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July 29 - 30, 2004 Meeting Agenda
FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
OPEN MEETING
JULY 29-JULY 30, 2004
FIFRA SAP WEB SITE https://www.epa.gov/scipoly/sap/
OPP Docket Telephone: (703) 305-5805
Docket Number: OPP-2004-0173
THURSDAY, JULY 29, 2004
Holiday Inn Rosslyn at Key Bridge
1900 North Fort Myer Drive
Arlington, VA 22209
(703) 807-2000
DIMETHOATE: ISSUES RELATED TO HAZARD AND DOSE RESPONSE ASSESSMENT
∙ 8:30 AM Introduction and Identification of Panel Members - Stephen M. Roberts, Ph.D. (FIFRA SAP Chair)
∙ 8:40 AM Administrative Procedures by Designated Federal Official - Ms. Myrta R. Christian
∙ 8:45 AM Welcome - Mr. Joseph J. Merenda, Jr. (Director, Office of Science Coordination and Policy, EPA)
∙ 8:50 AM Opening Remarks - Mr. Jim Jones (Director, Office of Pesticide Programs, EPA)
∙ 8:55 AM Opening Remarks - Margaret Stasikowski/Randolph Perfetti, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
∙ 9:00 AM PMRA/EPA Joint Dimethoate Risk Assessment - Ms. Cheryl Chaffey (Pest Management Regulatory Agency, Canada)
∙ 9:10 AM Background, Goals, Objectives and Focus of Dimethoate: Issues Related to Hazard and Dose Response Assessment - Kathleen Raffaele, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
∙ 9:20 AM Summary of study design for relevant data sources - Kathleen Raffaele, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
∙ 9:45 AM BREAK
∙ 10:00 AM Results: pup mortality, brain cholinesterase inhibition, maternal neglect - Kathleen Raffaele, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
∙ 11:00 AM Dermal penetration factor - Byong-Han (Paul) Chin, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
∙ 11:40 AM Summary - Kathleen Raffaele, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA), Byong-Han (Paul) Chin, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA), and Ms. Cheryl Chaffey (Pest Management Regulatory Agency, Canada)
∙ 12:00 PM LUNCH
∙ 1:00 PM Public Comments
∙ 2:30 PM BREAK
∙ 2:45 PM Public Comments (continued)
∙ 5:00 PM ADJOURNMENT
FIFRA SCIENTIFIC ADVISORY PANEL (SAP)
OPEN MEETING
JULY 29-JULY 30, 2004
FIFRA SAP WEB SITE https://www.epa.gov/scipoly/sap/
OPP Docket Telephone: (703) 305-5805
Docket Number: OPP-2004-0173
FRIDAY, JULY 30, 2004
Holiday Inn Rosslyn at Key Bridge
1900 North Fort Myer Drive
Arlington, VA 22209
(703) 807-2000
DIMETHOATE: ISSUES RELATED TO HAZARD AND DOSE RESPONSE ASSESSMENT
∙ 8:30 AM Introduction and Identification of Panel Members - Stephen M. Roberts, Ph.D. (FIFRA SAP Chair)
∙ 8:40 AM Administrative Procedures by Designated Federal Official - Ms. Myrta R. Christian
∙ 8:45 AM Follow-up from Previous Day's Discussion
- Kathleen Raffaele, Ph.D. (Health Effects Division, Office of Pesticide Programs, EPA)
- Ms. Cheryl Chaffey (Pest Management Regulatory Agency, Canada)
∙ 9:00 AM Questions to the Panel
Issue 1. Interpretation of the results from the developmental neurotoxicity (DNT) and related comparative ChE inhibition and cross-fostering studies
Question 1.1
In 2001, EPA was notified of unanticipated adverse effects in the DNT study. The adverse effects observed were a potential increase in the number of deaths in young pups when dams were exposed orally to dimethoate during gestation and lactation. Following a detailed review of this study, both EPA and PMRA have determined that there is a dose-related increase in pup mortality. Typically in developmental and reproductive toxicity studies, the litter is considered the appropriate unit of analysis. As part of the review of the dimethoate DNT study, the individual pup has been treated both qualitatively and statistically as the appropriate unit of analysis. This evaluation has included pups which died and whole litters which were humanely sacrificed and includes, for example, mortality of 15 pups which was limited to a litter from a single dam at 0.5 mg/kg/day.
Please comment on the biological and statistical considerations important in evaluating the dose-response data such as the pup mortality incidence reported in the DNT.
Question 1.2
Section II.D of the issue paper describes the total weight of the evidence used by EPA and PMRA to reach their conclusions regarding the pup mortality observed in the main DNT study.
Please comment on the clarity and completeness of this discussion.
Question 1.3
The underlying cause of the pup mortality is unclear. The study design for the DNT study includes both pre- and post-natal exposures; the impact of in utero exposure on pup mortality cannot be distinguished from post-natal exposures (either through lactation or direct dosing) in this study. In order to further characterize the cause of pup mortality, and specifically, the influence of maternal neglect, the pesticide registrant designed and performed a cross-fostering study where untreated dams reared pups exposed in utero; treated dams reared pups not exposed in utero; and treated dams reared their own litters. EPA and PMRA have reviewed the pup mortality reported in the cross-fostering study along with observations specifically targeted to evaluate maternal neglect (e.g., maternal restlessness, scattering of pups, absence of milk in the stomach). These data have been evaluated in context with observations from the main DNT study and related comparative ChE and range-finding studies.
Please comment on the information available for dimethoate which characterizes the underlying cause(s) of the pup mortality in the dimethoate DNT study and the degree to which this information can be used to determine impact of maternal neglect on pup mortality.
∙ 10:30 AM BREAK
∙ 10:45 AM Questions to the Panel (continued)
Issue 2. Determination of a dermal penetration factor for dimethoate
Question 2.1
Three different studies evaluating dermal penetration are available. These include: an in vitro study with rat and human tissue; an in vivo study conducted with dimethoate prepared in aqueous carboxymethyl cellulose suspension; and an in vivo study conducted with dimethoate prepared in commercial formulations. Although each study has scientific merit, there are uncertainties associated with each study: namely, effects of different vehicle/solvent used in the in vivo studies and lack of accuracy of estimating in vivo dermal absorption by in vitro procedure in the rat.
Please comment on the utility of these studies for purposes of estimating a dermal absorption factor for dimethoate.
∙ 12:15 PM ADJOURNMENT
Please be advised that agenda times are approximate. For further information, please contact the Designated Federal Official for this meeting, Ms. Myrta Christian, via telephone: (202) 564-8450; fax: (202) 564-8382; or email: christian.myrta@epa.gov