Document ID: EPA-HQ-OPP-2006-0297-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-09-19T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

				

MEMORANDUM

DATE:  	July 25, 2007

SUBJECT:	Desmedipham: Re-evaluation of Cancer Classification

		

		PC Code: 104801; DP Number: D341870; TXR 0054666

REVIEWER:	Elissa Reaves, Ph.D., Senior Toxicologist

		Reregistration Branch 2

Health Effects Division (7509P)

AND

William Burnam, Ph.D., Senior Science Advisor

Health Effects Division (7509P)

THROUGH:	William Hazel, Ph.D., Chief

		Reregistration Branch 2

Health Effects Division (7509P)

TO:		Susan Stanton, Environmental Scientist

Risk Integration, Minor Use and Emergency Response Branch

Registration Division (7505P)

This memo serves to address and update the “tentative” Group E
cancer classification for desmedipham.  Desmedipham is now classified as
“Not likely to be Carcinogenic to Humans” based on the lack of
carcinogenic potential noted in the available studies.  

Background

In 1995, the RfD/Peer Review Committee (TXR 0011729) considered the
carcinogenicity of desmedipham based on two studies: a chronic
toxicity/carcinogenicity study in Wistar rats (MRID 40387107) and a
carcinogenicity study in mice (MRID 40387106).  The Peer Review
Committee considered the rat and mouse carcinogenicity studies to be
acceptable and the data evaluation records (DERs) to be adequate.  The
dose levels tested in these two cancer studies were also considered
adequate for carcinogenicity testing.  However, the Committee questioned
the incidence of mammary gland fibroadenomas’s in the low and mid-dose
female rats even though the high-dose females had a similar incidence of
mammary gland fibroadenoma as the concurrent controls.  Historical
control data was not provided for this rat study.  Furthermore, the
number of females examined in the low and mid-dose groups for
histopathological lesions was reduced compared to all animals examined
in the control and high-dose females.  Based upon the information
available at the time of the peer review, desmedipham was
“tentatively” classified as “Group E” pending the receipt of
historical control data and information to address the number of animals
examined at the low and mid-doses for histopathology.  

To date, historical control data for the Wistar rat cancer study have
not been submitted to the Agency.  However, the need for this historical
control data is alleviated by the submission of a new
chronic/carcinogenicity study in Sprague Dawley rats (MRID 45468101). 
The new Sprague Dawley rat study examined doses comparable to those
examined in the Wistar rat study (MRID 40387107).  In this new cancer
rat study (MRID 45468101), there was no treatment related increase in
the incidence of mammary gland fibroadenoma and no increase in any other
tumor type or in the total number of tumors.

Therefore, a re-evaluation of the cancer data for desmedipham reveals no
treatment related increase or dose-response of any tumor type from any
the of available cancer studies.  Specifically, the increased incidence
of fibroadenoma in Wistar rats was observed only in the low and mid-dose
females, whereas the high dose group had the same number of tumors as
the controls. Furthermore, the lack of carcinogenic response in the new
Sprague Dawley rat study (MRID 45468101) after exposure to comparable
doses examined in the Wistar rat study mitigates the need for historical
control data for the Wistar rat cancer study.

In conclusion, desmedipham should now be classified as “Not likely to
be Carcinogenic to Humans” based on the lack of carcinogenic potential
noted in the available studies.  

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