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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2005
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment Significant methodological deficiencies Unsuitable test system Japanese original, English translation available.

Data source

Reference
Reference Type:
publication
Title:
Biological effects of rare earth oxides to respiratory organs.
Author:
Takaya M., Toya T, Takata A, Otaki N, Yoshida K, Kohyama N
Year:
2005
Bibliographic source:
J. Aerosol Res. 20(3), 207-212

Materials and methods

Type of study / information:
Pulmonary changes after acute and repeated intratracheal adminstration.
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute experiment: Intratracheal istillation of Lanthanum oxide in rats, 30 to 50 mg/rat, no details given.
Subchronic experiment: 10 mg of lanthanum oxide adminstered intrachaeally to rats (number of applications and duration unclear) observations bronchoalveolar lavage (BAL) and histopathology after 3, 7, 14, 30, 90, 180 days. Control: physiological saline. Other Rare earth oxides were examined as well.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): La2O3
- Molecular formula (if other than submission substance): La2O3
- Physical state: solid, particle size determined by scanning electron microscopy: D50: 1.89 micro-m, geometric standard deviation: 1.85
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
-Source: not reported

Results and discussion

Any other information on results incl. tables

Acute toxicity: According to the authors Lanthanum oxide showed low acute toxicity after single intratracheal administration to rats. Animlas died from suffocation after insitllation of 30 to 50 mg/rat, equivalent to 10 to 165 mg/kg bw.

The subchronic experiment used a dose of 10 mg/rat (appr. 34 mg/kg body weight).

BAL analysis results as reported by the authors:

The total cell number was increased 3 to 4 fold compared to saline treated controls throughout the study period. Most of the cells were neutrophils and alveolar macrophages. From the 14 day sampling period the number of alveolar macrophages was reported to9 have decreased and surfactant was identified as well as micrspheres and collapsed macrophages. LDH was increased from day 3 to day 90. Agranular substance staining PAS positive as well as a cross shaped myelin structure was reported as a histopathological finding increasing from day 7 to day 90 and then decreasing. Foreign body granuloma, but no fibrosis were reported. Cerium oxide (CeO2)of a particle size of D50: 2.48 (GSD 2.90) did not show comparable effects, only slight increases in total cells in BAL, neutrophils and LD on day 7, but not at later time points. However fine particles of cerium oxide (CeO2) (D50: 0.2 (GSD 1.0) were reported to have comparable findings, although slightly less pronounced as the lanthanum oxide exposed animals. The possible influence of particle sizes on their findings is not discussed further by the authors.

Due to the insufficient reporting of details and the intratracheal administration no firm conclusions on possible effects after inhalation exposure to lanthanumoxide can be drawn from this study.

Applicant's summary and conclusion

Conclusions:
Takaya et al. (2005) reported a low acute toxicity of lanthnum oxide after intratracheal adminstration to rats. The authors also reported results of a subchronic experiment with intratracheal administration of lanthanum oxide to rats. Increases of alveolar macrophages, neurophils, LDH and surfactant as well as foreign body granuloma and lung proteinosis were reported to nicrease up to 90days and then decrease gradually. No fibrotic changes were observed. No conclusions on possible effects of lanthanum oxide after inhalation exposure can be drawn from this study due to a lack of information on the methodology, durationn and details of administration, number and strain of rats used etc. and the method of administration.