Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1991 Jan;90:239–246. doi: 10.1289/ehp.90-1519476

Validation of biological markers for quantitative risk assessment.

P Schulte 1, L F Mazzuckelli 1
PMCID: PMC1519476  PMID: 2050067

Abstract

The evaluation of biological markers is recognized as necessary to the future of toxicology, epidemiology, and quantitative risk assessment. For biological markers to become widely accepted, their validity must be ascertained. This paper explores the range of considerations that compose the concept of validity as it applies to the evaluation of biological markers. Three broad categories of validity (measurement, internal study, and external) are discussed in the context of evaluating data for use in quantitative risk assessment. Particular attention is given to the importance of measurement validity in the consideration of whether to use biological markers in epidemiologic studies. The concepts developed in this presentation are applied to examples derived from the occupational environment. In the first example, measurement of bromine release as a marker of ethylene dibromide toxicity is shown to be of limited use in constructing an accurate quantitative assessment of the risk of developing cancer as a result of long-term, low-level exposure. This example is compared to data obtained from studies of ethylene oxide, in which hemoglobin alkylation is shown to be a valid marker of both exposure and effect.

Full text

PDF
239

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alavanja M., Aron J., Brown C., Chandler J. Cancer risk-assessment models: anticipated contributions from biochemical epidemiology. J Natl Cancer Inst. 1987 Apr;78(4):633–643. [PubMed] [Google Scholar]
  2. Brown S. L. Differential susceptibility: implications for epidemiology, risk assessment, and public policy. Basic Life Sci. 1988;43:255–269. doi: 10.1007/978-1-4684-5460-4_24. [DOI] [PubMed] [Google Scholar]
  3. Brugnone F., Perbellini L., Faccini G. B., Pasini F., Bartolucci G. B., DeRosa E. Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood. Int Arch Occup Environ Health. 1986;58(2):105–112. doi: 10.1007/BF00380761. [DOI] [PubMed] [Google Scholar]
  4. CRONBACH L. J., MEEHL P. E. Construct validity in psychological tests. Psychol Bull. 1955 Jul;52(4):281–302. doi: 10.1037/h0040957. [DOI] [PubMed] [Google Scholar]
  5. Calleman C. J., Ehrenberg L., Jansson B., Osterman-Golkar S., Segerbäck D., Svensson K., Wachtmeister C. A. Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupationally exposed to ethylene oxide. J Environ Pathol Toxicol. 1978 Nov-Dec;2(2):427–442. [PubMed] [Google Scholar]
  6. Farmer P. B., Neumann H. G., Henschler D. Estimation of exposure of man to substances reacting covalently with macromolecules. Arch Toxicol. 1987 Jun;60(4):251–260. doi: 10.1007/BF01234663. [DOI] [PubMed] [Google Scholar]
  7. Griffith J., Duncan R. C., Hulka B. S. Biochemical and biological markers: implications for epidemiologic studies. Arch Environ Health. 1989 Nov-Dec;44(6):375–381. doi: 10.1080/00039896.1989.9935910. [DOI] [PubMed] [Google Scholar]
  8. Hemstreet G. P., Schulte P. A., Ringen K., Stringer W., Altekruse E. B. DNA hyperploidy as a marker for biological response to bladder carcinogen exposure. Int J Cancer. 1988 Dec 15;42(6):817–820. doi: 10.1002/ijc.2910420602. [DOI] [PubMed] [Google Scholar]
  9. Hulka B. S., Wilcosky T. Biological markers in epidemiologic research. Arch Environ Health. 1988 Mar-Apr;43(2):83–89. doi: 10.1080/00039896.1988.9935831. [DOI] [PubMed] [Google Scholar]
  10. Inskeep P. B., Koga N., Cmarik J. L., Guengerich F. P. Covalent binding of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct, S-[2-(N7-guanyl)ethyl]glutathione. Cancer Res. 1986 Jun;46(6):2839–2844. [PubMed] [Google Scholar]
  11. Louis T. A. General methods for analysing repeated measures. Stat Med. 1988 Jan-Feb;7(1-2):29–45. doi: 10.1002/sim.4780070108. [DOI] [PubMed] [Google Scholar]
  12. Osterman-Golkar S., Bergmark E. Occupational exposure to ethylene oxide. Relation between in vivo dose and exposure dose. Scand J Work Environ Health. 1988 Dec;14(6):372–377. doi: 10.5271/sjweh.1906. [DOI] [PubMed] [Google Scholar]
  13. Osterman-Golkar S., Farmer P. B., Segerbäck D., Bailey E., Calleman C. J., Svensson K., Ehrenberg L. Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin. Teratog Carcinog Mutagen. 1983;3(5):395–405. doi: 10.1002/1520-6866(1990)3:5<395::aid-tcm1770030502>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  14. Perera F. P. The significance of DNA and protein adducts in human biomonitoring studies. Mutat Res. 1988 May-Aug;205(1-4):255–269. doi: 10.1016/0165-1218(88)90021-3. [DOI] [PubMed] [Google Scholar]
  15. Rosner B., Muñoz A., Tager I., Speizer F., Weiss S. The use of an autoregressive model for the analysis of longitudinal data in epidemiologic studies. Stat Med. 1985 Oct-Dec;4(4):457–467. doi: 10.1002/sim.4780040407. [DOI] [PubMed] [Google Scholar]
  16. Schulte P. A. A conceptual framework for the validation and use of biologic markers. Environ Res. 1989 Apr;48(2):129–144. doi: 10.1016/s0013-9351(89)80029-5. [DOI] [PubMed] [Google Scholar]
  17. Schulte P. A. Methodologic issues in the use of biologic markers in epidemiologic research. Am J Epidemiol. 1987 Dec;126(6):1006–1016. doi: 10.1093/oxfordjournals.aje.a114740. [DOI] [PubMed] [Google Scholar]
  18. Slaga T. J. Interspecies comparisons of tissue DNA damage, repair, fixation, and replication. Environ Health Perspect. 1988 Apr;77:73–82. doi: 10.1289/ehp.887773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yager J. W., Benz R. D. Sister chromatid exchanges induced in rabbit lymphocytes by ethylene oxide after inhalation exposure. Environ Mutagen. 1982;4(2):121–134. doi: 10.1002/em.2860040204. [DOI] [PubMed] [Google Scholar]
  20. de Serres F. J. Banbury Center DNA Adducts Workshop. Workshop on DNA Adducts, Banbury Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY (U.S.A.), Sept. 30-Oct. 2, 1986. Mutat Res. 1988 Feb;203(1):55–68. doi: 10.1016/0165-1161(88)90008-8. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES