Carboxylic acids, di-, C4-6

Endpoint summary

Additional information

Studies to assess the toxicokinetic behavior are not available for the multi-constituent Glutaric acid tech.. However, limited information is available for the single constituents, mainly the source adipic acid. In limited studies in animals and humans it was shown that adipic acid is nearly completely absorbed after oral administration, partially metabolized to various metabolites and CO2 which are excreted via urine and breath, respectively (OECD/ICCA HPV, 2004; for details see below). It is suggested that adipic acid is degraded via ß-oxidation (MAK, 2017a). In the EU, adipic acid is registered as food additive with the number E355 (EU Food Additives Database).
Glutaric acid is a central endogenous metabolite in the amino acid pathway and humans excrete approximately 2.4 g glutaric acid per day (MAK, 2019). Succinic acid is a component of the citric acid cycle which it is metabolized via fatty acid β-oxidation or the tricarboxylic acid cycle (citric acid cycle; MAK, 2017b). Also for glutaric acid ß-oxidation is the suggested degradation pathway (MAK, 2019).
In summary, the three dicarboxylic acids show comparable toxicokinetic behaviors.

 

Adipic acid:

OECD/ICCA high production volume chemicals program in 2004 evaluated adipic acid and concluded:

"After oral administration by gavage of radioactive adipic acid to fasted rats up to 70 % of the dose was exhaled as CO2. In the urine the parent compound adipic acid and metabolic products identified as urea, glutamic acid, lactic acid, beta-ketoadipic acid and citric acid were found (percentages not specified). Adipic acid was metabolized by beta-oxidation in a similar fashion as fatty acids and acetate was a metabolite of adipic acid. Radioactive glycogen was isolated in experiments where glycogen formation in the liver was encouraged by oral administration of glucose together with radioactive adipic acid."

"When adipic acid or its sodium salt was administered to non fasted rats, rabbits and one dog 18 to 71 % of the doses were excreted in the urine. Breath was not analyzed in these studies. In an oral 28-day subacute study in rats excretion of adipic acid was similar from day 1 to 28, indicating that adipic acid did not accumulate during the treatment. Breath was not analyzed. It is unclear whether the methods of detection in these early studies were reliable."

 

"Adipic acid was orally administered to humans to investigate compound excretion. The highest dose administered in one volunteer was 70 g over 10 days. 3 other persons took 19 to 23.4 g over up to 9 days. 15 - 75 % of the adipic acid dose was found unchanged in the urine after oral administration of up to 7 g of adipic acid over up to 10 days to 7 volunteers. Breath was not analyzed, and it is unclear whether the methods of detection used were reliable."