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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

direct observations: clinical cases, poisoning incidents and other
Type of information:
other: Case studies
Adequacy of study:
supporting study
other: reliability scoring for regulatory purposes is not appropriate for case studies.

Data source

Reference Type:
Pathological study of the effects of inhaled gypsum dust on human lungs.
Schepers GWH & Durkan TM
Bibliographic source:
A. M. A. Archives of Industrial Health. 12: 209 - 217

Materials and methods

Study type:
clinical case study
Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
according to guideline
other: no guideline available
Principles of method if other than guideline:
The data presented is the histopathological features of 4 cases of deceased employees of the gypsum industry who had no significant exposure to silica in any other industry.
GLP compliance:
not specified
Predates GLP

Test material

Constituent 1
Reference substance name:
Details on test material:
- Name of test material : Gypsum


Type of population:
- Number of subjects exposed: 4 cases were reported
- Sex: All subjects were male
- Age: Case 1 - 55 years, Case 2 - 73 years, Case 3 - 57 years and Case 4 - 49 years
- Race: Case 2 was reported to be German, information on the other subjects is not reported.
- Demographic information:
- Known diseases:
- Other:
Ethical approval:
not specified
Route of exposure:
Reason of exposure:
intentional, occupational
Exposure assessment:
not specified
Details on exposure:
The amount of dust in atmospheric suspension varies somewhat in different parts of the of a gypsum plant, but usually no more than a moderate amount of atmospheric dust is created. Since the airborne material in those areas is derived from raw or calcined gypsum, the free silica content of the dust is very low. The mixing and packing of plaster often liberates dust and men engaged in those operations may be exposed to variable amounts of atmospheric dust which is composed princiapally of calcined gypsum, even though the material being handled may have a quartz content as high as 50 %, which is due to the flocculating properties of the gypsum producing gypsum-quartz aggregates that settle out of the air rapidly.

In performing certain special operations in gypsum plants, such as chipping grooves in the buhrstones used to grind the gypsum, men are sometimes exposed to free-silica dust. Although the dust created by those operations could contain a substantial amount of quartz, the concentration of the atmospheric particles was low and usually held within a safe limit by exhaust ventilation or other means.

Exposure to calcined gypsum dust in warehouses constituted a significant factor in Cases 1 and 3. Cases 2 and 4 had considerable experience as gypsum miners, while Case 3 had additional exposure to gypsum dust in the mill and as a laborer in the yards of the gypsum plant.
- Tissue analysis: The lung tissue of the gypsum workers were analysed for their chemical content. Case 1 could not be analysed in detail as the tissue had been fixed in Zenker's solution and had undergone some postmortem autolysis before fixation.
- Histopathology: The lungs were examined for parenchymal lesions, pleural changes, bronchial changes, vascular damage, pigment and hilar lymph nodes.
Medical treatment:
Not reported

Results and discussion

Clinical signs:
With the exception of Case 2, the subjects had not presented any chest morbidity or symptoms prior to death, with two still actively employed at the time of their death (from non-pulmonary causes). The chest symptoms presented by Case 2 may have been partly due to the age of the subject or linked with exposure to coal-mining dust for an unknown period in Germany prior to his arrival in America at the age of 19. During that period, there were no restrictions on the age of employment for miners. The subject had a moderate degree of anthracosis and perifocal emphsema, the authors conclude that he had been employed several years as a coal miner.
Results of examinations:
Parenchymal lesions:
In the lungs examined, the parenchymal lesions associated with prolonged inhalation of calcined gypsum do not assume a pattern which would characterise them as a specific type of pneumoconiosis. In cases 1 and 2 but particularly in the latter, fibrous nodules were found which resembled silicotic nodules. In case 2, the nodules were surrounded by a stellate, heavily pigmented, cellular halo resembling the lesions characteristic of siderosilicosis and anthracosilicosis. In this case however, it is to be noted that the SiO2 content of the lung ash was remarkably low for an industrial worker. The man had been exposed to coal dust in his youth and it is to be presumed that these anthracotic nodules had such a remote occupational origin. It seems probable that these fibrous nodules have little to do with gypsum exposure. Occasionally nodules may be found which may be characterised as vascular granulomata in that they consist of cellular accumulations, supported on a delicate collagenous web surrounding clustered blood capillaries. Some pigment may be present in relation to the collagen. In other instances these small nodules have fewer vascular components and assume a more decisively fibrocellular character and stellate appearance. Such nodules are common to several pneumoconioses and may represent a nonspecific type of reaction to inhaled dust particles. They do not exceed 2 mm in maximum diameter. Some scarring of the interlobular septa is also present and was found most marked in Case 1.
A lesion which may be regarded as primordial to the nodules described above may be found at multiple foci. It consists of stromal foci of pigmentation with some associated capillary engorgement. These foci are apparently derive from densely infitrated alveolar walls. The pigmented granules seen in case 2 may be of anthracotic origin. The dominant cell types in these nodes are macrophages and occasionally polymorphonuclear leucocytes but almost never lymphocytes or plasma cells. While collagen is most poorly developed within these foci, there is a tendency towards increased pericapilliary and pericellular reticulum deposition. The elastic fires were well preserved even where they traverse nodules.
More extensive or diffuse types of parenchymal change may also be found. In some areas there are cellular accumulations which resemble pneumonitis. The main cells are clustered koniophores, macrophages and some plasma cells and lymphocytes. In other areas a delicate degree of collagen deposition and capillary infiltration has taken place. Such areas may be interpreted as foci of organising pneumonitis or pneumonia, but may represent a specific type of subacute reaction to the gypsum dust. They were present in men who had succumbed unexpectedly from nonpulmonary causes of death and who had not previously experienced any pulmonary symptoms. The diffuse lesions also have relatively well-defined septal boundaries and in many areas assume the appearance of perivascular granulomata which bulge into the alveolar spaces.
Emphysema is not a distinctive feature of this series. Case 2 manifested a moderately advanced degree of perifocal emphysema which is almost certainly to be related to the associated anthracosis but may have been enhanced through the advanced age of the patient.

Pleural changes.
Pleural adhesions are present at some areas of the lung, but do not appear to bear any relation to the dust lesions. The first assumes a form of a diffuse chronic pleuritis involving epipleural proliferation of blood capillaries and lymph plexuses and the deposition of a delicate collagenous stroma. The mesothelium tends to consist of cuboidal cells, some of which contain ingested pigment particles. This type of lesion is most prevelant in Case 1, who had experienced no pulmonary symptoms prior to death and who died of a coronary occlusion.
A type of diffuse pigmented subpleural sclerosis is present in Case 2. The pigment is probably anthracotic, but the dense collagen layers found in relation to it are unusual. Distended bood vessels and lymph sinuses are present in abundance. Two types of pleural plaques were also identified. The first occurs as isolated collagenous subpleural flat nodes and resembles the well-known silicotic pleural plaque. The other variety appears to consist of a perivascular accumulation of collagen and frequents the sites where pleural veins pass from interlobular septa to the lung surface.

Bronchial changes:
There may be remarkably little bronchial disturbance or relatively pronounced change. No evidence of chronic bronchitis with epithelial desquamation could be discerned in sections through the larger bronchi. In air passages of intermediate caliber there is a tendency toward mucosal fibrosis, with a diffuse collagen layer in the plane of transition to the adventitia. A layer of round-cell and macrophage infiltration generally intervenes between this zone and the basilar membrane, and this portion tends to be possessed of a generous lymphatic plexus. There is no tendency toward epithelial desquamation or metaplasia at these levels. Damage may, however, occur at the bronchiolar level. The main deviation appears to comprise a broad collar of cellular infiltration around and throughout the bronchiolar wall. In this way the muscularis mucosae may become completely disorganised. Associated with this infiltrative change, a tendency toward bronchiolectasia may be noted in some areas and in others the lumen may be virtually strangulated. A tendency toward epithelial hyperplasia and small areas of squamous metaplasia may be found. At some sites there is also an associated epithelization of alveolar ducts and proximal alveoli. The regional lymph nodes are not affected by all these changes which appear, therefore to be neither infective not due to any silica present in the dust.

Vasular damage:
Perivascular fibrosis is present at most sites but is limited generally to a delicate collagenous web found in association with the perivascular lymphatic plexuses. The perivascular collar may be minimal or may assume a quite prominent appearance with pigment either embedded in it or at its periphery. The vasa vasorum do not however appear to have suffered any change though embedded in this collageous layer and the affected blood vessels themselves generally retain their patency, quite unlike what may occur in the case of the other pneumoconioses.

Throughout these lungs, alveolar mural, perivascularm peribronchiolar and pleural foci of pigmentation are to be found. They are most prominent naturally in Case 2, where a known history of coal mining was on record. Unexpectedly though, the pigment in this instance reacted positively to the Prussian blue stain. Iron was demonstrable also in Cases 3 and 4. The latter employee had worked in a foundry for a short period before commencing his duties in the gypsum mine, which may account for the presence of iron dust in his lungs. It is also noted that the several pathological deviations thus far described bear no special relationship to the sites of maximal accumulation of the pigment, which may therefore rate as an incidental finding.

Hilar lymph nodes:
Pigmentation of the lymph node medullary regions is the most significant histopathological change observed. This pigment reacts positively to Perl's stain in all cases, though in Case 2, some of the pigment no doubt is carbonaceous. At no point is any fibrous or hyperplastic reaction demonstrable in relation to the pigment. Foci of calcification were discovered at autopsy in the root nodes of Class 1 and 4, and some a typical focal firbosis was macroscopically discernible in Case 3. The cause of this calcification has not been determined, though in Case 4 partially healed tuberculosis foci are probably not to be considered in this connection. Marked periadenitis may have been present at some time prior to death in Case 1, as there is dense fibrous capsular development around the lymph nodes. No vestige of the nature of the lesion remains, as the adjacent lymphatic tissue shows no corresponding change.
Effectivity of medical treatment:
Three of the four cases did not produce pulmonary symptoms prior to death. Their cause of death were non-pulmonary related.
Outcome of incidence:
All except one of the Cases died from non-pulmonary related causes. The pulmonary symptoms in Case 2 cannot be definitely attributed to gypsum exposure.

Applicant's summary and conclusion

No specific pneumoconiotic syndrome occurred, though parenchymal pleural, bronchial and vascular lesions were present which, though attributable to the gypsum-dust exposure, assumed a non-specific and minimal character.