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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Short description of key information:
No data available. In accordance with column 2 of REACH Annex VIII, the toxicity to reproduction study (reproduction screening test, 8.7.1) does not need to be conducted as two studies on prenatal developmental toxicity (8.7.2) are available for ascorbic acid (read across).

Effects on developmental toxicity

Description of key information

No study is available for Sodium ascorbyl phosphate. A read across was performed to the parent compound Ascorbic acid to fill the data gap. 
A developmental toxicity/teratogenicity study by Frohberg (1973) showed no maternally toxicity, fetotoxicicity, or teratogenic effects in rats and mice. Ascorbic Acid did also not affect embryonal, fetal, and postpartal development of rat pups. 
In a further study in rats and hamsters no developmental toxicity was observed by Alleva (1976) . 
Summarised, no developmental toxicity was observed in rats, mice and hamsters after oral administration during the gestation period up to the highest doses tested (1000 mg/kg /450 mg/kg. .
Thus, it can be concluded that Ascorbic acid and Sodium ascorbyl phosphate are not toxic to development and not teratogenic.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

450 mg/kg bw/day

Additional information

Teratogenicity/Developmental toxicity Study Frohberg (1973) – Read across from Ascorbic acid:

In a developmental toxicity study Ascorbic acid was administered to

- 17-22 female Wistar rats/dose in water at dose levels of 0, 250, 500, 1000 mg/kg bw/day from days 6 through 15 of gestation (Teratogenicity test).

- 24-27 female Wistar rats/dose in water at dose levels of 0, 250, 500, 1000 mg/kg bw/day from days 0 of gestation through 21 post partum (peri- and postnatal test).

- 21-23 female NMRI mice/dose in water at dose levels of 0, 250, 500, 1000 mg/kg bw/day from days 6 through 15 of gestation (Teratogenicity test).

Teratogenicity test (rats and mice):

The treatment did not produce maternally toxic, fetotoxic, or teratogenic effects. There was no effect on gestation or on maternal body weight gain. The number of abortions and resorptions, the mean number of live fetuses per dam, the mean fetal body weight, and the incidence of runts or malformed fetuses were not affected by treatment with the test substance.

Peri- and postnatal test (rats):

The test substance did not affect embryonal, fetal, and postpartal development of the pups. There was no substance-related effect on gestation, delivery, maternal raising instinct or lactation. In the high dose group, the mean number of implantations per dam and the mean number of live pups per dam was decreased when compared with vehicle controls and with basic controls. According to the authors, although these changes were not statistically significant, an effect of this "extremely high dose level" of the test substance on nidation could not be fully excluded.

No LOAELs can be evaluated as no adverse effects occurred. The maternal NOAEL is > 1000mg/kg bw/day. The developmental NOAEL is > 1000 mg/kg bw/day.

The developmental toxicity study in the rat is classified acceptable and meets generally accepted scientific standards, well documented and acceptable for assessment

Teratogenicity/developmental toxicity Study Alleva (1976) – Read across from Ascorbic acid:

In a developmental study Ascorbic acid was administered to

- 11 female Holtzman rats/dose orally at dose levels of 0, 50, 150, 450 mg/kg bw/day from day 1 to 19 of pregnancy.

- 10-14 female hamsters/dose orally at dose levels of 0, 50, 150, 450 mg/kg bw/day from day 1 to 15 of gestation.

Abortion, mortality of offspring, and live pup weights were determined. No other parameters were investigated. No increase in abortion or mortality of offspring was observed in all species. A slight increase in pup weight was observed in one group of hamsters. This is considered as no adverse effect.

No LOAEL can be evaluated as no adverse effects occurred. The NOAEL is > 450 mg/kg bw/day in female rats and hamsters.

Justification for classification or non-classification

Based on the results (no developmental tocicity, no teratogenicity - read across from Ascorbic Acid) Sodium ascorbyl phosphate is not classified reprotoxic according to EU Directive 67/548/EC amended and repealed by EU Regulation No.1272/2008 and CLP.