Lanthanum chloride, anhydrous

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Principles of method if other than guideline:

The biological effects and metabolic behaviors of lanthanum were studied by instilling lanthanum chloride intratracheally into male rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): lanthanum chloride (Wako Pure Chemicals Co., Osaka, Japan)
- Analytical purity: 99.9%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Clea Japan Co., Tokyo, Japn
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: 252 - 303 g
- Diet (ad libitum): commercial rat chow
- Water (ad libitum): distilled water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50

Administration / exposure

Route of administration:

other: intratracheal

Vehicle:

physiological saline

Doses:

first group: 0.4 mL of lanthanum chloride solution at doses of 0.5, 1, 10, 20, 50, 100 and 200 µg La/rat
second group: 0.4 mL of lanthanum chloride solution at a dose of 50 µg La/rat

No. of animals per sex per dose:

first group: 4 male animals per dose
second group: 4 male animals per time point (56 animals, time points: 3, 6, 12 and 24 hours and 2, 3, 5, 7, 14, 21, 28, 56, 84 or 168 days)

Control animals:

yes

Details on study design:

See any other information on materials and methods.

Statistics:

Data are presented as means ± SEM. Statistical analysis was performed by Dunnett´s test using the GLM procedure in SAS to compare the mean values between the control and exposed groups. A p-value < 0.05 was considered statistically significant.

Results and discussion

Any other information on results incl. tables

The Lanthanum content showed linear increases with doses of Lanthanum chloride in the lung (lung tissue + BALF) and lung tissue, while the contents in the supernatant and cellular fractions of BALF started to decrease after attaining peak values at a dose of 50 µg La/rat. This indicates that doses of Lanthanum higher than 50 µg were metabolised differently from the metal administered at lower doses. Therefore, a time course study (second exposure group) of the Lanthanum content was performed by administering Lanthanum chloride at a dose level of 50 µg Lanthanum/rat. The animals were sacrificed 3, 6, 12 and 24 hours and 2, 3, 5, 7, 14, 21, 28, 56, 84 or 168 days after instillation.

The biological half-time of Lanthanum in the lung was calculated to be 244 days when Lanthanum chloride was introduced intratracheally into rats at a dose level of 50 µg Lanthanum/rat. Lanthanum in the supernatant fraction of BALF decreased with time and was not detectable after 21 days. In contrast, Lanthanum increased with time in the pellet fraction of BALF up to 5 days post-administration and then leveled off.

Although Lanthanum was given as a soluble salt, the form accumulating mostly in the lung tissue was deposited in insoluble form. A marginally detectable amount was extracted into the supernatant fraction after 1 week. Lanthanum was not detectable in any femur samples from both the time-course and dose-related experiments in the study. Lanthanum was detected marginally in the liver and kidney samples from rats receiving lanthanum chloride at doses of 100 and 200 µg Lanthanum/rat in the dose-related study and after 168 days in the time-course study. At high concentrations, Lanthanum was also detected in the pulmonary hilum lymph nodes.

The numbers of macrophages and polymorphonuclear leukocytes increased in BALF in a dose-related manner up to 100 µg lanthanum/rat and then leveled off. Although eosinophils were marginally detectable in the control BALF, the number started to increase at a dose higher than 50 µg Lanthanum/rat, and was significantly higher at 200 µg Lanthanum/rat. 

In alveolar macrophages, many high electron-dense granular inclusions were detected in the lysosomes and cytoplasma. High electron-dense layers were detected on the surface and in the basement membrane of type I pneumocytes. X-ray microanalysis shows that the inclusions and layers contained lanthanum.

In conclusion, Lanthanum was detected in alveolar macrophages as high electron-dense inclusions in lysomsomes and cytoplasm. Lanthanum was also detected in type I pneumocytes as a high electron-dense layer, probably in the basement membrane and on the cell surface. These results would explain the long half-time of lanthanum. Further, the detection of high lanthanum content in pulmonary lymph nodes (qualitative experiment) suggests that lanthanum is partly cleared from the lung through the lymph nodes.