Evidence for delayed neurotoxicity produced by methylmercury.

Delayed toxicity as a result of developmental methylmercury exposure was identified in mice two decades ago by Spyker, who observed kyphosis, neuromuscular deficits, and other severe abnormalities as the mice aged. Delayed neurotoxicity was also observed in monkeys treated with methylmercury from birth to seven years of age. When these monkeys reached 13 years of age, individuals began exhibiting clumsiness not present previously. Further exploration revealed that treated monkeys required more time to retrieve treats than did nonexposed monkeys and displayed abnormalities on a clinical assessment of sense of touch in hands and feet, despite the fact that clinical examinations performed routinely during the period of dosing had not yielded abnormal results. Another group of monkeys, dosed from in utero to four years of age, also took longer to retrieve treats when assessed years after cessation of exposure. These observations were pursued in both groups of monkeys by objective assessment of somatosensory function in the hands: both groups of monkeys exhibited impaired vibration sensitivity. These results are strongly suggestive of a delayed neurotoxicity manifested when these monkeys reached middle age. Data from persons with Minamata disease also provide evidence for delayed neurotoxicity. Perhaps the strongest piece of evidence comes from a study of over 1100 Minamata patients over 40 years old, in which difficulty in performing daily activities increased as a function of age compared to matched controls. Methylmercury may represent the only environmental toxicant for which there is good evidence for delayed neurotoxicity that may be manifested many years after cessation of exposure.