Barium bis(dihydrogenorthophosphate)

Carcinogenicity

Description of key information

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

Oral, chronic (RA from CAS 10326 -27 -9; OECD 451; RL2), rat: NOAEL = 60 mg/kg bw/day for males and 75 mg/kg bw/day for females (highest dose tested) - not carcinogenic

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: 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:

rats

Effect level:

2 500 ppm (nominal)

Based on:

test mat.

Remarks:

equivalent to 60 and 75 mg barium/kg bw/day for males and females, respectively

Sex:

male/female

Basis for effect level:

other: no adverse effects at highest dose

Dose descriptor:

NOAEL

Remarks:

mice

Effect level:

2 500 ppm (nominal)

Based on:

test mat.

Remarks:

equivalent to 160 and 200 mg/kg bw/day for males and females, respectively

Sex:

male/female

Basis for effect level:

other: no adverse effects at highest dose

Key result

Critical effects observed:

no

Based on the water consumption data the average daily dose of barium chloride dihydrate received by rats was 15, 30, or 60 mg barium/kg bw for males, and 15, 45, or 75 mg barium/kg bw for females.

Concentrations of 500, 1250, and 2500 ppm barium chloride dihydrate delivered estimated daily doses of 30, 75, or 160 mg barium/kg bw to males and 40, 90, or 200 mg barium/ kg bw to females.

Conclusions:

There was no evidence of increased neoplasm incidences that could be attributed to barium chloride dihydrate administration in both sexes of rats and mice. Thus, as explained in the analogue justification barium bis(hydrogen orthophosphate) is also considered to have no carcinogenic potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

60 mg/kg bw/day

Study duration:

chronic

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 X, 8.9.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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

Additional information

No data regarding carcinogenicity 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 2-year carcinogenicity study in rats and mice with acceptable restriction was performed similar to OECD guideline 451 (NTP, 1994). The following acceptable deviations from the guideline study were observed: food consumption was not evaluated and the following organs were not examined: aorta, cervix, eye, harderian gland, lacrimal gland, peripheral nerve, skeletal muscle, vagina.

Rats:

Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1250, or 2500 ppm for 104 (males) or 105 weeks (females), corresponding to average daily doses of 15, 30, or 60 mg barium/kg bw/day for males and 15, 45, or 75 mg barium/kg bw/day for females. The high dose of 2500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4000 ppm groups in the 13-week study. Two-year survival of exposed male and female rats was similar to that of the controls. The final mean body weights of male and female rats that received 2500 ppm were (5% and 11%) lower than those of controls. Beginning as early as week 5, water consumption by male and female rats receiving 2500 ppm was substantially lower than that by controls (male: 11% to 30%; female: 19% to 33%). There were no chemical-related clinical findings. There were no chemical-related differences in hematology or clinical chemistry parameters in male or female rats. At the 15 months interim evaluation, the plasma barium concentrations (mg/mL) were significantly increased in males receiving 1250 and 2500 ppm and in all exposed groups of females (male: 0 ppm, 0.98; 500 ppm, 1.00; 1250 ppm, 1.23; 2500 ppm, 1.68; female: 0 ppm, 0.74; 500 ppm, 0.99; 1250 ppm, 0.97; 2500 ppm, 1.43). Barium levels in bone in rats from the 2500 ppm groups were about 400 times greater than those in the controls. At the end of 2 years, there were no increased incidences of neoplasms or non-neoplastic lesions that could be attributed to barium chloride dihydrate. However, there were dose-related decreased incidences of adrenal medulla pheochromocytomas and mononuclear cell leukemia in male rats.

In conclusion, there was no evidence of increased neoplasm incidences that could be attributed to barium chloride dihydrate administration in both sexes of rats. Thus, the highest applied concentration of 2500 ppm represents a NOAEL (corresponding to barium doses of 60 and 75 mg/kg bw/day to male and female rats, respectively).

Mice:

Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1250, or 2500 ppm for 103 (males) or 104 weeks (females), corresponding to average daily doses of 30, 75, or 160 mg barium/kg bw/day for males and 40, 90, or 200 mg barium/kg bw/day for females. The high dose of 2500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4000 ppm groups in the 13-week study. Two-year survival of male and female mice receiving 2500 ppm was significantly lower than that of the controls due to renal toxicity. Final mean body weights of 2500 ppm males and females were 9% and 12% lower than those of controls. Water consumption by male and female mice receiving barium chloride dihydrate was similar to that by the controls. There were no chemical-related clinical findings. There were no differences in hematology or clinical chemistry parameters measured at the 15 months interim evaluation. At the 15 months interim evaluation, plasma barium concentrations (mg/mL) were significantly increased in all exposed groups of mice (male: 0 ppm, 0.62; 500 ppm, 0.77; 1250 ppm, 0.89; 2500 ppm, 1.49; female: 0 ppm, 0.52; 500 ppm, 0.74; 1250 ppm, 1.01; 2500 ppm, 1.35). At the end of the 2-year study, there were increased incidences of nephropathy in male and female mice (male: 1/50, 0/50, 2/48, 19/50; female: 0/50, 2/53, 1/50,37/54). There were no chemical-related increased incidences of neoplasms in male or female mice. The incidence of hepatocellular adenoma was significantly decreased in male mice receiving 2500 ppm.

Conclusion: There was no evidence of increased neoplasm incidences that could be attributed to barium chloride dihydrate adminstration in both sexes of mice. Thus, the concentration of 2500 ppm represents a NOAEL (corresponding to barium doses of 160 and 200 mg/kg bw/day to male and female mice, respectively).