Reaction products of decanoic acid and lauric acid with glycerol and polyglycerol

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physicochemical, ecotoxicological and toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: the target and source substances are esterification products of fatty acids of varying chain lengths with glycerol and/or polyglycerol.
• the metabolism pathway leads to comparable products (glycerol and/or polyglycerol and medium or long chain fatty acids).

Therefore, read-across from the existing toxicity studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Objective of study:

absorption

distribution

excretion

metabolism

Radiolabelling:

yes

Species:

rat

Type:

metabolism

Results:

Hydrolysis of the esters occurred to a large extent prior to absorption.

Type:

other: absorption, metabolism

Results:

hexa-, penta- and higher polyglycerols are essentially not absorbed and excreted in the faeces unchanged

Type:

other: absorption, metabolism

Results:

mono-, di- and triglycerols are extensively absorbed from the intestinal tract and rapidly excreted in the urine unchanged

Type:

metabolism

Results:

fatty acids are metabolized extensively

Metabolites identified:

yes

Details on metabolites:

free fatty acids + free (poly)glycerol

Conclusions:

Based on teh available Metabolic studies it is concluded, that polyglycerin caprylate/caprinate is digested in the gut of the rat to give free polyglycerols and free fatty acids. Lower polyglycerols (up to three glycerol units) are absorbed and excreted unchanged in the urine while higher polyglycerols are excreted in the faeces. Up to 90% of the fatty acid material is absorbed and metabolized.

Description of key information

Polyglycerin caprylate/caprinate is digested in the gut of the rat to give free polyglycerols and free fatty acids. Lower polyglycerols (up to three glycerol units) are absorbed and excreted unchanged in the urine while higher polyglycerols are excreted in the faeces. Up to 90% of the fatty acid material is absorbed and metabolized.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

No experimental data are available for the target substancepolyglycerin caprylate/caprinate. However, in vivo toxicokinetic data are available for several glycerol, triglycerol and decaglycerol as well as tri- and decaglycerol esters with different numbers (1, 4, and 10) of oleic acid chains. A justification for read-across is given in iuclid section 13.

Data from metabolism studies clearly show that absorption of administered radioactivity was excellent for the fatty acid-labeled polyglycerol (G10) (oleic acid > 90 %; eicosanoic acid > 77%) and triglycerol (G3-oleate) esters. More than 90% of the triglycerol (G3) and - 40 % ofthe polyglycerol (G10) moieties were absorbed. Hydrolysis of the esters occurred to a large extent prior to absorption; the thoracic lymph duct was the major pathway for absorption of the fatty acid moieties, while absorption of the more polar G3 and G10 moieties occurred by some other pathway, presumably the portal vein.

Pancreatic enzymes hydrolyzed the oleate ester linkages of the tri-and polyglycerols as readily as they did those of natural fats (glycerides).

In catabolism studies involving triglycerol (G3*) and polyglycerol (G10*) labeled compounds, less than 4% of the 14C was excreted in the respiratory CO2. This quantity was, within experimental limits of detection, equal to the amount of glycerol contaminant in each sample that was fed. It is concluded that the polyglycerols were not catabolized and that the ether linkages within the molecule are inert to normal enzymatic hydrolysis.

The data also suggested that, unlike glycerol, the polyglycerols (G3* and G10*) were not retained appreciably in the carcass (approx. 5 %). In summary, these results show clearly that the polyglycerols were absorbed and excreted rapidly in the urine without being catabolized.