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EC number: 203-904-5
CAS number: 111-75-1
or Butylethanolamine (BEA) is
expected to be absorbed well after oral exposure, based on oral LD50 of
892-1310 mg/kg bw in rats, its low molecular weight (117.2 g/mol), high
water solubility (1000 g/L) and LogPow of 0.64. Concerning the
absorption after exposure via inhalation, as the chemical has vapour
pressure of 13.94 Pa (a value not indicative for absorption by
inhalation), it is clear, that the substance is moderately available for
inhalation. Given its lipophilicity (LogPow 0.64) - if absorbed - it is
expected to be absorbed directly across the respiratory tract epithelium
or through aqueous pores and/or be metabolized by the alveolar and
bronchial tissue. BEA may be absorbed to a limited extent following
dermal exposure into the stratum corneum and into deeper layers of the
epidermis, due to its high water solubility. Nevertheless, BEA does not
quite meet the criterion of having a LogPow value < 0 that would support
this assumption. Moreover, irritating properties of BEA due to its
charged form (free base) can affect the absorption, slowing the passage
through biological membranes. Concerning distribution in the body, BEA
is expected to distribute into the inner of cells and into the
intravascular compartment. The substance does not indicate a significant
potential for accumulation. BEA is expected to be metabolised via Phase
I reactions leading to hydroxylated derivatives and/or derivatives of
oxidative deamination. Further, they can either be involved into
intermediary metabolism for further oxidative reactions or be excreted.
BEA and its metabolites are expected to be eliminated mainly via the
if there are indications that the inhalation and dermal absorption rates
of BEA are low on the basis of physical-chemical properties and
available toxicological data, a worst-case approach i.e. 100 %
absorption, are assumed for the purposes of derivation of dermal or
inhalative systemic DNEL.
toxicokinetic profile of butylethanolamine (BEA) was not determined by
actual absorption, distribution, metabolism or excretion measurements.
Rather, the physico-chemical properties of this substance were
integrated with its available toxicological data as well as the data on
the read-across substance dibutylethanolamine (CAS 102-81-8) to create a
prediction of the toxicokinetic behavior. The read-across substance
shows very similar physico-chemical properties (high water solubility
(miscible in all proportions in water, similar LogPow, no hydrolysis in
water)) and is thus believed to behave very similar in aqueous solutions.
profile of Butylethanolamine
BEA is acutely
toxic via oral route of exposure. An oral LD50of 892 mg/kg bw
was established in an animal study in rats (BASF, 1977; Report No.
XXVI/45). No mortalities were observed in an acute inhalation study in
rats (LC0of 24.7 mg/L; BASF, 1977; Report No. XXVI/45); but
mucous membrane irritation was observed. In an acute dermal study, BEA
did not produce systemic effects in animals (LD50>2000 mg/kg
bw; Latven, 1977). The substance was irritating to rabbits’ skin and
produced severe damage to eyes (BASF, 2007; Report No. 18H0033/072033;
BASF 1977; Report No. XXVI/45). Since BEA has pH of 11.9 (GESTIS, 2011)
no testing of skin sensitisation was conducted. BEA was not mutagenic in
any of the bacterial strains tested (BASF, 1997, Report No.
40M0579/964373) and did not induce gene mutations at the hprt locus in
mouse lymphoma L5178Y cells (OECD 476, Covance Laboratories Ltd., 2012a;
Report No. 8260615). Additionally, no relevant increases in the number
of cells containing micronuclei in human lymphocytes were detected (OECD
487, Covance Laboratories Ltd., 2012b; Report No. 8260614).
Corrosion/irritation is primary effect of BEA and, in analogy to other
alkanolamines, the effects by prolonged exposures are confined to local
effects of respiratory tract and no systemic toxicity could be reached.
The only systemic effects observed in the Combined Repeated Dose and
Reproduction/Developmental Toxicity Screening Test in Wistar Rats (OECD
422; BASF, 2013, Project No. 87R0286/05I017, conducted with
dibutylethanolamine) were transiently reduced food consumption, body
weight and body weight gain. Reproductive and developmental parameters
were not affected.
analysis of Butylethanolamine
is a colourless liquid without specific odour (MW of 117.2 g/mol) at 20
°C. The substance is soluble in water (1000 g/L at 20 °C) and has a
LogPow of 0.64. It has a low vapour pressure of 13.94 Pa (at 20 °C) and
melts at -2.5 °C under atmospheric conditions. BEA is not expected to
undergo hydrolysis in the environment due to the lack of functional
groups that hydrolyse under environmental conditions.
absorption is favoured for small water-soluble molecules with MW up to
200 which can pass through aqueous pores or can be carried with the bulk
passage of water (TGD, Part I, Appendix IV, 2003). Based on the
molecular weight of 117.2 g/mol, the high water solubility and the
logPow of 0.64, BEA is expected to be readily absorbed via the
gastrointestinal (GI) tract by passive diffusion. This thesis is
supported by the fact that the substance induced systemic toxicity
effects in rats via oral route (Cat 4, harmful if swallowed; BASF, 1977;
Report No. XXVI/45). In this study, Sprague-Dawley rats were
administered 414, 607, 892, 1310, 1917, 2818, 4138 mg/kg bw/day of the
test substance. In the higher dose groups (1310-4138 mg/kg bw) irregular
respiration, apathy, staggering, diarrhea containing blood and a bad
general state was observed until all animals died. In the other groups,
except in the 414 mg/kg bw dose group, gasping, spastic gait, ruffled
fur, bad general state was observed. In animals that died prior to study
ending, dilatation of the heart and congestion, hyperemia, anemic
stomach with liquid content, atonic and reddened intestine was seen. The
LD50 was set at 892-1310 mg/kg bw. From this study, systemic
exposure to the test substance is indicated, possibly mediated by
passive diffusion along the gastrointestinal tract (for what a logPow is
indicative; ECHA R7.c, 2008). However, liquid content of the intestinal
tract might be more indicative for local corrosive effects of the test
substance rather than systemic availability.100 % oral absorption is
considered appropriate based on this acute toxicity data and on the
physico-chemical properties which are in the range suggestive of
absorption from the gastro-intestinal tract.
with logPow values above 0 have the potential for absorption directly
across the respiratory tract epithelium. BEA has a moderate logPow value
of 0.64 and is according to this criterion favourable for absorption
directly across the respiratory tract epithelium by passive diffusion.
Further parameter which should be considered is the volatility.
Substances with low volatility have a vapour pressure of less than 0.5
kPa. A vapour pressure of 13.94 Pa is indicative for low volatility,
assuming low availability for inhalation and consequently low systemic
exposure (ECHA R7.c, Table R. 7.12 -2, 2008). Based on low volatility of
BEA, exposure by inhalation is not really relevant for this substance.
It is unlikely, that considerable amounts of the substance reach the
lung and when this occurs, the substance is expected to be absorbed
directly across the respiratory tract epithelium or through aqueous
pores due to the logPow of 0.64. This was confirmed in the acute
inhalation study in rats (BASF, 1977; Report No. XXVI/45). In this
study, rats were exposed to a saturated vapour atmosphere of the test
substance for 8 hours. The mean nominal concentration of the test
substance was 24.69 mg/L. No animal died. Mucous membrane irritation was
observed and no abnormalities at necropsy. Irritating to the mucous
membranes can intensify the absorption. Based on these data, a low
absorption can be expected for inhalation (in this case, absorption by
inhalation cannot be higher than that by oral route). However, for the
purpose of derivation of inhalative systemic DNEL a absorption rate of
100% is assumed, follwing a worst-case approach.
based on the physico-chemical properties of BEA, the substance is likely
to penetrate the skin to only a limited extent as it is very soluble in
water (water solubility of 1000 g/L). According to TGD, Part I, Appendix
IV (2003), absorption through the skin is anticipated to be limited if
water solubility higher than 10,000 mg/L and logPow is below 0. In case
of BEA, the criterion for very high water solubility meets but the
criterion for logPow does not meet (it is slightly above 0). The
molecular weight of 117.2 g/mol is also suggestive of absorption through
the skin. However, the substance BEA may be too water solouble to cross
lipid rich environment of the stratum corneum and achieve deeper layers
of the epidermis. Low penetration rate is supported by the result of the
acute dermal study in rats where no systemic effects of toxicity were
observed in treated animals (Latven, 1977). Further, the charged
molecules of BEA will be hindered to be absorbed through the skin.
Additionally, BEA has highly irritating properties, which were confirmed
in the acute inhalation study described above, skin irritation study in
rabbits (BASF, 2007; Report No. 18H0033/072033) and in eye irritation
study (BASF, 1977, XXVI/45). Based on these properties of BEA and
taken into account the fact that the irritating property of the
substance is primary effect, systemic effect cannot be reached, which is
why a reduced dermal absorption rate is highly likely. Despite these
assumptions, a dermal absorption of 100% is assumed for BEA for the
purposes of derivation of dermal systemic DNEL, following a worst-case
and accumulative potential
significant amount of BEA via oral route is expected to be available for
distribution. As the cell membranes require a substance to be soluble in
both water and lipids to be taken up, BEA is expected to reach the inner
cell compartment due to its optimal molecular weight of 117.2 g/mol, its
LogPow of 0.64 and a sufficiently high solubility in water (1000 g/L).
The substance is also expected to be distributed into the intravascular
compartment. As it is known that “substances with LogPow values of 3 or
less would be unlikely to accumulate with the repeated intermittent
exposure patterns normally encountered in the workplace” (TGD, Part 1),
no enhanced risk for accumulation will be associated with the substance.
is not expected to undergo hydrolysis in gastrointestinal tract or in
body fluids, due to the absence of hydrolysable functional groups. It is
expected to be excreted unchanged due to its high water solubility and
optimal molecular weight. If case of entering the cell inner, BEA can
undergo Phase I reactions: hydroxylation at α-carbon leading to hydroxyl
derivatives (i.e. 4-[(2-hydroxyethyl)amino]butan-1-ol, or
4-[(2-hydroxyethyl)amino]butan-2-ol) or oxidative deamination with
splitting-off of butylamine and hydroxyacetaldehyde, hydroxyacetic acid
or oxoacetic acid. Further possible reactions are oxidation of
4-[(2-hydroxyethyl)amino]butan-1-ol to aldehyde
4-[(2-hydroxyethyl)amino]butanal with subsequent oxidation to
4-[(2-hydroxyethyl)amino]butanoic acid. Primary and secondary
metabolites can be involved into intermediary metabolism or excreted
unchanged or in form of conjugates. Excretion
BEA is a stable compound and sufficiently soluble in water, it can be
filtered by the kidneys and undergo primarily urinary excretion.
Molecular weight of BEA (117.2 g/mol) and vapour pressure of 13.94 Pa
are also suggestive of excretion via the urine (ECHA Guidance R7c.,
2008). Excretion via the urine is a major pathway for the oxidised
and/or hydroxylated derivatives of BEA as well. Metabolites which
re-enter the system are expected to occur in a lesser extent.
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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