Silicic acid, lithium salt

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation is insufficient for assessment

Data source

Reference

Reference Type:

publication

Title:

Rabbit lung after inhalation of lithium chloride

Author:

Johansson, A., et. al.

Year:

1988

Bibliographic source:

J Appl Toxicol. 1988 Oct;8(5):373-5

Materials and methods

Principles of method if other than guideline:

Rabbits were exposed to aerosols of lithium chloride in metal concentrations of 0.6 and 1.9 mg/m³ (mass median aerodynamic diameter of 1 µm) for 4-8 weeks, 5 days/week, 6 h/day. The lungs were studied by light and electron microscopy, with particular reference to inflammatory changes, structure of alveolar macrophages and alveolar epithelial cells. Macrophages recovered by lung lavage were studied by light and electron microscopy and their oxidative metabolic activity was measured. The content of phospholipids was analysed in lung tissue.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium chloride

EC Number:

231-212-3

EC Name:

Lithium chloride

Cas Number:

7447-41-8

IUPAC Name:

lithium chloride

Details on test material:

- Name of test material (as cited in study report): lithium chloride
- Analytical purity: no data given

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.4 +/- 0.5 kg
- Health status: apparently disease free

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

clean air

Remarks on MMAD:

MMAD / GSD: about 1 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: ultrasonic nebulizer (DeVilbiss 35B)

TEST ATMOSPHERE
- Brief description of analytical method used: concentrations were measured by air suction through a membrane filter (Gelman, Gn-4, 0.8µm) and amount of metal deposited on the filter was meeasured by atomic absorption spectrometry (Varian AA6)
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

concentrations were measured by air suction through a membrane filter (Gelman, Gn-4, 0.8 µm) and amount of metal deposited on the filter was meeasured by atomic absorption spectromery (Varian AA6)

Duration of treatment / exposure:

4 - 8 weeks

Frequency of treatment:

6 h/d, 5 d/week

Doses / concentrations

Remarks:

Doses / Concentrations:
1.9 +/- 0.6, 0.6 +/- 0.2 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

8 males

Control animals:

yes

Details on study design:

- Section schedule rationale (if not random): after 4 week's exposure two animals of each group were killed per week during the following weeks. Exposure was continued until all animals were killed.

Examinations

Observations and examinations performed and frequency:

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: post mortem
- Parameters checked examined: lithium in serum

Sacrifice and pathology:

GROSS PATHOLOGY: No
HISTOPATHOLOGY: Yes:
- upper lung lobe was used for light microscopy; tissue pieces of the middle part of the lower left lung lobe was used for electron microscopy

Other examinations:

- The right lung was Iavaged and the alveolar macrophages were collected and the concentration and the celt viability were measured. Their oxidative metabolic activity was estimated by measuring their ability to reduce nitroblue tetrazolium (NBT) to formazan at rest and in the presence of Escherichia coli. The structure of the macrophages was studied by light- and electron microscopy.
- The volume density of alveolar type II cells was measured on 21 randomly selected fields per rabbit. The remainder of the left lower lobe was used for lipid analysis (no further details given).
- The concentration of lithium in serum was determined by flame photometry (IL 543 Digital Flame Photometer, Instrumentation Laboratory, Milan, Italy).

Statistics:

For statistical evaluation of the rmorphological data,the Mann Whitney U and the chi-squared tests were used. NBT test data were evaluated with the Student's t-test. The level of significance was P < 0.05, without predicted direction.

Results and discussion

Results of examinations

Details on results:

ORGAN WEIGHTS
The weight of the left lower lung lobe was similar in the three groups.

HISTOPATHOLOGY:
- Two high-dose and two low-dose animals showed abnormal focal accumulation of enlarged macrophages in the alveolar spaces, associated with an interstitial infiltration of eosinophils, neutrophils and lymphocytes. The macrophages involved in this reaction had a granular or vacuolated cytoplasm. Some macrophages were multinucleated, and some showed degenerative features with nuclear pyknosis and disintegration of cell borders. The most prominent lesions were found in a low-dose animal. The difference between animals (combined groups) and controls as to the incidence of pathological macrophage reaction (4/ 15 vs 0/7) is not statistically significant.
- No abnormal ultrastructural features were detected in the lung parenchyma of lithium-exposed rabbits. Volume density values for type II cells were determined only for the high-dose group and the control group; mean and range values were 0.049 (0.032-0.064) (n = 7 ) and 0.050 (0.036-0.059) (n =7), respectively.
- The number of macrophages recovered by lung lavage, and the size and variance of the size of the macrophages did not differ significantly between the control group and the exposed groups (26 ± 9, 24 ± 8 and 27 ± 7 million in the high-dose, low-dose and control group, respectively)

CLINICAL CHEMISTRY
Total phospholipids (mean SD) in the high-dose, low-dose and control groups were 20.3 ± 3.3, 19.2 2.3 and 21.2 2.- 1.7 mg/g wet lung, respectively. For all exposed rabbits, the serum levels of lithium were below 0.1 mmo1/L.

OTHER FINDINGS
Neither at rest nor after stimulation of the macrophages with E. coli was there any significant difference in the oxidative metabolism between exposed animals and controls.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

0.6 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: based on histopathological findings and clinical chemistry

2

Dose descriptor:

NOAEC

Effect level:

1.4 mg/m³ air

Based on:

other: silicic acid, lithium salt

Sex:

male

Basis for effect level:

other: recalculated value based on the assumption that silicic acid, lithium salt contains 7% lithium (corresponding to MR: 2.8)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Inhalation of lithium chloride produced no significant effects on lung morphology, phospholipid content or alveolar macrophages.