Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Expert statement
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well prepared expert statement according to national and international standards

Data source

Reference
Reference Type:
other: expert statement
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Objective of study:
other: The absorption, distribution, metabolism and excretion of FAT 40069/D TE have been predicted in the absence of toxicokinetic studies.
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The absorption, distribution, metabolism and excretion of FAT 40069/D have been predicted in the absence of toxicokinetic studies.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
None

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Due to the high water solubility (257 g/L) of the test item and or metabolites absorption through passive diffusion from the gastro-intestinal tract could take place following oral administration, before entering the circulatory system via the blood. Furthermore, data derived from skin and eye irritation studies and a skin sensitization study that were conducted on a similar chemical substance produced by the study sponsor indicated the potential for limited absorption to also take place via topical exposure to the skin and eyes.
Details on distribution in tissues:
There is minimal information available relating to the distribution of FAT 40069/D; however, it is reasonable to assume once absorbed, the substance would be distributed in serum and thereby available systemically. The low log octanol/water partition coefficient (log10 Pow -3.11) and high water solubility (257 g/L) would also suggest that the test item is not lipophilic and unlikely to accumulate in body fat. The positive skin sensitization response identified in a closely related chemical to FAT 40069/D suggests that the test item may bind to carrier proteins in the circulatory systems thereby facilitating systemic distribution.
Details on excretion:
There is no evidence to indicate the route of excretion but high water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. Any test item that is not absorbed from the gastro intestinal tract would be excreted in the faeces.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
While there is no confirmatory evidence to indicate how FAT 40069/D nor its metabolites are metabolised; a genotoxicity assay did indicate the test item to be clastogenic albeit no information was provided to indicate whether this was in the absence or presence of metabolic activation; although the rat S9 metabolising system does not necessarily reflect human metabolism.

Applicant's summary and conclusion

Conclusions:
Bioaccumulation potential cannot be judged based on study results. The available information would suggest absorption of the test substance would take place via the gastrointestinal tract. Some absorption may also take place through topical exposure to the skin and eyes. Once absorbed, the substance would be distributed in the serum with urine the most plausible route of excretion with any unabsorbed test material excreted in faeces.
Executive summary:

The absorption, distribution, metabolism and excretion of FAT 40069/D have been predicted in the absence of toxicokinetic studies. FAT 40069/D being highly water solubility suggests absorption is likely to take place through passive diffusion from the gastro-intestinal tract following oral administration; thereby entering the circulatory system via the blood. Supporting information also indicated limited absorption may also take place via damaged skin. FAT 40069/D no uptake via inhalation is anticipated on the basis of the inhalable particle size (53.6 % at (<100 μm) permitting almost all inhaled particles to be cleared in the oral/nasal region and subsequently swallowed with the mucus. FAT 40069/D the test item was found to be mutagenic in bacteria. However, there was no confirmatory evidence to indicate how the test substance is metabolised, although no studies have yet been conducted to identify metabolites. Excretion of FAT 40069/D and any of its predicted metabolites following oral exposure is anticipated to be from the gastro intestinal tract via the urine with any unabsorbed test material excreted in faeces.