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Description of key information

As Jeffamine RFD 270 is an UVCB substance, not all physico-chemical properties are clearly defined but reflect the properties of a group of constituents. The below toxicokinetic assessment is thus indicative only as single constituents within the UVCB might have significant different physico-chemical properties.
For Jeffamine RFD 270, no experimental data are available on toxicokinetics. Therefore, a qualitative assessment of the absorption, distribution/accumulation, metabolism and elimination is performed on the basis of the physico-chemical properties of the substance (as indicated in the ECHA specific Guidance 7.c for the implementation of REACH). In addition, toxicological data on the substance are used to support this assessment.

Key value for chemical safety assessment

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

Additional information

Jeffamine RFD 270 is a UVCB with an average molecular weight of about 270. It is miscible with water in all proportions (water solubility of 100 g/L) with a partition coefficient log P in the range of 1.59 to 3.48 (using the measured peak area for each calculated partition coefficient, the weighted mean Log Kow for the test substance is 2.17) and a low vapour pressure (17 Pa at 20°C). Decomposition of the substance occurred at 137°C.

Jeffamine RFD 270 is an aliphatic amine containing both rigid (cycloaliphatic) and flexible (poyetheramine) segments in the same molecule. The dissociation constant (pKa) was determined to be 10.46 using the titration method.



Oral/Gastro-intestinal (GI) absorption

Mechanisms by which substances can be absorbed in the gastro-intestinal (GI) tract include the passage of small water-soluble molecules (molecular weight up to around 500) through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. As Jeffamine RFD 270 is miscible with water and has a mean molecular weight of 270 (within a range of 200 and 490 and a typical value of 289), this passive diffusion will be the predominant mechanism for absorption in the GI tract. In addition, moderate octanol/water partition coefficient (log P) values (between -1 and 4) are considered to be favorable for absorption by passive diffusion; as logP values between 1.59 and 3.48 were obtained, uptake of several constituents in Jeffamine RFD 270 might be possible. Ionized substances do not readily diffuse across biological membranes which makes the pKa is an important parameter to indicate ionization at a GI relevant pH. For UVCB substances, the pKa can however not easily be defined. Only one pKa value of an individual component in Jeffamine RFD 270 was determined (10.46) and based on this value it could be concluded that some ionization (amine groups) at the biologically relevant pH range might occur, thus hampering the uptake of these individual components. In addition, once absorbed, substances will go to the liver before entering the systemic circulation – first pass metabolism may then limit the systemic bioavailability of the parent compound. Although no information is available for Jeffamine RFD 270 related to the first pass metabolism, this could limit the systemic bioavailability.As a risk mitigation, taking into account all of the the above information, an oral absorption factor of 50% will be derived for Jeffamine RFD 270. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor. As signs of systemic toxicity have been observed in the acute and combined repeated dose/reproductive toxicity screening test via the oral route, absorption has occurred.


Respiratory absorption

Given the fact that the substance decomposes at 137 °C and the vapour pressure (Vp) of 17 Pa at 20°C, Jeffamine RFD 270 is not considered a highly volatile substance (Vp > 25 KPa or boiling point < 50°C). It is therefore unlikely that the substance is inhaled as a vapour at ambient temperature.

Jeffamine RFD 270 being a water soluble liquid will readily dissolve into the mucus lining the respiratory tract. Lipophilic substances (log P > 0) would then have the potential to be absorbed directly across the respiratory tract epithelium by passive diffusion. Hydrophilic substances might be absorbed through aqueous pores (for substances with molecular weights below around 200) or to be retained in the mucus and transported out of the respiratory tract, subsequently swallowed and becoming available for oral absorption. In view of its moderate log Pow values Jeffamine RFD 270 will mainly be absorbed directly across the respiratory tract epithelium. For risk assessment purposes the inhalation absorption of Jeffamine RFD 270 is set at 100%.


Dermal absorption

Jeffamine RFD 270 is a water soluble liquid and as such it is readily available for absorption through the skin. As Jeffamine RFD 270 is miscible with water and has a moderate log P (in the range of 1.59 to 3.48) it may contain components that can cross the lipid rich environment of the stratum corneum. With a molecular mass below 500 and logP in the range (-1, 4), the data meet the criteria for 100% dermal absorption (as given in the ECHA specific Guidance 7.c for the implementation of REACH). However, it is generally acknowledged that dermal absorption will not be higher compared to oral absorption; as a result, the dermal absorption factor for Jeffamine RFD 270 is set to 50%. The results of the available toxicity studies using the dermal route do not provide reason to deviate from this factor.

In addition, the substance is observed to be corrosive to the skin as observed in a primary dermal irritation study in rabbits (performed according to OECD Guideline 404).



In general, the smaller the molecule, the wider the distribution. Small water-soluble molecules, like Jeffamine RFD 270, will diffuse through aqueous channels and pores.

Based on the high water solubility and low molecular weight it could be expected that the substance will distribute widely through the body after absorption. However, as the substance contains ionizable amine groups its diffusion across membranes could limit its distribution.



In view of the moderate log Kow and the high water solubility, Jeffamine RFD 270 is not expected to accumulate in the body. Substances with log P values of 3 or less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace.


Metabolism and Excretion

Jeffamine RFD 270 is expected to undergo Phase I and Phase II metabolic reactions. Based on the high water solubility and relatively low molecular weights, Jeffamine RFD 270 and its conjugation products are expected to be mainly excreted in the urine.