Aluminium sulphate

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Type of sensitisation studied:

respiratory

Study type:

other: case-control study

Principles of method if other than guideline:

Aims: To assess the significance of individual risk factors in the development of occupational asthma of aluminium smelting (OAAS).
Methods: A matched case-control study nested in a cohort of 545 workers employed in areas with moderate to high levels of smelting dust and fume. The cohort comprised those who had their first pre-employment medical examination between 1 July 1982 and 1 July 1995; follow up was until 31 December 2000. Forty five cases diagnosed with OAAS and four controls per case were matched for the same year of pre-employment and age within ±5 years. The pre-employment medical questionnaires were examined, blinded as to case-control status, and information obtained on demographics and details of allergic symptoms, respiratory risk factors, respiratory symptoms, and spirometry. Data from the subsequent medical notes yielded subsequent history of hay fever, family history of asthma, full work history, date of termination or diagnosis, and tobacco smoking history at the end-point.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium oxide

EC Number:

215-691-6

EC Name:

Aluminium oxide

Cas Number:

1344-28-1

IUPAC Name:

1344-28-1

Details on test material:

- Name of test material :aluminium oxide
- Molecular formula :Al2O3
- Molecular weight :101.96 g mol−1
- Smiles notation :[Al+3].[Al+3].[O-2].[O-2].[O-2]
- InChl :1/2Al.3O/q2*+3;3*-2
- Structural formula attached as image file : see Fig.1
- Substance type:inorganic
- Physical state:white solid very hygroscopic
- Odor: odorless
- Density: 3.95-4.1 g/cm3
- Melting point: 2072 °C
- Boiling point: 2977 °C
- Solubility in water: insoluble
- Solubility :insoluble in diethyl ether, practically insoluble in ethanol

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

A matched case-control study nested in a cohort of 545 workers employed in areas with moderate to high levels of smelting dust and fume. The cohort comprised those who had their first pre-employment medical examination between 1 July 1982 and 1 July 1995; follow up was until 31 December 2000. Forty five cases diagnosed with OAAS and four controls per case were matched for the same year of pre-employment and age within ±5 years. The pre-employment medical questionnaires were examined, blinded as to case-control status, and information obtained on demographics and details of allergic symptoms, respiratory risk factors, respiratory symptoms, and spirometry. Data from the subsequent medical notes yielded subsequent history of hay fever, family history of asthma, full work history, date of termination or diagnosis, and tobacco smoking history at the end-point.

Clinical history:

To assess the significance of individual risk factors in the development of occupational asthma of aluminium smelting (OAAS).
A matched case-control study nested in a cohort of 545 workers employed in areas with moderate to high levels of smelting dust and fume. The cohort comprised those who had their first pre-employment medical examination between 1 July 1982 and 1 July 1995; follow up was until 31 December 2000. Forty five cases diagnosed with OAAS and four controls per case were matched for the same year of pre-employment and age within ±5 years.

Controls:

The pre-employment medical questionnaires were examined, blinded as to case-control status, and information obtained on demographics and details of allergic symptoms, respiratory risk factors, respiratory symptoms, and spirometry. Data from the subsequent medical notes yielded subsequent history of hay fever, family history of asthma, full work history, date of termination or diagnosis, and tobacco smoking history at the end-point.

Route of administration:

inhalation

Details on study design:

Study sample
The cohort consisted of all who had their pre-employment medical examination between 1 July 1982 and 1 July 1995 and commenced their employment in areas with at least weekly exposure to fluoride dust and fume (potrooms, potroom maintenance, pot reconstruction, potroom services, carbon rodding, and rodding maintenance). Follow up was until 31 December 2000.

Selection of cases
The case criteria used were those defined by the Australian Aluminium Council, which is consistent with American Thoracic Society guidelines.20 The criteria were:
• Symptoms of dyspnoea, chest tightness, and/or wheezing, often with cough, which may be brought about by exercise
• A period of initial exposure to fluorides of more than two weeks before symptom onset
• Symptoms temporally related to exposure, but often also nocturnal
• Symptoms improve when the subject is away from work for days or longer.

The symptoms were supported by objective evidence of significant reversible airflow obstruction and/or evidence of BHR on testing.
One respiratory physician diagnosed cases at the smelter between 1982 and 2000. Most cases were detected by regular medical surveillance, however, some cases self-referred. Persons with chronic obstructive disease due to welding or metal fume were excluded.


Selection of controls
Controls, four per case, were matched for age (-+5 years) and same year of commencing employment. Exclusion criteria were any respiratory pathology, significant non-transient respiratory symptoms, being investigated for respiratory pathology, and those employed in an aluminium smelter prior to the original pre-employment.

Data collection

The pre-employment medical questionnaires, examination, and recorded spirometry were examined for all subjects with blinding as to case or control status. Past or present history of hay fever, family history of asthma, past or present history of bronchitis (history of chronic chestiness with associated phlegm), history of asthma before age 15 years, tobacco smoking history at employment (never, ex, and current), past or present history of dermatitis, symptoms of wheeze, and symptoms of regular cough were recorded. Hay fever was defined as seasonal symptoms of itchy, runny nose (allergic rhinitis) with or without associated eye symptoms. Skin testing was not performed.
Physical examination data included height, weight, and ethnicity. Pre-employment spirometric data recorded were the forced vital capacity (FVC), the forced expiratory volume in 1 second (FEV1), and forced expiratory ratio (FER) (100 x FEV1/FVC). Percent predicted values for the FVC and FEV1 were calculated using in-house equations for Europeans, and equations calculated by de Hamel and Welford, for Maoris and Samoans.
Follow up data included hay fever and family history of asthma diagnosed or disclosed after the onset of employment, full work history while at the smelter, and tobacco smoking history at termination, diagnosis, or at the end date of the study. It was assumed that no subjects would develop OAAS after leaving the smelter.

Exposure assessment
Occupational hygiene monitoring provided the mean concentrations of respirable dust, fluorides, and sulphur dioxide in all areas. Exposure was categorised in five levels: potrooms and potroom services, grade 4 (highest risk); pot reconstruction, potroom maintenance, and carbon rodding, grade 3; rodding maintenance, grade 2; metal products and bath and alumina plant, grade 1; and all other areas on site, grade 0. A cumulative exposure index for each individual was calculated by adding the products of the exposure grade and the yearsworked in a specific area.

Statistical analysis
The data were analysed using STATA version 7. Results of the univariate analyses were presented as mean (SD) and proportions. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Adjustment for fluoride exposure was performed by using the exposure index as a continuous variable as well as grade of exposure as a five level categorical variable.

Results and discussion

Results of examinations:

There was a significant positive association between hay fever diagnosed either at or during employment and OAAS (adjusted OR 3.58, 95% CI 1.57 to 8.21). A higher forced expiratory ratio (FEV1/FVC%) at employment reduced the risk of developing OAAS (adjusted OR 0.93, 95% CI 0.88 to 0.99). The risk of OAAS was more than three times higher in individuals with an FER of 70.0–74.9% than in individuals with an FER 80.0% (adjusted OR 3.46, 95% CI 1.01 to 11.89).

RESULTS

Demographics

Table 1 summarises the demographic characteristics. The prevalence of hay fever at employment was higher for cases than controls, but both were lower than the general population in New Zealand (35%). The total prevalence for hay fever was higher at 16.9%. Ninety six per cent of individuals reporting a family history of asthma at employment did so in first degree relatives. Tobacco smoking was common at employment, more so in cases than controls (51.1% versus 43.9%). This differential was still present at diagnosis. Of the non-Europeans only one person was not a Maori or Samoan.

Employment and exposure information

The majority of cases, and a lesser majority of controls, were first employed as potroom operators: 91.1% and 73.9% respectively. Of all the cases and controls in the cohort, 209 (92.9%) started work in the potroom area of the plant (potrooms, potroom services, potroom maintenance, and pot reconstruction). This, and matching for year of employment, ensured similar exposures of cases and controls.
The mean (SD) duration of employment was 10.23 (5.53) years, 6.09 (4.04) years for cases (range 0–16 years), and 11.26 (5.38) years for controls (range 2–19 years). Forty three (95.6%) of the cases were still working in potroom areas at diagnosis. The mean exposure index for cases was 21.21 (SD 14.53, range 3–64) and 17.84 (SD 12.64, range 1.5–63) for controls.

Matched analysis for potential individual risk factors

Table 2 summarises the matched analysis for potential individual risk factors for OAAS. The odds ratio (OR) for hay fever at employment was raised, although not significantly, both before and after adjustment for confounders (crude OR 1.65, 95% CI 0.59 to 4.60; adjusted OR 2.28, 95% CI 0.76 to 6.89). Examining ‘‘all hay fever’’ (identified at employment and subsequently) showed a statistically significant increased risk, enhanced by adjustment for confounding. The magnitude of this association increased further on adjusting for smoking at termination or diagnosis as against smoking status at employment (adjusted OR 3.79, 95% CI 1.64 to 8.79). A family history of asthma, history of bronchitis, childhood asthma, and wheeze at pre-employment
revealed increased, but non-significant ORs. There was no significant association between OAAS and tobacco smoking. The remainder of the potential risk factors showed only weak associations. There was a statistically significant negative association between the FER at pre-employment and OAAS (crude OR 0.93, p=0.005; adjusted OR 0.93, p=0.017). Thus for each 1% lower FER at employment the risk of OAAS increased by 7%. In the stratified analysis, there was a significant positive association with an FER of 75.0–79.9% (crude OR 2.22, p=0.038). A pre-employment FER of 70.0–74.9% increased the risk for OAAS further (crude OR 3.35, p=0.026). Individuals with the lowest level of FER (,70.0%) also had an increased risk, but because of the small number (n=4), the finding was not statistically significant (adjusted OR 2.94, 95% CI 0.24 to 36.46, p=0.546).

Any other information on results incl. tables

Table 1	Characteristics of the cases and controls in the study
Characteristic		Controls (n = 180)	Cases (n = 45)	Total (n = 225)
Age (years)		26.7 (+-6.1)	26.6 (+-6.3)	26.7 (+-6.2)
Height (cm)		176.9 (+-5.9)	175.9 (+-6.6)	176.7 (+-6.0)
Weight (kg)		78.3 (+-11.7)	79.7 (+-10.4)	78.6+-11.2)
Body mass index		25.0 (+-3.23)	25.77 (+-3.2)	25.16 (+-3.2)
Ethnicity
Caucasian		166 (92.2%)	40 (88.9%)	206 (91.6%)
Maori/Samoan		20 (11.1%)	6 (13.3%)	26 (11.6%)
Other		1 (0.6%)	0	1 (0.4%)
Tobacco smoking (at employment)
Never smokers		79 (43.9%)	18 (40%)	97 (43.1%)
Ex smokers		22 (12.2%)	4 (8.9%)	26 ( 11.6%)
Current smokers		79 (43.9%)	23 (51.1%)	102 (45.3%)
Tobacco consumption
None		101 (56.1%)	22 (48.9%)	123 (54.7%)
Light smokers		10 (5.6%)	1 (2.2%)	11 (4.9%)
Moderate smokers		48 (26.7%)	17 (37.8%) `	65 (28.9%)
Heavy smokers		21 (11.7%)	5 (11.1%)	26 (11.6%)
Smoking at termination or diagnosis		59 (32.8%)	19 (42.3%)	78 (34.7%)
Hay fever at employment		15 (8.5%)	6 (13.3%)	21 (9.5%)
Hay fever (total)*		24 (13.3%)	14 (31.1%)	38 (16.9%)
Familial asthma (at employment)		18 (10.0%)	6 (14.3%)	24 (10.8%)
Familial asthma (total)*		40 (22.2%)	12 (26.7%)	52 (23.1%)
Childhood history of asthma		2 (1.1%)	1 (2.2%)	3 (1.3%)
Previous history of bronchitis		1 (0.6%)	1 (2.2%)	2 (0.9%)
Previous history of dermatitis		10 (5.6%)	3 (6.7%)	13 (5.8%)
Cough at employment		2 (1.1%)	0 (0%)	2 (0.9%)
Wheeze at employment		3 (1.7%)	0 (0%)	0 (0%)
*Total: The sum of people with such a history at the pre-employment examination and those with a subsequent history during their employment at the smelter.

Table2	The association between OAAS and potential individual risk factors
		Crude odds ratios	Adjusted odds ratios*	Alternative adjusted odds ratios�
Variable studied		(95% CI)	(95% CI)	(95% CI)
Hay fever (at employment)		1.65 (0.59 to 4.60)	2.28 (0.76 to 6.89)	2.66 (0.84 to 8.42)
All hay fever		2.91 (1.35 to 6.26)	3.58 (1.57 to 8.21)	3.32 (1.37 to 8.05)
Family history of asthma (at employment)
Family history of asthma		1.60 (0.58 to 4.42)	1.63 (0.57 to 4.69)	2.23 (0.71 to 7.03)
First degree family history		1.73 (0.61 to 4.89)	1.80 (0.61 to 5.33)	2.25 (0.71 to 7.10)
Numbers of family members		1.59 (0.80 to 3.13)	1.60 (0.79 to 3.21)	1.99 (0.91 to 4.34)
Family history of asthma (at employment and subsequently)
Family history of asthma		1.29 (0.60 to 2.79)	1.44 (0.64 to 3.24)	1.28 (0.55 to 2.97)
First degree family history		1.40 (0.64 to 3.07)	1.60 (0.69 to 3.68)	1.37 (0.58 to 3.25)
Numbers of family members		1.21 (0.60 to 2.43)	1.26 (0.61 to 2.61)	1.07 (0.51 to 2.24)
A history of hay fever and familial asthma		1.54 (0.71 to 3.35)	1.94 (0.85 to 4.43)	2.42 (0.99 to 5.93)
Tobacco smoking
Never smoker		reference	reference	reference
Ex-smoker at employment		0.81 (0.25 to 2.64)	0.70 (0.21 to 2.35)	0.83 (0.24 to 2.84)
Smoking at start of employment		1.31 (0.64 to 2.69)	1.29 (0.61 to 2.75)	1.46 (0.66 to 2.84)
Light smoker		0.47 (0.06 to 3.98)	0.43 (0.05 to 3.72)	0.60 (0.07 to 5.14)
Moderate smoker		1.62 (0.78 to 3.38)	1.49 (0.68 to 3.26)	1.82 (0.82 to 4.03)
Heavy smoker		1.11 (0.37 to 3.40)	1.64 (0.50 to 5.43)	1.23 (0.39 to 4.01)
Smoking at termination of employment or diagnosis		1.52 (0.77 to 3.00)	1.70 (0.84 to 3.42)	1.72 (0.85 to 3.51)
History of bronchitis		4.00 (0.25 to 63.95)	3.68 (0.20 to 66.49)	5.87 (0.31 to 112.00)
History of childhood asthma		2.00 (0.18 to 22.06)	3.02 (0.26 to 34.86)	11.61 (0.63 to 213.84)
History of dermatitis		1.21 (0.32 to 4.52)	1.96 (0.49 to 7.84)	1.79 (0.43 to 7.55)
Maori/Samoan ethnicity		1.48 (0.50 to 4.34)	1.42 (0.46 to 4.45)	1.18 (0.38 to 3.63)
Wheeze on auscultation at pre-employment examination		4.00 (0.56 to 28.40)	4.81 (0.65 to 35.44)	6.55 (0.56 to 77.10)
Being overweight (BMI 25.0–29.9)		1.13 (0.56 to 2.31)	1.10 (0.52 to 2.36)	1.41 (0.60 to 3.28)
Being obese (BMI >30.0)		2.09 (0.71 to 6.16)	2.17 (0.68 to 6.87)	2.82 (0.79 to 10.04)
Spirometric variables
FVC (% of predicted)		1.01 (0.97 to 1.04)	1.01 (0.98 to 1.05)	1.00 (0.96 to 1.04)
FEV1 (% of predicted)		0.98 (0.95 to 1.01)	0.99 (0.96 to 1.02)	0.98 (0.95 to 1.01)
FER (FEV1/FVC %)		0.93 (0.88 to 0.98)	0.93 (0.88 to 0.99)	0.93 (0.88 to 0.99)
Stratified analysis
FER >80.0%		reference	reference	reference
FER 75.0–79.9%		2.22 (1.05 to 4.72)	2.05 (0.93 to 4.52)	3.07 (1.26 to 7.50)
FER 70.0–74.9%		3.35 (1.15 to 9.75)	2.62 (0.85 to 8.07)	3.46 (1.01 to 11.89)
FER ,70.0%		2.04 (0.20 to 20.56)	2.09 (0.20 to 21.68)	2.94 (0.24 to 36.46)
*Adjusted for exposure index, current and ex smoking at employment, and Maori/Samoan ethnicity.

Applicant's summary and conclusion

Conclusions:

Individuals with hay fever may be more susceptible to occupational asthma when exposed to airborne irritants in aluminium smelting. The pathological basis may be reduced nasal filtration and increased bronchial hyperresponsiveness

Executive summary:

Aims:To assess the significance of individual risk factors in the development of occupational asthma of aluminium smelting (OAAS). Methods:A matched case-control study nested in a cohort of 545 workers employed in areas with moderate to high levels of smelting dust and fume. The cohort comprised those who had their first pre-employment medical examination between 1 July 1982 and 1 July 1995; follow up was until 31 December 2000. Forty five cases diagnosed with OAAS and four controls per case were matched for the same year of pre-employment and age within ±5 years. The pre-employment medical questionnaires were examined, blinded as to case-control status, and information obtained on demographics and details of allergic symptoms, respiratory risk factors, respiratory symptoms, and spirometry. Data from the subsequent medical notes yielded subsequent history of hay fever, family history of asthma, full work history, date of termination or diagnosis, and tobacco smoking history at the end-point. Results:There was a significant positive association between hay fever diagnosed either at or during employment and OAAS (adjusted OR 3.58, 95% CI 1.57 to 8.21). A higher forced expiratory ratio (FEV1/FVC%) at employment reduced the risk of developing OAAS (adjusted OR 0.93, 95% CI 0.88 to 0.99). The risk of OAAS was more than three times higher in individuals with an FER of 70.0–74.9% than in individuals with an FER Conclusions:Individuals with hay fever may be more susceptible to occupational asthma when exposed to airborne irritants in aluminium smelting. The pathological basis may be reduced nasal filtration and increased bronchial hyperresponsiveness