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Administrative data

Link to relevant study record(s)

Description of key information

Short description of key information on bioaccumulation potential result: 
Absorption by oral route is expected to be good. Absorption by respiratory route is undetermined. Some absorption should occur after dermal exposure.
Distribution is undetermined but no accumulation of the substance is expected: for the B criterion, the conclusion is “non-B”.
Liver metabolism is unsure. The substance may undergo various reactions (oxido-reductive reactions including hydratation, acido-basic reactions, other reactions), likely leading to the endogenous compounds.
Elimination is expected to be partly fecal (least polar compounds), partly urinary (most polar compounds) and to a minor extent expiratory (organic volatiles and carbon dioxide). The possibility of excretion into milk is undetermined.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

 


Non-human information


No study was performed and none is required by REACH. The following discussion takes into account relevant animal data on the substance summarized in other sections of this document.


Absorption:


Mortality has been observed in one oral repeat-dose toxicity study. This suggests that the substance is absorbed by oral route. Furthermore, the substance (a lipoaminoacid) being related to nutrient substances (lipids and aminoacids), it seems likely that it undergoes an extensive oral absorption.


Absorption upon inhalation is undetermined in the absence of studies involving inhalation of the substance. The substance is manufactured as a powder of significant granulometry (D10 < 55µm, so the possible absorption after inhalation should be moderate).


No systemic adverse effects have been noted in animals after single-dose dermal exposure and after induction and challenge dermal applications. This does not enable to conclude whether the substance is not absorbed by dermal route, or is absorbed but non-toxic at the dose-levels used. The moderate molar mass (241 g/mol), the intermediate lipophilicity (log Kow of 2.2) and the water solubility (81 mg/L) suggest that there may be some extent of dermal penetration of the substance. The physical form (powder) is also consistent with a possibility of dermal absorption.


Distribution:


There are no data on distribution after exposure to the substance: substance levels in organs and tissues were not determined, and no target organ or tissue was identified in the in vivo studies performed.


No accumulation of the substance is expected based on the various metabolic pathways which can be expected for the substance.


Metabolism


In the three in vitro genotoxicity tests, the addition of liver microsome fraction (S9 mix) had generally no clear influence on cytotoxic and genotoxic effects of the substance. When considering also the structural closeness of the substance to endogenous compounds (lipids and aminoacids), a liver metabolism can not be excluded.


The chemical reactions which may be hypothesised are essentially those which apply to aminoacids: oxido-reductive and acido-basic reactions. The C=O bond may also be hydrated into a diol group. In fact, a large variety of reactions can be imagined, so that it seems likely that the substance will be efficiently converted into endogenous compounds and undergo complete degradation.


Elimination:


No abnormal odor was noted in animal studies. There is therefore no indication of a noteworthy expiratory excretion of the substance and/or its degradation products. However, when considering the putative metabolism, it seems reasonable to predict a minor expiratory excretion of volatile carbon compounds.


No gastro-intestinal clinical signs and no coloration of feces were noted after repeated oral exposure to the substance. There is therefore no conclusion concerning a possible fecal excretion of the substance and/or its metabolites. However, when considering the putative metabolism, it seems reasonable to predict some fecal excretion of the least polar metabolites.


Neither clinical signs evocative of coloration of urine (e.g. coloured litter) nor microscopic effects on kidneys were noted after repeated oral exposure to the substance. There is therefore no conclusion concerning a possible urinary excretion of the substance and/or its metabolites. However, when considering the putative metabolism, it seems reasonable to predict some urinary excretion of the most polar metabolites. There are no data (notably distribution data to mammary glands) enabling to conclude on a possible excretion into milk.


 


Human information


No study was performed. The following discussion takes into account relevant clinical data on the substance summarized in other sections of this document.


Absorption:


Neither sensitisation nor systemic adverse effects were noted in a clinical sensitisation assay. This does not enable to conclude whether the substance was not absorbed by dermal route, or was absorbed but non-toxic and non-sensitising. The conclusion based on physicochemical characteristics remains the most reliable one.


Distribution / Metabolism / Elimination:


The available human data do not enable to derive any additional information on these aspects.


 Summary and discussion on toxicokinetics


Absorption by oral route is expected to be good. Absorption by respiratory route is undetermined.Some absorption should occur after dermal exposure.


Distribution is undetermined but no accumulation of the substance is expected: for the B criterion, the conclusion is “non-B”.


Liver metabolism is unsure. The substance may undergo various reactions (oxido-reductive reactions including hydratation, acido-basic reactions, other reactions), likely leading to the endogenous compounds.


Elimination is expected to be partly fecal (least polar compounds), partly urinary (most polar compounds) and to a minor extent expiratory (organic volatiles and carbon dioxide). the possibility of excretion into milk is undetemined.