Effect of Short-Term Exposure to Hexachlorophene on Rat Brain Cell Specific Marker Enzymes MEI-PING KUNG, PETER A. NICKERSON, FRANCES M. SANSONE, JAMES R. OLSON, PAUL J. KOSTYNIAK, MAUREEN A. ADOLF, PAMELA J. LEIN, AND JEROME A. ROTH' Departments of Pharmacology and Therapeutics, Anatomy, and Pathology, School ofMedicine and Biomedical Sciences, State University ofNew York, Bufalo, New York 14214 Received September 2, 1987; accepted May 9, 1988 Effect of Short-Term Exposure to Hexachlorophene on Rat Brain Cell Specific Marker En- zymes. KUNG, M-P., NICKERSON, P. A.. SANSONE, F. M., ORSON, J. R., KOSTYNIAK, P. J., ADOLF. M. A., LEIN, P. J., AND ROTH, J. A. (1988). Fundam. Appl. Toxicol. 11, 519-527. Seven cell specific marker enzymes in brain and optic nerve and morphological evaluation by light microscopy were used to characterize the neurotoxicity associated with exposure of rats to hexachlorophene (HCP; 40 mg/kg/day, po, for 9 days). In vitro exposure to HCP at concentra- tions up to 100 pM had no direct inhibitory effect on the marker enzymes, validating their use in evaluating brain function in vivo. Rats exhibited a reduction in body weight gain, weakness, and ataxia of the hind limbs by the ninth day of HCP exposure. At 24 hr following the last day ofexposure to HCP, the activities of the three neuron specific enzymes, glutamic acid decarbox- ylase, tyrosine hydroxylase, and choline acetyltransferase, in rat brain were unchanged from those of the vehicle-treated control group. Of the two astroghal enzyme markers measured, a small but significant increase was observed in the activity of nonneuronal enolase in the cerebel- lum and glutamine synthetase in the hippocampus of HCP-treated rats. The optic nerve ap- peared to be the most sensitive tissue in that the activity of both the astroghal marker, nonneuro- nal enolase, and the myelin marker, 2’,3’-cyclic nuceleotide phosphohydrolase, was significantly decreased following HCP exposure. This decrease in enzyme activity is consistent with the histo- logical observations demonstrating extensive vacuolization and edema in the optic nerve after exposure to HCP. 0 1988 Society ofToxicology. Hexachlorophene (HCP), 2,2’-methylene- bis(3,4,6-trichlorophenol), was widely used in the United States as a bacteriostatic agent in soaps and liquid detergents. In 197 1, Kim- brough and Gaines reported that HCP (25 mg/kg/day, po, for 10 weeks) was neurotoxic to rats, producing hindlimb paralysis, cere- bral edema of the white matter, and disrup- tion of myelin. Toxicity in humans has re- sulted from the accidental ingestion of solu- tions containing HCP or from dermal ’ To whom requests for reprints should be sent: De- partment of Pharmacology and Therapeutics, 127 Farber Hall, State University of New York, Buffalo, NY 142 14. application of HCP. In cases of fatal intoxica- tion with HCP, infants and young children exhibited status spongiosus of the white mat- ter similar to that observed in experimental animals (Kimbrough, 1976; Margin-Bouyer et al., 1982). The exact biochemical mecha- nism by which HCP exerts its toxic effects is not known although it is presumed to re- sult from the interaction of HCP with the plasma membranes of oligodendrocytes and Schwann cells, thus promoting the vacuoliza- tion of the myelin lamellae. HCP has also been reported to inhibit a number of enzymes in vitro, including Na+,K+-ATPase, adenylate cyclase, carbonic 519 0272-0590188 $3.00 Copyright 0 1988 by the Society of Toxicology. All rights of reproduction in any form reserved.