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Administrative data

Description of key information

Repeated dose toxicity: oral:
Weight of evidence: Read-across from experimental results from no-standard studies on rats with Sodium Acetate and Citric acid, sodium salt. All these studies showed no signs of toxicity, even though in one study, the limit dose was exceeded.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral
Remarks:
other: read-across from a subacute study with an analogue
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The analogue Sodium Acetate which shares the same functional group with Calcium Acetate, also has comparable values for the relevant molecular properties for the repeated dose toxicity endpoint.
Reason / purpose:
reference to other study
Principles of method if other than guideline:
Read-across approach from published experimental data from a non-standard study on the analogue Sodium acetate.
GLP compliance:
no
Limit test:
yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Based on the experimental results obtained with the analogue Sodium acetate (NOAEL >= 3600 mg/kg bw/day in male Wistar rats treated daily by feed for 4 weeks), and the molecular weights, the read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 3472.02 mg/kg bw/day.

The analogue Sodium acetate which shares the same functional group with Calcium acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -3.72 for Sodium Acetate and -1.38 for Calcium acetate,
- a high water solubility, which is 1.25 g/mL at 25 ºC for Sodium acetate and 1000 g/L at 25 ºC for Calcium acetate, and
- similar molecular weights, which are 82.0 for Sodium acetate and 158.17 for Calcium acetate.
Dose descriptor:
NOAEL
Effect level:
>= 3 472.02 other: mg/kg bw/day (estimated)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: overall effects
Critical effects observed:
not specified

The NOAEL with the substance Calcium acetate is calculated to be equal or greater than 3472.02 mg/kg bw/day.

Conclusions:
The NOAEL with the substance Calcium acetate is calculated to be equal or greater than 3472.02 mg/kg bw/day.
Executive summary:

Based on the experimental results (reported under the endpoint record 07.05.01_02 NaAc) obtained with the analogue Sodium acetate (NOAEL >= 3600 mg/kg bw/day in male Wistar rats treated daily by feed for 4 weeks), and the molecular weights, the read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 3472.02 mg/kg bw/day.

Endpoint conclusion
Dose descriptor:
NOAEL
3 472 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated-dose toxicity: oral:

Experimental results from non-standard studies with Sodium Acetate and Citric acid, sodium salt.

In the publication reported by Cory-Slechta DA (1986), male rats were chronically treated for 8 months via drinking water with 50 or 500 ppm (0.005 or 0.05 mg/kg bw/day) Sodium Acetate from weaning. No effects were mentioned on survival, reinforcement behaviour or body weight gain.

Based on this data and the molecular weights, the read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 0.048 mg/kg bw/day.

In the second paper, reported by Dryden LP et al. (1971), effects of Sodium Acetate were studied on male Wistar rats daily treated for 4 weeks by feed with ca. 3600 mg/kg bw/day. No effects on growth or survival were observed at this dose.

The read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 3472.02 mg/kg bw/day.

In the third publication, reported by Goldman M (1981), male Long-Evans rats received daily 0 or 21 mg/kg bw/day Sodium Acetate in the diet. The investigation was terminated 3 months later and several indices of thyroid function examined. The reported effects cannot be considered as being clearly adverse. This study is considered to be of limited use in evaluating the toxicity of the substance.

Applying the read-across approach, the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 20.25 mg/kg bw/day.

In the study reported by Massaro EJ et al. (1986), Sodium Acetate was daily administered to male Wistar rats by drinking water for 112 days beginning at weaning (day 21 postpartum). Training for the latent learning task began on day 143 for the young adults. No evidence of impairment of simple task performance was observed. This study is also considered to be of limited use in evaluating the toxicity of the substance. The NOAEL was equal or greater than 0.01 mg/kg bw/day.

The read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 0.0096 mg/kg bw/day.

The last study, reported by Bonting SL et al. (1956) was performed with the analogue substance Citric acid, sodium salt. Albino rats were maintained on diets to which citric acid, sodium salt was added in a quantity that represented, on the basis of body weight, the maximum daily intake of acid that would be possile if the entire daily caloric requirements were obtained solely from the sugar contained in soft drinks. The exposure lasted for ca. 1 year.

No harmul effects were produced by the acid diet in two successive generations of animals maintained on this diet for a considerable part of the life span, as shown by an extensive study of growth, reproduction, the blood picture, the gross and microscopical appareance of the organs, the mineral and nitrogen metabolism and the tissue composition. The NOAEL was equal or greater than 50 mg/kg bw/day (nominal in diet).

Based on these results obtained with the analogue Citric acid, sodium salt and the molecular weights, the read-across approach was applied and the NOAEL with the substance Calcium acetate is calculated to be equal or greater than 55.41 mg/kg bw/day.

Justification for classification or non-classification

Repeated dose toxicity:

Oral: NOAEL>100mg/kg bw: non- classification