2,3-didehydro-D-erythro-hexono-1,4-lactone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

review article or handbook

Title:

Final Report on the Safety Assessment of Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate,Erythorbic Acid, and sodium Erythorbate

Author:

F. Alan Andersen

Year:

1999

Bibliographic source:

International Journal of Toxicology

Materials and methods

Test guideline

Guideline:

other: Absorption, Distribution, Metabolism, and Excretion

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,3-didehydro-D-erythro-hexono-1,4-lactone

EC Number:

201-928-0

EC Name:

2,3-didehydro-D-erythro-hexono-1,4-lactone

Cas Number:

89-65-6

Molecular formula:

C6H8O6

IUPAC Name:

(5R)-5-[(1R)-1,2-dihydroxyethyl]-3,4-dihydroxy-2,5-dihydrofuran-2-one

Test material form:

solid: crystalline

Administration / exposure

Route of administration:

oral: feed

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Main ADME results 2

Type:

distribution

Main ADME results 3

Type:

metabolism

Main ADME results 4

Type:

excretion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Homig (1977) reported that absorption was approximately four-to-one in favor of ascorbic acid, but the availability of ascorbic acid decreased by 40-60% when administered with Erythorbic Acid. Further data indicated that Erythorbic Acid promoted the acceleration of oxidative destruction of ascorbic acid in the liver.
Another study by Suzuki, Kurata, and Arakawa (1991) determined that Erythorbic Acid was absorbed less efficiently than ascorbic acid in the small intestine of male Hartley guinea pigs. The data also suggested that Erythorbic Acid was absorbed from the small intestine by the same active transport mechanism as used for ascorbic acid. The absorption rates of both in the small intestine could be dependent on the concentration of ascorbic acid already present in the tissues of the guinea pig.

Details on distribution in tissues:

Erythorbic Acid was not transported in vivo into the brain, cerebrospinal fluid (Homig 1977), white blood cells, adrenal glands, and the globes as effectively as L-ascorbic acid.
In studies in which L-ascorbic acid intake was low, the greatest concentrations of Erythorbic Acid were in the liver, adrenal glands, spleen, and kidneys (Suzuki et al. 1986).

Details on excretion:

Tsao and Salimi (1983) gave 21 Swiss Webster female mice (4-week-old) feed containing 5% ascorbic acid or Erythorbic Acid crystals for 2 months. The mice (five per group) were then fed diet containing 10% ascorbic acid or Erythorbic Acid for 5 additional months. Eleven mice received ascorbic acid-free diet throughout the experiment. Urine was collected and analyzed 2 weeks before termination of the study. The mice were killed and their brains and livers were removed and stored for analysis. The amount of urinary Erythorbic Acid excreted from mice given Erythorbic Acid was approximately twice that of mice given ascorbic acid.
Erythorbic Acid apparently was not reabsorbed after glomerular filtration, and, therefore, was excreted from the kidneys more rapidly than L-ascorbic acid. In dogs, this resulted in a half-life of approximately 30 minutes for Erythorbic Acid in the plasma (Silber 1956). Wang, Fisher, and Dodds (1962) reported that Erythorbic Acid was excreted faster than L-ascorbic acid in humans.

Metabolite characterisation studies

Details on metabolites:

The reduced form of Erythorbic Acid was incorporated into human erythrocytes at the rate of 20% per 2 hours and the rate of uptake of this form was proportional to the extracellular concentration. The oxidized form of Erythorbic Acid, D-dehydroisoascorbic acid, became incorporated more rapidly than the reduced form, at a rate of 50% per 5 minutes, and 80% of the acid absorbed was subsequently reduced within the cells. The reduced form of Erythorbic Acid was more stable in plasma than the oxidized form, of which 61 % was degraded in 60 minutes. In erythrocytes, the reduced form was stable, as in plasma, and the oxidized form slightly less so (Teruuchi and Okamura 1972).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results