Registration Dossier
Registration Dossier
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EC number: 947-057-6 | CAS number: -
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
The available data suggest that 2-hydroxy-3-[(1-oxodocosyl)oxy]propyltrimethylammonium chloride (target substance) may be bioavailable via the oral and dermal routes and by inhalation following hydrolysis into dihydroxypropyltrimonium chloride (the source substance) and behenic acid . The carboxylic acid is then degraded following the cycle of carboxylic acids into acetyl Co-Enzyme A that will enter in the Krebs cycle. Regarding dihydroxypropyltrimonium chloride, it is probably metabolised and conjugated in the liver, distributed in the whole body and then excreted mainly in urine.
The toxicity of the target substance and the source substance is qualitatively assumed to be similar for systemic toxicity following the same pathway of absorption, distribution, metabolism and excretion with these chemicals being presented as analogues (see the RAAF document section 13).
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Quartamin BTC 131 is reaction mass of 3-(docosanoyloxy)-2-hydroxy-N,N,N-trimethylpropan-1-aminium chloride and 2-methylpentane-2,4-diol. The first constituent is considered as the target substance for which the toxicological concern must be addressed including the absorption, the distribution, the metabolism and the excretion.No data on absorption, distribution and excretion are available on the target substance. Only a dermal absorption study was performed on the source substance. No hydrolysis study is conducted with the target substance since it is readily biodegradable. No hydrolysis is conducted with the source substance based on the absence of readily hydrolysable functional groups. Hydrolysis of the target ester into the source substance is expected to occur at the physiological conditions in the stomach,i.e.37°C, acidic pH (pH=1.5) and hydrolytic enzymes.
The toxicokinetics of the second constituent, 2-methylpentane-2,4-diol (or hexylene glycol) has been already assessed in the REACH dossier (Annex X) available on the ECHA website.https://echa.europa.eu/fr/registration-dossier/-/registered-dossier/14212/7/2/1
Limited data is available to describe the likely ADME properties of hexylene glycol (HG). Given its relatively high water solubility, log Kow < 1 and molecular weight of < 500 Da., absorption might be expected following ingestion or inhalation exposure.
The predominant mechanism for the metabolism of HG appears to be conjugation of the parent compound or its intermediate metabolite with glucuronide, followed by excretion in the urine. HG is absorbed through the mucosa of the gastrointestinal tract.A study confirmed the source substance passage through the plasma to the milk compartment, although in limited quantities on day 1 post-partition.Man excretes about 35 % of a dose of HG slowly with the urine, about half as the unchanged substance and half as the glucuronide; rodents excrete 50 % to 60 % of the dose in the urine, mainly as the glucuronide. Oral absortion rate only based on the urine excretion will be underestimated as the fecal excretion via the enterohepatic cycle of the conjugates are not taken into account. A global absorption rate of 50% seems appropriate after oral administration. Considering its physicochemical properties, the absorption of HG after inhalation exposure is expected to be of the same order than after oral administration. Anin vitropercutaneous absorption study with human skin was performed to evaluate the dermal absorption at relatively low amount of the applied dose. For the purpose of risk assessment, an absorption rate of 5 % is used after dermal exposure.
TARGET and SOURCE substances:
Absorption:
Dihydroxypropyltrimonium chloride (source substance) and C22 carboxylic acid (behenic acid) could be generated from 2-hydroxy-3-[(1-oxodocosyl)oxy]propyltrimethylammonium chloride (target substance) following acidic hydrolysis in the stomach (pH<1.5) following ingestion.
Then, behenic acid may be absorbed and degraded following the cycle of carboxylic acids into acetyl Co-Enzyme A that will enter in the Krebs cycle.
Moreover, the physical chemical characteristics (Table 3) suggest that 2-hydroxy-3-[(1-oxodocosyl)oxy]propyltrimethylammonium chloride and dihydroxypropyltrimonium chloride are of adequate molecular size to participate in endogenous absorption mechanisms within the mammalian gastrointestinal tract following oral administration.
Being rather hydrophobic than hydrophilic, the source substance may be expected to cross gastrointestinal epithelial barriers.
Regarding the dermal absorption, as the molecular weight of the target substance is higher than 100 g/mol, dermal intake is expected to occur but its low water solubility and partition coefficient (Table 3) are not in favour of a high and rapid rate of transfer between the stratum corneum and the epidermis.
These assumptions are supported by the absence of systemic effects in skin irritation study and acute toxicity study by dermal route of the target substance up to approximately 9100 mg/kg bw and up to 2000 mg/kg bw for the source substance. This would suggest a limited systemic absorption through cutaneous. Moreover, enhanced skin penetration is not expected since both source and target substances are nor skin irritating/corrosive nor skin sensitizing.
For the potential of absorption by inhalation, no data is available with the target and the source substance. However, the log Kowof target substance, which is expected to be hydrolysed into the source substance by oral route, is not favourable for ready absorption directly across the respiratory tract epithelium by passive diffusion as 2-hydroxy-3-[(1-oxodocosyl)oxy]propyltrimethylammonium chloride is a highly lipophilic compound poorly soluble in water.Moreover, based on the results in the studies available by oral route, neither adverse systemic effects nor irritation of the respiratory tract are expected following absorption of the target and source substances.
Distribution
Systemic distribution of the target substance and the source substance can be predicted from their physical-chemical characteristics (Table 3). Considering that the target substance is highly hydrophobic (log Kow> 6) and poorly water soluble (< 23 µg/L), it is suggested that, upon systemic absorption, target substance may be transported through the circulatory system while its molecular weight is 492 g/mol.
The source substance following oral absorption, may be transported in the blood considering its high water solubility (838-861 g/L) in order to be quickly excreted with no potential of accumulation based on the Log Kow(1.15).
Metabolism
The results of the short-term repeated dose toxicity study in the rat with the target substance showed liver changes that are consistent with the increased metabolism associated with detoxification of a xenobiotic. This liver induction confirmed that a non-negligible part of 2-hydroxy-3-[(1-oxodocosyl)oxy]propyltrimethylammonium chloride or the hydrolysis products could be metabolised following gastrointestinal tract absorption. As the target substance is likely hydrolysed in the stomach into the source substance, it could be assumed that the metabolism of the source substance is similar.
Elimination
The target substance absorbed in the form as the source substance following acidic hydrolysis, is expected to be mainly excreted in urine and may be slightly excreted in bile based on the low molecular weight (<300 g/mol). It is expected also that the metabolites of the source substance are excreted unchanged or as their glucuronide and sulfate conjugates. The substance amount that may not be absorbed from the gastro-intestinal tract, following oral ingestion, will be excreted in the faeces.
Following dermal exposure, the target substance that has penetrated the stratum corneum but not totally penetrate the viable epidermis based on limited rate due to hydrophobicity, be sloughed off with skin cells.
For inhalation exposure, the elimination of the absorbed substance should be similar that the substances eliminated by oral route.
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