Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic information provided

Data source

Reference
Reference Type:
publication
Title:
Final Report on the Safety Assessment of Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and sodium Erythorbate
Author:
F. Alan Andersen, Cosmetic Ingredient Expert Review Panel
Year:
1999
Bibliographic source:
International Journal of Toxicology 1999 18 (suppl. 3): 1-26

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male F344 rats (five per group, 6-week-old) were given 5% Sodium Erythorbate in feed for 22 weeks. Urine pH, osmolality and metabolic breakdown products were examined.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Sodium erythorbate

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 week old

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Duration and frequency of treatment / exposure:
22 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
5%
No. of animals per sex per dose:
5 animals
Control animals:
yes, plain diet
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine

Results and discussion

Main ADME resultsopen allclose all
Type:
metabolism
Results:
The rats eliminated totals of 203.3 ± 33.2 mg/100 mL erythorbic acid and 9.0 ± 5.1 mg/100 mL dehydroerythorbic acid during the study. Ascorbic acid and dehydroascorbic acid were not detected.
Type:
excretion
Results:
Test substance - Urine pH: 6.98 ±0.31; Urine osmolarity: 1378 ± 277 mOsmol/kg. Basal diet alone - Urine pH: 6.31 ± 0.18 (p < 0.05); Urine osmolarity :1756 ± 200 mOsmol/kg H20

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Urine pH was 6.98 ±0.31, which was significantly different from that of rats given basal diet alone (6.31 ± 0.18; p < 0.05). Urine osmolarity also differed significantly from controls; osmolarity was 1378 ± 277 mOsmol/kg H20 in rats given Sodium Erythorbate and 1756 ± 200 mOsmol/kg H20 in rats of the control group. Crystals were detected in urine of rats given basal diet and Sodium Erythorbate or basal diet alone.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The rats eliminated totals of 203.3 ± 33.2 mg/100 mL erythorbic acid and 9.0 ± 5.1 mg/100 mL dehydroerythorbic acid during the study. Ascorbic acid and dehydroascorbic acid were not detected.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Executive summary:

In a dietary study, 3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone was administered to male F344 rats (five per group) at dose levels of 5% for 22 weeks.

The rats eliminated totals of 203.3 ± 33.2 mg/100 mL erythorbic acid and 9.0 ± 5.1 mg/100 mL dehydroerythorbic acid during the study. Ascorbic acid and dehydroascorbic acid were not detected. Urine pH was 6.98 ±0.31, which was significantly different from that of rats given basal diet alone (6.31 ± 0.18; p < 0.05). Urine osmolarity also differed significantly from controls; osmolarity was 1378 ± 277 mOsmol/kg H20 in rats given Sodium Erythorbate and 1756 ± 200 mOsmol/kg H20 in rats of the control group. Crystals were detected in urine of rats given basal diet and Sodium Erythorbate or basal diet alone.