Sebacic acid

Endpoint summary

Description of key information

Four studies are available with the analogon disodium sebacate (CAS 17625-14-4) concerning metabolism, excretion, formation of ketone bodies and interference with glucose metabolism in human volunteers. The key findings are as follows: A definite amount of disodium sebacate infused is taken up and oxidized in human tissues (Migrone et al., 1991). After bolus or continuous infusion the urinary excretion of disodium sebacate and its products of beta-oxidation was found to be low and the energy production high with sebacate being completely oxidized in the organism to CO2 and H2O (Migrone et al., 1992). Disodium sebacate did not increase the formation of ketone bodies or interfere with glucose metabolism after infusion in human volunteers (Migrone et al. 1993). No change in sebacate steady-state levels was observed during hyperinsulinemia, suggesting that insulin does not influence Sb plasma clearance (Raguso et al., 1994).

Additional information

No health surveillance or epidemiological data, direct observations (e.g. clinical cases or poisoning incidents) or sensitisation data in humans are available.

Other exposure related observations in humans:

In a publication (Migrone et al., 1991) the analogon disodium sebacate (CAS 17265-14-4) was used to study the sebacate (Sb) metabolism in 7 overnight-fasted healthy male volunteers, who received a constant i.v. infusion (99 mmol over 8 h) of disodium sebacate. The Sb serum level at the plateau phase was (mean ± SD) 4.54 ± 0.71 µmol/mL, the overall rate of tissue uptake was 180.89 ± 4.50 µmol/min, and the percent oxidation was 6.14 ± 0.44 %. At the end of Sb infusion the respiratory quotient dropped to 0.839 ± 0.043, the percent of calories due to sebacate oxidation was 1.59 ± 0 .52 %, and the calories derived from lipids increased to 37.77 ± 12 .90 %. These data show that a definite amount of the sebacate infused is oxidized in human tissues.

 

In another publication (Migrone et al., 1992), again using the analogon disodium sebacate (CAS 17265-14-4), one group of healthy male volunteers received 1000 mg of sebacate as a bolus and another group received 10 g of sebacate in 500 ml water (infusion rate: 3.33 g/h for 3 h). The data distribution half-life, elimination phase, volume of the central and tissue compartment showed a good tissue fixation of sebacate. The plasma and renal clearance indicated a tubular secretion of C10. The serum concentraton of sebacate rasied to the maximum at the end of infusion. The respiratory quotient decreased significantly, the percentage of calories derived from lipids increased during and after the infusion and the metabolic rate remained constant. In conclusion, the urinary excretion of C10 and its products of beta-oxidation was found to be low and the energy production high; with C10 being completely oxidized in the organism to CO2 and H2O.

 

In another publication (Migrone et al., 1993) 10 healty men received disodium sebacate (CAS 17265-14-4) via a constant i.v. infusion of either 0.15 g/kg bw/h for 5 h or an infusion of a 50 % mixture of medium and long-chain triglycerides (MCT/LCT). In spite of its urinary loss and slower tissue uptake compared with MCTs, Sb avoided ketone body formation or elevation in insulin levels and did not induce a significant increase in oxygen consumption. The Sb caloric equivalent was 6 .643 kcal/g, and the remaining amount of Sb administered (approximately 5 .2 g/h in a 70-kg subject) seemed to be energetically useful by furnishing 34.54 kcal/h, ie, 829 kcal over 24 hours. This caloric support is equivalent to or even higher than that usually given as MCTs; however, formation of ketone bodies and interference with glucose metabolism are avoided.

 

In another publication (Ragusso et al., 1994) the effect of a continuous i.v. infusion (6.6 g/h for 5 h on 2 different days) of disodium sebacate (CAS 17265-14-4) or saline on insulin-dependent glucose metabolism was investigated in 4 control subjects, 4 patients with insulin-dependent diabetes mellitus, and 4 obese subjects. After 3 hours of infusion, a 2-h euglycemic, hyperinsulinemic clamp procedure was performed (insulin infusion rate = 40 mU/m2 per minute) and glucose uptake, plasma sebacate, insulin, glucagon, C-peptide, and ketone bodies were measured . In conclusion, Sb administration was associated with a glucose-sparing effect as shown by the reduced glucose uptake in all patients studied. Sb did not stimulate insulin secretion, since no modification of C-peptide plasma levels was observed after 3 hours of Sb infusion. In addition, no change in Sb steady-state levels was observed during hyperinsulinemia, suggesting that insulin does not influence Sb plasma clearance.