Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-699-2 | CAS number: 109-73-9
- 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:
- 6.1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: adoption of workplace limit value
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.2 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: adoption of workplace limit value
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 6.1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: adaption of workplace limit value
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.2 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: adaption of workplace limit value
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic 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:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
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:
- medium hazard (no threshold derived)
Additional information - workers
Summary
Toxicological key items
n-Butylamine is assumed to be readily bioavailable by all potential routes of exposure. Exposure may mainly occur by inhalation and by skin contact. The substance is readily metabolised by sharing common metabolic pathways or excreted from the body in unchanged form, thus not accumulating.
The primary and most relevant effect is its irritating/corrosive effect on skin and mucous membranes. This severe local insult limits exposure to doses that potentially may induce systemic lesions: There were developmental effects following oral administration of the hydrochloride salt of n-butylamine to rats at an effective dose (LOAEC) of 400 mg/(kg bw*d), which is equivalent to about 265 mg base/(kg bw*d)]. The dose that was orally effective could not be achieved by inhalation ([see IUCLID 7.8.2, Gamer et al. 2002). It is evident that the prevention of local lesions will also be protective from systemic effects.
DNEL estimation
In a subacute inhalation toxicity study in rats no systemic toxic effects have been observed up to the highest concentration tested (150 ppm; 460 mg/m3). However, local effects were already observed at the lowest test concentration of 17 ppm (51 mg/m3) indicating that local irritancy is the most relevant effect for n-butylamine after inhalation exposure. Based on the local effects in this subacute inhalation study a theoretical DNEL of 0.3 mg/m3would result after application of the default procedure according to Guidance R.8 (analytical LOAEC of 51 mg/m3* 1/(2.5 (inter) x 5 (intra) x 3 (LOAEC/NOAEC) x 6 (time) = 0.2 mg/m3). An about 10-15 fold higher value of 3 mg/m3would result if the – probably more appropriate - procedure recommended by Bruening et al. (2014, Arch. Toxicol. 88:1855ff) for sensory irritants would be applied (transformation of rat LOAEC for respiratory sensitisation to a human NOAEC and adjustment for time; for justification see also MAK-value documentation). The limit value derived by application of the methodology suggested by Bruening et al. is in the same order of magnitude as the MAK value of 2 ppm (6.1 mg/m3). A MAK value of 2 ppm is supported by observations from the workplace: Daily exposure of workers with n-butylamine concentrations in the range of 5-10 ppm resulted in irritations of the nose, throat, and eyes and caused headaches. No complaints were reported if the workplace exposure was below 5 ppm (with actual exposures usually in the range between 1 and 2 ppm; Beard and Noe, 1981). The MAK value of 2 ppm for n-butylamine is further supported by experimental data for the structural similar substance cyclohexylamine for which no sensory irritation could be detected in investigations with volunteers who were exposed to 2 ppm and peak concentrations of 4 ppm. Cyclohexylamine is probably a more potent sensory irritant (RD50 in mice of 51 ppm) than n-butylamine (RD50 in mice of 84-112 ppm).
On basis of the NOAEC for systemic toxic effects observed in the developmental toxicity study (460 mg/m3; no systemic toxic effects observed up to the highest dose tested) and applying the default assumptions of the Guidance Chapter R.8. a theoretical DNEL of 4.3 mg/m3would result (460 mg/m3 *6h/8h *7/5 *6.7m3/10m3* 1/(2.5 (inter) x 5 (intra) x 6 (time)) = 4.3 mg/m3), which is numerically very close to the MAK value and supports the derived DNEL.
In the USA, no Time Weighted Averages (TWA) for the workplace were provided for n-butylamine. The respective ceiling values for the OSHA PEL, NIOSH REL, ACGIH TLV and Cal OSHA PEL are 5 ppm (15 mg/m3). The German MAK value was revised in 2006 and reduced from 5 to 2 mL/m3(6.1 mg/m3) [DFG 2007].
In synopsis of all available data, it is proposed to adopt the latest MAK value of 2 ppm (6.1 mg/m3) as a DNEL for repeated and prolonged inhalation, while for short-term exposure a DNEL of 4 mL/m3(12.2 mg/m3) (representing the short term MAK) is considered to be sufficiently protective. The concentration of 5 mL/m3should not be exceeded at any time. This value would be protective for systemic as well as for local effects of n-Butylamine.
__________________________________
Reference:
OSHA/ACGIH/NIOSH/Cal OSHA USA, see e.g.: https://www.osha.gov/chemicaldata/chemResult.html?recNo=99 (accessed 25 June 2018)
MAK-Kommission 2007:Toxikologisch-arbeitsmedizinische Begründung von MAK-Werten: n-Butylamin, sec-Butylamin, iso-Butylamin.
DFG (Deutsche Forschungsgemeinschaft); Wiley-VCH Verlag 2007
__________________________________
Overview of effects data following exposure to n-butylamine
Olfactory / nasal effects markers |
Exposure concentrations |
Reference |
Section IUCLID5 |
|
mL/m3 |
mg/m3 |
|||
Odor threshold (human) |
1 - 2 |
3 - 6 |
Beard and Noe 1981; Amoore amd Hautala 1983 |
7.10.3 |
Sensory nasal irritation threshold (human) |
5 |
15 |
Beard and Noe 1981 |
7.10.3 |
RD0 (mouse, 10 min) *) |
11.8 |
36 |
Nielsen and Vinggaard 1988 |
7.2.2 |
RD50 (mouse, 10 min) *) |
121 |
380 |
Nielsen and Vinggaard 1988 |
7.2.2 |
RD50 (mouse, 15 min) *) |
84 – 112 |
260 - 340 |
Gagnaire et al. 1989, 1993 |
7.2.2 |
NOEC (no clinical symptoms, rat, 5 d) |
40 |
120 |
Gamer et al. 1999 |
7.5.3 |
NOAEC (clinical symptoms, no histopathological changes, rat, 5d) |
115 |
350 |
Gamer et al. 1999 |
7.5.3 |
NOAEC (histopathological changes, rat, 14d) |
<17 |
<51 |
Gamer et al. 2002 |
7.5.3 |
*) RD0 = the exposure concentration resulting in no reflectory, sensoric irritation (no suppression of respiration rate).
RD50 = the exposure concentration resulting in reflectory, sensoric irritation expressed as 50% decrease in the respiratory rate.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.77 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- NOAEC
- Value:
- 460 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 115 mg/m³
- Explanation for the modification of the dose descriptor starting point:
In the underlying experimental study rats were exposed during 6 hours and every day over a period of 14 days. Therefore, the NOAEC from the developmental toxicity study was adapted to the consumer situation with 24 h exposure during 7 days/week.
- AF for dose response relationship:
- 1
- Justification:
- default value
- AF for differences in duration of exposure:
- 6
- Justification:
- default value for subchronic to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default value
- AF for other interspecies differences:
- 2.5
- Justification:
- default value for remaining uncertainties
- AF for intraspecies differences:
- 10
- Justification:
- default value
- AF for the quality of the whole database:
- 1
- Justification:
- default value
- AF for remaining uncertainties:
- 1
- Justification:
- default value
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
As outlined above a DNEL for systemic inhalative exposure could be derived on basis of the developmental toxicity study. Based on the NOAEL for systemic effects of 460 mg/m3, after adaption to the continuous exposure situation of consumers (x 6/24 x 7/7) and considering the default assessment factors for remaining interspecies differences (AF 2,5), intraspecies differences (AF 10) and time extrapolation (6) a DNEL 0.77 mg/m3 results. All other endpoints are evaluated in a qualitative manner, due to the acute toxicity and skin corrosivity of the substance.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.