Reaction product of fusion between 1000°C and 2000°C of aluminium oxide and calcium oxide based raw materials with at least CaO+Al2O3+Fe2O3 > 85%, in which aluminium oxide and calcium oxide in varying amounts are combined in various proportions into a multiphase crystalline matrix.

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: Epi observational

Adequacy of study:

other information

Study period:

1995 - 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given.

Data source

Reference

Reference Type:

publication

Title:

Relationships between alumina and bauxite dust exposure and cancer, respiratory and circulatory disease.

Author:

Friesen et al.

Year:

2009

Bibliographic source:

Occup Environ Med. 2009 Sep; 66(9):615-618.

Materials and methods

Study type:

cohort study (prospective)

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline required

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bauxite and alumina

IUPAC Name:

Bauxite and alumina

Details on test material:

Name of test material (as cited in study report): bauxite and alumina
Details were not provided on the physical state, impurities (identity and concentrations) or other co-exposures.

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study):
The objective of this study was “to examine the associations between alumina and bauxite dust exposure and cancer incidence and circulatory and respiratory disease mortality among bauxite miners and alumina refinery workers.”

STUDY PERIOD: 1983-2002

SETTING: Four bauxite mines and three alumina refineries in Western Australia

STUDY POPULATION & SAMPLE
- Inclusion criteria: Male workers hired on or after 1 January 1983, for whom work history information was available (n=5770). Fifty eight subjects were excluded because of unavailable job history information.
- Total number of subjects in the study: 5770
- Sex/age/race: male. Mean age at study entry 32 years (SD 10.5 years), maximum age at study entry – 64 years.
Mean duration of employment – 14.1 years (SD 8.7 years), maximum – 40 years. The study population included smokers and non-smokers (further detail is provided in the results section).
COMPARISON POPULATION
- Type: State registry / Regional registry / National registry / Control or reference group / Other:
- Details: unexposed workers within the cohort

METHOD OF DATA COLLECTION
Interview /
Questionnaire /
Record review /
Work history /
Clinical tests /
other: national mortality and national and state cancer incidence registries
- Details of data collection:
Work histories and smoking information for cohort members whose employment ended before 1995 were abstracted from company records. Work histories and smoking information for all other cohort members were collected at interviews during a 1995-1996 survey and later during the follow-up period. Mortality and cancer incidence information was obtained by linkage with national mortality and national and state cancer incidence registries for the period 1983-2002.
HEALTH EFFECTS STUDIED
- Disease(s):
Cancer incidence based on linkage with national and state cancer incidence registries
- Mortality:
Mortality from non-malignant respiratory diseases and from circulatory diseases (cardiovascular and cerebrovascular) based on linkage with the national mortality registry
FOLLOW-UP: 1983-2002

Exposure assessment:

estimated

Details on exposure:

TYPE OF EXPOSURE:
Inhalation

TYPE OF EXPOSURE MEASUREMENT: Area air sampling / Personal sampling / Exposure pads / Biomonitoring (urine) / Biomonitoring blood / other:

Individual cumulative exposures to bauxite and alumina were calculated as described below:
Time-weighted average monitoring data for inhalable dust were received from the company. Air sampling before 1998 was performed with a closed-face 37 mm cassette for total dust (NIOSH N-0500) which could underestimate the inhalable fraction. After 1998, the Institute of Medicine inhalable sampling head was used. The annual arithmetic mean was calculated for each combination of site, department, job and task. Tasks for which there were no monitoring data were assigned a proportion of value from a similar monitored task (from 5 to 100%, determined by a hygienist). Values were also extrapolated to years for which no measurements were available. A value of half the limit of detection was assigned to tasks with no monitoring data and considered to have very low exposure. For workers who quit before 1986 work histories were available only at the job level. For all workers, a job-exposure matrix was developed from the TEM by weighting tasks performed in each job using task weighting factors from the 1995-1996 interviews. It was assumed that workers with no interview data after the 1995/1996 survey remained in their last reported jobs until employment termination or until the study termination.

Statistical methods:

Relative risks for each exposure category compared to the unexposed category were calculated using Poisson regression with categorical covariates for age, calendar year (5-year intervals were used when the number of cases was sufficient) and smoking (see above). Exposure-response relationships were examined for endpoints for which there were at least 6 exposed cases and the risk in ever exposed was elevated compared to never exposed. Exposure categories were disease-specific and were based on distribution of exposure of cases applying cut-offs at the 33.3 and 66.6 percentiles. Tests for trend were performed by setting the ordinal exposure variable (0-3) to a continuous variable.

Results and discussion

Results:

EXPOSURE LEVELS
- Arithmetic mean:
Cumulative bauxite exposure for exposed workers (57%): 13.4 mg/m3-years
Cumulative alumina exposure for exposed workers (41%): 14.5 mg/m3-years
- Median: (for those exposed)
Cumulative bauxite exposure for exposed workers (57%): 5.7 mg/m3-years
Cumulative alumina exposure for exposed workers (41%): 2.8 mg/m3-years
- Other:
Maximum cumulative bauxite exposure for exposed workers (57%): 187 mg/m3-years
Maximum cumulative alumina exposure for exposed workers (41%): 210 mg/m3-years
Cumulative exposures to bauxite and alumina were not correlated; 32% had never been exposed to either dust, 16% had been exposed to both dusts.
FOLLOW-UP
A total of 93,420 person-years of follow-up; mean duration of follow-up 16.2 years (SD 4.8 years), maximum – 20 years.

RESULTS
Bauxite
Exposed vs. unexposed: non-significantly increased mortality from cerebrovascular diseases (RR=2.1; 95% CI 0.5-8.1; n=10) and from non-malignant respiratory diseases (RR=5.8; 95% CI 0.7-48; n=7). No increase in mortality from cardiovascular diseases (RR=0.9; 95% CI 0.6-1.4) was observed.
No exposure-response relationship was found for cerebrovascular disease mortality. There was a monotonic increasing trend in mortality from non-malignant respiratory diseases with increasing exposure category (see tables below). The 7 respiratory disease deaths included chronic obstructive pulmonary disease, asbestosis, unspecified bronchopneumonia, other interstitial pulmonary disease with fibrosis.

No significant association with bauxite exposure was observed for incidence of any cancer. A non-significant increase was observed for stomach cancer (RR=1.7; 95% CI 0.3-9.3; n=6) and brain cancer (RR=2.1; 95% CI 0.4-11; n=7). Because of the small number of cases, the exposure-response relationship was not examined for these cancers.
Exposure to alumina
Exposed vs. unexposed: A significantly increased mortality from cerebrovascular diseases (RR=3.8; 95% CI 1.1-13) was observed. No significant increase was observed for mortality from cardiovascular diseases (RR=1.1; 95% CI 0.7-1.8) or from non-malignant respiratory diseases (RR=0.9; 95% CI 0.2-4.5)
A significant (non-monotonic) trend was observed for mortality from cerebrovascular diseases and a suggestive trend (p=0.1) for mortality from all circulatory diseases.

Confounding factors:

Smoking
The cohort members were categorized as never, former, current smokers, non-smokers (if never or former smokers could not be distinguished), and with unknown smoking status.
Overall, 35% were never smokers, 27% - former smokers, 27% - current smokers, 5% non-smokers and 5% unknown. Workers exposed to bauxite had a slightly greater proportion of current smokers (29% vs. 24%) or former smokers (29% vs. 25%) and a smaller proportion of never smokers (32% vs. 38%) than unexposed workers. Alumina-exposed and unexposed workers did not differ by their smoking status distribution.

Strengths and weaknesses:

Strengths: rigorous exposure assessment
Limitations:
- The associations are based on very small numbers of deaths.
- Causes of death as determined from an administrative database may be of limited validity.
- Possible residual confounding by smoking

Any other information on results incl. tables

Table 1: Exposure to bauxite and mortality form cerebrovascular diseases

Unexposed	Low	Medium	High	P value for trend
Exposure categories				0.27
0 mg/m^3-years	>0-0.71 mg/m^3-years	0.71-16.5 mg/m^3-years	>16.5 mg/m^3-years
Number of deaths
3	2	3	2
Relative risks (95% CI) adjusted for age, calendar year and smoking
1	2.5 (0.4-15)	2.2 (0.4-11)	2.4 (0.4-15)

Table 2: Exposure to bauxite and mortality from non-malignant respiratory diseases

Unexposed	Low	Medium	High	P value for trend
Exposure categories				0.1
0	>0-16.0 mg/m^3-years	16.0-48.3 mg/m^3-years	>48.3 mg/m^3-years
Number of deaths
1	2	2	2
Relative risks (95% CI) adjusted for age, calendar year and smoking
0.4 (0.0-4.0)	1	2.6 (0.3-20)	6.4 (0.8-53)

Table 3: Exposure to alumina and mortality from all circulatory diseases

Unexposed	Low	Medium	High	P value for trend
Exposure categories				0.04
0	>0-6.05 mg/m^3-years	6.05-11.7 mg/m^3-years	>11.7 mg/m^3-years
Number of deaths
4	2	2	2
Relative risks (95% CI) adjusted for age, calendar year and smoking
1	2.7 (0.5-15)	8.7 (1.5-49)	4.2 (0.7-21)

Applicant's summary and conclusion

Conclusions:

There was statistical evidence for an association between mortality from non-malignant respiratory diseases and exposure to bauxite, and between mortality from cerebrovascular diseases and exposure to alumina. These associations were based on small numbers of cases and may reflect chance findings. Neither bauxite nor alumina exposure was associated with increased cancer risk.

Executive summary:

Friesen et al. (2009) investigated the associations between alumina and bauxite dust exposure and circulatory disease mortality, respiratory disease mortality and cancer incidence in a cohort of employees from four bauxite mines and three alumina refineries in. These individuals were employed on or after Jan 1, 1983. For employees employed before the survey in 1995 - 1996, work history and smoking status were obtained from company records. Outcomes were determined by linkage with the national mortality database and the national and state cancer incidence registries. Cumulative exposure to inhalable bauxite and alumina were estimated using a task-exposure matrix for those employed in 1995/6. A less detailed job-exposure matrix was required for subjects who left employment before 1996. Before 1998, total dust was measured using a NIOSH cassette subsequently found to underestimate the inhalable fraction. Post-1998, anofdevice was used. The study cohort had a mean age of 32 years (10.5, sd, standard deviation) at entry, a mean duration of employment of 14.1 years, a mean person-year (PY) contribution of 16.2 years (4.8, sd) providing a total of 93, 420 PYs of follow-up. A greater percentage of the bauxite-exposed workers were either current (29% v 24%) or former (29% v 25%) smokers compared to the unexposed group while alumina-exposed workers and unexposed workers did not differ with respect to smoking status. The median, mean and maximum cumulative exposures to bauxite among the bauxite-exposed workers were 5.7, 13.4, and 187 mg/m³-yr, respectively. The median, mean and maximum cumulative exposures to alumina among the alumina-exposed workers were 2.8, 14.5, and 210 mg/m³-yr, respectively. Exposure categories used in the analyses were defined based on the tertiles in the few cases. The relative risk of death from non-malignant respiratory disease showed a significant trend (7 deaths; p < 0.01) with cumulative bauxite exposure with adjustment for age, calendar year and smoking. The deaths were due to chronic obstructive pulmonary disease, asbestosis, unspecified bronchopneumonia and interstitial pulmonary disease with fibrosis. Cumulative alumina exposures showed a marginally significant trend with mortality from cerebrovascular disease (10 deaths; p = 0.04). No notable associations or trends were observed for cancer outcomes. The analyses in this study were based on only a few cases accrued during the relatively short follow-up and adjustment for smoking was done using only a crude categorical variable. Further follow-up and accrual of more cases will be required to determine the validity of the reported trends.