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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

As the substance is an UVCB, not all physico-chemical properties are clearly defined but reflect the properties of a group of substances. The toxicokinetic assessment is thus to be seen as indicative only, as single substances within the UVCB might have different physico-chemical properties. For this substance, 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. 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 (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
50

Additional information

The substance is an UVCB with a molecular weight in the range of 312 and 537. It is completely soluble in water (water solubility of 2054.232 g/L) with a partition coefficient log P of -3.738 and a low vapour pressure (37.5 Pa at 20°C). Surface tension is 72.4 mN/m. Decomposition of the substance occurred at 123°C in a melting point study according to EU method A.1 (Younis, 2014). The substance is a yellow-orange solid containing amic acid and TEPA salt compounds. The substance is marketed as a 50% solution. The dissociation constant (pKa) could not be determined. 

Absorption

Oral/Gastro-intestinal (GI) absorption

The substance has a molecular weight within the range of 312 to 537 which favours for absorption. The substance is completely soluble in water and will readily dissolve in gastrointestinal fluids.

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 200) through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. As the range of the molecular weight of the substance is higher than 200, this mechanism is not likely to occur.

In addition, moderate octanol/water partition coefficient (log P) values (between -1 and 4) are favorable for absorption by passive diffusion. As a log P value of -3.738 was obtained, the substance is not favorable for passive diffusion.

Ionized substances do not readily diffuse across biological membranes and the pKa is an important parameter to indicate ionization at a GI relevant pH. For UVCB substances this parameter can however not easily be determined. For the substance, the dissociation constants could not be determined.

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 the substance related to the first pass metabolism, this could limit the systemic bioavailability.

As no signs of systemic toxicity have been observed in the acute and combined repeated dose/reproductive toxicity screening test via the oral route, it is considered that the substance has a low toxicity. It is assumed that there was a low bioavailability due to low absorption. Taking into account the above information, a worst case oral absorption factor of 50% has been derived for the substance. 

Respiratory absorption

Given the substance decomposes at 123 °C and the vapour pressure (Vp) of 37.5 Pa at 20°C, the substance is not considered a highly volatile substance (Vp > 25 kPa or boiling point < 50°C) and therefore it is unlikely that the substance is inhaled as a vapour at ambient temperature.

The substance 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 log P value of -3.738 and a molecular weight within the range of 312 and 537, the substance is unlikely to directly absorb across the respiratory tract epithelium. As no signs of systemic toxicity have not been observed in the acute and combined repeated dose/reproductive toxicity screening test via the oral route, it is considered that the substance has a low toxicity. It is assumed there was a low bioavailability due to low absorption. For risk assessment purposes, and given the fact that vapour pressure is low, the inhalation absorption of the substance is set at 50%. 

Dermal absorption

The substance is readily available for absorption through the skin. As the substance is very soluble in water and has a log P of -3.738 it is probably too hydrophilic to cross the lipid rich environment of the stratum corneum. The substance has a surface tension of 72.4 mN/m at a test concentration of 1.01 g/L and at 20 °C and is not a surface active substance.

Therefore, dermal absorption of the substance is likely to be low. In addition, the substance is observed to be non-irritant to the skin. The substance, however, was observed to be a skin sensitizer, hence, some uptake must have occurred although it may only have been a small fraction of the applied dose. For risk assessment purposes, the dermal absorption of the substance is set at 50%. 

Distribution

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

Due to its molecular weight higher than 200, the substance is not likely to distribute widely through the body, although the substance has a high water solubility. The rate at which very hydrophilic molecules diffuse across membranes could limit their distribution.

As the substance is hydrophilic (log P = -3.738), the substance is not likely to distribute into cells through the membrane. 

Accumulation

In view of the low log P and the high water solubility, the substance 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

A preliminary assessment of the eight main constituents indicated that constituents 1 to 4 contained at least one potentially hydrolysable functional group; whereas, constituents 5 to 8 did not and therefore would be stable towards hydrolysis. The hydrolytic stability of constituents 1 to 4 was estimated using the specialist estimation software HYDROWIN v2.00. The test substance was considered stable towards hydrolysis at pH 4, 7 and 9.

As the substance is expected to have a low bioavailability due to low absorption, it is expected that a majority of the orally administered compound will be excreted via the faeces.

Based on the high water solubility potential bioavailable substance and its conjugates is expected to be mainly excreted in the urine.

In addition, ionised substances are expected to be eliminated by urine.