Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mattsson, J. L.
Right arrow Articles by Bus, J. S.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Mattsson, J. L.
Right arrow Articles by Bus, J. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1997 Oxford University Press

other

Single-Dose and Chronic Dietary Neurotoxicity Screening Studies on 2,4-Dichlorophenoxyacetic Acid in Rats1

Joel L. Mattsson*,2, Jeffrey M. Charles{dagger}, Barry L. Yano*, Helen C. Cunny{ddagger}, Ronald D. Wilson§ and James S. Bus*

*Dow Chemical Company, Midland Michigan, Durham, North Carolina {dagger}Charles, Conn, & van Gemert, LLC Durham, North Carolina {ddagger}Rhone-Poulenc Ag Company, Research Triangle Park North Carolina §John Wise & Associates, Ltd. Liberty, Missouri

Received March 4, 1997; accepted August 1, 1997

Forms of 2,4-dichlorophenoxyacetic acid (collectively known as 2,4-D) are herbicides used to control a wide variety of broadleaf and woody plants. Single-dose acute and 1-year chronic neurotoxicity screening studies 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 emphasized a Functional Observational Battery (which included grip performance and hindlimb splay tests), automated motor activity testing, and comprehensive 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 gait and coordination changes and clearly decreased motor activity at the time of maximal effect on the day of treatment (day 1). Mild locomotor effects occurred in one mid-dose rat (75 mg/kg), on Day 1 only. No gait, coordination, or motor activity effects were noted by day 8. In the chronic study, the only finding of neurotoxicologic significance was retinal degeneration in females in the high-dose group (150 mg/kg/day). 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 locomotor effect from high-level acute exposure, and retinal degeneration in female rats from high-level chronic exposure. Based on the results from these two studies, the no-observed-adverse-effect level for acute neurotoxicity was 15 mg/kg/day and for chronic neurotoxicity was 75 mg/kg/day.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.