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EC number: 931-295-2
CAS number: -
Etherdiamines/acetates are protonated under
ambient conditions. The substance has a cationic surfactant structure
which leads to high adsorptive properties to negatively charged surfaces
as cellular membranes which are easily disrupted by its surfactant
structure. Cytotoxicity at the local site of contact through disruption
of cell membrane is considered the most prominent mechanism of action
for toxic effects. The substance has high corrosive properties on skin
and shows gastro-intestinal irritation following oral ingestion. Uptake
is expected to be slow. Uptake and metabolisation is indicated by
metabolic adaption of the liver. The log Pow was found to be -0.4 which
indicates that the substance will not bioaccumulate.
common name for the substance “Reaction mass of 1,3-Propanediamine,
N-[3-(tridecyloxy)propyl]-, branched and 1,3-Propanediamine,
N-[3-(tridecyloxy)propyl]-, branched acetate” used in this dossier is
manufacturing process is a multi-step process. In the first step fatty
alcohol is reacted with acrylonitrile at elevated temperature to form an
ethernitrile. In the second step the ethernitrile is hydrogenated to the
corresponding primary etheramine. This process is repeated for the
conversion of the etheramine into an etherdiamine: The etheramine is
reacted with acrylonitrile and the resulting nitrile is again
hydrogenated to the corresponding primary amine of the resulting
etherdiamine. In the final step the etherdiamine is partially
neutralised with acetic acid to form a cationic-amine acetate salt. The
final product Etherdiamine C13i/acetate contains for about half the
etherdiamine acetate, and half etherdiamine without acetate.
are protonated under ambient conditions. This means that they will sorb
strongly to negatively charges substances like glassware, soil and
sediment constituents and also organisms.
C13i has a molecular weight of 314 (as acetate salt 374), and has a
calculated logP of 5.2 (KOWWIN). But under environmental and
physiological conditions at pH around 7, the logD is about 0.5, and from
pH 5 and lower -1 (http://www.chemicalize.org), which is related to the
protonation of the primary amine. This is confirmed by a measured Pow at
pH 6 of -0.4 (OECD 123 slow stirring at 1% of CMC, at 25 °C).
As the substance forms micelles in
water the water solubility is expressed as the critical micelle
concentration (CMC). For this substance the CMC has been determined to
be between 1300 – 2200 mg/L (pH 7, 23 – 25°C)
physiological circumstances both nitrogens are positively charged,
resulting to a cationic surfactant structure which leads to high
adsorptive properties to negatively charged surfaces as cellular
membranes. The apolar tails easily dissolve in the membranes, whereas
the polar head causes disruption and leakage of the membranes leading to
cell damage or lysis of the cell content. As a consequence, the whole
molecule will not easily pass membrane structures. Cytotoxicity at the
local site of contact through disruption of cell membrane is considered
the most prominent mechanism of action for toxic effects.
substance is a clear light-yellow liquid, with a melting point below
-30ºC and boiling point > 300ºC and has a measured vapour pressure of
0.005 Pa at 25°C, which represents a maximum vapour concentration in the
air of about 0.6 mg/m3 or 0.05 ppm. Evaporation rate is expected to be
Etherdiamine C13i/acetate is used in industrial settingsas
flotation agent in mining, involving potential exposures of only a
limited number of people working in industrial setting under controlled
view of its corrosive properties, handling takes place under controlled
conditions, minimising likelihood of exposures.
C13i was tested both with and without the acetate for dermal
irritation/corrosion in in vivo studies on rabbit skin. Both were
found to be corrosive to rabbit skin following 3 minutes exposure.
Consequently it is concluded that the presence of acetic acid does not
impact corrosive properties of the etherdiamine.
are two studies that evaluated the acute oral toxicity of Etherdiamine
C13i showing that its LD50 is within the range of 300-2000 mg/kg bw,
with LD50 cut-off value of 500 mg/kg body weight. Although both studies
have been performed on etherdiamine C13i without acetate, they are
considered to be relevant for the evaluation of etherdiamine C13i with
acetate as well. Dermal corrosion studies have shown that the presence
of acetate does not impact the corrosive properties of the compound.
Additionally, the conversion of about half of the etherdiamine to
etherdiamine-acetate salt, as is the case for the Etherdiamine /acetate
product mixture, is not considered to have a large impact as it will
probably be dissociated again in stomach and intestinal fluids.
to its corrosive properties, further acut ein vivo testing via
dermal and inhalation route is not justified.
the substance is corrosive, symptoms of local respiratory irritation are
expected, which should limit the systemic uptake of amount needed for
for acute dermal toxicity, effects will be characterised by local tissue
damage. Systemic uptake via skin is likely to be very limited, in view
of the use of protective measure related to the handling of corrosive
is no information on possible skin sensitisation available from testing.
Cross reading with primary alkylamines indicates that the substance
would not be sensitising to skin. Testing is in view of its corrosive
properties and only industrial use not required.
are no concerns for genotoxicity. Etherdiamine C13i/acetate is not
mutagenic in the Salmonella typhimurium reverse mutation assay,
is not clastogenic in human lymphocytes, and not mutagenic in the HPRT
mutation test with Chinese hamster V79 cells.
information combined from a 14-day (OECD 414 developmental toxicity
study), 28-day (OECD 407) and 90-day (OECD 408) repeated dose study show
all a comparable picture with respect to the inflammatory responses
observed: The macroscopic findings (thickened intestinal wall and
enlarged mesenteric lymph nodes) and the microscopic correlate (foamy)
macrophages in the lamina propria or granulocytic (necrotizing)
inflammation and granuloma(s) with or without central necrosis in the
lymph nodes) and the increase of neutrophils all point to a generalised
inflammatory response that is both increasing with dose and duration.
Actual systemic inflammatory responses extending to organs outside the
gastro-intestinal tract do occur after longer duration of dosing at
lower dose levels.
LOAEL of 0.5 mg/kg bw/day was established from the 90-day study in rat
by oral gavage, at which level leukocytosis was seen, inflammatory
responses in mesenteric lymph nodes and lungs, and effects in the
hindlegs and/or tail of few animals that were histopathologically
supported by occurrence of arthritis with or without hyperostosis.
MoA this is considered to be related to phospholipidosis effect,
resulting to the high partitioning into phospholipids and subsequent
accumulation of these phospholipids in mesenteric macrophages.
relevance to other routes of exposure:
Inhalation: Effects are mainly local lymph nodes. It is uncertain
whether similar effects in lung are to be expected. Based on the
available data and progression of effects from mesenteric lymph nodes to
lungs, similar sensitivity is assumed.
Dermal: Effects are mainly on local lymph nodes following absorption. On
skin local corrosive/irritant effects and lower absorption are to be
expected. However, based on local irritant effects that are possibly
inflammatory mediated, same sensitivity is assumed.
repeated dose studies on Etherdiamine C13i/acetate do not indicate
adverse effects on reproductive organs, including oestrous cycle
evaluation and histopathological examination of the male and female
reproductive organs. Study of Etherdiamine C13i/acetate in a prenatal
developmental toxicity study in rats has not shown reproductive or
teratogenic effects. Developmental effects characterised as increased
incidence of delayed ossification were only visible at maternal toxic
dose levels and are considered secondary to that. Also comparable fatty
amine-like substances lack of effects on reproduction.
Toxicokinetics, metabolism and
C13i is mainly protonated under environmental conditions. The protonated
fraction will behave as salt in water. Etherdiamine C13i is surface
active and has a low solubility in the form of CMC (1.3 – 2.2 g/L at pH
to other cationic fatty nitrile derivatives, Etherdiamine C13i is
expected to sorb strongly to sorbents and patitionates strongly into
phospholipid membranes. As a consequence, absorption from
gastro-intestinal system is likely to be slow.
With a vapour pressure of 0.005 Pa at
25°C and expected low evaporation rate, potential for inhalation is
limited. The substance is very corrosive and itsuse is limited to
industrial settings under controlled conditions which further limits the
likelihood of exposure.
mode of action of Etherdiamine follows from its structure, consisting of
an apolar fatty acid chain and a polar end of a primary amine from the
ether part with primary amine. The structure can disrupt the
cytoplasmatic membrane, leading to lyses of the cell content and
consequently the death of the cell.
C13i is corrosive to skin, and toxicity following dermal exposure is
characterised by local tissue damage, rather than the result of
percutaneously absorbed material. It is not expected to easily pass the
skin in view of its ionised form at physiological conditions. However,
as this is not quantitatively evaluated, 100% dermal absorption is
considered as worst case assumption.
log Pow was found to be -0.4 which indicates that the substance not will
document provide results from profiling. Etherdiamine C13i does not
trigger any alert for mechanistic or endpoint toxicity. The only alert
triggered Class III (high) Toxic hazard classification by Cramer. Class
III is described as: “Substances with chemical structures that permit no
strong initial presumption of safety or may even suggest significant
toxicity or have reactive functional groups.” Just the presence of an
aliphatic secondary amine causes this response.
QSAR Toolbox metabolism profilers,
MetaPrint2D and BioTransformer indicate that a large range of human
relevant phase I liver metabolism is possible.
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.
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