Prenatal-Toxic Risk Estimation Based on Dose-Response Relationships and Molecular Dosimetry

  • Thomas Platzek
  • Gerd Bochert
  • Reinhard Meister
  • Diether Neubert

Abstract

The final purpose of toxicological risk assessment is to determine a human exposure level with acceptable risk to the population. For the great majority of toxic effects the most frequently used approach is the NOAEL risk factor approach: 1. A dose is experimentally determined which induces “no effect” (“no-observed-adverse-effect-level”, NOAEL); 2. From this NOAEL a “safe dose” is assessed by division with an arbitrary factor.

Keywords

Toxicity HPLC Phenol Adduct Purine 

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References

  1. Biddle FG (1978) Use of dose-response relationships to discriminate between the mechanisms of cleft-palate induction by different teratogens: An argument for discussion. Teratology 18: 247–252.PubMedCrossRefGoogle Scholar
  2. Bochert G, Rahm U, Schnieders B (1978) Pharmacokinetics of embryotoxic direct-acting alkylating agents: Comparison of DNA alkylation of various maternal tissues and the embryo during organogenesis. In: Neubert D, Merker H-J, Nau H, Langman J (eds) Role of pharmacokinetics in prenatal and perinatal toxicology, G Thieme Publ Stuttgart, pp 235–251.Google Scholar
  3. Bochert G, Platzek T, Neubert D (1987) DNA modification in murine embryos: a primary cause of embryotoxic effects. In: Nau H, Scott WJ (eds) Pharmacokinetics in teratogenesis, Vol II Experimental aspects in vivo and in vitro, CRC Press, Boca Raton, Florida, pp 73–82.Google Scholar
  4. Bochert G, Platzek T, Rahm U, Neubert D (1991) Embryotoxicity induced by alkylating agents: 6. DNA adduct formation induced by methylnitrosourea in mouse embryos. Arch Toxicol, accepted for publication.Google Scholar
  5. Chahoud I, Kwasigroch TE (1977) Controlled breeding of laboratory animals. In: Neubert D, Merker H-J, Kwasigroch TE (eds) Methods in prenatal toxicology, G Thieme Publ, Stuttgart, pp 78–91.Google Scholar
  6. Dawson AA (1926) A note on the staining of the skeleton of cleared specimen with alizarin red S. Stain Technoll: 123-124.Google Scholar
  7. Finney DJ (1971) Probit analysis. Third edition, Cambridge University Press, London.Google Scholar
  8. Lutz WK (1979) In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis. Mutat Res 65: 289–356.PubMedGoogle Scholar
  9. Lutz WK (1986) Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens. J Cancer Res Clin Oncol 112: 85–91.PubMedCrossRefGoogle Scholar
  10. Lutz WK (1987) Quantitative evaluation of DNA-binding data in vivo for low-dose extrapolation. Arch Toxicol [Suppl] 11: 66–74.Google Scholar
  11. Neubert D, Zens P, Rothenwallner A, Merker H-J (1973) A survey of the embryotoxic effects of TCDD in mammalian species. Environna Health Perspect 5: 67–79.CrossRefGoogle Scholar
  12. Neubert D, Barrach HJ (1977) Organotropic effects and dose-response relationships in teratology. In: Neubert D, Merker H-J, Kwasigroch TE (eds) Methods in prenatal toxicology, Thieme Stuttgart, pp 405–412.Google Scholar
  13. Neubert D, Chahoud I, Platzek T, Meister R (1987a) Principles and problems in assessing prenatal toxicity. Arch Toxicol 60: 238–245.PubMedCrossRefGoogle Scholar
  14. Neubert D, Bochert G, Platzek T, Chahoud I, Fischer B, Meister R (1987b) Dose-response relationships in prenatal toxicity. Congen Anomal 27: 275–302.CrossRefGoogle Scholar
  15. Platzek T, Bochert G, Schneider W, Neubert D (1982) Embryotoxicity induced by alkylating agents: 1. Ethylmethanesulfonate as a teratogen in mice — a model for dose-response relationships of alkylating agents. Arch Toxicol 51: 1–25.CrossRefGoogle Scholar
  16. Platzek T, Bochert G, Rahm U (1983) Embryotoxicity induced by alkylating agents: Teratogenicity of acetoxymethyl-methylnitrosamine — dose-response relationship, application route dependency and phase specificity. Arch Toxicol 52: 45–69.PubMedCrossRefGoogle Scholar
  17. Platzek T, Bochert G, Rahm U (1987a) Embryotoxicity induced by alkylating agents: Some methodological aspects of DNA alkylation studies in murine embryos using ethylmethanesulfonate. Z Naturforsch 42c: 613–626.Google Scholar
  18. Platzek T, Meister R, Chahoud I, Bochert G, Krowke R, Neubert D (1987b) Studies on mechanisms and dose-response relationships of prenatal toxicity. In: F. Welsch (ed) Approaches to elucidate mechanisms in teratogenesis, Hemisphere Publ Corp, Washington, New York, pp 59–81.Google Scholar
  19. Platzek T, Bochert G, Pauli B, Meister R, Neubert D (1988) Embryotoxicity induced by alkylating agents: 5. Dose-response relationships of teratogenic effects of methylnitrosourea in mice. Arch Toxicol 62: 411–423.PubMedCrossRefGoogle Scholar
  20. Platzek T, Bochert G, Fischer B, Meister R (1989) Low dose prenatal-toxic risk estimation based on dose-response relationships and DNA adducts using MNU as model compound. Naunyn-Schmiedeberg Arch Pharmacol 339 (Suppl): R23.Google Scholar
  21. Platzek T, Bochert G (1990) DNA adduct formation induced by ethylmethanesulfonate in mouse embryos. Naunyn-Schmied Arch Pharmacol 341 (Suppl.): R26.Google Scholar
  22. Platzek T, Rahm U, Bochert G (1991) Comparative approaches for low dose prenatal toxic risk estimation of the alkylating model compound EMS in mice. Naunyn-Schmiedeberg Arch Pharmacol 343 (Suppl.): R31.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • Thomas Platzek
  • Gerd Bochert
  • Reinhard Meister
  • Diether Neubert

There are no affiliations available

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