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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Link to relevant study record(s)

Description of key information

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.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

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.


Oral/GI absorption:

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 diffusion.

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 study; Klimisch 1) performed according to the OECD 433 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 males and females 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, estrous cycling, mating, fertility and natural delivery. There were also no adverse effects on the 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 development toxicity study (Renaut, 2016; key study, Klimisch 1) 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 rabbit.

In a second prenatal development toxicity study (Noble ,2021; key study, Klimisch 1), Sprague Dawley rats were dosed at 0, 40, 125, 350 mg/kg/day for 20 days.  A dose-dependent decrease in mean T3 and T4 concentrations was observed in all groups of treated maternal females, but this change was considered inconclusive as T3 and T4 values were within the Historical Control Data range. At 350 mg/kg/day, maternal body weight gain and food intake were reduced with a slight body weight loss observed when adjusted for the contribution of the gravid uterine weight. A decrease in liver weights was also observed at 350 mg/kg/day. Other effects on body weight, body weight performance, and food intake were noted at 125 mg/kg/day. The extent of the effects on body weight gain and food intake, body weight performance, and liver weight observed at 350 and 125 mg/kg/day were not considered adverse. Similar to the observations in the prenatal development toxicity study in rabbits (see above), there was no adverse effect of treatment on embryo-fetal survival or development at any dose level, when the test substance is administered during organogenesis in the rats. The NOAEL for maternal toxicity and embryo-fetal survival and development was concluded to be 350 mg/kg/day.

Based on the high water solubility and repeated dose oral toxicity studies, the oral absorption factor for the test substance is set to 50%.


Respiratory absorption:

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%.

Dermal absorption:

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. 

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 blood.

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 corneum.


Based on the structure, the 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 the test substance from the systemic circulation is the urine. Though, it is expected that the 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 it can be swallowed again) or in the sweat since it is non-ionized and lipid soluble.