Fumes, silica

Repeated dose toxicity: other routes

Administrative data

Endpoint:

repeated dose toxicity: other route

Remarks:

other: single intratracheal study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study has some limitations related to the documentation of the study results (it has been published only as a conference proceeding). However, the methods used have been described in detail in the reports by Glømme (1965) and Glømme (1966-1967). Therefore, the study can be regarded reliable.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

other: proceedings

Title:

Tissue reaction to different types of amorphous silica.

Author:

Swensson, Å.

Year:

1967

Bibliographic source:

In: Davies, C.N., ed. Inhaled particles and vapours II. (Proceedings of an International Symposium Organized by the British Occupational Hygiene Society, Cambridge, 28 September - 1 October 1965.) Pergamon Press, Oxford, pp. 95-102.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Single intratracheal injections of different forms of silica (silica pume, pyrogenic silica, quartz, quartz-glass and kieselguhr=diatomite) suspended in 1 ml of physiological saline was given to female rats. Animals were killed 1, 2, 4 and 8 months after injection. Silica content of the lungs and lymph nodes were measured and histological studies were performed.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

silica fume

IUPAC Name:

silica fume

Constituent 2

Reference substance name:

amorphous silicon dioxide

IUPAC Name:

amorphous silicon dioxide

Constituent 3

Reference substance name:

crystalline silica

IUPAC Name:

crystalline silica

Constituent 4

Reference substance name:

pyrogenic silica

IUPAC Name:

pyrogenic silica

Constituent 5

Reference substance name:

quartz-glass

IUPAC Name:

quartz-glass

Constituent 6

Reference substance name:

Kieselguhr

IUPAC Name:

Kieselguhr

Details on test material:

- Amorphous silicon dioxide from the smoke of a ferrosilicon smelting furnace: silica fume with silica content 85%, crystalline components less than 1%, round particles, mean primary particle diameter 0.05 μm
- Crystalline silica: contains 98.3% quartz, angular and irregular particles, particle mean size 1.2 μm
- Pyrogenic silica: produced by combustion of silicon-halogen in an atmosphere of hydrogen gas, no crystalline, spherical particles, mean diameter 0.10 μm
- Quartz-glass: produced by smelting rock crystals, silica content 85%, no crystalline, angular, mean size 0.3 μm
- Kieselguhr: purified from organic matter by treatment with bichromate-sulphuric acid, silica content 81%, no crystalline, ground, most particles <5 μm
- Kieselguhr that has been heated to 800oC for 24 hr: silica content 86%, no crystalline

Test animals

Species:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Weight at study initiation: 200 g

Administration / exposure

Route of administration:

other: intratracheal

Vehicle:

physiological saline

Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml
- concentration (if solution): 40 mg/ml

Duration of treatment / exposure:

single exposure

Frequency of treatment:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
40 mg of different forms of silica suspended in 1 ml of physiological saline

No. of animals per sex per dose:

10-20 rats, half of them (5-10) was used for the analysis of silica content

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

- Tissues and body fluids sampled: lungs andassociated lymph nodes
- Time and frequency of sampling: 1, 2, 4 or 8 months after the instillation

Sacrifice and pathology:

Animals were killed 1, 2, 4 and 8 months after injection. One-half of each group was used for histological studies, and the other half for chemical analysis for hydroxyproline and silica.

Results and discussion

Results of examinations

Details on results:

BODY WEIGHT AND WEIGHT GAIN
The tissue reaction progress in respect of development of body weight was substantially less with silica fume than after administration of pyrogenic silica, but otherwise its course was the same.

ORGAN WEIGHTS
Collagen content in the lungs increased to some extent during the first month or months, but during the latter part of the observation period remained practically unchanged or showed an increase that corresponds to the normal increase in the collagen content of the lungs with increasing age of the experimental animals. During the entire period the weight of lymph glands gradually rose. The increase of total weight was substantially smaller with silica fume than those after the intratracheal administration of particles of pyrogenic silica and quartz-glass. The increase of the collagen content of the lymph glands was considerably smaller with silica fume than that following the administration of quartz-glass. However, there was a small progressive increase of the tissue reaction during the whole study period.

HISTOPATHOLOGY: NON-NEOPLASTIC
The macroscopic reaction was substantially smaller with silica fume than that obtained after the administration of crystalline silica, pyrogenic silica or quartz-glass. The tissue reaction (histologically observed formation of collagen) mainly developed during the first month after the administration of the particles and, subsequently, there were very little progress. In histology, for the most part the reaction takes place during the first month, whereas practically no further progress occurs.

Quartz-glass particles resemble quartz most closely in respect of tissue reactions. Quartz-glass particles produced also a progressive reaction, although the progress was substantially less than after the administration of the same amount of quartz. Pyrogenic silica and silica fume had a divergent reaction in as much as the main part of the reaction took place within one month following the administration of the particles; and, subsequently, practically no progress in the reaction was observed. With pyrogenic silica the tissue reaction during the first month was much greater and stronger than that following the administration of quartz; with silica fume the reaction was less than that after the administration of quartz.

OTHER FINDINGS
More than 50% of the amount of quartz injected was found in the lungs of the animals that were given quartz after an observation period of 8 months. In the animals that received pyrogenic silica, quartz-glass and silica fume not more than 20-30% of the amount administered was found. Among these three, the highest percentage of retention (≈ 30 % compared to some 20% with other types) was found in the animals that received silica fume the type that produced the smallest tissue reaction. The transport of silica to, and its retention in, the hilar lymph glands was the highest following the administration of quartz: about 4.5 mg remained in the hilar lymph glands after 8 months. For pyrogenic silica, quartz-glass and silica fume, retention in the lymph glands was between 2.5-3 mg.

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

In an intratracheal injection study, Swensson (1967) exposed rats to 40 mg/ml concentration of amorphous silicon dioxide, chrystalline silica, silica, quartz-glass and two types of kieselguhr. With silica fume the macroscopic reaction was substantially smaller than that obtained after the administration of crystalline silica, pyrogenic silica or quartz-glass. In tissue reaction (histologically observed formation of collagen) there was very little progress.