Barium bis(dihydrogenorthophosphate)

Endpoint summary

Description of key information

No data regarding repeated dose toxicity is available for Barium bis(dihydrogen orthophosphate). Reliable data is available for the structural similar substance barium chloride dihydrate (CAS 10326 -27 -9).

Oral, subchronic (RA from CAS 10326 -27 -9; OECD 408; RL2), rat: NOAEL = 110.0 mg/kg bw/day for males and 115.0 mg/kg bw/day for females; LOAEL = 200 mg/kg bw/day for males and 180 mg/kg bw/day for females

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the analogue justification attached to chapter 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Remarks:

rat

Effect level:

2 000 ppm

Based on:

test mat.

Remarks:

equivalent to 110 and 115 mg barium/kg bw/day for males and females, respectively

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

mortality

Dose descriptor:

NOAEL

Remarks:

mouse

Effect level:

2 000 ppm

Based on:

test mat.

Remarks:

equivalent to 205 and 200 mg barium/kg bw/day for males and females, respectively

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

mortality

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

4 000 ppm

System:

urinary

Organ:

kidney

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Drinking water containing 125, 500, 1000, 2000, or 4000 ppm barium chloride dihydrate was estimated to deliver daily doses of 10, 30, 65, 110, or 200 mg barium/kg bw to male rats and 10, 35, 65, 115, or 180 mg barium/kg bw to female rats.

Drinking water containing 125, 500, 1000, 2000, or 4000 ppm barium chloride dihydrate was estimated to deliver daily doses of 15, 55, 100, 205, or 450 mg barium/kg bw to male mice and 15, 60, 110, 200, or 495 mg barium/kg bw to female mice.

Conclusions:

The no observed adverse effect level (NOAEL) for source substance barium chloride dihydrate in drinking water for rats and mice was estimated to be approximately 2000 ppm based on increased mortality and renal toxicity. The dose of 2000 ppm corresponds to NOAEL values of 110 and 115 mg barium/kg bw/day to male and female rats, respectively and of 200 and 205 mg barium/kg bw/day for male and female mice, respectively. As explained in the analogue justification the target and the source substances are considered to be similar in their toxicological behvior. Therefore, it is considered that the target and the source substances are unlikely to lead to differences in repeated toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

110 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details).
The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

System:

urinary

Organ:

kidney

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

No data regarding repeated dose toxicity is available for barium bis(dihydrogen orthophosphate). Reliable data is available for barium chloride dihydrate (CAS 10326-27-9). Since the main toxicity of barium bis(dihydrogen orthophosphate) can be attributed to barium, barium chloride dihydrate can be used as read across. For more details please refer to the analogue justification provided in section 13.

Toxicology studies were performed within the National Toxicology Program (NTP) in order to characterize and evaluate the toxicological potential, including carcinogenic activity, of barium chloride dihydrate in rats and mice. A 13-week repeated dose toxicity study in rats and mice was performed similar to OECD guideline 408 (NTP, 1994). The following acceptable deviations from the guideline study were observed: parameters of clinical biochemistry were limited, no ophthalmologic examination was performed, and weights from spleen, ovaries and uterus were not measured. In the study with mice there were additionally no hematology and chemistry parameters examined.

Rats:

A 13-week study in rats similar to OECD guideline 408 (NTP, 1994) was performed with rats. Groups of 10 male and 10 female Fischer 344 rats received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1000, 2000, or 4000 ppm for 13 weeks, corresponding to average daily doses of 10, 30, 65, 110, or 200 mg barium/kg bw/day to males and 10, 35, 65, 115, or 180 mg barium/kg bw/day to females. The selected doses were based on a range finding study. Three males and one female in the 4000 ppm groups died during the last week of the study. The final mean body weights of male and female rats receiving 4000 ppm were significantly lower (13% and 8%) than those of the controls. Water consumption by male and female rats in the 4000 ppm groups was approximately 30% lower than that by the controls. No clearly chemical-related clinical findings of toxicity or neurobehavioral or cardiovascular effects were noted. Serum phosphorus levels in 2000 and 4000 ppm male and female rats were significantly higher than those in controls, but there were no biologically significant differences in hematology parameters or in serum sodium, potassium, or calcium levels. Renal tubule dilatation in the outer stripe of the outer medulla and cortex occurred in male and female rats receiving 4000 ppm.

The no observed adverse effect level (NOAEL) for barium chloride dihydrate in drinking water for rats was estimated to be approximately 2000 ppm based on the final mean body weights, mean body weight gains, decreased water consumption, mortality, and renal toxicity. The dose of 2000 ppm corresponds to NOAEL values of 110 and 115 mg barium/kg bw/day to male and female rats, respectively. The LOAEL was 200 and 180 mg barium/kg bw/day for males and females, respectively.

Mice:

In a 13-week supporting study also performed similar to OECD 408 groups of 10 male and 10 female B6C3F1 mice received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1000, or 2000 ppm for 13 weeks, corresponding to average daily doses of 15, 55, 100, 205, or 450 mg barium/kg bw/day to males and 15, 60, 110,200, or 495 mg barium/kg bw/day to females (NTP, 1994). The doses were selected based on a dose range finding study. In the 13-week study six males and seven females that received 4000 ppm and one male that received 125 ppm died during the study. Final mean body weights of male and female mice receiving 4000 ppm were significantly lower (> 30%) than those of controls. Water consumption by male mice in the 4000 ppm group was 18% lower than that by the controls; water consumption by other exposed groups of male and female mice was similar to that by the controls. Clinical findings of toxicity were limited to debilitation in the surviving male and female mice receiving 4000 ppm. The absolute and/or relative liver weights of mice receiving 1000, 2000, and 4000 ppm were significantly lower than those of the controls. Multifocal to diffuse nephropathy characterized by tubule dilatation, regeneration, and atrophy occurred in 4000 ppm male and female mice. Atrophy of the thymus and spleen was observed in the majority of early death male and female mice receiving 4000 ppm. Grossly, the thymuses were small or not visible and the spleens were small and mottled or discolored. The thymic lesions consisted of necrosis or moderate to marked depletion of thymic lymphocytes. In some mice, the thymus consisted of only remnants of stromal cells, while in others, the thymus was not even identifiable in the tissue section. The splenic atrophy was characterized by a diminution of the hematopoietic elements of the red pulp and depletion of lymphocytes in the periarteriolar lymphoid sheath, leaving only a thin layer of mature lymphocytes surrounding the arterioles.

The no-observed-effect level (NOAEL) for barium chloride dihydrate in drinking water for mice was estimated to approximately 2000 ppm based on the final mean body weights, mean body weight gains, decreased water consumption, mortality, and renal toxicity. The dose of 2000 ppm corresponds to NOAEL values of 205 and 200 mg barium/kg bw/day to male and female mice, respectively.

Justification for classification or non-classification

The available data on repeated dose toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.