Reaction product of C16-22, even, C18-rich, unsaturated and saturated triglycerides with, N-(2-hydroxypropylamine)

Endpoint summary

Description of key information

Minimal absorption via oral, dermal or inhalation routes of exposure is expected based on the experimental data and the physico-chemical properties of the substance. Any absorbed test item is expected to be widely distributed through the body, metabolised and excreted mainly in the urine. The substance will not bioaccumulate.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Physico-chemical properties

 

The test item is a UVCB with 34 identified components. The components have a molecular weight range of 75.1 to 885.4 g/moL of which the lower molecular weight (<282 g/moL) components constitute a minor fraction of the substance (~0.4%). The substance is a dark yellow viscous liquid with a determined water solubility of 0.01 mg/L. The octanol/water partition coefficient is estimated as log Pow 5.75 to > 10, (which is >4, the bioaccumulation limit), and the vapour pressure is low (0.027 Pa at 25oC). The substance is not known to have surface active properties.

Absorption

 

Oral route 

Passive diffusion (transcellular) and passage through the aqueous pores (para-cellular) are the primary absorption mechanisms of molecules from the gastro-intestinal (GI) tract. Key physicochemical properties that determines the mechanism of absorptionsare molecular weight (MW), Log p and aqueous solubility.Molecules that pass through the transcellular route aresmall (molecular weight up to around 200) water-soluble molecules. Log p values in the range of 0 - 3 and a MW less than 500 favours paracelluar transport.Based on the above, the test item is expected to be poorly absorbed from the GI tract because of the poor aqueous solubility, high log Pow(5.75 to > 10) and a molecular weight distribution for the main components of 282.5 to 885.4 g/moL. It can be concluded that oral bioavailability of the substance is expected to be low. However, since the UVCB test material contains multiple components with differing physio-chemical properties, their ability to cross the GI barrier could vary between individual components.

 

Poor absorption of the UVCB substance from the GI tract is supported by the absence of any evidence of toxicity in an acute oral gavage toxicity study at 2000 mg/kg bw. The NOAEL for systemic toxicity was considered to be 1000 mg/kg/day based on the lack of adverse test item-related effects in the 100, 350, 500, and 1000 mg/kg/day groups (OECD 422).

 

Dermal route

 

The skin absorption rate of molecules with a log Powvalue in the range of < -1 or > 4 and the molecular weight of > 500 g/moL is considered low. The test item is expected to be poorly absorbed through the skin considering its poor water solubility and the relatively high log Pow. Additionally, the substance has very low vapour pressure at room conditions which minimise the potential for exposure through the dermal route at ambient temperature. However, since the UVCB test material contains multiple components with differing physio-chemical properties, their ability to cross the lipid rich environment of the skin could vary between individual components.

 

Poor absorption via the dermal route is supported by the absence of observed systemic effects following dermal application of the test item in an acute study (LD50 > 2000 mg/kg). The substance did produce well-defined erythema, slight edema, moderate desquamation and crust formation in a skin irritation study involving application of the substance to intact skin of two rabbits. However, both treated skin sites appeared normal at the 14 -day observation. In a sensitisation study in mice (LLNA) the substance was concluded not to be a sensitiser. Therefore, these results are considered to be evidence of non-absorption via the dermal route.

 

Inhalation route

 

Volatility, aqueous solubility and log Pow values determine the inhalation uptake. Since the test item is a liquid with very low vapour pressure at room temperature, the potential for exposure through inhalation route is expected to be very low. Being poorly water soluble, the substance will not readily dissolve into the mucus lining the respiratory tract and because of the high log Pow value it would not be absorbed directly across the respiratory tract epithelium. However, since the UVCB test materialcontains multiple components with differing physio-chemical properties, their ability to cross the alveolar membrane barrier could also vary between individual components.

 

Distribution

 

The extent of distribution of molecules is affected by molecular weight, lipid solubility, pKa, and plasma protein binding (PPB). Molecules that are lipophilic at pH 7.4 and show high plasma protein binding are likely to have high volume of distribution (Vd). Physicochemical properties that influence PPB include lipophilicity and pKa. In general, chemicals with high lipophilicity and/or ones with acidic character will have a greater degree of PPB, than more hydrophilic or basic compounds.Once absorbed, the test item is expected to have a high volume of distribution due to its high log Pow values. High log Pow of the substance can result in initial partitioning preferentially into highly vascularized lipid rich areas with subsequent slow redistribution into body fat, where they may remain for long periods of time.The Vd directly influences the half-life of a compound, whereby large Vd can lead to a longer half-life.The UVCB test material contain components with differing lipophilicity their distribution could vary from one another.

 

Metabolism and excretion

 

The test item contains a distribution of compounds with different carbon tail lengths. Some of the key components include monoamide of hydroxypropropyl amine, mono ester of hydoxypropylamine, Glycerol-1-monoalkylate, Glycerol-1, 2-dialkylate, Glycerol-1,3-dialkylate and bis-amide/ester. The chemical structures of the key components include metabolically liable amide and/or ester linkages. The amide and ester bonds can undergohydrolysis by amidases/esterases in-vivo, resulting the formation of the respective acid and hydroxylamine moieties, which can undergo further metabolic reactions forming several products that are expected to be hydrophilic and mainly excreted in the urine.

 

Conclusion

 

A qualitative judgement on thetoxicokineticbehavior of the substance was performed based on the physico-chemical characteristics. Since the test material is a UVCB substance, not all physico/chemical properties are clearly defined but reflect the properties of a group of substances. The toxicokinetic assessment is thus indicative only as single substances within the UVCB might have significant different physico/chemical properties. The test material is expected to be poorly absorbed via the oral, dermal and inhalation routes. Any absorbed test item is expected to be widely distributed through the body, metabolised and excreted mainly in the urine.