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Description of key information

No experimental toxico-kinetic data are available for assessing adsorption, distribution, metabolisation and excretion of the substance. Based on effects seen in the human health toxicity studies and physico-chemical parameters Salicynalva is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption.

Key value for chemical safety assessment

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

Additional information


The test material Salicynalva (Cas no 3508-98-3) has an aromatic ring to which an alkyl chain with a nitrile group is attached. It is a clear colourless liquid with a molecular weight of 173 that does not preclude absorption. The test material will hydrolyse at pH 4, 7 and 9, 26, 15 and 5 days at 25oC, respectively. The substance has a low volatility of 6.4 Pa.


Oral:The results of the acute oral and the oral repeat dose toxicity of the Salicynalva show that the substance is being absorbed by the gastro-intestinal tract following oral administration, because adverse effects on rats were seen. The relatively low molecular weight and the moderate octanol/water partition coefficient (Log Kow 3.14) and water solubility 37.7 mg/l) would favour absorption through the gut. According to Martinez and Amidon (2002) the optimal log Kow for oral absorption falls within a range of 2-7. This shows that Salicynalva is likely to be absorbed orally and therefore the oral absorption is expected to be > 50%. 

Skin: Based on the physico-chemical characteristics of the substance, being a liquid, its molecular weight (173), log Kow (3.14) and water solubility (37.7), indicate that (some) dermal absorption is likely to occur. The optimal MW and log Kow for dermal absorption is < 100 and in the range of 1-4, respectively (ECHA guidance, 7.12, Table R.7.12-3). The MW of the substance is just outside optimal range and therefore the skin absorption is not expected to exceed 50%. This can also be seen in the 14-day dermal repeated exposure in which adaptive liver effects were seen at a highest dose of 1000 mg/kg bw, while similar effects were much more pronounced in the 28-day the oral gavage dose at 250 mg/kg bw.

Lungs: Absorption via the lungs is also indicated based on these physico-chemical properties. Though the inhalation exposure route is thought minor, because of its low volatility (6.4 Pa), the octanol/water partition coefficient (3.14), indicates that inhalation absorption is possible. The blood/air (BA) partition coefficient is another partition coefficient indicating lung absorption. Buist et al. (2012) have developed BA model for humans using the most important and readily available parameters:

Log P (BA) = 6.96 – 1.04 Log (6.4) – 0.533 (Log) Kow 3.14 – 0.00495 MW 173.

For the substance the B/A partition coefficient would result in:

Log P (BA) = 6.96 – 0.838 – 1.67 – 0.85 = 3.6

This means that Salicynalva has a tendency to go from air into the blood. It should, however, be noted that this regression line is only valid for substances which have a vapour pressure > 100 Pa. Despite the substance being somewhat out of the applicability domain and the exact BA may not be fully correct, it can be seen that the substance will be readily absorbed via the inhalation route and will be close to 100%.


The moderate water solubility of the test substance would limit distribution in the body via the water channels. The log Kow would suggest that the substance would pass through the biological cell membrane. Due to the expected log Kow and metabolisation the substance as such would not accumulate in the body fat.


There are no actual data on the metabolisation of Salicynalva. In the information below some theoretical metabolites using the rat liver simulator of the OECD Toolbox 3.0 are shown. Hydroxylation can be expected on the ring or at the end of the alkyl chain. Though not presented in the OECD Toolbox the alpha-carbon attached at the nitrile group is expected to show some reactivity because of the phenyl ring and the nitrile group may result in a somewhat reactive alpha-C atom according to DeVito (1996).

Fig. 1   The metabolisation pathway of the Salicynalva according to OECD Toolbox rat liver S9 simulator.



Effects seen in the kidney of the rats indicate that the primary route of excretion is through the urine. Any unabsorbed substance will be excreted via the faeces.


Salicynalva is expected to be readily absorbed, orally and via inhalation, based on the human toxicological information and physico-chemical parameters. The substance also is expected to be absorbed dermally based on the physic-chemical properties. The MW and the log Kow are higher than the favourable range for dermal absorption but significant absorption is likely.

The IGHRC (2006) document of the HSE and mentioned in the ECHA guidance Chapter 8 will be followed to derive the final absorption values for the risk characterisation.

Oral to dermal extrapolation

There are adequate data via the oral route and the critical toxic effect is related to systemic effects and therefore route to route extrapolation is applicable. The toxicity of the substance will be due to the parent compound but also to its metabolites. The overriding principle will be to avoid situations where the extrapolation of data would underestimate toxicity resulting from human exposure to a chemical by the route to route extrapolation. The substance is not expected to hydrolyse to a significant extent in the gut. The toxicity of the dermal route will not be underestimated because absorption will be slower and the compound will also pass the liver as can be observed in the 14 dermal toxicity test compared to the oral repeated dose toxicity tests. Therefore it will be assumed that the oral absorption will equal dermal absorption. Using the asymmetric handling of uncertainty the oral absorption will be considered 50% (though likely to be higher) and the dermal absorption will be considered also 50% (though likely to be lower).

Oral to inhalation extrapolation

Though the substance is not a volatile liquid the inhalation exposure will be considered. The substance is not a corrosive for skin and eye and the systemic effect will overrule the effects at the site of contact. In the absence of bioavailability data it is most precautionary that 100% of the inhaled vapour is bioavailable. For the oral absorption 50% has been used for route to route extrapolation to be precautionary for the dermal route. For inhalation absorption 100% will be used for route to route extrapolation, because this will be precautionary for the inhalation route.


Salicynalva is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route based on toxicity and physico-chemical data. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption.


Buist, H.E., Wit-Bos de, L., Bouwman, T., Vaes, W.H.J., 2012, Predicting blood:air partition coefficient using basis physico-chemical properties, Regul. Toxicol. Pharmacol., 62, 23-28. 

De Vito, S.J., 1996, Designing Safer Nitriles, Chapter 10, ACS Symposium Series, American Chemical Society, Washington D.C.

IGHRC, 2006, Guidelines on route to route extrapolation of toxicity data when assessing health risks of chemicals,[1].pdf

Martinez, M.N., And Amidon, G.L., 2002, Mechanistic approach to understanding the factors affecting drug absorption: a review of fundament, J. Clinical Pharmacol., 42, 620-643.