Neurobehavioral testing in human risk assessment

Abstract

Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. The field of neurobehavioral toxicology has evolved from research which initially focused on using traditional neuropsychological tests to identify “abnormal cases” to include methods used to detect sub-clinical deficits, to further incorporate the use of neurosensory assessment, and to expand testing from occupational populations to vulnerable populations including older adults and children. Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations. This paper reflects a summary of the talks presented at the Neurobehavioral Testing in Human Risk Assessment symposium presented at the 11th meeting of the International Neurotoxicology Association.

Introduction

Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. Advances are available regarding the assessment of behavioral and sensory changes and the statistical treatment of neurobehavioral data. This paper reflects a summary of the talks presented at the Neurobehavioral Testing in Human Risk Assessment symposium presented at the 11th meeting of the International Neurotoxicology Association.

The field of neurobehavioral toxicology or behavioral neurotoxicology has been rapidly evolving. Since the early research which focused on using traditional neuropsychological tests to identify “abnormal cases” (Hänninen, 1966), the field has evolved to include methods used to detect sub-clinical deficits (Lucchini et al., 2005), to further incorporate the use of neurosensory assessment (van Thriel et al., 2007), and to expand testing from occupational populations to vulnerable populations including older adults and children (Amler et al., 1994, Weiss, 1990). Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations.

Risk assessment can be divided into four separate states: hazard identification, dose–response assessment, exposure assessment, and risk characterization (US NAS, 1983). Neurobehavioral research provides information for the first three steps. The first summary, “Does human behavioral neurotoxicology research address risk assessment needs?” evaluates the utility of neurobehavioral methods to provide information needed for risk assessment. Risk assessment requires evidence from the scientific research literature that effect measures, in this case behavioral changes such as attention or memory loss, are associated with measures of external and internal dose in a dose-dependent fashion. Selected literature from 1990 to 2007 was reviewed to determine if behavioral neurotoxicology research is providing the data for risk assessment. Another important aspect of risk assessment is interpreting the findings from a study and defining the critical adverse effect. The second summary “Interpretation of small effect sizes in neurotoxicological studies: characterizing individual versus population risk,” discusses this issue. As exposures in the workplace have decreased, clinical cases of neurotoxicity are less common and the concern is identifying subtle deficits. Interpreting neurobehavioral findings and their implication for individual and population risk is discussed.

Developing sensitive methods for detecting adverse effects of exposure is an important goal of risk assessment. A variety of metals and solvents are known to affect sensory function such as vision, hearing and olfactory function. These chemicals irritate the upper respiratory tract and the eyes and may be sensitive measures of exposure. Incorporating chemosensory methods and neurobehavioral methods is a growing area of research and is described in the summary “Risk assessment of local irritants—new challenges for neurobehavioral research.”

As chemicals in the environment increase there is concern about the impact of these chemicals on the health and development of children. The summary “Assessment of neurobehavioral effects in vulnerable populations: the example of pesticide exposure in children” describes methods to assess exposure in children using exposure to pesticides as an example. The final summary “Lifetime exposure to cumulative neurotoxicants: how to define effective preventive strategies to avoid the risk of long-term effects” discusses the changing world of neurotoxiology where exposure is not limited to the workplace but is occurring across the lifespan. The implications of this change and the implications for risk assessment are discussed.