Benchmark dose calculation from epidemiological data.
A threshold for dose-dependent toxicity is crucial for standards setting but may not be possible to specify from empirical studies. Crump (1984) instead proposed calculating the lower statistical confidence bound of the benchmark dose, which he defined as the dose that causes a small excess risk. This concept has several advantages and has been adopted by regulatory agencies for establishing safe exposure limits for toxic substances such as mercury. We have examined the validity of this method as applied to an epidemiological study of continuous response data associated with mercury exposure. For models that are linear in the parameters, we derived an approximative expression for the lower confidence bound of the benchmark dose. We find that the benchmark calculations are highly dependent on the choice of the dose-effect function and the definition of the benchmark dose. We therefore recommend that several sets of biologically relevant default settings be used to illustrate the effect on the benchmark results and to stimulate research that will guide an a priori choice of proper default settings.
Budtz-Jørgensen
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Department of Biostatistics, University of Copenhagen, Denmark. ebj@biostat.ku.dk
Keiding
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Grandjean
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D000818:Animals; D001699:Biometry; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004812:Epidemiologic Methods; D005312:Fetal Blood / Q000737:chemistry; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008452:Maximum Allowable Concentration; D008628:Mercury / Q000097:blood; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity; D019055:No-Observed-Adverse-Effect Level
D008767:Methylmercury Compounds; D008628:Mercury