Disodium sebacate

Endpoint summary

Description of key information

Four studies are available with disodium sebacate in human volunteers.

Disodium sebacate was taken up and oxidized in human tissues (Migrone, 1991).

Disodium sebacate was completely oxidized in the organism to CO2 and H2O (Migrone, 1992).

Disodium sebacate did not increase the formation of ketone bodies or interfere with glucose metabolism in human (Migrone, 1993).

No change in disodium sebacate steady-state levels was observed during hyperinsulinemia (Ragusso, 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, 1991) disodium sebacate 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, 1992), 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 raised 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, 1993) 10 healty men received disodium sebacate 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, i.e. 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, 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.