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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [insert name and telephone number with area code]

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:

Clariant Corporation

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from Clariant

Corporation, 4000 Monroe Road, Charlotte, NC 28205 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)

1. NA-Remove by establishing a tolerance for residues of

2. to establish an exemption from the requirement of a tolerance for

D-Glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivs. (CAS Reg. No. 1591782-

62-5) under 40 CFR § 180.910 when used as an inert ingredient (surfactant) not to exceed

40% in pesticide formulations applied pre- and post-harvest to all raw agricultural

commodities. 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. [NA-Remove. No specific plant metabolism data is available, nor

is it required for the establishment of a tolerance exemption.]

2. Analytical method. [NA-Remove. An analytical method is not required for

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enforcement purposes since the Agency is establishing an exemption from the requirement of

a tolerance without any numerical limitation.]

3. Magnitude of residues. [NA-Remove. Information regarding the nature and

magnitude of chemical residues resulting from the use of this inert ingredient is not

required for the establishment of a tolerance exemption.]

B. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, and

reliability as well as the relationship of the results of the studies to human risk. EPA has

also considered available information concerning the variability of the sensitivities of major

identifiable subgroups of consumers including infants and children.

1. Acute toxicity. C8-10-Glucamide exhibits moderate toxicity by the oral route and

no evidence of systemic toxicity via dermal or inhalation exposure under normal use

conditions. The compound is severely irritating to the eyes but non-irritating to the skin

and non-sensitizing.

2. Genotoxicty. C8-10-Glucamide showed no evidence of mutagenicity in bacteria or

mammalian cells or induction of micronuclei in mice following oral exposure.

3. Reproductive and developmental toxicity. Oral administration of C8-10-Glucamide.

to rats in a guideline complainant reproductive and developmental screening study was

without adverse effects on systemic, reproductive or developmental endpoints up to the

highest dose tested (312.5 mg/kg bw/day). In addition, data on a structural analog, C12-14-

Glucamide, produced no evidence of reproductive and developmental toxicity when

examined in a one-generation reproductive study and FDA Segment II teratology study,

both in rats, with no observed adverse effect levels (NOAELs) for these endpoints of 344.9

and 363 mg/kg bw/day, respectively. The parental and maternal NOAELs for these two

studies were 147.8 and 150 mg/kg bw/day, respectively.

4. Subchronic toxicity. Oral administration of C8-10-Glucamide to rats for 28-days

resulted in a NOAEL of 250 mg/kg bw/day. Subacute and subchronic oral studies on the

read-across compounds (C12-14-Glucamide) in rats had no observed effect levels (NOELs) of

100 and 200 mg/kg bw/day, respectively. Furthermore, the systemic NOAEL from the onegeneration study in rats for the read-across compound was 147.8 mg/kg bw/day. These

repeated dose toxicity studies, on either compound, did not indicate a clear target organ

with main, consistent effects on body weight and food consumption, stress related findings,

and findings related to the irritative nature of the compound/dosing regimen employed

(bolus gavage dosing) including clinical findings and effects on the non-human relevant rat

forestomach.

5. Chronic toxicity. There is no evidence that the C8-10-Glucamide would be a

concern for chronic toxicity based on the limited effects observed in the repeated dose

studies. In addition, no concern is noted for carcinogenicity based on the observation that

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the compound lack structural alerts for genotoxicity via DNA reactivity (covalent binding)

or non-genotoxic mechanisms. The prediction that the compounds lack of structural alerts

is supported by the data (negative findings in genotoxicity assays). The conclusions

regarding C8-10-Glucamide is further supported by the lack of mutagenicity observed in

studies with C12-14-Glucamide. Lastly, analysis of the structures using in silico programs

indicates a lack of concern for carcinogenicity.

6. Animal metabolism. C8-10-Glucamide is expected to undergo enzymatic hydrolysis

of the amide linkage catalyzed by fatty acid amide hydrolase. The resulting metabolites are

meglumine, an amino sugar (normally derived from sorbitol) and fatty acids. Meglumine

would be expected to be rapidly excreted in the urine and the fatty acids are metabolized

via the general ß-oxidation pathway to generate acetyl-CoA. The projected metabolism

was evaluated using accepted in silico programs. In addition, data are available regarding

absorption, distribution, metabolism and elimination (ADME) of a surrogate Glucamide

(C12). These data indicate oral absorption of over 80% and dermal absorption of less than

1% of the administered dose; the major route of excretion is via the urine.

7. Metabolite toxicology. No concern is noted for the metabolites of C8-10-Glucamide.

Meglumine itself is acutely practically non-toxic, is not irritant to skin, not a skin sensitizer,

is considered non-genotoxic, and is mainly unchanged rapidly excreted from the body while

fatty acids are a normal component of the diet.

8. Endocrine disruption. C8-10-Glucamide was negative for interaction with or

binding to estrogen receptors as evaluated in the Estrogen Receptor Binding (Rat Uterine

Cytosol, OPPTS 890.1250) assay. In addition, repeated dose studies did not indicate any

adverse findings with regard to endocrine related parameters (histopathological or

functional observations with regard to gonads, including fertility and maintenance of

pregnancy as well as development of offspring). Furthermore, in silico evaluations of the

target and source compound using DEREK found no concern for oestrogenicity, thyroid

toxicity, and adrenal gland toxicity. As such, endocrine disruptive potential therefore is of

low concern for C8-10-Glucamide.

C. Aggregate Exposure

1. Dietary exposure. The exposures numbers used to calculate the %cPAD are

taken from the EPA review of similar surfactants, the Alkyl Alcohol Alkoxylates

(AAA), which have similar use patterns to those covered in this petition.

Exposure

(mg/kg/day)

100% Crop

Treated,

40% Surfactant

cPAD

1.50% cPAD

General U.S. Population 0.153207 10

Infants (< 1 year old) 0.317666 21

Children 1-2 years old 0.499204 33

Children 3-5 years old 0.369566 25

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Children 6-12 years old 0.204248 14

Youth 13-19 years old 0.115298 8

Adults 20-49 years old 0.115521 8

Adults 50+ years old 0.121661 8

Females 13-49 years old 0.116311 8

i. Food. The dietary exposure above is the result of modeling to represent residues

on food with 100% crop treated with a maximum concentration of 40% surfactant in the

formulation. This is a worst case scenario, since it is expected that these materials will be

used at a maximum percent crop treated of 1%.

ii. Drinking water. In their review of another group of inerts, the Alkyl Alcohol

Alkoxylates, EPA modeled expected drinking water concentrations and considered that the

maximum concentration would be 100 parts per billion. This result is included in the

exposure estimates in the dietary exposure table.

2. Non-dietary exposure. In examining aggregate exposure, section 408 of the

FFDCA directs EPA to consider available information concerning exposures from the

pesticide residue in food and all other non-occupational exposures, including drinking

water from ground water or surface water and exposure through pesticide use in gardens,

lawns, or buildings (residential and other indoor uses). Because this petition is for use in

pesticide formulations pre- and post-harvest to crops, the only expected exposure will be

dietary.

D. Cumulative Effects

We have not found a common mechanism of toxicity finding regarding C8-10-

Glucamide and any other substances.

E. Safety Determination

1. U.S. population. Based on these risk assessments, there is a reasonable certainty

that no harm will result to the general population or to infants and children from aggregate

exposure to residues of C8-10-Glucamide.

2. Infants and children. Based on these risk assessments there is a reasonable

certainty that no harm will result to the general population or to infants and children from

aggregate exposure to residues of C8-10-Glucamide.

F. International Tolerances

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Clariant Corporation is not aware of any country requiring a tolerance for the

petitioned substances nor have any CODEX Maximum Residue Levels been established for

any food crops at this time.

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