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Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Oral absorption

The test item has a molecular weight of 184.3 g/mol, which is below the value of 500 g/mole above which reduced absorption is anticipated. Based on the slight water solubility and the highly lipophilic nature of the substance, oral absorption may be limited by the low ability to dissolve in GI fluids. Hence, the test item is expected to be available in soluble form at the mucosal surface.

 

Furthermore, the calculated pka of the substance is 16. Absorption for basic substances is favoured at pHs above the pka. Hence, oral absorption in expected to be low.

 

In the acute oral toxicity study performed with the test item, mild signs of local gastro-intestinal toxicity (e.g., diarrhoea) were observed in two animals during the day of dosing. In the absence of any signs for systemic toxicity such as body weight loss, oral absorption is considered to be low.

 

In contrast, administration of the substance to pregnant animals revealed effects on gestation length, pre-coital time, post-implantation loss, number of viable pubs, mean litter size and pup body weight. Such observations in absence of further effects on the dams, indicate some absorption following oral administration.

 

Based on the information given above, an oral absorption factor of 100 % is suggested, which is considered a conservative estimate.

Dermal absorption:

Quantitatively relevant dermal absorption (low to moderate) of the substance cannot be completely ruled out based on water solubility of the substance (18 mg/L at 20°C/pH 7.4). However, since the octanol/water partition coefficient is high (log Pow 5.3), the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis. Nevertheless, uptake into the stratum corneum is expected to be high.

 

Furthermore, the lack of toxicity in the acute dermal toxicity study up to a concentration of 2000 mg/kg bw may be seen as an indication that this is not a preferential route of entry into the body. Nevertheless, it is noted, that despite the fully valid LLNA skin sensitisation study (OECD 429; GLP, 2008) results in a negative outcome (SI <3), a dose response relationship was recorded (test concentration 5, 10, 25 % v/v), indicating some penetration of the epidermis.

 

Considering the above and that no study on dermal absorption for the substance under consideration is available, a default value of 100% in accordance with the ECHA guidance on information requirements and chemical safety assessment, chapter R. 7c: endpoint specific guidance, version 2.0, November 2014 will be used for risk assessment, which is considered a conservative estimate.

Inhalation absorption

No experimental data are available. The calculation of the Henry`s law constant on the basis of the experimental determination of water solubility and vapour pressure including the molecular weight, indicates that the substance is moderately volatile (2.87 Pa m³/mol at 25°C).

The test item is only slightly soluble in water (18 mg/L (20°C/pH 7.4) and has a moderate vapour pressure (0.14 Pa at 20 °C; boiling point 267.5 °C), hence inhalation to vapours is considered to be low. Therefore, the test material can safely be assumed to have a low potential for human inhalation hazard during handling or application.

 

However, based on the log Pow of > 4 (5.3) and the molecular weight < 200 g/mole (184.3 g/mole) The test item might be absorbed through aqueous pores (Guidance on information requirements and chemical safety assessment-chapter R.7c: Endpoint specific guidance, November 2014).

 

Based on the lack of further information on bioavailability via inhalation and in light of the physicochemicalcharacteristics, it may be assume as a worst-case that the absorption factor via inhalation is 100 %.

Distribution:

The test item shows a slight water solubility of 18 mg/L and a high log Pow of 5.3, which is indicative for an elevated ability of the substance to cross cell membranes by diffusion (particularly in fatty tissues). The calculated logBCF (3.164) does not indicate a potential for bioaccumulation. Based on the small molecular weight, the slight water solubility and no signs of protein binding capacity (QSAR Toolbox evaluation, Database version: 3.8.3/3.1.2), a wider systemic distribution is anticipated.

Metabolism and elimination:

The test item is a primary alcohol with a cyclohexyl groupfor which one metabolic reaction pathway was identified: multi-step oxidation of the terminal hydroxyl group and breakup into a cyclohexanoic acid and propanoic acid (see attachment: Pathway prediction results). The reactions are catalysed by oxygenases (such as the cytochrome P450 monooxygenase system), which predominantly occur in the liver. The resulting phase 1 metabolites are sufficiently polar, allowing renal elimination.

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