BaP cumulative exposure provided a modest improvement in model fit and model precision over BSM for bladder and lung cancer incidence. No differences were observed between metrics for AMI. Similar conclusions were made regarding associations between exposure to coal tar‐derived substances and the health outcome of interest regardless of exposure metric.
Previous aluminium smelter studies have assessed BaP exposure using the ratio of BaP to BSM, since much less sampling data are available for BaP than for BSM.2,3
These studies have accounted for work area and job differences in the BaP:BSM ratio, but have assumed through necessity that these ratios were stable throughout the study period. In this study, we assessed BaP exposure independently from BSM, and so could account for time‐varying factors that influenced BaP exposure, but were unable to account for differences in the relationship between BaP and other PAHs, which has been found to vary across time, job and work area.26
Exposure misclassification may be introduced by the use of an individual compound if its relationship with the causal components varies.
A quantitative comparison of two different exposure metrics becomes complicated when the metrics have different units of exposure or scales of exposure. To facilitate comparisons between BSM and BaP, we defined exposure categories on the basis of the cumulative exposure of the cases to minimise bias due to cutpoint selection and treated exposure as a continuous variable in Poisson's regression.23
Both the improvement in model fit and the precision of the dose–response relationship indicated that cumulative BaP exposure was the better index for all three health outcomes. However, both measures are sensitive to the units and scale of the exposure metric owing to the logarithmic relationship with RR and exposure. For the log‐linear model, changing the scale of the exposure metric (ie, dividing BaP by 10 to be on the same scale as BSM) did not change the magnitude of the improvement in model fit, but did slightly change the magnitude of the precision. The log–log model was particularly sensitive to the scale of these measures, with both the improvement in model fit and the magnitude of the precision changing with the scale of the metric. Regardless, BaP provided a better fit in all cases.
A levelling off of risk at the highest exposure categories (log–log model) has been observed in many retrospective studies. Non‐differential exposure misclassification has been shown in simulation studies to have this effect.27
The highest exposure categories were strongly influenced by pre‐1977 exposure levels, when no exposure measurements were available. While we extrapolated backwards from 1977 exposure estimates, assumptions regarding the shape of the time trend were required.19
The linear relationship between bladder cancer incidence and BaP exposure seen here provides indirect support for the validity of the BaP exposure metric. Sensitivity analyses could be conducted in future analyses to examine the impact of different assumptions regarding the backwards extrapolation.28,29
Other possible explanations for the levelling off of risk at high exposure categories include confounding by other risk factors, healthy worker survivor effect; depletion of the number of susceptible people at high exposure levels; a natural limit on RRs for diseases with high background rates; and the saturation of key disease pathways.30
Several of these reasons may be attributed to this cohort; however, these explanations would be expected to have a similar impact for both the BaP and BSM exposure indices.
Other aluminium smelter exposures—namely, benzo(b)fluoranthene and naphthalene—have been proposed as indicators of PAH. Aubin and Farant31
suggested benzo(b)fluoranthene as a more stable indicator of PAH environmental exposure because BaP levels are more influenced by environmental factors; however, it was very highly correlated with BaP (r
0.97) within this smelter. Rappaport et al32
proposed naphthalene as a potential surrogate for occupational PAH exposure because it is the most abundant PAH and because it is present almost entirely in the gas phase and therefore can be measured easily. The relationship between BaP and naphthalene at this smelter is not known, as naphthalene has not been monitored regularly. Naphthalene has been found to be only moderately correlated (r
0.54) with BaP at another Söderberg aluminium smelter,16
suggesting that it would be a useful indicator as it measures alternative exposures. The correlation between BaP and amino‐PAHs and nitro‐PAHs has not been reported, but amino‐PAHs and nitro‐PAH levels were very low in one aluminium smelter and were found to be well controlled by current ventilation processes.11
The consistently strong and more precise dose–response relationships observed with the BaP metric provides support for the use of BaP as a measure of exposure to the PAH mixture in examinations of cancer and heart disease in aluminium smelters. The strength of the comparison between dose–response relationships presented here was the substantial number of cases for each outcome, the examination of the continuous dose–response relationships, and the measurement‐based exposure assessment strategy that independently assessed BaP and BSM exposure levels. The levelling off of risk at high exposure categories may result from exposure misclassification, but may also result from time‐varying differences between BaP and other specific causal exposure agents, or may suggest that different causal components may be associated with the different disease outcomes. Morbidity outcomes, such as hospitalisation for respiratory or cardiovascular disease, may provide a better comparison of the usefulness of BaP and BSM as indices of exposure to coal tar‐derived substances, as there is more confidence in the exposure estimates in more recent time periods. The relationship between BaP and other coal tar constituents, and factors that influence that relationship should continue to be examined, in order to shed light on the specific causal agents.
- The occurrence of polycyclic aromatic hydrocarbons (PAHs) as a mixture creates significant challenges for exposure assessment in epidemiology, including choosing an appropriate indicator of the carcinogenic or toxic potential of the mixture.
- Benzo(a)pyrene (BaP) and benzene‐soluble materials (BSMs) were both strongly associated with bladder and lung cancer, and similar conclusions regarding the associations could be made regardless of the exposure metric.
- Cumulative BaP exposure provided a modest improvement in the precision of the exposure–response relationship for bladder cancer and lung cancer incidence than cumulative BSM metrics.
- Evaluating the difference metrics of PAH exposure was facilitated by examining continuous exposure–response relationships and comparing the model fit and precision of the model slope.
Comparing exposure–response relationships using multiple quantitative exposure metrics will improve our knowledge of the aetiological agents, and can facilitate risk assessment and exposure standard setting.