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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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 36.8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
- Explanation for the modification of the dose descriptor starting point:
Substance is not classified for actute inhalative hazard thus no hazard conclusion needs to be drawn.
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.67 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Explanation for the modification of the dose descriptor starting point:
The dermal DNEL can be derived based on an oral NOAEL as starting point. As only an inhalation NOAEC is available as dose descriptor, this inhalation NOAEC has to be converted to a corrected "oral" NOAEL. In a first step, the total dose is calculated received by the test animals within the 6 hour exposure period using the standard rat respiratory volume. In a second step, the differences in exposure time and respiratory volume of workers are accounted for. As result, an "oral" NOAEL for workers is derived (267 mg/kg bw/day).
Using this starting point NOAEL, the dermal systemic DNEL is deduced. Factor for the transfer from the oral to dermal route is 1. With an overall assessment factor of 100 (allometric scaling factor 4, factor for remaining interspecies differences 2.5, intraspecies factor 5 (worker), sub-chronic to chronic exposure factor 2 ), a DNEL of 2.676 mg/kg bw/day for butyric acid is calculated.
Dermal systemic DNEL butyric acid: 2.67 mg/kg bw/day
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
Acute / short-term exposure - systemic effects
In acute toxicity studies, butyric acid has been shown to be of moderate to low systemic toxicity.
LD50 oral: 1632 mg/kg bw in rats (BASF, 1978)
LC0 inhalation, 4-h exposure: 5.1 mg/L (Celanese / Biodynamics, 1989); 8-h exposure: 4.18 mg/L (BASF, 1978)
LD50 dermal: 6096 mg/kg bw
From present studies, reliable short-term dose response relations cannot be deduced. Available data do not provide sufficient information on sublethal toxic effects to gather NOAELs as starting points. DNELs cannot be derived.
Acute /short-term exposure - local effects
Butyric acid is corrosive to skin and to the eye. Corrosive effects are observed after topical application of as little as 10 µL test substance (Smyth 1954). Weaker effects have not been examined. Dose descriptors for the deduction of a DNEL for acute local effects are not available.
Unlike these findings, inhalational exposure to saturated vapor concentrations was possible for 8 hours without mortality. But severe mucosal irritation and closed eyelids are reported as local effects. For inhalation exposure, severe effects are reported as are for dermal application, but this information is not suited as dose descriptors for the deduction of a DNEL.
Long term exposure systemic effects
Data for butyric acid on long term-exposure could not be identified. To assess the risk of long-term exposure - systemic effects for butyric acid, data for n-butyl acetate as supporting substance will be used as substitute on the following reasons.
After administration, n-butyl acetate will be rapidly metabolized in vivo in blood and various tissues by ubiquitous esterases. Half-life of this transformation is short resulting in complete cleavage of the ester. n-Butanol is formed which is rapidly metabolized in vivo to n-butyraldehyde by alcohol dehydrogenases and subsequently to n-butyric acid by aldehyde dehydrogenases. Thus, in the course of metabolic transformation of n-butyl acetate, butyric acid is generated rapidly and predominant as intermediary metabolite. Thus, it is justified to use n-butyl acetate as supporting substance in the evaluation of the systemic toxic effects of butyric acid.
Supporting substance: n-butyl acetate - Derivation of DNELs for butyric acid
There are several studies available where n-butyl acetate was administered using repeated doses.
In an inhalation subchronic repeated dose toxicity study (Bernard and Davis, 1996), test animals were exposed to n-butyl acetate for 6 h/d and 5 d/week over 91 days. The NOAEC determined was 500 ppm (2400 mg/m³).
In an inhalation 2-generation reproductive toxicity study (Nemec, 2007), F0 and F1 generation animals were exposed to n-butyl acetate for 6 h/d and 7 d/week over a period of 113 to 127 days and 134 to 154 days, respectively. The NOAEC for systemic toxicity was determined to be 750 ppm (3620 mg/m³).
In two inhalation developmental toxicity studies (Hackett et al, 1982 and Saillenfait et al, 2007), female test animals were exposed 7 h/d or 6 h/d for shorter time periods. The LOAEC for maternal and developmental toxicity in one study was 1500 ppm (7240 mg/m³) (Hackett et al). In the second study (Saillenfait et al), the NOAEC for maternal toxicity was 500 ppm (2400 mg/m³) and for developmental toxicity was 2000 ppm (9650 mg/m³).
In all studies available, exposure was by inhalation. Data/dose descriptors for other exposure routes are not available.
In the repeated dose toxicity study (Bernard and Davis, 1996), a NOAEC of 500 ppm was determined. The same concentration is the NOAEC maternal identified in the developmental toxicity study of Saillenfait. Being most conservative, this NOAEC will be used as dose descriptor in the derivation of DNELs.
Dermal systemic DNEL
Due to the lack of other data, the dermal DNEL will be obtained based on the inhalation NOAEC for n-butyl acetate of 500 ppm (Bernard and Davis, 1996; Repeated dose toxicity, Sect. 7.5.3 ). Using the molecular weight (butyric acid: 88.11) and the molar volume, the NOAEC for n-butyl acetate is converted to a NOAEC for butyric acid.
Inhalation systemic NOAEC for butyric acid: 1830 mg/m³
The dermal DNEL can be derived based on an oral NOAEL as starting point. As only an inhalation NOAEC is available as dose descriptor, this inhalation NOAEC has to be converted to a corrected "oral" NOAEL. In a first step, the total dose is calculated received by the test animals within the 6 hour exposure period using the standard rat respiratory volume. In a second step, the differences in exposure time and respiratory volume of workers are accounted for. As result, an "oral" NOAEL for workers is derived (267 mg/kg bw/day).
Using this starting point NOAEL, the dermal systemic DNEL is deduced. Factor for the transfer from the oral to dermal route is 1. With an overall assessment factor of 100 (allometric scaling factor 4, factor for remaining interspecies differences 2.5, intraspecies factor 5 (worker), sub-chronic to chronic exposure factor 2 ), a DNEL of 2.676 mg/kg bw/day for butyric acid is calculated.
Dermal systemic DNEL butyric acid: 2.67 mg/kg bw/day
Inhalation DNEL
The long-term inhalation NOAEC for butyric acid will be used to derive a systemic inhalation DNEL.
Inhalation systemic NOAEC for butyric acid: 1830 mg/m³(see above)
Exposure period in the study was 6 h per day. This NOAEC has to be modified with respect to exposure conditions of workers (exposure time 8 h/d, increased respiratory rate = wRV of 10 m³/8h) resulting in a corrected starting point NOAEC of 920 mg/m³. The overall assessment factor (25) consists of a factor for remaining interspecies differences of 2.5, an intraspecies factor of 5 (Workers) and a sub-chronic-to-chronic exposure factor of 2. The allometric scaling factor is already accounted for in the derivation of the corrected inhalation starting point NOAEC. With this overall assessment factor, a DNEL of 36.8 mg/m³ for butyric acid is calculated.
Inhalation systemic DNEL for butyric acid: 36.8 mg/m³
Long-term exposure - local effects
For butyric acid, no data on local effects resulting from long-term exposure are available. Long term exposure studies with butyric acid have not been conducted. Due to the severe corrosive reaction of butyric acid, effects similar to acute toxicity tests will occur. Dose descriptors for the derivation of DNELs are not available.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 9.15 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 50
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.66 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.66 mg/kg bw/day
DNEL related information
- Overall assessment factor (AF):
- 200
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - General Population
Acute / short-term exposure - systemic effects
In acute toxicity studies, butyric acid has been shown to be of moderate to low systemic toxicity.
LD50 oral: 1632 mg/kg bw in rats (BASF, 1978)
LC0 inhalation, 4-h exposure: 5.1 mg/L (Celanes / Bio/dynamics, 1989); 8-h exposure: 4.18 mg/L (BASF, 1978)
LD50 dermal: 6096 mg/kg bw
From present studies, reliable short-term dose response relations cannot be deduced. Available data do not provide sufficient information on sublethal toxic effects to gather NOAELs as starting points. DNELs cannot be derived.
Acute /short-term exposure - local effects
Butyric acid is corrosive to skin and to the eye. Corrosive effects are observed after topical application of as little as 10 µL test substance (Smyth 1954). Weaker effects have not been examined. Dose descriptors for the deduction of a DNEL for acute local effects are not available.
Unlike these findings, inhalational exposure to saturated vapor concentrations was possible for 8 hours without mortality. But severe mucosal irritation and closed eyelids are reported as local effects. For inhalation exposure, severe effects are reported as for dermal application, but this information is not suited as dose descriptors for the deduction of a DNEL.
Long term exposure systemic effects
Data for butyric acid on long term-exposure could not be identified. To assess the risk of long-term exposure - systemic effects for butyric acid, data for n-butyl acetate as supporting substance will be used as substitute on the following reasons.
After administration, n-butyl acetate will be rapidly metabolized in vivo in blood and various tissues by ubiquitous esterases. Half-life of this transformation is short resulting in complete cleavage of the ester. n-Butanol is formed which is rapidly metabolized in vivo to n-butyraldehyde by alcohol dehydrogenases and subsequently to n-butyric acid by aldehyde dehydrogenases. Thus, in the course of metabolic transformation of n-butyl acetate, butyric acid is generated rapidly and predominant as intermediary metabolite. Thus, it is justified to use n-butyl acetate as supporting substance in the evaluation of the systemic toxic effects of butyric acid.
Supporting substance: n-butyl acetate - Derivation of DNELs for butyric acid
There are several studies available where n-butyl acetate was administered using repeated doses.
In an inhalation subchronic repeated dose toxicity study (Bernard and Davis, 1996), test animals were exposed to n-butyl acetate for 6 h/d and 5 d/week over 91 days. The NOAEC determined was 500 ppm (2400 mg/m³).
In an inhalation 2-generation reproductive toxicity study (Nemec, 2007), F0 and F1 generation animals were exposed to n-butyl acetate for 6 h/d and 7 d/week over a period of 113 to 127 days and 134 to 154 days, respectively. The NOAEC for systemic toxicity was determined to be 750 ppm (3620 mg/m³).
In two inhalation developmental toxicity studies (Hackett et al, 1982 and Saillenfait et al, 2007), female test animals were exposed 7 h/d or 6 h/d for shorter time periods. The LOAEC for maternal and developmental toxicity in one study was 1500 ppm (7240 mg/m³) (Hackett et al). In the second study (Saillenfait et al), the NOAEC for maternal toxicity was 500 ppm (2400 mg/m³) and for developmental toxicity was 2000 ppm (9650 mg/m³).
In all studies, exposure was by inhalation. Data/dose descriptors for other exposure routes are not available.
In the repeated dose toxicity study (Bernard and Davis, 1996), a NOAEC of 500 ppm was determined. The same concentration is the NOAEC maternal identified in the developmental toxicity study of Saillenfait. Being most conservative, this NOAEC will be used as dose descriptor in the derivation of DNELs.
Dermal systemic DNEL
Due to the lack of other data, the dermal DNEL will be obtained based on the inhalation NOAEC for n-butyl acetate of 500 ppm (OPP/CMA, 1996; Repeated dose toxicity, Sect. 7.5.3 ). Using the molecular weight (butyric acid: 88.11) and the molar volume, the NOAEC for n-butyl acetate is converted to a NOAEC for butyric acid.
Inhalation systemic NOAEC for butyric acid: 1830 mg/m³
The dermal DNEL can be derived based on an oral NOAEL as starting point. As only an inhalation NOAEC is available as dose descriptor, this inhalation NOAEC has to be converted to an corrected "oral" NOAEL. In a first step, the total dose is calculated received by the test animals within the 6 hour exposure period using the standard rat respiratory volume. In a second step the difference in exposure time between test animals and general population are accounted for. As result, an "oral" NOAEL for the general population is derived (132.7 mg/kg bw/day).
Using this starting point NOAEL the dermal systemic DNEL is deduced. Factor for the transfer from the oral to dermal route is 1. With an overall assessment factor of 200 (allometric scaling factor 4, factor for remaining interspecies differences 2.5, intraspecies factor 10 (general population), sub-chronic to chronic exposure factor 2 ), a DNEL of 0.66 mg/kg bw/day for butyric acid is calculated.
Dermal systemic DNEL for butyric acid: 0.66 mg/kg bw/day
Inhalation DNEL
The long-term inhalation NOAEC for butyric acid will be used to derive a systemic inhalation DNEL.
Inhalation systemic NOAEC for butyric acid: 1830 mg/m³(see above)
Exposure period in the study was 6 h per day. This NOAEC has to be modified with respect to exposure conditions of the general population resulting in a corrected starting point NOAEC of 457,5 mg/m³. The overall assessment factor (50) consists of a factor for remaining interspecies differences of 2.5, an intraspecies factor of 10 (general publication) and a sub-chronic-to-chronic exposure factor of 2. The allometric scaling factor is already accounted for in the derivation of the corrected inhalation starting point NOAEC. With this overall assessment factor, a DNEL of 9.15 mg/m³ for butyric acid is calculated.
Inhalation systemic DNEL for butyric acid: 9.15 mg/m³
Oral systemic DNEL
An "oral" starting point was already calculated as basis for the deduction of the dermal systemic DNEL. To derive an oral systemic DNEL the same procedure is used. Dose descriptor is the inhalation systemic NOAEC.
Inhalation systemic NOAEC for butyric acid: 1830 mg/m³ (see above)
The corrected starting point is an "oral" NOAEL of 132.7 mg/m³ as above under Dermal systemic DNEL. With an overall assessment factor of 200 (allometric scaling factor 4, factor for remaining interspecies differences 2.5, intraspecies factor 10 (general population), sub-chronic to chronic exposure factor 2 ), a DNEL of 0.66 mg/kg bw/day for butyric acid is calculated.
Oral systemic DNEL for butyric acid: 0.66 mg/kg bw/day
Long-term exposure - local effects
For butyric acid, no data on local effects resulting from long-term exposure are available. Long term exposure studies with butyric acid have not been conducted. Due to the severe corrosive reaction of butyric acid, effects similar to acute toxicity tests will occur. Dose descriptors for the derivation of DNELs are not available.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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