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Endpoint summary

Description of key information

Introduction

Octadecanoic acid, reaction products with tetraethylenepentamine is an UVCB (organic) substance. Physico-chemical properties of Octadecanoic acid, reaction products with tetraethylenepentamine, together with the results of in vitro and in vivo studies that were conducted with the substance have been used to determine, as far as possible, a toxicokinetic profile for the substance.

Physicochemical properties

Octadecanoic acid, reaction products with tetraethylenepentamine is an UVCB (organic) substance with a molecular weight range of ≥676 to ≤960 g/mol. It is described as an amber solid at room temperature with a melting point of 31-69°C. It decomposes before boiling.

Its relative density and vapour pressure at 20°C are 0.9816 g/cm³ and 0.00325 Pa, respectively. No granulometry has been conducted as the substance is a waxy solid, which precludes conduct of the test.

The partition coefficient (log Pow) could not be determined experimentally as the substance was insoluble in four organic solvent-water mixes where water was present at 25% or above. It was shown to be soluble at 5 g/L in pure methanol.

Water solubility was estimated to be 45-220 mg/L at 20°C and corresponded to 24.2% to 45.3% of nominal concentration (100 to 800 mg/L). No exact value could be determined as solubility was dependent on nominal concentration.

Absorption

Oral absorption

In an acute oral toxicity test in female rats (OECD TG423) the LD50 was reported to be >2000 mg/kg. Piloerection and dyspnoea were observed during the observation period and a decrease in body weight (3/6 animals) and stagnation of body weight (1/6 animals) were observed between the first and second week after administration of the test item. During necropsy, increased amount of gas in gastrointestinal tract, microsplenia and atrophy of thymus were observed in 3/6 animals (the same animals where decreased body weight were observed).

In a repeat dose study (combined with the reproduction/developmental screening test; OECD TG422) some sporadic clinical signs and body weight losses/reduced bodyweight gain were observed in males (but not females) at the highest dose, although these were considered to not be adverse. Treatment-related findings were limited to epithelial hyperplasia of the non- glandular stomach, seen in the stomach of males and females dosed at 750 mg/kg/day. Moderate atrophy of thymus and spleen was also seen in one high dose treated animal together with hyperplasia of the non-glandular epithelium. These changes (which were consistent with effects seen in the acute toxicity study) were concluded to be due to the local irritant effects of the substance in the stomach and therefore do not provide any information regarding bioavailability.

It is considered that limited information on oral absorption can be inferred from the acute or repeat dose toxicity tests. Although some adverse findings were observed these were attributed to local irritation effects in the stomach and were not clearly indicative of absorption from the GI tract. 

The physicochemical properties of the substance would suggest minimal absorption occurs in the GI tract. The molecular weight ranges from approximately 676 to 960 g/mol, which is less favourable for absorption. The substance is a waxy solid and although water solubility was estimated to be between 45-220 mg/L, it was shown to be dependent on nominal concentration, with lower solubility in lower nominal concentration preparations. Furthermore, no partition coefficient could be established. 

In the absence of suitable exposure data, a default value of 100% would be assumed for oral absorption. However, based on the physicochemical properties of the substance and the lack of any evidence of bioavailability in the repeat dose or acute toxicity studies, oral absorption of Octadecanoic acid, reaction products with tetraethylenepentamine is considered limited. Consequently, the default value is considered too highly conservative and a value of 50% absorption is considered justified for use for human health risk assessment purposes.

Dermal absorption

In an acute dermal toxicity test in female rats (OECD TG402) the LD₅₀was reported to be >2000 mg/kg. No signs of toxicity, mortality or gross necropsy findings were seen.

An in vitro skin irritation/corrosion study concluded Octadecanoic acid, reaction products with tetraethylenepentamine was not corrosive or irritating to the skin. However Octadecanoic acid, reaction products with tetraethylenepentamine has been identified as a skin sensitiser and therefore is able to pass the skin barrier. 

The physicochemical properties of the substance would suggest very little dermal absorption occurs. The substance is a waxy solid with an estimated water solubility of between 45-220 mg/L, which would allow for low to moderate dermal penetration. However, dermal absorption is likely to be greatly hindered by the large molecular size of the substance, reported to range from approximately 676 to 960 g/mol. According to ECHA guidance, molecular weights greater than 500 g/mol are likely to be too large to penetrate the skin. No partition coefficient could be established, although the substance was soluble in pure methanol at 5 g/L. 

The ECHA default value for dermal absorption is 10% for substances with a molecular weight greater than 500 g/mol and a partition coefficient of logP in the range -1 to 4. Although the physicochemical properties of Octadecanoic acid, reaction products with tetraethylenepentamine predict low penetration, dermal absorption must occur to some extent as the substance has been identified as a skin sensitiser in a local lymph node assay (OECD TG 429). Consequently, in the absence of any other data a value of 25% dermal absorption is considered suitable for use for human health risk assessment purposes.

Inhalation absorption

No data are available on inhalation toxicity. 

 

The physicochemical properties of the substance suggest inhalation of the substance is unlikely. The substance is a waxy solid with a melting point between 31 to 69°C and has limited solubility in water (45-220 mg/L); consequently, inhalation of particles or liquid is not expected to occur.

In the absence of any other information and although it is considered that no exposure via inhalation can occur, absorption following inhalation is set at 100%.

Distribution, Metabolism and Elimination

No in vivo information is available to describe the distribution, metabolism or elimination of Octadecanoic acid, reaction products with tetraethylenepentamine. However, its molecular size and low water and methanol solubility would suggest any absorbed substance is unlikely to be distributed widely.

Information on metabolism is limited to observations that cytotoxicity in the Ames test (gene mutation in bacteria; TG471) were comparable following treatments in the absence and presence of an exogenous rat liver S9 metabolism system. It is therefore unknown if the S9 was capable of metabolising the substance.

No information on elimination can be inferred from the available data.

Bioaccumulation is considered unlikely to occur.

Conclusions

Based on the available data for Octadecanoic acid, reaction products with tetraethylenepentamine, oral absorption is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 25%.

There is no potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100