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Budtz-Jorgensen, Esben

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Budtz-Jorgensen

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Esben

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Budtz-Jorgensen, Esben

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2002 - 20042

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Author's Publications: search.filters.isAuthorOfPublication.781b5b31-a6d2-4a06-8efb-a59b53207d56

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    Effects of Exposure Imprecision on Estimation of the Benchmark Dose
    (Wiley-Blackwell, 2004) Budtz-Jorgensen, Esben; Keiding, Niels; Grandjean, Philippe
    In regression analysis failure to adjust for imprecision in the exposure variable is likely to lead to underestimation of the exposure effect. However, the consequences of exposure error for determination of safe doses of toxic substances have so far not received much attention. The benchmark approach is one of the most widely used methods for development of exposure limits. An important advantage of this approach is that it can be applied to observational data. However, in this type of data, exposure markers are seldom measured without error. It is shown that, if the exposure error is ignored, then the benchmark approach produces results that are biased toward higher and less protective levels. It is therefore important to take exposure measurement error into account when calculating benchmark doses. Methods that allow this adjustment are described and illustrated in data from an epidemiological study on the health effects of prenatal mercury exposure.
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    Benchmark Dose Calculations for Methylmercury-Associated Delays on Evoked Potential Latencies in Two Cohorts of Children
    (Wiley-Blackwell, 2002) Murata, Katsuyuki; Budtz-Jorgensen, Esben; Grandjean, Philippe
    Delays in evoked potential latencies were observed at increased exposures to methylmercury from seafood in two cohorts of children. Because this outcome parameter appeared to be virtually independent of confounders, including cultural differences, a joint analysis of benchmark doses was carried out. Comparable cohort members included 382 Faroese and 113 Madeiran children without middle ear infection or neurological disease at age seven years. Maternal hair-mercury concentrations at parturition in the Faroese cohort ranged from 0.6 to 39.1 μg/g (geometric average, 4.49 μg/g). In Madeira, mothers who had not changed their diet since pregnancy had current hair-mercury concentrations ranging from 1.1 to 54.4 μg/g (geometric average 10.14 μg/g). The mercury-associated delay in peak III latencies at two frequencies (20 and 40 Hz) showed similar regression equations in the two groups of children, and benchmark dose calculations were therefore carried out for the two groups separately and jointly. For a doubling of a 5% prevalence of abnormal results of the peak III latencies at 40 Hz in a linear dose-response model, the benchmark dose for the maternal hair-mercury concentration was 8.79 μg/g for the Faroese children; 8.04 μg/g for the Madeiran children; and 9.46 μg/g for both groups. Results were similar for the 20 Hz condition. Benchmark dose results were substantially lower using a logarithmic or square root curve function, although the difference in fit between the curves was far from statistically significant. The benchmark results using evoked potential latencies are in close agreement with results based on neuropsychological test performance.