Samarium

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

The surface of samarium metal oxidises on contact with air to form an outer layer of samarium oxide. It is therefore considered appropriate to read across information from samarium oxide to the metal where testing on the metal is not technically possible.

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

no guideline followed

Principles of method if other than guideline:

Distribution of samarium (Sm) in mice was investigated after inhalation exposure to Sm2O3 particles of 5 µm diameter and 15 mg/m³. Concentrations of Sm were determined by ICP-MS.

GLP compliance:

not specified

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 weeks

Route of administration:

inhalation: dust

Vehicle:

unchanged (no vehicle)

Details on exposure:

During the exposure period, mice inhaled test material in an exposure chamber (Shibata Scientific Technology, Japan), at 15 mg/m³.

Duration and frequency of treatment / exposure:

Mice were exposed to test material 7 hours a day, 5 days a week, in accordance with the working conditions of an 8 hour workday with 1 hour rest.
The exposure period was 1 week or 4 weeks, namely total exposure periods were 35 or 140 hours. These groups were expressed as Sm-35 h and Sm-140 h, respectively.

Dose / conc.:

15 mg/m³ air

Control animals:

yes

yes, concurrent no treatment

Details on study design:

- Terminal procedures:
On the next day and after 4 weeks housing of final exposure, five mice of each group were sacrificed. Lung, liver, kidney, spleen, and inferior branch regions were excised. The tibia bone was isolated by removing muscle and marrow cells.
Organ samples, 0.02-0.1 g were accurately weighed and put into a PFA Teflon bottle, were digested with concentrated nitric acid 0.4 mL and hydrogen peroxide 0.2 mL in a microwave oven. Concentrations of Sm were determined by ICP-MS (Eran6000, PerkinElmer, Japan) at m/z 149 using an external standard. Silicon was measured by ICP-AES (Optima 2100, PerkinElmer Japan). Hematoxylin and eosin stain and transmission electron microscopy with energy dispersive X-ray analysis (TEM 2100, JEOL, Japan) were performed for lung specimens to observe the pathologic characteristics and to check the particles and their chemical composition.

Details on distribution in tissues:

- Distribution of Sm in organs
The instrumental detection limit of Sm at m/z 149 was single ng/L level and the detection limit in original sample was 0.1 ng/g level, because digested samples were applied to ICP-MS at a state of 100 times dilution of original sample. Unfortunately, an appropriate certified reference material for Sm was not found. In order to evaluate the analytical technique and procedure, the recovery rate of Sm (200 ng) added to 20 mg of the bovine muscle powder (NIST-SRM 8414) was examined, and was 99.2 ± 2.8 %.
The concentrations of handling control and particle exposure control groups were almost the same; scarcely detected. Lung showed the highest concentrations. Average concentrations were different depending on inhalation period and time passed after final inhalation. Individual concentrations, however, varied widely and there was no difference between next day and after 4 weeks for Sm-140 h group, and between Sm-35 h and Sm-140 h groups.
Sm concentrations in liver were much lower than in lung, sub-µg/g in order, were correlated with inhalation period on the next day, and decreased with time passage for Sm-140 h group. Those in kidney and in spleen were lower than in liver. Sm concentrations in bone were expressed per dry weight, because isotonic water used for removing bone marrow cells remained unequally and was deleted. They were dependent on inhalation period; however, their time-dependent change was different from other organs, that is, increased twice in 4 weeks time passage for Sm-35 h group.
The concentrations of Si in lung of particle exposure control groups were about one tenth of Sm, though the inhalation conditions were the same. Those in other organs were very low, the same levels with the handling control, indicating a relative long stay of Sm in lung and bone.
In lung, decreasing ratio of Sm by 4 weeks time passage was 78 % for Sm-35 h group but statistically significant decrease was not observed for Sm-140 h group, suggesting that the half-life time of Sm in lung might change according to dosage.
Observed particle size in lung was less than 0.5 µm. Samarium oxide particles used had a normal distribution of granular size, where ratio of particles smaller than 0.5 µm was only about 1 %. If samarium oxide particles with smaller size were inhaled in mice, larger amounts of Sm would be deposited in lung. Samarium oxide with sub-micrometer or ten nanometer order diameter is commercially available and actually used
as raw materials.
Time-dependent changes of Sm distribution in organ specimens suggested that a part of Sm particles once deposited in lung was solved and transferred to organs.
Solubility of samarium oxide was very low, but was about 0.8 % of samarium oxide in saline in our experiment.

- Distribution of Sm in mouse body
Amounts of Sm in lung, liver, kidney and spleen were calculated, and those in bone were estimated assuming that bone weights were about 10 % of body weights and water contents of 20 %. Amounts in kidney and in spleen were extremely small; less than 1 % of detected amounts, and were neglected. Total amounts of Sm-140 h groups were about 4 times those in Sm-35 h groups, both on the next day and after 4 weeks, though the amounts in the latter period were two-third of those in the former. Distribution pattern of Sm among three organs was similar on the next day, where about 90 % of Sm was deposited in lung. After 4 weeks, Sm ratio in bone increased and became 40 % in Sm-35 h group. These results indicate that inhaled Sm is accumulated in lung and then re-distributed in bone.

Body and organ weights

The growth rates of mice of Sm exposure groups were similar to those of corresponding control groups during inhalation period and following 4 weeks. Relative lung weights of Sm-140 h group on the next day were about 29 % higher than that of corresponding handling control. This increase was temporal and not statistically significant. Significant changes in macro observation, diet and water consumptions, and haematocrit values were not observed in either Sm-35 or Sm-140 h groups during the observation period, suggesting the toxicity of samarium oxide particles is not considerable.

Pathological characteristics of lung and detection of particles

Increase of macrophages was observed in lung specimen of Sm-140 h and Si-140 h groups on the next day, however, was obscure in Sm-35 h, Si-35 h, and in all groups after being kept for 4 weeks. Inflammatory changes and other abnormal signs of lung were not seen in any specimens. Crystals, smaller than 0.5 µm, were detected within and between pulmonary alveolus in lung of Sm-140 h group on the next day and also after 4 weeks though the number was smaller, however, were not detected in lung of Sm-35 h group. These crystals were confirmed to contain Sm by energy dispersive X-ray analysis.

Conclusions:

Samarium oxide particles of 5 µm diameter inhaled by male mice at 15 mg/m³ for 35 or 140 h were deposited mainly in lung. Individual Sm concentrations varied widely and there was no statistically significant difference between next day and after 4 weeks for 140 h exposure group, and between 35 and 140 h exposure groups. Sm was also distributed in liver, kidney, spleen, and bone, though the concentrations were much lower than in lung. Sm concentrations in bone of Sm-35 h group were increased after 4 weeks. These results suggest that a part of Sm in lung was transported to other organs via the blood flow, and that bone was the accumulating organ of the inhaled Sm.

Executive summary:

Distribution of samarium (Sm) in mice was investigated after inhalation exposure to samarium oxide particles of 5 µm diameter and 15 mg/m³.

Mice were exposed to test material 7 hours a day, 5 days a week, in accordance with the working conditions of an 8 hour workday with 1 hour rest.

The exposure period was 1 week or 4 weeks, namely total exposure periods were 35 or 140 hours. These groups were expressed as Sm-35 h and Sm-140 h, respectively.

On the next day and after 4 weeks housing of final exposure, five mice of each group were sacrificed. Lung, liver, kidney, spleen, and inferior branch regions were excised. The tibia bone was isolated by removing muscle and marrow cells.

Organ samples, 0.02-0.1 g were accurately weighed and were digested with concentrated nitric acid and hydrogen peroxide. Concentrations of Sm were determined by ICP-MS. Haematoxylin and eosin stain and transmission electron microscopy with energy dispersive X-ray analysis were performed for lung specimens to observe the pathologic characteristics and to check the particles and their chemical composition.

Under the conditions of the study, samarium oxide particles were deposited mainly in lung. Individual Sm concentrations varied widely and there was no statistically significant difference between next day and after 4 weeks for 140 h exposure group, and between 35 and 140 h exposure groups. Sm was also distributed in liver, kidney, spleen, and bone, though the concentrations were much lower than in lung. Sm concentrations in bone of Sm-35 h group were increased after 4 weeks. These results suggest that a part of Sm in lung was transported to other organs via the blood flow, and that bone was the accumulating organ of the inhaled Sm.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of 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: Study conducted on read-across material

Justification for type of information:

The surface of samarium metal oxidises on contact with air to form an outer layer of samarium oxide. It is therefore considered appropriate to read across information from samarium oxide to the metal where testing on the metal is not technically possible.

Reason / purpose for cross-reference:

read-across source

Description of key information

Distribution of Sm following inhalation exposure to samarium oxide powder

Samarium oxide particles of 5 µm diameter inhaled by male mice at 15 mg/m³ for 35 or 140 h were deposited mainly in lung. Individual Sm concentrations varied widely and there was no statistically significant difference between next day and after 4 weeks for 140 h exposure group, and between 35 and 140 h exposure groups. Sm was also distributed in liver, kidney, spleen, and bone, though the concentrations were much lower than in lung. Sm concentrations in bone of Sm-35 h group were increased after 4 weeks. These results suggest that a part of Sm in lung was transported to other organs via the blood flow, and that bone was the accumulating organ of the inhaled Sm.

The surface of samarium metal oxidises on contact with air to form an outer layer of samarium oxide. It is therefore considered appropriate to read across information from samarium oxide to the metal where testing on the metal is not technically possible.

Additional information

Distribution of Sm following inhalation exposure to samarium oxide powder

Distribution of samarium (Sm) in mice was investigated after inhalation exposure to samarium oxide particles of 5 µm diameter and 15 mg/m³.

Mice were exposed to test material 7 hours a day, 5 days a week, in accordance with the working conditions of an 8 hour workday with 1 hour rest.

The exposure period was 1 week or 4 weeks, namely total exposure periods were 35 or 140 hours. These groups were expressed as Sm-35 h and Sm-140 h, respectively.

On the next day and after 4 weeks housing of final exposure, five mice of each group were sacrificed. Lung, liver, kidney, spleen, and inferior branch regions were excised. The tibia bone was isolated by removing muscle and marrow cells.

Organ samples, 0.02-0.1 g were accurately weighed and were digested with concentrated nitric acid and hydrogen peroxide. Concentrations of Sm were determined by ICP-MS. Haematoxylin and eosin stain and transmission electron microscopy with energy dispersive X-ray analysis were performed for lung specimens to observe the pathologic characteristics and to check the particles and their chemical composition.

Under the conditions of the study, samarium oxide particles were deposited mainly in lung. Individual Sm concentrations varied widely and there was no statistically significant difference between next day and after 4 weeks for 140 h exposure group, and between 35 and 140 h exposure groups. Sm was also distributed in liver, kidney, spleen, and bone, though the concentrations were much lower than in lung. Sm concentrations in bone of Sm-35 h group were increased after 4 weeks. These results suggest that a part of Sm in lung was transported to other organs via the blood flow, and that bone was the accumulating organ of the inhaled Sm.

The surface of samarium metal oxidises on contact with air to form an outer layer of samarium oxide. It is therefore considered appropriate to read across information from samarium oxide to the metal where testing on the metal is not technically possible.