Reaction mass of undec-8-enal and undec-9-enal and undec-10-enal

Endpoint summary

Description of key information

Intreleven aldehyde is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route. The final absorption values derived for oral, dermal and inhalation are 50, 50 and 100% absorption. This information does not need to be used for route to route extrapolation because ‘no hazards are identified’ via the oral route and therefore no hazards are expected for the dermal and inhalation route. Intreleven aldehyde as such is lipophilic and may accumulate in the body fat.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Toxicokinetic behaviour of Intreleven aldehyde

 

Introduction

The toxicokinetic behaviour of Intreleven aldehyde (generic CAS no.58296-81-4) is assessed to the extent that can be derived from the relevant available information, as is required at Annex VIII level according to the REACH requirements.

Intreleven aldehyde is a multi-constituent substance. It consists of the following main constituents: Undec-10-enal, (9E, 9Z) Undec-9-enal and (8E, 8Z) Undec-8-enal, and (7E, 8Z) Undec-7-enal. These constituents are aldehydes with a linear carbon backbone and contain one C=C double bond at various positions ranging from C7 to 10. Intreleven aldehyde is a liquid with a molecular weight of 168.28 that does not preclude absorption. The substance has a volatility of 6.0 Pa at 24°C, water solubility of 26.1 mg/L and a Log Kow of 4.47.

 

Absorption

Oral: Intreleven aldehyde is a liquid and has a relatively low molecular weight (168.28), moderate water solubility (26.1mg/L) and a log Kow of 4.47, all favouring gastrointestinal absorption. According to Martinez and Amidon (2002) the optimal log Kow for oral absorption falls within a range of 2-7. This shows that the substance is likely to be fully absorbed orally and at least in > 50%. 

Skin: Intreleven aldehyde is a liquid and its physico-chemical properties allow dermal absorption: its molecular weight (168.28), log Kow (4.47) and water solubility (26.1 mg/L). The optimal molecular weight 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 log Kow of the substance is above 4, therefore the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Based on these characteristics dermal absorption will not exceed oral absorption.

Lungs: For Intreleven aldehyde, the volatility (6.0Pa) indicates that the substance may be available for inhalation and absorption via inhalation as a vapour. The log Kow (4.47) indicates that the substance is moderately lipophilic and can be absorbed in the lung via diffusion but also via micellar solubilisation (ECHA guidance, 7.12, Table R.7.12-1). The blood/air (B/A) partition coefficient is another partition coefficient indicating lung absorption. Buist et al. 2012 have developed B/A portioning model for humans using the most important and readily available parameters:

Log PBA = 6.96 – 1.04 (Log VP) – 0.533 (Log Kow) – 0.00495 MW.

For Intreleven aldehyde the B/A partition coefficient would result in:

Log P (BA) = 6.96 – 1.04 x 1.42 – 0.533 x 4.47 – 0.00495 x 168.28 = 2.27.

This means that Intreleven aldehyde 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 Intreleven aldehyde being out of the applicability domain and the exact B/A portioning may not be fully correct, it indicates that the substance will be readily absorbed via the inhalation route and an inhalation absorption of 100% can be used.

 

Metabolism

There are no experimental data on the metabolism of the substance. The theoretical Phase 1 metabolism is presented in Figure 1 in the attached file as predicted by the OECD Toolbox (3.3.5.17). This means that these aldehydes can oxidise into carboxylic acids which are processed in the mitochondrion resulting finally in CO₂and H₂O. This pathway is also mentioned in Annex III of The EFSA Journal (2008) 616-75. The final metabolite could be processed further as an unsaturated fatty acid, or it will be detoxified through phase II metabolic pathways such as glucuronidation.

Fig. 1 For Intreleven aldehyde auto-oxidation of the aldehyde group is expected. Oxidation to a carboxylic acid would yield a C11 fatty acid, which is processed in the mitochondrion resulting finally in CO₂ and H₂O. The final metabolite could be processed further as an unsaturated fatty acid, or it will be detoxified through phase II metabolic pathways such as glucuronidation.

 

Distribution

Based on the water solubility of the test substance (26.1mg/L), it may partly diffuse through aqueous channels and pores. However, the log Kow (4.47) would suggest that the substance would pass through the biological cell membrane. It is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.

 

Excretion

Intreleven aldehyde is expected to be fully consumed in the mitochondria but excretion via the kidney may occur when metabolic pathway is overloaded. The physico-chemical properties of this substance, such as low molecular weight (<300) and moderate water solubility would enable renal excretion. 

Bioaccumulation: Intreleven aldehyde as such is lipophilic and may accumulate in the body fat.

Conclusion

Intreleven aldehyde is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route. The final absorption values derived for oral, dermal and inhalation are 50, 50 and 100% absorption. This information does not need to be used for route to route extrapolation because ‘no hazards are identified’ via the oral route and therefore no hazards are expected for the dermal and inhalation route.

 

References

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

- 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.

- Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) on a request from the Commission Flavouring Group Evaluation 6, Revision 1 (FGE.06Rev 1): Flavouring Group Evaluation 6, Revision 1 (FGE.06Rev1): Straight- and branched-chain aliphatic unsaturated primary alcohols, aldehydes, carboxylic acids, and esters from chemical groups 1 and 4 (Commission Regulation (EC) No 1565/2000 of 18 July 2000). The EFSA Journal 616, 1-74.