Challenges in Interpreting Biomonitoring Data: Special Considerations in Childhood and Pregnant Women

摘要

Pharmacokinetics encompasses the absorption, distribution, metabolism, and elimination of a chemical from the body and can be influenced by life stages. Biomonitoring, the measurement of a chemical or metabolite, usually in blood or urine, is a tool to assess human exposure. This presentation will focus on how biomonitoring measurements and their interpretation can be affected by physiologic differences in childhood relative to adulthood and changes that occur during pregnancy. Examples will illustrate the following situations: 1. Children have a smaller muscle mass than adults, so the typical child produces less creatinine than the adult. When used to "adjust" a urinary biomarker measurement, the child's lower urinary creatinine concentration can lead to confusing results, with a considerably higher "adjusted" concentration than the original (volumetric) measurement. Numerous other factors including time of day, age, sex, race/ethnicity, and certain disease states also affect urine creatinine, limiting its value as a urinary dilution adjustor. Alternatives to creatinine adjustment have been proposed, including use of urine creatinine as a covariate in regression models and calculation of the biomarker excretion rate. Compared to adults, children may demonstrate behaviors (e.g., mouthing), dietary (e.g., reliance on dairy and less dietary variety) and other differences (e.g., higher respiratory rate, greater ventilation ratio relative to adults) that influence exposure likelihood to ingest or inhale chemicals. The child's resulting exposure may be greater than the adult, on a bodyweight basis. 1. During the first trimester of pregnancy, renal clearance and total body water increase dramatically. Non-persistent chemicals that are primarily eliminated in urine may have a shortened elimination time. Depending on collection timing, urine concentrations may be exceptionally high if maximum elimination occurred during the sampling interval, or very low or non-detectable if most of the chemical was eliminated prior to sampling. 2. Placental transfer and breast milk can be significant elimination routes for low molecular weight or lipid soluble chemicals. Particularly for lipid soluble chemicals that are stored in fat, successive pregnancies may reduce serum chemical concentrations, so parity is an important variable to ascertain in studies of women exposed to these chemicals. Epidemiologists should be attentive to physiologic and behavioral differences that may influence sample collection design and the interpretation of biomonitoring measurements.