 

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  >

<EPA Registration Division contact: [P.V. Shah, 703-308-1846]>

 

<INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green, i.e., “[insert company
name],” with the information specific to your action.>

<TEMPLATE:>

<[Dow AgroSciences, LLC]>

<8E7504>

<	EPA has received a pesticide petition (8E7504) from [Dow AgroSciences,
LLC], [9330 Zionsville Rd, Indianapolis, IN, 46268] proposing, pursuant
to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA),
21 U.S.C. 346a(d), to amend 40 CFR part 180.>

<	 to establish an exemption from the requirement of a tolerance for>

<	[2-Propanol, 1,1’,1”-nitrilotris-(TIPA) under 40 CFR 180.910 when
used as an inert ingredient for use as a neutralizer in a pesticide
formulation].  EPA has determined that the petition contains data or
information regarding the elements set forth in section 408 (d)(2) of 
FDDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of the
petition. Additional data may be needed before EPA rules on the
petition.>

<A. Residue Chemistry [This information is not available, nor required
for the establishment of a tolerance exemption.]

>

<	1. Plant metabolism. [omit -per above, not needed.]>

<	2. Analytical method. [omit -per above, not needed.]>

<	3. Magnitude of residues. [omit -per above, not needed.]>

<B. Toxicological Profile [TIPA belongs to the general class of
alkanolamines which typically exhibit low acute oral and dermal
toxicity, but also display eye and skin irritancy.  EPA has already
reviewed and granted 40 CFR 180.920 tolerance exemptions for other
similar alkanolamines.]>

<	1. Acute toxicity.  [TIPA exhibits low acute toxicity; the acute oral
LD50 is 5994 mg/kg/day and the acute dermal value is >5000 mg/kg/day. 
TIPA is a known eye irritant and can cause moderate skin irritation. 
Based on the acute LD50 values, no acute reference dose is needed for
risk assessment.]>

<	2. Genotoxicity. [For TIPA, the results of three different in vitro
mutagenicity tests were negative.]>

<	3. Reproductive and developmental toxicity. [In a 1-generation
reproductive toxicity test with TIPA in rats, no adverse clinical,
histological, or reproductive effects were noted, and the NOAEL was
reported to be >609 mg/kg/day for males and 700 mg/kg/day for females,
the highest dose levels tested.  In addition, repeated-dose toxicity
studies on TIPA have failed to identify any effects in the gonads of
male or female rats or dogs.

To assess the developmental toxicity for TIPA, surrogate data is
available from the related diisopropanolamine analogue, DIPA.  An OECD
414 study for developmental toxicity with DIPA found no
treatment-related effects on the incidence of fetal alterations at dose
levels up to 1000 mg/kg/day.  The reported NOEL for maternal and
developmental toxicity was 1000 mg/kg/day.

Given the low developmental toxicity and the lack of developmental
effects, an FQPA Safety Factor of 1X is proposed for TIPA.]>

<	4. Subchronic toxicity. [For TIPA, a 90-day repeat dose study in dogs
yielded at NOAEL of >272 mg/kg/day based on the 7500 ppm highest study
dose.  No treatment related effects were noted for any test group.  This
repeat dose study is used to propose the chronic reference dose for risk
assessment.]>

<	5. Chronic toxicity. [A 2-yr study in rats with 2% TIPA revealed no
evidence of increased liver foci.  Together with the negative
genotoxicity studies for TIPA, these data support the conclusion that
the material is not likely to be carcinogenic.  TIPA is not listed by
ACGIH, IARC, NTP, or CA Prop 65.]>

<	6. Animal metabolism. [Orally administered TIPA was rapidly and
extensively absorbed; a minimum of 83%.  Virtually all was rapidly
excreted primarily as unchanged TIPA in the urine.]>

<	7. Metabolite toxicology. [This information is not available, nor
required for the establishment of a tolerance exemption.]>

<	8. Endocrine disruption. [TIPA is not compatible with direct endocrine
activity on the basis of structural activity relationships.  In
addition, there is no histopathological or behavioral evidence of an
endocrine function in any toxicity evaluations of TIPA or its close
analogue (DIPA) conducted in laboratory animals.  The TIPA
one-generation toxicity study conducted in rats included pre-mating,
mating period, gestation, lactational and post-lactation dosing.]>

<C. Aggregate Exposure >

<	1. Dietary exposure. [Based on the low acute toxicity, no acute
reference dose is established.  Based on the 90-day studies for TIPA the
following is proposed: chronic oral – NOAEL of 272 mg/kg bw/day with
UF=100 for a cRfD of 2.7 mg/kg/day = cPAD (chronic population adjusted
dose).]>

erts within the Dietary Exposure Evaluation Model software with the Food
Commodity Intake Database (DEEM-FCID™, Version 2.14).  Exposure from
food, animal commodities and drinking water are included.  Children 1-2
years old are found to be the most exposed subpopulation with an
estimated exposure of 0.425 mg/kg/day for drinking water and food from
EPA IDEEM calculations.

The dietary (food plus drinking water) exposures for TIPA are expressed
as a percentage of the proposed cPAD for the general US population and
children 1-2 years old.  Based on I-DEEM screening level calculations,
the chronic dietary exposures are estimated to be 1.4% of the cPAD for
the general U.S. population and <5% of the cPAD for children 1-2 years
old.]>

<	ii. Drinking water. [Drinking water estimates have been included in
the I-DEEM model.]>

<	2. Non-dietary exposure. [No exposure to TIPA is expected through
residential herbicidal products.  Some exposure to TIPA from
non-pesticide uses may occur via coatings of paper, personal care
products, lubricants, pigments, or plastics.  Comparison of the
predicted exposure from IDEEM to the NOAEL value of 272 mg/kg/day for
TIPA results in an MOE of >2000 for children 1-2 years of age.  MOE
values for other subpopulations are higher.  Because the MOE values from
the dietary assessment range from >2000 to over 10,000, the large
additional margins of safety above 100 is deemed adequate to cover any
other aggregate exposure from non-dietary or post harvest uses.]

>

<D. Cumulative Effects>

<	[For the purposes of this tolerance action, it is not assumed that
TIPA has a common mechanism of toxicity with other substances.]>

<E. Safety Determination>

<	1. U.S. population. [For the general population, the estimated
exposure is 1.4% of the cRfD. A reasonable certainty of no harm has been
established for the proposed use of TIPA as an inert in pesticide
formulations for the general population.]>

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 as well as registration decisions for TIPA-herbicide salts which
indicate no developmental or reproduction concerns.  Estimated exposure
for children represents <5 % of the proposed cPAD; a reasonable
certainty of no harm has been established for children.]>

<F. International Tolerances>

<	[Omit – not applicable.  There are no known tolerances.]>

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