Barium

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

combined repeated dose and carcinogenicity

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well-documented study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male and female white Swiss mice were exposed to barium acetate ( 5 ppm barium) in a life-time drinking study in order to investigate effects of barium.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

1

Reference substance name:

Barium di(acetate)

EC Number:

208-849-0

EC Name:

Barium di(acetate)

Cas Number:

543-80-6

Molecular formula:

C2H4O2.1/2Ba

IUPAC Name:

barium diacetate

Specific details on test material used for the study:

Form: solid

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Charles River Mouse Farm, Inc., N. Wilmington, Mass.- Age at study initiation: 19 to 20 days- Housing: 6 mice per cage; Cages were plastic with stainless steel tops and stacked on wooden racks.- Diet: Composed of whole untreated Balbo rye flour (60%), powdered skim milk (30 59, corn oil (9 %9, and iodized sodium chloride (1 %), with added vitamins and iron .- Water: Basal drinking water, doubly deionized and with no detectable cations, contained soluble salts as simple complexes ( in ppm): zinc, 50; manganese, 10; copper, 5; chromium, 5; cobalt, 1; and molybdenum, 1.No further information on details on test animals and environmental conditions were stated.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Barium acetate (5 ppm barium) basal drinking water was fed to the mice.No further information on details on oral exposure was stated.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

life-time

Frequency of treatment:

ad libitum in drinking water

Doses / concentrations

Remarks:

Doses / Concentrations:5 ppm barium in basal drinking waterBasis:nominal in water

No. of animals per sex per dose:

42 males / 36 females

Control animals:

yes, concurrent vehicle

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes- Cage side observations: mortality/survival and growthDETAILED CLINICAL OBSERVATIONS: No dataBODY WEIGHT: Yes- Time schedule for examinations: Body weight taken at 30, 60, 90, 120, 150, 180, 360, 540 daysFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD EFFICIENCY:- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No dataOPHTHALMOSCOPIC EXAMINATION: No dataHAEMATOLOGY: No dataCLINICAL CHEMISTRY: No dataURINALYSIS: No dataNEUROBEHAVIOURAL EXAMINATION: No dataNo further information on observations and examinations performed and frequency were stated.

Sacrifice and pathology:

Animals were dissected, gross tumors were detected, and some sections were made of heart, lung, liver, kidney, and spleen for microscopic examination. Tumors were considered malignant when they were mulitple. In the study the investigators looked for edema and bleeching of the incisor teeth.No further information on sacrifice and pathology was stated.

Statistics:

Student's t test and chi-square

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITYBarium reduced the longetivity in male mice slightly.BODY WEIGHT AND WEIGHT GAINMice fed barium were remarkably uniform in respect to weight. In all cases the 540-day weights were less than thos at a year of age. This loss of weight also occurered in the controls.HISTOPATHOLOGY: NEOPLASTIC Barium did not increase the incidence of tumors.GROSS PATHOLOGY:Barium had no significant effect on oedema or bleeching of the teeth.

Effect levels

Basis for effect level:

other: see 'Remark'

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Barium reduced the longevity in male mice slightly, but weight was not significantly affected. In all cases the 540-day weights were less than those at a year of age. This loss of weight also occurred in the controls. Barium did not increase the incidence of tumours.