Tissue distribution as a factor in species susceptibility to toxicity and hazard assessment. Example: methylmercury

Data on the tissue distribution and pharmacokinetics of methylmercury(MeHg) in cats and humans were utilized as an example of how such data can assist in extrapolating toxicity data between animal species. These data demonstrate that the whole-body half-time for clearance of MeHg was the same for cats (76.2 +/- 1.6 days) and humans (78 +/- 5 days) and that the concentration of MeHg in the brain at comparable signs of toxicity were the same (10 ppm) in the two species. However, the blood:brain ratio of MeHg concentration was 10 times as high in cats (1:1) as humans (1:10). From these data it was hypothesised that the no-effect level of methylmercury intake in cats should be 10 times that for humans. This hypothesis was verified from data o MeHg toxicity in cats and humans which demonstrated that ataxia developed in cats at a minimum dose of 46 microgram MeHg/kg body wt/day with blood MeHg levels of 6 to 8 ppm; humans developed ataxia with blood MeHg levels of 0.6 to 0.8 ppm and an estimated intake of 4 microgram MeHg/kg body wt/day.