Summary

The use of spot sampling to measure urinary concentration of biomarkers is a common practice in biological monitoring of occupational exposure. To take account of the degree of urine dilution, the urinary concentrations measured in spot samples are usually corrected based on creatinine or urinary specific gravity.  However, some authors question one or the other of these correction methods because they are too variable or do not accurately reflect the excretion mechanisms of biological indicators.

The purpose of this research was to determine the best correction method for taking account of the degree of urine dilution in spot samples.

A literature review on the topic was done for the period from January 1990 to June 2013. The IRSST’s Laboratory Information Management System (LIMS) was queried for the years 1985 to 2010 in order to document the correlation between corrected or uncorrected urinary concentrations of biological indicators of 22 substances investigated in this study. Descriptive statistics and modelling, using linear mixed effects models, were also applied to creatinine and specific gravity data.

The results of the literature review within this study show that creatinine correction may cause a significant bias in the measurement of exposure in individuals or populations of different age, gender, ethnicity and muscle mass, whereas specific gravity correction is apparently less influenced by  these factors.  Moreover, specific gravity measurement uses a simpler, more cost-effective method than creatinine measurement. These data suggest that specific gravity correction is a promising alternative to creatinine correction. Although specific gravity correction seems the most suitable, the choice of correction method should take into account the units in which the biological indicators of exposure (BIEs) are expressed. However, BIE values expressed based on these two correction methods can be rigorously calculated using the linear regression equations calculated in this study from LIMS data. These equations describe the correlation between creatinine-corrected and specific gravity-corrected concentrations for the indicators  under investigation.

Changes in urinary output affect the excretion of most biological indicators, including creatinine and specific gravity measurement.  Accordingly, in biological monitoring, it seems justified to reject urine samples that are too diluted (specific gravity < 1.010; creatinine < 4.4 mmol/l) or too concentrated (specific gravity > 1.030; creatinine > 26.5 mmol/l).  Authors have proposed a correction method that takes account of the urinary output effect on the renal excretion of biological indicators. However, although this correction method seems justified and promising, its use is greatly restricted by a lack of reference value.

Descriptive statistics were done on creatinine and specific gravity data contained in the LIMS database. The mean creatinine values calculated in men (n=17,873) and women (n=2, 323) are 15.0 ± 6.4 and 10.9 ± 6.1 mmol/l, respectively. The results of the modelling suggest that creatinine concentrations in women are 25% to 30% lower on average than in men. The creatinine values found in this study are comparable to data published in other studies on workers.

The mean specific gravity values calculated in this study for men (n=17,811) and women (n=2,385) are 1.023 ± 0.006 and 1.019 ± 0.007, respectively. According to the modelling results, the specific gravity values are 10% (end of shift) and 15% (beginning of shift) lower on average in women than in men. For men, the results are 5% higher at the end of a work shift compared to a sample taken at the beginning of the shift. Other authors also report significantly lower mean specific gravity values in women compared to men. Thus, like creatinine, specific gravity values seem to be lower in women than in men, possibly due to a lower muscle mass in women.

The review of literature findings showed that specific gravity-corrected urinary concentrations and biological indicators are less influenced by an individual’s age, gender and muscle mass than creatinine-corrected results. However, because several reference values currently available in the literature are expressed based on creatinine, it is important to consider the units in which those reference values are expressed before choosing a correction method. This will allow for adequate interpretation and comparison of biological monitoring data.  In our opinion, specific gravity correction has many advantages over creatinine correction, and so should be considered, if not prioritized, as a correction method in future studies aiming to propose reference values for biological monitoring of occupational exposure.