Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Test material for this study report is barium chloride - a highly soluble barium salt which dissociates to the Ba2+ ion and Cl- ions in solutions in a similar way to barium nitrate dissociating to Ba2+ and NO3- ions. It is generally accepted that it is the Ba2+ ions that control the toxicology of barium compounds and not the anions, and it is deemed reasonable to consider barium chloride as a good surrogate to the nitrate for toxicology end points.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:

Test material

Specific details on test material used for the study:
Purity : 99.999%

Test animals

Details on test animals and environmental conditions:
Age: male (8-week), female (9-week)
Weighing: male (265.4-290.7 g), female (220.0-263.5 g)

Environmental conditions
Temperature: 20.7-22.9 °C
Relative humidity : 42.5-49.2 %
Air ventilation frequency: 10-15 times/hr
Light intensity: 150-300 Lux
Light/dark cycle: 12-hour/day

Administration / exposure

Type of coverage:
unchanged (no vehicle)
Details on dermal exposure:
Individual dose was calculated based on the animal’s body weight taken just before dosing. A dose for each animal was weighed using an electronic balance (CP323S, Sartorius, Germany). The area of dorsal skin (approximately 5 cm x 6 cm) on each animal’s back was clipped free of hair with an electric clipper (5000ADII, NATUME, Japan, size: 0.05 m). The area of 4 cm x 5 cm on the back was established as the application site. After the application of the test substance to gauze, the gauze was moistened with the water of injection (Lot No. : GBA8003, Choongwae Pharma Corp., stored at normal temperature) sufficiently, and the application site was covered with the gauze and plastic film. Each animal’s back was over-wrapped with a Soft Cloth Tape with Liner (5 cm width, 3M Co., Ltd., Korea). At the end of a 24-hour exposure period, the gauze, plastic film, and Soft Cloth Tape with Liner were removed, and any residual test substance was removed using absorbent cotton moistened with tepid water. The application site of the control animals was dressed without topical application of the test substance in the same manner as the treatment group.
Duration of exposure:
24 hours
Control : 0 mg/kg
Test concentration : 2000 mg/kg
No. of animals per sex per dose:
Control animals:
Details on study design:
On the day of administration, clinical signs (including general appearance, motility, function of the autonomic nervous system, and discharge) and mortality were observed continuously for up to 30 minutes after dosing, and then observed at 1, 2, 4, and 6 hours after dosing. During a 14-day observation period, clinical signs were observed once daily.
[Body weight]
Body weights were measured prior to dosing (Day 0), on Day 1, 3, 7, and the day of necropsy (Day 14).
After the end of the observation period, all of the animals were exsanguinated by transecting the abdominal aorta under CO2 gas anesthesia and observed macroscopically about full external surface and organs of thoracic and abdominal cavities.
[Histopathological findings]
Since no gross findings were observed at necropsy, histopathological examinations were not performed
Statistical analysis was performed using the statistical Program (SAS 9.1.3, SAS Institute Inc., U.S.A.). Folded-F test was done to test for variance homogeneity at the 5.0% one-tailed probability level. Student t-test was employed on homogeneous data for the control group versus treatment group comparison at the 5.0 and 1.0% two-tailed probability level.

Results and discussion

Preliminary study:
The dose levels for the study were determined referring to the result of the preliminary study (Study No.; B08069p). There were no toxic signs on mortality, clinical signs, body weight change and gross findings at the 2000 mg/kg levels of the preliminary study. Therefore, the limit dose level of 2000 mg/kg was selected
Effect levels
Key result
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
During the observation period, there were no deaths of all males and females in the control and treatment groups
Clinical signs:
A hematuria was observed in one female rat treated with 2000 mg/kg from Day 2 to Day 11 after administration. From Day 12 after administration, this abnormality was returned to normal appearance. This abnormality was not considered to the toxic effect from the test substance treatment by considering that the results of body weight gain and necropsy did not show the treatment-related differences. Other animals did not show any abnormal clinical sign. A crust formation was observed on application site on Day 6 and Day 7 after administration in one male rat treated with 2000 mg/kg, and this abnormality was recovered on Day 8 after administration. This result was considered to the treatment-related alteration
Body weight:
During the observation period, male and female administration group of test substance there was no significant difference between the control and treatment groups. The decrease in body weight gain was observed in 2-4 animals of the control and treatment groups both gender on Day 1 after administration. On Day 3 after administration, the decrease in body weight gain was observed in 1-2 female rats of the control and treatment groups. From Day 7 after administration, normal developments in body weight gain were revealed in all animals.
Gross pathology:
No treatment-related gross findings were observed in all animals

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Based on these results, no toxic effect was observed and the LD50 value of barium chloride in acute dermal toxicity study was considered to be more than 2000 mg/kg bw on male and female rats.