PMID: 6540742Aug 1, 1984Paper

A method for determining the maximum tolerated dose for acute in vivo cytogenetic studies

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
E D Thompson, D P Gibson

Abstract

A method for establishing a maximum tolerated dose for use in in vivo cytogenetic studies is proposed. Probit analyses were performed on acute (ip and po) LD50 studies for triethylenemelamine, chlorambucil, methyl methanesulphonate, glycidol, phenol, Triton X-15, and dimethylsulphoxide. The concentrations corresponding to the calculated LD30, LD10 and LD1 values were given both ip and po to groups of female and male rats. Half of the animals in each group were killed about 20 hr after treatment for bone marrow cytogenetic analyses, and body weights were recorded for 10 days for the other half. The following conclusions were drawn: (1) LD50 values and consequently the maximum tolerated dose (MTD) values differ for males and females; (2) the mitotic index is not a reliable indicator of toxicity; (3) the LD1 value approximates the MTD for these compounds; (4) this value and hence the MTD is not a fixed percentage of the LD50 value; (5) body-weight changes appear to be an accurate parameter for determining whether or not an animal received an MTD level.

References

Jun 1, 1972·Toxicology and Applied Pharmacology
Jun 1, 1981·Food and Cosmetics Toxicology·E D Thompson, R A Hiles

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Citations

Jan 1, 1988·Mutation Research·M D Shelby
Jun 1, 1992·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K L McCarthyR Valencia
Feb 1, 1995·Journal of Toxicology and Environmental Health·A A NomeirM Chadwick
Jan 1, 1994·Environmental and Molecular Mutagenesis·S H RobisonA L Kraus
Jan 1, 1991·Environmental and Molecular Mutagenesis·E D ThompsonD B Cody
Sep 23, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Hiroshi HamamotoKazuhisa Sekimizu
Jan 1, 1986·Environmental Mutagenesis·E D Thompson
Jan 1, 1995·Environmental and Molecular Mutagenesis·G Krishna, J C Theiss
Jan 1, 1993·Environmental and Molecular Mutagenesis·M D ShelbyR R Tice
Jan 1, 1985·Environmental Mutagenesis·J A Skare, K R Schrotel

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