title: Benchmark dose calculations for methylmercury-associated delays on evoked potential latencies in two cohorts of children.
abstract: 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 microg/g (geometric average, 4.49 microg/g). In Madeira, mothers who had not changed their diet since pregnancy had current hair-mercury concentrations ranging from 1.1 to 54.4 microg/g (geometric average 10.14 microg/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 microg/g for the Faroese children; 8.04 microg/g for the Madeiran children; and 9.46 microg/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.
authors.affiliation: Department of Hygiene, Akita University School of Medicine, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Murata
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Jørgensen
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D006197:Hair / Q000737:chemistry; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D008628:Mercury / Q000032:analysis; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011174:Portugal; D011247:Pregnancy; D018570:Risk Assessment
chemical_list: D008767:Methylmercury Compounds; D008628:Mercury