Sodium ascorbate

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:

For justification please refer to read across justification in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

CAS number: 134-03-2

Details on absorption:

Results from source substance:

Ascorbic acid is rapidly absorbed from the intestine by a sodium-dependent active transport process. The absorption efficiency is up to 98% at low doses and 2 % are excreted into faeces. The tranporter is saturable, the absorption efficiency therefore gradually decreases at higher intakes to 80-90% at up to 180 mg, 75 mg at 1g and 16% at 12g (Hornig and Moser, 1981).

Details on distribution in tissues:

Results from source substance:

Ascorbic acid is readily oxidised to dehydroascorbic acid which can be reduced back to ascorbic acid or hydrolysed (irreversibly) to diketogulonic acid. The latter is partly excreted with urine and partly oxidised to mainly oxalic acid and threonic acid (and to a lesser extent to xylose, xylonic acid and lyxonic acid). Oxidation to carbon dioxide is not a major route but may occur at high doses, possibly as a result of metabolism of unabsorbed ascorbate by the intestinal microflora. To some extent, ascorbic acid may also form a conjugate with sulphate which is excreted in the urine as is unchanged ascorbic acid. The percentage that is excreted depends on the dose. Only 3% of a 60 mg dose is excreted in the faeces, while the majority is excreted in the faeces at very high doses, e.g. 1 g or more. At total daily intakes above 80-100 mg, most of the ascorbic acid above this dose range is excreted unchanged in the urine, indicating that tissues reserves are saturated.

Details on excretion:

Results from source substance:

cf. sections above

Results from source substance:

The pharmacokinetics of ascorbic acid and calcium ascorbate were investigated in 20 dogs. The animals received single oral doses at two dose levels, 15 and 50 mg/kg bw. A rapid increase of the ascorbic acid plasma level was seen. The obtained Cmax and area under the curve values increased in a non-linear fashion with the increased dose.

There was no significant difference in pharmacokinetic parameters between ascorbic acid and calcium ascorbate. (Wang et al., 2001).

The EFSA ANS Panel considered that sodium and calcium ascorbate are fully dissociated in the stomach, and that the bioavailability would be expected to be similar to that of ascorbic acid in the gastrointestinal tract (EFSA ANS Panel, 2015).

Description of key information

The absorption rate is high at low and moderate doses up to 80 -100 mg/day. Most of excess dose is excreted with the urine and faeces.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Additional information

Ascorbic acid is rapidly absorbed, metabolised and excreted following oral intake. The absorption is complete at low doses whereas most of ascorbic acid above this dose range is excreted unchanged in the urine because the transporter from the gut is saturated.

Data for ascorbic acid can be adopted for sodium ascorbate because following oral intake either substance will dissociate and be protonated at the low pH value in the stomach which results in a similar absorption from the gut.