Document ID: EPA-HQ-OPP-2011-0190-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-03-30T04:00Z

N6-Benzyladenine 

Preliminary Work Plan and Summary Document

Registration Review: Initial Docket

March 2011

 

Case 2040

PC Code 

116901

Approved by:

Keith Matthews

Director, Biopesticides and 

Pollution Prevention Division

Date

TABLE OF CONTENTS  TOC \o "1-3" \u  

I.	PRELIMINARY WORK PLAN	4

A.	Introduction	4

B.	Background and Regulatory Information	4

C.	Anticipated Risk Assessment and Data Needs	5

1.	Product Analysis	5

2.	Human Health Risk Assessment Status	6

3.	Environmental Fate and Ecological Risk Assessment Status	9

4.	Risk to Threatened and Endangered Species	10

5.	Endocrine Disruptor Screening Program	10

6.	Incidents	11

D.	Timeline	12

E.	Guidance for Commenters	12

F.	Environmental Justice	12

G.	Water Quality	13

H.	Trade Irritants	13

I.	Next Steps	13

II.     FACT SHEET	14

BIBLIOGRAPHY	18

 

LIST OF TABLES

  TOC \h \z \c "Table"    HYPERLINK \l "_Toc264130234"  Table 1. 
Chemical Identity Data	5 

  HYPERLINK \l "_Toc264130235"  Table 2.  Product Chemistry Data
Requirements	6 

  HYPERLINK \l "_Toc264130236"  Table 3.  Toxicology Data	7 

  HYPERLINK \l "_Toc264130237"  Table 4.  Ecotoxicity Data	9 

  HYPERLINK \l "_Toc264130238"  Table 5.  Projected Timeline	1 2

  HYPERLINK \l "_Toc264130239"  Table 6.  Products Containing
N6-Benzyladenine 	1 5

  

N6-BENZYLADENINE REGISTRATION REVIEW TEAM

Product Chemistry  

Jacob Moore

Human Health  

Angela L. Gonzales

Environmental Effects  

Russell Jones, Ph.D

Risk Management  

	Chris Pfeifer

Office of General Counsel  

	Philip Ross, Esq.

I.	PRELIMINARY WORK PLAN

	A.	Introduction

	The Food Quality Protection Act (FQPA) of 1996 mandated the continuous
review of existing pesticides.  All pesticides distributed or sold in
the United States must generally be registered by the U.S. Environmental
Protection Agency (EPA or the Agency), based on scientific data showing
that they will not cause unreasonable risks to human health or the
environment when used as directed on the product labeling.  The
Registration Review program is intended to make sure that, as the
ability to assess risk evolves and as policies and practices change, all
registered pesticides continue to meet the statutory standard of no
unreasonable adverse effects.  Changes in science, public policy, and
pesticide use practices will occur over time.  Through the Registration
Review program, the Agency periodically reevaluates pesticides to make
sure that as change occurs, products in the marketplace can continue to
be used safely.  Information on this program is provided at: 
http://www.epa.gov/oppsrrd1/registration_review/.  

	The Agency has begun to implement the Registration Review program
pursuant to Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
section 3(g) and will review each registered pesticide every 15 years to
determine whether it continues to meet the FIFRA standard for
registration. The Agency will consider benefits information and data as
required by FIFRA.  The public phase of Registration Review begins when
the initial docket is opened for each case.  The docket is the
Agency’s opportunity to state what it knows about the pesticide and
what additional risk analyses and data or information it believes are
needed to make a Registration Review decision.  After reviewing and
responding to comments and data received in the docket during this
comment period, the Agency will develop and commit to a final work plan
and schedule for the Registration Review.

	This Registration Review Summary Document evaluates the biochemical
pesticide active ingredient (a.i.) N6-Benzyladenine, PC Code 116901. 

	B.	Background and Regulatory Information

N6-Benzyladenine is a plant growth regulator (PGR), which is registered
for use to enhance flowering, fruit shape, fruit size, later and basal
bud break, and shoot growth. It is also registered for use as a thinning
agent. Historically, the Agency classified the chemical as a synthetic
cytokinin. However, more recent data indicate that the chemical is
naturally occurring in plant tissues (EPA, 1994; van Staden & Crouch,
1996).

N6-Benzyladenine was first registered by the Agency in 1979.  It is
formulated as a liquid and is applied as a spray to apples, pears,
pistachios, nonbearing sweet cherries and ornamental plants. In 1995,
N6-Benzyladenine was exempted from the requirement of a tolerance for
use on apples under 40 CFR 180.1150. The exemption was amended in 2004
to include pistachios, and again in 2007 to include pears. 

 	

Applications to apples and pears are limited to a rate of less than or
equal to182 grams of active ingredient per acre per season; and
applications to pistachios are limited to a rate of less than or equal
to 60 grams of active ingredient per acre per season. There are
currently 14 registered products containing the active ingredient.  Four
of these products are manufacturing-use products (MPs); the remaining 10
are end-use products (EPs).  Of the 10 EPs, six contain N6-Benzyladenine
in combination with another plant growth regulator – Gibberellic Acid;
and the remaining four EPs contain N6-Benzyladenine as the sole active
ingredient. 

	

C.	Anticipated Risk Assessment and Data Needs

	Below is a discussion of how the current data requirements for
N6-Benzyladenine, are satisfied by available data.  The pertinent data
areas include:  Product Analysis, Toxicology (human health), and
Nontarget Organisms and Environmental Fate (ecotoxicology).    

	1.	Product Analysis 

		 (40 CFR 158.2030)

	

	The Agency has conducted a review of the available product chemistry
data and information for N6-Benzyladenine and has concluded that all
biochemical pesticide data requirements for the technical grade active
ingredient have been satisfied.  Table 1 provides information on
chemical identity; and Table 2 reflects the fulfillment of the product
chemistry data requirements.

Table 1.  N6-Benzyladenine Chemical Identity

Table 2.  N6-Benzyladenine Product Chemistry Data Requirements Summary 

Guideline No.	Physical and Chemical Properties	Status1	Value

830.1100	Product Identity and Composition	A	Refer to Table 1.

830.1200	Description of starting materials, production and formulation
process	A	CBI

830.1400	Discussion of formation of impurities	A	CBI

830.1700	Preliminary analysis	A	CBI

830.6302	Color	A	Pale yellow

830.6303	Physical state		A	Solid @ 20°C

830.6304	Odor	A	None

830.6313	Stability to normal and elevated temperatures, metals and metal
ions	A	Stable

830.7000	pH	A	4.25 @ 20°C

830.7050	UV/Visible light absorption	A	Neutral λ=270.0nm, ε=19580

830.7200	Melting point/melting range	A	230-232°C

830.7220	Boiling point/boiling range	N/A	N/A

830.7300	Density	A	1.27 g/cc @ 20°C

830.7520	Particle size, fiber length, and diameter distribution	N/A	N/A;
water soluble

830.7550

830.7560

830.7570	Partition coefficient (n-Octanol/Water)	N/A	N/A; compound is a
polar organic material

830.7840	Water solubility 	A	Soluble

830.7950	Vapor pressure	A	Very low; typical solid

A=Acceptable, N/A=Not Applicable, N/D=Not Determined

	Sources:  EPA MRID 447102-02, -03, and -04.

	2.	Human Health Risk Assessment Status 

		(40 CFR 158.2050)

Based on available data and information, the Agency does not foresee the
need for new data or new human health risk assessments for this active
ingredient.  Hazard and exposure information as well as Agency risk
assessments on N6-Benzyladenine were evaluated against current safety
standards established by the Agency’s scientific policies and
regulations, and it was determined that there is no need to conduct
additional risk assessments.  The active ingredient is a naturally
occurring cytokinin, has a non-toxic mode of action, and is of low
toxicity. This toxicity information supporting the registration of
N6-Benzyladenine is summarized in Table 3, below. 

	All occupational and non-occupational risk is expected to be
insignificant because of the nontoxic mode of action and low exposure
resulting from the low application rates of products containing
N6-Benzyladenine.  The end-use product labels intended for food use
state that no more than 182 g may be applied per acre per year; and none
of the non-food use application rates exceed that limitation. 
Additionally, all food use labels specify that no more than two
applications can be made in a growing season. And all labels limit
applications to three or seven day intervals between applications,
depending on the particulars of the plant growth stage or the seasonal
conditions. Labels for all products containing N6-Benzyladenine require
the following personal protective equipment (PPE) for
applicators/handlers: long sleeve shirt, long pants, shoes, socks,
waterproof gloves, and for exposure in enclosed areas or outdoors,
dust/mist filtering NIOSH approved respirator. Because of a lack of
significant acute toxicity and the minimal exposure associated with use
of this plant growth regulator, EPA does not foresee the need for new
data or for a new human health risk assessment for N6-Benzyladenine.

Table 3. Human Health Assessment Data Requirements for N6-Benzyladenine

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

Acute oral toxicity (rat)

(870.1100)

	LD50 = 1,300 mg/kg	III	120681

	LD50 = 2,094 mg/kg (95% C.I. = 1,641-2,675 mg/kg) (males) 1

LD50 = 814 mg/kg (95% C.I. = 598-1,087) (females) 1

LD50 = 1,584 mg/kg (95% C.I. = 1,395-1,871) (males and females combined)
	III	44264804

Acute dermal toxicity (rabbit)	

(870.1200)

	LD50 > 5,000 mg/kg	IV	120681

	LD50 > 2,000 mg/kg	III	44264805

Acute inhalation toxicity	 (rat)

(870.1300)	LC50 = 5.2 mg/L	IV	41623701

	LC50 > 5.25 mg/L	IV	44264806

Primary eye irritation (rabbit)	

(870.2400)	Moderate irritant	III	120681

	Moderate irritant	III	44264807

Primary dermal irritation (rabbit)

(870.2500)	Slight irritant	IV	41895206

	Non-irritating	IV	44264808

Dermal sensitization  (guinea pig)

(870.2600)	Not a sensitizer

41623702

	Not a sensitizer

44264809

Hypersensitivity incidents

(885.3400)	Must be reported as adverse effects data.

N/A

90-Day oral toxicity (rat)

(870.3100)	NOEL = 111 mg/kg bw-day.  

LOEL = 304 mg/kg bw-day. Toxicity based on decreased body weight and
body weight gain, increase in blood urea/nitrogen (BUN) level and
minimal histologic changes in kidneys.  

42329201

90-Day dermal toxicity

(870.3250)	No purposeful dermal application or prolonged dermal exposure
anticipated due to current use patterns and appropriate personal
protective equipment (PPE) requirements on EP labels.  90-day oral data
have been submitted and there is no information available to the Agency
indicating that N6-benzyladenine will be metabolized differently by the
dermal route than by the oral route of exposure.  

N/A

90-Day inhalation toxicity

(870.3465)	Based on the current use patterns and PPE requirements on EP
labels, significant levels of repeated inhalation exposure to the active
ingredient as a gas, vapor or aerosol are not anticipated.

N/A

In vitro mammalian cell assay 

(870. 5300)

	Not mutagenic

41573002

41747701

43340501

	

Not mutagenic in the absence of metabolic activation.  In the presence
of metabolic activation there was a significant increase in the mutation
frequency at 400 µg/ml and 450 µg/ml. 

44264811

In vitro mammalian cell assay 

(870. 5375)

	No reproducible evidence of clastogenic activity (chromosome
aberrations) at concentrations of 125 to 1,000 µg/ml in the presence or
absence of metabolic activation.  

44264812

Bacterial reverse mutation test 

(870.5100)

	Not mutagenic

41573001

	Not mutagenic

44264810

Unscheduled DNA synthesis (rat hepatocyte) 

(870.5550)	Not mutagenic

41573003

Developmental toxicity (rat)

 (870.3700)	Maternal and developmental NOEL = 50 mg/kg bw-day.  

Maternal and developmental LOEL = 175 mg/kg bw-day. Maternal toxicity
based on significantly decreased body weight and body weight gain and
food consumption. Developmental toxicity based on altered growth,
decreased fetal body weight, hydrocephalus, increased unossified
sternebrae, and incompletely ossified phalanges. 

41623703

Reproduction and fertility effects (rat)

(870.3800)

	Parental systemic toxicity: 

NOAEL = 31.5-37.5 mg/kg bw-day.  

LOAEL = 58.6-70.4 mg/kg bw-day.  Toxicity based on reduced body weight
and weight gain in F0 and F1 males.  

Reproductive toxicity:

NOAEL > 115.7-144.2 mg/kg bw-day (males) and > 133.0-139.2 mg/kg bw-day
females.

LOAEL could not be determined.

Offspring toxicity:

NOAEL = 35.8-36.0 mg/kg bw-day

LOAEL = 66.7-68.1 mg/kg bw-day.  Toxicity based on decreased body weight
and weight gain in F1 and F2 males and females. 

46388302

		

3.	Environmental Fate and Ecological Risk Assessment Status

		(40 CFR 158.2060)

	All current nontarget organism toxicology data requirements for
N6-Benzyladenine have been satisfied and continue to support its
registration. (See Table 4. below.) N6-Benzyladenine is relatively
non-toxic to nontarget organisms.  It has no known toxicity to plants
(when applied exogenously) and data confirm that the active ingredient
is only slightly toxic to mammals, birds, and freshwater fish.  Given
the negligible toxicity to nontarget organisms and the minimal
application rates associated with this plant growth regulator, no
further ecotoxicity data are expected to be required to support
registration.  

Table 4.  Summary of Non-Target Organism Data

Study Type/OPPTS Guideline	

LD50/LC50/EC50 Results	

Toxicity Category	MRID

 Acute Oral Toxicity

/OPPTS 870.1100  	1300 mg/kg (rat)	Tox Category III	00120681

	1584 mg/kg (rat)	Tox Category III	PPDB, 2011

 Subchronic Oral Toxicity (rat), 90-day

/OPPTS 870.3100  	NOEL = 1500 ppm

LOEL = 5000 ppm	

Practically non-toxic	42329201

 Avian Acute Oral Toxicity

/OPPTS 850.2100  	1599 ppm	

Slightly toxic 1	41895204

	2875 ppm	

Practically non-toxic	PPDB, 2011

 Avian Dietary Toxicity

/OPPTS 850.	>5620 ppm	

Practically non-toxic	41895205

Freshwater Fish Acute Toxicity, 96 hr

/OPPTS 850.1075  	21.4 ppm 2	Slightly toxic	41895206

	42.0 ppm 3	Slightly toxic	PPDB, 2011

Aquatic Freshwater Invertebrate Toxicity, 48-hr /OPPTS 850.1010 	

17.0 mg/L 4	Slightly toxic	41895207

	

>20.5 mg/L 4	No toxicity at highest tested dose	PPDB, 2011

	4.52 mg/L 5	Moderately toxic	PPDB, 2011

Other Arthropods (non-Guideline)	80 g/hectare 6	Not applicable	PPDB,
2011

	36.2 g/hectare 7	Not applicable	PPDB, 2011

Earthworms (non-Guideline) (14-day)	>500 mg/kg	No toxicity at highest
dose tested	PPDB, 2011

Non-target Plants

	Waiver	

No expected adverse effects	N-6-BA RED (1994)

Non-target Insects (Honey Bee Contact Toxicity, 48-hr)/OPPTS 850.3020	
>25 ng/bee	

Practically non-toxic	41623704

	>58.73 ng/bee	

Practically non-toxic	PPDB, 2011

1	The Benzyladenine RED incorrectly categorized avian acute oral
toxicity as practically non-toxic and avian dietary toxicity as slightly
toxic, when the reverse was true based on the data (see EPA, 1994).

2	Onchorhyncus mykiss

3	Brachydanio rerio

4	Daphnia

5	Chironomus riparius (96-hr)

6	Typhlodromus pyri

7	Aphidius rhopalosiphi

	

	4.	Risk to Threatened and Endangered Species 

	

		Based on the N6-Benzyladenine’s relative non-toxicity to nontarget
organisms and on its minimal use rates, EPA has determined that
N6-Benzyladenine will have "No Effect" on any currently listed
threatened or endangered species or any designated critical habitat. 
The Terrestrial Exposure Model (T-REX; EPA, 2005) was run using maximum
use rates and the risks to terrestrial nontarget organisms were
determined to be significantly below the level of concern. Similarly,
aquatic risks were assessed using the Generic Estimated Environmental
Concentration Model, Version 2 (GENEEC 2; EPA, 2001) and determined to
be negligible.  EPA’s Endangered Species Assessment for
N6-Benzyladenine (including risk quotients for each class of nontarget
organisms) can be found in the docket - EPA-HQ-OPP-2011-0190 – under
the memorandum title “Nontarget Organism and Endangered Species
Screening Risk Assessment for the N6-Benzyladenine Registration
Review.”

	5.	Endocrine Disruptor Screening Program 

	As required by FIFRA and FFDCA, EPA reviews numerous studies to assess
potential adverse outcomes from exposure to chemicals.  Collectively,
these studies include acute, subchronic and chronic toxicity, including
assessments of carcinogenicity, neurotoxicity, developmental,
reproductive, and general or systemic toxicity. These studies include
endpoints which may be susceptible to endocrine influence, including
effects on endocrine target organ histopathology, organ weights, estrus
cyclicity, sexual maturation, fertility, pregnancy rates, reproductive
loss, and sex ratios in offspring.  For ecological hazard assessments,
EPA evaluates acute tests and chronic studies that assess growth,
developmental and reproductive effects in different taxonomic groups. 
As part of its reregistration decision, EPA reviewed these data and
selected the most sensitive endpoints for relevant risk assessment
scenarios from the existing hazard database.  However, as required by
FFDCA section 408(p), N6-Benzyladenine is subject to the endocrine
screening part of the Endocrine Disruptor Screening Program (EDSP). 

	EPA has developed the 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 1 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 1 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. 

 	Under FFDCA section 408(p), the Agency must screen all pesticide
chemicals.  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 9 inert ingredients. 
N6-Benzyladenine is not among the group of 58 pesticide active
ingredients on the initial list to be screened under the EDSP. 
Accordingly, as part of registration review, EPA will issue future EDSP
orders/data call-ins, requiring the submission of EDSP screening assays
for N6-Benzyladenine.  For further information on the status of the
EDSP, the policies and procedures, the list of 67 chemicals, future
lists, the test guidelines and the Tier 1 screening battery, please
visit our website:   HYPERLINK "http://www.epa.gov/endo/"
http://www.epa.gov/endo/ .

	6.	Incidents 

	According to the Agency’s Office of Pesticide Programs Incident Data
System (IDS), there have been two reported incidents from the use of
EPA-registered products containing N6-Benzyladenine as their only active
ingredient. On April 1, 1993 a human illness was attributed to an early
reentry infraction and a misuse of PPE; no additional information was
available concerning this incident.  On January 1, 1999, there was an
incident of spotting and burning on the crop (likely phytotoxicity), and
a worker developed a rash.  There is no explanation associated with the
incident report; but phytotoxicity and rash would be consistent with an
over-application of the pesticide.  The Agency is not requiring more
information or a revised risk assessment based on these incidents
because none of the preceding reported incidents are attributable to
information unknown to the Agency regarding the nature of
N6-Benzyladenine. Label language, including the requirement of PPE, for
N6-Benzyladenine products are appropriate and sufficient to protect the
users/handlers of these products. The Agency will consider any incident
data or comments submitted to this docket in response to this
preliminary work plan.

D.	Timeline

	The projected timeline for the Registration Review of N6-Benzyladenine,
Case 2040, is shown in Table 5, below.

	

Table 5.  Projected Timeline for the Registration Review of Case 2040

Activities	Estimated Month/Year

Open Public Comment Period for N6-Benzyladenine	March 2011

Close Public Comment Period 	May 2011

Develop Final Work Plan (FWP)	September 2011

Open Public Comment Period for Proposed Reg. Review Decision 	March 2012

Close Public Comment Period 	May 2012

Final Decision 	June 2012

Total (years)	1.25

E.	Guidance for Commenters

	The public is invited to comment on EPA’s preliminary work plan and
rationale.  The Agency will consider all comments as well as any
additional information or data provided in a timely manner prior to
issuing a final work plan for the case.

 

	

	F.	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, in the development, implementation, and
enforcement of environmental laws, regulations, and policies.  To help
address potential environmental justice issues, the Agency seeks
information on any groups or segments of the population who, as a result
of their location, cultural practices, or other factors, may have
atypical, unusually high exposure to N6-Benzyladenine compared to the
general population.  Please comment if you are aware of any
subpopulations that may have atypical, unusually high exposure compared
to the general population.

G.	Water Quality

	N6-Benzyladenine is not identified as a cause of impairment for any
water bodies listed as impaired under section 303(d) of the Clean Water
Act, based on information provided at:  http://www.epa.gov/owow/tmdl/. 
In addition, no Total Maximum Daily Loads (TMDL) have been developed for
N6-Benzyladenine based on information provided at: 
http://iaspub.epa.gov/tmdl_waters10/text_search.tmdl_search_form.  More
information on impaired water bodies and TMDL’s can be found at: 
http://www.epa.gov/owow/tmdl/.  The Agency invites submission of water
quality data for this pesticide.  To the extent possible, data should
conform to the quality standards in Appendix A of the Office of
Pesticide Program’s (OPP) Standard Operating Procedure:  Inclusion of
Impaired Water Body and Other Water Quality Data in OPP’s Registration
Review Risk Assessment and Management Process (see: 
http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm)
to ensure they can be used quantitatively or qualitatively in pesticide
risk assessments.

	H.	Trade Irritants

	Through the Registration Review process, the Agency intends to solicit
information on trade irritants and, to the extent feasible, take steps
toward facilitating irritant resolution.  Growers and other stakeholders
are asked to comment on any trade irritant issues resulting from lack of
Maximum Residue Limits (MRL’s) or disparities between United States
tolerances and MRL’s in key export markets, providing as much
specificity as possible regarding the nature of the concern.  In the
case of N6-Benzyladenine (Case 2040), there are currently no established
residue tolerances.  Additionally, there is no MRL established for
N6-Benzyladenine.  Therefore, the Agency does not anticipate that
current uses of N6-Benzyladenine will pose concerns as trade irritants.

I.	Next Steps

	After the 60-day comment period closes, the Agency will review and
respond to any comments received in a timely manner and then issue a
Final Work Plan for Case 2040: N6-Benzyladenine.  

II.  	FACT SHEET for N6-BENZYLADENINE 

Background Information 

Registration Review Case Number: 2040

PC Code: 116901

CAS #:  1214-39-7

Common Name: Benzyladenine

Synonyms and Abbreviations:  6-Benzylaminopurine, benzyl adenine, 6-
Benzyladenine, N-6-BA, 6-BA, BAP

First Registered: 1979

Products: 4 MPs, 10 EPs

Physical Description:  Pale yellow liquid

Mode of Action:  Plant Growth Regulator to enhance flowering, fruit
shape, fruit size, later and basal bud break, and shoot growth. It is
also registered for use as a thinning agent.

Use Sites: For commercial use on apples, pears, pistachios and
ornamentals.

Method of Application: Primarily spray applications; but there are also
paint-on and drip applications.

Use Limitation: Food applications are limited per 40 CFR 180.1150

Previous Regulatory Documents: RED Fact Sheet, Exemption from the
Requirement of a Tolerance 

Registration Review Lead: Chris Pfeifer; pfeifer.chris@epa.gov

Products Labels

Labels for the N6-Benzyladenine products may be found at: 
http://oaspub.epa.gov/pestlab1/ppls.home, which is the Office of
Pesticide Programs’  Pesticide Product Label System (PPLS) website.  

B.	Description of Active Ingredient

N6-Benzyladenine is a naturally occurring plant growth regulator (PGR),
which is registered for use to enhance flowering, fruit shape, fruit
size, later and basal bud break, and shoot growth. It is also registered
for use as a thinning agent. It is formulated as a liquid and is applied
as a spray to apples, pears, pistachios, nonbearing sweet cherries and
ornamental plants. N6-Benzyladenine is used to enhance flowering, fruit
shape, fruit size, later and basal bud break, and shoot growth. It was
exempted from the requirement of a tolerance for use on apples in 1995
under 40 CFR 180.1150. The exemption was amended in 2004 and 2007 to
include pistachios and pears. Applications to apples and pears are
limited to a rate of less than or equal to 182 grams of active
ingredient per acre per season; and applications to pistachios are
limited to a rate of less than or equal to 60 grams of active ingredient
per acre per season.  All labels specify that no more than two
applications be made in a growing season, with either a three or seven
day interval between applications depending on plant growth stage and
seasonal conditions.

C.	Use Information 

	Screening estimates for N6- Benzyladenine usage in 2010 indicate a
maximum usage of 4000 pounds of active ingredient.  Half the estimated
use of N6- Benzyladenine is attributed to applications to apples; and
the balance of the use is evenly divided among pears, pistachios,
potatoes, cotton and ornamentals.

Table 6. Products Containing N6-Benzyladenine

EPA Reg. #	Registration Name	Company Name	Current Status	% of Active
Ingredient

55146-77	BA6 TECHNICAL	NUFARM AMERICAS INC.	Registered 1999	98.2

55146-78	TYPY PLANT GROWTH REGULATOR	NUFARM AMERICAS INC.	Registered
1999	1.8

55146-86	AGTROL 6-BA	NUFARM AMERICAS INC.	Registered 2000)	1.8

62097-5	BAP TECHNICAL	FINE AGROCHEMICALS, LTD	Registered 1998	99.8

62097-6	PERLAN	FINE AGROCHEMICALS, LTD	 Registered 1998	1.8

62097-9	EXILIS PLUS	FINE AGROCHEMICALS, LTD	 Registered 2000	2

62097-19	CONFIGURE	FINE AGROCHEMICALS, LTD	  HYPERLINK
"javascript:viewStatus(486160,0,14)"  Registered 2007 	2

71368-60	RITEWAY	NUFARM, INC.	  HYPERLINK
"javascript:viewStatus(476141,0,13)"  Registered 2005 	1.9

72992-10	CHRYSAL BVB	CHRYSAL INTERNATIONAL BV	  HYPERLINK
"javascript:viewStatus(39898,0,14)"  Registered 2003 	1.8

73049-29	ACCEL PLANT GROWTH REGULATOR SOLUTION	VALENT BIOSCIENCES
CORPORATION	Registered 2000

	1.8

73049-41	PROMALIN PLANT GROWTH REGULATOR SOLUTION	VALENT BIOSCIENCES
CORPORATION	Registered 2000

	1.8

73049-59	6-BENZYLADENINE TECHNICAL	VALENT BIOSCIENCES CORPORATION
Registered 2000	97.9

73049-407	MAXCEL	VALENT BIOSCIENCES CORPORATION	Registered 2004	1.9

83028-5	6-BENZYLAMINOPURINE TECHNICAL	NCA BIOTECH, INC.	  HYPERLINK
"javascript:viewStatus(486754,0,14)"  Registered 2007 	99

* Products featured in the highlighted rows also contain the plant
growth regulator Gibberellic Acid.

D.	Recent Actions

The Agency issued a RED for N6-Benzyladenine in June of 1994.  The RED
concluded that there was sufficient information on file to support the
uses of N6-Benzyladenine but required the submission of confirmatory
toxicological data for dermal sensitization and mutagenicity for future
applications.  Adequate confirmatory data regarding mutagenicity and
dermal sensitization data were subsequently submitted as part of an
application to amend a registration that was accompanied by a request
to amend the tolerance exemption to include pistachios. The exemption
was amended in April of 2004 to include pistachios, and again in March
of 2007 to include pears. 

 

E.	Product Analysis

	The Agency has conducted a review of the available product chemistry
data and information for N6-Benzyladenine.  Product chemistry
information for N6-Benzyladenine, provided by the registrants, is
sufficient to fulfill the respective product chemistry data requirements
outlined in 40 CFR 158.2030.  

F.	Human Health Risk Assessment 

		Meeting the Current Data Requirements:  Status

The Agency does not foresee the need for new data or for a new human
health risk assessment for N6-Benzyladenine. All data requirements as
outlined in 40 CFR 158.2050 have been satisfied for N6-Benzyladenine. 

		Exposure Assessment

	All occupational and non-occupational risk associated with
N6-Benzyladenine end-use products (EPs) is expected to be insignificant
because of the nontoxic mode of action and low exposure resulting from
the low application rates of these products. 

	 

Dietary (Food and Water).  Products containing N6-Benzyladenine may be
applied to apples pears and pistachios; however, their use is not
expected to result in any significant dietary exposure to humans. 
Applications occur approximately four months before harvest and
application rates are low. Applications to apples and pears are limited
to a rate of less than or equal to 182 grams of active ingredient per
acre per season; and applications to pistachios are limited to a rate of
less than or equal to 60 grams of active ingredient per acre per season.
 All labels specify that no more than two applications be made in a
growing season, with either a three or seven day interval between
applications, depending on the stage of growth and seasonal conditions.
The residues resulting from the low use rates are not expected to
significantly increase dietary intake over that anticipated from
consumption of these substances as they natural occur in plants that are
part of a normal human diet. Regarding exposure through drinking water,
N6-Benzyladenine has not been identified as a cause of impairment for
any water bodies listed as impaired under section 303(d) of the Clean
Water Act.  

Residential exposure is expected to be insignificant via the dermal and
inhalation routes due to the commercial nature of the use patterns and
the low percentages of AI and low application rates for N6-Benzyladenine
EPs. 

 

Occupational exposure is expected to individuals who handle this
pesticide through mixing and loading and to those who apply the
pesticide. All occupational risk is expected to be insignificant due to
low application rates of these products and PPE requirements. The active
ingredient does not exceed 2% of any EP. No applications exceed 182 g
per acre per year.  And all labels for these products currently require
the follow PPE for applicators/handlers: long sleeve shirt, long pants,
shoes, socks, waterproof gloves, and for exposure in enclosed areas or
outdoors, dust/mist filtering NIOSH approved respirator.   

	Tolerance Exemption 

	

40 CFR 180.1150: 6-Benzyladenine; exemption from the requirement of a
tolerance.  The biochemical plant regulator 6benzyladenine (6BA) is
exempt from the requirement of a tolerance in or on apple and pear when
applied at a rate of less than or equal to 182 grams of active
ingredient per acre per season, and in or on pistachio when applied at a
rate of less than or equal to 60 grams of active ingredient per acre per
season.  [72 FR 13179, March 21, 2007]

Environmental Fate and Ecological Risk Assessment 	

Meeting the Current Data Requirements:  Status

The Agency considers the nontarget organisms and environmental fate
biochemical data requirements, as outlined in 40 CFR 158.2060, to be
complete for N6-Benzyladenine at this time. 

	Exposure Assessment

	N6-Benzyladenine is a naturally-occurring plant hormone, has a
non-toxic mode of action, and is of low toxicity.  It has no known
toxicity to nontarget plants; and data confirm that the active
ingredient is only slightly toxic to mammals, birds, and freshwater
fish.  A screening level assessment was conducted to evaluate the risks
posed by exposure to nontarget organisms.  The risk quotients for all
nontarget organisms were significantly below any LOC.  The assessment
determined that nontarget exposures to N6-Benzyladenine will have "No
Effect" on any currently listed threatened or endangered species or any
designated critical habitat. 



BIBLIOGRAPHY

Studies 

MRID	Citation

120681	Majors, K.; Emerson, J.; Levin, S.; et al. (1976) Acute Toxicity
Evaluations of ABG-3001 and Ingredients: Study Nos. T76-276 through
T76-281, T76-304, T76-305, T76-357 and T75-591. (Unpublished study
received Jan 13, 1977 under 275-32; submitted by Abbott Laboratories,
North Chicago, IL; CDL:095728-D) 

41573001	Jagannath, D. (1987) Mutagenicity Test on 6-Benzyladenine in
the Ames Salmonella/Microsome: Reverse Mutation Assay: Lab Project
Number: 9975-0-401. Unpublished study prepared by Hazleton Laboratories
America, Inc. 34 p. 

41573002	Ivett, J. (1987) Mutagenicity Test on 6-Benzyladenine 16262 in
the In Vivo Mouse Micronucleus Assay: Lab Project Number: 9975-0- 455.
Unpublished study prepared by Hazleton Laboratories America, Inc. 20 p. 

41573003	Cifone, M. (1988) Mutagenicity Test on 6-Benzyladenine in the
Rat Primary Hepatocyte: Unscheduled DNA Synthesis Assay: Lab Project
Number: 9975-0-447. Unpublished study prepared by Hazleton Laboratories
America, Inc. 23 p. 

41623701	Hoffman, G. (1990) An Acute Inhalation Toxicity Study of
6-Benzyladenine in the Rat: Lab Project Number: 89/8248. Unpublished
study prepared by Bio/dynamics Inc. 141 p. 

41623702	Kreuzmann, J. (1990) Delayed Contact Hypersensitivity Study in
Guinea Pigs of: 6-Benzyladenine: Lab Project Number: 90-4028-21.
Unpublished study prepared by Hill Top Biolabs, Inc. 57 p. 

41623703	Hui, J. (1990) Evaluation of the Effects of Orally Administered
6-Benzyladenine (ABBOTT-39313) on the Embryonic and Fetal Development of
the Rat (Segment II TFR): Lab Project Number: TA90-007. Unpublished
study prepared by Abbott Laboratories. 17 p. 

41623704	Atkins, E. (1990) Bee Adult Toxicity Dusting Test Evaluating
Comparative Acute Contact & Stomach Poison Toxicity of 6-Benzyladenine
to Honey Bee Worker Adults: Lab Project Number: 90-834. Unpublished
study prepared by Univ. of California, Dept. of Entomology & Apiology.
26 p. 

41747701	Ivett, J. (1990) Supplemental Data for MRID 415730-02:
Mutagenicity Test on 6-Benzyladenine 16262 in the in vivo Mouse
Micronucleus Assay: Lab Project Number: 9975-0-455. Unpublished study
prepared by Hazleton Laboratories America, Inc. 10 p. 

41895204	Campbell, S. (1991) 6-Benzyladenine (Encapsulated): An Acute
Oral Toxicity Study with the Northern Bobwhite: Lab Project Number:
161-120. Unpublished study prepared by Wildlife Int., Ltd. 21 p. 

41895205	Beavers, J. (1991) 6-Benzyladenine: A Dietary LC50 Study with
the Northern Bobwhite: Lab Project Number: 161-119. Unpublished study
prepared by Wildlife Int., Ltd. 41 p. 

41895206	Shults, S. (1991) Primary Dermal Irritation Study in Albino
Rabbits with 6-Benzyladenine: Lab Project Number: 91-0095. Unpublished
study prepared by Ricerca, Inc. 19 p. 

41895207	Murphy, D. (1991) 6-Benzyladenine/Code 16262: A 48-Hour Static
Daily Renewal Acute Toxicity Test with the Cladoceran (Daphnia magna):
Lab Project Number: 161A-102. Unpublished study prepared by Wildlife
Int., Ltd. 61 p. 

42329201	Salamon, C. (1992) 13-Week Dietary Toxicity Study with
6-Benzyladenine in Rats: Lab Project Number: 6161-117. Unpublished study
prepared by Hazleton Wisconsin, Inc. 262 p. 

43340501	Ivett, J. (1987) Mutagenicity Test on 6-Benzyladenine 16262 in
the In vivo Mouse Micronucleus Assay: Supplemental: Lab Project Number:
9975-0-455. Unpublished study prepared by Hazleton Labs America, Inc. 7
p. 

44264804	McRae, L. (1997) BAP 99% Technical: Acute Oral Toxicity to the
Rat: Lab Project Number: FNA 30: FNA 93/963173/AC. Unpublished study
prepared by Huntingdon Life Sciences, Ltd. 30 p. 

44264805	McRae, L. (1997) BAP 99% Technical: Acute Dermal Toxicity to
the Rat: Lab Project Number: FNA 31: FNA 31/962595/AC. Unpublished study
prepared by Huntingdon Life Sciences, Ltd. 21 p. 

44264806	Jackson, G. (1997) Acute Inhalation Toxicity to Rats of BAP
99%: Lab Project Number: FNA 22/962519. Unpublished study prepared by
Huntingdon Life Sciences Ltd. 34 p. 

44264807	Parcell, B. (1997) BAP 99% Technical: Eye Irritation to the
Rabbit: Lab Project Number: FNA 33/962930/SE: FNA 33. Unpublished study
prepared by Huntingdon Life Sciences Ltd. 21 p. 

44264808	Liggett, M. (1997) BAP 99% Technical: Skin Irritation to the
Rabbit: Lab Project Number: FNA 32/962647/SE: FNA 32. Unpublished study
prepared by Huntingdon Life Sciences Ltd. 19 p. 

44264809	Allen, D. (1997) 6-BAP(6-Benzylaminopurine): Magnusson &
Kligman Maximisation Study in the Guinea Pig: Lab Project Number:
673/001R. Unpublished study prepared by Safepharm Labs Ltd. 33 p. 

44264810	May, K. (1997) BAP: Bacterial Mutation Assay: Final Report: Lab
Project Number: 96/0936: FNA/027: 96/FNA027/0936. Unpublished study
prepared by Huntingdon Life Sciences Ltd. 35 p. 

44264811	Lloyd, J. (1997) BAP: Mammalian Cell Mutation Assay: Final
Report: Lab Project Number: 96/0945: FNA/029: 96/FNA029/0945.
Unpublished study prepared by Huntingdon Life Sciences Ltd. 35 p. 

44264812	Kitching, J. (1997) BAP: Metaphase Chromosome Analysis of Human
Lymphocytes Cultured in vitro: Lab Project Number: FNA 28/962244.
Unpublished study prepared by Huntingdon Life Sciences Ltd. 51 p. 

44710202	Jacobson, S. (1998) Agtrol 6 Benzylaminopurine, 99%--Product
Chemistry Volume I: Lab Project Number: 98704. Unpublished study
prepared by Compliance Services International. 41 p. {OPPTS 830.1550,
830.1600, 830.1620, 830.1650, 830.1670} 

44710203	Jacobson, S. (1998) Agtrol 6 Benzylaminopurine 99%--Product
Chemistry Volume II: Lab Project Number: 98705. Unpublished study
prepared by Compliance Services International. 60 p. {OPPTS 830.1700,
830.1750, 830.1800} 

44710204	Jacobson, S. (1998) Agtrol 6 Benzylaminopurine 99%--Product
Chemistry Volume III: Final Report: Lab Project Number: 98721.
Unpublished study prepared by Compliance Services International. 75 p.
{OPPTS 830.6302, 830.6303, 830.6304, 830.6313, 830.7000, 830.7050,
830.7200, 830.7300, 830.7370, 830.7840, 830.7860, 830.7950} 

46388302	Barton, S.; Jardine, L. (2003) ABG-3191: Two Generation
Reproduction Study in Rats. Project Number: 20716. Unpublished study
prepared by Inveresk Research International. 512 p.

EPA Reviews

		Memorandum from Angela L. Gonzales to Chris Pfeifer. Toxicology
Scoping Document for the Registration Review of N6-benzyladenine. U.S.
Environmental Protection Agency Office of Pesticide Programs. February
3, 2011.  

EPA,  1990.  Classification of N6-Benzyladenine (Chem. No. 116901) as a
Biochemical.  Memorandum from J. T. McClintock to R. Engler

EPA.  1994.  Registration Eligibility Decision.  N6-Benzyladenine.  List
B.  Case 2040.  Environmental Protection Agency, Office of Pesticide
Programs, Special Review and Registration Division.  188 p.    HYPERLINK
"http://www.epa.gov/oppsrrd1/REDs/old_reds/n6benzyladenine.pdf" 
http://www.epa.gov/oppsrrd1/REDs/old_reds/n6benzyladenine.pdf 

EPA.  2001.  GENEEC 2.0 (Generic Estimated Environmental Concentration
Model, Version 2).  Environmental Fate and Exposure Division, Office of
Pesticide Programs.

EPA.  2008.  T-REX (Terrestrial Exposure Model) Version 1.4.1. 
Terrestrial Biology and Exposure Technical Teams, Environmental Fate and
Exposure Division, Office of Pesticide Programs.

Other Information

Van Staden, J & Crouch, NR. (1996). Benzyladenine and Derivatives- Their
Significance and Interconversion in Plants.  Plant Growth Regulation,
19, 153-175.

Pesticide Product Data Base (PPDB).  2011.  6-Benzyladenine (Ref: 
ABG-3191).  Agricultural and Environmental Research Unit, University of
Hertfordshire, UNITED KINGDOM.  January 17, 2011 update,  

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Docket ID: EPA-HQ-OPP-2011-0190	regulations.gov