L-Ascorbic acid, 2-(dihydrogen phosphate), sodium salt (1:3)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 96/54/EG, B.7; OECD 407 (1995)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

425-180-1

EC Name:

-

Cas Number:

66170-10-3

Molecular formula:

C6H6Na3O9P

IUPAC Name:

trisodium (2R)-2-[(1S)-1,2-dihydroxyethyl]-5-oxo-4-(phosphonatooxy)-2,5-dihydrofuran-3-olate

Test material form:

solid: particulate/powder

Test animals

Species:

other: rat, Wistar Chbb:THOM (SPF)

Strain:

other: Wistar Chbb:THOM (SPF)

Administration / exposure

Route of administration:

oral: unspecified

Details on oral exposure:

Method of administration:
Trinkwasser (drinking water)

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 83 mg/kg bw/day
Male: 5 animals at 424 mg/kg bw/day
Male: 5 animals at 1426 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 90 mg/kg bw/day
Female: 5 animals at 512 mg/kg bw/day
Female: 5 animals at 1662 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
The males (1426 mg / kg) and females (1662 mg / kg) of the 15000 ppm dose showed an increased water consumption. Studies on neurofunction did not reveal any effects on the nervous system.

no. of studies subacute: 1
no. of applications/duration: 28x/28 d recovery period:
14d
species: rat
route of application: oral (drinking water)
Relevant toxic effects:
dose levels (mg/kg): 1000 5000 15000 rec/15000
no. of animals/sex: 5m 5f 5m 5f 5m 5f 5m 5f
water consum increased X X X
organ weight
increased absolute ovary weight X
microscopic findings
-organ system/lesion
urinary bladder/urothel hyperplasia 5X 1X
urinary bladder/cystitis 4X
thymus/starry sky cells increased 3X 4X

Comment:
The substance concentrations were equivalent to 83, 424, and 1426 mg/kg in males and 90, 512, and 1662 mg/kg in females. The primary toxic effect induced by the test substance was urothel hyperplasia in males and one female of the high dose groups and cystitis in high dose males. Increased occurrence of starry sky cells in the thymic cortex indicating increased thymocyte cell death/apoptosis was not corroborated by other immunotoxic effects. Therefore it was considered of minor toxicological significance. Microscopic lesions were absent in the ovaries with lower absolute weights. All effects beside increased water consumption were reversible.
No-observed-adverse-effect-level (NOAEL):
90 mg/kg in female rats, 424 mg/kg in male rats
Laboratory findings:
No treatment related effects.

Effects in organs:
The absolute ovary weight was reduced in the females of the high dosage; there was no morphological correlate.
In the thymus of three females of the 512 mg / kg dose, star sky macrophages were increasingly detected in the cortex area. All males of the 1426 mg / kg dose had mild to moderate diffuse hyperplasia of the urinary bladder epithelium; four males of this dose had cystitis, and one of these males also showed ulceration of the urothelium. Poor multifocal hyperplasia of the urinary bladder epithelium has been demonstrated in a female of the high dose. In four females of this dosage, more starry sky cells were found in the thymus cortex.
After the end of the recovery period, all effects were reversible with the exception of increased water consumption in the females.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

90 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

90 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as: Not classified