Fumes, silica

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Hypertension due to inhaled submicron amorphous silica.

Author:

Schepers, G. W.

Year:

1959

Bibliographic source:

Toxicol Appl Pharmacol.1: 487-500.

Materials and methods

Principles of method if other than guideline:

Rabbits were exposed to submicron amorphous silica at concentrations of 28, 134, 360 mg/m3 for 8 h/d, 5d/wk up to 27 months.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

submicron amorphous silica

Test animals

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4 months
- Diet (e.g. ad libitum): standard vegetable diet

Administration / exposure

Route of administration:

inhalation: dust

Duration of treatment / exposure:

up to 27 months

Frequency of treatment:

8 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
28, 134, 360 mg/m3
Basis:

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Parameters examined: electrocyte count, hemoglobin, hematocrit

CLINICAL CHEMISTRY: Yes
- Parameters examined: chloride, sodium, potassium, calcium, and magnesium concentrations

URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No

OTHER: ventricular pressures, serial radiography, electrocardiography, physiological studies

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

erythrocyte count, hemoglobin, hematocrit

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

lung weight

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Details on results:

CLINICAL SIGNS AND MORTALITY
Elevation of right and left ventricular pressures was seen in rabbits. The elevations were partly reversible after cessation of dust exposure. Concomitant radiographic changes, electrocardiographic deviations, modifications of lung functions, hematologic and electrolyte disturbances were detected.

BODY WEIGHT AND WEIGHT GAIN
The high dose increased body weight.

HAEMATOLOGY
Erythrocyte count (23.5%), hematoglobin level (25.5%) and hematocrit readings (20%) increased with the high dose.

CLINICAL CHEMISTRY
The potassium level increased with 14% with the highest dose.
ORGAN WEIGHTS
Lung weights doupled with the high dose.
GROSS PATHOLOGY
Pulmonary emphysema.

HISTOPATHOLOGY: NON-NEOPLASTIC
Autopsy findings consisted anatomical cor pulmonare, congestive cardiac failure, emphysema, and chemical pneumonitis were the main responses to the inhaled amorphous silica dust.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)

Effect levels

Dose descriptor:

NOAEL

Effect level:

mg/m³ air

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Based on the findings with right and left ventricular pressures, the silicate seem to act not only at the pulmonary level, but also peripherally after absorption.

Applicant's summary and conclusion

Executive summary:

Schepers (1959) exposed rabbits to submicron amorphous silica at concentrations of 28, 134, 360 mg/m³for 8 h/d, 5d/wk up to 27 months. Ventricular pressures, concomitant findings (weight changes, dyspnea, serial radiography, electrocardiography, physiological studies, haematology, electrolyte disturbances), and necropsy findings were observed.

Elevation of right and left ventricular pressures was seen in rabbits. The elevations were partly reversible after cessation of dust exposure. Concomitant radiographic changes, electrocardiographic deviations, modifications of lung functions, hematologic and electrolyte disturbances were detected. Autopsy findings consisted anatomical cor pulmonare, congestive cardiac failure, emphysema, and chemical pneumonitis were the main responses to the inhaled amorphous silica dust.