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EC number: 204-101-2
CAS number: 115-70-8
Short description of key information on bioaccumulation potential result: see toxicokinetics, metabolism and distribution.
There were no experimental studies available
in which the toxicokinetic properties of 2-amino-2-ethyl-1,3-propanediol
(AEPD) were investigated. Therefore, whenever possible, toxicokinetic
behaviour was assessed taking into account the available information on
physicochemical and toxicological characteristics of AEPD according to
the “Guidance on information requirements and chemical safety assessment
Chapter R.7c: Endpoint specific guidance (ECHA, 2009)”.
In its pure state, AEPD (119.17 g/mol) is a
solid, whereas the commercial product is a transparent, yellow, viscous
liquid. However, as there is a manufacturing process in use leading
directly to chemical conversion of the solid to the liquid state of
AEPD, only the liquid state is of relevance for human health risk
assessment. Therefore, all experimental studies were performed with
Absorption and distribution
AEPD is highly soluble in water (> 950 g/L),
has a low vapour pressure (0.29 Pa) and possesses a relatively low
partition coefficient (log Kow = -1.02), resulting in a low potential to
accumulate in biological systems.
Acute oral toxicity studies have been
conducted in rats and mice. According to OECD 423, a LD50 value of 5000
mg/kg for female rats was calculated (Nishimura, 2004). In this study,
no mortality was observed and no clinical signs of toxicity or
abnormalities of gross pathology were recorded.
In another oral toxicity study, after dosing
of 2500, 3500 and 5000 mg/kg bw and using 10 animals per dose and sex,
the mortality was 0, 1, 5 and 5 for the male rats and 0, 1, 2 and 9 for
the female rats (Parekh, 1982). Animals found dead during the
observation period had severe stomach and intestinal hemorrhage,
indicating a local irritating effect of the test substance due to the
alkaline pH value. The remaining organs examined grossly appeared
normal. The calculated LD50 for females was 3882 mg/kg bw and for males
the LD50 was 4571 mg/kg bw, respectively.
A relatively old study (Rubenkoenig, 1955)
with mice was also available. The animals were orally administered 1000,
1500, 2000, 3000, 3600 and 4250 mg/kg bw AEPD, using 10 animals per dose
level. The mortality was 0, 1, 3, 7, 10 and 10, respectively, by
increasing dose. No further data were given. The estimated LD50 was 2470
The findings of the acute oral toxicity
studies evidenced that the main cause of acute toxicity was most
probably local irritation due to the highly alkaline test substance.
With regard to the dose administered and the nature of effects observed,
systemic bioavailability of the test substance is considered to be
In addition, in combined repeated dose
toxicity study with the reproduction/developmental toxicity screening
test, rats showed no effects on gross pathology. The histopathological
examinations displayed reversible effects in the forestomach and corpus.
The main cause of these effects was again most probably local irritation
due to the highly alkaline test substance administered by gavage.
No data on acute inhalation toxicity are
available. As the physical state of AEPD which is relevant for human
risk assessment is a liquid and because of its relatively low vapour
pressure of 0.29 Pa, inhalation is not considered to be a significant
route of exposure. In case of spray applications of technical products
containing the neat substance, the concentration is very low (< 1%),
therefore the potential for acute toxicity via the inhalation route is
considered to be negligible.
The dermal acute toxicity was assessed by
exposing rabbits skin to undiluted AEPD (2000 mg/kg bw; pH 11.78) under
occlusive conditions (Parekh, 1982). After 24 hours, the skin area was
cleaned and the animals were observed for 14 days following
administration. No mortality was observed and no clinical signs or
unusual findings were noted at necropsy. However, the treated skin areas
of all the rabbits were necrotic and oedematous, likely due to the
alkalinity of the test substance. The LD50 value was > 2000 mg/kg bw.
For AEPD, a QSAR based modelling published by Potts and Guy
(1992), taking into account molecular weight and low Kow, estimated a
dermal permeability constant Kp of 6.34E-05 cm/h. Similar to the
approach taken by Kroes et al. (2007), the maximum flux Imax (Imax = Kp
[cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal
absorption of 60.2 µg/cm²/h AEPD. Usually, this value is considered as
indicator for a dermal absorption of 80% (Mostert and Goergens, 2011).As
no systemic toxicity was found in the acute dermal toxicity study up to
2000 mg/kg bw, it is expected that systemic bioavailability of AEPD is
Metabolism and excretion
According to the chemical structure of AEPD,
it can be assumed that AEPD is not metabolised in-vivo. Modelling of
potential metabolites via OECD QSAR toolbox v.2.0 (2010) confirms this
assumption. No relevant metabolites were generated by the liver
metabolism simulator, by the skin metabolism simulator or by the
microbial metabolism simulator. Based on this information, it seems to
be very unlikely that AEPD will be metabolised by cytochrome P450
Moreover studies on genetic toxicity in
vitro (Ames test, gene mutation in mammalian cells in-vitro,
chromosome aberration in-vitro) were all negative, indicating that there
is no evidence of reactivity of AEPD under in-vitro test conditions.
With respect to skin sensitisation data, there was no evidence that the
test substance exhibits direct protein reactivity which would cause skin
sensitisation. Since no interactions with proteins were determined and
no relevant metabolites were generated via QSAR modelling, reactivity of
the test substance is considered rather unlikely under in-vitro and
Since AEPD is a polar substance, highly water
soluble and has a molecular weight below 500, the substance is mainly
excreted via the kidneys in a non-metabolised form.
The hypothesis that AEPD is not metabolised in
vivo and is readily excreted predominantly via urine is confirmed by
the toxicokinetic study of Saghir et al. (2008). This study was
conducted to determine absorption, distribution, metabolism and
excretion of the biocide Bioban™ CS-1246 following oral and dermal
exposure in rats. Orally administered Bioban™ CS-1246 was rapidly
absorbed and readily eliminated predominantly via urine within 144-168 h
after dosing. Furthermore the biocide was completely metabolised,
detecting AEPD as the only metabolite above 5% of the administered dose
in all urine and faeces samples and analysed from all dose groups.
Compared to the oral administration, dermal absorption was low and slow
(43% of the applied dose remained unabsorbed) likely due to cornified
layer of cells on the skin surface that work as a barrier. In compliance
with limited absorption of the applied dose, elimination was also low.
AEPD was detected as the only metabolite above 5% of the dermally
applied dose in all urine and faeces samples. Based on the results of
this study, AEPD is not expected to accumulate upon exposure.
Taking into account all available data, the
biological properties of AEPD are mainly governed by its intrinsic
alkalinity. AEPD possesses a low acute toxicity and is expected to have
only a low potential to accumulate in biological systems.
Potts, R. and Guy, R. (1992) Predicting skin permeability. Pharm.
Res. 9(5): 663-669
Kroes, R. et al. (2007) Application of the threshold of
toxicological concern (TTC) to the safety evaluation of cosmetic
ingredients. Food Chem. Toxicol. 45, 2533–2562
Mostert, V. and Goergens, A. (2011) Dermal DNEL setting: using
QSAR predictions for dermal absorption for a refined route-to-route
extrapolation. Society of Toxicology, Annual Meeting, ISSN 1096-6080
(http://www.toxicology.org/AI/PUB/Toxicologist11.pdf), 120(2): 107
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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