Interaction between neurotoxicities induced by organophosphorus and long-chain hexacarbon compounds.
Neurotoxicology 1983 Jan; 4(4):117-135
Data concerning the respective neurotoxic effects produced by organophosphorus and long chain hexacarbon compounds is reviewed. Combined exposure to leptophos and n-hexane has been implicated in the development of severe human neurological dysfunction. The subchronic oral administration or intraperitoneal injection of n- hexane type compounds causes neurotoxicity in hens. The subchronic continuous inhalation of technical grade methyl-butyl-ketone also produces a dose dependent neurotoxicity. It has been suggested that 2,5-hexanedione may be the active neurotoxic agent in n-hexane, methyl-n-butyl-ketone, and 2,5-hexanediol exerting a direct influence on certain axonal components. The gamma diketones, 2,5- heptanedione and 3,6-octanedione, are also proven neurotoxins. O- ethyl-O-4-nitrophenyl-phenylphosphonothioate and n-hexane type chemicals produce identical clinical signs of neurotoxicity, characterized by axon and myelin degeneration in both the central and peripheral nervous systems. It has been suggested that the biochemical mechanism of the delayed neurotoxicity induced by organophosphorus esters differs from that of the neurotoxicity caused by n-hexane type chemicals. All organophosphorus compounds identified as neurotoxic to date are organophosphorus esters which either directly or indirectly inhibit esterases. N-hexane type chemicals, which contain a hexacarbon skeleton with or without one or two oxygen atoms, produce a neurotoxicity that is characterized by the accumulation of 10 nanometer neurofilaments within swollen axons, accompanied by myelin sheath thinning and retraction. Although the mechanisms of the respective neurotoxic effects produced by organophosphorus esters and long chain hexacarbons seem to differ, simultaneous exposures to both types of substances make nerve tissues more sensitive to the respective neurotoxic effects that each substance produces. The author concludes that simultaneous exposure to both organophosphorus esters and n-hexane type compounds may be more dangerous than exposure to either type of chemical alone.
NIOSH-Grant; Toxic-effects; Chemical-indicators; Analytical-models; Exposure-levels; Toxic-materials; Histology; Body-distribution; Tissue-distribution; Cytology
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Duke University, Durham, North Carolina