Fatty acids, tall-oil, reaction products with pentaethylenehexamine

Endpoint summary

Description of key information

There are no studies available in which the toxicokinetic properties of the test substance were investigated. Based on the absence of adverse findings in toxicity studies and slight changes in liver weight indicating bioavailability and probably metabolism, a potential for bioaccumulation is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of the test substance were investigated. Based on the absence of adverse findings in toxicity studies and slight changes in liver weight indicating bioavailability and probably metabolism, a potential for bioaccumulation is unlikely. Further details for this assessments are given below.

 

Chemistry

The test substance is a viscous UVCB of tall oil fatty acids with pentaethylenehexamine those water solubility (deionised water) is 5 - 19 mg/l. The material is a honey-like liquid with no definite logPow. Also a definite molecular weight of the substance does not exist (UVCB), the range of the molecular weight is from minimum 232 Da (reactant) to 1351 Da (modified fatty acid). The test material is not expected to be surface active.

 

Absorption

In acute oral and dermal toxicity studies, rats were administered to the test substance. No mortalities or clinical signs of toxicity were observed at dose levels of 2000 mg/kg bw, indicating primarily a very low level of oral and dermal toxicity. The NOAEL in male and female rats in a subacute oral repeated dose study (OECD guideline 422) is 100 mg/kg bw due to liver effects. The high molecular weight of the modified fatty acid-complexes (500 - 780 Da) may hamper gastrointestinal absorption. On the other hand, lower liver weight and increased enzyme level (ALAT, ASAT) indicate that the substance is bioavailable. The single fatty acids of the UVCB mixture for exemple may be taken up via micelles with bile acids.

Based on a model calculation (Fitzpatrick, et al., 2004) the substance is slightly skin permeable. This calculation is based on the log Pow and molecular weight of substances. Since the target substance is an UVCB, it has no definite logPow and the molecular weight ranges from minimum 232 Da (reactant) to 1351 Da (modified fatty acid). Therefore, the above mentioned result is of limited relevance.

The test substance is a highly viscous material and decomposes before boiling. This indicates that absorption of the substance via vapour inhalation is not relevant.

 

Metabolism

Single oral application of the test item to male and female rats did not provoke any effect up to 14 days post observation period. Subacute oral administration of the test substance to Wistar rats at doses of 30, 100 and 300 mg/kg/day resulted in reduced food consumption and subsequently slightly decreased body weight in the high dose group. In addition increased ALAT and ASAT levels as well as lower liver weight were observed in the 300 mg/kg bw animals. Based on the results of this study, 100 mg/kg/day was considered to be the no observed-adverse-effect-level (NOAEL).

As mentioned before, the test material is an UVCB and consists of several compounds and reaction products. It is therefore difficult to make a detailed statement on the phase I and II metabolism. Fatty acids in general are metabolized by conjugation with acetyl-CoA and subsequent beta-oxidation. Excessive fatty acid uptake results in lipid storage. Though, an increase in body weight, changes in food consumption or fatty changes in tissues and organs were not observed. This indicates that only a small part of the fatty acids are taken up (bolus effect) or the whole substrate is degradated and metabolized. The reaction products consisting of fatty acids and pentaethylenehexamine are presumbly initially degradated by gastrointestinal bacteria (shortening of fatty acid chains). The downsized compound then can be absorbed and metabolized by hydroxylation of the fatty acid chain residues. Subsequent conjugation by UGT and SULT and excretion via feces and urine seems plausible. Reaction products of high molecular weight (> 500 g/mol) are most likely not absorbed but exreted unchanged.

Dermal application caused skin irritation in rats and rabbits, signs of systemic toxicity were not observed which suggests that the test item induces primarily local effects. Besides tall oil fatty acids pentaethylenehexamine is another edukt of the chemical reaction. This substance is legally classified as corrosive (and skin sensitizing). Remaining edukt may be responsible for the local irritating effects.

  

Excretion 

As described above, high molecular weight components of the UVCB are expected to be excreted unchanged via the feces. In case of gastrointestinal uptake and metabolism through hydroxylation and conjucation it is expected that the test substances might be excreted in urine and feces. Small metabolites like pentaethylenehexamine will be excreted via urine. Overall, the test material is not expected to accumulate in the body.

 

Used references:

Fitzpatrick, D., et al. (2004). "Modelling skin permeability in risk assessment-the future." Chemosphere 55 (10): 1309-14.