Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication meeting basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Pulmonary response to kaolin, mica and talc in mice.
Author:
Sahu, A.P. et al.
Year:
1978
Bibliographic source:
Exp Pathol (Jena);16(1-6):276-82.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Following intratracheal inoculation the pulmonary fibrogenic response of kaolin, mica and talc was investigated in mice over a period of 210 days to investigate the fibrogenic potential.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Kaolin
- Source: Bihar, Rajasthan and West Bengal provinces of India
- Chemical composition: see Table 1

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Industrial Toxicology Research Centre
- Weight at study initiation: 20 g
- Diet: stock laboratory diet (Hindustan Lever Pellet) and leafy vegetables
- Water: ad libitum

Administration / exposure

Route of administration:
other: intratracheal
Vehicle:
physiological saline
Details on exposure:
The particle size below 5 μm was made according to a procedure described by Zaidi (1969). Prior to inoculation the suspensions were sterilized.
Doses:
5.0 mg dust/ 0.1 mL NaCl per animal
No. of animals per sex per dose:
80.
Group 1: 80 mice receiving Kaolin.
Group II: 80 mice receiving Mica.
Group III: 80 mice receiving Tale.
Group IV: 40 control mice.
Animals were exposed for different duration intervals.
Control animals:
yes
Details on study design:
2 animals from each group were killed at 24 h, 48 h and 7, 15, 30, 60, 90, 120, 150, 180 and 210 days post inoculation for necropsy.

Results and discussion

Gross pathology:
All the three dusts incited acute inflammatory reaction at early periods but with mica dust the acute reaction persisted longer. Subsequently there was gradual increase in the fibroblastic activity in the focal areas and mica produced, in addition, many cholesterol cleft-like structures together with marked fibroblastic activity and lymphocytic infiltration. Towards the termination of experiment at 210 days the fibrosis, in general, remained restricted to grade II with kaolin and mica while talc produced thickened interalveolar septa. The transport of dust from lungs to lymph nodes occurred earlier with mica than with kaolin or talc dust accompanied with little fibrotic reaction.
Other findings:
The authors stated that the used animals strain might not be suitable to model human pneumoconiosis as the histological lesions in mouse do not simulate the human lesions.

Any other information on results incl. tables

Summary of all results:

In the present studies the pulmonary response in mice, inoculated with three silicate dusts, was in the form of acute inflammatory reaction at early periods followed by macrophage reaction, proliferation of fibroblasts and formation of focal fibrotic areas comprised of thick dense reticulination (grade II) with kaolin and mica and thickened interalveolar septa observed with talc at 210 days.

 

Results upon intratracheal kaolin application

GROSS PATHOLOGY

No significant gross changes were observed in the lungs of mice killed up to 30 days except for a varying degree of patchy congestion of the lobes. Later, occasional dirty white patches were observed on the left lobe of lung in group 1 and III (kaolin and tale) and pink to brown discoloration in group II (mica) animals. These patches increased in area and became prominent at the termination of experiment (210 days). The left and right tracheobronchial lymph nodes became enlarged from 90 days onwards in experimental groups and appeared quite prominent at 210 days

 

HISTOPATHOLOGY: NON-NEOPLASTIC

At 24 h post application, the respiratory bronchioles and their alveolar sacculations contained varying amounts of extracellular dust particles infiltrated with a few mononuclear and polymorphonuclear leucocytes as well as congested capillaries. However, by 48 hours diffuse irregular areas of consolidation were developed. At 7 days, there was proliferation of macrophages and the formation of many large irregular but compact areas of dust laden macrophages in alveolar tissue. At 15 days small to large irregular areas consisting of dust laden macrophages and occasional fibroblasts were found around bronchioles and blood vessels.

The dust lesions at 60 days were surrounded by many cells resembling plasma cells which were in different stages of development. Subsequently there was increased fibroblastic reaction at the periphery of dust areas (grade I) which became quite prominent at 120 days. Many small to large areas of birefringent particles were encountered in the cortex and medullary cords of the nodes, in which dust laden macrophages showed swollen appearance as well as multinucleate structures filled with dust particles. Besides, medullary cords revealed marked proliferation of plasma cells which resembled to some extent those seen in the lung parenchyma.

At 150 days, the fibrogenic response was comparable to that seen at 120 days except that focal areas contained more fibroblasts. The fibrotic area at 210 days showed marked fibroblastic reaction (grade II maximum) together with infiltration of lymphocytes. The nodes revealed many small focal areas of dust cell reaction indicative of cytotoxic action of dust in the form of vacuolization of macrophages together with little reticulin reaction. 

Applicant's summary and conclusion