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Description of key information

Key value for chemical safety assessment

Additional information

Inhalation absorption

The moderate water solubility (1.95 mg/L) and lipophilicity (log Pow= 3.68/3.79) indicate that the substance (stable for hydrolysis) may easily be absorbed by the respiratory tract epithelium. Furthermore, clinical signs of systemic toxicity observed (hunched posture, piloerection) in the acute oral toxicity study indicate that absorption of the substance is also likely to occur if it is inhaled. However, the low volatility indicates a marginal potential for inhalation exposure to vapours. The potential for inhalation absorption is addressed as follows:

 

The material was subjected to a test to determine the potential of the dust to be airborne (modified Heubach procedure (DIN 55992-1:2006)), yielding an MMAD of26.9 µm with a GSD of 1.69. Based on this information, the fractional deposition in the respiratory tract was calculated with the MPPD model (using predominantly default settings), as presented in Appendix I.

The results of this calculation can be briefly summarised as follows: the deposition frequency in the entire respiratory tract is only 51%, corresponding to the large particle size of approx. 27 µm which renders the particles only partly inhalable. The bulk of this material (0.508 regional vs. 0.5097 total, i.e. 99.7%) is deposited in the extra-thoracic region, and will therefore be translocated to the GI tract within a few minutes; only a minimal amount (~0.2%) of the material present in air will be deposited in the tracheobronchial region, also cleared to the GI tract by mucociliary flow. Merely 0.08% in of the material present in air will be deposited in the alveolar region. Thus, only minimal amounts penetrate to the deep lung tissue, whereas the overwhelming bulk of inhaled material is cleared rapidly to the GI tract, where oral bioavailability will determine its uptake.

 

For current lack of other information on oral bioavailability and in light of the physicochemical characteristics, it may be assume as a worst-case that the absorption factor both from the alveolar region and the GI tract is 100%, thus yielding an overall inhalation absorption factor of 51% based on particle-size dependant deposition in the lung.

 

The substance is a solid at 20°C and 101.3 kPa and not sufficiently volatile for inhalation exposure as vapour.

 

Oralabsorption

From the physico-chemical data (water solubility (1.95 mg/l), partition coefficient logPow of 3.68 (isomer 1) / 3.79 (isomer 2) and molecular weight (308 g/mol)) the substance can be assumed to have a probably moderate oral bioavailability. However, assumed on a worst case basis, the absorption factor from the GI tract is assessed to be about 100 %.

 

Dermalabsorption

SymHelios 1031 is intended to be used at a low application rate (≤ 1%) as a topical in cosmetic preparations to prevent long term sun damage to the skin.

Due to the slight water solubility (1.95 mg/L) and lipophilicity (log Pow = 3.68/3.79), quantitatively relevant dermal absorption cannot be ruled out. Hence, QSAR calculation was initiated which results in a permeability coefficient (Kp) for SymHelios 1031 of ~0.01 cm/hr (see appendix II and III).

However, due to the (i) absence of measured data on dermal absorption, (ii) in view of the current guidance which suggests the assignment of either 10% or 100% default dermal absorption rates and (iii) since SymHelios 1031 is only slightly water soluble (1.95 mg/L) and lipophilic (log Pow = 3.68/3.79), 100% dermal absorption is assessed for hazard assessment.

Metabolism and Excretion

No definitive conclusions can be drawn on the likely metabolism or elimination of the substance Based on available data (e.g. sub-chronic oral toxicity data: liver weight increase, mild diffuse hepatocellular hypertrophy), metabolism by the liver can be considered to occur and therefore urinary excretion is likely to be the favourable route of excretion forSymHelios 1031 derivates. Based on the lipophilic character it is also predicted that metabolites of SymHelios 1031 would likely be eliminated in breast milk.