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Description of key information

Short description of key information on bioaccumulation potential result:
POPDA is a corrosive substance; therefore, it is difficult to test at high levels.

Toxicokinetic information is not available for this substance. However, based on physical/chemical properties, POPDA 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 vapor 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) 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). POPDA is a base with a dissociation constant (pKa) of 9.3 at 24°C. The product is also corrosive to skin (category 1C).

POPDA 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, POPDA 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 of POPDA.


Oral/GI absorption:

POPDA 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) 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 necropsy. The no observable effect level (NOEL) and no 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 %).

Furthermore, 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 no adverse effect level (NOAEL) of POPDA 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 inappetance 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 POPDA is administered during organogenesis in the rabbit.

Based on the high water solubility and repeated dose oral toxicity study, the oral absorption factor for POPDA is set to50%.


Respiratory absorption:

Given the low vapour pressure of 0.9 hPa (at 20°C), POPDA is not 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>0), POPDA 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 POPDA, but an acute respiratory study (Bio/dynamics, 1979) 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.

Based on these conclusions, the respiratory absorption factor is set to100%.

Dermal absorption:

Since POPDA 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, POPDA 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 (ertythema, 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 kindneys 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 no observable adverse effect level (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 POPDA. 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; there are indications that dermal absorption is much lower than oral absorption.

Based on the physicochemical parameters and repeated dose dermal toxicity studies, the dermal absorption factor is set to10%


The high water solubility and moderate molecular weight predict that POPDA will probably distribute through the body due to diffusion through aqueous channels and pores. POPDA is also lipophilic (log Pow>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.


POPDA 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 < 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 POPDA, no (or little) accumulation is expected within the lungs, bones or stratum corneum.


Based on the structure, POPDA 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 POPDA from the systemic circulation is the urine. Though, it is expected that POPDA 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 bood 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, POPDA can be excreted in the saliva (where in can be swallowed again) or in the sweat since it is non-ionized and lipid soluble.