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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Remarks:
review of existing data
Type of information:
other: review of existing data
Adequacy of study:
key study
Study period:
2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
A paper-based toxicokinetic assessment (TKA) was conducted in accordance with Annex VIII Section 8.8 of Regulation (EC) No. 1907/2006 and based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2014).
Objective of study:
absorption
distribution
excretion
metabolism
Qualifier:
according to guideline
Guideline:
other: Regulation (EC) No. 1907/2006, Annex VIII Section 8.8
Qualifier:
according to guideline
Guideline:
other: ECHA, 2014, Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance
Principles of method if other than guideline:
Paper-based review of the available literature
GLP compliance:
no
Radiolabelling:
no
Type:
absorption
Results:
Low absorption via oral, dermal and inhalation routes
Type:
distribution
Results:
Low observed toxicity suggests minimal distribution or absorption into the systemic compartment. Theoretically, absorbed material may be broken down into fatty acid derivatives, which are distributed through the systemic circulation and metabolised.
Type:
metabolism
Results:
In in vitro mutagenicity studies, metabolism by rat hepatic S9 fraction did not result in formation of mutagenic products.
Type:
excretion
Results:
Elimination of unabsorbed and unchanged ZEF 6099/100, as well as fatty acid esters, is likely via fecal excretion.
Details on absorption:
ZEF 6099/100 is very slightly water soluble, has a relatively high log Kow with a high molecular weight polymeric structure which suggests low potential for absorption across the skin and gastrointestinal tract. Lipophilic substances have limited solubility in gastrointestinal fluids. While dermal absorption data for ZEF 6099/100 are not available, topically applied fatty acid methyl esters are theoretically able to penetrate to the living cells of normal epidermis, enter into metabolism and significantly modify endogenous epidermal lipids. Due to its molecular weight, ZEF 6099/100 will not readily penetrate the epidermis and due to the low water solubility, ZEF 6099/100 will not readily pass from epidermis to dermis. The low vapor pressure exerted is an indication of low potential exposure by the inhalation route as well.
Details on distribution in tissues:
No evidence of systemic target organ toxicity was seen in a repeated dose study in the rat with ZEF 6099/100 by oral administration. The low water solubility and relatively high partitioning into octanol of ZEF 6099/100 indicates that it may accumulate in body fats and/or breast milk. Fatty acid esters are distributed into plasma and will be distributed to highly perfused tissues such as the liver.
Details on excretion:
Fecal excretion is likely a major route of elimination of unabsorbed and unchanged ZEF 6099/100. Fecal excretion is also a likely major pathway of elimination of any fatty acid esters.
Metabolites identified:
no
Details on metabolites:
ZEF 6099/100 is not active in mutagenicity assays in the absence and presence of metabolic activation by rat liver S9-mix induced by Aroclor 1254. ZEF 6099/100 also did not induce gene mutations at the HPRT locus in V79 cells in the absence and presence of metabolic activation by rat liver S9-mix induced by Aroclor 1254, nor did it induce the formation of micronuclei in human lymphocytes in vitro in the absence and presence of metabolic activation by rat liver S9-mix induced by Aroclor 1254 (Allnex, 2016, 2017). In each of these assays, metabolism by S9 rat liver enzymes did not result in increased mutation frequency.
Individual fatty acids found in the plasma lipid fraction will be circulated throughout the body, especially in perfused tissues. Fatty acids can undergo acylation by acyl transferases to triglycerides, phosphatidylcholine and cholesteryl ester which are found in the plasma lipid fraction. Fatty acids can also be oxidized via the β-oxidation cycle. Once in the β-oxidation cycle most fatty acids are completely oxidized to carbon dioxide. Β-oxidation is higher in rodents than in humans and is slower with increasing fatty acid saturation.

ZEF 6099/100 is a UVCB of complex reaction products, many of which are polymers/oligomers which have a high molecular weight over 1000 d. Results from computer models ((QSAR, EPI-Suite and OECD QSAR Toolbox) of the individual components of the UVCB show high log Kow values ranging from 10.46 -16.95.

Conclusions:
The substance ZEF 6099/100 is expected to show low absorption by the oral, dermal and inhalation routes. If absorbed, it may be distributed to highly perfused organs, and the fatty acid components metabolised as triglycerides through the β-oxidation cycle. Metabolites are not expected to be systemically toxic. The substance is expected to show significant fecal elimination.

Description of key information

A literature review of toxicokinetics was undertaken with low absorption via oral, dermal and inhalation routes, and possible moderate absorption of breakdown products of the fatty acid residues. The potential for bioaccumulation is low.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
10

Additional information

ZEF 6099/100 is not toxic by the oral route in animal studies. Low water solubility, relatively high log octanol water partition coefficients and high molecular weight polymeric structure would suggest somewhat lower potential for absorption across the skin, gastrointestinal tract and respiratory tract. It is likely that ZEF 6099/100 may be digested to individual fatty acid esters which are more readily absorbed in the digestive tract. ZEF 6099/100 would be absorbed by the gastrointestinal tract with an absorption rate < 50%. Dermal absorption rate is likely <10%. Low volatility, the lack of hydrolysis, and limited solubility do not favor respiratory tract absorption. Inhalation absorption rate is also likely < 10%.