Rice D C
Toxicology Research Division, Health and Welfare Canada.
Neurotoxicology. 1992 Winter;13(4):757-70.
Monkeys (Macaca fascicularis) were dosed with 0 or 1500 micrograms/kg/day of lead as lead acetate according to one of four regimens: Group 1, vehicle continuously from birth; Group 2, lead continuously from birth; Group 3, lead from birth to 400 days of age and vehicle thereafter; Group 4, vehicle from birth to 300 days of age and lead thereafter. Blood lead values of the three treated groups were approximately 20-35 micrograms/dl, depending on age. Performance on a multiple fixed interval-fixed ratio (mult FI-FR) schedule of reinforcement was assessed when monkeys were three years of age, and again at 7-8 years of age following exposure to other behavioral tasks. Results of the first assessment were largely negative, with lead-treated monkeys failing to exhibit the rate increases on the FI observed in previous groups of monkeys tested at the same age. The second assessment revealed increased run rates and decreased average IRTs on the FI in all three treated groups. Effects on the FR component were minimal and transient during both assessment periods, which is consistent with previous results. Monkeys in previous studies had a history of tasks with trials procedures, in which every correct response was reinforced, before being tested on the mult FI-FR. The monkeys in the present study had no such history before the first assessment, but extensive exposure to trials procedures between the first and second assessment. It may be that the negative results of the first assessment and positive results of the second are the result of an interaction of lead with such a behavioral history. This suggestion is especially compelling in view of the results from Group 3, dosed only during infancy. These monkeys were unaffected during the first assessment, performed two years after cessation of dosing, but performed differently from controls on the second assessment, performed 5-6 years after cessation of dosing. This finding, combined with data from previous experiments, suggests that the greater total dose of lead accumulated by Groups 2 and 4 between the first and second assessment is not an explanation for the difference in results. These results also indicate that exposure to lead during infancy is not necessary for FI performance to be affected, and that exposure only during infancy is sufficient to produce effects.