Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay

Figures & data

Table 1.  Treatment groups of the carcinogenicity study

Treatment (intratracheal instillation, PVNO: subcutaneous injection)	No. of instillations × dose (at intervals of days or months, respectively)	Animals/group
Control, 0.9% NaCl-solution	10 × 0.3 ml (7 days)	50 (+ 9)**
Crystalline SiO2 (Quartz DQ12)	1 × 3 mg	50 (+ 9)
Crystalline SiO2 (Quartz DQ12) + PVNO	1 × 3 mg Quartz 7 × 20 mg PVNO s.c. (4 months)	50 (+ 9)
Amorphous SiO2 (Aerosil^® 150, 0.014 µm*)	30 × 0.5 mg (14 days)	50 (+ 9)
Carbon black (PRINTEX^®, 0.014 µm*)	10 × 0.5 mg (7 days)	50 (+ 9)
Coal dust (4 µm*)	10 × 1 mg (7 days)	50 (+ 9)

*Average arithmetical diameter of primary particles.

**Reserve animals for further possible special investigations in brackets.

Table 2.  Incidences of tumors, tumor types and preneoplasias in the lungs of female Wistar rats after intratracheal instillation of granular dusts

	Control	Crystalline silica Quartz DQ12	Crystalline silica Quartz DQ12 + PVNO	Amorphous silica Aerosil^® 150	Carbon black PRINTEX^® 90	Coal dust
No. of rats examined	55	53	56	53	59	51
No. of rats with lung tumors	0 (0%)^a	21 (39.6%)	12 (21.4%)	5 (9.4%)	9 (15%)	0 (0%)
No. of rats with multiple tumors	0 (0%)	11 (21%)	4 (7%)	0 (0%)	2 (3.3%)	0 (0%)
Total number of lung tumors/group	0	46	18	5	13	0
Frequency of lung tumor types
No. of rats with bronchiolo-alveolar adenoma	0 (0%)	6 (11.3%)	2 (3.6%)	2 (3.8%)	2 (3.4%)	0 (0%)
No. of rats with bronchiolo-alveolar carcinoma	0 (0%)	14 (26.4%)	6 (10.7%)	2 (3.8%)	6 (10.2%)	0 (0%)
No. of rats with cystic keratinizing epithelioma	0 (0%)	5 (9.4%)	2 (3.6%)	0 (0%)	1 (1.7%)	0 (0%)
No. of rats with squamous cell carcinoma	0 (0%)	7 (13.2%)	2 (3.6%)	1 (1.9%)	2 (3.4%)	0 (0%)
No. of rats with adenosquamous carcinoma	0 (0%)	0 (0%)	1 (1.8%)	0 (0%)	0 (0%)	0 (0%)
Frequency of preneoplasias graded severe/very severe with signs of cytological atypia
No. of rats with bronchiolo-alveolar hyperplasia	1 (2%)^a	23 (43.4%)	7 (21.4%)	1 (1.9%)	9 (15%)	1 (2%)
No. of rats with squamous cell metaplasia	0 (0%)	4 (7.6%)	5 (8.9%)	0 (0%)	4 (6.8%)	0 (0%)
Total number of rats with preneoplastic lesions	1 (2%)	23 (43.4%)	10 (17.9%)	1 (1.9%)	12 (20.3%)	1 (2%)

^aNumber of tumor-bearing rats expressed as a percentage of the total number of rats examined in this treatment group.

Figure 1.  Incidences of primary lung tumors in the lungs of female Wistar rats after intratracheal instillation of granular dusts.

Figure 2.  Histograms of severity scores across groups and histological findings Percent (%) of animals with the corresponding severity score of the histological finding 1: very slight 2: slight 3: moderate 4: severe 5: very severe.

Figure 3.  Slight (multi)focal interstitial fibrosis and inflammatory cell infiltration after repeated intratracheal instillation of ultrafine amorphous SiO₂ (Aerosil^®150). H&E × 50.

Figure 4.  Severe fibrosis, inflammation and bronchiolo-alveolar hyperplasia after a single intratracheal instillation of Quartz DQ12. H&E, × 50.

Figure 5.  Slight multifocal intra-alveolar and interstitial accumulation of particle-laden macrophages associated with only minimal interstitial inflammatory cell infiltration after repeated intratracheal instillation of fine coal dust. H&E × 200.

Figure 6.  Slight multifocal accumulation of partly degenerating particle-laden macrophages, slight interstitial fibrosis, inflammatory cell infiltration and bronchiolo-alveolar hyperplasia after repeated intratracheal instillation of ultrafine carbon black (PRINTEX^® 90). H&E × 100.

Figure 7.  Invading squamous cell carcinoma after repeated intratracheal instillation of ultrafine carbon black (PRINTEX^® 90). H&E × 10.

Figure 8.  Bronchiolo-alveolar carcinoma with metaplasia to goblet cells and mucin production after repeated intratracheal instillation of ultrafine amorphous SiO₂ (Aerosil). H&E.