Brain exposure assessment

Additional selectivity profihng and pharmacokinetics of the maleimides are ideally required to assess their attractiveness and importance as in vivo tools. Nevertheless, exciting cellular inhibition of tau, in conjunction with varied degrees of brain exposure, suggests that these compounds could prove to be extremely interesting tools. 

National Academy of Sciences (1991) Human exposure assessment for airborne pollutants advances and opportunities. National Academy Press, Washington, DC Nazaroff W, Weschler C (2004) Cleaning products and air fresheners exposure to primary and secondary air pollutants. Atmos Environ 38 2841-2865 Oberdorster G, Sharp Z, Atudorei V et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhala Toxicol 16 437 145... 

The in vivo effect of chronic lead exposure on the acquisition of neural cells in the developing rat brain was assessed by measuring the rate of pH]thymidine incorporation into DNA. Wistar rats were used throughout the entire study and were maintained at 20°C and in a 12 h light/dark cycle. The animals had ad libitum access to food and water at all times. The pups were exposed to lead from their time of conception to the required postnatal period via their dams, who had ad libitum access to drinking water containing 400 mg PbCl2/l. Food and water intake was constantly monitored over exposure periods, and no difference in food and water intake was observed between control and lead-exposed animals. 

Research with animals can make a valuable contribution to two of the areas discussed earlier outcome measures and exposure assessment. It can indicate which outcome measures are most sensitive to lead effects and which outcomes are insensitive, provide information on the types of processes involved, and inform the choice of outcome measures for studies of children it also provides an opportunity to study the kinetics of lead in relation to the measures of body lead burden most frequently obtained in studies of humans. The effect of chelation therapy on lead levels in the brain, and the relation of these to levels of lead in blood and bone, is another area where animal work can inform studies of children. The limitations of extrapolation from animal data to studies of humans are addressed in the review section of this book. While it is unlikely that the rat provides an adequate model of... 

Rasmussen K, Jeppesen HJ, Sabroe S. 1993c. Psychometric tests for assessment of brain function after solvent exposure. Am J Ind Med 24 553-565. 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

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