Barium di(acetate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic toxicity data are not available for barium di(acetate). Since the acetate anion in barium di(acetate) does not contribute to the overall toxicity of barium di(acetate) (see additional information), it is concluded that only the effect of “barium” will further be considered in the human health hazard assessment of barium di(acetate). However, studies conducted with soluble barium substances were included in the dossier. In conclusion no mutagenic / genotoxic effects were observed in relevant in vitro tests.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Read-across concept:

Genetic toxicity data specifically for barium di(acetate) are not available. Instead, read-across from studies performed with barium dichloride dihydrate and acetate are considered to be justified without restriction.

Barium di(acetate) completely dissolves upon contact with water to Ba2+and 2*CH3COO-. The water solubility (CRC handbook, 2008) of barium di(acetate) indicates a complete dissolution and a rapid formation of Ba2+and 2*CH3COO-(792 mg/L at 25°C). The pH of a saturated aqueous solution of barium di(acetate) is pH 7.9. Considering that systemic human health effects of barium di(acetate) are due the dissolved concentrations of Ba2+and CH3COO-in physiological solutions, read-across to soluble (i.e., > 10 g/L at room temperature) inorganic barium compounds and acetic acid and its salts (i.e., > 10 g/L at room temperature) is performed and considered to be very conservative with regard to systemic toxicity.

 

There are reliable studies addressing the genetic toxicity of barium dichloride. However, there are no reliable studies available in the public domain which address the genotoxic effects of acetate. Nevertheless, the registrant of barium di(acetate) is of the opinion that the toxicity of barium di(acetate) is driven by the barium moiety, and that the acetate anion does not contribute to the overall toxicity of the substance barium di(acetate) to any relevant extent. For completeness, the toxicological relevance of the counter-ion acetate is addressed below:

 

Acetate:

Acetic acid, calcium acetate, and sodium diacetate have a well-established history of use in food where they are considered safe at any concentration level, consistent with their intended physical, nutritional or other technical effect. They are also widely used in human and veterinary medicine, cosmetics, as plant protection agents and in a variety of household products as buffering agents or because of their anti-microbial properties.

The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded “Acetic acid, sodium diacetate, and calcium acetate are permitted food additives that may be added directly to food intended for human consumption without any limitation. This authorisation followed the assessment of safety by JECFA (1974, 1998) and the EU Scientific Committee on Food (SCF, 1990).

JECFA considered acetic acid, calcium acetate, and sodium diacetate separately although data on acetic acid were primarily considered in each evaluation as no specific studies on sodium diacetate and calcium acetate were identified at that time. JECFA allocated an ADI of “not limited” (i.e., “not specified”) to acetic acid and its calcium salt in 1974 and this conclusion was retained when JECFA evaluated a group of saturated linear primary alcohols, aldehydes, and acids that included acetic acid in 1998.” (EFSA 2012).

Based on the above information, one can therefore safely assume that the acetate anion in barium di(acetate) does not contribute to the overall toxicity of barium di(acetate). It is concluded that only the effect of “barium” it further considered in the human health hazard assessment of barium di(acetate).

 

Barium(II):

Systemic effects observed for barium dichloride are considered to be very conservative compared with barium di(acetate). This is supported by the results of acute oral toxicity testing with barium dichloride and barium di(acetate). A study performed with barium dichloride resulting in an LD50 ≥ 100 till ≤ 300 mg/kg bw whereas a study with barium di(acetate) (toxic if swallowed) resulting in an LD50 of 500 mg/kg bw. (harmful if swallowed). Based on test results barium dichloride is considered to be toxic if swallowed whereas barium di(acetate) requires classification as harmful via ingestion. In both studies systemic effects were observed.

 

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation tests (TK assay) or in mammalian cell chromosome aberration tests, thus the barium di(acetate) is considered to be not a germ cell mutagenic substance.

 

References:

EFSA (2012) Scientific Opinion on the safety and efficacy of acetic acid, sodium diacetate and calcium acetate as preservatives for feed for all animal species, EFSA Journal 10(2):2571

 

Joint FAO/WHO Expert Committee On Food Additives (JECFA), 1974. Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents. WHO food additives series NO. 5. World Health Organisation, Geneva. Available at:http://www.inchem.org/documents/jecfa/jecmono/v05je01.htm

 

Joint FAO/WHO Expert Committee On Food Additives (JECFA), 1998. Safety Evaluation of Certain Food Additives and Contaminants. WHO Food Additives Series, No. 40. World Health Organisation, Geneva. Available at:http://www.inchem.org/documents/jecfa/jecmono/v040je01.htm

Justification for classification or non-classification

Mutagenic / genotoxic effects were not observed in relevant in vitro tests with soluble inorganic barium substances. A similar conclusion is derived for barium di(acetate) since potential effects would be regarded to as barium-ion related effects. Hence, classification and labelling of barium di(acetate) is not required.