1-ethylazepan-2-one

Endpoint summary

Description of key information

Experimental studies on toxicokinetics are not available. The molecular weight, physicochemical properties including water solubility and octanol-water partition coefficient of the substance suggest that oral, inhalative and dermal absorption occur. The substance is expected to distribute throughout the body due to its high water solubility and low molecular weight. Although the substance is expected to dissolve in lipids, accumulation in adipose tissue due to its log Pow is considered unlikely. Excretion of the test item is expected to occur mainly via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

The theoretical assessment was based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance, taking into account the physical/chemical properties and the toxicity data of the substance.

After exposure, a substance can enter the body via the gastrointestinal tract, the lungs, and the skin. Since different parameters are relevant for absorption via the different routes of exposure, the uptake via these three routes will be addressed individually.
After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract (1). Since the water solubility of N-ethylcaprolactam is very high with >1000 g/L at 20 °C, the substance can be expected to completely dissolve into the gastrointestinal fluids and become available for uptake. Based on its molecular weight (approx. 141 g/mol), uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage across membranes with the bulk passage of water) is possible. Nethylcaprolactam has a moderate partition coefficient (log Pow = 0.6), which implies that this substance will dissolve in lipids and can thus cross epithelia by passive diffusion. The substance does not have ionisable groups that could hamper uptake.

For risk assessment purposes oral absorption of N-ethylcaprolactam is set at 100%, based on its high water solubility, its low molecular weight and its moderate log Pow. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Once absorbed, distribution of the substance throughout the body is expected based on its high water solubility and moderate molecular weight. Absorbed N-ethylcaprolactam is expected to be excreted mainly via urine (2). Based on its moderate partition coefficient (log Pow = 0.6), it is unlikely that N-ethylcaprolactam will accumulate significantly in adipose tissue.
N-ethylcaprolactam has been found to have a low vapour pressure (8.8 Pa at 25 °C), which indicates that exposure via air is expected to be limited. N-ethylcaprolactam is a liquid at room temperature, which implies that exposure via aerosols is possible. Aerosols can reach the tracheobronchial region, in which case N-ethylcaprolactam will dissolve in the mucus lining the respir atory tract and will get absorbed. Furthermore, N-ethylcaprolactam can dissolve in lipids and is therefore able to cross biological membranes. Taking these considerations intonaccount it is concluded that for risk assessment purposes as worst case the inhalation absorption of N-ethylcaprolactam should be set at 100%.

N-ethylcaprolactam is a liquid, which may enable uptake through the skin. The compound’s ability to dissolve in lipids will furthermore favour easy crossing of epidermal barriers. The water solubility of N-ethylcaprolactam is high, allowing partitioning from the stratum corneum into the epidermis. Its moderate molecular size is expected to facilitate uptake through dermal epithelium. According to the criteria given in the REACH Guidance (3), 10% dermal absorption will be considered in case MW >500 and log Pow < -1 or > 4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of N-ethylcaprolactam do not meet the criteria for limited dermal absorption (MW 141.21 g/mol; log Pow = 0.3), for risk assessment purposes dermal absorption should be set at 100%.

 

References:

1.     Martinez MN, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals.J Clin Pharmacol 2002; 42: 620-43.

2.     Parkinson A. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.

3.     Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, Version 6.0 November 2016.