Document ID: EPA-HQ-OPP-2016-0661-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2017-02-07T05:00Z

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

EPA Registration Division contact: Tony Kish; 703-308-9443

Taminco US LLC, A subsidiary of Eastman Chemical Company

PP# 6E8495

	EPA has received a pesticide petition (6E8495) from Taminco US LLC, A
subsidiary of Eastman Chemical Company, Two Windsor Plaza, Suite 400,

7540 Windsor Drive, Allentown, PA 18195 requesting, 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

	1. by establishing a tolerance for residues of

	chlormequat chloride in or on the raw agricultural commodities [barley
grain at 3 ppm; wheat grain at 4 ppm; oat grain at 15 ppm; swine-kidney,
bovine, sheep, goat-kidney and cattle-milk at 0.5 ppm; swine-muscle,
bovine, sheep, goat-muscle at 0.2 ppm; swine-liver and bovine, sheep,
goat-liver at 0.15 ppm; poultry-liver and eggs at 0.1 ppm; bovine,
sheep, goat-fat at 0.06 ppm; poultry-muscle at 0.04 ppm; poultry-fat at
0.03 ppm; and swine-fat at 0.02 ppm.] 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

	1. Plant metabolism. [The nature of the residue was studied in cereal
grains, wheat, lettuce, and radish. The parent, chlormequat chloride,
was the only major component found in the residues.]

	2. Analytical method. [Validated LC-MS/MS methods are available for
enforcement purposes for determination of residues of chlormequat
chloride in plants and animal products.]

	3. Magnitude of residues. [The following residue field trials were
conducted to support the import tolerances requested above for
chlormequat chloride. Six field trials were conducted with wheat in
Canada. In Europe, 32 field trials were conducted with wheat, 21 trials
were conducted with barely, and 17 trials were conducted with oats. In
addition, animal feeding studies were conducted to determine the
residues of chlormequat chloride in meat, milk, poultry, and eggs.]

B. Toxicological Profile

	1. Acute toxicity.  [The acute oral LD50 for chlormequat chloride was
522 mg/kg for male and female rats. Therefore, chlormequat chloride is
considered moderately toxic (Toxicity Category II) via the oral route of
exposure. A waiver request was submitted to satisfy the acute
neurotoxicity data requirement.]

	2. Genotoxicty. [Chlormequat chloride was negative for mutagenicity in
several standard in vivo and in vitro assays.]

	3. Reproductive and developmental toxicity. [A prenatal developmental
rat study produced clinical signs such as salivation and
chromorhinorrhea, as well as decreased body weight gain and decreased
food consumption at 90 mg/kg/day (NOAEL 30 mg/kg/day). The highest dose
tested (180 mg/kg/day) caused more severe toxicity in the form of
decreased motor activity, tremors, ataxia, lacrimation, rales, gasping,
body jerks, and increased incidences of chromodacryorrhea. The maternal
NOAEL and LOAEL were 30 mg/kg/day and 90 mg/kg/day, respectively. The
developmental NOAEL was 180 mg/kg/day. In a rabbit prenatal
developmental toxicity study, no adverse effects were noted up to the
highest dose tested (12 mg/kg/day). In a 2-generation reproduction
study, no quantitative or qualitative susceptibility was observed in the
offspring compared to the adult animals. Parental effects beginning at
255 mg/kg/day (HDT) included decreases in body weight and body weight
gains with tremors and hypersensitivity occurring mainly during
lactation (NOAEL 86 mg/kg/day). The reproductive LOAEL was based on
decreased fertility indices also at the highest dose tested (255
mg/kg/day) with the offspring LOAEL (255 mg/kg/day) based on decreased
mean litter size, body weights, and delayed development (auditory canal
opening, eye opening, and pinna unfolding). 

A waiver request was submitted to satisfy the developmental
neurotoxicity data requirement.]

	4. Subchronic toxicity. [Decreases in body weight and body weight gain
were consistently observed in the available oral repeat dosing studies
in rats and dogs. Dogs showed decreased body weight gains (males), as
well as clinical signs of toxicity including salivation (both sexes),
vomiting (females), and diarrhea (males) at 10 mg/kg/day (NOAEL 5
mg/kg/day) in the chronic dog study. Decreased body weight and body
weight gains were the only adverse effects observed in the 90-day
dietary rat study at 190 mg/kg/day (NOAEL 61 mg/kg/day). A waiver for
the 90-day neurotoxicity data requirement was previously granted by the
Agency.]

	5. Chronic toxicity. [Long-term feeding studies (carcinogenicity)
produced decreased body weights and decreased food consumption in rats
(125 mg/kg/day) and in mice (363 mg/kg/day). No potential signs of
carcinogenicity were noted.]

	6. Animal metabolism. [The pharmacokinetic behavior of chlormequat
chloride was evaluated in two studies. In each study, more than 85% of
the test substance was excreted to more than 85% within the urine. Most
of the radioactively was excreted between two and four hours. The
highest residues were found in the liver and kidney]

	7. Metabolite toxicology. [NA-Remove.]

	8. Endocrine disruption. [Per EPA’s 2007 Human Health Risk Assessment
for the Chlormequat Chloride RED, the Agency concluded that there is no
estrogen-, androgen-, and/or thyroid-mediated toxicity observed in the
available toxicity studies with chlormequat chloride.]

C. Aggregate Exposure

	1. Dietary exposure. [DEEM-FCID v.4.02 was used to estimate acute and
chronic dietary exposure. The acute toxicological endpoint for acute
exposure is 0.09 mg/kg/day, including an extra 10x safety factor
required by EPA because an acute neurotoxicity study is not currently
available. Acute exposure to Children 1-2 years at the 95th percentile
is 0.010529 mg/kg/day, representing 11.7% of the acute RfD. (The 95th
percentile of exposure is appropriate because 100% crop treated was
assumed.) The chronic toxicological endpoint is 0.05 mg/kg/day. The most
highly exposed group, Children 1-2 years, is exposed to 0.003447
mg/kg/day, representing 6.9% of the chronic RfD.]

	i. Food. 

	ii. Drinking water. [There will be no potential contamination of
drinking water from the proposed import tolerance uses. However, there
currently are products containing chlormequat chloride that are used on
indoor ornamentals and outdoor ornamentals in containers. EFED conducted
a Tier 1 assessment during re-registration of chlormequat chloride with
many conservative assumptions and found the EDWCs to be acceptable,
based upon the acute toxicity endpoint of 0.9 mg/kg/day at the time.
However, with the extra 10x added to the acute toxicity endpoint the
dietary exposure through drinking water based on the Tier 1 EDWCs will
not be acceptable.

In the 2007 Registration Eligibility Decision (RED) for chlormequat
chloride, EPA discussed the reasons that the models and scenarios used
in their drinking water assessment were developed to simulate pesticide
applications in open agricultural fields and not specifically for
containerized ornamentals and bedding plants in nurseries and shade
houses, which generally are not present in large contiguous acreages.
EPA’s reasons for determining that drinking water exposure from use on
containerized nursery plants is minimal can be found on page 9 of the
RED (US EPA, OCSPP, EPA 738-R-07-014, 2007, OPP-2007-0968). 

As part of the RED, EPA required changes to the label to further ensure
limited exposure to drinking water and non-target organisms. Label
changes were implemented for ornamental uses in September, 2007,
including a prohibition against using mechanical (tractor-drawn) ground
boom multi-nozzle sprayer applications. Outdoor use is limited to
targeted hand wand applications so that less of the pesticide is
available for potential runoff and there is less drift with associated
potential for off-target exposures.  Furthermore, applicators using hand
wands do not treat large contiguous acreages in a short time frame as is
typical for tractor-mounted ground booms.  

Other reasons given by EFED as to why their exposure estimate was overly
conservative include:

There is no standard Percent Cropped Area for nurseries/shadehouses, so
their assessment was based on the assumption that an entire 178-ha
watershed consists of containerized nursery/shadehouse ornamentals all
of which are treated simultaneously with chlormequat chloride.

The model assumes 100% of the product is absorbed into the ground and/or
runs off (i.e., none is absorbed by the plants in containers, all
product makes ground contact).

The standard Tier 1 models used in their assessment were developed to
simulate pesticide applications in open agricultural fields and not
specifically for containerized ornamentals in nurseries/shadehouses. The
impact of rainfall and corresponding pesticide transport is likely
dampened due to the use of containers and/or shade covers relative to
open agricultural fields, which also leads to a protective assessment.  

There is a relatively low amount of chlormequat chloride applied per
year on a nationwide basis.

In addition, the DEEM-FCID model assumes that every drop of water that
is consumed, whether it comes from your tap, a bottle, a restaurant,
food product, or a water purifier, contains a residue of chlormequat
chloride. This is an extreme overestimate for a low use chemical like
chlormequat chloride.]

	2. Non-dietary exposure. [NA-Remove.]

D. Cumulative Effects

	[NA-Remove.]

E. Safety Determination

	1. U.S. population. [The potential exposure to the most highly exposed
group, Children 1-2 years, from consuming wheat, oat, barley, meat,
milk, poultry and egg products, all of which are assumed to contain
chlormequat chloride, is very small, at less than 12% of the acute RfD
of 0.09 mg/kg/day (which includes the added 10x safety factor). Chronic
exposure to the same group is also very small, at less than 7% of the
chronic RfD of 0.05 mg/kg/day. The realistic potential exposure to
chlormequat chloride through drinking water is also negligible.
Therefore, there is reasonable certainty of no harm to any population
group as a result of granting the requested import tolerances.]

	2. Infants and children. [The potential exposure to the most highly
exposed group, Children 1-2 years, from consuming wheat, oat, barley,
meat, milk, poultry and egg products, all of which are assumed to
contain chlormequat chloride, is very small, at less than 12% of the
acute RfD of 0.09 mg/kg/day (which includes the added 10x safety
factor). Chronic exposure to the same group is also very small, at less
than 7% of the chronic RfD of 0.05 mg/kg/day. The realistic potential
exposure to chlormequat chloride through drinking water is also
negligible. Therefore, there is reasonable certainty of no harm to any
population group as a result of granting the requested import
tolerances.]

F. International Tolerances

[Comparison between U.S. proposed tolerances and harmonized EU and CODEX
MRLs

Commodity	Proposed tolerances for the U.S. (mg/kg)	EU Recommended
(mg/kg)	Existing CODEX (mg/kg)

Barley grain	3	3	3

Oats grain	15	15	15

Wheat grain	4a	4a	4

Swine-muscle	0.2	0.2	0.2

Swine-fat	0.02	0.02	--

Swine-liver	0.15	0.15	0.15

Swine-kidney	0.5	0.5	0.5

Bovine, Sheep, Goat-muscle	0.2	0.2	0.2

Bovine, Sheep, Goat-fat	0.06	0.06	--

Bovine, Sheep, Goat-liver	0.15	0.15	0.15

Bovine, Sheep, Goat-kidney	0.5	0.5	0.5

Poultry-muscle	0.04	0.04	0.04

Poultry-fat	0.03	0.03	--

Poultry-liver	0.1	0.1	0.1

Cattle-milk	0.5	0.5	0.5

Eggs	0.1	0.1	0.1

a When all EU data for wheat were used, the OECD calculator recommended
an MRL of 8.0 mg/kg.  However, the EU analysis excluded two outliers
from the data set used for the calculation, and the same outliers were
removed from Taminco’s calculations.]

 PAGE   

 PAGE   5