Methylmercury: exposure duration and regional distribution as determinants of neurotoxicity in nonhuman primates
Evans, H.L.; Garman, R.H.; Weiss, B.
Toxicology and Applied Pharmacology 41(1): 15-33
1977
ISSN/ISBN: 0041-008X PMID: 408941 Document Number: 112331
Exposure duration appears to be an important determinant, along with dosage, blood and brain Hg concentration, of sublethal methylmercury toxicity in macaque [Macaca arctoides and M. nemestrina] and squirrel [Saimiri sciureus] monkeys. Animals were evaluated for objective neural signs while maintained with blood and brain Hg near equilibrium. Chronic methylmercury, orally, produced similar bodily distributions of Hg and neural signs for both species. The characteristic brain regional distribution of Hg is established well in advance of signs, emphasizing the importance of exposure duration and arguing against a major redistribution of Hg as the critical event preceding toxic signs. The calcarine cortex, lateral geniculate and corpus striatum are candidates for critical brain regions. When near equilibrium, the primate brain Hg concentration is 1.8-4.9 times that of whole blood, depending upon region; higher brain/blood ratios are obtained 1 wk or more following the end of exposure. Clearance of Hg from most regions of the macaque brain appeared to be similar to the rate of clearance from whole blood (t 1/2 [half-time] = 21 days) and thus is considerably shorter than half-times reported from primate hair and whole body. The latent period preceding neural signs was inversely related to whole blood Hg concentration within the range associated with neurological signs in humans (0.5-4.5 ppm). Evidence of a no-effect dose in the primate will require lower level exposures in excess of 1000 days. This experimental model can suggest critical indices of human long-term, low-level exposures and it provides a basis for evaluating results from nonprimate species.