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June 2002 Meeting Agenda

June 24, 2002

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
OPEN MEETING
JUNE 26-27, 2002
FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/
OPP Docket Telephone: (703)305-5805

WEDNESDAY, JUNE 26, 2002
SHERATON CRYSTAL CITY HOTEL
1800 JEFFERSON DAVIS HIGHWAY
ARLINGTON, VIRGINIA 22202
703-486-1111

Determination of the Appropriate FQPA Safety Factor(s) in the Organophosphorous Pesticide Cumulative Risk Assessment: Susceptibility and Sensitivity to the Common Mechanism, Acetylcholinesterase Inhibition

THURSDAY, JUNE 27, 2002
SHERATON CRYSTAL CITY HOTEL
1800 JEFFERSON DAVIS HIGHWAY
ARLINGTON, VIRGINIA 22202
703-486-1111

Determination of the Appropriate FQPA Safety Factor(s) in the Organophosphorous Pesticide Cumulative Risk Assessment: Susceptibility and Sensitivity to the Common Mechanism, Acetylcholinesterase Inhibition

Question 1.1

Lead Discussant: John Bigbee, Ph.D.
Associate Discussants: Amira Eldefrawi, Ph.D., Carey Pope, Ph.D., Steven Brimijoin, Ph.D., and Jean Harry, PhD.

Please comment on the extent to which the report adequately summarizes the current state of knowledge. Does the scientific evidence support the conclusion that perturbation of the cholinergic nervous system during development by inhibiting AChE can potentially lead to deficits in the structure and function of the central and peripheral nervous systems?

Issue 2. Age-Dependent Sensitivity to Cholinesterase inhibition in Animal Studies

Report Coordinators: Lester Sultatos, Ph.D., and Carey Pope, Ph.D.

Age-dependent sensitivity (i.e., young animals can exhibit higher levels of cholinesterase (ChE) inhibition at the same dose or inhibition at lower doses compared to adults) has been observed in several laboratory studies following treatment (acute and/or repeated oral gavage doses) of neonatal, juvenile, and adult rats with organophosphorus (OP) pesticides. The exact mechanisms of this age-dependent sensitivity are not known, but several studies have demonstrated that toxicokinetic factors may be responsible. Most notably, the more limited ability of the young to detoxify OP pesticides by A-esterases and carboxylesterases appears to be an important factor underlying the increased sensitivity of the immature rat to ChE inhibition. There appears to be more rapid recovery of inhibited AChE (synthesis of new ChE enzyme) in postnatal (and fetal) rat tissues, but information on comparative recovery in children and human adults is lacking.

Question 2.1

Lead Discussant: Jean Harry, Ph.D.
Associate Discussants: Lester Sultatos, Ph.D., Carey Pope, Ph.D., Steven Brimijoin, Ph.D.

Please comment on the extent to which the report adequately discussed and summarized the current understanding of age-dependent sensitivity to ChE inhibition, the prevailing views in the scientific community concerning the biological factors involved, and the role esterases may play as a major factor accounting for potential increased sensitivity of the immature rat.

Question 2.2

Lead Discussants: Carey Pope, Ph.D., and Steven Brimijoin, Ph.D.,

Please comment on the timing of administration (i.e., the developmental stage treated) and the differential found between adults and the young animal.

 

Please be advised that agenda times are approximate. For further information, please contact the Designated Federal Official for this meeting, Mr. Paul Lewis, via telephone: (202) 564-8450; fax: (202) 564-8382; or email:lewis.paul@epa.gov

  Agenda: SAP Open Meeting - June 26 - 27


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