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Endpoint summary

Description of key information

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 50% (oral), 100% (inhalation) and 10% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

After exposure, a substance can enter the body via the gastrointestinal tract, the lungs and the skin. Since different parameters are relevant to estimate adsorption depending on the route of exposure, the three routes will be addressed individually.
In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration1. Pergafast 425 has a relatively high molecular weight (513.6), which will limit passage through biological membranes. Pergafast 425 shows low water solubility of 0.00474 mg/L and a high partition coefficient (Log Pow: 4.3) which makes the substance not favorable for absorption by the GI-tract via passive diffusion.
However, the substance could be taken up via micellular solubilization by bile salts and uptake via the lymphatic system or transport via pinocytosis. Based on these physicochemical properties of Pergafast 425, a moderate uptake by the GI-tract is anticipated, and for risk assessment purposes the oral absorption of Pergafast 425 is set at 50%. The results of the toxicity studies do not provide reasons to deviate from the proposed oral absorption.
For inhaled substances the process of deposition of the substance on the surface of the respiratory tract and the actual absorption have to be differentiated. Pergafast 425 has a low vapour pressure (20°C: < 8.4 x 10-7 Pa) and was found to decompose before a boiling point was reached, which indicates that the substance is not very volatile and exposure to the substance as a vapour is unlikely. Pergafast 425 is a powder. Since 90% of the particles is smaller than 55.0 μM, the largest part of the substance has the potential to be inhaled and may reach the thoric region. Furthermore, 50% is smaller than 12.9 μM, which means that at least 50% of the substance may reach the alveolar region of the respiratory tract. If these particles reach these regions, Pergafast 425 is likely to be taken up via micellular solubilization.
Therefore, it is concluded that for risk assessment purposes the inhalation absorption of Pergafast 425 is set at 100%.

As Pergafast 425 is a powder, uptake through the skin is unlikely to occur unless it is dissolved in a body fluid (sweat). Pergafast 425 is poorly soluble in water (below 1 mg/L), therefore is the partition from the stratum corneum into the epidermis is expected to be limited. Its ability to dissolve in lipids will favour uptake into stratum corneum. Its high molecular weight makes the substance not favourable for dermal uptake. According to the guidance2, a default value of 10% skin absorption is used when the molecular mass is above 500 and log Pow is outside the range [-1, 4]. Since the substance has a molecular weight of 513.6 and a log Pow of 4.3, it those meet both criteria and the dermal absorption of Pergafast 425 for risk assessment purposes is thus set at 10%. The dermal toxicity data do not provide reason to deviate from the proposed dermal absorption factor.
Generally, substances with a high log Pow value have long biological half-lives. Daily exposure to substances with a log Pow of around 4 or higher could result in a buildup of that substance within the body. Pergafast 425 showed a BCF below 100, which indicates a low bioaccumulation potential. Therefore, the bioaccumulation potential of Pergafast 425 is expected to be low.