Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Based on physicochemical properties, no potential for bioaccumulation is to be expected.
Significant absorption of the substance from the gastro-intestinal tract is to be expected. For risk assessment purposes the oral absorption of the substance is set at 100% as a worst case assumption.
In the absence of experimental data, the inhalation and dermal absorption of the substance are set to 100% as a worst case assumption.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Data from in vitro or in vivo studies, which were designed to identify the toxicokinetic properties of Amphopropionates C12-18, are not available. Therefore, for the assessment of the toxicokinetic behaviour of Amphopropionates C12-18 all available relevant physical-chemical data of the substance were considered.

 

Table 1: Physical-chemical information that was considered for the toxicokinetic expert statement:

Parameter

Value used for CSR

Molecular Weight

ca. 380 g/mol (C12) – ca. 440 g/mol (C18)

Melting Point

No melting point could be determined due to decomposition

Boiling Point

No boiling point could be determined due to decomposition

Vapour Pressure

8.9E-27 hPa at 25°C (calculation)

Partition coefficient n-octanol/water (log Kow)

log Kow 3.43 (weighted mean)

Water solubility

at least 400 g/L

Surface tension

30.48 mN/m at 20°C and 1g/L

pKa

3.6±0.4, 7.4±0.4, 14.3±0.5 and 15.4±0.5 at 25°C (Amphopropionate C12)

Particle size

Amphopropionates C12-18 is manufactured and used only in water-based solutions

 

Oral absorption

The high water solubility of Amphopropionates C12-18 indicates that uptake after oral administration can take place through passive diffusion. However as the substance is highly water soluble (at least 400 g/L), this absorption will be limited by the rate at which the substance partitions out of the

gastrointestinal fluid. The substance is not considered to be highly lipophilic (weighted mean log Kow = 3.43) thus not further influencing the absorption via passive diffusion. The molecular weight (380 g/mol (C12) – 440 g/mol (C18)) below 500 is favourable for absorption. The presence of ionisable groups however will impair the absorption as ionised substances do not easily pass the gastro-intestinal wall. The calculations show that there is no pH at which all ionisable groups are in their non-ionised form.

Based on the physical and chemical properties, significant absorption of the substance from the gastro-intestinal tract is to be expected. For risk assessment purposes the oral absorption of the substance is set at 100% as a worst case assumption.

 

Respiratory absorption

The boiling point could not be determined, but decomposition starts at 190°C. As the substance is ionic/amphoteric, the vapour pressure of the pure substance is expected to be extremely low (8.9E-27 hPa at 25°C based on calculation). Therefore substance evaporation and uptake by inhalation as vapour is unlikely. The uptake after direct inhalation of substance dust particles is also very unlikely since the substance is produced and used only as an aqueous solution.

If Amphopropionates C12-18 reaches the tracheobronchial region, absorption through aqueous pores will be limited, taking the molecular weight of > 200 g/mol into account. However, the high water solubility of Amphopropionates C12-18 is favourable for dissolution of the substance in the mucus lining of the respiratory tract. In addition, based on the presence of hydrophobic and hydrophilic parts and a moderate log Kow Amphopropionates C12-18 has the potential of crossing the alveolar and capillary membranes by passive diffusion.

Based on its physical and chemical properties, it is likely that Amphopropionates C12-18 will be absorbed after inhalation via the lungs, although the extent cannot clearly be predicted. For risk assessment purposes the inhalation absorption of the substance is therefore set at 100% as a worst case assumption.

 

Dermal Absorption

As Amphopropionates C12-18 is a liquid with a low surface tension, it has the potential to partition from the stratum corneum into the epidermis, although the high water solubility might impair this process.As the substance has been identified as a skin sensitizer some uptake must have occurred although the high EC3 value of 30.6% indicates that it may only have been a small fraction of the applied dose. Due to the complexity of the UVCB substance a realistic log Kow value could not be determined experimentally. However, the moderate lipophilic character of the surfactant constituents with various lengths of a lipohilic alkyl chains may indicate that the transfer between the stratum corneum and the epidermis could occur for some of the constituents.

As a first approach, based on the molecular weight (between 359 and 443 g/mol for the different forms of the major constituent), the criteria for 10% dermal absorption as given in the Endpoint specific guidance Chapter R.7.12 (MW > 500 and log Kow < -1 or > 4) are not met. However, high water solubility and ionization state are expected to influence significantly the dermal absorption potential.

Nevertheless, in the absence of other data, a dermal absorption is set to 100% as worst case assumption for chemical safety assessment.

 

Distribution, Metabolism, Elimination

Once absorbed, distribution of the substance throughout the body is expected based on its relatively low molecular weight. Based on its relatively hydrophilic character, extracellular concentration is expected to be higher than intracellular concentration. Absorbed Amphopropionates C12-18 might undergo conjugation. Further conclusions on metabolism and excretion are difficult to be drawn based on the available data. It is expected that excretion will be mainly via urine (low molecular weight and high water solubility) but conjugation might shift it to excretion via bile.

 

Bioaccumulation

Based on a log Kow of 3.43 (weighted mean) and a calculated BCF of 70.79 L/kg for the C8 and C18 chains the substance is unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace.