Lifetime cumulative exposure as a threat for neurodegeneration: need for prevention strategies on a global scale.

Exposure to neurotoxic agents represents a concern of high priority in modern society. The nervous system can compensate for the toxic effects caused by low doses, but prolonged and lifetime exposure can also lead to delayed neurodegenerative effects for very low levels. The reported frequency of neurodegenerative diseases is constantly increasing, resulting in serious negative impacts on the health of the worldwide population. Future estimates indicate that Parkinson's Disease will increase mostly in industrialized countries during the next few years. Exposure to neurotoxic agents can take place during the various phases of life, beginning from the embryonic stage. The time variable plays an important role in neurotoxicity, both in terms of exposure duration and the period of life when it occurs. Prevention and the standards necessary to achieve it are needed to avoid health effects due to lifetime exposure. Risk assessment is a fundamental requirement for risk management and related preventive policies. Therefore, the relationship between exposure and effects should consider measures of cumulative exposure, to integrate both the historical exposure and the exposure to mixed agents, and the related cumulative effects. Examples and suggestions of different metrics for lifetime and cumulative exposure are illustrated in this paper, which reflects a summary of the key note lecture presented at the 10th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health of the International Commission on Occupational Health.