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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

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Description of key information

- The bioavailability of the substance can be confirmed through different routes. But the uptake may be limited due to the physical-chemical properties if the substance.

- Possible uptake routes are dermal, oral and inhalation, whereas via dermal and inhalation route the absorption is expected to be lower.

- It can be assumed that the substance is wide distributed but not able to accumulate.

- Metabolites may be integrated in common metabolic pathways.

- The main route of elimination is expected to be via kidney / urine and to some extend, especially for metabolites biliary excretion and exhalation may happen.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the test item were investigated. The expected toxicokinetic behaviour is derived based on information about the physical-chemical properties, the results from the available toxicological studies and the available literature following the information given in guidance document 7c. Please note that the real behaviour may be different but can only be determined with ADME studies, which are not justified based on the very low toxicity of the substance.

 

Physical-chemical properties:

The test item, having a molecular weight of 351 g/mol, is a white solid which is only used in dissolved (water diluted) form. It has a water solubility of > 320 g/L and a low volatility (vapour pressure 0.45 Pa). The structure show carboxyl groups whereas one is neutralised and the counter ion is sodium. Therefore the substance has ionic character and it is highly hydrophilic (log Pow ≤-2.12). The surface tension of the aqueous solution common handle is 28.7 mN/m. Furthermore the substance is not acute toxic but it is irritating to the skin and to the eyes. Most affected target organs are the liver and kidney, which were observed using a structurally similar substance in a OECD guideline 422 at large dosages (600mg/kg bw/d).

 

Oral and GI absorption:

The test item contains ionisable groups and is a sodium salt, therefore it is highly soluble in water (> 320g/l) and highly hydrophilic (Log Pow ≤-2.12). Based on the low molecular weight (below 500 g/mol), the high hydrophilicity and the water solubility, it is assumed that the substance is easily absorbed in the GI tract via passive diffusion. The solid material may easily be dissolved in the GI fluid, but as the substance is mostly used after dilution (diluted with water), contact with the substance in its solid form may not happen and the dissolved material may be more easily available in GI tract. Whereas no systemic availability could be confirmed as no effects are observed in acute toxicity studies, a long term study with a structural similar substance shows clearly the systemic availability due to various effects in the highest dosage group. Summarising based on the available information the substance is expected to be well absorbed in the GI tract. 

 

Respiratory absorption:

In general based on the low vapour pressure, inhalation of vapours is not expected (extreme low volatile substance, 0.45 Pa). Inhalation of dust is also not assumed as route of exposure because the substance is used only in (aqueous) dilutions. Only spray application may be of interest but due to the droplet size inhalation may not occur. As spray applications are uncommon, oral and dermal route is expected to be predominant. Nevertheless if droplets below 15µm are generated the substance may reach the alveolar region, however due to the hydrophilicity of the substance, it is likely that the substance may be retained in the upper mucosa area. In the respiratory system the uptake is expected to be via passive diffusion due to the low LogPow (≤-2.12) and the high water solubility. Summarising the substance may be inhaled if the right droplet size is generated and may also be absorbed, but the low toxicity is limiting the effect of intoxication.

 

Dermal absorption:

The molecular weight of the substance is between 100 and 500 g/mol therefore a moderated dermal absorption may be possible. But based on the ionic structure, the high water solubility (>> 10g/L) and the low log Pow (<<-1), the substance is expected to be not sufficiently lipophilic to cross the stratum corneum. Therefore dermal absorption is expected to be low. In contrast, the substance may stay long on the skin due to the low vapour pressure which increases the possibility of dermal absorption. However, as there are no signs of systemic toxicity in dermal acute toxicity tests, the uptake is assumed limited. Nevertheless the irritating properties of the substance indicates that the dermal uptake may be increased. Based on the predominant physical-chemical properties, which are the water solubility and hydrophilicity, absorption is expected to be low. Taking the paper of Kroes et al. into account a default dermal absorption of 10% is expected (Kroes et al., Food Chem Toxicol 2007 Dec; 45(12): 2533-62) based on the behaviour of known cosmetic chemicals having a MW > 300 g/mol and a logPow < -1.

Distribution:

The substance is expected to be wide distributed based on its molecular weight. Furthermore the high water solubility, the ionic character and the high hydrophilicity indicates high distribution as the substance may be able to pass through aqueous pores. Even though distribution into cells may be possible, due to the hydrophilicity higher intracellular concentration are not expected. Therefore no concentration in adipose tissue is assumed. Wide distribution is also indicated due to effects observed in liver and kidney during a OECD 422 study with a structural similar substance. Effects on the CNS are not observed. Summarising the substance is expected to be widely distributed and it is systemic available. Low toxicity or fast elimination due to high hydrophilicity and ionic character may limit the effect of intoxication.

 

Accumulative potential:

Based on the physical-chemical data, the structure and how the substance is used, accumulation in lung or bone is not expected as it is used as liquid and contains no metal ions. Due to the high hydrophilic character and the high water solubility the substance may not accumulate in adipose tissues and stratum corneum.

 

Metabolism:

Based on the structural features, the possible major metabolic fate of sodium lauriminodipropionate is described. As this compound is a N,N-dicarboxyethyl substituted dodecan-1-amine derivative it is likely that O-glucuronidation of the acid group will take place to form a metabolite. The formation of acyl glucuronides from carboxylic acids is an important reaction in chemical metabolism. The reaction has been demonstrated for sterically hindered acids and unsaturated acids as well as a few carbamate derivatives. Next, the compound may be a substrate undergoing the metabolic route of oxidative N-dealkylation of tertiary amine group to form corresponding metabolites. Oxidative N dealkylation (sometimes called deamination) is an important biotransformation in mammalian xenobiotic metabolism. The reaction is of wide scope and has been demonstrated for secondary and tertiary amines. The reaction is nearly always catalysed by cytochrome P450s. The mechanism involves hydrogen abstraction and oxidation addition (hydroxylation) at a carbon atom alpha to the nitrogen atom. Furthermore, the C-hydroxylation reactions on the alkyl chain of compound could also take place to yield metabolites. For the longer alkyl chain, hydroxylation at the methylene group and hydroxylation at the terminal methyl group may be favourable. In addition, the metabolite may undergo the beta-oxidation pathway to yield another metabolite due to the high tendency of chain shorten reaction of fatty acids (CIR, 2011).

 

Reactivity:

Available studies on genotoxicity were negative, i. e. there is no indication of a reactivity under the test conditions.

 

Excretion:

The substance may be excreted mainly via kidney / urine due to molecular weight near to 300 g/mol and the ionic hydrophilic character. Exhalation via lung of the major parent compound is not expected as the vapour pressure is low. Nevertheless degradation products of metabolisation may be carbon dioxide which is afterwards exhaled. Due to the molecular high hydrophilic character and high water solubility a excretion via bile is expected only in less amounts. Molecular weight might be increased by phase II metabolisation and these products may be excreted biliary. Also enterohepatic circulation may happen to these metabolites afterwards. Further derived from the hydrophilicity a concentration in breast milk and excretion via salvia/sweat is not possible as well as exfoliation as dermal applied substance may not reach the lipophilic area of the stratum corneum. As the substance is no metal ion excretion via hair and nails is very unlikely. Summarising the substance is expected to be excreted via kidney / urine as predominant route. Small amounts may be also excreted biliary especially if the substance is metabolised. Metabolic degradation products, like CO2, may be exhaled if build.

 

In summary: The bioavailability of the substance can be confirmed through different routes. But the uptake may be limited due to the physical-chemical properties. Possible uptake routes are dermal, oral and inhalation, whereas via dermal and inhalation route the absorption is expected to be low. It can be assumed that the substance is wide distributed but not able to accumulate. Metabolites may be integrated in common metabolic pathways. The main route of elimination is expected to be via kidney / urine and to some extent, especially for metabolites biliary excretion and exhalation may happen.