Validation of biomarkers for improved assessment of exposure and early effect from exposure to crystalline silica
Date
2010-03-09T07:25:49Z
Authors
Makinson, Kerry Sue
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Abstract
This is the third phase of a project to identify, confirm, and operationalise biomarkers
for crystalline silica dust exposure that could be used for surveillance of dust exposure
levels in South African mines. The first phase of the project involved a comprehensive
review of the relevant literature [Gulumian et al., 2006] from which ten potential
biomarkers of effect were identified as being worthy of further investigation. The
second phase of the project examined the ten identified biomarkers in silica dustexposed
and unexposed black male subjects [Murray et al., 2006]. Two of the ten short
listed biomarkers, namely erythrocyte glutathione peroxidase (GPx) and serum Clara
cell protein 16 (CC16), were found to have significantly reduced levels in the silica
dust-exposed versus unexposed subjects. In addition, the biomarkers were found to be
unaffected by HIV sero-status, smoking, age and the presence of silicosis. As a result,
this third phase of the project aimed to confirm the levels of and further analyze GPx
and CC16 in miners exposed to crystalline silica dust. This third phase involved the measurement of the levels of erythrocyte GPx and serum
CC16 in 80 adult male gold miners upon their return from leave and then again two to
six months after they had returned to work (involving exposure to crystalline silica).
Before the field work was conducted, however, the optimal operational parameters for
the biomarkers (namely storage temperature, delay in time between blood collection and
separation, laboratory temperature and storage duration) were established. The results of
these optimization experiments were used to develop Standard Operating Procedures
(SOPs) for biomarker specimen handling and storage under field conditions, and for
laboratory assays. In this phase, the findings of the second phase were confirmed in that the levels of GPx
and CC16 were lowered in miners exposed to crystalline silica dust and were unaffected
by age, race and cigarette smoking. In addition, while CC16 was unaffected by the
presence of radiological silicosis, GPx may have been affected. Finally, the decrease in
the levels of GPx activity and CC16 concentration observed in the study were
unaffected by the level of silica dust exposure (high or low) as determined by job
category or by the duration of crystalline silica exposure.
Regarding the levels of GPx activity, the results suggested that GPx levels decrease
after two to six months of chronic exposure to crystalline silica dust and remain
decreased (throughout the working week and over a weekend) and then increase or even
recover to normal levels during a period of leave. It was therefore concluded that GPx
activity levels rise and fall, in response to silica dust exposure, gradually and over
periods of some time, possibly months.
The CC16 results were, however, less promising. After two to six months of chronic
exposure to crystalline silica dust there was a significant change in CC16 on a
Wednesday afternoon following an 8-hour shift and during the duration of a shift. In
addition, there is the possibility that the observed changes were due to a time-dependent
diurnal variation in the CC16 levels.
It was concluded that the results of the current phase warrant further research into the
use of erythrocyte GPx and serum CC16 as biomarkers of early effect from crystalline
silica exposure.