Barium dilaurate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles. Minor deviations: (i) The observation period was 1 day instead of 14 days

Data source

Reference

Reference Type:

publication

Title:

Short-term toxicity (one- and ten-day gavage) of barium chloride in male and female rats

Author:

Borzelleca, J.F. et al.

Year:

1988

Bibliographic source:

Journal of the American College of Toxicology Vol. 7 Nr. 5: 675-685

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adpoted: 24 Feb. 1987

Deviations:

yes

Remarks:

observation period was 1 day instead of 14 days

Principles of method if other than guideline:

one-day exposure: concentrations 30, 100 and 300 mg/kg bw. (0.75 - 1.5 % BaCl2 solutions). 10 males and 10 femals per dose level, observation period 1 day.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barium chloride

EC Number:

233-788-1

EC Name:

Barium chloride

Cas Number:

10361-37-2

Molecular formula:

BaCl2

IUPAC Name:

barium dichloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Barium chloride (BaCl2)
- Analytical purity: >99 % (Aldrich Chemical Company)
- Lot No.: 20245L

No further significant information on test material was stated.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: 22-30 days of age
- Weight at study initiation: 100-125 g
- Fasting period before study: Rats were deprived of food but had free access to water for 16-18 hr before being dosed.
- Housing: The rats were housed individually in stainless steel wire-bottomed suspended cages.
- Diet (ad libitum): Purina Rodent Chow No. 5001 (Ralston Purina Co., St. Louis, MO)
- Water (ad libitum)
- Acclimation period: Quarantined for 1 week before initiation of the studies


ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 24 °C
- Humidity: 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

The rats within any exposure level were caged vertically to minimize light, temperature, and airflow differences between exposure groups.

No further significant information on test animals were stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

10 males and 10 femals per group
Vehicle controls received deionised water at a dose of 20.0 ml/kg body weight
MAXIMUM DOSE VOLUME APPLIED: up to 20.0 ml/kg body weight.

No further details on oral exposure was given.

Doses:

30 mg/kg bw., 100 mg/kg bw., 300 mg/kg bw. BaCl2 solution

No. of animals per sex per dose:

10 males/10 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 1 day
ONE-DAY EXPSOURE STUDY
Frequency of observations and weighing: Animals were observed continuously for approx. 5 hr after dosing. Body weights were determined initially (day 1) and at termination of the study (24 hr after dosing).
Necropsy of survivors performed: At the termination of the study animals were killed with ether. Gross pathological examination was performed, followed by the removal and weighing of selected organs (brain, liver, spleen, lungs, thymus, kidneys, and testes or ovaries). All tissues were preserved in 10 % neutral buffered formalin. Histopathological evaluation was performed on liver, kidney, and heart tissue.
Other examinations performed: Urinalysis and various hematological and clinical chemistry parameters were determined.
Hematology: Determination of leukocyte, erythrocyte, platelet number, microhematocrits, prothrombin times and plasma fibrinogen levels; hemoglobin assyed as cyanomethemoglobin; Evaluation of leukocyte differentials
Serum chemistry: Serum ion concentrations were determined. Serum chemistry included SGPT (ALT), SGOT (AST), ALP, BUN, protein, glucose, cholesterol, bilirubin, creatinine, calcium phosphorous, albumin, and chloride.

No further significant information on study design.

Statistics:

All data were subjected to an analysis of variance and test for homogeneity and a Dunnett`s t-test. Nonhomogeneous data were subjected to a Wilcoxon Rank Sum Test. Those values that differed from the vehicle group at P≤ 0.05 were considered significant. The acute oral LD50 values were calculated using the method of Finney.

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 100 - < 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: calculation of 95% CL is not possible

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 100 - < 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: calculation of 95% CL is not possible

Mortality:

No deaths occured at the two lower doses. However, at 300 mg/kg bw., 8 of 10 males (80%) and 7 of 10 females (70%) died within 24 hr.

Clinical signs:

other: not stated

Gross pathology:

Changes observed at necropsy in a majority of male animals at the 300 mg/kg dose only included an ocular discharge, fluid in the trachea and darkened liver. Inflammation of the small and large intestines was seen in both sexes at 300 mg/kg.

Other findings:

Organ weights: At 30 and 100 mg/kg bw. BaCl2, there were no significant differences from vehicle control in males. In females, the lungs/brain weight, and ovaries/brain weight ratios were significantly lower at 30 mg/kg bw.. At 300 mg/kg bw., both sexes exhibited significantly lower liver/brain weight ratios, and high kidney/body weight ratios. In males only, liver weight was significantly reduced at the highest dose.

Clinical chemistry: There were no significant differences at 300 mg/kg bw in either males or females. Increases seen in SGPT (ALT), SGOT (AST), 5'-nucleotidase and phosphorous at 30 and/or 100 mg/kg bw were not dose related.
Hematology: Hematological values exhibited no significant differences from control in either sex at dosage levels of 30 and 300 mg/kg bw.. There were elevations in hemoglobin and hematocrit in males receiving 100 mg/kg bw.. Coagulation data and differential cell counts indicated no significant differences from control in either sex at any of the dosage levels.

Any other information on results incl. tables

High mortality occurred up to 80% at the highest dose level of 300 mg/kg bw whereas no mortality occurred at dose levels of 30 and 100 mg/kg bw. Due to this no exact calculation of the LD50 was performed. It could be concluded that the LD50 of BaCl2 is > 100 and < 300 mg/kg bw. Therefore, a calculation of a confidence interval is not possible.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the test design choosen in this study, it can be concluded that the LD50 of BaCl2 is >100 mg/kg bw but <300 mg/kg bw. According to the test result the substance has to be classified as harmful im swallowed (Xn; R22) due to the fact that high mortality was observed at dose levels of > 200 mg/kg bw (accroding to 67/548/EEC) and toxic category III (LD50 >50 and < 300 mg/kg bw.) according to GHS.

Executive summary:

The results indicated that LD50 of Ba2+ is >66 mg/kg bw. and <198 mg/kg bw.