Association between mercury concentrations in blood and hair in methylmercury-exposed subjects at different ages☆
Introduction
The two biomarkers most frequently used to determine individual exposures to methylmercury are the mercury concentrations in scalp hair and in whole blood (Grandjean et al., 1994). The convenience of sampling and storage has made the former parameter advantageous for monitoring and field studies, and the total mercury concentration in hair is thought to reflect the average methylmercury concentrations circulating in the blood (IPCS, 1990; Cernichiari et al., 1995b). Yet environmental mercury vapor may bind to the hair (Yamaguchi et al., 1975), while hair permanent treatments may remove endogenous mercury from the hair (Yamamoto and Suzuki, 1978; Yasutake et al., 2003). Also, hair color may affect the mercury concentration (Grandjean et al., 2002).
From a toxicological viewpoint, the blood concentration is the appropriate indicator of the absorbed dose and the amount systemically available. Methylmercury binds to hemoglobin, and its high affinity to fetal hemoglobin results in a higher mercury concentration in cord blood than in maternal blood (Tsuchiya et al., 1984; Stern and Smith, 2003). While routine analyses of total mercury concentrations will include inorganic mercury, cord blood mercury is almost entirely in the methylated form, which passes easily through the placenta (Kelman et al., 1982; Tsuchiya et al., 1984; IPCS, 1990).
In comparing results of these two biomarkers, temporal factors must also be considered. Methylmercury is incorporated into the hair during its formation in the hair follicle, but it will take at least a month for the metal content to become detectable in a hair sample cut with scissors close to the scalp (Grandjean, 1984; Suzuki, 1988). Depending on the length of the hair sample, the mercury concentration may reflect exposures that extend far into the past. Still, because the half-life of methylmercury in the body is about 1.5–2 months (Smith and Farris, 1996; Swartout and Rice, 2000), the hair closest to the scalp reflects recent exposures that also contribute to the current blood concentration (Grandjean et al., 2003).
The association between the two exposure biomarkers will depend on the circumstances of individual studies, and, as a result, some prospective cohort studies on developmental methylmercury toxicity have used both biomarkers (Grandjean et al., 1992; Steuerwald et al., 2000). Factor analysis has been used to determine the total imprecision, i.e., laboratory imprecision and all preanalytical variation, of these two biomarkers (Budtz-Jørgensen et al., 2003). The total imprecision of the hair-mercury concentration was found to be almost twice that of the blood determination. This finding is in accordance with the toxicological prediction and empirical observation that the cord-blood mercury concentration is a better predictor of mercury-associated neurobehavioral deficits (Grandjean et al., 1999). However, even the cord-blood parameter had a surprising imprecision (expressed by the coefficient of variation, CV) of about 30%. A nondifferential error in the biomarker is likely to cause underestimation of the true association with the outcome variables (Carroll, 1998). Adjustment can be made only if the extent of the total imprecision is known.
Translation between studies that have applied different biomarkers requires information about conversion factors. Under reasonably constant conditions of exposure, the human hair-mercury concentrations (in μg/g) are thought to average about 250× the whole-blood mercury concentrations (in μg/mL) (US EPA, 2001). However, concentration ratios expressed as regression coefficients appear to vary somewhat in European and American population groups (Haxton et al., 1979; Phelps et al., 1980; Turner et al., 1980; Sherlock et al., 1982; Akagi, 1998). A limitation of regression analyses is that they do not take into account that both biomarkers are affected by imprecision, and the concentration ratio will therefore depend on the choice of the dependent variable.
We have conducted a prospective study of a Faroese birth cohort, where mercury concentrations were assessed in cord blood and maternal hair at parturition, and in the child's hair and blood at the ages of 7 and 14 years. We have now performed advanced statistical analyses to ascertain the total imprecision of these two biomarkers, the average ratio between them, and the possible concentration dependence of this ratio.
Section snippets
Subjects and biomarker assessment
A cohort of 1022 singleton births was assembled in the Faroe Islands during a 21-month period of 1986–1987 (Grandjean et al., 1992). This North Atlantic population is of Scandinavian origin, is relatively uniform, and is covered by a modern health care service. The Faroese are of particular interest in environmental epidemiology, because pilot whale is included as a traditional food item in the marine diet. Pods of this small whale species are occasionally caught and the meat and blubber are
Results
The overall results of the mercury analyses are shown in Table 1. The subjects covered a considerable exposure interval, as is also apparent from Fig. 1, Fig. 2. The children's postnatal exposure levels were substantially lower than the prenatal levels, and a significant increase occurred between the two most recent examinations (P<0.001) (Table 1). The median ratio between mercury in hair and cord blood was 190–200 for the two sets of maternal hair data, but postnatal ratios were clearly
Discussion
The present study provides new data on the reliability of exposure biomarkers routinely applied to assess environmental exposures to methylmercury. The findings suggest that the hair-mercury concentration is less precise than previously thought, that the hair-to-blood ratio is concentration-dependent, and that conversion factors obtained by routine regression analysis may yield misleading results.
Conversions between hair and blood mercury concentrations are frequently applied in regard to
Acknowledgements
We are grateful to Brita Andersen for conducting mercury analyses and to the children and their mothers for participating in this prospective study.
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This study was supported by the US National Institute of Environmental Health Sciences (ES09797) and the Danish Medical Research Council. The study was carried out in accordance with the Helsinki convention and with the approval of the ethical review committee for the Faroe Islands and the institutional review board in the US.