Document ID: EPA-HQ-OPP-2005-0290-0013
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-22T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

Office of Prevention, Pesticides and Toxic Substances

  

February 8, 2007					

MEMORANDUM

SUBJECT:	Maleic Hydrazide:  Response to Public Comments on the Maleic
Hydrazide Tolerance Reassessment Eligibility Decision

		PC Code: 051501

		DP Barcode: 326315

FROM:	Becky Daiss

Biologist

Reregistration Branch 4/HED (7509C)

THROUGH:	Susan Hummel

Branch Senior Scientist

Reregistration Branch 4/HED (7509C)

TO:		John Pates

Reregistration Branch 1

Special Review and Reregistration Division (7508C)

This provides the Health Effects Division’s (HED) response to public
comments on the November 23, 2005 Tolerance Reassessment Eligibility
Decision for Maleic Hydrazide.  This memorandum addresses comments
pertaining to the HED Risk Assessment for Maleic Hydrazide dated
September 2, 2005.  A summary of the comments followed by HED’s
response is provided below.  William Dykstra provided responses to
comments pertaining to the toxicology assessment, Thurston Morton
provided responses to comments on the residue chemistry assessment, and
Becky Daiss responded to comments on the occupational exposure
assessment and general risk assessment related comments.Comments on the
Toxicological Assessment

Comment:  Crompton Corporation, Drexel Chemical Company;  Based on the
criteria provided in EPA/OPP HED SOP2002.01, the toxicological, chemical
and physical characteristics of maleic hydrazide do not justify the
requirement for a 28-day inhalation toxicity study under established
criteria.  The requirement should be waived.

HED Response:  Guidance provided in EPA/OPP HED SOP2002.01 on Waiver
Criteria for Multiple-Exposure Inhalation Toxicity Studies states that,
“a waiver may be granted for an active ingredient that is Toxicity
Category IV for inhalation provided an extrapolated inhalation MOE
(based on an oral NOAEL) exceeds a target MOE of 1000 or greater.” 
Malice hydrazide is Toxicity Category IV for inhalation and therefore
meets the first criteria.  However, inhalation MOEs estimated using an
oral NOAEL, unit exposures for mixing/loading for aerial application to
fallow land and potato crops, and maximum application rates, are less
than the target MOE of 1000 required to grant a waiver for the
inhalation study.  Estimated MOEs for these activities ranged from 300
to 600.  

Comments on the Residential Exposure Assessment

Comment:  Crompton Corporation;  Regarding the need for a statement on
all labels restricting application to professional applicators only,
such wording is ambiguous, unnecessarily harsh, and, in fact confusing
to the user.  A label statement such as “for agricultural use only”,
or “not for Homeowner use” would be sufficient to cover the
Agency’s concern.  Alternatively, restricting use to “commercial
applicators” (as opposed to “professional applicators”) would be
much better understood by the user public, and would still fulfill the
Agency’s goal of protecting the postulated untrained homeowner user. 

HED Response:  HED agrees that the alternate label statements suggested
by Crompton would be sufficient to ensure against misuse of malice
hydrazide containing products by homeowners. 

Comments on the Residue Chemistry Assessment

Comment: Drexel Chemical Company;  EPA required analytical methods for
data collection and tolerance enforcement for maleic hydrazide residues
of concern.  The Maleic Hydrazide Task Force II submitted an analytical
method to quantitate maleic hydrazide and its conjugates (6/5/96 letter
to OPP).  Drexel recommends use of the submitted method as the
enforcement method for the determination of maleic hydrazide glucoside
in meat, meat-by-products, fat and whole milk.   

HED Response:  EPA has reviewed the analytical method for maleic
hydrazide and its glucoside in livestock commodities.  The DER summary
is as follows:

“Under the conditions and parameters used in the study, the analytical
method residue data are classified as scientifically acceptable.  If the
method is intended for the enforcement of tolerances for livestock
commodities, an explanation for the poor recovery from cattle liver
samples during radiovalidation should be provided.  In addition, the
method should be rewritten to include instructions for all livestock
commodities for which tolerances are needed (i.e., for matrices in
addition to beef liver, chicken egg, and cow milk), and a confirmatory
method or an interference study will be required.  The registrant may
wish to modify the name of the analytical method to make it clear that
conjugates in addition to maleic hydrazide glucoside are determined by
the method.”

Comment:   Drexel Chemical Company, Crompton Corporation;  EPA required
storage stability studies for onions and potatoes.  Drexel submitted a
study on determination of the stability of residues of maleic hydrazide
in potato tubers during post-harvest refrigerated storage (Dykeman, R.
1993) to satisfy this requirement.  Crompton asserted that no additional
storage residue studies should be required for potatoes and onions and
that the data requirement should be waived.  Crompton argued that based
on the OPPTS storage stability study guidelines, extrapolation the
required information from existing stability data for MH in both potato
and onion Raw Agricultural Commodities (RACs) is reasonable and
sufficient.  

HED Response:  After reviewing MRID 46740701, EPA agrees that no
additional storage stability data are required for potatoes and onions. 
Existing onion residue data, adjusted for loss on storage, were used to
determine if the existing tolerance was appropriate.  Based on the
adjusted data, the existing tolerance on onion is deemed appropriate.

Comment:   Drexel Chemical Company;  EPA required additional data on
magnitude of residue in meat, milk, poultry, and eggs to confirm and to
establish tolerances.  Animal testing is not necessary because more than
an adequate margin of safety exist with the use of MH in potatoes and
the implementation of tolerances as recommended by the MH Task Force.  

HED Response:  Since the only livestock feed stuff with a tolerance is
potato, EPA agrees the total radioactive residue from the 28 day nature
of the residue study on cattle can be used to set tolerances.  Tolerance
reassessment/establishment for these commodities is addressed in an
addendum to the residue chemistry assessment (T. Morton, DP330764,
2/7/07).  Also, a livestock feeding study will be required for any
request for new use of maleic hydrazide on commodities with livestock
feed stuffs.  

Comment: Crompton Corporation;  The need for a 120 day plantback
interval for all rotational crops is not justified by the facts of MH
metabolism.

HED Response:  After reviewing the confined rotational crop study, EPA
recommends a 30 day plantback interval instead of the previously
recommended 120 day plantback interval.  If the registrant desires a
shorter interval limited field rotational crop data will be required.

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