This paper demonstrates how toxicokinetic studies can contribute to the interpretation of toxicology studies by helping the toxicologist distinguish between the pharmacokinetic and pharmacodynamic factors in dose-response toxicity. It also shows the limitations of plasma concentration data.
MonroAM. Interspecies comparisons in toxicology: The utility and futility of plasma concentrations of the test substance. Reg Toxicol Pharmacol. 1990;12: 137–160.
2.
MukherjeeAHaghaniZBradyJBushLMcBrideWBujaLMWillersonJT. Differences in myocardial a- and b-adrenergic receptor numbers in different species. Am J Physiol. 1983;245:H957–H961.
3.
PalciosJMHoyerDCortésR. α1-Adrenoreceptors in the mammalian brain: Similar pharmacology but different distribution in rodents and primates. Brain Research. 1987;419: 65–75.
4.
LanginDPortilloMPSaulnier-BlacheJ-SLafontanM. Co-existence of three β-adrenoreceptor subtypes in white fat cells of various mammalian species. Eur J Pharmacol. 1991;199: 291–301.
5.
HoyerDPazosAProbstAPalaciosJM. Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Research. 1986;376: 85–96.
6.
KaoH-TAdhamNOlsenMAWeinshankRLBranchekTAHartigPR. Site-directed mutagenesis of a single residue changes the binding properties of the serotonin 5-HT2 receptor from a human to a rat pharmacology. Fed Eur Biochem Soc. 1992;307: 324–328.
7.
KilpatrickGJTyersMB. Inter-species variants of the 5-HT3 receptor. Biochem Soc Trans. 1992;20: 118–121.
8.
GoodmanGWilsonR. Quantitative prediction of human cancer risk from rodent carcinogenic potencies: A close look at the epidemiological evidence for some chemicals not definitively carcinogenic in humans. Reg Toxicol Pharmacol. 1991;14: 118–146.
9.
WaldNJDollR, eds. Interpretation of negative epidemiological evidence for carcinogenicity. Lyon, France: International Agency for Research on Cancer; 1985, Sci Publ No 65.
10.
ButterworthBE. Non-genotoxic carcinogens in the regulatory environment. Reg Toxicol Pharmacol. 1989;8: 244–256.
11.
GrassoPSharratMCohenAJ. Role of persistent, non-genotoxic tissue damage in rodent cancer and relevance to humans. Ann Rev Pharmacol Toxicol. 1991;31: 253–287.
12.
RoeFJC. Non-genotoxic carcinogenesis: Implications for testing and extrapolation to man. Mutagenesis. 1989;4: 407–411.
13.
MonroAM. What is an appropriate measure of exposure when testing drugs for carcinogenicity in rodents?Toxicol Appl Pharmacol. 1992;12:171–181.
14.
MoolgavkarSHKnudsonAG. Mutation and cancer: A model for human carcinogenesis. J Natl Cancer Inst. 1981;66: 1037–1052.
15.
ConnollyRBReitzRHClewellHJAndersenME. Pharmacokinetics, biochemical mechanism, and mutation accumulation: A comprehensive model of chemical carcinogenesis. Toxicol Lett. 1988;43: 189–200.
16.
CohenSMEllweinLB. Genetic errors, cell proliferation, and carcinogenesis. Cancer Res. 1991;51: 6493–6505.
17.
DruckreyHKüpfmüllerK. Quantitative Analyse der Krebsentstehung. Z Naturforsch. 1948;96: 254–266.
18.
PetoRRoeFJCLeePNLevyLClarkJ. Cancer and aging in mice and men. Br J Cancer. 1975;32: 411–426.