Lead-impaired neurodevelopment. Mechanisms and threshold values in the rodent

Mechanisms underlying the cognitive deficits arising from chronic low level lead exposure are viewed as a consequence of impaired neurodevelopmental events. These events are exemplified within the cerebellum which is formed completely after birth and, therefore, encompasses all major epochs of development. Further, the unique pharmacokinetic distribution of juvenile blood lead levels is developmentally regulated and can be correlated to the periods of impaired structuring and threshold values indicating no-effect levels established. Here, the endpoint value is related to lead-induced dysfunctioning of a morphoregulator--the neural cell adhesion molecule (NCAM). During final synaptic structuring its normal developmental sequence is perturbed when blood lead levels exceed 20 micrograms/dl. These events are similar, and compared to, those seen in the cerebellum of the staggerer mouse mutant (sg/sg) where the selection of circuits to be preserved from those transiently overproduced during development is impaired.