Absorption, Distribution and Excretion
Bronopol was rapidly absorbed in animal studies. It may be absorbed via aerosol inhalation, dermal contact, and ingestion. In rats, approximately 40% of the topically applied dose of bronopol was absorbed through the skin within 24 hr. Following oral administration of 1 mg/kg in rats, the peak plasma concentrations of bronopol were reached up to 2 hours post-dosing.
Metabolism studies indicate that bronopol is primarily excreted in the urine. In rats, about 19% of dermally-applied bronopol was excreted in the urine, feces and expired air. Following oral administration of 1 mg/kg radiolabelled bronopol in rats, approximately 81% and 6% of the administered radioactivity was recovered in the urine and expired air, respectively, within a period of 24 hours. Following intravenous administration in rat, the recoveries in the urine and expired air were 74% and 9% of the dose, respectively.
The highest concentrations of bronopol were detected in the excretory organs of rat such as kidney, liver, and lung. The lowest concentration was in the fat.
No data available.
The rat metabolism data for bronopol consist of four separate studies conducted with male and female Sprague-Dawley rats. Animals were treated by gavage with (14)C bronopol (radiochemical purity: >95-100%). In the first study animals received a single dose of 10 mg/kg. The second study employed a higher dose of 50 mg/kg. Doses higher the 50 mg/kg caused respiratory problems and death. The third study's dose was 10 mg/kg (14 daily doses of nonradioactive, 100% pure, bronopol, followed by one dose of (14)C-bronopol). Urine, feces and CO2 were collected for 7 days after dosing, at which time the rats were killed and the tissues examined for radioactivity. Because, irrespective of the dose, most of the administered (14)C was excreted in urine (64-78% in 24 hours and 68-83% in 7 days), urine was used for the identification of metabolites in the fourth study. Feces, CO2 and tissues represented minor routes of excretion of (14)C. Very little (14)C was also detected in the whole blood and plasma. From the results of these four studies... /it was/ concluded that bronopol administered orally was rapidly absorbed and rapidly excreted by the rats of both sexes, with urine being the major route of excretion.
Oral doses are rapidly absorbed and rapidly excreted, mainly in the urine /in animals/.
The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.
Approximately 40% of the topically applied dose of antibacterial agent [(14)C] bronopol([(14)C]BP) was absorbed through the rat skin within 24 hr. Of the applied radioactivity, about 19% was excreted in the urine, feces and expired air. The 24 hr recoveries of (14)C in the urine and expired air were 15 and 2%, respectively, of the dose applied to the skin, and 74 and 9%, respectively, of the dose given intravenously.

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Metabolism / Metabolites
Bronopol undergoes degradation in aqueous medium to form bromonitroethanol from a retroaldol reaction with the liberation of an equimolar amount of formaldehyde. Formaldehyde is a degradation product of bronopol, which may cause sensitization. Bromonitroethanol further decomposes to formaldehyde and bromonitromethane. Bromonitroethanol may also break down to release a nitrite ion and 2-bromoethanol.
Approx. 40% of the topically applied dose of antibacterial agent [(14)C] bronopol([(14)C]BP) was absorbed through the rat skin within 24 hr. Of the applied radioactivity, about 19% was excreted in the urine, feces and expired air. The 24 hr recoveries of (14)C in the urine and expired air were 15 and 2%, respectively, of the dose applied to the skin, and 74 and 9%, respectively, of the dose given intravenously. The TLC of the urines showed three metabolites, but no unchanged [(14)C]BP in both groups. The results suggest that rat skin is quite permeable to bronopol.
Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo-2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol.
The major metabolite /in animals/ has been identified as 2-nitropropane-1,3-diol.
The only metabolite identified in urine was BTS 23 913 (2-nitropropane-1,3- diol or desbromo-bronopol), accounting for 45-50% of the radioactivity taken for analyses. The remaining radioactivity was not identified (one radioactive peak and radioactivity not resolved into peaks). Unchanged bronopol was not detected.
Nitrosamines can enter the body via ingestion, inhalation, or dermal contact. Once in the body, nitrosamines are metabolized by cytochrome P-450 enzymes, which essentially activates them into carcinogens. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase. Formaldehyde may be absorbed following inhalation, oral, or dermal exposure. It is an essential metabolic intermediate in all cells and is produced during the normal metabolism of serine, glycine, methionine, and choline and also by the demethylation of N-, S-, and O-methyl compounds. Exogenous formaldehyde is metabolized to formate by the enzyme formaldehyde dehydrogenase at the initial site of contact. After oxidation of formaldehyde to formate, the carbon atom is further oxidized to carbon dioxide or incorporated into purines, thymidine, and amino acids via tetrahydrofolatedependent one-carbon biosynthetic pathways. Formaldehyde is not stored in the body and is excreted in the urine (primarily as formic acid), incorporated into other cellular molecules, or exhaled as carbon dioxide. (A2878, A2879, L1892, L962)

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Biological Half-Life
The half-life of bronopol in the biological systems is not reported in the literature. The half-life value reported for bronopol reflects the environment fate of the compound. When released into the air as vapours, bronopol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals where the half life for this reaction is approximately 11 days. The photolysis half-life is 24 hours in water but may be up to 2 days under natural sunlight.

Toxicity Summary
While Bronopol is not in itself a nitrosating agent, under conditions where it decomposes (alkaline solution and/or elevated temperatures) it can liberate nitrite and low levels of formaldehyde. These decomposition products can react with any secondary amines or amides (which may contaminate cosmetic products) to produce significant levels of nitrosamines, which are believed to be carcinogenic. Once in the body, nitrosamines are activated by cytochrome P-450 enzymes. They are then believed to induce their carcinogenic effects by forming DNA adducts at the N- and O-atoms. Formaldehyde itself is also carcinogenic. It is likely that formaldehyde toxicity occurs when intracellular levels saturate formaldehyde dehydrogenase activity, allowing the unmetabolized intact molecule to exert its effects. Formaldehyde is known to form cross links between protein and DNA and undergo metabolic incorporation into macromolecules (DNA, RNA, and proteins). (L962, L643, L1889, A2878, A2879, A2880, A2881, L1893)

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Protein Binding
No data available.

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Toxicity Data
LD50: 250 mg/kg (Oral, Dog) (A547)

LD50: 64-160 mg/kg (Dermal, Rat) (A546)

LC50: >5 mg/L over 6 hours (Inhalation, Rat) (A547)

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Non-Human Toxicity Values
LD50 Mouse oral 350 mg/kg
LD50 Rat (female) oral 342 mg/kg
LD50 Rat (male) oral 307 mg/kg
LD50 Rat (male) dermal 64-160 mg/kg
For more Non-Human Toxicity Values (Complete) data for BRONOPOL (6 total), please visit the HSDB record page.

Pharmacodynamics
At concentrations of 12.5 to 50 μg/mL, bronopol mediated an inhibitory activity against various strains of Gram negative and positive bacteria _in vitro_. The bactericidal activity is reported to be greater against Gram-negative bacteria than against Gram-positive cocci. Bronopol was also demonstrated to be effective against various fungal species, but the inhibitory action is reported to be minimal compared to that of against bacterial species. The inhibitory activity of bronopol decreases with increasing pH of the media. Bronopol also elicits an anti-protozoal activity, as demonstrated with _Ichthyophthirius multifiliis_ _in vitro_ and _in vivo_. It is proposed that bronopol affects the survival of all free-living stages of _I. multifiliis_.

C3H6BRNO4

199.99

198.948

52-51-7

Bronopol-d4

2450

White crystalline powder
Crystals from ethyl acetate-chloroform

2.0±0.1 g/cm3

358.0±42.0 °C at 760 mmHg

130-133 °C(lit.)

170.3±27.9 °C

0.0±1.8 mmHg at 25°C

1.575

1.72

2

4

2

9

107

0

OCC([N+]([O-])=O)(Br)CO

LVDKZNITIUWNER-UHFFFAOYSA-N

InChI=1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2

2-bromo-2-nitropropane-1,3-diol

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)

H2O : ~100 mg/mL (~500.03 mM)
DMSO : ~100 mg/mL (~500.03 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.50 mM) (saturation unknown) 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.
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 3: ≥ 2.5 mg/mL (12.50 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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Solubility in Formulation 4: 50 mg/mL (250.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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