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Description of key information

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

As the two moieties of barium 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, barium dibenzoate in all probability has also no potential for systemic toxicity leading to a classification.

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

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Barium

Repeated dose toxicity, oral, rat

Comparing the results of the different oral studies it becomes obvious that the findings of all these studies are not contradictory. The studies conducted by NTP (1994) and Dietz and co-workers (1992) in rats and mice found similar targets of toxicity; although some differences in sensitivity were found. The main adverse effect caused by barium chloride was the nephrotoxicity in rats and mice of both sexes.

The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice were identified from the 13-week drinking water study by Dietz et al. (1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats and 81 mg/kg bw/d in female rats and of about 165 mg Ba/kg bw/d in male mice and166 mg Ba/kg bw/d in female mice.

The no-observable-effect concentration of the 13-weeks NTP study (1994) conducted with barium chloride was estimated to be 2000 ppm as based on changes of the final mean body weights, mean body weight gains, mortality, and renal toxicity at 4000 ppm in both species (LOAEL). The dose of 2,000 ppm represents the NOAEL value of this study corresponding to 62.0 and 65.3 mg Ba/kg bw/d in male and female rats, respectively. Thus, the dose of 62.0mg Ba/kg bw/d in male rats and 65.3 mg Ba/kg bw/d in female rats can be regarded as relevant NOAEL for chronic barium toxicity in this 13-week study.

Taken the results for male and female rats from both studies (NTP and Dietz et.al) into consideration, an average NOAEL could safely be calculated at 61.5 mg Ba/kg bw/d, which results in a re-calculated value of 93.3 mg/kg bw/d for barium chloride.

It is explicitly noted that according to the precautionary principle the “worst case value” of 61 mg Ba/kg bw/d (in male rats according to Dietz et al.) is used for the derivation of DNELs. This value refers to approx. 92.5 mg BaCl2/ kg bw/d. However, for classification and labelling purposes it appears appropriate to consider all relevant data on repeated dose oral toxicity. As already mentioned above, the results of the NTP study (1994) and the study performed by Dietz et al. (1992) are not contradictory, and in both investigations similar target organs of toxicity were found and no differences in susceptibility of gender was seen. Therefore, it could safely be stated that the calculation of an average value, using the NOAELs for male and female rats coming from the NTP and the Dietz studies, is considered to be a valid approach for the classification and labelling discussion.

 

Benzoate

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).

Barium dibenzoate

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

As the two moieties of barium 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, barium dibenzoate in all probability has also no potential for systemic toxicity leading to a classification.

Justification for classification or non-classification

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, barium dibenzoate does not require classification, since both moieties are not classified for the repeated oral toxicity endpoint.

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