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EC number: 203-532-3 | CAS number: 107-92-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Information about ADME of butyric acid is present in several studies and a review.
Absorption, Distribution
Mahadevan (1969)
In fasted human subjects, the natural background levels of butyric acid in serum was 9.7 ± 5.5 µg/100mL and in plasma 25 ± 5 µg/100 mL (mean ± S.D., n= 6)
Daniel (1989)
Tissue distribution in mice after oral and ip administration
In a pharmacokinetic study, the distribution of butyric acid (butyrate) in plasma and tissue was examined after ip as well as oral administration. (1-14C) radiolabeled butyric acid was administered after neutralization as sodium salt in phosphate buffer at a single dose of 0.5 mL of a 50 mmol solution (2 µCi) to 4 male Swiss mice for each observation time point. Plasma, liver, kidney, brain, and muscles were harvested at four different time points (ip application 30 min to 24 hr, oral application 5 to 120 min). Tissue distribution was examined by scintillation counting of preprocessed tissue samples.
After oral and intraperitoneal (ip) administration, transport of butyric acid into the blood and into tissues was fast. Peak radioactivity levels in plasma and liver were observed after 5 to 30 min (oral) and after 30 and 60 min (ip). Levels decreased until the end of observation (24 hr). For other tissues (kidney, brain, muscle) after a first peak (30 to 60 min), a slight decrease of radioactivity was observed at 2 hr. At the end of observation (24 hr) radioactivity had increased again to values exceeding the levels at 60 min.
More than 40% of radioactivity was still present in blood and organs examined after 24 hr.
Plasma levels and elimination in mice after ip administration
In the same study, butyric acid (butyrate) plasma levels were examined after ip administration of salts of butyric acid (arginine and sodium butyrate) to male Swiss mice. Butyrate was administered as arginine butyrate at a single dose of 1 mL of an isotonic 5% solution (16.8 mg butyric acid, 672 mg/kg) or after neutralization of butyric acid as sodium salt in phosphate buffer at a single dose of 1 mL of a 370 mmol solution (32 mg butyric acid, 1280 mg/kg). Plasma was collected at 5, 10, 15, 30, 60, and 120 min. Butyric acid (butyrate) in plasma was analyzed by GLC.
After ip administration of arginine butyrate at 672 mg/kg bw, peak butyric acid (butyrate) concentrations in plasma (8 mmol/L) were reached within 5 min. Elimination was rapid. Between 5 and 15 min nearly 57% of butyric acid was eliminated from plasma. At 120 min, plasma butyric acid concentration had declined to ca. 0.1 mmol/L.
For sodium butyrate, similar results were observed.
Plasma levels and elimination in rabbits after iv administration
Butyric acid (butyrate) plasma levels were examined after iv administration of salts of butyric acid. Butyrate was administered as arginine butyrate and as sodium butyrate at a single dose of 1 mmol (88 mg butyric acid, 25 mg/kg) to common rabbits (average weight 3.5 kg). Plasma was collected at 2, 5, 10, 15, 20, and 25 min. Butyric acid (butyrate) in plasma was analyzed by GLC.
After iv administration of arginine butyrate at 25 mg/kg bw, a peak mean concentration of butyric acid (butyrate) in plasma was reached within 2 min (0.49 mmol/L). Elimination was rapid with a half-life of approx. 4.5 min. At 25 min, plasma butyric acid (butyrate) concentration had declined to ca 0.001 mmoL/L.
For sodium butyrate, similar results were observed.
Steady state plasma levels and elimination in humans, iv infusion
A steady state level of butyrate in serum was only reached by infusion of a 5% isotonic solution of arginine butyrate at a rate of 112 mL/h over 90 min resulting in a total dose of 8.4 g (32 mmol). Steady state plasma concentration was 146 ± 10 µmol/L.
After termination of infusion, elimination of butyric acid (butyrate) from blood was very rapid during the first minutes with a half-life of 30 sec. Subsequently elimination rate slowed down to a half-life of 13 min 42 sec.
Metabolism / Excretion
Medes (1945)
In an in vitro experiment, 13C enriched butyric acid (C-1 position) was incubated with slices of rat liver from fasted rats for two hours at pH 7.3 and 37.5°C. Acetoacetic acid and hydroxybutyric acid were separated from the incubation mixture and analyzed after transformation to CO2 for the amount and distribution of 13C using mass spectroscopy.
By evaluating the relative amount and distribution of 13C, two mechanisms for the formation of ketone bodies from butyric acid could be established (cleavage by ß-oxidation and recombination to ketone body and direct ß-oxidation and formation of ketone body with conservation of the C4 structure).
In two experiments, butyric acid was utilized to 51 and 32% respectively. Respiratory CO2 amounted to 13.5 and 12.3%. Acetoacetic acid (35.7 and 45.8%) and ß-hydroxybutyric acid (11.7 and 9.3%) were demonstrated to be metabolites of butyric acid. Other metabolites (volatile and non volatile) of unknown structure were also isolated.
Von Oettingen (1969, review)
After oral administration to rats, considerable amounts of butyric acid are metabolized to acetic acid (Bloch 1944). Metabolism proceeds rapidly as indicated by experiments of Rittenberg et al (1937). Metabolic transformations take place in the liver as indicated by perfusion experiments (Embden, 1906, 1908) and by experiments with liver slices and liver juice (Leloir, 1939). Similar oxidative processes may also occur in the kidney (Ciaranfi, 1938; Kleinzeller, 1943).
In addition after subcutaneous injection of butyric acid into dogs, ß-hydroxybutyric acid, acetoacetic acid, and acetone were excreted (Blum, 1919), ß-hydroxybutyric acid presumably formed secondarily from acetoacetic acid. The formation of ketone bodies following administration of butyric acid is confirmed by investigations of Marx and Ehrmann. Marx (1910) found that oral administration of butyric acid to fasted dogs resulted occasionally and intraperitoneal injection regularly in the excretion of acetoacetic acid. Ehrmann (1913) found acetoacetic acid and aceton in the urine of rabbits after oral administration of butyric acid.
Conclusion
Butyric acid is a naturally present component in human blood. In fasted humans (6 subjects) an average serum concentration of 9.7 µg/100 mL (plasma 25 µg/100 mL) was detected (Mahadevan, 1969).
Butyric acid and its salts are rapidly absorbed and transported into blood and various organs of the body after administration by different routes. Peak plasma levels are reached within several minutes. After oral and ip administration of radiolabeled butyric acid (C-1 14C) considerable amounts of radioactivity were still present in blood, liver, kidney, brain, and muscle 24 hours after administration (40% and more) (Daniel, 1989).
Elimination of butyric acid from blood is rapid (half live in mice and rabbits ca 5 to 15 min). In man after termination of a 90 min iv infusion (steady state plasma concentration 146 µmol/100 mL), elimination of butyric acid from blood was very fast at the beginning (half-life 30 sec) and subsequently slowed down to a half life of 13 min 42 sec (Daniel, 1989).
Butyric acid is metabolized by ß-oxidation resulting in either acetic acid or ketone bodies (acetoacetic acid, ß-hydroxybutyric acid) as metabolites (von Oettingen, 1969; Mendes, 1945). It follows the pathway of fatty acid metabolism. Via metabolic intermediates, it can enter other intermediary metabolic pathways (e.g. citric acid cycle). Thus the continuing presence of radioactivity in blood and tissues can be explained by formation of intermediary transformation products.
Butyric acid has no potential for bioaccumulation.
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