Document ID: EPA-HQ-OPP-2008-0528-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-07-31T04:00Z

Petition for an exemption from the requirement of a tolerance for
residues of products containing the active ingredient “Extract of
Chenopodium ambrosioides near ambrosioides” in or on all agricultural
commodities

AUTHOR

Nicholas Wright

SUBMITTED BY 

AgraQuest Inc. 

1540 Drew Avenue

Davis, California 95618

(EPA Co. No. 69592)

DATE

December 3, 2007

 

TABLE OF CONTENTS

Section A:	Product Name and Proposed Use
Practices………………………3

Section B:	Product Identity /
Chemistry……………………………………...4	

Section C:	Mammalian Toxicological
Profile………………………………..6

Section D:	Aggregate
Exposure………………………………………………8

Section E:	Cumulative
Effects……………………………………………....10

Section F:	Safety
Determination………………………………………….....11

Section G:	Effects on Immune and Endocrine
Systems……………………..12

Section H:		Existing
Tolerances………………………………………………13

Section I:		International
Tolerances………………………………………….14

SECTION A: PRODUCT NAME AND PROPOSED USE PRACTICES

This petition is for an exemption from the requirement of a tolerance of
residues of products containing the biochemical pesticide active
ingredient “Extract of Chenopodium ambrosioides near ambrosioides.” 

Extract of Chenopodium ambrosioides near ambrosioides is the active
ingredient in the proposed formulated end-use products Facin 25EC and
Keynote 25EC.   Both products are intended for use as a contact
insecticide / acaricide for the control or suppression of  foliage
feeding pests including lepidopterous larvae, aphids, mites, whiteflies,
mealy bugs, leafminers, thrips, lygus bugs, scale, leaf hoppers, and
certain psyllids.   Facin 25EC is intended for use on ornamentals in
greenhouses and nurseries (application for registration is currently
pending at EPA), and Keynote 25EC is intended for use on a variety of
agricultural crops.  End-use products consist of an emulsifiable
concentrate formulation that is mixed with water and applied as a foliar
spray with conventional application equipment. Products would be applied
at a maximum application rate of 4 quarts of the 25EC formulation per
acre. In a typical volume of 100 gallons of water per acre this is
equivalent to a 1% emulsifiable concentrate solution (0.25% active
ingredient). 

SECTION B:  PRODUCT IDENTITY / CHEMISTRY

1.	Identity of the pesticide and corresponding residues.

Extract of Chenopodium ambrosioides near ambrosioides is a biochemical
pesticide active ingredient composed of a modified essential oil extract
of Chenopodium ambrosioides near ambrosioides. Chenopodium is a common
plant in the US, Mexico, and Central America and is used as a spice and
herb in cooking.  Extract of Chenopodium ambrosioides near ambrosioides
is a complex mixture of terpenes and terpene derivatives, including
three main terpenes making up over 70% of the mixture, that is subjected
to a processing step that removes a toxic component, ascaridole, from
the finished extract. Extract of Chenopodium ambrosioides near
ambrosioides is a contact insecticide/acaricide. The mode of action has
not been completely determined, however, based on laboratory and field
trial observations the primary mechanism for controlling and suppressing
insect pests is thought to involve the degradation of the cuticle of
soft-bodied insects and mites after contact. 

2.	Magnitude of residues at the time of harvest and method used to
determine the residue. 

No residues of Extract of Chenopodium ambrosioides near ambrosioides are
expected to occur at the time of harvest because the components of the
active ingredient are volatile and dissipate soon after application. 
Residue studies have been previously submitted to support the currently
pending registration application for use on ornamentals in greenhouses
and nurseries.  Data submitted clearly demonstrates that the active
ingredient components are not detectable shortly after application, even
at 2 - 4X the maximum label rate, and as such Extract of Chenopodium
ambrosioides near ambrosioides will not be present or detectable at the
time of harvest.  

Results of a residue decline study conducted by AgraQuest Inc. with the
25EC product showed that residues of the three major terpene components
of the active ingredient declined to non-detectable levels within 10
minutes after foliar applications on Primrose at 4X the recommended
application rate (MRID 47209101). The product was applied three times
using an application rate 4X the a.i. concentration listed on label.
Plants were sampled at specified intervals after each application.
Consistent results were obtained after each application. Essentially, by
the time the leaves have dried there is no detectable residual product.
Thus, the potential for any post-application oral exposure is virtually
non-existent and supports the argument that exposure to residual product
is of minimal concern. 

Results of the Primrose study are consistent with and supported by a
second residue decline study submitted by AgraQuest Inc. on application
of the 25EC product to tomatoes (MRID 46858903).  The tomato study
demonstrated rapid dissipation of the major terpene components in the
active ingredient at 0, 3, 6, 12, and 24 hr post-treatment. All
constituents were less than the limit of quantitation (<LOQ) of 0.01
mg/kg at all time intervals. The product was applied four times using an
application rate 2X the a.i. concentration listed on label. In summary,
results of both the Primrose study and the Tomato study demonstrate that
multiple applications of the 25EC end-use product at 2-4X label rates
result in no detection of residue shortly after application and no
accumulation of residues over multiple applications.  

on the plant leaf samples. A limit of quantitation (LOQ) of 1.0 μg/ml
(ppm) was determined for each of the three active ingredient components.
The estimated limit of detection (LOD) was ~ 0.01 μg/ml for each
component. 

The procedure used for residue detection and identification in the
residue decline study on tomatoes was a GC/MS method. A limit of
quantitation (LOQ) of 0.01 mg/kg (ppm) was determined for each of the
three active ingredient components. The estimated limit of detection
(LOD) was 0.005ng for each component. 

3.	A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. 

An analytical method for residues is not applicable.  It is expected
that, when used as proposed, Extract of Chenopodium ambrosioides near
ambrosioides would not result in detectable residues or residues that
are of toxicological concern.   

SECTION C: MAMMALIAN TOXICOLOGICAL SUMMARY

Studies to evaluate the safety to mammals have been conducted on the
technical grade active ingredient of Extract of Chenopodium ambrosioides
near ambrosioides (referred to below as “tgai” and on the formulated
end-use products (25% emulsifiable concentrate referred to below as
“25EC”), and are summarized as follows:

1.	Acute Oral Toxicity (OPPTS 870.1100):  Acute Oral LD50s in rats were
2,000 – 5,000 mg/Kg and >5,000 mg/Kg in studies with the tgai and the
25EC, respectively. (MRIDs 46396207 and 46396105, respectively)

2.	Acute Dermal Toxicity (OPPTS 870.1200):  The dermal LD50  in rats for
both the tgai  and the 25EC was greater than 5,000 mg/kg.  No clinical
signs were noted in any of the test animals and no gross abnormalities
were noted at necropsy. (MRIDs 46396208 and 46396106, respectively)

Acute Inhalation Toxicity (OPPTS 870.1300):  In acute inhalation
toxicity limit tests no adverse effects or deaths were seen in rats
exposed for four hours to the tgai and the 25EC as an aerosol at a
concentration of 2.03 mg/L and 2.02 mg/L, respectively. No gross
abnormalities were noted at necropsy. The LC50 for the tgai and the 25EC
was > 2.03 mg/L and > 2.02 mg/L, respectively. (MRIDs 46396209 and
46396107, respectively)

Primary Eye Irritation (OPPTS 870.2400):  In an eye irritation study on
rabbits, the tgai was classified as mildly to moderately irritating to
the eye.  The tgai did not cause corneal opacity or iritis in any of the
treated animals, while conjunctival irritation in one animal was
resolved by day 4. In a similar test the 25EC showed no corneal opacity
or iritis in any of the treated animals, while conjunctival irritation
in one animal was resolved by 24 hours. The 25 EC was classified as
minimally to mildly irritating. (MRIDs 46396210 and  46396108,
respectively)

Primary Dermal Irritation (OPPTS 870.2500):  In a skin irritation study
on rabbits, the tgai was classified as moderately irritating to the
skin.  One hour after patch removal, well-defined erythema was noted on
all rabbits, but was reduced to very slight erythema on two rabbits by
24 hours and on the third rabbit by 72 hours. The very slight erythema
persisted through the end of the study (14 days). In a similar study,
the 25EC was classified as moderately irritating to the skin. All
rabbits had very slight edema one hour after patch removal, with
resolution on two rabbits by 72 hours and on the third by day 7. (MRIDs
46396211 and 46396109, respectively)  

	

6. 	Dermal Sensitization (OPPTS 870.2600): In a dermal sensitization
study in Guinea pigs (Buehler method), the tgai was classified as a
dermal sensitizer. After three consecutive inductions, faint erythema
and moderate erythema were noted on 10/20 and 1/20 test animals,
respectively, 24 hours after challenge. Faint erythema and moderate
erythema were noted on 6/20 and 1/20 test animals, respectively, 48
hours after challenge. In a similar study, the 25EC was classified as a
dermal sensitizer. After three consecutive inductions, faint erythema
and moderate erythema were noted on 15/20 and 1/20 test animals,
respectively, 24 hours after challenge. Faint erythema and moderate
erythema were noted on 8/20 and 1/20 test animals, respectively, 48
hours after challenge.  Naïve control animals in both studies did not
have any positive reactions after challenge. (MRIDs 46396212 and
46396110, respectively)

7. 	Genotoxicity (OPPTS 870.5100, 870.5375, and 870.5550):   Three
genotoxicity studies were performed on the tgai. A bacterial reverse
mutation assay, an in vitro mammalian chromosome aberration test, and an
unscheduled DNA repair assay.  The reverse mutation assay showed that 
the tgai was not mutagenic to bacterial strains TA98, TA100, TA1535,
TA1537, and E. coli strain WP2 uvrAW. The test material produced no
statistically significant increases in chromosome/chromatid aberrations
in human lymphocytes with, or without, metabolic activation. The third
mutagenic assay was also negative because the tgai did not cause
unscheduled DNA repair in cultured rat hepatocytes.  (MRIDs 46456301,
46396214, and  46396215, respectively)

Waivers have been requested for all other Tier 1 biochemical pesticide
data requirements including reproductive and developmental toxicity,
immunotoxicity, sub-chronic toxicity and acute toxicity to non-target
species.  Data waiver rationales are based on the lack of residues
shortly after application; ubiquity in nature of the major terpene
components in the extract; history of use the major terpene components
in the extract in the food, fragrance, and flavoring industries;
favorable toxicological profile in acute toxicological studies; and the
inconsequential exposure resulting from the label-directed use rates.

The results of toxicity testing and information found in published
literature support the conclusion that the proposed use of AgraQuest’s
processed Extract of Chenopodium ambrosioides near ambrosioides poses no
foreseeable risks to human health or the environment. Both dietary and
non-dietary exposures would not be expected to pose any quantifiable
risk due to a lack of residues of toxicological concern. 

  

SECTION D: AGGREGATE EXPOSURE

1)	Dietary Exposure

	i.	Food:    SEQ CHAPTER \h \r 1 Dietary exposure from use of Extract of
Chenopodium ambrosioides near ambrosioides, as proposed, is virtually
non-existent.   Extract of Chenopodium ambrosioides near ambrosioides is
intended for application to ornamentals and agricultural crops to
suppress or control certain insect pests.  Extract of Chenopodium
ambrosioides near ambrosioides is an essential oil derived from a plant
that is common in the US, Mexico, and Central America, and is used as a
spice and herb in cooking. The extract is a complex mixture of terpenes
and terpene derivatives, including three major terpene components that
make up over 70% of the mixture.   

  

		No residues of Extract of Chenopodium ambrosioides near ambrosioides
are expected to occur on food due to the fact that the components of the
active ingredient are volatile and dissipate soon after application.
Residue decline studies on an ornamental and a food crop demonstrate
that multiple applications for the formulated end-use product at 2 –
4X the label rates results in no detection of residue shortly after
application and no accumulation of residues over multiple applications. 

		Acute toxicity studies show that Extract of Chenopodium ambrosioides
near ambrosioides is not toxic and is mildly to moderately irritating to
mammals.  The major terpene components in Extract of Chenopodium
ambrosioides near ambrosioides are naturally occurring in a multitude of
fruits, vegetables, herbs, spices, and other foods and beverages,
including coffee, tea, alcoholic beverages, baked and fried potatoes,
bread and cheese.  In addition the major terpene components are approved
as direct food additives by the US Food and Drug Administration, and are
approved as fragrances in cosmetics.  The lack of residues on treated
crops, the results of toxicity testing on the extract, and information
found in published literature on the major terpene components in the
extract support the conclusion that the proposed use of AgraQuest’s
processed Extract of Chenopodium ambrosioides near ambrosioides poses no
foreseeable risks to human health or the environment. Dietary exposures
would not be expected to pose any quantifiable risk due to a lack of
residues of toxicological concern.

	ii.	Drinking water:  Similarly, exposure to humans from residues of
Extract of Chenopodium ambrosioides near ambrosioides in consumed
drinking water would be unlikely.  Potential exposure to surface water
would be negligible and exposure to drinking water (well or ground
water) would be impossible to measure. Extract of Chenopodium
ambrosioides near ambrosioides is intended for application to
ornamentals and agricultural crops.  The product is not applied directly
to water.

	

		The lack of residues on treated crops, the results of toxicity testing
on the extract, and information found in published literature on the
major terpene components in the extract support the conclusion that the
proposed use of AgraQuest’s processed Extract of Chenopodium
ambrosioides near ambrosioides poses no foreseeable risks to human
health or the environment.  Drinking water exposures would not be
expected to pose any quantifiable risk due to a lack of residues of
toxicological concern.

3)	Non-Dietary Exposure

	The potential for non-dietary exposure to the general population,
including infants and children, is limited.  Extract of Chenopodium
ambrosioides near ambrosioides is intended for application to
ornamentals and agricultural crops to control insect pests.  

	The lack of residues on treated crops, the results of toxicity testing
on the extract, and information found in published literature on the
major terpene components in the extract support the conclusion that the
proposed use of AgraQuest’s processed Extract of Chenopodium
ambrosioides near ambrosioides poses no foreseeable risks to human
health or the environment.  Non-dietary exposures would not be expected
to pose any quantifiable risk due to a lack of residues of toxicological
concern.

SECTION E: CULMULATIVE EFFECTS

  SEQ CHAPTER \h \r 1 It is not expected that, when used as proposed,
Extract of Chenopodium ambrosioides near ambrosioides would result in
residues that are of toxicological concern. Extract of Chenopodium
ambrosioides near ambrosioides is an essential oil derived from a plant
that is common in the US, Mexico, and Central America, and is used as a
spice and herb in cooking. The extract is a complex mixture of terpenes
and terpene derivatives, including three major terpene components that
make up over 70% of the mixture.   

  

Toxicity studies show that Extract of Chenopodium ambrosioides near
ambrosioides is not acutely toxic and is mildly to moderately irritating
to mammals.  The major terpene components in Extract of Chenopodium
ambrosioides near ambrosioides are naturally occurring in a multitude of
fruits, vegetables, herbs, spices, and other foods and beverages,
including coffee, tea, alcoholic beverages, baked and fried potatoes,
bread and cheese.  In addition the major terpene components are approved
as direct food additives by the US Food and Drug Administration, and are
approved as fragrances in cosmetics.  

Extract of Chenopodium ambrosioides near ambrosioides is intended for
application to ornamentals and agricultural crops to control insect
pests.  The lack of residues on treated crops, the results of toxicity
testing on the extract, and information found in published literature on
the major terpene components in the extract support the conclusion that
the proposed use of AgraQuest’s processed Extract of Chenopodium
ambrosioides near ambrosioides poses no foreseeable risks to human
health or the environment.  

SECTION F: SAFETY DETERMINATION

1)	U.S. Population

Extract of Chenopodium ambrosioides near ambrosioides is an essential
oil derived from a plant that is common in the US, Mexico, and Central
America, and is used as a spice and herb in cooking. The extract is a
complex mixture of terpenes and terpene derivatives, including three
major terpene components.  Acute toxicity studies have show that Extract
of Chenopodium ambrosioides near ambrosioides is not toxic and is mildly
to moderately irritating to mammals.  The major terpene components in
Extract of Chenopodium ambrosioides near ambrosioides are naturally
occurring in a multitude of fruits, vegetables, herbs, spices, and other
foods and beverages, including coffee, tea, alcoholic beverages, baked
and fried potatoes, bread and cheese.  In addition the major terpene
components are approved as direct food additives by the US Food and Drug
Administration, and are approved as fragrances in cosmetics.    

When used as proposed, Extract of Chenopodium ambrosioides near
ambrosioides would not result in residues that are of toxicological
concern. Extract of Chenopodium ambrosioides near ambrosioides is
intended for application to ornamentals and agricultural crops to
control insect pests.  The lack of residues on treated crops, the
results of toxicity testing on the extract, and information found in
published literature on the major terpene components in the extract
support the conclusion that the proposed use of AgraQuest’s processed
Extract of Chenopodium ambrosioides near ambrosioides poses no
foreseeable risks to human health or the environment. There is a
reasonable certainty of no harm to the general US population from
exposure to this active ingredient.

2)	Infants and Children

As mentioned above, it is not expected that, when used as proposed,
Extract of Chenopodium ambrosioides near ambrosioides would result in
residues that are of toxicological concern. There is a reasonable
certainty of no harm for infants and children from exposure to Extract
of Chenopodium ambrosioides near ambrosioides from the proposed uses.  

SECTION G: EFFECTS ON IMMUNE AND ENDOCRINE SYSTEMS

To date there is no evidence to suggest that the Extract of Chenopodium
ambrosiodes near ambrosioides will compromise the immune or endocrine
systems, or that it functions in a manner similar to any known hormone,
or that it acts as an endocrine disrupter.  

SECTION H:		EXISTING TOLERANCES

There is no US. EPA Tolerance for Extract of Chenopodium ambrosiodes
near ambrosioides. 

SECTION I:		INTERNATIONAL TOLERANCES

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 PAGE   

AgraQuest Inc.		Page   PAGE  1  of   NUMPAGES  14 

Exemption Petition

Keynote - Chenopodium extract