	

                                

BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Sarmentine	

PC Code :	373501

	U.S. Environmental Protection Agency

	Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

August 7, 2014

TABLE OF CONTENTS

  TOC \o "1-4" \h \z \u    HYPERLINK \l "_Toc394409661"  I.	EXECUTIVE
SUMMARY	  PAGEREF _Toc394409661 \h  5  

  HYPERLINK \l "_Toc394409662"  II.	ACTIVE INGREDIENT OVERVIEW	  PAGEREF
_Toc394409662 \h  6  

  HYPERLINK \l "_Toc394409663"  III.	REGULATORY BACKGROUND	  PAGEREF
_Toc394409663 \h  6  

  HYPERLINK \l "_Toc394409664"  A.	Classification	  PAGEREF
_Toc394409664 \h  6  

  HYPERLINK \l "_Toc394409665"  B.	Food Clearances/Tolerances	  PAGEREF
_Toc394409665 \h  6  

  HYPERLINK \l "_Toc394409666"  IV.	RISK ASSESSMENT	  PAGEREF
_Toc394409666 \h  6  

  HYPERLINK \l "_Toc394409667"  A.	Active Ingredient Characterization	 
PAGEREF _Toc394409667 \h  6  

  HYPERLINK \l "_Toc394409668"  1.	Toxicology	  PAGEREF _Toc394409668 \h
 7  

  HYPERLINK \l "_Toc394409669"  2.	Dose Response Assessment	  PAGEREF
_Toc394409669 \h  9  

  HYPERLINK \l "_Toc394409670"  3.	Drinking Water Exposure and Risk
Characterization	  PAGEREF _Toc394409670 \h  9  

  HYPERLINK \l "_Toc394409671"  4.	Occupational, Residential, School and
Day Care Exposure and Risk Characterization	  PAGEREF _Toc394409671 \h 
9  

  HYPERLINK \l "_Toc394409674"  5.      	Risk Characterization	  PAGEREF
_Toc394409674 \h  10  

  HYPERLINK \l "_Toc394409675"  C.	ENVIRONMENTAL ASSESSMENT	  PAGEREF
_Toc394409675 \h  10  

  HYPERLINK \l "_Toc394409676"  1.	Ecological Hazards	  PAGEREF
_Toc394409676 \h  10  

  HYPERLINK \l "_Toc394409677"  2.	Environmental Fate and Ground Water
Data	  PAGEREF _Toc394409677 \h  10  

  HYPERLINK \l "_Toc394409678"  3.	Ecological Exposure and Risk
Characterization	  PAGEREF _Toc394409678 \h  10  

  HYPERLINK \l "_Toc394409679"  4.   	Endangered Species Assessment	 
PAGEREF _Toc394409679 \h  10  

  HYPERLINK \l "_Toc394409680"  D.	PRODUCT PERFORMANCE DATA (EFFICACY)	 
PAGEREF _Toc394409680 \h  10  

  HYPERLINK \l "_Toc394409681"  V.	Risk Management Decision	  PAGEREF
_Toc394409681 \h  11  

  HYPERLINK \l "_Toc394409682"  A.	Determination of Eligibility for
Registration	  PAGEREF _Toc394409682 \h  11  

  HYPERLINK \l "_Toc394409683"  B.	Regulatory Decision	  PAGEREF
_Toc394409683 \h  11  

  HYPERLINK \l "_Toc394409684"  1.	Conditional/Unconditional
Registration	  PAGEREF _Toc394409684 \h  11  

  HYPERLINK \l "_Toc394409685"  C. 	Environmental Justice	  PAGEREF
_Toc394409685 \h  11  

  HYPERLINK \l "_Toc394409686"  VI.	ACTIONS REQUIRED BY REGISTRANTS	 
PAGEREF _Toc394409686 \h  12  

  HYPERLINK \l "_Toc394409687"  A.  	Reporting of Adverse Effects	 
PAGEREF _Toc394409687 \h  12  

  HYPERLINK \l "_Toc394409688"  B.	Reporting of Hypersensitivity
Incidents	  PAGEREF _Toc394409688 \h  12  

  HYPERLINK \l "_Toc394409689"  VII.	Appendix A. Data Requirements (40
CFR Part 158-Subpart U)	  PAGEREF _Toc394409689 \h  12  

  HYPERLINK \l "_Toc394409690"  VIII. 	Appendix B.	  PAGEREF
_Toc394409690 \h  15  

  HYPERLINK \l "_Toc394409691"  IX.	Appendix C.	  PAGEREF _Toc394409691
\h  16  

  HYPERLINK \l "_Toc394409692"  X.  	GLOSSARY OF ACRONYMS AND
ABBREVIATIONS	  PAGEREF _Toc394409692 \h  16  

 

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs:

Biopesticides and Pollution Prevention Division

Biochemical Pesticides Branch (BPB)

Leonard S. Cole, Jr., M.S.						Senior Regulatory Specialist

EXECUTIVE SUMMARY

Sarmentine is a new biochemical active ingredient intended for use as an
herbicide to control grasses and broadleaf weeds in and around crops. It
is used as a foliar and spot treatment spray on non-food crops in
agricultural, residential, and other areas such as golf courses and
parks. It is a naturally occurring constituent of peppercorns that has
been extracted from fruit, foliage and roots of a variety of pepper
plants. Sarmentine has been characterized in alcohol extracts from a
variety of edible peppers, including Piper sarmentosum, Piper longnum,
and Piper nigrum, the source of both common black and white peppers.
Sarmentine has also been isolated from vines in the Vitus family, which
includes grapes. Although the specific mode of action of sarmentine is
not completely understood, it is believed that the substance damages and
degrades the integrity of plant cell walls. Based on this information,
the Agency considers the mode of action to be non-toxic. 

The Biopesticides and Pollution Prevention Division (BPPD) has reviewed
all of the data and other information submitted in support of the
registration of sarmentine as an herbicide under section 3(c)(5) of the
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), and has
determined that the current data requirements (40 CFR part 158.2010
through 158.2070) for registration of a biochemical pesticide have been
satisfied. Given that sarmentine is of low toxicity and presents little,
if any, risks to humans, including infants and children, and the
environment, the U.S. Environmental Protection Agency (EPA or the
Agency) has concluded that it is in the best interest of the public to
issue registrations for the manufacturing-use product (MP), MBI-011 TGAI
(EPA File Symbol No. 84059-RO), and the end-use product (EP), MBI-011 EP
(EPA File Symbol No. 84059-EN) which contain this new active ingredient,
sarmentine. The basis for this decision is described in more detail in
section IV of this Biopesticide Registration Action Document (BRAD).  

On October 1, 2009, EPA announced a new policy to provide a more
meaningful opportunity for the public to participate on major
registration decisions before they occur. According to this policy, EPA
provides a public comment period prior to making a registration decision
for the following types of applications:  new active ingredients, first
food use, first outdoor use, first residential use, and any registration
decisions for which the Agency believes there may be substantial public
interest. 

Consistent with the new policy of making registration actions more
transparent, sarmentine is subject to a 15 day comment period as a
“new active ingredient”. EPA has established a comment period of 15
days on the basis of sarmentine’s low toxicity, the determination that
sarmentine presents low risk of any adverse effects to human health and
the environment, and a need for this active ingredient. The notice for
this comment period includes the draft Biopesticides Registration Action
Document (BRAD), and a draft product label for the MP, MBI-011 and EP,
MBI-011, which contain this new active ingredient, sarmentine. The
docket ID is EPA-HQ-OPP-2014-0003. The Agency believes that based on the
risk assessment and information submitted in support of the registration
of sarmentine, it is in the best interests of the public to issue the
registration of MBI-011 TGAI and MBI-011 EP. The basis for this decision
can be found in the risk assessment for sarmentine, which is
characterized in this BRAD.

II.		ACTIVE INGREDIENT OVERVIEW

Common Name: 			Sarmentine

Chemical Names: 	(E,E)-1-(1-oxo-2,4-decadienyl) pyrrolidine

Trade & Other Names: 	MBI-011

CAS Registry Number: 	78910-33-5

OPP Chemical Code: 	373501

Type of Pesticide: 		Herbicide

III.	REGULATORY BACKGROUND

On December 31, 2012, EPA received an application filed by Marrone Bio
Innovations, 2121 Second Street, Suite B107, Davis, California 95618 to
register the products, MBI-011 TGAI (EPA File Symbol 84059-RO) and
MBI-011 EP (EPA File Symbol 84059-EN), containing the new biochemical
active ingredient (E,E)-1-(1-oxo-2,4-decadienyl) pyrrolidine known as
sarmentine. A notice of receipt of this application, allowing for a
30-day comment period, was published in the Federal Register of April
18, 2014 (79 FR 75). No comments were received following this
publication.  

A.	Classification

On October 14, 2010, the Biochemical Classification Committee determined
that sarmentine can be classified as a biochemical pesticide due to its
non-toxic mode of action, natural occurrence in the environment, and
history of exposure to humans and the environment demonstrating minimal
toxicity.  

B.	Food Clearances/Tolerances 

Currently, sarmentine is not intended for use on food or feed
commodities; therefore, a tolerance or exemption from the requirement of
a tolerance is not relevant. Sarmentine has been determined to be a
non-food use.

IV.			RISK ASSESSMENT

Active Ingredient Characterization

The new active ingredient sarmentine (MP, MBI-011) will be formulated as
an EP to be used as an herbicide on non-food use sites. Sarmentine is a
naturally-occurring biochemical isolated from pepper fruit, foliage and
roots. Sarmentine is naturally occurring and is found in many plants
within the Piper family, which is the source of the spice “pepper”.
Sarmentine has also been isolated from vines in the Vitus family, which
includes grapes. Sarmentine has been characterized in alcohol extracts
from a variety of edible peppers, including Piper sarmentosum, Piper
longnum, and Piper nigrum, the source of both common black and white
peppers.

Descriptions of the product formulation and production process, as well
as the formation of impurities, were examined by BPPD and found to be
acceptable in meeting current guideline standards. 

All product chemistry data requirements for registration of sarmentine
have been satisfied. 

B.	Human Health Assessment

1.	Toxicology 

For acute toxicity data requirements, toxicity categories are assigned
based on the hazard(s) identified from studies and/or information on
file with the Agency.  The active ingredient is classified into acute
Toxicity Category I, II, III or IV where Toxicity Category I is the
level of highest toxicity and Toxicity Category IV indicates low
toxicity. 

Adequate mammalian toxicology data/information are available to support
registration of sarmentine. All toxicology data requirements for
sarmentine have been satisfied.

	a.	Acute Toxicity

Acute toxicity testing is required to 1) determine systemic toxicity
from acute exposure via the dermal, inhalation and oral routes, 2)
determine irritant effects from exposure to the eyes, and 3) determine
the potential for skin sensitization (allergic contact dermatitis). 

Tier I acute toxicity studies submitted and reviewed showed that
sarmentine is a Toxicity Category II (moderately irritating) compound
via primary eye irritation exposure. Sarmentine is a Toxicity Category
IV for acute inhalation, primary dermal irritation, and acute oral
toxicity routes of exposure. Submitted information confirmed that
sarmentine is a dermal sensitizer. 

For more information regarding acute toxicity data requirements, refer
to Table 3 in Appendix A of this document. 

 

	b.	Subchronic Toxicity 

Subchronic data are required to determine a no-observed-effect-level
(NOEL) and toxic effects (if any) associated with repeated or continuous
exposure to a test substance for a period of 90 days.

Data waivers requested for the subchronic [90-day oral (OSCPP 870.3100),
90-day dermal (OSCPP 870.3250), and 90-day inhalation (OSCPP 870.3465)]
studies were granted by BPPD, based on the product’s toxicological and
exposure profile below.

Sarmentine is for non-food use; therefore, repeat oral exposure to
humans is not anticipated.

Prolonged exposure to human skin is not anticipated based on the use
pattern and the use of personal protective equipment is required in
occupational settings.

Significant inhalation exposure is not expected based on the use
pattern. 

For more information regarding the subchronic data requirements, refer
to Table 3 in Appendix A of this document.

      	c.   	Developmental Toxicity and Mutagenicity 

Data waivers were granted for Tier I Subchronic, Developmental and
Mutagenicity data requirements (OSCPP 870.3100 to 870.5375) due to the
nature of the A.I. and its intended uses. Significant exposure to humans
is unlikely based on the proposed use pattern of the active ingredient.
Exposure via the oral route is not anticipated as sarmentine is intended
for non-food uses. Further, applicators and handlers must wear PPE to
preclude significant dermal and inhalation exposure. Significant
residential exposures are also not anticipated because any exposures
would be acute in nature and not prolonged. Further, exposure will be
mitigated because sarmentine is expected to degrade rapidly into
innocuous substances once applied; thus, significant post-application
exposure is not likely.

d. 	Tier II/Tier III 

Tiers II and III data were not triggered due to low toxicity profile of
sarmentine and low exposure to humans and non-target species. 

	e.	Effects on the Endocrine System tc \l4 "e.	Effects on the Endocrine
System 

As required under Federal Food, Drug, and Cosmetic Act (FFDCA) section
408(p), EPA has developed the Endocrine Disruptor Screening Program
(EDSP) to determine whether certain substances  (including pesticide
active and other ingredients) may have an effect in humans or wildlife
similar to an effect produced by a “naturally-occurring estrogen, or
other such endocrine effects as the Administrator may designate.” The
EDSP employs a two-tiered approach to making the statutorily required
determinations. Tier I consists of a battery of 11 screening assays to
identify the potential of a chemical substance to interact with the
estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals
that go through Tier I screening and are found to have the potential to
interact with E, A, or T hormonal systems will proceed to the next stage
of the EDSP where EPA will determine which, if any, of the Tier 2 tests
are necessary based on the available data. Tier 2 testing is designed to
identify any adverse endocrine related effects caused by the substance,
and establish a dose-response relationship between the dose and the E,
A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data
call-ins for the first group of 67 chemicals, which contains 58
pesticide active ingredients and nine inert ingredients. This list of
chemicals was selected based on the potential for human exposure through
pathways such as food and water, residential activity, and certain
post-application agricultural scenarios. This list should not be
construed as a list of known or likely endocrine disruptors.

Sarmentine is not among the group of 58 pesticide active ingredients on
the initial list to be screened under the EDSP. Under FFDCA section
408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA
anticipates issuing future test orders/data call-ins for all pesticide
active ingredients.

For further information on the status of the EDSP, the policies and
procedures, the list of 67 chemicals, the test guidelines and the Tier I
screening battery, please visit our website:  http://www.epa.gov/endo/. 

2.	Dose Response Assessment

There are no available repeat dose studies; therefore, a dose response
cannot be established.  

3.	Drinking Water Exposure and Risk Characterization

No significant exposure via drinking water is expected when sarmentine
is used according to the product label directions. Sarmentine is not to
be applied directly to water or to areas where surface water is present,
and if used as labeled, is not likely to accumulate in drinking water.
Sarmentine is expected to degrade rapidly in the environment once
applied, based on the half-life of 30-45 minutes. In the unlikely event
that exposure via drinking water did occur, the health risk would be
expected to be minimal based on the rapid degradation of sarmentine. 

4.	Occupational, Residential, School and Day Care Exposure and Risk
Characterization

	a.	Occupational Exposure and Risk Characterization

An occupational exposure assessment was not conducted for sarmentine.
Based on the proposed use pattern and toxicity data available to the
Agency, expected exposure is not likely to result in unreasonable risk
to applicators/handlers. Occupational exposure is not anticipated
because applicators and handlers are required to wear PPE that would
mitigate exposure to the active ingredient. Additionally, sarmentine is
expected to degrade rapidly into innocuous substances once applied,
which would greatly reduce the potential for post-application exposure.
In the event that exposure does occur, adverse effects are not expected
due to the low toxicity of the A.I. 

	

b.	Residential, School and Day Care Exposure and Risk Characterization

Based on the proposed use pattern and toxicity data available to the
Agency, residential exposure is not likely to result in unreasonable
risk to humans. Although significant exposures are not anticipated, any
exposures that might occur would be incidental, acute in nature, and not
prolonged because of the way in which the proposed product is intended
for use. That is, as a spot treatment to weeds applied via a tank
sprayer as a course spray. Further, exposure will also be reduced
because sarmentine is expected to degrade rapidly into innocuous
substances once applied. Thus, post application exposure is not likely.
No relevant toxicological endpoints were identified and therefore,
exposure should it occur, will be appropriately mitigated for the
reasons stated above in addition and when proper label instructions are
followed.

5.   Risk Characterization

The Agency considered human exposure to sarmentine after reviewing the
available toxicity data. A determination has been made that no
unreasonable exposure to the U.S. population in general, and to infants
and children in particular, will result from the use of sarmentine when
label instructions are followed. 

C.	ENVIRONMENTAL ASSESSMENT

1.	Ecological Hazards

Adequate non-target toxicology data/information are available to support
the registration of the biochemical pesticide, sarmentine. All
non-target toxicology data requirements for sarmentine have been
satisfied. Non-Target Organisms and Environmental Fate data requirements
were waived or satisfied by data/information submitted by the applicant.

2.	Environmental Fate and Ground Water Data 

The need for environmental fate and groundwater data was not triggered
because results of the acute toxicity studies did not trigger any
additional Tier II studies. Further, sarmentine degrades rapidly into
innocuous substances in the environment once applied.

3.	Ecological Exposure and Risk Characterization

Data waivers were granted for non-target plants and non-target insect
testing based on data/information which demonstrate that sarmentine is
non-toxic to ladybugs when applied to the beetle’s food source and
corn earworn eggs. Appropriate mitigation language on the EP label will
prevent exposure to desirable or non-target plants. In addition, avian
dietary exposure is not anticipated based on the use pattern and rapid
degradation in the environment. 

4.   Endangered Species Assessment 

Sarmentine is not toxic to non-target organisms, and based on its use
pattern EPA has determined it will have No Effect on threatened and/or
endangered species or any designated critical habitat. 

D.	PRODUCT PERFORMANCE DATA (EFFICACY)

Product Performance data must be developed for all pesticides to ensure
that pesticide products will perform as intended and that unnecessary
pesticide exposure to the environment will not occur as a result of the
use of ineffective products. The Agency reserves the right to require on
a case-by-case basis, submission of efficacy data for any pesticide
product registered or proposed for registration that are intended to be
used to control a pest of significancant public health importance and a
public health pest as defined in FIFRA section 28(d) and section 2(nn).
For further guidance on product performance requirement, refer to
Pesticide Registration Notice (PR) Notices 96-7, 2002-1 and Explanation
of Statutory Framework for Risk-Benefit Balancing for Public Health
Pesticides (  HYPERLINK "http://www.epa.gov/PR_Notices/pr1996-7.pdf" 
http://www.epa.gov/PR_Notices/pr1996-7.pdf ) (  HYPERLINK
"http://www.epa.gov/PR_Notices/pr2002-1.pdf" 
http://www.epa.gov/PR_Notices/pr2002-1.pdf ) and (  HYPERLINK
"http://www.epa.gov/pesticides/health/risk-benefit.htm" 
http://www.epa.gov/pesticides/health/risk-benefit.htm . 

The EP submitted with this new active ingredient did not list pests of
significant public health importance or a public health pest as defined
in FIFRA section 28(d) and section 2(nn). Therefore, product performance
(efficacy) was not evaluated. 

V.		Risk Management Decision

A.	Determination of Eligibility for Registration 

Section 3(c)(5) of FIFRA provides for the registration of new active
ingredients if it is determined that: (A) its composition warrants
proposed claims; (B) its labeling and other materials comply with the
requirements of FIFRA; (C) it will perform its intended function without
unreasonable adverse effects on the environment; and (D) when used in
accordance with widespread and commonly recognized practice, it will not
generally cause unreasonable adverse effects on the environment.

The four criteria of the Eligibility Determination for Pesticidal Active
Ingredients are satisfied by the science assessments supporting products
containing sarmentine. Such products are not expected to cause
unreasonable adverse effects and are likely to provide protection as
claimed when used according to label instructions. Therefore, sarmentine
is eligible for registration for the labeled uses.

B.	Regulatory Decision

The data submitted fulfill the requirements of registration for
sarmentine for use as an herbicide. Refer to Appendix B for
product-specific information.

1.	Conditional/Unconditional Registration

All data requirements are fulfilled and EPA has determined that
unconditional registration of sarmentine is appropriate.

C. 	Environmental Justice

EPA seeks to achieve environmental justice--the fair treatment and
meaningful involvement of all people regardless of race, color, national
origin, or income--with respect to the development, implementation, and
enforcement of environmental laws, regulations, and policies. At this
time, EPA does not believe that use of sarmentine pesticide products
will cause harm of a disproportionate impact on at-risk communities. For
additional information regarding environmental justice issues, please
visit EPA’s website at   HYPERLINK
"http://www.epa.gov/compliance/environmentaljustice/index.html" 
http://www.epa.gov/compliance/environmentaljustice/index.html . 

VI.	 	ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all of the data submitted in connection with the initial
registration of sarmentine and determined that these data are sufficient
to satisfy current registration data requirements.  No additional data
are required to be submitted to the Agency at this time.  For new uses
and/or changes to existing uses, additional data may be required.  

Not withstanding, the information stated in the previous paragraph, it
should be clearly understood that certain, specific, data are required
to be reported to the Agency as a requirement for maintaining the
Federal registration for a pesticide product. A brief summary of these
types of data are listed below.   

A.  Reporting of Adverse Effects

Additionally, all incidents of hypersensitivity (including both
suspected and confirmed incidents) must be reported to the Agency under
the provisions of 40 CFR § 158.2050(d). 

B.	Reporting of Hypersensitivity Incidents

Additionally, all incidents of hypersensitivity (including both
suspected and confirmed incidents) must be reported to the Agency under
the provisions of 40 CFR Part 158.2050(d).

VII.	Appendix A. Data Requirements (40 CFR Part 158-Subpart U)

*NOTE:  MRID numbers listed in the following tables are representative
of supporting data for the original registration of the product
containing this active ingredient.  Subsequent to this registration,
there may be additional MRIDs that support registration of other
products containing this active ingredient.   

TABLE 1. Product Chemistry Data Requirements for Sarmentine (40 CFR §
158.2030)

OPPTS Guideline No.	Study	Results 

830.1550

to

830.1670	Product identity;

Manufacturing process;

Discussion of formation of unintentional ingredients	Submitted data
satisfy the requirements for product identity, manufacturing process,
and discussion of formation of impurities. 

830.1700	Analysis of samples	Submitted data satisfy the requirements for
analysis of samples.

830.1750	Certification of limits	Limits listed in the CSF are
acceptable.

830.1800	Analytical method	Acceptable.



	TABLE 2. Physical and Chemical Properties of Sarmentine (MBI-011 TGAI)
(40 CFR § 158.2030)

OCSPP Guideline 	Property	Description of Result	MRID

830.6302	Color	Light yellow	49020301

830.6303	Physical State	Solid (powder)	49020301

830.6304	Odor	None detected	49020301

830.6313	Stability to Normal and Elevated Temperatures, Metals and Metal
Ions	Not expected to be stable at temperatures between 25°C and 40°C.
The active ingredient is not anticipated to come in contact with metals
or metal ions during storage.	49020303

830.6315	Flammability	N/A: product does not contain combustible liquids.
49020303

830.6317	Storage Stability	A storage stability study is ongoing.
49020303

830.6319	Miscibility	N/A: product is not an emulsifiable liquid to be
diluted with petroleum solvents.	49020303

830.6320	Corrosion Characteristics	A corrosion characteristics study is
ongoing. 	49020303

830.7000	pH	4.34	49020301

830.7050	UV/Visible Light

Absorption	ɛ= 3071 (neutral), 3090 (acidic), 3127 (basic)	49020301

830.7100	Viscosity	N/A: test substance is a solid.	49020301

830.7200	Melting Point/Range	Method needed

	830.7220	Boiling Point/Range	>400°C	49020301

830.7300	Bulk Density	1.28 g/ml	49020301

830.7520	Particle Size, Fiber Length and Diameter Distribution	5.707µm
Unassigned MRID

830.7550

830.7560

830.7570	Partition Coefficient (n-

Octanol/Water)	

Not required: test substance is partially soluble in water.	

49020303

830.7840	Water Solubility	1.57 g/100ml	49020302

830.7950	Vapor Pressure	Test substance is too unstable for testing.
49020302



Table 3. Mammalian Toxicology Data for Sarmentine  (40 CFR § 158.2050)

Study/OCSPP Guideline No.	Results	Toxicity Category/Description	MRID

Acute oral toxicity (rat)

(870.1100)	LD50 > 5000 mg/kg (females)	IV	49020306

Acute dermal toxicity (rat)

(870.1200)	LD50 > 5050 mg/kg (females and males)	IV	49020307

Acute inhalation toxicity	 (rat)

(870.1300)	LC50 > 2.22 mg/l (females and males)	IV	49020308

Primary eye irritation (rabbit)

(870.2400)	Moderately irritating	II	49020309

Primary dermal irritation (rabbit)

(870.2500)	Slightly irritating	IV	49020310

Dermal sensitization (guinea pig)

(870.2600)	Is a sensitizer	N/A	49020311

90-Day oral toxicity

(870.3100)	Waived. Sarmentine is for non-food uses only. Uses are not
anticipated to result in repeat oral exposure to humans.

49020319

49131901

49207902

90-Day dermal toxicity

(870.3250)	Waived. Purposeful application and prolonged exposure to the
human skin is not anticipated based on the use pattern. Applicators and
handlers are required to wear appropriate PPE. Residential exposures
would be incidental and short in duration; thus, repeated exposure is
not anticipated. Additionally, sarmentine degrades rapidly into
innocuous substances in the environment once applied which further
mitigates exposure.

49020319

49131901

49207902

90-Day inhalation toxicity

(870.3465)	Waived. Significant repeat inhalation exposure to the active
ingredient as a gas, vapor or aerosol is unlikely. Applicators and
handlers are required to wear appropriate PPE. Residential exposures
would be incidental and short in duration; thus, repeated exposure is
not anticipated. Additionally, sarmentine degrades rapidly into
innocuous substances in the environment once applied which further
mitigates exposure.

49020319

49131901

49207902

Mutagenicity-in vitro studies

(870.5100)	Waived. Significant human exposure is unlikely based on use
pattern. Sarmentine is for nonfood-uses only. Applicators and handlers
are required to wear appropriate PPE. Residential exposures would be
incidental and short in duration; thus, repeated exposure is not
anticipated. Additionally, sarmentine degrades rapidly into innocuous
substances in the environment once applied which further mitigates
exposure.

49020319

49131901

49207902

Mutagenicity-in vivo micronucleus assay

(870.5395)	Waived. Significant human exposure is unlikely based on use
pattern. Sarmentine is for nonfood-uses only. Applicators and handlers
are required to wear appropriate PPE. Residential exposures would be
incidental and short in duration; thus, repeated exposure is not
anticipated. Additionally, sarmentine degrades rapidly into innocuous
substances in the environment once applied which further mitigates
exposure.

49020319

49131901

49207902

Developmental toxicity

(870.3700)	Waived. Significant exposure to females is unlikely based on
use pattern. Sarmentine is for non-food uses only. Applicators and
handlers are required to wear appropriate PPE. Residential exposures
would be incidental and short in duration; thus, repeated exposure is
not anticipated. Additionally, sarmentine degrades rapidly into
innocuous substances in the environment once applied which further
mitigates exposure.

49020319

49131901

49207902



TABLE 4.  Nontarget Organism Toxicity Requirements for Sarmentine
(MBI-011 TGAI) (40 CFR § 158.2060)

Study/OCSPP Guideline No.

/MRID No.	Results	Toxicity Category/Description	MRID

Avian acute oral toxicity

Colinus virginianus

(850.2100)	LD50 > 2,000 mg/kg	Practically non-toxic	49020314

Avian dietary toxicity

Colinus virginianus and Anas platyrhynchos 

(850.2200)	Waived. Avian dietary exposure is not anticipated based on
the use pattern. The proposed EP containing sarmentine is applied as a
foliar spray to weeds and is not in a granular form that could be
attractive to birds. Sarmentine is expected to degrade rapidly into
innocuous substances in the environment once applied which would further
mitigate dietary exposure to birds. 	N/A	49020319

49207902

Freshwater fish LC50

(Oncorhynchus mykiss)

(850.1075)	LC50 = 9.38 mg/l	Moderately toxic	49020313

Aquatic invertebrate acute toxicity

(Daphnia magna)

(850.1010)	

EL50 = 3.83 mg/l	

Moderately toxic	

49020312

Non-target plant studies-seedling emergence

(850.4100)	Waived. Sarmentine is a non-selective herbicide that will be
applied to weeds. The proposed EP label will include language to prevent
or mitigate exposure to desirable or nontarget plants. Exposure to
non-target plants will be further mitigated because sarmentine is
expected to degrade rapidly into innocuous substances in the
environment. 	N/A	49020319

49131901

Non-target plant studies-vegetative vigor

(850.4150)	Waived. Sarmentine is a non-selective herbicide that will be
applied to weeds. The proposed EP label will include language to prevent
or mitigate exposure to desirable or non-target plants. Exposure to
non-target plants will be further mitigated because sarmentine is
expected to degrade rapidly into innocuous substances in the
environment.	N/A	49020319

49131901

Nontarget insect testing (Apis mellifera)

(880.4350)	Honey bee: LD50 > 100 µg a.i./bee

Ladybird beetle: practically non-toxic when sarmentine was applied to
the beetle’s food source, corn earworm eggs.

Green lacewing:  practically non-toxic when sarmentine was applied to
the lacewing’s food source, corn earworm eggs.

	Practically non-toxic	49020315

49020316

49020317





VIII. 	Appendix B.

For product specific information, please refer to   HYPERLINK
"http://www.epa.gov/pesticides/pestlabels" 
http://www.epa.gov/pesticides/pestlabels . 

IX.			Appendix C.

REFERENCES

Bernabeu, M., Chinchilla, R. and Najera, C. 1995.
(2E,4E)-5-Tosyl-2,4-pentadienamides: New Dienic Sulfones for the
Stereoselective Synthesis of (2E,4E)-Dienamides, Tetrahedron Letter. 36:
3901-3904

Débieux J-L, & Bochet, CG, 2010. Photoinduced acyl transfer. J.
Physical Organic Chem. 10:1002/poc.1639.

HSDB, 2014. Succinic Acid. National Library of Medicine. Hazardous
Substances Data Bank (HSDB). May 23,	2014. <
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~3QhRRm:1>

Kiuchi, F., Nakamura, N., Tsuda, Y., Kondo, K and Yoshimura, H. 1988.
Studies on Crude Drugs Effective on Visceral Larva Migrans. IV.
Isolation and Identification of Larvicidal Principles in Pepper Chemical
and Pharmaceutical Bulletin 36: 2452.

Likhitwitayawuid, K., Ruangrungsi, N, Lange, G and Decicco, C.. 1987.
Structural Elucidation and Synthesis of New Components isolated from
Piper Samentosum Tetrahedron 43: 3689-3694.

Trigui M, Pulvin S, Poupin P, Thomas D. 2003. Biodegradation of cyclic
amines by a Pseudomonas strain involves an amine mono-oxygenase. Can J.
Microbiol 49: 181-188. 

WHO, 2006. Food Additive Series 56: Aliphatic and Aromatic Amines and
Amides. FAO/WHO Joint Expert Committee on Food Additives.
http://www.inchem.org/documents/jecfa/jecmono/v56je13.pdf

X.  		GLOSSARY OF ACRONYMS AND ABBREVIATIONS

BRAD	Biopesticides Registration Action Document

C.F.R.	Code of Federal Regulations

cSt	centistokes	

EDSP	Endocrine Disruptor Screening Program

EP	end-use pesticide product

EPA	United States Environmental Protection Agency (the “Agency”)

FFDCA	Federal Food, Drug, and Cosmetic Act

FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act

FR	Federal Register

g/cm3	grams per cubic centimeter

lb/gal	pounds per gallon

LD50	median lethal dose. A statistically derived single dose that can be
expected 

	to cause death in 50% of the test animals when administered by the
route 

	indicated (oral, dermal, or inhalation). It is expressed as a weight of


	substance per unit weight of animal (e.g., mg/kg).

mg/kg	milligrams per kilogram

mL	milliliter

MP	manufacturing-use pesticide product

MPCA 	microbial pest control agent

MRID No.	Master Record Identification Number

NIOSH 	National Institute for Occupational Safety and Health

OPP	Office of Pesticide Programs

PC Code	Pesticide Chemical Code

PPE	personal protective equipment

TGAI 	technical grade of the active ingredient

U.S. 		   United States

Biopesticides Registration Action Document

Sarmentine

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