Amines, C12-18-alkyl, reaction products with acrylic acid, sodium salts

Endpoint summary

Description of key information

The available experimental data in animals show evidence of oral absorption and systemic distribution of the test substance and/or its metabolites or degradation products since effects on kidneys (histopathology + clinical biochemistry), food consumption and body weight gain were observed following repeated oral exposure in rats. No systemic effects were observed when the test substance was dermally applied in both acute dermal toxicity studies (in rats and rabbits). No specific indication on the test substance metabolism or excretion was obtained from the toxicity studies.

Additional information

No specific toxicokinetic studies are available on disodium cocoiminodipropionate. A toxicokinetic assessment was made based on the physico-chemical properties of the test substance and the results of the toxicity studies.

 

-         Physico-chemical properties:

·          Water solubility: 350 g/L (at 20°C)

·          Partition coefficient in octanol/water: -1.3 (at 20°C)

.     Vapour pressure ≤ 0.009Pa (at 20°C)

·          Boiling point: 218°C (at 101 kPa)

·          Density: 1.077 (at 20°C)

 

-         Absorption:

Inhalation:

No data are available for inhalation route of exposure. However, the test substance is a liquid with a very low volatility, as evidenced by the low vapour pressure and the elevated boiling point. Therefore it can be considered that the absorption resulting from potential exposure by the inhalation route is limited.

 

Oral route:

The results obtained in the repeated oral dose toxicity study (OECD 422) confirmed the oral absorption of disodium cocoiminodipropionate as histopathological changes in internal organs such as kidneys were observed, together with changes in clinical biochemistry, indicative of effects of the substance and/or its metabolites or degradation products distant from the site of administration.

 

Dermal route:

There was no evidence of systemic toxicity in the acute dermal toxicity studies in rats and rabbits at the limit dose of 5000 mg/kg bw. There were neither any signs of toxicity or sensitisation after intradermal injection in a guinea pig assay.

According to the Guidance on information requirements and chemical safety assessment (Chapter R.7c: Endpoint specific guidance), Log P values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal). In the present case, the partition coefficient in octanol/water of -1.3 is not in favour of a dermal uptake of the test substance. This capacity is also offset by the relatively high molecular mass of the substance (348 g/mol): molecules above 500 g/mol are considered to be too large to penetrate the skin. Therefore it can be assumed that dermal absorption, if any, is limited.

For the oral-to-dermal route-to-route extrapolation used in DNEL derivation, a worst-case absorption of 10% was considered for the dermal route [Ref. Kroes R et al. Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem Toxicol. 45(12): 2533-62, 2007].

 

-         Distribution:

In the repeated oral dose toxicity study, histopathology evidenced microscopic changes in the kidneys. In the kidneys, there was increased incidence and severity of hyaline droplets/granules in male rats. The effects observed in kidneys support a systemic distribution of the test substance and/or its metabolites or degradation products.

 

-         Metabolism:

Three in vitro (Ames test, chromosome aberration test, HPRT gene mutation assay) studies assessed the potential genotoxicity of a direct analogue. In vitro, the test substance was assessed with and without an exogenous mammalian metabolic activation system. Under both metabolic conditions, the test substance showed a similar behaviour and was cytotoxic but not genotoxic. In the absence of specific metabolism studies, it is not possible to conclude on the metabolisation potential of the test substance.

 

-         Elimination:

There is no indication of a preferred route of excretion for disodium cocoiminodipropionate but its high water solubility indicate that excretion of unchanged parent substance and/or metabolites could occur by renal or biliary routes and that tissue bioaccumulation is unlikely. The parent substance could likely not be eliminated via the lungs in expired air due to its low volatility.