Biological neurological effects

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on biomarkers for neurological effects see OTA (1990). 

Neurological Effects. Little information was available to determine the neurotoxicity or the mechanism of neurotoxicity of HDI after inhalation, oral, or dermal exposure. Headache was reported in only one human exposure case (Malo et al. 1983). Neurotoxic effects (convulsions) may occur in laboratory animals if concentrations reaeh high levels in the air (Haskell Laboratory 1961) however, sinee HDI is metabolized quickly in a biological matrix (Berode et al. 1991), little intaet HDI is expected to reach the nervous tissue to elicit a toxic response, except possibly at very high eoneentrations. No neurological effects have reported in laboratory animals, or in hiunans exposed chronieally to low concentrations of HDI (Mobay Corporation 1989). HDI, in addition to other isocyanates, have been shown to inhibit acetylcholinesterase in human erythrocytes (Dewair et al. 1983), human serum acetylcholinesterase (Brown et al. 1982), as well as equine serum, bovine erythrocyte, and eel acetylcholinesterase (Brown et al. 1982). 

PCB congeners were measured in the Faroe study, and stated that it seems likely that mercury was measured more accurately than the biologically relevant PCB exposure. Consequently even if the neurological effects seen in this study were caused entirely by PCBs, it is possible that mercury would still be more highly correlated with these effects than PCBs. The Statistics/Design Panel also said that the best method to deal with this problem would be to study a population where exposure to PCBs is not an issue. This statement points directly to the Seychelles study as the study most appropriate for MRL derivation. 

As far as I can tell by talking with contemporary thermo-dynamicists, especially those who grew up with the traditions of classical thermodynamics, these revolutionary ideas have had very little effect on them. But the impacts of the Shannon and Jaynes papers on others has been most dramatic. A few months ago I ordered a computer search of one particular data base. We looked for all papers published between 1970 and 1975 in which Shannon or Jaynes or both appeared as references. There were over 400 literature citations in such fields as systems theory, biology, neurology, meteorology, statistical mechanics, thermodynamics, irreversible processes, reliability, geology, psychiatry, communications theory and even urban studies, transportation and architecture. 

The partition coefficient and concepts derived from it are particularly important in explaining the mode of action of neurological drugs, such as anticonvulsants (chapter 8, section 8.1.5) and general anesthetics, which must penetrate the blood-brain barrier prior to exerting their biological effect. 

---