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Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
88 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Read across BaCl2to BaCO3:

However, 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. Therefore, it was decided to waive repeated dose oral toxicity testing of barium carbonate and to read across from barium chloride for animal welfare reasons. However,read across from barium chloride to barium carbonate is inherently very conservative.

 

The reference Dietz (1992) is considered as the key study for repeated dose toxicity via oral application and will be used for classification. Rats were dosed at 61.1 and 80.9 mg Ba2+/kg bw/day to male and female rats via feed for 90 days. The values refer to 88 and 115 mg/kg bw/day. The NOAEL for barium toxicity in this study is based on depressed body weight gains, elevated phosphorus levels, neurobehavioral effects and chemically related lesions in the kidney and lymphoid tissue at the highest dose level. Individual effects observed were regarded as non treatment-related.

The NOAEL for barium toxicity in this study is based on depressed body weight gains, elevated phosphorus levels, neurobehavioural effects and chemically related lesions in the kidney and lymphoid tissue at the highest dose level of 4000 pm. Individual effects observed at 2000 ppm barium chloride in drinking water (corresponding to the final barium dose of 61.1 and 80.9 mg Ba/kg bw/day to male and female rats respectively) were regarded as not treatment-related and this dose levels represents the NOAEL.

Repeated dose toxicity, dermal

 

According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for sub-chronic dermal toxicity is not considered to be required, for the following reasons:

-         Repeated dose toxicity study via dermal route does not need to be performed since the physico-chemical and toxicological properties do not suggest potential for a significant rate of absorption through the skin.

 

-         In accordance with ECHA guidance on information requirements and chemical safety assessment-chapter R.8: characterisation of dose [concentration]-response for human health, May 2008, a DNEL for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study in rats with BaCl2.

 

Repeated dose toxicity, inhalation

After exposure of rats to 33 or 5.2 mg/m3barium carbonate for 1 or 4 months, respectively, signs of moderate perivascular and peribronchial sclerosis in the lungs with focal thickening of the interalveolar septa and collagenation were seen (Tarasenko et al, 1977). Signs of granular dystrophy in the heart, liver, and kidneys were also reported by these authors.

Only 2 animal studies with repeated inhalation exposure to barium carbonate were found during literature search. Studies investigated selected endpoints of sub-chronic toxicity after exposure for one and 4 months. None of the studies established concentration-response relationships of the adverse effects. Thus the determination of a concentration without effect (NOAEC) in order to provide a basis for risk assessment purposes was not possible.

 

However,inaccording to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for sub-chronic inhalation toxicity is not considered to be required, for the following reasons:

 

-                     barium carbonate is poorly soluble in solution of neutral pH. Therefore, local effects could not be excluded. As a worst case approach the DNEL for long term inhalation local effects was derived by taking the IOEL value of 0.5 mg Ba2+/m3into consideration.

 

-                     in accordance with ECHA guidance on information requirements and chemical safety assessment-chapter R.8: characterisation of dose [concentration]-response for human health, May 2008, a DNEL for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study in rats with BaCl2.

 

In conclusion, it is neither scientifically nor justified due to animal welfare reasons to initiate testing.


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: lymph nodes; urogenital: kidneys

Justification for classification or non-classification

Repeated dose toxicity, oral:

The reference Dietz (1992) is considered as the key study for repeated dose toxicity via oral application and will be used for classification. Rats were dosed at 61.1 and 80.9 mg Ba2+ /kg bw/day to male and female rats via feed for 90 days. The values refer to 88 and 115 mg/kg bw/day. The NOAEL for barium toxicity in this study is based on depressed body weight gains, elevated phosphorus levels, neurobehavioral effects and chemically related lesions in the kidney and lymphoid tissue at the highest dose level. Individual effects observed were regarded as non treatment-related.

 

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – repeated exposure, oral are not met

because the effects observed in the 90 -day study can not be regarded as "significant" or "severe", and do not indicate functional disturbance or morphological changes of toxicological relevance. For this reason, no classification for specific target organ toxicant (STOT) – repeated exposure, oral is required.

No classification and labelling according to regulation (EC) 1272/2008 are expected for long term dermal and long term inhalation (local and systemic) are expected.