Table 3.
Details of calculated toxicity risk parameters for compound P-902 and control drug topotecan.
| Properties | P-902 | Topotecan | |
|---|---|---|---|
| Maximum recommended therapeutic dose, administered orally | Below 3.16 mg/kg/day | Above 3.16 mg/kg/day | |
| Estrogen receptor (rats) | Non-toxic | Toxic | |
| Quantitative measure of estrogen receptor toxicity in rats | Non-toxic | 4.3531 | |
| Androgen receptor toxicity | Toxic | Toxic | |
| Quantitative measure of androgen receptor toxicity in rats | 0.037 | 0.0599 | |
| Allergenic skin sensitization (mice) | No sensitization | No sensitization | |
| Allergenic respiratory sensitization in rat | No sensitization | No sensitization | |
| Fathead minnow lethal toxicity after 96 hours of exposure | 0.31 mg/L | 1.5 mg/L | |
| Daphnia magna (water flea) lethal toxicity after 48 hours of exposure | 0.893 mg/L | 0.549 mg/L | |
| Bio concentration factor | 3.781 | 4.688 | |
| Biodegradation | No | No | |
| Likelihood of the hERG potassium channel inhibition in human | No (95%) | No | |
| Affinity towards hERG K+ channel and potential for cardiac toxicity | 5.060 mol/L | 5.24 mol/L | |
| LD50 for lethal rat acute toxicity | 204.531 mg/kg | 782.92 mg/kg | |
| Tumorogenic dose, rat | 84.385 mg/kg/day | 9.94 mg/kg/day | |
| Tumorogenic dose, mice | 381.422 mg/kg/day | 74.25 mg/kg/day | |
| Triggering the mutagenic chromosomal aberrations | Non-toxic | Toxic | |
| Hepatotoxicity | levels of Alkaline Phosphatase enzyme | Elevated | Elevated |
| levels of GGT enzyme | Normal | Normal | |
| levels of LDH enzyme | Elevated | Normal | |
| levels of SGOT enzyme | Normal | Elevated | |
| levels of SGPT enzyme | Normal | Normal | |
| Causing phospholipidosis | Non-toxic | Non-toxic | |
| Reproductive/developmental toxicity | Non-toxic | Non-toxic | |
| Mutagenicity (pure compound) | TA97 and/or TA1537 strains of S. typhimurium | Negative | Positive |
| TA98 strain of S. typhimurium | Negative | Negative | |
| TA100 strain of S. typhimurium | Negative | Negative | |
| S. typhimurium and/or WP2 uvrA strain of E. coli | Negative | Positive | |
| TA1535 strain of S. typhimurium | Negative | Negative | |
| Mutagenicity (microsomal rat liver metabolites) | TA97 and/or TA1537 strains of S. typhimurium | Negative | Positive |
| TA98 strain of S. typhimurium | Negative | Negative | |
| TA100 strain of S. typhimurium | Negative | Negative | |
| TA102 strain of S. typhimurium | Negative | Negative | |
| TA1535 strain of S. typhimurium | Negative | Negative | |
Abbreviations: LD50, lethal dose 50%; hERG, human Ether-a-go-go-Related Gene; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamate-pyruvate transaminase; GGT, gamma-glutamyl transpeptidase; LDH, lactate dehydrogenase.