Creatinine and specific gravity normalization in biological monitoring of occupational exposures

Reference values for the biological monitoring of occupational exposures are generally normalized on the basis of creatinine (CR) concentration or specific gravity (SG) to account for fluctuations in urine dilution. For instance, the American Conference of Governmental Industrial Hygienists (ACGIH(®)) uses a reference value of 1g/L for CR. The comparison of urinary concentrations of biomarkers between studies requires the adjustment of results based on a reference CR and/or SG value, although studies have suggested that age, sex, muscle mass, and time of the day can exert non-negligible influences on CR excretion, while SG appears to be less affected. The objective of this study was to propose reference values for urinary CR and SG based on the results of samples sent for analysis by occupational health practitioners to the laboratory of the Occupational Health and Safety Research Institute of Québec (IRSST). We analyzed a database containing 20,395 urinary sample results collected between 1985 and 2010. Linear mixed-effects models with worker as a random effect were used to estimate the influence of sex and collection period on urinary CR and SG. Median CR concentrations were 25-30% higher in men (1.6 g/L or 14.4 mmol/L) than in women (1.2 g/L or 10.2 mmol/L). Four percent of the samples for men and 12% for women were below the acceptable threshold for CR (4.4 mmol/L). For SG, 5% of samples for men and 12% for women were below the threshold of 1.010. The difference in SG levels between sexes was lower than for CR, with a median of 1.024 for men compared to 1.020 for women. Our results suggest that the normalization of reference values based on a standard CR value of 1 g/L as proposed by the ACGIH is a conservative approach. According to the literature, CR excretion is more influenced by physiological parameters than SG. We therefore suggest that correction based on SG should be favored in future studies involving the proposal of reference values for the biological monitoring of occupational exposures.