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Administrative data

Link to relevant study record(s)

Description of key information

The available experimental data in animals obtained on analogues substances (Cocamidopropylhydroxysultaine C8-18 [CAS 68139-30-0 or CAS 70851-08-0] and Cocamidopropylhydroxysultaine C12-18 [CAS 68139-30-0 or CAS 70851-08-0]) show evidence of oral absorption and systemic distribution of the test substance and/or its metabolites or degradation products since adverse effects were reported in the kidneys following repeated oral exposure in rodents. No systemic effects were observed when the test substance was dermally applied in the acute dermal toxicity study. No specific indication on the test substance metabolism or excretion was obtained from the toxicity studies.

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on Lauramidopropyl hydroxysultaine. A toxicokinetic assessment was made based on the physico-chemical properties of the test substance and the results of toxicity studies (acute oral and dermal toxicity, skin irritation, skin sensitisation, in vitro genotoxicity and repeat dose toxicity studies) obtained on the analogue substances cocamidopropylhydroxysultaines which contain alkylamidopropylhydroxysultaine with carbon chain from C8/C12 to C18. The main component of Cocamidopropylhydroxysultaine is lauramidopropylhydroxysultaine. Justification for the read-across is documented in a separate document attached in Iuclid Section 13.

Physico-chemical properties:

Water solubility: 556 g/L (at 20°C)

Partition coefficient in octanol/water: 2.1 (at 25°C)

Vapour pressure: 2.3*10-8Pa (at 25°C)

Boiling point: 311.6 (at 101 kPa)

Density: 1.304 (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 cocamidopropyl hydroxysultaine as histopathological changes in internal organs such as kidneys were observed, indicative of effects of cocamidopropyl hydroxysultaine 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 study in rats at the dose of 2000 mg/kg bw with cocoamidopropyl hydroxysultaine (C8-18 and C12-18 carbon chain length). There were neither any signs of toxicity or sensitisation after intradermal injection and topical challenge in a guinea pig maximisation test with the analogue substance. In a human repeated insult patch test performed with the registered substance diluted at 12%, no signs of skin sensitisation were observed.

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) particularly if water solubility is high. In the present case, the partition coefficient in octanol/water of 2.1 and the highly water solubility are in favour of a dermal uptake of the test substance. However this capacity is offset by the relatively high molecular mass of the substance (422 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.

 

Distribution:

In the repeated oral dose toxicity study performed on cocamidopropylhydroxysultaine (C8-18 carbon chain length), histopathology evidenced microscopic changes in the stomach, lungs, trachea and kidneys. In the forestomach, squamous cell hyperplasia was most likely due to irritant properties of the test item. Pulmonary bronchioalveolar inflammation and tracheal epithelial alteration were attributed to the aspiration of compound after regurgitation at dosing. In the kidneys, there were minimal to slight degeneration/hypertrophy of the tubular epithelium, principally in males, and minimal tubular vacuolation in some females. The effects observed in kidneys support a systemic distribution of the test substance and/or its metabolites or degradation products. It can be therefore assumed a systemic distribution of the registered substance.

 

Metabolism:

Three in vitro (Ames test, a chromosome aberration test in cultured human lymphocytes, a mouse lymphoma assay) and one in vivo (bone marrow micronucleus test in rats)studies assessed the potential genotoxicity of Cocamidopropyl hydroxysultaine. 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 non genotoxic. In the absence of specific metabolism studies, it is not possible to conclude on the metabolisation potential of the test substance and thereby of the registered substance.

Elimination:

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