Behavioural Effects of Low-level Developmental Exposure to Lead in the Monkey

  • D. C. Rice


Cynomolgus monkeys (Macaca fascicularis) dosed from birth onward with 0, 50, 100, or 500 µg/kg per day of lead had blood lead (PbB) levels of 3, 15, 25, or 55 µg/dl, respectively, before withdrawal of infant formula at 200 days of age, and later steady-state PbB levels of 3, 11, 13 or 33 µg/dl. Beginning at age 3 years these monkeys began performance on behavioural tasks designed to assess types of deficits found in children with moderate body burdens of lead, including various forms of intellectual impairment, distractibility and short attention span, and hyperactivity. The first task used here was an intermittent schedule of reinforcement, the fixed interval (FI), which required the monkey to make one response after a specified time had elapsed in order to receive a fruit juice reward. Although responding before the specified time had no consequences, monkeys (as well as other animals and humans) typically respond throughout the interval. Thus, this schedule is capable of measuring the ongoing activity of the monkey. Treated monkeys made more responses under these conditions than did control monkeys, and the effect was dose-related. Moreover, response rates for treated monkeys were more variable, both between days and even across a 50-min session, than for the control animals.

Following FI schedule testing, each monkey was tested on another intermittent schedule, the DRL (differential reinforcement of low rate), which assessed the monkey’s ability to inhibit responding. This required the monkey to wait at least 30 s before responding in order to receive a reward. Although the lead-treated monkeys were able to learn the task, they did so at a slower rate than controls and were more variable in their performance from day to day than the controls (similar to the FI results).

Short-term memory and attention were measured by two techniques: (1) delayed matching to sample, which required the monkey to remember a stimulus and signal this by choosing the correct stimulus out of three samples; and (2) a test of spatial memory, which required the monkey simply to alternate responses between two buttons, with a delay interposed between responses. On both tasks, treated monkeys were markedly deficient compared to controls.

The final task measured the monkeys’ ability to adapt to changes in the behavioural requirements of their environment. Each monkey was required to learn a series of discrimination tasks and, once learned, to learn the exact opposite task; that is, the correct answer became the incorrect, and vice-versa. Again, treated monkeys were impaired relative to controls in regard to such reversal behaviour.

These results collectively provide strong evidence for developmental exposure to lead causing behavioural impairment in the monkey, even at PbB levels near the current average for children in the United States and below presently accepted US criteria for undue risk of lead toxicity.


Lead Exposure Lower Dose Group Control Monkey Lead Toxicity Form Discrimination 
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  1. Angell, N.F. and Weiss, B. (1982) Operant behavior of rats exposed to lead before or after weaning. Toxicol. Appl Pharmacol., 63, 62–71PubMedCrossRefGoogle Scholar
  2. Bush, B., Doran, D. and Jackson, K. (1982) Evaluation of erythrocyte protoporphyrin and zinc protoporphyrin as micro screening procedures for lead poisoning detection. Ann. Clin. Biochem., 19, 71–76PubMedGoogle Scholar
  3. Bushnell, P.J. and Bowman, R.E. (1979a) Reversal learning deficits in young monkeys exposed to lead. Pharmacol Biochem. Behav., 10, 733–742PubMedCrossRefGoogle Scholar
  4. Bushnell, P.J. and Bowman, R.E. (1979b) Persistence of impaired reversal learning in young monkeys exposed to low levels of dietary lead. J. Toxicol Environ. Health, 5, 1015–1023PubMedCrossRefGoogle Scholar
  5. Cavalleri, A., Baruffini, A., Minoia, C. and Bianco, L. (1981) Biologic response of children to low levels of inorganic lead, Environ. Res., 25, 415–423PubMedCrossRefGoogle Scholar
  6. Centers for Disease Control (1985) Preventing lead poisoning in young children–United States. Morbidity and Mortality Weekly Report, 34, 66–73Google Scholar
  7. Cory-Slechta, D.A., Weiss, B. and Cox, C. (1983) Delayed behavioral toxicity of lead with increasing lead exposure. Toxicol Appl Pharmacol, 71, 342–352PubMedCrossRefGoogle Scholar
  8. Harlow, H.F., Harlow, M.K., Schiltz, K.A. and Mohr, D.J. (1971) The effect of early adverse and enriched environments on the learning ability of rhesus monkeys, in Jarrard, L.E. (ed), Cognitive Processes of Nonhuman Primates, pp. 121–149 ( New York: Academic Press )Google Scholar
  9. Hernberg, S. (1980) Biochemical and clinical effects and responses as indicated by lead concentration, in Singhal, R. and Thomas, J. (eds), Lead Toxicity, pp. 367–399 ( Baltimore: Urban & Schwartzenberg )Google Scholar
  10. Laties, V.G. (1978) How operant conditioning can contribute to behavioral toxicology. Environ. Health Perspect., 26, 29–35PubMedCrossRefGoogle Scholar
  11. Levin, E.D. and Bowman, R.E. (1983) The effect of pre- and post-natal lead exposure on Hamilton search task in monkeys. Neurobehav. Toxicol Teratol, 5, 391–394PubMedGoogle Scholar
  12. Mahaffey, K., Annest, J., Roberts, J. and Murphy, R. (1982) National estimates of blood lead levels: United States, 1976-1980. N. Engl. J. Med., 307, 573–579PubMedCrossRefGoogle Scholar
  13. Needleman, H.L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H., Maher, C. and Barrett, P. (1979) Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N. Engl. J. Med., 300, 689–695PubMedCrossRefGoogle Scholar
  14. Piomelli, S., Seaman, C., Zullow, D., Curran, A. and Davidow, B. (1982) Threshold for lead damage to heme synthesis in urban children, Proc. Natl Acad. Sci. USA, 79, 3335–3339PubMedCrossRefGoogle Scholar
  15. Rice, D.C. (1984a) Behavioral deficit (delayed matching to sample) in monkeys exposed from birth to low levels of lead. Toxicol Appl Pharmacol, 75, 337–345PubMedCrossRefGoogle Scholar
  16. Rice, D.C. (1984b) Effect of lead on schedule-controlled behavior in the monkey, in Seiden, L.S. and Balster, R.L. (eds), Behavioral Pharmacology: The Current Status, pp. 473–486 ( New York: Alan R. Liss )Google Scholar
  17. Rice, D.C. (1985a) Chronic low-lead exposure from birth produces deficits in discrimination reversal in monkeys. Toxicol Appl Pharmacol, 77, 201–210PubMedCrossRefGoogle Scholar
  18. Rice, D.C. (1985b). Behavioral toxicity in monkeys exposed to low levels of lead from birth. Toxicologist, 5, 23Google Scholar
  19. Rice, D.C. and Gilbert, S.G. (1985). Low lead exposure from birth produces behavioral toxicity (DRL) in monkeys. Toxicol. Appl Pharmacol, 80, 421–426PubMedCrossRefGoogle Scholar
  20. Rice, D.C. and Willes, R.W. (1979). Neonatal low-level lead exposure in monkeys: effect on two-choice non-spatial form discrimination. J. Environ, Pathol. Toxicol, 2, 1195–1203Google Scholar
  21. Rice, D.C., Gilbert, S.G. and Willes, R.W. (1979) Neonatal low-level lead exposure in monkeys: locomotor activity, schedule-controlled behavior, and the effects of amphetamine. Toxicol Appl Pharmacol, 51, 503–513PubMedCrossRefGoogle Scholar
  22. US Environmental Protection Agency (1984) Regulation of fuel and fuel additives; lead phase down. Fed. Regist., 49 (150), 31032–31050Google Scholar
  23. Willes, R., Kressler, P. and Truelove, J. (1977). Nursery rearing of infant monkeys (Macaca fascicularis) for toxicity studies. Lab. Animal Sci., 27, 90–98Google Scholar
  24. Willes, R.F., Rice, D.C. and Truelove, J.F. (1980). Chronic effects of lead in nonhuman primates, in Singahl, R.L. and Thomas, J.A. (eds), Lead Toxicity, pp. 213–240 ( Baltimore: Urban & Schwartzenberg )Google Scholar
  25. Winneke, G., Kramer, V., Brockhaus, A., Ewers, U., Kujanek, G., Lechner, H. and Janke, W. (1983) Neuropsychological studies in children with elevated tooth-lead concentration. Int. Arch. Environ. Health, 51, 231–252CrossRefGoogle Scholar
  26. Yule, W., Lansdown, R., Millar, I.B. and Urbanowicz, M.A. (1981) The relationship between blood lead concentrations, intelligence, and attainment in a school population: a pilot study. Dev. Med. Child. Neurol 23, 567–576PubMedCrossRefGoogle Scholar

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© ECSC-EEC-EAEC, Brussels — Luxembourg; EPA, USA 1989

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  • D. C. Rice

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