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McDonald et al  present an updated analysis of a cohort of mostly
women who made gas masks incorporating crocidolite asbestos between
1944. They found a high risk of death from pleural and peritoneal
mesothelioma, confirming the carcinogenicity of crocidolite, but during
last 8 years of follow-up there were no further deaths from mesothelioma
(their Figure 1 and Table 3).
They noted that th...
They noted that the mesothelioma rate (number of mesothelioma per
100,000 person years at risk) did not continually increase with time since
exposure, as is often believed, but levelled off after about 30 years.
attributed these observations on the mesothelioma rate to clearance of the
fibres from the lung, although they recognised that the absence of deaths
the final years of follow-up could not be explained by clearance alone.
We agree with the authors that clearance of fibres from the lungs is
viable explanation for all of their observations. To illustrate this we
modelled the risk with a few simplifying assumptions, in order to look at
time course of the predictions compared to the reported data. We
deaths from mesothelioma for a hypothetical group of women exposed a high
concentration of crocidolite for one year starting at age 20, using the
approach to estimating risks of mesothelioma outlined by US Health Effects
Institute . This model has been widely used to predict future risks for
populations exposed to asbestos. We adjusted the multiplicative
(i.e. nominal exposure level) to produce the same total number of
mesothelioma as reported in total by McDonald et al (i.e. 65
Key issues to be taken into account when predicting risks of
using standard models are the effects of competing deaths (implicitly
adjusted for in observational studies) and clearance of fibres from the
Figure 1 shows the effects of these adjustments separately and in
combination on the predicted annual deaths from mesothelioma. We
adjusted for clearance by including a term to account for clearance of the
fibres from the lung as recommended by Berry , assuming a clearance
time of 20 years. Essentially, this model includes an exponential decay
function to reduce the predicted annual risk. It represents the
that there is some progressive elimination of the crocidolite fibres from
lung. Information on risk of death from all causes by age was obtained
the UK Office of National Statistics.
It is clear that without including terms of clearance or competing
death the mesothelioma risk increases continuously. With only the
term in the model the predicted number of deaths is much lower and tends
plateau at about 1.8 deaths per year. Including competing causes of death
rather than clearance causes the predicted number of deaths to peak in
1990, when the age of those exposed would have been 70 years, and then
decline rapidly. The combination of clearance and competing causes of
produces a pattern of predicted deaths from mesothelioma similar to that
observed by McDonald and his co-workers, i.e. a rise in the predicted
of deaths, then relatively steady number of deaths each year between about
1970 and 1990 followed by a rapid decrease in the deaths per year.
the model still predicts a number of mesothelioma deaths in the latter
The inclusion of the elimination function and the competing cause
led to a reasonably good agreement with observed data in each period, as
shown in Figure 2. In this figure, the observed number of mesothelioma
necessarily integers, whereas the predictions are not rounded to whole
numbers. The difference between prediction and observed has been rounded
to the nearest whole number. Our simplified model confirms that whereas
the “elimination factor” does suffice to reproduce the trend over the
eight periods, it does not account for the dearth of mesothelioma in the
We suggest that there might be at least two possible explanations for
absence of mesothelioma deaths in these later periods.
1. Those surviving into the final 8 years might be people who had least
exposure among that workforce (e.g. they might have been people who left
school in 1944 and thus were also relatively young and would therefore be
the final survivors). This would correspond to there essentially being two
groups of people in the factory: one with high exposure and a second,
younger group, with little or no exposure.
2. Alternatively, the elevated levels of respiratory cancer in the whole
workforce might suggest that lung cancer, having a shorter latency ,
claimed the victims before mesothelioma did, i.e. some people with high
exposure may have been at risk of both diseases and succumbed to the lung
cancer earlier than mesothelioma.
We believe that it is important to take account of both clearance and
from causes other than mesothelioma in asbestos risk assessments. Any
methods that do not include both these terms will provide an overestimate
risk, particularly for young people exposed to asbestos. Further research
needed to understand whether there are other processes affecting the risk
after very long periods of follow-up.
John W Cherrie
Head of Statistics and Epidemiology
Head of Fibre Research
1. McDonald JC, Harris JM, Berry G. Sixty years on: the price of
military gas masks in 1940. Occup Environ Med. 2006; 63: 852-5.
2. Health Effects Institute. Asbestos in public and commercial
literature review and synthesis of current knowledge. 1991. Cambridge, MS:
3. Berry G. Models for mesothelioma incidence following exposure to
in terms of timing and duration of exposure and the biopersistence of the
fibres. Inhal Toxicol 1999; 11: 111-30.
4. Selikoff IJ, Hammond EC, Seidman H. Latency of asbestos disease
insulation workers in the United States and Canada. Cancer. 1980; 46:
Figure 1. Predicted mesothelioma deaths, including terms for
death from competing causes.
Figure 2. Number of mesothelioma in the 10 observation periods
Table 3 of McDonald et al, i.e. 9 five-year periods from 1956 to 2000, and
one three-year period from 2001 to 2003.