Creatinine adjustment of biological monitoring results.

BACKGROUND: Biological monitoring (BM) aids exposure assessment but where this is based on incomplete collections of single urine voiding measurement of creatinine is often used to adjust analyte concentrations for the effects of fluid balance. AIMS: To provide reference data on creatinine concentrations in urine samples from a population of UK workers. METHODS: Urine samples sent to the Health and Safety Laboratory were analysed for creatinine by an automated kinetic Jaffe technique using alkaline picric acid and the results stored in a database. Statistical analysis of the data used linear mixed effects models on the natural log-transformed data. RESULTS: Between 1996 and 2007, the laboratory analysed 49 506 urine samples from 20 433 UK adult workers. In the 42 817 samples where gender was known, 93% were from men and 7% were from women. The overall mean and median creatinine concentrations were both 12 mmol/l corresponding to 1.36 g/l. The mean (13 mmol/l) and median (12 mmol/l) creatinine concentrations for men were higher than those (9 and 10 mmol/l, respectively) for women. CONCLUSIONS: Gender differences in creatinine concentrations and the range of 0.3-3.0 g/l (2.653 and 26.53 mmol/l) traditionally used for confirming acceptability of urine samples mean that 2.5% of samples from male and 9% from female workers were flagged as 'low creatinine' and required a repeat sample. In addition, care should be taken interpreting any apparent gender differences in BM results to ensure that they are due to exposure and not an artefact of creatinine adjustment.

Evaluation and further development of EASE model 2.0.

EASE (Estimation and Assessment of Substance Exposure) is a general model that may be used to predict workplace exposure to a wide range of substances hazardous to health. First developed in the early 1990s, it is now in its second Windows version. This paper provides a critical assessment of the utility and performance of the EASE model, and on the basis of this review, recommendations for the structure of a revised model are outlined. Twenty-seven stakeholders were interviewed about their previous use of EASE, perceived advantages and limitations of the model and suggestions for improvement. A subset of stakeholders was contacted on a second occasion to determine their views on the preferred outputs for an ideal exposure assessment model. Overall, stakeholders felt that the model should be updated to provide more accurate and precise exposure assessments. However, users also expressed the view that the simplicity and usability of the software model should not be compromised. Six studies investigating the validity of the inhalation exposure assessment section of EASE were identified. These showed that the model generally either predicted close to the measured exposures or overestimated exposure; though performance was highly variable. Two studies investigated the validity of the dermal exposure assessment and found that EASE produced considerable overestimates of actual dermal exposure (the amount of a substance that actually lands on the skin). A conceptual model of exposure was developed to investigate whether the structure of the EASE model is appropriate. Although EASE has a number of characteristics that describe exposure, it is a greatly simplified model and does not include all the important exposure determinants. More importantly, EASE can produce estimates of exposure that are ambiguous or incomplete. Our conceptual model may provide a rational basis for developing an improved version of EASE but further consultation is needed to decide the purpose and intended use of any successor to EASE.

A Dirichlet Tessellation-based sampling scheme for measuring whole-body exposure.

Dermal sampling can be conducted using small pads or patches attached to various areas of the skin or clothing, or by using a whole-body coverall. Both techniques are recognized standardized methods for collecting chemicals. Patch sampling is simple to perform and inexpensive to analyse compared with an entire overall, but may require some user intervention. Extrapolation from a small sampled area to the total body area can lead to inaccurate estimates of total body exposure because of a lack of uniformity of deposition. Whole-body overall analysis eliminates the problems associated with using patches and gives a more accurate estimate of total body exposure. Therefore, if it were possible to measure the whole-body overall accurately and quickly, we would have a better assessment of dermal exposure. In this study we develop a working protocol using a standardized approach, to measure the contamination over an entire overall. The protocol takes into account size differences and establishes a reproducible pattern of sampling in order to map the distribution of contamination over each overall. The working protocol has been applied to 10 overalls collected from companies using copper-based biocides. A portable X-ray fluorescence spectrometer (PXRF) was used to measure the copper in the biocide. The exposure estimate from the PXRF results uses an averaging scheme based on the Dirichlet tessellation of the sampling locations. This allows unbiased estimates to be obtained from a complex sampling scheme that allocates more measurements to areas of high exposure. The Dirichlet tessellation method has been compared to the patch sampling method and the conventional total digestion of the entire overall method. Using the whole-suit digestion method as the benchmark, exposures ranged from 92.0 to 5848.5 mg. Mean absolute percentage errors (from the benchmark acid digestion of the whole suit) varied from approximately 20% for the Dirichlet-based PXRF method to 60% for the patch methods. The patch methods underestimated the true dermal exposure (-28 to -82% for acid digestion of the patches). Analysis of this data indicates that the Dirichlet PXRF method gives a more accurate estimate of whole-body contamination than the patch method. Furthermore, the 104 measurements give a much greater spatial resolution to the exposure data than analysis of the whole overall or patches by inductively coupled plasma-atomic emission mass spectrometry (ICP-AES). This detailed knowledge of the pattern of deposition on the body is of potential importance in chemical risk assessments.