Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Materials and methods

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 route 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 flakes or pellets.
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 components of the UVCB may undergo acido-basic, oxido-reductive 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:

All these comments are reported in the CSR documents enclosed to the IUCLD 5 file. the different sections listed are from this report.

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:

No systemic adverse effects have been noted after single-dose (see 5.2.1.1) and repeat-dose (see 5.6.1.1, 5.9.1.1 and 5.9.2.1) oral exposure in animals. This does not enable to conclude whether the substance is not absorbed by oral route, or is absorbed but non-toxic. However, 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 flakes or pellets (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 exposure (see 5.2.1.3 and 5.3.1.1) and after induction and challenge dermal applications (see 5.5.1.1). This does not enable to conclude whether the substance is not absorbed by dermal route, or is absorbed but non-toxic. However, the molar mass (ranging 299–651 g/mol for individual components of the substance), the high to very high lipophilicity (log Kow ranging 4.3-9.7 for individual components of the substance) and the very low water solubility (≤ 1 mg/L) may be expected to considerably limit the dermal penetration of the substance. Furthermore, the substance is manufactured as flakes or pellets (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 adverse effects in all the 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 (see 5.7), the addition of liver microsome fraction (S9 mix) had no influence on cytotoxic and genotoxic effects of the substance (however two of these tests did not include the maximal recommended concentration). There is therefore 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-eiconasol (C20) and 1-doconasol (C22) inside the UVCB (confidential data) may be hypothesised 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. 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-eiconasol and 1-doconasol (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.

No gastro-intestinal clinical signs and no coloration of feces were noted after repeated oral exposure to the substance (see 5.6.1.1). 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 (see 5.6.1.1). 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

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 (see 5.5.1.2). 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 (see 5.1.1) remains the most reliable one.

Distribution / Metabolism / Elimination:

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

Absorption by oral route is expected to be good. For the substance per se, absorption by respiratory route is undetermined and absorption by dermal route 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 flakes or pellets.

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 components of the UVCB may undergo acido-basic, oxido-reductive 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.