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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: - no guideline followed - summary of case reports with limited individual information

Data source

Reference
Reference Type:
publication
Title:
Diatomaceous earth silicosis.
Author:
Vigliani EC, Mottura G
Year:
1948
Bibliographic source:
Br J Ind Med. 1948 Jul;5(3):148-60. PMID: 18873553

Materials and methods

Study type:
clinical case study
Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Workers of two factories making filtercandles from calcinated kieselgur, who had worked in the turning department from more than one year, were x-rayed and examined in 1944, and from then on once a year. More serious cases were admitted to the Clinic for Occupational Diseases of the University of Milan. In some cases vital capacities and breath holding time was measured, some patients were tested for tuberculosis and an autopsy was carried out for one of the cases after his death.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Kieselguhr, soda ash flux-calcined
EC Number:
272-489-0
EC Name:
Kieselguhr, soda ash flux-calcined
Cas Number:
68855-54-9
Molecular formula:
SiO2
IUPAC Name:
dioxosilane
Details on test material:
- Name of test material (as cited in study report): diatomaceous earth
- Substance type: anorganic solid
- Physical state: pressed powder of calcinated diatomaceous earth
- Analytical purity: technical grade
- Composition of original raw material, percentage of components: SiO2 82 %, water 12.4 %, aluminium and iron oxide 4.2 %, chalk 0.55 %, magnesia 0.45 %
- Other: processing of raw material:
Diatomaceous earth is mixed with small amounts of calcined pure magnesite and charcoal, ground and formed with water in parallelepipeds of 35 x 10 x 10 cm. After drying in open they were turned into cylinders manually and calcinated at 1250 °C. After calcination diatomaceous earth was white or slight yellow and had a light, talc-like, very finely spongy texture.
Subsequentialy the candles are bored, limed and finished, all steps generating dusts.

Method

Type of population:
occupational
Subjects:
- Number of subjects exposed: 21
- Sex: male (8) and female (6) and 7 of unspecified sex
- Age: males:31 - 60, females: 40 -50
- Race: from Italy, so probably caucasian
- Demographic information: no
- Known diseases: see table 1
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
unintentional, occupational
Exposure assessment:
not specified
Details on exposure:
Grinding of raw material generating dust, but dusts from raw material are very likely unproblematic
Turning, boring, liming and finishing of candles generats dusts.
Workers from 3 different plants were analysed:
5 workers clearly allocated to IG plant with a badly ventilated turning department (no measurements available)
15 workersclearly allocated to ZA plant with a better ventilation with 400 parts per cubic centimeter (dust counts with thermal precipitatior, particle size 0.5 - 4 µm).
1 worker from a third, unspecified factory
all workers were employed for more than 1 year
Examinations:
- Urine analysis: no
- Haematology: erythrocyte sedimentation rate, hemoglobin measurement, red cell count, white cell count in some cases
- Lung function parameters:
vital capacity, breath holding time in some cases; analysis of breathing sounds in all cases,
- Other: chest x-ray radiography in all cases, electrocardiogram in some cases
Medical treatment:
No

Results and discussion

Clinical signs:
generally: cough (productive or unproductive), shortness of breath on exertion, loss of weight, tiredness, closeness or pains in the chest,
Results of examinations:
see table 1:
Effectivity of medical treatment:
not applicable
Outcome of incidence:
see table 1

Any other information on results incl. tables

CASE REPORTS

- of 5 workers in plant IG 2 were without symptoms while 3 were with symptoms of silicosis; the latter 3 are cases 1 - 3

- of 15 workers in plant ZA 5 were without symptoms while 10 were with symptoms of silicosis; the latter 11 are cases 4 - 14

- 1 worker in the unspecified factory was with symptoms of silicosis; this is case 15

(please note that case 13 is not described in the original article and therefore the cases 13 and 14 in this study summary refer to cases 14 and 15 of the original publication)

- Table 1: summary of case reports

Case

sex

age

job

Clinical signs

measurements

diagnosis

1

35

Candle turner for 10 years,

IG plant

- Shortness of breath (for 2 years)

- Dullness in upper lung

- high pitched breath sound

- e. s.: 2 mm in first hour,

- Katz index of 2.5

- vital capacity of 2.5 L

- b. h. t.: 25 sec

- x-ray: reticular-nodular fibrosis with large coalescence in upper lung, emphysema in lower lung

nodular-interstitialcoalescent silicosis

2

36

Raw candle turner for 5 years,

IG plant

- Shortness of breath (for 1 years)

- dry cough

- chest pains

- loss of weight and appetite (height 165, weight 46 kg)

- dull percussion note in upper lung

- occasional slight fever

 

- e. s.: 2 mm in first hour,

- Katz index of 2

- vital capacity of 3.0 L

- b. h. t.: 27 sec

- x-ray: reticular-micronodular fibrosis (subclavicular zone) with conglomerations, emphysemas in both lower lungs

micronodular silicosis with conglomerations

3

31

candle turner for 7 years

IG plant

- used to be very sportive up to 1942

- 38 °C fever in March 1944, subsequently:

- productive cough

- marked shortness of breath on exertion

- loss of weight and appetite

- tiredness

- in June 1944: wasted physique and pale toxic appearance

- dullness of left lung

- death in Octobre 1944

- x-ray: intense irregular fibrosis of right lung with reticulation, nodules and fluffy patches; left lung almost total opacity and a large cavity in the middle

 

coalescent silicosis with tuberculous cavitation of the left lung

4

42

Raw candle turner for 2 years, then calcinated candle turner and approver for 9 years,

ZA plant

- dyspnoea on exertion

- productive cough since 1944

- feverish bronchitis in winter

- January 1947 :

- severe dyspnoea, cough and slight fever

- atypical breathing sounds in both lungs

-x-ray:upper lunglarge fluffy shadows and fibrosis; lower lung intense reticulation and pneumothorax at the left apex.

conglomerate silicosis with left pneumothorax.

5

60

calcinated candle driller for 12 years, then calcinated candle turner and approver for 9 years,

ZA plant

- progressive dyspnoea since 1943

- persistent unproductive cough since 1944

- in sanatorium for 11 in 1943 with diagnosis of silicosis

in 1947:

- severe wasting

Severe dyspnoea

- productive cought, but negative for tuberculosis

- e. s.: 2 mm in first hour,

- Katz index of 2

- tuberculin test negative

- vital capacity of 1.0 L

- b. h. t.: 10 sec

-x-ray:marked pulmonary and pleural fibrosis, interstitial-nodular conglomerates, fibro-thorax on the left side and marked emphysema.

interstitial-nodular conglomerated

silicosis, with fibro-thorax on the left side and marked

emphysema..

6

45

Fitter in candle-turning department for 4.5 years (until May 1945), afterwards cleaning woman in the factory offices,

ZA plant

- in 1944 feeling of weight in shoulders and bronchitis in winter

After 1945:

- light dyspnoea at rest

- persistent cough

- stabbing pain in the heart region

- wasted physique (height 153 cm, weight 39 kg)

-slight cyanosis of lips

- 30 breaths per minute, pulse 100

- atypical breathing sounds

- hemoglobin: 70

- red cell count 3’320’000 per µL

- e. s. 30 mm in the first h

-Katz index 30

- normal temperature

- tuberculin test negative

- x-ray: reticular and micro-nodular fibrosis with slight conglomarations, pneumothorax in upper right pleural cavity

reticulo-nodular silicosis with right pneumothorax.

7

41

candle turner for11 years,

ZA plant

- dyspnoea on exertion since 1944

- cough

- subsequent weight loss of 10 kg and fever up to 38 °C

- in 1945 bilateral pneumothorax in April1945, recovered after 2 months, subsequentialy incapacitated, several cases of bronchitis with productive cough and fever

- at 1946 dyspnoea at rest, persistent cough dyspepsia and wasting (height 163, weight 42 kg) respiration rate 24 and pulse 106

- in Jan 1947 suddenly extreme severe dyspnoea, faintness and stabbing pain in ribs, death after 2 h

-x-ray:extensive reticular and patchy fibrosis in upper lungs and marked emphysema in lower lungs

conglomerate silicosis with emphysema.

 

This patient was autopsied.

8

44

Fitter in candle-turning department for 6 years,

ZA plant

 

- x-ray: moderately diffused reticular fibrosis

moderately diffused reticular fibrosis.

9

40

candle-finisher for 5.5 years,

ZA plant

 

- x-ray: marked diffuse reticular fibrosis with early nodulation in the lower parts of the lungs

marked diffuse reticular fibrosis with early nodulation in the lower parts of the lungs

10

48

Fitter in candle-turning department for 4 years,

ZA plant

 

- x-ray: reticular fibrosis with early nodulation

reticular fibrosis with early nodulation

11

50

Previously cup turner in pottery works (wet process) for 14 years,

then fitter in candle-turning department for 7 years,

ZA plant

- frequently bronchitis in winter

- productive cough

- dyspnoea on exertion

- loss of weight

- x-ray: reticular fibrosis with early nodulation

marked reticular fibrosis with scattered little fibrotic patches

12

56

candle washer for 10 years, and 12 years manager of candle turning department,

ZA plant

- high blood pressure (200/115 mm Hg)

-x-ray:marked reticular fibrosis with micronodulation in the lower lung regions

marked reticular fibrosis with micronodulation in the lower lung regions

13

(14 in paper)

40

candle-finisher for 10 years,

ZA plant

 

- x-ray: moderately advanced reticulation, especially in the lower fields

moderately advanced reticulation, especially in the lower fields

14

56

candle turner for 3 years,

ZA plant

 

-x-ray:reticulation in the lower fields

reticulation in the lower fields

15

43

Candle turner for 10 years (1930 – 1940) in an unspecified filtering candle producing factory

- since 1940 has suffered from cough, exertion dyspnea, progressive wasting and empyema

- repeated stays in tuberculosis sanatorium (negative tuberculin test)

- in July 1947: wasted physique(height 168 cm, weight 48 kg), atypical breathing sounds,

- hemoglobin: 54

- red cell count 3’610’000 per µL

- white cells 4’100

- e. s. 4 mm in the first h, 7 in second h

-Katz index 4

- vital capacity of 1.6 L

- b. h. t.: 16 sec

- x-ray: interstitial

nodular fibrosis, with coalescence in the left subclavicular zone and

intense emphysema at the left lower lobe.

calcified lymph nodes at the right root, and costotomy at the tenth rib, with pleural adherences at the right base.

interstitial nodular silicosis, with coalescence and marked emphysema

 

e. s. = erythrocyte sedimanteation rate (Westergren)

b. h. t. = breath holding time

- The authors state that out of twenty workers radiographed (case 15 not included) in the

two factories, thirteen were silicotic (case 15 not included). 7 of these were diagnosed with an advanced state of the disease. One worker had open tuberculosis.

- From 1944 until 1947 two workers died, one of silicosis and one of silico-tuberculosis.

- A unclear number of the other cases with diagnosed silicosis became incapacitated during this period

- 6 were accepted to be pensioned by the National Accident Insurance Institute.

AUTOPSY OF CASE 7

- The lungs were solidified and fibrotic in the cranial and middle parts. Condensed parts were less hard and compact as in ordinary massive silicosis.

Air spaces were filled partly with iron pigments and very fine blackish-grey grains that did not react as iron and Infiltration of mononuclear cell distrupted the architecture of the alveoli (destruction of alveolar membrane and occlusion of the lumina). Areas less affected showed evidence of emphysematous dilatation of alveolar ducts and of the alveoli. Unstriped muscular cells both of the bronchi and small arteries were increased in quantity.

- In lymphnodes around the lungs most of the tissue consisted of epithelioid cells (round, spindle-shaped or polygonal) containing greyish powdery granules and their walls were thickened and intimately associated with the reticulum. A fibrous network was formed by the cells and small foci of calcification were sometimes seen.

- After incineration of samples of lung, spleen and lymphnode tissues at 500 °C, ashes were analysed for crystaline structure before and after treatment with nitrohydrochloric acid. Generally only very fine grains of unclear crystaline nature were found:

in the lungs: mainly on the thickened walls of the air spaces, in the consolidated masses, and in the free alveolar cells.

in the lymph nodes: ubiquitious but rather sparse in the lymphocytic tissue while abundant in the epithelioid cells and in the sclerotic masses.

in the spleen: usually sparse and made up of quite small particles, mainly stored in the nodes of epithelioid cells; rest in the red pulp.

- conclusion: the found diffuse fibrotic and hyaline sclerosis are fairly similar to that of the massive quartz silicosis but the lack hyalinized single or conglomerated nodules, and different feature of the changes leading to sclerosis lead to a unique histo pathologic picture of diatomaceous earth indiced silicosis: diffuse cell wall thickening of the alveolar air spaces, produced by proliferation of dust phagocytes leading to finally to complete occlusion of air space initiation of a massive granuloma which only in a very late stage becomes fibrotic.

X-RAY DIFFRACTION STUDIES ON DIATOMACEOUS EARTH BEFORE AND AFTER CALCINATION

- raw diatomite, and diatomite calcined at 1250 °C were analyzed with the x-ray diffraction method using a Micro-Metalix apparatus with Debye-Scherrer equipment, and a Siemens apparatus with Laue equipment.

- raw diatomite (mainly dried at 500 to 600 °C) showed no crystalline structure.

- flux calcinated diatomite (three hours at 1250 °C in presence of coal and magnesite) as used for filter candles showed an intense cristobalite pattern.

- purified diatomite with small quantities of electrolytes added, and heated at 900 °C. for one hour, began showing the most intense line of the cristobalite spectrum while at at the sixth hour of heating the intensity of the pattern reached its maximum; no tridimite pattern was seen in the experiments.

Applicant's summary and conclusion

Conclusions:
The report consists of 15 summarized case reports that describe development of a certain form of silicosis in the lungs of workers who were exposed to high amounts of calcinated diatomaceous earths (kieselgur) in three italian factories that lead to incapacitation or death of the workers.
Results of one autopsy with gross and histologic analysis of lung, spleen and adjacent lymph nodes, reveiled specific changes where phagocytosis of fine dust grains leads to diffuse cellular thickening of that cause occlusion of alveoli in the lungs, marked fibrotic changes in the lymph nodes and slight fibrotic changes in the spleen. The changes are fairly similar to massive quarz silicosis.
Finally by using X-ray diffraction analysis it could be shown, that that the amorphous silica matrix of untreated diatomaceous earth is transferred to a significant amount into cristballite through flux-calcination at 1250 °C.
Executive summary:

The present report (Vigliani & Mottura 1948) consists of 15 summarized case reports that describe development of a certain form of silicosis in the lungs of workers who were exposed to high amounts of calcinated diatomaceous earths (kieselgur) in three italian factories that lead to incapacitation or death of the workers.

20 workers of two factories were examined first in 1944 including a X-ray radiography of the chest. Of these 13 were considered positive for silicosis based on the radiographs, analysis of lung parameters and clinical signs. They were subsequently radiographed and examined yearly until 1947. From 1944 up to 1947 two workers died (one of silico-tuberculosis and the other of silicosis). Several became incapacitated and were obliged to leave work, six-were pensioned by the National Accident Insurance Institute.

One additional case from a third factory that was examined only once was also included in the report.

Results of one autopsy of one worker that died after 11 years of exposure to dusts of calcinated diatomaceous earth with gross and histologic analysis of lung, spleen and adjacent lymph nodes, reveiled specific changes where phagocytosis of fine dust grains leads to diffuse cellular thickening that cause occlusion of alveoli in the lungs, marked fibrotic changes in the adjacent lymph nodes and slight fibrotic changes in the spleen. The changes are fairly similar to massive quarz silicosis.

Finally by using X-ray diffraction analysis it could be shown, that that the amorphous silica matrix of untreated diatomaceous earth is transferred to a significant amount into cristobalite through flux-calcination at 1250 °C.

The authors summarize the findings as a certain form of silicosis induced by exposure to calcinated diatomaceaous earths that cobntain significant amount of cristobalite.

The silicosis is described by a rather rapid development, general wasting, shortness of breath, cough and diffuse, reticular (early stages) or conglomerated (later stages) fibrosis of the lung accompanied by compensatory emphysema, enlaged root and mediastinal lymphnodes and in late stages by spontaneous pneumothorax.

The cristobalite content of flux-calcinated diatomaceous earth (kieselgur) is regarded as the main factor for the severeness of this silicosis.