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Administrative data

Description of key information

No repeated dose toxicity study with calcium dibenzoate is available, thus the repeated dose toxicity will be addressed with existing data on the individual moieties calcium and benzoate.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

Additional information

Calcium

According to the World Health Organization the recommended lifelong daily calcium intake via diet or supplements is about 1000-1300 mg Ca. The tolerable upper intake level was determined by several intervention studies with supplemental calcium, predominantly in the form of calcium salts but also with milk products or with elemental calcium from chicken egg-shell powder, which have been performed in children, pregnant and lactating women and elderly men and women. They were exposed to total calcium of up to 3000 mg Ca/day for up to 4 years. Because none of these intervention studies showed adverse effects on human health, the Scientific Committee on food proposed a tolerable upper intake level (UL) of 2500 mg of calcium per day from all sources for adults and pregnant/lactating women (Scientific Committee on Food- Scientific Panel on Dietetic Products, Nutrition and Allergies, 2006). Hence, no adverse effects are to be expected within a daily calcium consumption of 2500 mg, constituting a human NOAEL.

 

Benzoic acid

Oral:

No adequate studies with benzoic acid are available. Several studies are available on the structural analogue sodium benzoate.

 

A short-term dietary study (10 days) with sodium benzoate in rats and mice (Fujitani, 1993) showed a NOAEL of 905 mg/kg bw in rats and of 3571 mg/kg bw in mice. Effects included decreased body weight and increased (rel) liver weights with enlarged (glossy) hepatocytes and eosinophilic foci around the protal vein. In high dosed decreased kidney weights were reported without histopathological changes. In addition, in a 35 day study in rats with sodium benzoate (Sodemoto, 1979) animals at the highest dose groups died. Symptoms in descendants were severe decrease in body weight. Morphological effects were limited to atrophy of the spleen and lymph nodes at 4 and 8% in diet. At the NOAEL 2% in diet no morphological changes were reported. In a limited reported 90-day study on sodium benzoate in rats (Weil, 1953) a NOAEL of 2,620 mg/kg bw/day was established based on reduced body weight gain, increased relative liver and kidney weights and pathological changes in liver and kidneys at 6,290 mg/kg bw/day. The overall NOAEL for repeated dose toxicity is based on a chronic toxicity study and is set at 1,000 mg/kg bw/day (Sodemoto, 1979).

For further information on the toxicity of benzoic acid, please refer to the relevant sections in the IUCLID and CSR.

 

Calcium dibenzoate

Since no repeated dose toxicity study is available specifically for calcium dibenzoate, information on the individual moieties calcium and benzoate respectively benzoic acid will be used for the hazard assessment and when applicable for the risk characterisation of calcium dibenzoate.

Justification for classification or non-classification

As the two moieties of calcium dibenzoate do not induce adverse effects up to and including and even 3-fold above the OECD/EC Guidelines limit dose for repeated oral dose toxicity testing, calcium dibenzoate in all probability has also no potential for systemic toxicity leading to a classification.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, calcium dibenzoate does not have to be classified and has no obligatory labelling requirement for Specific target organ toxicity by repeated exposure (STOT-RE).