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

Endpoint summary

Description of key information

One 28-day repeated dose toxicity study (oral administration) is available (dose levels 0, 1000, 5000, 15000 ppm). Only minor effects were seen such as increased water consumption (high dose group) and histopathological changes in the urinary bladder (high dose group, males only) and thymus (high and mid dose group, females only). The no observed adverse effect level (NOAEL) under the conditions of this study was 5,000 ppm (424.1 mg/kg body weight) in males and 1,000 ppm (90.3 mg/kg body weight) in females. 
No repeated dose toxicity studies for dermal and inhalative administration are available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

90.3 mg/kg bw/day

Additional information

28-day study (oral administration):

In a subacute toxicity study (BASF AG, 1998) Sodium ascorbyl phosphate (85.4 %) was administered to Wistar rats (5/sex/dose) in water at dose levels of 0, 1000, 5000, 15000 ppm [0, 82.8, 424.1, 1426.0 mg/kg bw/day (male); 0, 90.3, 512.0, 1661.7 mg/kg bw/day (female)]. Only minor effects were seen such as increased water consumption and histopathological changes in the urinary bladder and thymus (slight increase in starry sky cells in females). However, the toxicological relevance of these findings is regarded to be rather low as no other alteration were observed and the effects noted can be explained as:

- nonspecific inflammation (urinary bladder)

- high sodium content in test substance (water consumption).

- thymus effects only in females might also be of secondary nature (complete reversible within the 2 week-recovery period).

After a 2-week recovery period, no treatment related microscopic findings were noted, whereas the water consumption was still increased in females. There were no compound related effects in mortality, clinical signs, body weight, hematology, clinical chemistry, organ weights, or gross pathology.

Based upon the results obtained, the no observed adverse effect level (NOAEL) under the conditions of this study was 5,000 ppm (424.1 mg/kg body weight) in males and 1,000 ppm (90.3 mg/kg body weight) in females.  

This subacute toxicity study in the rat is acceptable and satisfies the guideline requirement for a subchronic oral study (EU-method B.7; OECD 408) in rats.

Justification for classification or non-classification

Based on the results of the oral 28 -day repeated dose toxicity study (lowest NOAEL 90.3 mg/kg bw/day) Sodium ascorbyl phosphate is not classified according to EU Directive 67/548/EC amended and repealed by EU Regulation No.1272/2008.

Classification according to CLP/GHS:

In the 28-day repeated dose toxicity study a NOAEL of 90.3 mg/kg bw/day was reported. This NOAEL is only observed for female animals due to minor histopathological changes in the thymus (3 of 5 animals), that were completely reversible within recovery period of 14 days. The toxicological relevance of these findings is regarded to be rather low and not relevant to justify category 2 for specific target organ systemic toxicity - repeated exposure. Thus in conclusion Sodium Ascorbyl Phosphate is not classified according to CLP.