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Description of key information

Experimental toxicokinetic studies are not available for Amphopropionate C8. The log Kow of 1.1 (weighted mean) and the molecular weight of 302.42 g/mol are suggestive of oral absorption from gastro-intestinal tract, by dermal route or from the lungs. It is generally thought that ionised substances do not readily diffuse across biological membranes. However, due to the lack of experimental data, 50% absorption by the dermal an oral route and 100% by inhalation is assumed as worst case default for chemical safety assessment. Based on physicochemical properties, no potential for bioaccumulation is to be expected.

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 Amphopropionate C8, are not available. Therefore, for the assessment of the toxicokinetic behaviour of Amphopropionate C8 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

302.42 g/mol

Melting Point

no melting point identified,decomposition starting at 150 °C

Boiling Point

no boiling point identified,decomposition starting at 150 °C

Vapour Pressure

<1.47E-03 Pa at 20°C

Partition coefficient n-octanol/water (log Kow)

1.1 (weighted mean)

Water solubility

>/=1 kg/L at 20.5°C

Surface tension

38.2 mN/m at 20°C and 1.11 g/L

 

Oral absorption

The high water solubility of Amphopropionate C8 indicates that uptake after oral administration can take place through passive diffusion. However as the substance is highly water soluble (>/= 1000 g/L), this absorption will be limited by the rate at which the substance partitions out of the gastrointestinal fluid. The molecular weight (302.42 g/mol) 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 50% by default.

 

Inhalation absorption

The boiling point could not be determined, but decomposition starts at 150°C. As the substance is ionic/amphoteric, the vapour pressure of the substance is low (<1.47E-03 Pa at 20°C). 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 Amphopropionate C8 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 Amphopropionate C8 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 Amphopropionate C8 has the potential of crossing the alveolar and capillary membranes by passive diffusion.

Based on its physical and chemical properties, it is likely that Amphopropionate C8 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% by default.

 

Dermal Absorption

As Amphopropionate C8 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.

Based on the molecular weight and log Kow, 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 50% by default 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 Amphopropionate C8 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 1.1 (weighted mean), the substance is unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace.