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Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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28. Lead as a Paradigm for the Study of Neurodevelopmental Toxicology
Pages 297-302

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From page 297...
... MARKERS OF EXPOSURE TO LEAD There have been many improvements in the biologic markers of exposure to lead. The following discussion includes the relatively imprecise use of surrogate markers and the more precise physiologic assessments.
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From page 298...
... Tooth Lead Bone biopsy is an impractical measure, but lead in dentin of deciduous teeth is a good marker for integrated exposure over time (Altshuller et al., 1962; Needleman et al., 1972, 1974; Steenhout and Pourtois, 1981~. This tissue is correlated with blood lead content obtained 3 years before shedding.
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From page 299...
... The thresholds are based on a consensus of investigators doing research on responses to lead exposure. 1.0~ O , W\<~ / \ Ao Bo O CO Aloo Bloo ClooDo LEAD DOSE Dtoo FIGURE 281 Distribution of frequencies of four putative responses to internal lead dose.
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From page 300...
... LL LL a an z z ~as agreed / l~uPOn be 100% NEURODEVELOPMENTAL TOXICOLOGY Unsafe as agreed / upon by 100'/ ~ ' ~ 1 1 l 1 Lead dose resulting in earliest detectable etfec t METHODOLOGIC CONSIDERATIONS IN THE ESTABLISHMENT AND EVALUATION OF MARKERS OF DEVELOPMENT Differentiating Markers of Exposure and Effect At first glance, the difference between markers of exposure and markers of effect seems self-evident. However, the concentration of an internal dose of a toxicant, which seems clearly a marker of exposure, involves the organism's inherent responsiveness to the stimulus (i.e., external dose of the agent)
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From page 301...
... . 10 10 15 40 50 60 35 10 Moderate Moderate Moderate Low High Low Low Low IQ deflate increased 15 Low Attention deflate appear 10 Low Speech and language deficits appear 35 Low Other effects 1,25-vitamin D hydroxylase activity altered Na-K ATP-ase activity altered 12 20 High Low Threshold blood lead concentration for indicating that an effect has occurred.
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From page 302...
... It is a function of three variables: the number of subjects studied, the effect size under scrutiny, and the significance criterion selected by the examiner. Many studies that have argued for a lack of causal effect have done so on the basis of sample sizes with less than a 50% chance of finding an effect at a statistical significance of 0.05.
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Key Terms

  • blood lead
  • lead dose
  • lead exposure
  • erythrocyte protoporphyrin
  • tissue concentrations

  • activity altered
  • deciduous teeth
  • internal doses
  • free erythrocyte
  • internal lead

  • neurodevelopmental toxicology
  • exposure variable
  • lead concentration
  • lead content
  • moderate moderate

  • threshold blood
  • chelatable lead
  • heme production
  • causal hypotheses
  • surrogate markers

  • recent exposure
  • accepting spurious
  • toxicant dose
  • protoporphyrin lead
  • biologic covariates

  • differentiating markers
  • lead bone
  • tracks lead
  • increased dentin
  • lead doses


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