Document ID: EPA-HQ-OPP-2004-0292-0031
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-09-12T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES, AND

TOXIC SUBSTANCES

TXR No:	0053479

MEMORANDUM

DATE:	July 19, 2005

SUBJECT:	PYRACLOSTROBIN: Third Report of the Dose Adequacy Review Team
(DART)  	

PC code: 099100

DP Barcode: D315662

FROM:	Jessica Kidwell, Executive Secretary

Dose Adequacy Review Team

Health Effects Division (7509C)

THROUGH:	Jess Rowland, Chair			

Dose Adequacy Review Team

Health Effects Division (7509C)

TO:		Ghazi Dannan, Toxicologist

Paula Deschamp, Chief

Registration Action Branch 3

Health Effects Division (7509C)

John Bazuin/Cynthia Giles-Parker, PM Team 22

Fungicide Branch

Registration Division (7505C)

	

On March 31, 2005 the DART met to discuss BASF’s request to terminate
a supplemental female mouse carcinogenicity study.  Attached please find
the DART’s final report and recommendations.

Note to Registrant: Please reference this DART memo in the formal
submission of the supplemental study. 

Team Members in Attendance at the March 31, 2005 DART Meeting:
(Signature indicates concurrence with report unless otherwise noted:)			

Karl Baetcke						____________________________________

William Burnam					____________________________________

Marion Copley					____________________________________

Jessica Kidwell (Executive Secretary)	
____________________________________

Jess Rowland						____________________________________

Yung Yang						____________________________________

Other Attendees: Ghazi Dannan (HED/RAB3), Kelly O’Rourke (HED/RAB3),
Paula Deschamp (HED/RAB3), Robert Mitkus (HED/RAB1), conference call
with Health Canada’s PMRA (Catherine Adcock, Andrea Katynski)

The DART met on March 31, 2006 to discuss BASF’s request to terminate
the single dose supplemental female mouse carcinogenicity study based on
the study results through month six.  This data was submitted in
response to the DART’s request in a March 7, 2005 memo (TXR No.
0053177) to continue the study through 6 months to see if decreases in
body weight/body weight gain are temporary or if the body weight
divergence is sustained.

Upon review of the Registrant’s submission, the DART agreed that the
dose level of 360 ppm in the supplemental female mouse carcinogenicity
study can be terminated.  This was based on sustained and severe
decreases in body weight (20-24%)/body weight gain (46-52%) compared to
control from month four through month six. 

It is evident from the observed toxicity at 6-months that a dose of 360
ppm is excessive for female mice.  In the previous carcinogenicity study
(MRID No. 45118330), no toxicity was seen at 180 ppm, the highest dose
tested.  Taken together, the results of these studies show that an
“optimal” dose that would not elicit excessive toxicity would be
higher than 180 ppm but certainly lower than 360 ppm.  Since the dose
tested in the previous study was one-half of the dose that caused
excessive toxicity in the current study after only 6 months of treatment
and because of the narrow “dose spread” between the toxic and
non-toxic doses, the DART determined that no further testing is required
pending formal submission of the 6-month supplemental study.

Pyraclostrobin                                 Dose Adequacy Review Team
Report                     Final                

( PAGE  3 (