Absorption, Distribution and Excretion
Following a single oral administration of 20 mg/kg (in the form of 14C-bromodichloromethane) to rats, the compound was rapidly eliminated. Only 32% was recovered from the gastrointestinal tract and cadaver after 3 hours, and 41% after 6 hours. Most of the compound was recovered from the stomach, with higher concentrations in adipose tissue than in any other tissue. Less than 1% was found in urine, with the remainder likely exhaled. This study investigated the physiological distribution, metabolism, storage, and elimination rates of bromodichloromethane in rat adipose tissue and serum using a 31-day rat dosing regimen. For volatile compounds, tissue concentrations fluctuated, but no increase in storage over time was observed. The concentration difference between adipose tissue and serum never exceeded 3-fold. Within 3–6 days after the end of administration, most of the halogenated compound was eliminated from the tissues examined. Bromodichloromethane is rapidly absorbed via inhalation or ingestion, widely distributed, preferentially distributed in tissues with high lipid content, and partially exhaled. This study investigated the pharmacokinetics and tissue distribution of bromodichloromethane in rats and monkeys. This compound is primarily excreted via the lungs, either unchanged or as a metabolite. For more complete data on the absorption, distribution, and excretion of bromodichloromethane (13 compounds in total), please visit the HSDB records page.

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Metabolism / Metabolites
Studies have shown that administration of haloacetates to rodents increases the production of thiobarbituric acid reactants and 8-hydroxydeoxyguanosine in the liver. These reactions appear to be affected by pretreatment. To investigate the potential mechanisms leading to alterations in oxidative stress, this study examined the effects of trichloroacetic acid (TCA) or dichloroacetic acid (DCA) pretreatment on bromodichloroacetic acid (BDCA) metabolism and the distribution of its metabolites in male B6C3F1 mice. Two-week pretreatment with 1 g/L DCA and TCA in the mouse drinking water altered the initial hepatic metabolism of BDCA and the further metabolism of its metabolite, DCA. DCA pretreatment inhibited the metabolism of 1 mM DCA or BDCA in the cytoplasm by up to 70%. Conversely, DCA pretreatment increased BDCA metabolism in hepatic microsomes by 1.3-fold, but had little effect on the metabolism of DCA in microsomes. This enhanced BDCA microsomal metabolism appears to be attributed to the induction of a metabolic pathway that produces CO2 and bromodichloromethane (BDCM) as metabolites. TCA pretreatment inhibited up to 70% of BDCA metabolism in the cytosol and up to 30% in the microsomes, but had little effect on DCA metabolism. These results indicate that hepatic metabolism of haloacetic acids becomes quite complex at high doses used in cancer bioassays. BDCA is a prime example, as it is metabolized into at least two carcinogenic metabolites with different mechanisms of action: BDCM and DCA. The proportions and amounts of these metabolites (as a percentage of the administered dose) change significantly when the dose approaches the carcinogenic dose in mice. This study demonstrates that co-treatment with haloacetic acids also leads to these interactions. The drinking water disinfection byproduct bromodichloromethane (CHBrCl₂) has previously been shown to be mutagenic to Salmonella typhimurium overexpressing rat glutathione transferase θ1-1 (GSTT1-1). This study used multiple experimental methods to explore the covalent binding potential of the active intermediates generated by GSTT1-1-mediated CHBrCl₂ metabolism to DNA. First, rodent hepatocytes containing ¹⁴CHBrCl₂, supplemented with glutathione (GSH), and calf thymus DNA were incubated. The results showed that the total radioactivity (RAD) of the purified DNA increased approximately 3-fold (rat hepatocytes) and 7-fold (mouse hepatocytes) compared to the control group (without rodent cytoplasm). This result was obtained by liquid scintillation counting (LSC) of the isolated DNA. The relative increase in DNA labeling was consistent with the binding activity of these rodent cytosols to CHBrCl₂. Second, exposure of Salmonella Typhimurium expressing GSTT1-1 to (14)CHBrCl₂ resulted in a concentration-dependent increase in the total radioactivity of the bacterial DNA binding. DNA digestion and subsequent HPLC analysis failed to attribute the DNA binding radioactivity to specific deoxynucleoside adducts. One possible explanation for this is the formation of unstable transient adducts during the DNA separation and hydrolysis processes employed. To overcome the instability of the adduct, the reaction of recombinant rat GSTT1-1-catalyzed (14)CHBrCl₂ with GSH was conducted in the presence of calf thymus DNA or the model nucleophile deoxyguanosine. Hydroxyapatite chromatography was used to analyze the 14C-labeled DNA, and high-performance liquid chromatography was used to analyze the 14C-labeled deoxyguanosine derivative. The results showed that the covalent binding yield of the 14CHBrCl₂-derived metabolite to DNA and deoxyguanosine was low (approximately 0.02% of the 14CHBrCl₂ biotransformed by GSTT1-1 generated DNA adducts). The biotransformation of CHBrCl₂ catalyzed by cytochrome P450 (CYP) and glutathione S-transferase (GST) in rat tissues (kidney and large intestine) that developed tumors after long-term exposure to CHBrCl₂ was compared with that in rat liver (non-target tissue). Compared to the kidney and large intestine, the rat liver exhibited significantly greater CHBrCl₂ detoxification capacity (converting it to carbon dioxide), primarily attributed to CYP-catalyzed oxidation. When comparing intrinsic clearance rates (Vmax/Km), the liver's detoxification efficiency was approximately 16 times that of the kidney and large intestine. Conversely, the GST-mediated binding efficiency of CHBrCl₂ to GSH in the kidney and large intestine was only slightly lower than in the liver (approximately 2 to 4 times lower). Therefore, the relative abundance of reactive intermediates capable of covalently modifying DNA may be increased in these extrahepatic tissues. The significance of these findings lies in the fact that the binding of CHBrCl₂ to GSH can lead to covalent modification of DNA, and that the detoxification capacity of rat tumor target tissues is significantly reduced compared to the liver (a non-target tissue in rats), but the bioactivation capacity is only slightly decreased. Halogens are metabolized to carbon monoxide by hepatic mixed-function oxidases, a reaction significantly stimulated by thiol compounds. The stimulatory effect is strongest at a glutathione concentration of 0.5 mmol/L. This paper proposes a mechanism for the conversion of haloforms to carbon monoxide. /Haloforms/ Trihalomethanes (halogens) are metabolized to carbon monoxide in rat liver microsomal fractions, a process requiring NADPH and molecular oxygen to reach maximum activity. The results indicate that haloforms are metabolized to carbon monoxide via a cytochrome P450-dependent mixed-function oxidase system. /Trihalomethanes/ For more metabolic/metabolite (complete) data on dichlorobromobromomethane (9 metabolites), please visit the HSDB record page.

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Biological Half-Life
In rats, the drug was rapidly eliminated after a single oral dose of 20 mg/kg (in the form of 14C-bromodichloromethane). In monkeys, a similar dose resulted in a half-life of 4 to 6 hours.

Interactions
This study evaluated the effects of glutathione (GSH) on in vivo toxicity of dichlorobromomethyl (BDCM) and on in vitro macromolecular binding of BDCM. The study investigated the toxicity of BDCM in animals pretreated with butyrate sulfoxide imine (BSO, a glutathione synthesis inhibitor) and untreated male Fischer 344 rats. In another experiment, (14C)BDCM was incubated with liver microsomes and S9 fractions, as well as kidney microsomes, from F344 rats under aerobic and anaerobic conditions, with and without GSH, and the covalent binding of BDCM to proteins and lipids was quantitatively analyzed. Following oral administration of BDCM, compared with animals administered BDCM alone, animals pretreated with BSO showed significantly elevated levels of serum hepatotoxicity markers and serum and urinary nephrotoxicity markers. Histopathological examination revealed more severe liver necrosis than kidney necrosis in BSO-treated rats. Adding GSH under aerobic culture conditions reduced protein binding rates in liver microsomes and the S9 fraction by 92% and 83%, respectively. In anaerobic liver microsome culture, GSH also reduced lipid binding rates by 55%. Adding GSH reduced protein (aerobic) and lipid (anaerobic) binding rates in kidney microsomes by 20% and 43%, respectively. These data indicate that GSH is an important protective factor against BDCM-related toxicity. This study determined the acute hepatotoxicity and nephrotoxicity of two trihalomethane water pollutants—bromodichloromethane (BrCHCl2) and dibromochloromethane (Br2CHCl)—in male Sprague-Dawley rats. Br₂CHCl showed higher hepatotoxicity and lethality than BrCHCl₂. However, compared to the associated trihalomethane CHCl₃, both Br₂CHCl and BrCHCl₂ showed weaker hepatotoxicity. Br₂CHCl and BrCHCl₂ only caused liver injury at near-lethal doses. Neither of the two trihalomethanes induced significant kidney damage during the 24-hour challenge period. Pretreatment of rats with acetone (15 mmol/kg, orally) significantly enhanced the hepatotoxicity of BrCHCl₂ and Br₂CHCl. The enhancement observed with acetone in combination with BrCHCl₂ or Br₂CHCl was equal to or greater than that observed with acetone in combination with an equimolar dose of CHCl₃. In other words, acetone appears to convert these weak hepatotoxic substances into strong hepatotoxic substances. This study used a rodent model of hereditary renal cancer to investigate the carcinogenicity of a mixture of drinking water disinfection byproducts (DBPs). Rats carrying the Tsc2 tumor suppressor gene mutation (Eker rats) are prone to renal precancerous lesions and tumors and are highly sensitive to renal carcinogens. Male and female Eker rats were exposed to single or mixed DBPs via drinking water for 4 or 10 months, respectively. Potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, and dichlorobromomethane were prepared at low concentrations of 0.02, 0.005, 0.4, and 0.07 g/L, respectively, and at high concentrations of 0.4, 0.07, 1.8, and 0.7 g/L, respectively. Low-dose and high-dose mixtures were prepared from the four chemicals at low and high concentrations, respectively. Following necropsy, each kidney was examined microscopically for precancerous lesions (atypical tubules and hyperplasia) and tumors. While some mixture responses observed in male rats were indeed within the expected additive response range, particularly at high doses, the low-dose mixture primarily showed antagonistic effects on kidney lesions in male rats, while the high-dose mixture primarily showed antagonistic effects in female rats. These data suggest that the current default risk assessment, assuming an additive effect, may overestimate the cancer risk associated with exposure to low-concentration disinfection byproduct mixtures. Pretreatment of Fischer 344 rats with butyrate sulfoxide reduced liver glutathione levels by 86%, significantly exacerbating the hepatotoxicity and nephrotoxicity associated with a single oral administration of dichlorobromodimethylformamide (400 mg/kg body weight). For more complete data on the interactions of dichlorobromodimethylformamide (a total of 6 types), please visit the HSDB record page.

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Non-Human Toxicity Values
The oral LD50 for adult female and male Swiss ICR mice was 900 mg/kg (range: 811-999) and 450 mg/kg (range: 326-621), respectively. The oral LD50 for female rats was 969 mg/kg. The oral LD50 for male rats was 916 mg/kg. The oral LD50 for rats was 1388 mg/kg. For more complete non-human toxicity data on bromodichloromethane (6 types), please visit the HSDB record page.

[1]. Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: contrasting results with bromodichloromethane off chloroform. Toxicol Appl Pharmacol. 1997 May;144(1):183-8.

[2]. Bromodichloromethane inhibits human placental trophoblast differentiation. Toxicol Sci. 2004 Mar;78(1):166-74.

Bromodichloromethane is a colorless, non-flammable liquid. Small amounts of bromodichloromethane are naturally produced by algae in the ocean. Some bromodichloromethane is soluble in water but highly volatile into the air. The United States produces only small amounts of bromodichloromethane, primarily for laboratory or other chemical production. However, most bromodichloromethane is a byproduct of chlorination in drinking water. According to the U.S. Environmental Protection Agency (EPA), bromodichloromethane may be carcinogenic. Bromodichloromethane is a transparent, colorless liquid (NTP, 1992). Bromodichloromethane is a halomethane, where one hydrogen atom in the dichloromethane molecule is replaced by a bromine atom. It is a drinking water contaminant, used as a reagent, and also an environmental pollutant. Bromodichloromethane has been reported in Ascophyllum nodosum, Mastocarpus stellatus, and other organisms with available data. Bromodichloromethane is a colorless, liquid haloalkanes. It is used in chemical synthesis and as a reagent in laboratory research. It is also a byproduct of water chlorination. Bromodichloromethane is reasonably expected to be a human carcinogen. (NCI05) The reference number (RN) given here refers to the parent compound.

CHBRCL2

163.83

161.864

75-27-4

6359

Typically exists as solids at room temperature

-67 °F (NTP, 1992) ; -57 °C ; -57 °C ; -57.1 °C

0

0

4

13.5

0

C(Cl)(Cl)Br

FMWLUWPQPKEARP-UHFFFAOYSA-N

InChI=1S/CHBrCl2/c2-1(3)4/h1H

bromo(dichloro)methane

dichlorobromomethane

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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