Fatty acids, tall-oil, reaction products with linseed oil, maleic anhydride and methanol

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

review of the literature

Type of information:

other: study report

Adequacy of study:

key study

Study period:

April-May 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:

toxicokinetics

Qualifier:

according to guideline

Guideline:

other: Annex VIII Section 8.8 of Regulation (EC) No. 1907/2006

Qualifier:

according to guideline

Guideline:

other: Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2014)

Principles of method if other than guideline:

Paper-based review of the published scientific literature

GLP compliance:

no

Specific details on test material used for the study:

no test material used

Radiolabelling:

no

Type:

absorption

Results:

Relatively low by the oral, dermal and inhalation routes

Type:

distribution

Results:

No systemic toxicity suggests no significant distribution. Theoretically, lipophilic substances can accumulate in body fats and/or breast milk. Fatty acids are distributed into plasma and may appear in the liver

Type:

metabolism

Results:

The test substance was negative in genotoxicity studies in the presence of rat liver metabolic activation. Fatty acids in the plasma lipid fraction can undergo acylation to triglycerides and are oxidised by the β-oxidation cycle to CO2.

Type:

excretion

Results:

Primarily by fecal extraction

Details on absorption:

ZWA 5496/100 is slightly water soluble, has a relatively high log octanol water partition coefficient with a high molecular weight polymeric structure which suggests somewhat lower potential for absorption across the skin and gastrointestinal tract. Lipophilic substances have limited solubility in gastrointestinal fluids. It is likely that ZWA 5496/100 may be digested to individual fatty acids and esters which are more readily absorbed in the digestive tract. 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 repeat dose studies in the rat given ZWA 5496/100 by the oral route. The low water solubility and relatively high estimated partitioning into octanol of ZWA 5496/100 indicates that it may accumulate in body fats and/or breast milk. Fatty acids are distributed into plasma and therefore 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 ZWA 5496/100. Fecal excretion is also a likely major pathway of elimination of any fatty acids.

Metabolites identified:

no

Details on metabolites:

ZWA 5496/100 was negative for the ability to induce gene mutations in tester strains of Salmonella typhimurium and Escherichia coli, as measured by reversion of auxotrophic strains to prototrophy. The following five tester strains were used: TA1535, TA1537, TA98, TA100 and WP2 uvrA. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with Phenobarbital and 5-6 Benzoflavone (Allnex, 2015g). ZWA 5496/100 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 (Allnex, 2016d). ZWA 5496/100 did not 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, 2017a). 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 and will be circulated throughout the body, especially in perfused tissues. Fatty acids can undergo acylation by acyl transferases to triglycerides, phosphatidylcholine and cholesteryl ester (Emken, 1994) 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 (Dupont and Mathias, 1969).

ZWA 5496/100 is a UVCB of multiple individual components, many of a high molecular weight polymeric structure > 1000 d. Estimated behaviour of a model representative compound shows a low water solubility (estimated at 2.03 x 10^-6mg/L) and a relatively high log octanol water partition coefficient (estimated at 9.96). This indicates a relatively lower potential for absorption via oral, dermal and inhalation routes of exposure.

Conclusions:

The substance ZWA 5496/100 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 through the β-oxidation cycle. Metabolites are not expected to be systemically toxic. The substance is expected to show fecal elimination.

Description of key information

A review of existing data relating to toxicokinetics: low absorption by the oral, dermal and inhalation routes.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

20

Absorption rate - inhalation (%):

10

Additional information

The substance ZWA 5496/100, 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 through the β-oxidation cycle.  The substance is expected to show fecal elimination.