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Link to relevant study record(s)

Description of key information

The available experimental data in animals support negligible oral absorption and systemic distribution of the test substance and/or its metabolites or degradation products since no systemic toxicity was reported in rodents treated with some analogs to Dermalcare MAP L213/S. Owing to its very low vapour pressure, it can be considered that the absorption resulting from potential exposure by the inhalation route is limited.  Systemic effects were observed in lung, liver, gall bladder and digestive tract when a high dose of an analog to Dermalcare MAP L213/S was dermally applied in an acute dermal toxicity study. There was no obvious indication on the test substance metabolism or excretion from the toxicity studies.

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on Dermalcare MAP L213/S or on analogs. A toxicokinetic assessment was made based on the physico-chemical properties of the test substance and the results of toxicity studies performed on the registered substance or analogs (acute oral and dermal toxicity, skin irritation, skin sensitization and in vitro genotoxicity studies).

 

Physico-chemical properties:

Molecular Weight: 328.1 g/mol

Partition coefficient in octanol/water: -2.5 (at 20°C)

Vapour pressure: 0.00000045 Pa (at 25°C).

Density: 1.07 (at 20°C)

 

Absorption and distribution:

Inhalation:

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

Oral route:

There was no evidence of systemic toxicity in the acute oral toxicity study in female rats given a dose of 2000 mg/kg bw of the analogs Dermalcare MAP L213/K or L210. Absorption and systemic distribution of the test substance and/or its metabolites or degradation products is therefore expected to be negligible by the oral route.

Dermal route:

In the acute dermal toxicity study performed in rabbits with the analog Ethoxylated lauryl phosphate, signs of toxicity were reported at doses above 3160 mg/kg bw. Toxicity was characterized by mortality and macroscopic findings in lung, liver, gall bladder and digestive tract in animals found dead. There was no evidence of systemic toxicity in surviving animals. The mortality and macroscopic findings observed in dead animals are consistent with an absorption and systemic distribution of the test substance and/or its metabolites or degradation products. Despite their irritating potential, no evidence of systemic toxicity was reported with the analogs Dermalcare MAP L213/K and L210 in the skin irritation study performed in rabbits and the skin sensitization study performed in the Guinea Pig. In addition, although the test substance has good water solubility, the molecular weight above 300 g/mol and the partition coefficient in octanol/water below 1 tends to support a limited capacity for absorption through the skin.

 

Metabolism:

Three in vitro studies assessed the potential genotoxicity of Dermalcare MAP L213/S both with and without auxiliary metabolic activation. An Ames test (Sarlang, 2012), an HPRT test in hamster V79 cells (Verspeek-Rip, 2015) and a Micronucleus test in human lymphocytes (Morris, 2015), all gave negative results with no indication of cytotoxicity either with or without metabolic activation. As such, these studies confirmed that Dermalcare MAP L213/S does not have genotoxic potential but did not provide any information on metabolism.

 

Elimination:

There is no indication of a preferred route of excretion for Dermalcare MAP L213/S but its good water solubility tend to indicate that excretion of unchanged parent substance and/or metabolites could occur by the renal route and that bioaccumulation is unlikely. Elimination of the main components via the lungs in expired air is unlikely owing to its low volatility.