Document ID: EPA-HQ-OPP-2013-0590-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-10-25T04:00Z

<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:>

<[Technology Sciences Group Inc.]>

<[IN-10622Insert petition number]>

<	EPA has received a pesticide petition ( ) from [Technology Sciences
Group Inc.], [1150 18th Street NW Suite 1000, Washington DC] 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.>

<(Options (pick one)>

<	>

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

<	coco alkyl dimethyl amines

] 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. [NA-Remove]>

<	2. Analytical method. [NA-Remove]>

<	3. Magnitude of residues. [NA-Remove]>

<B. Toxicological Profile>

<	1. Acute toxicity.  [The oral LD50 in rats was determined to be
between 1000 and 1300 mg/kg for females.> An acute dermal toxicity assay
performed on the coco alkyl dimethyl amines was reported in rabbits. The
LD50 was determined to be 4.29 mL/kg bw, equivalent to 3385 mg/kg bw. 
No studies of acute inhalation toxicity were identified for coco alkyl
dimethyl amines. An LC50 of >0.6 mg/L was derived in rats for the
structurally similar hydroxylated amine.  The LC50 of >0.6 mg/L places
this compound into acute inhalation toxicity Category III. Coco alkyl
dimethyl amines were corrosive to rabbit skin.
N,N-dimethyl-1-hexadecanamine, N,N-dimethyl-1-tetradecanamine, and
N,N-dimethyl-1-tetradecanamine are compounds that constitute coco alkyl
dimethyl amines. All three of these compounds were irritating to rabbit
eyes.]

 

  

<	2. Genotoxicity. [ Ames assays were reported on three dimethyl alkyl
amines that together comprise a large percentage of coco alkyl dimethyl
amines. There was no evidence of mutagenicity under the conditions of
this study for any of the three compounds.    

An in vivo mammalian erythrocyte micronucleus test of a commercial
product containing ~ 70 % C12-, 25 % C12-14- and 5 %
C16-dimethylalkylamine) was conducted. Significant increases in the
percentage of micronucleated polychromatic erythrocytes in treated mice
were not found. ]

>

<	3. Reproductive and developmental toxicity. [A
reproductive/developmental toxicity screening study (OECD TG 421) of
N,N-dimethyl-1-dodecanamine (CAS #112-18-5) was conducted in rats.
Animals received gavage doses of 0, 50, 150, 300, or 450 mg/kg bw/day of
the test compound for 14 days prior to mating, 14 days during mating,
and for females, during pregnancy and lactation.  One male and two
females from the highest dose group died by day 5 and this group was
discontinued. In the 300 mg/kg bw group, one male and six females died
and only one pup was born alive. At the 150 mg/kg bw dose, two dams died
and two dams did not deliver pups. The mean post-implantation loss was
significantly higher than the controls (50.4% vs. 13.3%) and the mean
viability index was significantly lower (36.9 % vs. 99.3%).The birth
weight of male pups was significantly lower than that of controls.
Maternal behavior was also affected, as evidenced by an unsevered
umbilical cord, cannibalization, and lack of care of pups.  No
reproductive or developmental effects were observed in the absence of
maternal toxicity. The NOAEL for systemic toxicity and for
reproductive/developmental toxicity was determined to be 50 mg/kg
bw/day.] 

>

<	4. Subchronic toxicity. [A repeat dose study in rats conducted
according to OECD Test Guideline 407 was carried out on
N,N-dimethyl-1-dodecanamine. Animals received gavage doses of 0, 50,
150, or 300 mg/kg bw/day N,N-dimethyl-1-dodecanamine for 28 days.  At
the highest dose, three of five females died; nothing significant was
observed in the histopathology exams of these animals. At the middle
dose, animals displayed mild adverse behavior, including snout rubbing,
but no effects on body weight, food consumption, hematology, clinical
biochemistry, urinalysis or organ weights. A NOAEL of 50 mg/kg/day was
determined in this study.]

>

<	5. Chronic toxicity. [Chronic studies are not available for coco alkyl
dimethyl amines]>

<	6. Animal metabolism. [Studies specific to the metabolic pathway or
other toxicokinetic properties of coco alkyl dimethyl amines in mammals
were not identified in a search of the literature. The primary metabolic
pathway of coco alkyl dimethyl amines is proposed based on its
characteristic molecular structure and known metabolic pathways for
structurally similar compounds. In mammals, hepatic dealkylation readily
occurs with secondary and tertiary amines with the methyl groups leaving
preferentially. Oxidation of the alpha carbon via cytochrome P450, forms
a carbinolamine intermediate that will spontaneously cleave to form a
secondary amine and carbonyl compound. Subsequent dealkylation of the
secondary amine will take place at a slower rate]>

<	7. Metabolite toxicology. [No metabolites of toxicological concern
have been identified.]>

<	8. Endocrine disruption. [Toxicity related to endocrine disruption was
not observed in the currently available database and the recent OECD 421
testing.]>

<C. Aggregate Exposure>

<	1. Dietary exposure. [Concentrations will be less than 0.5% in food 
use applications of coco alkyl dimethyl amine.  As a result, humans may
be exposed to very low residue levels through the diet from food and
water.] >

<	i. Food. [Exposure to residues in food are not anticipated to be of
toxicological concern because the coco alkyl dimethyl amine biodegrades
readily in the environment after application, and is of low general
toxicity. Estimated dietary exposure was  based on the assumption that
the inert  will be used in all agricultural pesticides at a proposed
limit of 0.5% of the  spray volume. The highest exposed subpopulation
was children age 1-2 years old, which had an estimated average exposure
of 0.0186 mg/kg/day, while the estimated average exposure of the general
population was 0.00496 mg/kg/day. Thus, potential dietary exposure will
be low and toxicity is generally low, such that a safety finding can be
concluded for exposures via the diet.] >

<	ii. Drinking water. [Exposure via drinking water is not expected to be
significant.  Exposure via the drinking water was estimated assuming a
concentration of 100 ppb.  This estimated exposure via drinking water
did not contribute significantly to the overall dietary exposure.  Thus,
potential drinking water exposure will be low, such that a safety
finding for coco alkyl dimethyl amine can be concluded for exposures via
the drinking water and the diet combined.]>

<	2. Non-dietary exposure. [Workers may experience dermal exposure
during application of pesticide products if personal protective clothing
is not worn. Humans may also be exposed through the use of non-food use
pesticidal products. Concentrations of coco alkyl dimethyl amine are
less than 1.0% and dermal exposure will be limited by the irritation
potential of the ingredient. Systemic toxicity of coco alkyl dimethyl
amine is low.  Thus, a safety finding for coco alkyl dimethyl amine  can
be concluded for non-dietary exposures.] >

<D. Cumulative Effects>

<	[There are no available data or other reliable information that
suggests that any toxic effects produced by coco alkyl dimethyl amine
would be cumulative with those of any other chemical compounds. Coco
alkyl dimethyl mine does not appear to produce toxic metabolites in
common with other substances. It is assumed that coco alkyl dimethyl
amine does not share a common mechanism of toxicity with other
pesticidal substances.]>

<E. Safety Determination>

<	1. U.S. population. [There is a reasonable certainty that no harm to
humans will result from the use of coco alkyl dimethyl amine as an inert
ingredient in pesticide products. The main effects of oral exposure to
coco alkyl dimethyl amine are behavioral effects and developmental
toxicity at maternally toxic dose levels . A NOAEL of 50 mg/kg/day
following both 28-day repeat dose testing and developmental/reproductive
toxicity screening was used to derive the Reference Dose. Intraspecies
and interspecies uncertainty factors were combined for a total
uncertainty factor of 100.  For the total US population, the estimated
chronic dietary exposure from food and drinking water for coco alkyl
dimethyl amine, calculated as 0.5% of all agricultural formulations, is
1.0% of RfD.] >

<	2. Infants and children. [A developmental/reproductive toxicity
screening study n rats demonstrates that slight developmental effects
occurred only at maternally toxic doses. An RfD of 0.5 mg/kg/day was
derived for coco alkyl dimethyl amine. The estimated chronic dietary
exposure from food and drinking water was highest (3.7% of RfD) for
children aged 1 to 2 years old.]>

<F. International Tolerances>

<	[NA-Remove]>

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