.2% ± 9.2% to 18.8% ± 12.9% after 28 days of treatment with 2000 mg/L DBA. Dibromoacetic acid increased the mRNA expression of both c-myc and IGF-II genes in mouse liver. A dose-dependent increase in c-myc mRNA expression was also observed in rats. In both mice and rats, DBA induced dose-dependent glycogen accumulation and increased peroxisome lauroyl-CoA oxidase activity. Therefore, similar to dichloroacetic acid and trichloroacetic acid, DBA induces hypomethylation of DNA and both c-myc and IGF-II genes, increases the mRNA expression of these two genes, and leads to peroxisome proliferation. Similarly, DBA also induces glycogen accumulation. These results indicate that DBA shares common biochemical and molecular activities with dichloroacetic acid and/or trichloroacetic acid, suggesting that it may also be a hepatotoxic carcinogen. Haloacetic acids (HA) are common embryotoxic contaminants in drinking water. The embryotoxic mechanism of HA may be partly mediated by inhibition of protein kinase C (PKC). This study aimed to evaluate the pathogenesis of hyaluronic acid (HA) embryotoxicity and compare these data with those of specific (Bis I) and non-specific (astrosporin) protein kinase C (PKC) inhibitors. Embryos were incubated with various HA, Bis I, asteroidin, or Bis V (negative control) for different durations. Cell cycle analysis was performed by flow cytometry after propidium iodide (PI) staining; apoptosis was assessed by fluorescence microscopy after LysoTracker staining. At concentrations producing 100% embryotoxicity but not lethality, only asteroidin disrupted the cell cycle. However, flow cytometry analysis showed that sub-G1 phase events (an apoptosis marker) accumulated over time after treatment with bromochloroacetic acid, dichloroacetic acid, and astrococcus, while this phenomenon was not observed after treatment with dibromoacetic acid, Bis I, or Bis V. Sub-G1 phase events were particularly pronounced in the head region, while in the heart they remained at control levels. Lysosomal tracer staining confirmed a similar apoptotic pattern in intact embryos; BCA and DCA produced strong staining in the forebrain, but almost no staining in the heart. These data suggest that while cell cycle dysregulation may not be the pathogenic mechanism of HA embryotoxicity, these drugs do induce embryonic cell apoptosis. Furthermore, the lack of apoptosis induced by Bis I suggests that PKC inhibition is unlikely to be the sole mediator of HA embryotoxicity. The relevant mechanisms of HA carcinogenicity include the oncogenic mechanisms of DCA and TCA. Clearly, there is more than one mechanism leading to the effects of these compounds, and these mechanisms vary in importance to the activity of different members of this class of compounds. Some of these mechanistic differences may be related to differences in the induced tumor phenotypes. One phenotype appears to be associated with previous characterizations of peroxisome proliferator-induced tumors and is induced by trichloroacetic acid (TCA). A second phenotype involves tumors with low glycogen content that show strong staining responses to c-Jun and c-Fos antibodies. This phenotype is produced by dichloroacetic acid (DCA). These effects may be due to the selective induction of lesions with different defects in cell signaling pathways that control cell division and cell death. Brominated heterocyclic amines (HAAs) are about 10 times more likely to induce point mutations than their chlorinated analogs. This does not necessarily demonstrate that they induce cancer in vivo through mutagenic mechanisms, but such activity must be considered as data on their carcinogenic activity become more comprehensive. Heterocyclic amines vary considerably in their ability to induce oxidative stress and increase the content of 8-hydroxydeoxyguanosine (8-OH-dG) in liver nuclear DNA. This characteristic is particularly pronounced in brominated compounds. Notably, brominated analogs are not more likely to induce liver tumors than their corresponding chlorinated heterocyclic amines. Therefore, it remains questionable whether this mechanism is the most important factor determining this effect.

C2H2BR2O2

217.84

215.842

631-64-1

12433

Hygroscopic crystals

2.382 g/mL at 25ºC(lit.)

128-130ºC16 mm Hg(lit.)

32-38ºC(lit.)

>230 °F

1.598

1.186

1

2

1

6

60.6

0

C(C(=O)O)(Br)Br

SIEILFNCEFEENQ-UHFFFAOYSA-N

InChI=1S/C2H2Br2O2/c3-1(4)2(5)6/h1H,(H,5,6)

2,2-dibromoacetic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL (459.05 mM)

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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)