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: 618-561-0
CAS number: 9046-10-0
The test substance is a corrosive substance; therefore, it is
difficult to test at high levels. Toxicokinetic information is not
available for this substance. However, based on physico-chemical
properties, the test substance would be expected to be highly soluble in
water (hydrophilic). It is not expected to be lipophilic nor
bioaccumulate in tissues. It is a liquid with a low vapour pressure, and
therefore, is not expected to be available via the inhalation route. If
absorbed at low doses, the substance would be expected to be excreted
without any adverse systemic effects based on chronic dosing studies.
Polyoxypropylene diamine (POPDA, the test substance) is a
colorless liquid with a high boiling point (232°C), a low vapour
pressure (0.9 hPa at 20°C), a high water solubility (miscible with
water) and a moderate partition coefficient (log Pow 1.34). The test
substance is a base with a dissociation constant (pKa) of 9.3 at 24°C.
The test substance confirmed to be also corrosive to skin (category 1C).
The test substance is a polyamine with repeating oxypropylene
units in the backbone and is a reaction product of the reductive
amination of di-, tri- and tetrapropoxylated propane-1,2-diol. The
molecular formula is H2N(C3H6O)nC3H6NH2 with n=2-6. Due to its variable
composition, the test substance is categorized as a UVCB. The main
constituents are tripropylene glycol diamine (n=2, 35-55%),
tetrapropylene glycol diamine (n=3, 20-35%), pentapropylene glycol
diamine (n=4, 5-20%), hexapropylene glycol diamine (n=5, 0-10%) and
heptapropylene glycol diamine (n=6, 0-5%). Its average molecular weight
is 230 g/mol.
No toxicokinetic data (animal or human studies) are available on
this substance. The data present in this dossier are based on
physico-chemical and toxicological parameters and will allow a
qualitative assessment of the toxicokinetic behaviour.
The test substance is a water-soluble molecule which will readily
dissolve into the gastrointestinal (GI) fluids through the aqueous pores
or through carriage across membranes (epithelial barrier) with the bulk
passage of water (passive diffusion). The predominant site of absorption
along the gastrointestinal tract is the small intestine through passive
A repeated dose oral toxicity study (American Cyanamid Company,
1968; supporting study; Klimisch 4) carried out for 30 days on Albino
Wistar rats at dose levels of 93 (0.083%) and 239 mg/kg/day (0.208%) in
feed indicated that this 30-day exposure did not produce any mortality
or evidence of systemic toxicity. No changes were observed related to
food intake or body weight gain for the study animals. There were no
histopathological findings noted in any of the study animals at
necroscopy. The no observable effect level (NOEL) and no observable
adverse effect level (NOAEL) was determined to be equal to or greater
than the highest dose level tested (>= 239 mg/kg/day or 0.208 %).
However, the reliability of this study cannot be guaranteed.
In an extended one generation reproductive toxicity study (Barnett
J., 2020; key; Klimisch 1) performed according to the OECD 443
guideline, 25 males and 25 females Sprague - Dawley rats were given by
daily oral gavage the doses of 50, 150, 450 mg/kg bw/day for 104-108
days (females), 113-116 days (males). The results show that for both
male and female of P and F1 generation, an increased incidence of
microscopic findings was observed, including inflammation, neutrophilic
exudates and squamous metaplasia of the nasopharynx, in the 150 and 450
mg/kg/day groups. treatment related inflammation was observed within the
nasopharynx and multifocally within the nasal cavity of rats dosed at
150 or 450 mg/kg/day.
Other treatment related effects included mortality on a single
occasion, clinical signs such as suspected dehydration, labored
breathing, abnormal breathing sounds, hunched posture, thin fur cover
erect fur, hyperreactivity and decreased activity on some occasions and
a few incidences of reduction in body weight (gain). All these effects
could be considered linked to the corrosive nature of the test
substance. There were no adverse effects in hematology, clinical
chemistry, thyroid hormone levels, the estrous cycling, mating,
fertility and natural delivery. There were also no adverse effects on
growth and development of the offspring. It was concluded that the NOAEL
for the P- and F1 generation systemic toxicity was set at 150 mg/kg/day,
the reproductive and developmental NOAEL was set at 450 mg/kg/day (the
highest dose tested).
Based on the results of a prenatal developmental toxicity study
(Renaut, 2016) with New Zealand White rabbits at dose levels 0, 15, 50
and 115 mg/kg/day, it was concluded that the NOAEL for maternal toxicity
was 50 mg/kg/day as the higher dose of 115 mg/kg/day caused low food
consumption, resulting in a single mortality, and clinical signs
relating to inappetence and overall body weight loss during gestation
compared with body weight gain in all other groups. The NOAEL for
embryo-fetal survival, development and growth was set at 115 mg/kg/day
when the test substance is administered during organogenesis in the
Based on the high water solubility and repeated dose oral toxicity
study, the oral absorption factor for the test substance is set to 50%.
Given the low vapour pressure of 0.9 hPa (at 20°C), the test
substance is considered not to be a volatile liquid, hence the
availability for inhalation as a vapour is limited.
It is expected that in the respiratory tract the liquid would
readily diffuse/dissolve in the mucus lining the respiratory tract and
due to its lipophilic character (log Pow 1.34 >0), the test substance
has the potential to be absorbed directly across the respiratory tract
epithelium by passive diffusion. The hydrophilic substance will probably
be retained in the mucus and transported out of the respiratory tract
based on its average molecular weight of above 200 g/mol.
There is no repeated dose study available to determine the toxic
effects after inhalation of the test substance, but an acute respiratory
study (Bio/dynamics, 1979; key, Klimisch 2; equivalent to OECD 403) has
been carried out. No abnormal clinical signs were observed during the
exposure. During the 14-day observation period dry rales, mucoid nasal
discharge, moist rales, excessive lacrimation, yellow staining of the
ano-genital fur, fried red material around the nose and a white spot on
the left eye were observed sporadically for some animals. Necroscopy
examinations revealed lung discoloration in 9 of 10 animals and kidney
discoloration in 6 of 10 animals. The frequency of lung and kidney
discoloration was higher than normally observed in this type of test
animals and this type of exposure and may have been indicative of a
response to the exposure. The LC50 value was calculated to be > 0.74
mg/L, as there was no mortality observed at this dose level.
Based on these conclusions, the respiratory absorption factor is
set to 100%.
Since the test substance is a water soluble liquid, it is expected
to be readily taken up by the skin. The log Pow value of 1.34 also
indicates that the product is sufficiently lipophilic to cross the
stratum corneum favouring dermal absorption. Furthermore, the test
substance is classified as skin corrosive potentially causing enhanced
penetration due to skin surface damage.
A 28-day repeated dose dermal toxicity study (Pharmakon Research
International, 1989) on 6 Sprague-Dawley rats at dose levels 50, 100,
250, 500 and 750 mg/kg led to treatment related clinical signs in the
three highest dose groups (250, 500 and 750 mg/kg). The severity of the
signs (erythema, edema, fissuring and sloughing of skin and scattered
necrosis of the dose area) were dose-dependent. Terminal necroscopy
revealed mottled lungs, red foci throughout the lungs, yellow
discoloration of the left lateral lobe of the liver, tan foci on the
medial lobe of the liver and mottled kidneys in treated groups. The
control group showed small, granular, yellow-brown discoloration of the
left lateral liver lobe in 1 animal. The lowest observable adverse
effect level (LOAEL) for local effects was determined to be 250
mg/kg/day, while the NOAEL was 100 mg/kg/day. The LOAEL for systemic
effects was 50.0 mg/kg/day.
A 90-day repeated dose dermal toxicity study (Pharmakon Research
International, 1990) with doses of 0, 50, 80 and 250 mg/kg applied to
Sprague-Dawley rats showed no clinical signs of systemic toxicity
attributed to the test substance. The mild skin irritation caused by the
test substance was primarily observed in the high dose group and was
reversible after discontinuation of the treatment during the recovery
period. Significant differences were observed in body weight, daily body
weight gain and daily food consumption, while no statistically
significant differences in the absolute organ weights or relative organ
to brain weight ratios were detected. Except for the mild skin
irritation at the treatment site of the high dose animals, there were
not histomorphological alterations attributable to the test
substance. Based on these findings, dermal application of the test
substance to rats did not produce a systemic toxicity when administered
five days per week for 30 and 90 days at doses 50, 80 or 250 mg/kg. As
the NOAEL after 90 days of dermal exposure was established as
250mg/kg/day, but the LOAEL after short-term exposure via oral exposure
was 115 mg/kg/day.
Based on the physicochemical parameters and repeated dose dermal
toxicity studies, the dermal absorption factor is set to 50%.
The high water solubility and moderate molecular weight predict
that the test substance will probably distribute through the body due to
diffusion through aqueous channels and pores. The test substance is also
lipophilic (log Pow 1.34 >0) and therefore likely to distribute into
cells leading to a higher intracellular concentration in comparison to
the extracellular concentration especially in fatty tissues. The
conclusions of the dermal and respiratory toxicity studies indicate that
the target organs are among others the lungs, kidneys and liver.
The test substance is a lipophilic substance, so it will tend to
concentrate in adipose tissue and depending on the exposure conditions
it may accumulate. Due to the log Pow value 1.34 < 3, the product is
unlikely to accumulate with the repeated intermittent exposure patterns
normally encountered in the workplace, but may accumulate if exposures
are continuous. Once exposure stops, the substance will gradually be
eliminated at a rate dependent on the half-life of the substance. If fat
reserves are mobilized more rapidly than normal, there is the potential
for large quantities of the parent compound to be released into the
Based on the physicochemical properties (high water solubility,
moderate partition coefficient, etc.) of the test substance, no (or
little) accumulation is expected within the lungs, bones or stratum
Based on the structure, test substance might undergo phase I
biotransformation such as hydroxylation or oxidative deamination
followed by conjugation reactions (phase II) such as glucuronidation (by
the enzyme glucuronosyltransferase) and sulphation (by the enzyme
sulfotransferase. The Phase II conjugation reactions largely increase
the hydrophilic character of the product. Metabolism can take place in
the liver, gastrointestinal (GI) flora or within the GI tract epithelia
(mainly in the small intestine), respiratory tract epithelia (in the
nasal cavity, trachea-bronchial mucosa and alveoli and skin), etc.
Given its high water solubility and low molecular weight (<300), a
possible route of excretion of test substance from the systemic
circulation is the urine. Though, it is expected that test substance is
only ionized to a small extent at the pH of urine, given its high pKa
value (9.3) which doesn’t favour urinary excretion. However, conjugated
metabolites such as glucuronides and sulphates from Phase II
biotransformation reactions are generally excreted in the urine. Most of
them will have been filtered out from the blood by the kidneys, though a
small amount can enter the urine directly by passive diffusion. Another
route of excretion of conjugated derivatives (such as glucuronides) is
the bile. The excretion via the bile is highly influenced by hepatic
function since metabolites formed in the liver may be excreted directly
into the bile without entering the bloodstream. Products in the bile
pass through the intestine before excretion in the faeces and can thus
undergo enterohepatic recycling which will prolong their half-life.
Furthermore, the test substance can be excreted in the saliva (where in
can be swallowed again) or in the sweat since it is non-ionized and
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again