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Description of key information

For the test substance, no experimental data is available on toxicokinetics. Therefore, a qualitative assessment of the absorption, distribution/accumulation, metabolism and elimination is performed based on the physico-chemical properties of the substance.

Key value for chemical safety assessment

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

Additional information

1-(bis(3-(dimethylamino)propyl)amino)-2-propanol(CAS 67151-63-7; hereafter named 'the test substance') is a clear colourless liquid with an ammoniacal odour at ambient conditions (Huntsman, 2012). The test substance has a high water solubility (> 100 g/L; miscible) (Younis, 2012) with a moderate log Kow (0.587 at 22 °C; Tarran, 2012) and a low vapour pressure (1.7 Pa at 20°C; Younis, 2012). Its pKa values are 9.6 (pKa1) and 8.9 (pKa2) at 20°C. The test substance surface tension is 65.3 mN/m at test concentration of 1g/L and at 20°C and therefore the substance doesn’t have surface active properties. The substance is found to be corrosive to skin and eyes but not skin sensitising.

No toxicokinetic data (animal or human studies) are available on this substance. The information present in this document is mostly based on physico-chemical parameters which allow a qualitative assessment of the toxicokinetic behaviour of the test substance rather than a quantitative assessment.



Oral/Gastro Intestinal absorption

Following its high water solubility, the test substance will readily dissolve into the gastrointestinal (GI) fluids and subsequently pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Based on the moderate log Kow, absorption by passive diffusion will be favoured. Although its molecular weight is 245 g/mole, passive diffusion is not considered to be significantly hindered.

It is generally thought that ionised substances do not readily diffuse across biological membranes. The pKa of the test substance suggest that this substance will be predominantly in its ionised form in the GI tract and hence diffusion can be hampered in some extent.

The test substance is corrosive to the skin. It is likely that absorption at GI level will be favored in some extent due to local effects at the mucosae.

In an acute oral toxicity study (Mallory, 1983), the test substance was tested via gavage at 800, 1000, 1250, 1600 and 2000 mg/kg male/female Sprague-Dawley rats. The acute oral LD50 for male and female rats was determined to be 1344 mg/kg. Observed effects and findings can be linked to the corrosive properties of the substance (local effects) rather than systemic effects. Therefore it cannot clearly concluded that the substances was absorbed.

In a combined repeated dose toxicity with reproductive/developmental screening performed with the test substance, male and female rats were exposed to 0, 25, 100 and 250 mg/kg bw/d via oral gavage according to OECD 422 (Huntsman, 2013). Animals receiving 100 and 250 mg/kg bw/d exhibited macroscopic and microscopic changes in liver and gastric mucosa. Similar effects were observed in unmated satellite animals dosed at 250 mg/kg bw/day. At 25 mg/kg bw/day, microscopic findings were limited to the gastric mucosa in one animal and the liver in another animal. Under the experimental conditions of the study, the NOAEL of the test substance was < 25 mg/kg/day for males and females. The NOAEL for embryo-fetal toxicity was 100 mg/kg bw/day. These results support the assumption for oral absorption of the test substance.

In addition, a 90-day repeated dose toxicity study is performed in rats. Male and female animals were dosed via oral gavage at dose levels of 0, 10, 25 or 75 mg/kg/day, according to OECD guideline 408. The NOEL (NOAEL) for oral repeated dose toxicity is determined at 10 mg/kg/day (males) and 25 mg/kg/day (females). No toxicological relevant effect was seen in mortality, clinical signs, water consumption, ophthalmology, hematology, functional performance, sensory activity. There was an overall reduction in body weight gain in males and females at 75 mg/kg/d (accompanied by lower food conversion efficiency), and in males dosed at 25 mg/kg/d. Males and females at 75 mg/kg/d showed a significant increase in clinical chemistry parameters like total protein, aspartate aminotransferase and alanine aminotransferase. Females treated at 75 mg/kg/d showed a significant increase in liver weight. Toxicologically relevant findings in liver and kidney were observed.

The primary observations in the study were 1) vacuolation in liver and spleen of males and females treated at 75 mg/kg bw/day and 2)centrilobular single-cell necrosis (Grade: minimal) in the liver of males and females at 75 mg/kg/day and males at 25 mg/kg/day. Regardingvacuolation in the liver and spleen, the vacuoles observed are considered transient and non-adverse based on scientific peer-reviewed literature regarding weakly basic aliphatic amines and supporting evidence from similar Huntsman compounds within the same chemical family of aliphatic amines. Regarding necrosis observed in the liver, the observation was described as “Centrilobular single-cell necrosis at a minimal level”. This description does not meet the criteria of “multi-focal or diffuse”as stated in theECHA Guidance on the Application of the CLP Criteria for consideration of STOT RE classification. Therefore, these effects do not, by themselves or together, indicate “significant” toxicity in relation to Specific Target Organ Toxicity - Repeated Exposure (STOT RE) classification in GHS. Since these observations in the OECD 408 study are considered not to support STOT RE classification, the substance is not classified.

The oral absorption factor is set to 50%, based on the anticipated hampered diffusion of the test substance as an ionized substance. The results of the toxicity studies do not provide reasons to deviate from this proposed value.

Respiratory absorption

Given the vapour pressure of 1.7 Pa, the test substance is a low volatile substance and the availability for inhalation as a vapour is limited.

Once in the respiratory tract, the test substance would deposit on the walls of the airways. Deposited substances may be absorbed directly from the respiratory tract or, through the action of clearance mechanisms, may be transported out of the respiratory tract and swallowed. In that last case the substance needs to be considered as contributing to the oral/GI absorption rather than to the inhalation rate.

Although absorption directly across the respiratory tract epithelium by passive diffusion is favoured in view of the moderate log Kow value, the test substance is a very water-soluble substance and, as suggested by its pKas values, predominantly in its ionised form at physiological pH. Based on this ionization diffusion can be hampered in some extent.

Based on the above considerations, the inhalatory absorption factor is set to 100%.


Dermal absorption

In view of its high water solubility and moderate log Kow, penetration into the lipid-rich stratum corneum and hence dermal absorption through deeper epidermis layers might be limited although its physical form (liquid) favours dermal absorption.

In an acute dermal toxicity study (Mallory, 1983), New Zealand White male/female rabbits were exposed to 2500, 3200, 4000 and 5000 mg test substance/kg bw. After 14 days of observation, an LD50 value of 3570 mg/kg bw was derived for the test substance. Signs observed included necrosis and edema of the application sites. Necropsy revealed hemorrhages in the muscle layers at the application sites and dark fluid-filled bladders. These observations may indicate some absorption of the test substance although clear differentiation between local effects or systemic effects is not without difficulty due to the corrosive properties of the test substance.

The substance is found to be corrosive to the skin but not a skin sensitiser.

Generally default values of 10% and 100% are used for dermal absorption, based on molecular weight and log Kow value (ECHA guidance on IR&CSA, R.7c). The dermal absorption factor is therefore set to 100% (default), based on a molecular weight < 500 and a log Kow in the range of -1 to 4. However, it is also generally acknowledged that dermal absorption will not be higher compared to oral absorption; as a result, the dermal absorption factor for the test substance is set to 50%. The results of the available toxicity studies using the dermal route do not provide reasons to deviate from this proposed value.


The high water solubility, moderate log Kow and low molecular weight predict that the substance will distribute widely through the body.


In view of the moderate log Kow and the high water solubility, the test substance will not easily accumulate in the body (lung, adipose tissue, stratum corneum).


Once absorbed, the test substance might undergo phase I biotransformation followed by conjugation reactions (phase II).


Given the high water solubility and low molecular weight (amplified by the expected cleavage of the ether bond), the test substance and its metabolites will be mainly excreted via the urine.