N,N,N-tri-C8-C10-alkyl-N-methyl-1-aminium sulfate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Data from in vitro or in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available. Therefore, the assessment of the toxicokinetic behaviour is based on physical-chemical data of the substance.

 

Absorption:

Since the target substance is ionized, it will not readily diffuse across biological membranes. The molecular weight of approximately 403 Da (mean, cation only) implies a moderate absorption potential after oral intake, but a passage through aqueous pores or the epithelial barrier by the bulk passage of water is only favourable for substances with a molecular weight of less than 200 Da. The log Kow of 3.1 is favourable for passive diffusion, thus, some oral uptake can be expected. With a water solubility of485mg/L, the target substance is assumed to dissolve in the gastrointestinal fluid. In the acute oral toxicity study available for the substance, a LD50 of 200-2000 mg/kg was deduced. However, the effects appeared at the site of contact and were attributed to the corrosive potential of the substance. The corrosivity is assumed to enhance penetration. In a repeated dose toxicity study (combined with the reproduction / developmental toxicity test) in rats the substance caused signs of systemic toxicity (decreased food consumption and decreased body weight parameters), revealing that absorption has occurred. However, apart from that, no specific data concerning oral absorption of the test substance are available. Therefore, by default an oral absorption of 50% is assumed.

 

With regard to absorption after inhalation, the target substance has a low vapour pressure of 4.26E-4 Pa at 20°C, indicating that inhalation as vapour will be negligible. If the substance reaches the respiratory tract, some passive diffusion is likely due to the log Pow of 3.1 but the rather high molecular weight will limit the amount taken up. Because of the good water solubility, the substance is likely to dissolve in the mucus of the upper respiratory tract, and consequently will at least partly be removed before reaching the lower respiratory tract. Due to the lack of data as a worst case 100 % absorption after inhalation is assumed.

 

The relatively high molecular weight (mean 403 Da) and especially the ionic nature suggests a limited dermal uptake at non-corrosive concentrations. Substances containing ammonium groups are known to bind to skin components, which reduces the dermal absorption. It can be assumed that the log Kow of 3.1 limits the entrance into the stratum corneum, thus the bioavailability after dermal contact will be limited at non-corrosive concentrations. In the absence of experimental data, by default a dermal absorption of 50% is assumed (same as oral).

 

Metabolism and Excretion

The part of the target substance that is systemically available is expected to undergo a N-dealkylation reaction (Phase I metabolism) in which the methyl group can be removed. The resulting metabolite could then be conjugated to glucuronic acid, catalyzed by the enzyme UDP-glucuronosyltransferase (UGT), which takes place in most mammalian species except cats. The conjugated metabolites are assumed to be excreted mainly via bile, as suggested by the molecular weight > 500 Da. The target substance as such could in principle be excreted via urine, because of the smaller size and the already good water solubility of the parent compound.

After dermal exposure, the target substance is not expected to penetrate the stratum corneum at a large extent at non-corrosive concentrations. Consequently, it will be removed with the exfoliation of the skin or in the sweat.

Bioaccumulation is not expected, considering the physico-chemical properties and the mechanisms for excretion of the target substance and potential metabolites.