UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

				

MEMORANDUM						          December 5, 2006

							

SUBJECT:	HED Response to Comments Submitted to the Agency Concerning the
Triadimefon Reregistration Eligibility Decision (RED) and the
Triadimenol Tolerance Reassessment Eligibility Decision (TRED).

			Triadimefon Docket ID Number:  EPA-HQ-OPP-2005-0258

			Triadimenol Docket ID Number:  EPA-HQ-OPP-2006-0038 

			DP Barcodes:		           333573, 333685

FROM:	Richard Griffin, Risk Assessor

		Reregistration Branch II

Health Effects Division (7509P)

THROUGH:	Alan Nielsen, Branch Senior Scientist

		Reregistration Branch II

Health Effects Division (7509P), and

William Hazel, Chief

Reregistration Branch II

Health Effects Division (7509P)

			

TO:		John Pates, Jr., Chemical Review Manager

		Reregistration Branch I

		Special Review and Reregistration Division  (7508P)

In the August 30, 2006 Federal Register, the EPA published (as one
document) the Reregistration Eligibility Decision (RED) for triadimefon
and the Tolerance Reassessment Eligibility Decision (TRED) for
triadimenol.  Following closure of the comment period on October 30,
2006 the primary registrant (and data provider) for both chemicals,
Bayer CropScience, sent a letter to the Agency with comments to the
decision document.  The following memo is the Health Effects
Division’s response to Bayer’s comments.  

Bayer Comment 

Referring to Page 5, Section II.B.2 of the Decision Document, Bayer
comments that the published structure for triadimenol is not correct.

HED Response

HED concurs with Bayer’s comment that the published structure is not
correct.  The triadimefon/triadimenol Decision Document should be
amended to show the correct triadimenol structure.  HED suggests SRRD
refer to the structure in Bayer’s comment letter, or refer to the HED
Residue Chemistry Chapter for triadimenol (S. Ary. 11/17/05. D314891).  

Bayer Comment

Referring to Page 11, Section III.A.I of the Decision Document, Bayer
quotes the Decision memo’s discussion of the Agency’s requirement
for acute and subchronic neurotoxicity studies for triadimenol, and the
requirement of a DNT study based on the results of the acute and
subchronic studies.  Bayer also refers to the 6/20/2006 HED memo that
states the opposite, that the Agency would not require acute and
subchronic neurotoxicity studies for triadimenol.  

HED Response

HED concurs with Bayer that a conclusion had been made that the
triadimefon neurotoxicity studies are adequate to assess triadimenol.
The Triadimefon/Triadimenol Decision Document should be amended to
remove the stated requirement for additional triadimenol neurotoxicity
studies.  (Note that a triadimefon DNT study remains a data
requirement).

Bayer Comment

Referring to Page 19, Section III.A.4b, Table 7, of the Decision
Document, Bayer notes the Agency’s estimated concentrations of
triadimefon and triadimenol in drinking water reflect three applications
and not the agreed upon 2 applications.  The Estimated Environmental
Concentration (EEC) numbers presented in Table 7 of the Decision
Document are 100.8 ppb (acute), 24.94 ppb (annual mean), and 4.07 ppb
(overall mean), and not the corrected (for 2 applications) 93.4 ppb,
19.6 ppb, and 9.0 ppb (respectively).

HED Response

HED concurs with Bayer that the EEC estimates presented in Table 7 are
not the corrected estimates, and would like to confirm as suggested by
Bayer that the correct estimates were, in fact, used for the risk
assessment.  The Triadimefon/Triadimenol Decision Document should be
amended to show the correct concentrations.

Bayer Comment

Referring to Page 19, Section III.A.4b, (Dietary Exposure from Drinking
Water, Groundwater Exposure) of the Decision Document, Bayer notes the
assertion (by the Environmental Fate and Effects Division) that the
potential for groundwater based triadimefon contamination may be greater
than originally supposed.  This assertion is based on the results of a
ground water monitoring study that showed a peak concentration of 25
ppb, compared to the Agency’s model for ground water concentrations
(SciGrow) showing an estimate of 5 ppb.  Bayer also comments that the
correct concentration is 6.6 ppb (0.2 ppb triadimefon and 6.4 ppb
triadimenol) and notes that residues quickly dissipate in the
environment, resulting in actual EEC’s at a lower level than
predicted.  

HED Response

HED will defer to the Environmental Fate and Effects Division (EFED) to
determine the correct concentrations for ground water, and notes that
the HED dietary and aggregate risk assessment relied only on surface
water concentration estimates (since they are higher).  

Bayer Comment

Referring to Page 38, Section III.A.10, (Human Incident Data,
Conclusion) of the Decision Document,  Bayer objects to the conclusions
drawn by HED in regard to worker reactions to triadimefon exposure. 
Referencing both California and Poison Control Center data, HED made the
statement that irritation to skin, eyes, and respiratory passages occur
“readily” among unprotected handlers, or others having substantial
contact.  Citing other human incident databases (PCC, IDS, CDPR, NPIC,
and NIOSH SENSOR, Bayer asserts that the rate of irritation occurrence
in workers is very low, and triadimefon use has been safe for over
twenty years.  

HED Response

HED can concur with Bayer that, overall, the use of triadimefon appears
to be relatively safe, when all human incident databases are
collectively used for assessment.  However, it is also apparent that
exposure to triadimefon can result in irritation to the skin, eyes, and
respiratory passages in humans, as predicted in the acute studies in
test animals.   

Bayer Comment

Referring to Page 66, Section V.C., (Data Requirements for Triadimenol,
Toxicology) of the Decision Document, Bayer notes that acute and
subchronic neurotoxicity studies are listed as data requirements. 

HED Response

HED concurs with Bayer that previous HED documents had concluded that
the existing triadimefon neurotoxicity studies are adequate to assess
triadimenol.  As discussed under Bayer comment 2 (above) HED recommends
that the Triadimefon/ Triadimenol Decision Document be amended to
clarify that acute and subchronic neurotoxicity studies are not
currently required.  (Note that a triadimefon DNT study remains a data
requirement).

Bayer Comment

Referring to Page 66, Section V.C., (Data Requirements for Triadimenol)
of the Decision Document,  Bayer cites the Agency requirement for
“separate metabolism studies with triazole-14C and phenyl-14C labeled
triadimenol applied as a seed treatment to wheat and corn.”  On April
25, 2006 Bayer submitted four triadimenol plant metabolism studies (EPA
MRIDs 46826001–46826004).  With the submission of these studies Bayer
asserts that the metabolism of triadimenol is adequately defined and
asks for a waiver of the requirement for additional metabolism studies
with wheat, corn, or cotton.  Also, referencing a 3/16/06 e-mail from
the Agency (J. Pates to M. Tolliver), Bayer requests further
clarification of the required data, if the waiver is not granted by the
Agency.

HED Response

Triadimefon readily metabolizes to its primary metabolite, triadimenol,
and it is apparent that most pesticidal and toxicological activity is
attributable to triadimenol.  For this reason, some of the data
requirements for triadimenol (notably toxicological data) have been
adequately addressed by a translation of triadimefon data for the
purposes of risk assessment.  However, in the case of residue chemistry
data (data that support tolerance setting for food uses and residue
levels for dietary risk assessment), a translation of data from
triadimefon field trials is not adequate due to the very different types
of application (foliar vs. seed treatment).  

The residue chemistry data for triadimefon is based primarily on field
trial data for apples, grapes, pears, raspberries, and pineapple (food
uses that are now subject to cancellation, except pineapple).  In field
trials for these commodities triadimefon was applied to the foliage to
control rust and mildew diseases.  Triadimefon data does not readily
translate to triadimenol, since triadimenol is applied to seeds, in
advance of planting.  

At this time, HED has not reviewed the plant metabolism studies listed
above, and on that basis cannot make a judgement as to whether the
submitted data is adequate.  

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