Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Materials and methods

Principles of method if other than guideline:
Weight of evidence strategy based on all data available

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Absorption by oral route is expected to be good. For the substance per se, absorption by respiratory route is undetermined and absorption by dermal exposure is most probably limited; furthermore for both routes, absorption is virtually null for workers at the manufacturing steps as the substance is in the form of pearls.
the conclusion is “non-B”. Liver metabolism is unsure. The components of the UVCB may undergo acido-basic, oxidoreductive reactions and deglycosylation, leading to the same endogenous metabolism as that of fatty acids and glucose. Elimination is expected to be mainly fecal (fatty acids and metabolites) and to a minor extent expiratory (organic volatiles and carbon dioxide). No urinary excretion is expected, notably as the putative metabolite glucose, due to regulation of glycemia. The possibility of excretion into milk is undetermined.
Executive summary:

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:

No systemic adverse effects have been noted after single-dose oral exposure. However, minor systemic effects (lower weight gain, biochemical changes) have been noted after repeat-dose oral exposure in animals. This suggests that the substance is absorbed by oral route. Furthermore, the components of the UVCB being chemically related to absorbable molecules such as glucose and fatty alcohols, an extensive oral absorption is almost certain.

Absorption upon inhalation is undetermined in the absence of studies involving inhalation of the substance. The substance is manufactured as pearls (no grinding is performed), so under these actual exposure conditions the possibility of absorption after inhalation is virtually null.

No systemic adverse effects have been noted in animals after single-dose dermal 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 (possibly due to a different metabolism than by oral route). However, the molar mass (242-595 g/mol for individual components of the substance), the high to very high lipophilicity (log Kow ranging 2.4-10.7 for individual components of the substance) and the very low water solubility (≤ 60 mg/L) may be expected to considerably limit the dermal penetration of the substance. Last, the substance is manufactured as pearls (no grinding is performed), so under these actual exposure conditions the dermal absorption is virtually null.

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 absence of relevant adverse effects in all the studies performed.

No accumulation of the substance is expected based on the various metabolic pathways and excretion routes which can be expected for the substance (see below).

Metabolism

There is no conclusion concerning a possible liver metabolism of the unchanged components of the UVCB. Such a metabolism can not be excluded, in particular for the metabolites of the components.

The 1-hexadecanol and 1-octadecanol inside the UVCB (confidential data) may be hypothesized to undergo acido-basic and oxido-reductive reactions of the terminal -OH in exposed organisms, in their gut (after oral exposure) and at systemic level (after systemic absorption). They may therefore notably turn into fatty acids, and then possibly undergo the same metabolism as endogenous fatty acids, leading to physiological molecules and complete degradation.

The alkylmonoglucosides and alkyldiglucosides inside the UVCB (confidential data) may be hypothesised to undergo hydrolytic deglycosylation, leading to formation of additional amounts of 1-hexadecanol and 1-octadecanol (with the aforementioned metabolism) and of glucose (with endogenous metabolism).

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 of the components of the UVCB, it seems reasonable to predict a minor expiratory excretion of volatile carbon compounds, notably carbon dioxide produced from glucose catabolism.

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 of the components of the UVCB, it seems reasonable to predict a fecal excretion of the degradation products related to fatty acid metabolism.

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. Considering the components of the UVCB, a urinary excretion of the glucose-related metabolites is chemically possible, but should not occur due to regulation of glycemia.

There are no data (notably distribution data to mammary glands) enabling to conclude on a possible excretion into milk.

Human information:

This endpoint is not a mandatory data requirement according to Annex VI-X of the REACH regulation 1907/2006/EEC

Absorption:

Neither sensitisation nor systemic adverse effects were noted in a clinical sensitisation assay performed on acetalization product between glucose and C16/18(even numbered) alcohol. This does not enable to conclude whether the substance is not absorbed by dermal route, or is 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.