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

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

15

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

75.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Short-term and local effects DNELS:

Acute/short-term DNELS were not determined as no acute toxic effects occured after oral and dermal administration to rats. Also no local dermal or iritating effects were observed on skin and eye irritation/corrosion and sensitisation. No inhalation irritation and sensitisation properties are expected from experience in handling and use of Sodium Ascorbyl Phosphate.

The following DNEL(s) for local and short term effects were not determined:

- Dermal DNEL for acute / short-term exposure - systemic effects

- Inhalation DNEL for acute / short-term exposure - systemic effects

- Dermal DNEL for acute / short-term exposure - local effects

- Inhalation DNEL for acute / short-term exposure - local effects

- Dermal DNEL for long-term exposure - local effects

- Inhalation DNEL for long-term exposure - local effects

Long-term systemic effects DNELS:

Derivation of DNEL_{long-term, dermal}

The NOAEL_{long-term, dermal}was 90.3 mg/kg bw/day, calculated from the NOAEL_{long-term, oral}, assuming 1 % resorption through the skin (see dermal absorption study). The NOAEL_{long-term, oral} was 90.3 mg/kg bw/day derived in a 28 day toxicity study (EU-B.7) with rats. An assessment factor of 120 was applied to the NOAEL_{long-term, dermal} consisting of a factor of 4 for the allometric scaling from rat to humans, a factor of 5 for the intraspecies differences (workers) and a factor of 6 for extrapolation from subacute to chronic exposure. No additional factor of 2.5 for other interspecies differences was used as Sodium Ascorbyl Phoshate is metabolized to Ascorbic Acid (physiological molecule). Thus no additional differences in toxicokinetics and metabolism are expected.

This results in a DNEL _{long-term, dermal} of 75.25 mg/kg bw/day.

Derivation of DNEL_{long-term, inhalation}

The DNEL_{long-term, inhalation}was derived from the NOAEL_{long-term, oral}of 90.3 mg/kg bw/day. The NOAEL_{long-term, oral}was 90.3 mg/kg bw/day derived in a 28 day toxicity study (EU-B.7) with rats.

The corrected NOAEL_{long-term, inhalation}was derived according to the following formula assuming a 50 % absorption for rat, oral and a 100 % absorption for inhalation:

NOAEL_{long-term, inhalation}= NOEL_{long-term, oral}* 1/standard Resp. Vol._rat* Absorption_oral-rat/Absorption_inh-human* standard Resp. Vol._human/worker Resp. Vol.

                                           = 90.3 mg/kg bw/day * 1/(0.38 m³/kg/d) * 50 %/ 100 % * 6.7m³/10 m³

                                           = 79.6 mg/m³

For DNEL derivation, an assessment factor of 15 was applied to the NOAEL_{long-term, inhalation}consisting of a factor of 5 for the intraspecies differences (workers) and a factor of 3 (based on the evaluation of approx. 2200 repaeted dose studies on 661existing chemicals in the RepDose database, Escher et al.(2009) Evaluation of risk assessment factors for inter-species and time-extrapolation. Tox Letters 189S, S247, H34) for extrapolation from subacute to chronic exposure. No additional factor of 2.5 for other interspecies differences was used as Sodium Ascorbyl Phoshate is metabolized to Ascorbic Acid (physiological molecule). Thus no additional differences in toxicokinetics and metabolism are expected.

This results in a DNEL_{long-term, inhalation}of 5.2 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

No DNELS for the general population (Consumer) were determined. The use of Sodium Ascorbyl Phosphate in cosmetical products is covered by an other legislation and has thus not to be regarded under REACH.