Aluminium hydroxide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: Epidemiological observational

Adequacy of study:

supporting study

Study period:

Not stated.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Data source

Reference

Reference Type:

publication

Title:

Aluminosis--detection of an almost forgotten disease with HRCT.

Author:

Kraus et al.

Year:

2006

Bibliographic source:

J Occup Med Toxicol. 2006; 1:4.

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

respiratory irritation

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

This cross-sectional study included 62 male workers from 8 departments at two plants producing aluminium powder in Germany. The participants completed a standardized questionnaire on occupational history, including exposures to fibrotic agents. They were subjected to a physical examination of the cardiopulmonary system, lung function assessment, conventional X-rays and high resolution computed tomography. Lung function was assessed according to the American Thoracic Society criteria. This included measurements of the vital capacity (VC), forced expiratory volume (FEV1), total resistance (Rtot) and total lung capacity (TLC). Aluminium in urine and plasma was determined by graphite furnace atomic absorption spectrometry. Conventional X-rays were evaluated according to the International Labour Office classification of pneumoconiosis by a radiologist who was unaware of the workers’ exposure status or clinical data. CT scans were evaluated according to a semi-quantitative score system for computed tomography developed by Krauz, Raithel and Hering, 1996 (Int. Arch. Occ. Environ Health 68:249-254). When changes potentially related to aluminium exposure were detected, further diagnostic tests were performed to exclude other interstitial lung diseases. These tests included ergometry, diffusion capacity, blood gas analysis, and immunological parameters. Smoking was quantified by cumulative cigarette smoking in pack-years. Unpaired t-test was used for univariate evaluation of distributional differences between cases of occupational disease and non-cases of the following factors: age, weight, height, body mass index, duration of exposure, plasma Al, urine Al and lung function parameters.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

aluminium powder

IUPAC Name:

aluminium powder

Details on test material:

There were few details provided on the aluminium powder exposure in the article; “barely-greased or non-greased aluminium flake powder”.

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study): The aim of the study was “to check whether sensitive tools for the detection of interstitial lung diseases, such as high resolution computed tomography (HR-CT), allow for the early detection of aluminium induced lung disease.” A hypothesis was not explicitly stated.METHOD OF DATA COLLECTION- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / otherDetails: - Standardized questionnaire on occupational history, including exposures to fibrotic agents.- Physical examination of the cardiopulmonary system - Lung function assessment - Conventional X-rays - High resolution computed tomography. - When changes potentially related to aluminium exposure were detected, further diagnostic tests were performed: ergometry, diffusion capacity, blood gas analysis, immunological parameters. STUDY PERIOD: Unclear.SETTING: Two plants for aluminium powder production in GermanySTUDY POPULATIONTotal population (Total no. of persons in cohort from which the subjects were drawn): 120Selection criteria: all workers from 8 departments at 2 plants for aluminium powder production who had “high exposure” to aluminium powder”. The definition for high exposure was not provided. Total number of subjects participating in study: 62Participation rate: 52% (44.7% in one plant and 63.6% in the other). The authors stated that non-participation was not related to medical reasons.Sex/age/race: male; age range 22-64 years, median 41 years, mean 41.4 (SD 9.9) years. Smoker/nonsmoker: 20 non-smokers, 32 current smokers and 10 former smokersTotal number of subjects at end of study: Not longitudinal.Matching criteria: Not done; it was cross-sectional descriptive. COMPARISON POPULATION- Type: State registry / Regional registry / National registry / Control or reference group / Other comparison group: - Details: No control group was used. HEALTH EFFECTS STUDIED- Disease(s): “Aluminium induced lung disease” or “aluminosis”- ICD No.: - Year of ICD revision: - Diagnostic procedures/examinations: - Physical examination of the cardiopulmonary system - Conventional X-rays evaluated according to the International Labour Office classification of pneumoconiosis by a radiologist who was unaware of the workers’ exposure status or clinical data. X-rays were performed for the first 28 examined workers and were discontinued because of “the lack of aluminium-related findings in the chest X-rays.”- High resolution computed tomography. CT scans were evaluated according to a semi-quantitative score system for computed tomography developed by Krauz, Raithel and Hering, 1996 (Int. Arch. Occ. Environ Health 68:249-254).- Lung function was assessed according to the American Thoracic Society criteria (Am J Respir Crit Care Med 1995, 152: 1107-1136). This included measurements of the vital capacity (VC), forced expiratory volume (FEV1), total resistance (Rtot) and total lung capacity (TLC). - When changes potentially related to aluminium exposure were detected, further diagnostic tests were performed to exclude other interstitial lung diseases. These tests included ergometry, diffusion capacity, blood gas analysis, and a battery of immunological parameters. FOLLOW-UPNot applicable.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: InhalationTYPE OF EXPOSURE MEASUREMENT: Biomonitoring (urine) / Biomonitoring bloodEXPOSURE LEVELS: Adequate environmental monitoring results were not available.EXPOSURE PERIOD: Not specified. POSTEXPOSURE PERIOD: Unclear.DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: Not applicable.

Statistical methods:

The unpaired t-test was used for univariate evaluation of differences between cases of occupational disease and non-cases of the following factors: age, weight, height, body mass index, duration of exposure, plasma Al, urine Al and lung function parameters. Differences in distribution of smoking history were analyzed using λ² tests. Multivariate analysis using a logistic regression model was performed to assess associations between the occurrence of aluminosis and factors for which the p value in the univariate analysis was below 0.4. A p-value of 0.05 was considered statistically significant.

Results and discussion

Results:

No information was provided on the particle size distribution. It is stated that in workers exposed in stamping workplaces “most aluminium dust is respirable with a diameter smaller than 5 µm.”Duration of exposure: median 123 months, range 13-360 monthsDuration of exposure for 15 workers with parenchymal lung changes detected at high resolution CT (see below) was between 78 and 360 months. Plasma AlFrom the text: Median 12.5 µg/L; range 2.5-84.4 µg/LAmong 15 workers with parenchymal lung changes detected at CT (see below), measurements of Al in plasma were reported as 5.7-256 µg/L(Table in the publication). Historical biomonitoring data was available for 11 of these 15 workers; maximum Al in plasma - 9.8-183 µg/L (median 85 µg/L, arithmetic mean 84.6 µg/L). Urine AlFrom the text: Median 83.3 µg/L; range 3.7-630.0 µg/L Median 104.3 µg/g creatinine; range 7.9-821 µg/ g creatinine.In 20 individuals (32.3%) the “biological tolerance value at workplace” of 200 µg/L was exceeded. There was a significant correlation between aluminium concentrations in plasma and in urine (r=0.83 for urinary Al concentrations expressed in µg/L and r=0.93 for urinary Al concentrations expressed in µg/ g creatinine)Aluminium concentrations in plasma and urine were dependent on the workplace; both were highest in stampers.CO-EXPOSURESExposure to fibrotic agents in previous occupations was reported by 14 workers (11 were exposed to asbestos and 3 to silica dusts). Exposure to “other fibrotic agents at the current workplace (e.g. other metals including cobalt, beryllium etc.)” could not explain the study results. FINDINGSSelf-reported symptoms: chronic cough and phlegm was reported by 15 workers (11 of them smokers); shortness of breath during exercise by 4 workers.Medical history: 9 workers had a history of pneumonia, pleuritis or tuberculosis. Chest X-ray: X-rays were performed for the first 28 workers who were examined and were discontinued because of “the lack of aluminium-related findings in the chest X-rays.” In 3 of the 28 workers, “small rounded and irregular opacities” were seen, which were classified by the radiologist as non-specific. High resolution CT findings: Parenchymal changes of the same pattern were detected in 15 (24.2%) of the workers. These changes were characterized by “small rounded opacities” (maximum diameter of 3 mm) mainly in the upper lobe of the lung. In 4 cases, the opacities were also located in the middle and lower lobes. In 3 cases, there were signs of thickening of the interlobular septae. Nine of the 15 workers had worked as stampers; 10 had urine Al concentrations over 200 µg/L. 4 of 15 (26.7%) workers with parenchymal lung changes (“affected” workers) and 10 of 42 (23.8%) unaffected workers were exposed to fibrotic agents in previous occupations, 5 ‘affected” workers reported symptoms of chronic bronchitis (cough and phlegm) and 4 - shortness of breath during physical exercise. Nine of the 15 “affected” workers were current smokers, 3 were former smokers and 3 non-smokers. Four affected workers had an exercise-induced decrease in pO2. Eight affected workers had positive results of immunological tests for specific IgE indicating sensitization to environmental antigens, but none of them had symptoms suggestive of any clinical relevance of these positive results. Three workers had “slightly positive” results on tests for auto-antibodies without clinical symptoms of corresponding diseases. Therefore, the authors concluded that “etiologic agents and pathogenetic considerations other than aluminium cannot be supported.” Parenchymal changes were detected only in participants who were exposed to non-greased or barely-greased aluminium powder (stearin content<0.1%)STATISTICAL RESULTSLogistic regression analysisParenchymal changes in the lung were significantly correlated with higher (≥200 µg Al/g creatinine ) urine concentration (OR=1.008; 95% Wald Confidence Interval 1.002-1.013) and longer (≥ 120 days) duration of exposure (OR=1.015; 95% CI 1.002-1.029). The reasons for choosing (≥200 µg Al/g creatinine and 120 days as the cut-offs is unclear.There was no significant effect of age (OR=0.94; 95% CI 0.84-1.07), smoking (OR=1.52; 95% CI 0.17-13.2), VC (OR=0.94; 95% CI 0.87-1.006), FEV1/VC (OR=1.25; 95% CI 0.98-1.59) or resistance (OR=0.007; 95% CI <0.001-632.5). In all these cases, the reference category is not indicated. Descriptions of categories used in the analyses were lacking in this article. - Other: Univariate comparisons:Workers with changes detected at CT had significantly higher plasma Al concentrations (p=0.01), urine Al concentrations (p=0.007) and a significantly lower VC (p=0.01). There was no difference between workers with and without lung changes in terms of age (p=0.39), duration of exposure (p=0.17), TLC, (p=0.11) Rtot (p=0.14) and FEV1/VC (p=0.07). There were no differences between the “affected” group and the “unaffected” group in smoking habits and history (λ² test, p=0.5)

Confounding factors:

Exposure to fibrotic agents in previous occupations, smoking history

Strengths and weaknesses:

Strengths: Detailed examination including instrumental methods and laboratory tests to detect early changes in the lung potentially related to aluminium exposure and to rule out other interstitial lung diseases. Limitations: This is a cross-sectional study among current workers; workers who left before the study initiation were “lost” to the study leading to a possible selection bias. The participation rate was low (even though the authors state that non-participation was unrelated to medical reasons). No information was provided on the “physical examination of the cardiopulmonary system” and on the questionnaire used for collection of data on occupational history, medical history, respiratory symptoms and smoking. It is not clear whether the questionnaire was self-administered or interviewer-administered. This makes it difficult to evaluate the quality of the data. Inclusion of a control group examined in the same way would make the study results more valid. The description of the logistic regression analyses and results required clearer definitions and justification of categories and cut-offs that were employed.

Applicant's summary and conclusion

Conclusions:

In 15 of 62 workers exposed to aluminium powder, high resolution CT scans revealed changes in the lungs suggestive of “alveolitis without fibrotic activity”. These early changes could not be detected at regular medical check-ups involving lung function tests and conventional chest X-rays. The results of this study provide additional evidence that lung function tests and chest X-rays may lack the sensitivity necessary to detect possible aluminium-related lung changes. The study findings suggest that exposure to aluminium powder may induce inflammatory changes in the lung and that high resolution CT is a sensitive tool for detecting these early changes in exposed workers.

Executive summary:

Sixty-two male workers from 8 departments at two plants producing aluminium powder inwere participants of this study. The participation rate was 44.7% in one plant and 63.6% in the other (overall 52%). The authors stated that non-participation was not related to medical reasons. The participants completed a standardized questionnaire on occupational history, including exposures to fibrotic agents. They were subjected to a physical examination of the cardiopulmonary system, lung function assessment, conventional X-rays and high resolution computed tomography. Lung function was assessed according to the American Thoracic Society criteria. This included measurements of the vital capacity (VC), forced expiratory volume (FEV1), total resistance (Rtot) and total lung capacity (TLC). Aluminium in urine and plasma was determined by graphite furnace atomic absorption spectrometry. Conventional X-rays were evaluated according to the International Labour Office classification of pneumoconiosis by a radiologist who was unaware of the workers’ exposure status or clinical data. CT scans were evaluated according to a semi-quantitative score system for computed tomography developed by Krauz, Raithel and Hering, 1996 (Int. Arch. Occ. Environ Health 68:249-254). When changes potentially related to aluminium exposure were detected, further diagnostic tests were performed to exclude other interstitial lung diseases. These tests included ergometry, diffusion capacity, blood gas analysis, and immunological parameters. Smoking was quantified by cumulative cigarette smoking in pack-years. There were 20 non-smokers, 32 current smokers and 10 former smokers among the participants.

Chest X-rays were performed for the first 28 examined workers and were discontinued because of “the lack of aluminium-related findings in the chest X-rays.” In 3 of the 28 workers, “small rounded and irregular opacities” were seen, which were classified by the radiologist as non-specific.

At high resolution CT, parenchymal changes were detected in 15 (24.2%) of the workers. These changes were characterized by “small rounded opacities” (maximum diameter of 3 mm) mainly in the upper lobe of the lung. Four of 15 (26.7%) workers with parenchymal lung changes detected at CT (“affected workers”) and 10 of 42 (23.8%) unaffected workers were exposed to fibrotic agents in previous occupations. Parenchymal changes were detected only in study participants who were exposed to non-greased or barely-greased aluminium powder (stearin content <0.1%) and not in all workers who experienced the higher exposures. Eight affected workers had positive results of immunological tests for specific IgE indicating sensitization to environmental antigens, and three workers had “slightly positive” results on tests for auto-antibodies in the absence of clinically-relevant symptoms. The authors concluded that “etiologic agents and pathogenetic considerations other than aluminium cannot be supported.”

Univariate comparisons showed that workers with lung changes detected at CT had significantly higher plasma Al concentrations (p=0.01), urine Al concentrations (p=0.007) and a significantly lower VC (p=0.01) than workers without such changes. There was no difference between workers with and without lung changes in terms of age (p=0.39), duration of exposure (p=0.17), TLC, (p=0.11), Rtot (p=0.14) and FEV1/VC (p=0.07). There were no differences between the “affected” group and the “unaffected” group in smoking habits (c²test, p=0.5).

Logistic regression analysed showed that parenchymal changes in the lung were significantly correlated with higher (≥ 200 µg Al/g creatinine) urine concentration and longer (≥ 120 days) duration of exposure. There was no significant effect of age, smoking, VC, FEV1/VC or Rtot.

The authors noted that changes in the lungs detected at high resolution CT in 15 of 62 workers exposed to aluminium powder were suggestive of “alveolitis without fibrotic activity”. These early changes could not be detected at regular medical check-ups involving lung function tests and conventional chest X-rays.The study findings suggest that exposure to aluminium powder may induce inflammatory changes in the lung and that high resolution CT is a sensitive tool for detecting these early changes in aluminium-exposed workers.