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Administrative data

Description of key information

Acute oral toxicity: LD50 = 1690 mg/kg bw
Acute dermal toxicity: derogation statement included; according to SIAR 2008 an LD50 >1895 mg/kg was stated in the NIAR report 2008 (based on barium carbonate)
Acute inhalation toxicity: data waiving

Key value for chemical safety assessment

Additional information

Acute toxicity, oral:

A reliable acute oral toxicity study with BaCO3 (Müller, 1983) results in an LD50 of 1690 mg/kg for males and females. Based on the results of this study, it was concluded that BaCO3 requires a classification and labelling as "acute tox 4"; H302 (harmful if swallowed) according to GHS.

Read-across BaCl2to BaCO3:

The classification as 'harmful' is supported and confirmed by read-across with BaCl2. The toxicity of barium substances such as barium carbonate can reasonably assumed to be determined by the availability of barium ions in solution. This was investigated for barium carbonate experimentally in a test for comparative bio-accessibility with barium carbonate and barium chloride in artificial gastric juice (HCl, pH=1.5): an excess of each test item was added to a freshly prepared HCl solutions (pH=1.5) to obtain saturation (for details, please refer to IUCLID section 4.20 “pH” of this dossier). It could be shown that the solubility of barium carbonate in acidic media at 37°C is 3.7 g/L, whereas 510.4 g/L of barium chloride could be dissolved under equal conditions. In consequence, the solubility of barium carbonate under these conditions is more than two orders of magnitude less than that of barium chloride. The available acute oral toxicity data of barium chloride can be used to read-across to barium carbonate as follows:

(i) two reliable studies describing the acute oral toxicity of barium chloride (Borzelleca_1988 and Tardiff 1980) were found in the public domain. Both were used to support the endpoint acute oral toxicity for barium chloride. The study performed by Borzelleca in 1988 yielded an LD50 >100 and <300 mg/kg bw, wereas the study conducted by Tardiff 1980 resulted in an LD50 of 300 mg/kg bw. Taking both studies into consideration for classification, an LD50 ≤ 300 mg BaCl2/kg bw was derived, resulting in a classification and labelling requirement of "acute tox. 3"; H301 (toxic if swallowed) according to regulation (EC) 1272/2008 for barium chloride.

(ii) When reading across from these data to barium carbonate, initially an LD50 of ≤ 284 mg/kg bw can be calculated stochiometrically. The proximity of this value to the thresholds for classification as toxic (≤ 300 mg/kg bw according to regulation EC 1272/2008 and > 200 mg/kg bw according to directive 67/548/EEC) and the more than 100-fold lower solubility of barium carbonate (3.7g/L at 37°C / media pH 1.5) compared to barium chloride (510.4 g/L at 37°C / media pH 1.5) is taken as reasoning to confirm classification of barium carbonate as “harmful if swallowed”.

Acute toxicity, dermal:

The toxicity of barium carbonate and barium chloride may reasonably be considered to be determined by availability of Ba2+cations. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Barium carbonate is poorly soluble in water whereas barium chloride is well water soluble.Read-across from soluble to the poorly soluble barium compound is considered acceptable because toxicokinetic data on the poorly soluble barium carbonate indicates a markedly lesser bioavailability than the soluble barium chloride. However, it is to be concluded that this read-across will likely lead to rather conservative no-effect levels.

Annex VIII, point 8.5 of Regulation No 1907/2006 specifies that information on the acute toxicity of substances shall be provided according to the relevant exposure routes. According to point 8.5.3, column 2, testing by the dermal route is appropriate if (1) inhalation of the substance is unlikely, and (2) skin contact in production and/or use is likely, and physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. For barium carbonate, inhalation can be anticipated. Therefore, provision (1) of point 8.5.3 is not fulfilled. However, according to the SIAR, an acute dermal toxicity study on barium chloride was conducted under OECD TG 402 in compliance with GLP: in this study, the dermal LD50was greater than 2000 mg/kg bw in rats. Nevertheless, the primary source for this study is not available: the SIAR refers to a NIER report dated 2008.

Acute toxicity, inhalation:

A pre-test was performed to develop a design for generating a stable testing atmosphere. However, based on the technical properties of barium carbonate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound. Due to (i) the particle size which is much larger than the pestled substance used for the pre-study, (ii) the low mobility and (iii) the negligible volatility of barium carbonate, the test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application.

Justification for classification or non-classification

Acute oral toxicity

In a reliable GLP study performed to OECD Guideline 401 (Müller, 1983), barium carbonate was administered by gavage at 1470 , 1780 and 2150 mg/kg bw to 5 male and 5 female rats (Sprague-Dawley). The animals were observed for clinical signs and mortality for 14 days. male The study results in an LD50 of 1690 mg/kg bw and therefore it was concluded that BaCO3 requires a classification and labelling as "acute tox 4"; H302 (harmful if swallowed) according to GHS. The classification as 'harmful' is supported by read-across with BaCl2

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw in addition to this effects which were responsible for the death of the animals. No classification required.

 

Acute dermal toxicity

According to the SIAR 27 prepared for barium chloride, an acute dermal toxicity study on barium chloride was conducted according to OECD TG 402, in compliance with GLP. In this study, the dermal LD50 was greater than 2000 mg BaCl2/kg bw in rats. It is note here that the primary data could not be made available to the registrant but using the secondary information no classification according to regulation (EC) 1272/2008 will be necessary for barium carbonate (LD50> 1895 mg/kg bw.). For argumentation on read across please refer to the discussion above.

Acute inhalation toxicity

Based on the technical properties of barium carbonate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound. Due to the MMAD/GSD and the particle size which are much higher than the pestled substance used for the pre-study, the low mobility and the negligible volatility of barium carbonate, the test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application. No classification is required according to regulation (EC) 1272/2008.

Specific target organ toxicant (STOT) – single exposure: inhalation

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation are not met since the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound.

The test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application. No effects are expected at the guidance value, inhalation for a Category 1 classification of <= 1 mg/L/4h and at the guidance value, oral for a Category 2 <= 5 mg/L/4h - > 1 mg/L/4h.No additional classification required.