SINGLE-DOSE AND CHRONIC DIETARY NEUROTOXICITY SCREENING STUDIES ON 2,4-DICHLOROPHENOXYACETIC ACID IN RATS

Forms of 2,4-dichlorophenoxyacetic acid (collectively known as 2,4-D) are herbicides used to control a wide variety of broadleaf and woody p lants, Single-dose acute and 1-year chronic neurotoxicity screening st udies in male and female Fischer 344 rats (10/sex/dose) were conducted on 2,4-D according to the U.S. EPA 1991 guidelines. The studies empha sized a Functional Observational Battery (which included grip performa nce and hindlimb splay tests), automated motor activity testing, and c omprehensive neurohistopathology of perfused tissues. Dosages were up to 250 mg/kg by gavage for the single-dose study, and up to 150 mg/kg/ day in the diet for 52 weeks in the repeated-dose study. In the acute study, gavage with 250 mg/kg test material caused slight transient gai t and coordination changes and clearly decreased motor activity at the time of maximal effect on the day of treatment (day 1). Mild locomoto r effects occurred in one mid-dose rat (75 mg/kg), on Day 1 only. No g ait, coordination, or motor activity effects were noted by day 8. In t he chronic study, the only finding of neurotoxicologic significance wa s retinal degeneration in females in the high-dose group (150 mg/kg/da y). Body weights of both sexes were slightly less than controls in the mid-dose group, and 10% less than controls in the high-dose group. In summary, the findings of these studies indicated a mild, transient lo comotor effect from high-level acute exposure, and retinal degeneratio n in female rats from high-level chronic exposure. Based on the result s from these two studies, the no-observed-adverse-effect level for acu te neurotoxicity was 15 mg/kg/day and for chronic neurotoxicity was 75 mg/kg/day. (C) 1997 Society of Toxicology.