Developmental neurotoxicity mechanisms

Costa LG Signal-transduction mechanisms in developmental neurotoxicity the phosphoinositide pathway. Neurotoxicology 15 19-27, 1994... 

In a few cases, studies to evaluate developmental neurotoxicity or other postnatal functions may have been conducted, and these can provide amore complete evaluation of potential developmental effects. In addition to the standard guideline studies, data from experimental studies on mechanisms of action, etc., can provide useful data for consideration in the risk assessment process. 

More in-depth behavioral tests are required if dose-related toxicant effects are noted in screening tests. These tests may also be required as part of more selective toxicological screening, such as for developmental neurotoxicity. Focused tests of neuromotor function and activity, sensory functions, memory, attention, and motivation help to identify sites of toxicant-mediated lesioning, aid in the classification of neurotoxicants, and may suggest mechanisms of action. Some of these tests, like the schedule-controlled operant behavior tests for cognitive function, require animal training and extensive operator interaction with the animals. 

Brenneman KA, Cattley RC, Ali SE, et al. 1999. Manganese-induced developmental neurotoxicity in the CD rat Is oxidative damage a mechanism of action Neurotoxicology 20 477-488. 

Whitney, K, D Seidler, E, J and Slotkin, T. A. (1995). Developmental neurotoxicity of chlorpyrifos Cellular mechanisms. Toxicol. Appl. Pharmacol. 134, 53-62,... 

Qiao, D, Seidler, F. J, and Slotkin, T. A. (2(X)5). Oxidative mechanisms eontribuiing to the developmental neurotoxicity of nicotine and chlorpyrifos. Toxical. Appl. Pharmacol., 2(16, 17-26. 

Identify and elucidate mechanisms that underlie the developmental neurotoxicities of OP compounds... 

The mechanisms of Pb developmental neurotoxicity in particular and multisystem toxicity in general are likely multiple. To date, no global, single mechanism explaining the element s toxicity, and particularly its neurotoxicity, has emerged. Rather, organ- and system-specific effects appear to be linked to specific mechanisms. In the case of neurotoxic effects, and aU other effects in general, studies have typically focused on processes at the subcel-lular and biomolecular level to explain whole-animal results. The focus of... 

The mechanisms of developmental National Institute of neurotoxicity (rat) Environmental Health... 

Data adequacy The key study was well designed, conducted, and documented used 20 human subjects and utilized a range of concentrations and exposure durations. Occupational exposures support the 8-h AEGL value. The mechanism of headache induction (vasodilation) is well understood and occurs following therapeutic administration of nitrate esters to humans. Animal studies utilized several mammalian species and addressed metabolism, neurotoxicity, developmental and reproductive toxicity, and potential carcinogenicity. ... 

In the cases in which human aluminum toxicity has occurred, the target organs appear to be the lung, bone, and the central nervous system. No specific molecular mechanisms have been elucidated for human toxicity to aluminum. In animal models, aluminum can also produce lung, bone, and neurotoxicity, as well as developmental effects in offspring. 

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