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Table 3 Quantitative evaluation on interspecies differences using human and animal data

From: Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?

Substances dataset Dose metric Species Results Reference
Poisonous metal compounds Toxic doses Rat 2.5<Toxic doseRat/Toxic doseHuman<152 [31]
    Geometric mean (GM) = 12  
18 chemotherapeutical agents Lethal Dose (LD)10 and Maximum Tolerated Dose (MTD) Mouse, rat, hamster, dog, monkey LD10 (mg/m2)/3 carries 5.9% probability of exceeding MTDHuman [62, 63]
10 pesticides (single dose) and 12 pesticides (repeated doses) Various toxic doses Rat, dog, pig, calf, cow, horse, sheep, steer 1.9<Acute non fatal doseAnimal/Acute non fatal doseHuman<100 [31, 64]
    GM = 11.  
    0.58 <Chronic doseAnimal/Chronic doseHuman<9.4  
    GM = 2.9.  
40 anticancer agents MTD Dogs, monkeys MTD/10 carries a clinical risk human toxicity of 3% (3 out of every 100 drugs) [65]
107 pharmaceuticals (?) Toxicity indices 4 to 6 laboratory animal species Extrapolation of doses (mg/kg) from white rats to man exaggerated tolerable dose 5.5- to 40-fold [66]
25 chemotherapeutic agents LD10 and MTD Mouse, rat, hamster, dog, monkey The predicted MTDHuman is overestimated for 20% of agents using 0.75 power (caloric demand) scaling, less with body surface scaling [52]
26 pharmaceuticals Maximum therapeutic equivalent dose and toxicokinetic parameters Up to 4 laboratory animal species Scaling according to metabolic rate underestimated risk to man in 59% of cases [67]
63 anti-neoplastic drugs LD10, Toxic Dose Low (TDL) and MTD Rat, mouse, hamster, dog, monkey LD10 or TDLMouse/MTDhuman = 8.0 (P95 = 50.9) [68]
    LD10 or TDLHamster/MTDhuman = 7.6 (P95 = 52.1)  
    LD10 or TDLRat/MTDhuman = 2.6 (P95 = 21.7)  
    LD10 or TDLMonkey/MTDhuman = 2.4 (P95 = 15.3)  
    LD10 or TDLDog/MTDhuman = 1.2 (P95 = 7.0)  
61 anti-neoplastic drugs LD10 and MTD Mouse, rat, dog, monkey LD10Mouse /MTDHuman >10 for 37% compounds [69]
    LD10Rat /MTDHuman >10 for 19% compounds  
    LD10Monkey /MTDHuman >10 for 5% compounds  
    LD10Dog/MTDHuman >10 for 3% compounds  
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Environmental Health

ISSN: 1476-069X