Central nervous system measurements

Demonstrated Sensitivity of Central Nervous System Measures... 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

L-Glutamate acts as an excitatory neurotransmitter at many synapses in the mammalian central nervous system. Electrophysiological measurements and the use of various selective agonists and antagonists indicate that different glutamate receptors co-exist on many neurons. 

Many different types of sensory receptors are located throughout the body. These receptors monitor the status of the internal environment or that of the surroundings. Sensory receptors are sensitive to specific types of stimuli and measure the value of a physiological variable. For example, arterial baroreceptors measure blood pressure and chemoreceptors measure the oxygen and carbon dioxide content of the blood. The information detected by these sensors then travels by way of afferent neuronal pathways to the central nervous system (CNS). The CNS is the integrative portion of the nervous system and consists of the (1) brain and the (2) spinal cord. 

A 3-year-old boy consumed a liquid from a container in the family garage He shows central nervous system (CNS) depression, acidosis, suppressed respiration, and oxalate crystals in the urine. Besides supportive and corrective measures, ethanol was administered to the child. 

Occupational exposures and the study with human volunteers indicate that exposures at low concentrations cause headaches and signs of central nervous system depression. No headaches were reported and no equilibrium disturbances were measured during occupational exposures of healthy workers to Otto Fuel II (measured as PGDN) at concentrations <0.22 ppm (average of approximately 0.06 ppm) for periods of 30-60 min, although subtle changes in eye movements were recorded (Horvath et al. 1981). In a study with healthy but previously unexposed male volunteers, the threshold for odor detection was 0.2 ppm (Stewart et al. 1974). Mild headaches were reported in one of three subjects after a 6-h exposure at 0.1 ppm, in two of three subjects after a 2-h exposure at 0.2 ppm, and in one of three subjects after a 1-h exposure at 0.5 ppm. Severe headaches occurred after an 8-h exposure at 0.2... 

Human exposures with measured concentrations were limited to occupational reports. Symptoms of exposed workers ranged from no adverse health effects to mild discomfort to frank central nervous system effects. Repeated or chronic exposures have resulted in hypothyroidism. Inhalation studies resulting in sublethal effects, such as incapacitation, and changes in respiratory and cardiac parameters were described for the monkey, dog, rat, and mouse lethality studies were available for the rat, mouse, and rabbit. Exposure durations ranged from a few seconds to 24 hours (h). Regression analyses of the exposure duration-concentration relationships for both incapacitation and lethality for the monkey determined that the relationship is C2xt= k and that the relationship for lethality based on rat data is C2 6xt=k. 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

The status of the study of variation and inheritance of structure in the central nervous system may be summarized as follows. The brain is extremely variable in every character that has been subjected to measurement. Its diversities of structure within the species are of the same general character as are the differences between related species or even between orders of animals. Some of the structural variations have been shown to correlate with functional disturbances. From what is known of the variations in other systems, it may be concluded that the variants which produce pathological symptoms are not discontinuous characters but are the extremes of a normal distribution. Lesser deviations in the same direction, resulting in behavior which is not classed as pathological, are to be expected. 

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