Document ID: EPA-HQ-OPP-2004-0285-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-08-25T04:00Z

July, 9 2009

MEMORANDUM

 

SUBJECT:  		Inert Ingredient Decision Document for Pesticide Petition
4E6841:  1,2-ethanediamine, N,N,N’,N’-tetramethyl-, polymer with
1,1’-oxybis[2-chloroethane] (CAS Reg. No. 31075-24-8), PC Code 900835

		

FROM:	Keri Grinstead

		Inert Ingredient Assessment Branch

		Registration Division (7505P)

TO:		P. V. Shah, Chief  

		Inert Ingredient Assessment Branch

		Registration Division (7505P)

OVERVIEW

	This decision document is the assessment for
1,2-ethanediamine,N,N,N’,N’-tetramethyl-, polymer with
1,1’-oxybis[2-chloroethane] (CAS Reg. No. 31075-24-8) when used as an
inert ingredient (adjuvant or water conditioner) in pesticide
formulations applied to cotton or wheat only under 40 CFR 180.920.  For
ease of reading throughout this document,
1,2-ethanediamine,N,N,N’,N’-tetramethyl-, polymer with
1,1’-oxybis[2-chloroethane] is referred to as BCETMD copolymer.

EPA received a petition from Buckman Laboratories International, Inc.
requesting an exemption from the requirement of a tolerance in 40 CFR
180.920 for residues of BCETMD copolymer when used as an inert
ingredient in pesticide products applied to growing crops.  The Notice
of Filing for this petition was published in the Federal Register on
September 17, 2004 (69 FR 56062).  No substantive comments were received
in response to this notice.  The petitioner subsequently amended their
petition specifying that the inert ingredient use of BCETMD copolymer
will be as an adjuvant or water conditioner in pesticide products
applied only to cotton and to wheat prior to boot stage.     

	 

EXECUTIVE SUMMARY 

This assessment summarizes available information on the use,
physical/chemical properties, toxicological effects, exposure profile,
and environmental fate of BCETMD copolymer when used as an inert
ingredient in pesticide formulations applied pre-harvest to cotton and
wheat under 40 CFR 180.920 (growing crops only).  BCETMD copolymer has
the same chemical composition as Busan 77, a registered pesticide active
ingredient.  As a result of the Busan 77 registration, sufficient data
have been submitted to support this action.  The petitioner has
submitted the Agency’s reviews of the Busan 77 studies in support of
this tolerance exemption petition for BCETMD copolymer.  The Agency has
determined that these reviews are adequate and appropriate to
characterize the toxicity of BCETMD copolymer.  Excerpts and summaries
of these reviews are presented in this document.  The purpose of this
document is to assess, as required under the Federal Food Drug and
Cosmetic Act (FFDCA), the risk to human health and the environment from
the use of BCETMD copolymer as an inert ingredient in pesticide
formulations applied to cotton and wheat under 40 CFR 180.920.         	

Based on the results of animal studies, BCETMD copolymer exhibits low to
moderate oral toxicity, slight irritation to the rabbit eye and skin,
and is not a skin sensitizer in Guinea pigs.  Reproductive/developmental
toxicity was only seen at dosage levels at or above those which also
caused maternal effects and it was determined not to be mutagenic or
carcinogenic.  In metabolism studies, most (≥86%) of the chemical was
excreted in the feces.  

The primary route of exposure to BCETMD copolymer from its use as an
inert ingredient in pesticide products applied pre-harvest to cotton and
wheat would most likely be through consumption of food to which
pesticide products containing it as an inert ingredient have been
applied, and possibly through drinking water (from runoff).  The use of
this chemical is limited to pesticide formulations pre-harvest to cotton
or wheat crops only, therefore, there are no residential uses of this
chemical, and thus no residential (dermal and inhalation) exposures are
expected. 

Residues of concern are not anticipated for dietary exposure (food and
drinking water) from the use of BCETMD copolymer as an inert ingredient
in pesticide products applied pre-harvest to cotton and wheat.  No
adverse effects attributable to a single exposure of BCETMD copolymer
were seen in the toxicity database.  Therefore, an acute dietary risk
assessment is not required.  EPA determines whether pesticide chemical
exposures are safe by comparing aggregate exposure estimates to the dose
at which no adverse effects were seen in the most sensitive animal
species.  In the case of BCETMD copolymer, the estimated exposures are
compared to a dose level equal to the chronic RfD of 0.45 mg/kg/day
(based on the developmental toxicity study in rabbits).  Utilizing a
highly conservative aggregate exposure assessment, the resulting chronic
exposure estimates do not exceed the Agency’s level of concern; the
chronic dietary estimate for the U.S. Population was 6.7% (non-nursing
infants were the most highly exposed population with a chronic exposure
estimate occupying 20.0% of the cPAD).  

	Taking into consideration all available information on BCETMD
copolymer, EPA has determined that there is a reasonable certainty that
no harm to any population subgroup will result from aggregate exposure
to BCETMD copolymer when used as an inert ingredient in pesticide
formulations applied pre-harvest to cotton and wheat when considering
dietary exposure and all other nonoccupational sources of pesticide
exposure for which there is reliable information.  Therefore, the
establishment of an exemption from tolerance under 40 CFR 180.920 for
residues of BCETMD copolymer when used as an inert ingredient in
pesticide formulations applied to cotton or wheat only, can be
considered safe under section 408 of the FFDCA.

	

Background

	Buckman Laboratories International, Inc. submitted a petition (4E6841)
requesting a tolerance exemption for BCETMD copolymer, CAS number
31075-24-8.  The company requested an exemption from the requirement of
a tolerance for residues of this chemical when used as an inert
ingredient in pesticide formulations applied to growing crops only under
40 CFR 180.920.  The petitioner subsequently amended their petition
specifying that the inert ingredient use of BCETMD copolymer will be as
an adjuvant or water conditioner in pesticide products applied only to
cotton and to wheat prior to boot stage.  Agency data reviews were
submitted by the petitioner to support their request for a tolerance
exemption and these reviews are summarized in this document.  

Table 1.  Tolerance Exemption

Inert Ingredient	Limits	Uses

1,2-ethanediamine, N,N,N’,N’-tetramethyl-, polymer with
1,1’-oxybis[2-chloroethane] (CAS Reg. No. 31075-24-8)	For use in
pesticide formulations applied to cotton or wheat only 	Adjuvant or
water conditioner 

	

BCETMD has the same chemical composition as Busan 77.  Busan 77 is
registered as an active ingredient biocide in a variety of non-food
antimicrobial pesticide products with use sites such as swimming pools,
whirlpools, spas, ornamental ponds and fountains, commercial and
industrial cooling water systems, metalworking cutting fluids,
industrial airwashing systems, paper mills, and recirculating cooling
water and industrial systems.  

Physical and Chemical Properties

BCETMD copolymer is a water-soluble, cationic ionene polymer with an
average molecular weight of 3,386 g/mol.

 Table 2.  Physical and Chemical Properties

Parameter	Value

Chemical	

1,2-Ethanediamine,N,N,N’,N’-tetramethyl-, polymer with
1,1’-oxybis[2-chloroethane] (9CI)

CAS Reg. No. 31075-24-8

Chemical Abstract Services (CAS) Online

Molecular formula	(C6H16N2.C4H8Cl2O)x

Color	Light amber/pale yellow 

(MRID 468320601/42372401)

Physical State	Clear Liquid

(MRID 46832601)

Molecular weight	3,368 g/mol (Average )

(Buckman letter 7/10/91)

Flammability	>99.5(

(MRID 46832601)

Viscosity	1.521 (20(C)/1.005 (40(C)

(MRID 46832601)

Boiling Point	111(C

(MRID 42372401)

Density	1.013-1.1417 g/mL

(MRID 46832601/42372401)

III.  	Human Health Assessment

Toxicological Data

	

	Sufficient data were submitted to the Agency in support of this action.
 The Agency has determined that these data are appropriate and adequate
to characterize the toxicity of BCETMD copolymer.  Excerpts and
summaries of these reviews are presented in this document.    

	

Acute Toxicity

Table 3.  Acute Toxicity

Parameter	Toxicity Value	Toxicity Category	MRID

Oral LD50 - rats	1951 mg/kg males

2587 mg/kg females	III	413734-01

Dermal LD50 - rabbit	>2000 mg/kg	III	413271-01

Inhalation LC50 - rat	2.9 mg/L	III	418775-01

Eye irritation - rabbit	Slightly irritating	III	413617-01

Dermal irritation - rabbit	Slightly irritating	IV	412986-01

Dermal sensitization – guinea pig	Non-sensitizer	--	407503-01

Subchronic Toxicity 

		In a 90-day study (MRID 400250-01) of male and female rats given the
test material in the diet at dose levels of 0; 3,000; 10,000; 30,000; or
40,000 ppm (equivalent to 0; 221; 752; 2,604; or 3,685 mg/kg/day), the
NOAEL was 221 mg/kg/day and the LOAEL was 752 mg/kg/day due to
mineralization of the renal tubules.  The following were observed at the
two highest dosages:  decreases in body weights and possibly absolute
organ weights (heart, liver, kidney and gonads); an equivocal decrease
in red blood cell counts; elevated leukocyte counts; non-suppurative
inflammation of the choroid plexus of the brain; and death.  

		In a 90-day dermal toxicity study (MRID 401706-01), male and female
rabbits received dermal application of the test material at dose levels
of 0, 10, 100, or 1000 mg/kg/day.  No systemic toxicity was observed at
any doses.  The systemic NOAEL was determined to be >1000 mg/kg/day
(limit dose).  The dermal irritation NOAEL was 10 mg/kg/day and the
LOAEL was 100 mg/kg/day.  Treatment related dermatological changes
consistent with chronic irritation/inflammation were seen in males and
females receiving 100 and 1,000 mg/kg/day.  The skin lesions consisted
of one or more combinations of ulceration of the epidermis, chronic
inflammation of the dermis, acanthosis, hyperkeratosis, parakeratosis,
folliculitis and epidermatitis. 

Chronic Toxicity

In a 52-week study, male and female beagle dogs were dosed in the diet
at 0, 10,000, 20,000 or 40,000 ppm (equivalent to 0, 250, 500, or 1000
mg/kg/day).  In males, the NOEL was 250 mg/kg/day and the LOEL was 500
mg/kg/day based on testicular hypoplasia, atrophy/degeneration,
aspermia, dysplasia and cellular debris of testicular origin in
epididymis.  In females, the NOEL was 500 mg/kg/day and the LOEL was
1,000 mg/kg/day based on gastrointestinal disturbances, emaciation and
neurological signs, bloody stools, weight loss and ataxia (MRID
93062016; 41234501).  

 Reproductive/Developmental Toxicity: 

		The Agency reviewed a developmental toxicity study (MRID 414230-01;
93062018) of rats administered the test material by oral-gavage on
gestation days 6-15 at dosages of 0, 70, 350, or 700(later reduced to
500 mg/kg/day).  At 700 mg/kg/day mortality was observed, as was
morbidity, including lungs (mottled, red and/or firm), brain (dilated
meningeal vessels and/or hemorrhages), stomach (black contents, corroded
areas) and intestines (distended, filled with reddish contents).  For
maternal effects, the NOEL was 70 mg/kg/day based on the decreased food
consumption and body weight gain (not statistically significant) seen at
the LOEL of 350 mg/kg/day.  For developmental effects, the NOEL was 500
mg/kg/day and the LOEL was >500 mg/kg/day (highest dose tested).  	

		In a developmental toxicity study (MRID 412480-01; 93062019), pregnant
rabbits were administered 0, 15, 45, or 125 mg/kg/day of the test
material via gavage on gestation days 6 through 18.  Maternal NOEL was
45 mg/kg/day based on increased incidence of abortions (late Day 28 and
Day 29), clinical signs (reduced defecation and emaciation),
significantly reduced feed consumption and body weight gain during the
treatment.  Developmental NOEL was 45 mg/kg/day based on increased
incidence of 13th rudimentary ribs and unossified sternebrae #5 and #6
seen at the LOEL of 125 mg/kg/day.  No evidence of teratogenic effect
was observed in this study. 

		The endpoints of a rat reproduction study (MRID 40578201) were
reevaluated by the HED RfD/Peer Review Committee.  The following are the
conclusions from that reevaluation.  In a two-generation reproduction
study, the test material was administered in the diet to male and female
Crl:CD(SD)BR rats at dose levels of 0, 6,000, 12,000, or 18,000 ppm
(approximately 0, 300, 600, or 900 mg/kg/day) for two generations. 
Maternal toxicity was observed at 6000 ppm and above consisting of
reduced body weight, reduced absolute and relative liver weight,
inflammation of the choroid plexus in the brain, and tubular
mineralization of the kidney.  The systemic LOEL is 6000 ppm or less
based on the above changes.  The NOEL is less than 6000 ppm. 
Reproductive toxicity was observed at 12000 ppm as a decrease in number
of live pups observed on days 0 and 4 after birth in both generations. 
The reproductive LOEL is 12000 ppm based on decreased live pups.  The
NOEL is 6000 ppm.  The RfD/Peer Review Committee concluded that there
was no evidence to suggest that the test material was associated with
any significant reproductive or developmental toxicity under the testing
conditions.	

Genotoxicity

		Five mutagenicity studies were conducted and none demonstrated any
genotoxic potential associated with the test material.  In an Ames
Reverse Mutation Assay (MRID 415737-01) using S. typhimurium strains TA
1535, 1537, 1538, 98, and 100, the test material (up to 3300 ug/plate)
was not mutagenic both with and without activation.  Unscheduled DNA
synthesis in primary rat hepatocytes was negative at dose levels up to
2,000 mg/kg.  The sex-linked recessive lethal assay was negative at all
dose levels (0.08, 0.3 or 0.8 mg/L; MRID 93062023, previously MRID
151205).  It was negative for clastogenicity in the in vivo mouse
micronucleus assay (MRID 93062021, previously MRID 151206).  In an In
Vivo/In Vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay
(MRID 409787-01), the test material was not mutagenic to primary rat
hepatocytes in cultures established from rats treated by oral gavage at
doses up to 1500 mg/kg.  

	

Carcinogenicity 

In a 2-year combined chronic toxicity and carcinogenicity study in rats
(Crl:CD®(SD)BR)(MRID 415613-01, 418091-01), the test material was
administered as a dietary admix at dose levels of 0, 2000, 6000 or 18000
ppm (equivalent to 0, 100, 300, or 900 mg/kg/day in male and female
rats).  Fifty male and female rats were exposed via diet for 105 weeks
and ten male and female rats were exposed via diet for 55 weeks.  At
6000 ppm, reduced body weight gain in females, reduced albumin (males),
reduced total protein (males), increased urine pH (females) and a dose
related increase in bloody crusts(males) were observed.  In addition, at
18000 ppm, hyperesthesia, bloody crusts, decreased body weight gain,
decreased prothrombin time, globulin and total protein and increased
brain-to-body weight ratio associated with mineralization of the brain
in the thalamic region, in males and females; decreased albumin, glucose
and cholesterol in males and increased urine pH in females, were
observed.  Histological exams showed mineralization in the brains of
high dose animals.  There were no significant compound-related tumors in
male rats.  Female rats had no significant increasing trends, but did
have significant differences in the pair-wise comparisons of the 6000
ppm dose group with the controls for thyroid C-cell adenomas, and
adenomas and/or carcinomas combined, both at p < 0.05.  The NOEL for
systemic toxicity in rats was determined to be 2,000 ppm (100
mg/kg/day).  The LOEL was 6000 PPM (300 mg/kg/day).

		In a 78-week oncogenicity study (MRID 414943-01), Crl: CD-1 (ICR) BR
mice were administered the test material in the diet at dose levels of
0, 4000, 8000, or 16,000 ppm (equivalent to 0, 600, 1200, or 2400
mg/kg/day).  At 4000 ppm, large kidney pelvis and diffuse rough kidney
in females; and histologically in kidneys, a dose related increase in
the proteinaceous casts in males and pelvic and tubular dilatation in
males and females, was observed.  At 8000 ppm and above, convulsions
(dose related), and urine stains were observed in male and female rats. 
There was no evidence of any oncogenic (cancer) activity that would be
considered treatment related.  The systemic NOEL could not be
established but the LOEL was determined to be less than 600 mg/kg/day. 
The test material was found not to be carcinogenic in mice at doses up
to 2,400 mg/kg/day (16,000 ppm) in the diet. 

Carcinogenicity Classification

	The RfD Committee (1994) classified Busan 77 as group D (not
classifiable as to human carcinogenicity) carcinogen based on lack
carcinogenicity in mice, lack of evidence of carcinogenicity in male
rats and increased incidence of thyroid C cell adenomas/carcinomas in
female rats (pair wise comparison) and lack of mutagenicity concerns.

Metabolism and Pharmacokinetics

In a rat metabolism study (MRID 402686-01; 93062024) ), test animals
were dosed with 14C-labeled test material at oral doses of 10 mg/kg or
1000 mg/kg, or at repeated oral doses (14 daily doses) of unlabeled test
material at 10 mg/kg followed by a single oral dose of labeled test
material at 10 mg/kg.  In the single oral and repeated oral dose groups,
most (88%-106%) of the test compound administered was excreted in the
urine (3% of the dose) and feces (85-103% of the dose).  The highest
amount of residual radioactivity was found in the kidneys, liver, and
spleen.  The residues in the tissues including the carcass were not more
than 0.14% thus indicating that the potential for bioaccumulation of the
test material is minimal after low single or repeated oral dose
exposures.  In the high (1,000 mg/kg/day) oral dose group, most (85%) of
the dose was excreted in urine (14-17% of the dose) and feces (68-71%). 
Seven days after dosing, residues were low in all tissues except for the
kidneys, liver, and spleen.  

Dermal absorption of the test material was negligible (0.2% of the dose)
in rats (MRID 40139201).

  

Special Consideration for Infants and Children

The Agency concluded that the FQPA Safety Factor for increased
susceptibility to infants and children be reduced to 1X.  This decision
was based on the following:

The database is considered adequate for FQPA assessment.  The studies
included in the toxicological database are:  90-day toxicity study in
rats via oral route, 90-day dermal toxicity study in rabbits, chronic
toxicity study in dogs, carcinogenicity study in mice, combined
chronic/carcinogenicity study in rats, several mutagenicity studies (in
vivo and in vitro), metabolism study in rats and dermal penetration
study in rats.  There are no acute and/or subchronic neurotoxicity
studies available in the database.  There was no evidence of clinical
signs of neurotoxicity in the database except ataxia in the chronic
toxicity study in dogs (1000 mg/kg/day) and convulsions in a
carcinogenicity study in mice (1200 mg/kg/day).  These effects are
considered due to excessive toxicity and not of a neurologic origin. 
Therefore, there is no need for acute and subchronic neurotoxicity
studies for this chemical.  EPA also concluded that there is no need for
a developmental neurotoxicity study for this chemical because there is
no evidence in the database of neurotoxicity or increased susceptibility
to infants and children.  

There is no evidence of increased qualitative or quantitative
susceptibility in the developmental toxicity study in rats and rabbits
and in the two-generation reproduction study in rats.  No developmental
effects were observed in the rat developmental toxicity study at doses
up to 500 mg/kg/day (highest dose tested) in the presence of maternal
toxicity. In the rabbit developmental toxicity study, the maternal and
developmental NOAELs were 45 mg/kg/day.  In this study, skeletal
variations (developmental effects) were observed in the presence of
equally severe maternal toxicity (abortions).  In the 2-generation
reproduction study in rats, pup weights were decreased at a dose level
higher than the dose that produced maternal toxicity.

The highly conservative dietary exposure assessment using default
assumptions would not underestimate the risk to infants and children.

IV.	Environmental Fate and Ecotoxicity Considerations

BCETMD copolymer “is a water-soluble, cationic ionene polymer with an
average molecular weight of 3,386 g/mol.  Based on its miscibility in
water and high molecular weight, volatility from water is unlikely.  It
is also stable to both abiotic degradation (hydrolysis and photolysis)
and to metabolism in soil and sediment:water systems.  In the presence
of soil or sediment, tight sorption of nearly all residues was observed
almost immediately.”  It “was almost exclusively (96%) found in the
top two inches of 12 inch columns leached with water.  Less than 1% was
found in the leachate collected at the bottom of the columns.”  The
mobility conclusions are consistent with the fact that the chemical is
positively charged and soil/sediment is negatively charged (USEPA
Breithaupt).  Based on this information, the use of BCETMD copolymer as
an inert ingredient in pesticide products applied pre-harvest to cotton
and wheat is not expected to result in contributions of concern to
drinking water (from surface and ground waters).

BCETMD copolymer is toxic to aquatic organisms, particularly to aquatic
invertebrates and it exhibited low to moderate oral toxicity in animal
studies.  Its limited use as an inert ingredient in pesticide
formulations applied pre-harvest to cotton and wheat allows for binding
of the chemical to soil and sediment thus limiting its availability to
non-target aquatic and terrestrial species.  Based on this information,
the inert ingredient use of BCETMD copolymer is not expected to result
in exposures of concern to non-target aquatic and terrestrial species.  

V.	Exposure Assessment

	

In examining aggregate exposure, the FFDCA section 408 directs EPA to
consider available information concerning exposures from the pesticide
residue in food and all other non-occupational exposures, including
drinking water from ground water or surface water and exposure through
pesticide use in gardens, lawns, or buildings (residential and other
indoor uses).  The primary route of exposure to BCETMD copolymer from
its use as an inert ingredient in pesticide products applied pre-harvest
to cotton and wheat would most likely be through consumption of food to
which pesticide products containing it as an inert ingredient have been
applied, and possibly through drinking water (from runoff).  The use of
this chemical as an inert ingredient in pesticide formulations is
limited to pre-harvest applications to cotton and wheat only, therefore,
there are no residential uses of this chemical and thus no residential
(dermal and inhalation) exposures are expected. 

	No adverse effects attributable to a single exposure of BCETMD
copolymer were seen in the toxicity database.  Therefore, an acute
dietary risk assessment is not required.  

There are no data provided regarding BCETMD copolymer residues in food
or any other nonoccupational exposures to BCETMD copolymer.  In the
absence of actual residue data for BCETMD copolymer, the Agency
performed a chronic dietary (food and drinking water) exposure
assessment for BCETMD copolymer when used as an inert ingredient in
pesticide formulations applied pre-harvest to cotton and wheat. A
chronic reference dose (cRfD) of 0.45 mg/kg/day was based on the NOAEL
of 45 mg/kg/day in the developmental toxicity study in rabbits and a
safety factor of 100 (10x for interspecies and 10x for intraspecies
variations).  Since the FQPA safety factor is reduced from 10x to 1x,
the chronic population adjusted dose (cPAD) is equal to the cRfD.  The
dietary exposure was calculated as a percentage of the cRfD.  The
chronic dietary estimate for the U.S. Population was 6.7% (non-nursing
infants were the most highly exposed population with a chronic exposure
estimate occupying 20.0% of the cPAD).  The complete dietary exposure
assessment is included in Appendix A.  In addition, this exposure
assessment was calculated based on the following assumptions:  a) BCETMD
copolymer would be used as an inert ingredient in all food use pesticide
formulations applied pre-harvest to cotton and wheat only, b) one
hundred percent of all cotton and wheat crops would be treated with
pesticide products containing BCETMD copolymer, c) BCETMD copolymer
residues would be present in all cotton and wheat crops at levels equal
to or exceeding the highest established tolerance levels for any
pesticide active ingredient, and d) a conservative default value of 100
ppb for the concentration of an inert ingredient in all sources of
drinking water was used.  This approach is highly conservative as it is
extremely unlikely that BCETMD copolymer would have such use as a
pesticide product inert ingredient and be present in cotton and wheat
food commodities and drinking water at such high levels.  

VI.	Cumulative Exposure

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether
to establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a
particular pesticide's residues and "other substances that have a common
mechanism of toxicity."

	Unlike other pesticide ingredients for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity, EPA
has not made a common mechanism of toxicity finding as to BCETMD
copolymer and any other substances and BCETMD copolymer does not appear
to produce a toxic metabolite produced by other substances.  For the
purposes of this tolerance action, therefore, EPA has not assumed that
BCETMD copolymer has a common mechanism of toxicity with other
substances.  For information regarding EPA’s efforts to determine
which chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see the policy statements released
by EPA’s Office of Pesticide Programs concerning common mechanism
determinations and procedures for cumulating effects from substances
found to have a common mechanism on EPA’s website at     HYPERLINK
"http://www.epa.gov/pesticides/cumulative/." 
http://www.epa.gov/pesticides/cumulative/. 

VII. 	Human Health Risk Characterization

(≥86%) of the chemical was excreted in the feces. 

The primary route of exposure to BCETMD copolymer from its use as an
inert ingredient in pesticide products applied pre-harvest to cotton and
wheat would most likely be through consumption of food to which
pesticide products containing it as an inert ingredient have been
applied, and possibly through drinking water (from runoff).  The use of
this chemical is limited to pesticide formulations applied pre-harvest
to cotton and wheat only, therefore, there are no residential uses of
this chemical, and thus no residential (dermal and inhalation) exposures
are expected. 

Residues of concern are not anticipated for dietary exposure (food and
drinking water) from the use of BCETMD copolymer as an inert ingredient
in pesticide products applied pre-harvest to cotton and wheat. 
Residential exposures are not expected from this use.  EPA determines
whether pesticide chemical exposures are safe by comparing aggregate
exposure estimates to the dose at which no adverse effects were seen in
the most sensitive animal species.  In the case of BCETMD copolymer, the
estimated exposures are compared to a dose level equal to the chronic
RfD of 0.45 mg/kg/day (based on the developmental toxicity study in
rabbits).  Utilizing a highly conservative aggregate exposure
assessment, the resulting chronic exposure estimates do not exceed the
Agency’s level of concern; the chronic dietary estimate for the U.S.
Population was 6.7% (non-nursing infants were the most highly exposed
population with a chronic exposure estimate occupying 20.0% of the
cPAD).  

     	Taking into consideration all available information on BCETMD
copolymer, EPA has determined that there is a reasonable certainty that
no harm to any population subgroup will result from aggregate exposure
to BCETMD copolymer when used as an inert ingredient in pesticide
formulations applied pre-harvest to cotton and wheat when considering
dietary exposure and all other nonoccupational sources of pesticide
exposure for which there is reliable information.  Therefore, the
establishment of an exemption from tolerance under 40 CFR 180.920 for
residues of BCETMD copolymer when used as an inert ingredient in
pesticide formulations applied to cotton or wheat only, can be
considered safe under section 408 of the FFDCA.

	

VIII. 	Endocrine Disruption

EPA is required under the Federal Food, Drug and Cosmetic Act (FFDCA),
as amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) “may have an effect in humans that is similar to an
effect produced by a naturally occurring estrogen, or other such
endocrine effects as the Administrator may designate.”  Following
recommendations of its Endocrine Disruptor and Testing Advisory
Committee (EDSTAC), EPA determined that there was a scientific basis for
including, as part of the program, the androgen and thyroid hormone
systems, in addition to the estrogen hormone system.  EPA also adopted
EDSTAC’s recommendation that the Program include evaluations of
potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being
considered under the Agency’s EDSP have been developed, BCETMD
copolymer may be subjected to further screening and/or testing to better
characterize effects related to endocrine disruption.  

REFERENCES

                                                                    

USEPA 011338, Memorandum, Rfd/Peer Review Report of Busan 77 [Poly
(oxyethylene(dimethylimino)ethylene(dimethylimino)ethylene dichloride,
11/16/1994.

USEPA 011090, Memorandum, Busan 77 – Reevaluation of the Rat
Reproduction Study Endpoints as a Result of the Rfd/Peer Review Meeting
held on 6/23/1994, July 6, 1994.

USEPA DER MRID 414943-01, Data Evaluation Report, 18-Month Study with
Busan 77 in Mice, 9/14/93.

USEPA DER MRID 413734-01, Data Evaluation Report, Acute Oral Toxicity
Study in Rats with Busan 77, 8/25/93)

USEPA DER MRID 413271-01, Data Evaluation Report, Acute Dermal Toxicity
Study in Rabbits with Busan 77, 5/13/93.

USEPA DER MRID 418775-01, Data Evaluation Report, An Acute Inhalation
Toxicity Study of Busan 77 in the Rat, 5/13/93.

USEPA  DER MRID 413617-01, Data Evaluation Report, Primary Eye
Irritation Study  in Rabbits with Busan 77, 5/13/93.

USEPA DER MRID 412986-01, Data Evaluation Report, Primary Dermal
Irritation Study in Rabbits with Busan 77, 5/13/93.

USEPA DER MRID 407503-01, Data Evaluation Report, Dermal Sensitization
Study in Guinea Pigs with WSCP, 5/13/93.

USEPA DER MRID 401706-01, Data Evaluation Report, 13-Week Dermal
Toxicity Study with Busan 77 in Rabbits, 5/13/93.

USEPA DER MRID 412480-01, Data Evaluation Report, Teratology Study in
Rabbits with Busan 77, 9/14/93.

USEPA DER MRID 409787-01, Data Evaluation Report, Busan 77 – In
Vivo/In Vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay,
8/26/93.

USEPA DER MRID 415737-01, Data Evaluation Report, Mutagenicity Test on
Busan 77 in the Salmonella/Mammalian-Microsome Reverse Mutation Assay
with Confirmatory Assay, 8/26/93.

USEPA DER MRID 402686-01, Data Evaluation Report, Metabolism Study With
Busan 77 (WSCP) in Rats, 8/5/93.

	

USEPA D189108 8/9/1993, EEB Review of Busan 77, Anthony Maciorowski,
August 9, 1993.

USEPA 010597, EPA Record Number S425253, Memorandum, Busan 77.  Phase V
Review of Studies, September 23, 1993.

USEPA 9/12/88, Data Evaluation Record of MRID #’s 00159311, 00159312,
00157906, 00157907, Allan Reiter, August 12, 1988.  

USEPA Shamim, Dietary Risk Assessment (Indirect Food Contact) Uses in
Paper Manufacturing Process of
Poly[(oxyethylene)(dimethylimino)ethylene(dimethylimino)ethylene
dichloride] [Busan 77], A. Najm Shamim, 9/30/2007.

USEPA Breithaupt, Revised Environmental Fate Science Chapter for the
Busan 77 Reregistration Eligibility Decision (RED) Document, James
Breithaupt, 9/30/2007.

APPENDIX A

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for BCETMD COPOLYMER Cotton and  wheat
(1994-98 data)

Analysis Date 03-04-2009/08:01:25     Residue file dated:
03-04-2009/07:59:09/8

Reference dose (RfD, Chronic) = .45 mg/kg bw/day

NOEL (Chronic) = 45 mg/kg bw/day

COMMENT 1: Cotton and wheat + drinking water (1000 ppb)

========================================================================
=======

                    Total exposure by population subgroup

------------------------------------------------------------------------
-------

                                                    Total Exposure

                                        
-----------------------------------

          Population                         mg/kg       Margin of  
Percent 

           Subgroup                       body wt/day   Exposure 1/  of
RfD 

--------------------------------------   -------------  ---------- 
---------

U.S. Population (total)                     0.029947        1,503       
6.7%

U.S. Population (spring season)             0.029860        1,507       
6.6%

U.S. Population (summer season)             0.031199        1,442       
6.9%

U.S. Population (autumn season)             0.029286        1,537       
6.5%

U.S. Population (winter season)             0.029434        1,529       
6.5%

Northeast region                            0.028617        1,573       
6.4%

Midwest region                              0.030772        1,462       
6.8%

Southern region                             0.028343        1,588       
6.3%

Western region                              0.032813        1,371       
7.3%

Hispanics                                   0.031969        1,408       
7.1%

Non-hispanic whites                         0.029669        1,517       
6.6%

Non-hispanic blacks                         0.028372        1,586       
6.3%

Non-hisp/non-white/non-black                0.034266        1,313       
7.6%

All infants (< 1 year)                      0.072886          617      
16.2%

Nursing infants                             0.027624        1,629       
6.1%

Non-nursing infants                         0.090061          500      
20.0%

Children 1-6  yrs                           0.050356          894      
11.2%

Children 7-12 yrs                           0.033526        1,342       
7.5%

Females 13-19 (not preg or nursing)         0.022839        1,970       
5.1%

Females 20+ (not preg or nursing)           0.027212        1,654       
6.0%

Females 13-50 yrs                           0.027484        1,637       
6.1%

Females 13+ (preg/not nursing)              0.027988        1,608       
6.2%

Females 13+ (nursing)                       0.037861        1,189       
8.4%

Males 13-19 yrs                             0.025515        1,764       
5.7%

Males 20+ yrs                               0.026014        1,730       
5.8%

Seniors 55+                                 0.026474        1,700       
5.9%

Children 1-2 yrs                            0.052202          862      
11.6%

Children 3-5 yrs                            0.050763          886      
11.3%

Children 6-12 yrs                           0.035333        1,274       
7.9%

Youth 13-19 yrs                             0.024279        1,853       
5.4%

Adults 20-49 yrs                            0.026805        1,679       
6.0%

Adults 50+ yrs                              0.026530        1,696       
5.9%

Females 13-49 yrs                           0.026458        1,701       
5.9%

------------------------------------------------------------------------
-------

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

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