Document ID: EPA-HQ-OPP-2007-0834-0013
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-03-23T04:00Z

SEQ CHAPTER \h \r 1 							

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

September 30, 2007

MEMORANDUM

SUBJECT:	Revised Post Error Comment: Preliminary Risk Assessment for
Busan 77 for the Reregistration Eligibility Decision (RED) Document.  PC
Code: 069183 (active). Case No. 3034.  

		Regulatory Action:  Reregistration Eligibility Decision (RED) (Phase
I)

FROM:	Talia Lindheimer, Chemist/Risk Assessor

		Antimicrobials Division (AD) (7510P)

		And

		Genevieve Angle, Biologist

		James Breithaupt, Agronomist

		Jonathan Chen, Ph.D., Toxicologist

		Tim McMahon, Ph.D., Senior Toxicologist

		Siroos Mostaghimi, Ph.D.

		A. Najm Shamim, Ph.D. Chemist 

		Cassi Walls, Ph.D., Chemist

		

		Antimicrobials Division (AD) (7510P)

THRU:		Nader Elkassabany, Team Leader, Team II

		Norm Cook, Branch Chief

		Risk Assessment Science Support Branch (RASSB)

		Antimicrobials Division (AD) (7510P)

TO:		ShaRon Carlisle, Chemical Review Manager

		Mark Hartman, Branch Chief

		Regulatory Management Branch II

		Antimicrobials Division (7510P)     

        

Attached is Preliminary Risk Assessment for Busan 77 and reflects the
comments that were provided for the Error Comment Phase.  The
disciplinary science chapters are also included, and have been revised
accordingly.  These documents are listed as attachments and are listed
on the following page.  

Supporting chapters discussed in this Risk assessment and are included
as Appendices:

Busan 77 – Incident Report Summary.  Memorandum from J. Chen, August
3, 2007.

Revised Busan 77: Toxicology Chapter for Issuance of the Reregistration
Eligibility Decision (RED) Document.  Memorandum from T. McMahon,
September 30, 2007.

Revised Dietary Risk Assessment (Indirect Food Contact) Uses in Paper
Manufacturing Process of  Poly [oxyethylene(dimethylminino)
ethylene(dimethyliminio)ethylene dichloride] [Busan 77].  Memorandum
from A. N. Shamim, September 30, 2007.

Revised Environmental Exposure Assessment for Releases of BUSAN 77 from
Once-through Cooling Water System.  Memorandum from S. Mostaghimi,
September 30, 2007.

Revised Environmental Fate Science Chapter for the Busan 77
Reregistration Eligibility Decision (RED) Document. Memorandum from J.
Breithaupt, September 30, 2007.

Occupational and Residential Exposure Chapter for the Busan 77
Reregistration Eligibility Decision (RED) Document (Case 3034).
Memorandum from C. Walls, July 27, 2007.

Physical/Chemical Characteristics of Busan 77.  Memorandum from A. N.
Shamim, September 30, 2007.

Revised Preliminary Ecological Hazard and Environmental Risk Assessment
Science Chapter for the Busan 77 Reregistration Eligibility Decision
(RED) Document.  Memorandum from G. Angle, September 30, 2007.

1.0	Executive
Summary………………………………………………………
……………...4

2.0	Physical and Chemical
Properties……………………………………………………
…9

3.0	Hazard
Characterization………………………………………………
…………....….10

		3.1	Hazard
Profile………………………………………………………
…...10

		3.2	Dose-Response
Assessment……………………………………………..10

		3.3	FQPA
Considerations………………………………………………….
.12

		3.4	Endocrine
Disruption…………………………………………………...12

4.0	Incidence
Reports………………………………………………………
……………….12

5.0	Exposure Assessment and
Characterization…………………………………………..13

		5.1	Summary of Registered
Uses……………….…………………………..13

		5.2	Dietary Exposures and
Risk……………………………………………13

		5.3	Drinking Water Exposure and
Risk…………….………..……………14

		5.4	Residential Exposure and Risk...
………………………………………14

6.0	Aggregate Risk Assessment and Risk
Characterization………………………………16

7.0	Cumulative Exposure and
Risk………………………………………………………...17

8.0	Occupational Exposure and
Risk………………………………………………………17

9.0	Environmental
Fate…………………………………………………………
…………..20

10.0	Environmental
Risk…………………………………………………………
…………..23

		10.1	Summary of Ecological Toxicology Data
Conclusions………………..23

		10.2	Environmental Risk
Assessment……………………………………….24

11.0	Deficiencies and Data
Needs…………………………………………………………
…27

12.0
References……………………………………………………
………………………….28

Appendix A:  Residential and Occupational Uses and
Rates…………………………………37

Appendix B:	Subchronic, Chronic, and Other Toxicity
Profiles……………………………40

1.0 	EXECUTIVE SUMMARY  tc "1.0 	EXECUTIVE SUMMARY" 

	The chemical evaluated in this risk assessment is Poly
[oxyethylene(dimethylminino) ethylene(dimethyliminio)ethylene
dichloride], which is commonly referred to as Busan 77.  Throughout this
risk assessment and supporting chapters, the ingredient under
consideration will be referred to as Busan 77 for simplicity.  This
chemical is currently is registered as an active ingredient in end use
products (EUPs) and serves the function as an algaecide, bacteriostat,
fungicide, microbiocide/microbiostat and molluscicide.  Concentrations
of Busan 77 in these products range from 1.7% to 60%.  There are no
current registrations for Busan 77 as an inert ingredient.

	The registered products that contain Busan 77 are formulated as liquid
concentrates and granules.  Some examples of the use sites that products
containing Busan 77 are used for include: swimming pools, spas,
whirlpools, hot tubs, metal working fluids, fire water protection
systems, cooling water towers, petroleum secondary recovery systems,
paper mill process water, air washer water systems, ornamental ponds,
aquariums and various sorts of fabrics.  These various EUP sties can be
summarized by five Use Site Categories, which are residential and public
access (IV), materials preservation (Use Site Category VII), industrial
mildewcide for cooling tower and air washer water systems (Use Site
Categories VIII), swimming pools (XI) and aquatic areas (XII).

Hazard Profile:

	Based on the conclusions provided in the supporting toxicology chapter,
the toxicology studies available for Busan 77 were considered to be
acceptable.  The acute toxicity of Busan 77 is low for oral toxicity
(Toxicity Category III), dermal toxicity (Toxicity Category III),
inhalation toxicity (Toxicity Category III) and primary eye irritation
(Toxicity Category III); it is even lower for primary dermal irritation
(Toxicity Category IV).  It was not found to be a dermal sensitizer.  In
addition, based on the results of the developmental toxicity studies,
there were no significant neurological effects to warrant a
neruotoxicity study.  In mutagenicity studies (reverse mutation assay,
mouse micronucleus assay, unscheduled DNA synthesis assay, sex-linked
recessive lethal assay) Busan 77 was found to be non-mutagenic.  Busan
77 is currently classified as a ‘Group D’ (inadequate evidence)
carcinogen. Negative results were observed in a mouse carcinogenicity
study, but in a rat chronic toxicity/carcinogenicity study, increases in
the incidence of thyroid C-cell adenomas were observed in female rats at
doses of 300 and 900 mg/kg/day. The increase in thyroid C-cell adenoma
was statistically significant at 300 mg/kg/day

Toxicity Endpoints:

	The toxicity endpoints utilized for assessing potential risks are
summarized below.  

	Acute Reference Dose (RfDs):  There were no endpoints identified in the
toxicity database for Busan 77 for selection of an acute RfD.   

	Chronic Reference Dose (cRfD):   A chronic RfD was derived from the
chronic toxicity /carcinogenicity study in rats (MRID 41809101) using
the NOAEL of 100 mg/kg/day based on effects observed at 300 mg/kg/day
(decreased body weight gain, decreased albumin and total protein,
increased urine pH). Using a standard uncertainty factor of 100, the RfD
was calculated as 1.0 mg/kg/day. 

	Incidental Oral Exposure:  For the short-term oral exposure (1-30
days), a NOAEL of 500 mg/kg/day was selected based on a developmental
toxicity study in the rat, in which increased mortality was observed
(MRIDs 41423001/93062018).  For intermediate-term (30 days – 6 months)
incidental oral exposure, a NOAEL of 221 mg/kg/day was selected based on
a subchronic toxicity study in rats and was based on renal tubular
mineralization (MRIDs 40025001/93662014).  The target margin of exposure
(MOE) is 100 for both ST and IT durations.

	Dermal Exposure:  For short term dermal exposures, a NOAEL of 125
µg/cm2 (equivalent to 10 mg/kg/day) was selected from a 90 day dermal
toxicity study in rabbits (MRID 40170601) and based on dermal
irritation. This is a TGAI based dermal endpoint that was calculated as
follows: (10 mg/kg  x  0.2 kg x  1000 µg/mg) / 16 cm2 = 125 µg/cm2. 
The target MOE is 100 for the ST dermal duration, and there were no
endpoints identified for intermediate and long-term durations.  

	Inhalation Exposure:  For the short-term inhalation exposure (<30
days), an oral NOAEL of 500 mg/kg/day was selected based on a
developmental toxicity study in the rat, in which increased mortality
was observed (MRIDs 41423001/93062018).  For intermediate-term (30 days
– 6 months) inhalation exposure, an oral NOAEL of 221 mg/kg/day was
selected based on a subchronic toxicity study in rats and was based on
renal tubular mineralization (MRIDs 40025001/93662014).  .  The target
margin of exposure (MOE) is 100 for both ST and IT durations. 	 It
should be noted that since the inhalation NOAEL is based on an oral
study that an additional 10X (i.e., MOE = 1,000) may be warranted to
request that an inhalation-specific study be conducted.   

FQPA Safety Factor:

	The Antimicrobials Division’s Toxicology endpoint Selection Committee
has recommended that the special hazard-based FQPA safety factor for
Busan 77 be removed.  This conclusion is based upon the availability of
acceptable developmental and reproductive toxicity studies with Busan 77
that adequately characterize the dose-response of this compound along
with the lack of evidence for any sensitivity of offspring to the
adverse effects of Busan 77.  Please refer to Busan 77 Revised Report of
the Antimicrobials Division’s Toxicology Endpoint Selection Committee
(ADTC) (Dated July 10, 2007 from T. McMahon (PC Code; 069183)) for a
complete discussion of this recommendation.

Dietary Exposure and Risk: 

	A dietary assessment was generated for this chemical because (see
memorandum from A.N Shamim, September 2007) upon querying all of the
registered labels for Busan 77, three labels: Bio/TEC 112 ( EPA Reg#
55137-1),  Bioguard Algae All 60 (EPA Reg# 5185-339), and BUSAN 77 (EPA
Reg# 1448-42) could potentially result in dietary exposures.  This is
because they are either directed to be used in the paper manufacturing
processes as a slimicide for the pulp and paper mill technologies or for
starch preservation. 

	AD has conducted dietary risk assessments for various REDs for
application rates in the range of 1,000 to 1,200 ppm levels for pulp and
paper mill uses and concluded for these rates that there were not any
dietary risks to any set of population groups.  Based on this, it is
assumed that the low application rate of 10 ppm for the label Busan 77
is not of a concern.  Additionally, the registrant indicated to the
Agency that they no longer plan to support the starch uses, and that
they will be removed (e-mail from Dr. Carl Watson of Buckman
Laboratories to the Agency, 7/19/07).

  SEQ CHAPTER \h \r 1 Residential (Non-Occupational) Exposure and Risk: 

	The residential uses of Busan 77 are primarily aquatic and include
pools, spas, whirlpools, hot tubs, ornamental ponds/fountains, and
aquariums.  In addition, it can be used to control odor-causing and
slime-forming bacteria in waterbed mattress water.   For this screening
level assessment, the Agency selected scenarios based on the end-use
product application/handling methods and use amounts.  The specific
scenarios selected for purposes of the assessment was done so based on
the fact that they are believed to be representative of the vast
majority of the residential uses and provide the high-end estimates for
exposure risks.	

	The criteria and calculations pertinent to the residential assessment
are discussed within the detailed discussion of the exposure assessment
as well in the Busan 77 exposure assessment chapter.   The duration of
exposure for most homeowner applications of algaecide products is
believed to be best represented by the short-and intermediate-term
durations because the applications occur episodically (i.e., weekly) not
daily.  For the residential post-application assessment, short- and
intermediate-term durations were also assessed.

	Residential Handler Risk Estimates:	The resulting short- and
intermediate-term exposures and MOEs for the representative residential
handler scenarios are above the target dermal and inhalation MOE of 100
for all scenarios.  Furthermore, all inhalation MOEs exceeded 1,000 and
therefore, a confirmatory inhalation toxicity study is not warranted
based on the results of these exposure scenarios.

	Residential Postapplication Risk Estimates:  	  For the purposes of
this screening level assessment, postapplication scenarios resulting
from Busan 77 are associated with the industrial textile use and
recreational swimming pool and spas/whirlpool use.   Due to the
extremely low vapor pressure of Busan 77, it was not necessary to assess
inhalation exposures (vapor).   For purposes of the industrial textile
use, 	Busan 77 can be used “to control the growth of bacteria and
fungi in holding and processing tanks of industrial fresh water systems
supplying water to pulp and paper mills, textile mills, and other
manufacturing plants” (EPA Reg. No. 1448-42).   As stated on the label
“absorbents rapidly absorb the product.”  Therefore, it is
anticipated that absorbents such as textiles will absorb Busan 77 and
post-application residential dermal and incidental oral exposures to
treated textiles may occur.  However, a textile residue study is needed
in order to conduct the post-application residential exposures since
there is no data available to calculate the levels of the residues
remaining on the textile post-treatment.  

	

	The remaining residential risks associated with the swimming pool and
spa uses were able to be assessed and there were no MOEs of concern.  

 

Aggregate Exposure and Risk:

	In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.”  Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

	Short-Term Aggregate:  The use patterns of the products and probability
of co-occurrence must be considered when selecting scenarios for
incorporation into the aggregate assessment.   It should be noted that a
complete aggregate assessment for Busan 77 was not conducted at this
time because it needs to include the post-application exposures to
swimming pool water residues as well as post-application exposure to
textile residues.  In addition, it is recognized that there is the
potential for an adult to apply Busan 77 to a swimming pool and
subsequently swim in the treated pool in one day.  However, because the
dermal toxicological effect is skin irritation and not a systemic
effect, any product remaining on the handler following an application
would be diluted or “washed off” once the handler enters the
swimming pool.  Therefore, an aggregate assessment incorporating these
scenarios would actually overestimate dermal exposure and thus are not
appropriate to assess in this case. 

Occupational Exposure and Risk

	  SEQ CHAPTER \h \r 1 Based on examination of product labels describing
uses for the product, it has been determined that exposure to handlers
can occur in a variety of occupational environments such as material
preservation as well as industrial processes and water systems via
liquid pour and liquid pump applications.  In addition, there is the
potential for occupational handlers to come into contact with treated
products (e.g. metalworking fluids, etc).  The representative scenarios
selected by the Agency for assessment were evaluated using maximum
application rates as recommended on the product labels for Busan 77. 
The routes and durations of exposures assessed for the occupational
handler include short- and intermediate-term inhalation.  It is
important to note short-term dermal exposures were not assessed for most
of the occupational handler scenarios because the endpoint is based on
dermal irritation.  An intermediate-term dermal endpoint was not
provided.  There is the exception for machinists using biocide treated
metalworking fluids in which a dermal assessment was conducted.  This is
because it is not feasible to place PPE restrictions for a handler that
comes into contact with already treated fluids.  As a result, all of the
dermal irritation exposures and risks, with the exception of the
metalworking fluid machinist, will be mitigated using default personal
protective equipment requirements.  Most of the labels currently do not
require PPE; however, based on the assessment, all of the labels will
need to be updated to reflect the PPE requirement.

	To assess the handler risks, the Agency used surrogate unit exposure
data from the proprietary Chemical Manufacturers Association (CMA)
antimicrobial exposure study and for the instances when the CMA data was
insufficient, other data and methods were applied and are discussed in
the supporting chapter.  All of the calculated MOEs for handlers of
Busan 77 in the occupational setting were above the target MOE of 100
for ST and IT inhalation exposures.  Furthermore, the calculated
inhalation MOEs for all of the scenarios assessed are all above 1,000
such that a confirmatory inhalation toxicity study is not warranted
based on these uses.   

	For purposes of the assessment of the machinist handling already
treated metalworking fluids, the inhalation MOE was above the target
MOE; however the dermal MOE was less than 100 (ST dermal MOE = 20) for
the maximum application rate and is therefore of a concern.  This risk
can not be mitigated with PPE restrictions because this route of
exposure occurs after the chemical has been incorporated into the
metalworking fluid and a machinist is using/handling this treated
end-product.  AD also assessed the short term dermal risks posed to a
machinist handling fluids that have been treated at a minimum
application rate; and the MOE at this lower rate was greater than the
Target MOE of 100 and is not a concern (MOE = 200).

Water Exposure and Environmental Fate:

	Busan 77 is a water-soluble, cationic ionene polymer with an average
molecular weight of 3,886 g/mol.  Based on its miscibility in water and
high molecular weight, volatility from water is highly 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 in the studies available to the Agency.  It supports
that Busan 77 becomes sediment-bound in both aerobic and anaerobic
aquatic systems and as  a result, it is conclusive that Busan 77 is 
positively charged and soil/sediment is negatively charged.  As a result
of this behavior, Busan 77 is not expected to contaminate surface and
ground waters. 

Environmental Hazard and Risk: 

	An ecological risk assessment is not typically conducted for the types
of uses registered for Busan 77 because the uses are considered indoor
and to have minimal to no environmental exposure potential following
use.  However an ecological risk assessment was necessary to conduct for
the once-through cooling water use.  The results of the comprehensive
assessment of this use indicates that there may be risk to freshwater
fish, freshwater invertebrates and estuarine/marine invertebrates from
the use of Busan 77.  Additionally there are several data gaps as
identified below with the corresponding EPA guideline number:

1)  850.1300: Aquatic invertebrate life-cycle study (using TGAI and most
sensitive species -                        freshwater or
estuarine/marine)

2)  850.1400: Fish early-life stage study (using TGAI and most sensitive
species - freshwater     or estuarine/marine)

3)  850.4225: Seedling emergence study - dose response using rice (Oryza
sativa)

4)  850.4400: Freshwater floating macrophyte duckweed study

5)  850.5400: Aquatic plant growth (algal toxicity) – 2 studies
outstanding (marine diatom -                         Skeletonema
costatum and green algae - Selenastrum capricornutum); Tier II          
                (using TGAI or TEP)

6)  850.1735: Whole sediment, acute invertebrates (freshwater) (using
TGAI)

7)  850.1740: Whole sediment, acute invertebrates (estuarine/marine)
(using TGAI)

	8)  Depending on the results of the whole sediment, acute invertebrate
studies, the following data may be required: Whole sediment - chronic
invertebrates (freshwater and/or estuarine/marine) (using TGAI or TEP)

	Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  This was considered
for the assessment and it was for purposes of the preliminary analysis
for the once-through cooling water uses of Busan 77, there is a
potential for Busan 77 use to overlap with listed species.  A more
refined assessment is warranted, to include direct, indirect and habitat
effects, such that an endangered species effect determination will not
be made at this time.  

	

2.0	PHYSICAL AND CHEMICAL PROPERTIES

	 

	The physical and chemical properties for Busan 77 are provided in Table
1.  The product chemistry chapter (memo from A.N. Shamim, September
2007) provides a comprehensive discussion of the various
physical/chemical properties.

			

Table 1: Physical and Chemical Properties reported for Busan 77

Parameter	Busan 77

PC Chemical Code	069183

CAS Number	31512-74-0

Molecular Formula	Variable as the polymeric units differ

Synonyms	WSCP

Molecular Weight	3,886 g/mol

Melting Point	Waived

Boiling Point	111o C

Henry Law Constant	NA

Water Solubility	Completely soluble in water

log Kow	Waived

Vapor Pressure	10.8 mm Hg (20 o C),

14.4 mm Hg (25 o C) 1

Half life in air	NA

1 The vapor pressure studies were conducted on TGAI which is 60% active
in 40% water.  It is, therefore, likely that some of the measured values
may not be attributed the pure TGAI. Considering the fact the study was
conducted with 60/40: polymer/water ratio, the extremely high vapor
pressure value is likely due to water vapor. It should be further noted
that a preliminary EPISuite analysis estimated a very low vapor pressure
(i.e., <<1 x 10-10 mm Hg) of Busan 77.  Given the fact that the cited
vapor pressure is likely of water not the polymer, the high molecular
weight, and extremely low vapor pressure estimated from EPISuite, vapor
inhalation exposures were not necessary to assess.

3.0	HAZARD CHARACTERIZATION tc "

3.0	HAZARD CHARACTERIZATION" 

   3.1 Hazard Profile  tc "3.1 Hazard Profile " \l 2 

	A detailed Toxicology Assessment for Busan 77 is presented in the
attached memorandum from T. McMahon (Dated September 2007).  A detailed
summary of the key toxicological studies is presented in Appendix B
because of the large number toxicological information on this compound. 
A brief hazard assessment is presented below. 

	Acute Toxicity: The acute toxicity database for Busan 77 is complete. 
Busan 77 tested at 61.6% a.i. has a moderate order of acute toxicity via
the oral, dermal and inhalation routes of exposure (Toxicity Category
III).  For dermal irritation, Busan 77 has a low order of acute toxicity
(Toxicity Cateogry IV) and  is not a dermal sensitizer.  Busan 77 is
also identified to be a slight eye irritant.  The acute toxicity data
for Busan 77 is summarized below in Table 2.

Table 2.  Acute Toxicity Profile for Busan 77

Guideline Number	Study Type/Test substance (% a.i.)	MRID Number/

Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute Oral- Rat

purity 61.6% -Busan 77	41373401/

93062009	LD50 = 1951 (1727-2203) mg/kg (M); LD50 = 2587 (2059-3250)
mg/kg (F)	III

870.1200

(§81-2)	Acute Dermal- Rabbit

purity 61.6% – Busan 77	41327101/

93062010	LD50 > 2000 mg/kg	III

870.1300

(§81-3)	Acute Inhalation- Rabbit

Purity 60% - Busan 77	41877501	LC50 = 4.0 (2.3-7.1) mg/L (M); 2.4
(1.7-3.3) mg/L (F); 2.9 (2.3-3.7) mg/L (combined)	III

870.2400

(§81-4)	Primary Eye Irritation- Rabbit purity 61.6% -Busan 77	41361701/

93062011	Redness cleared on day 3	III

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit

61.6% - Busan 77	41298601/ 

93062012	Slight Irritant	IV

870.2600

(§81-6)	Dermal Sensitization - Guinea pig

purity 60.1 % - Busan 77	40750301/

93062013	Not a sensitizer.	NA

3.2 Dose-Response Assessment  tc "3.3 Dose-Response Assessment " \l 2  

	The toxicity endpoints generated for Busan 77 are reported in Table 3
and discussed in the supporting toxicological chapter (from T. McMahon
September 2007).



Table 3:  Summary Table of Toxicological Dose and Endpoint

Exposure Scenario	

Dose (mg/kg/day) UF / MOE	

Hazard Based Special FQPA Safety Factor	

Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary (gen pop)	

This risk assessment is not required.

Acute Dietary (females 13+)	This risk assessment is not required.

Chronic Dietary	

NOAEL = 100 mg/kg/day

UF = 100

Chronic RfD = 1.0 mg/kg/day	

1x	

Chronic toxicity in rats

LOAEL = 300 mg/kg/day based on clinical alterations and reduced body
weight gain

Incidental Oral

Short-Term

(1 - 30 Days)

 	

NOAEL = 500 mg/kg/day

MOE = 100	

	

Developmental Toxicity - Rat

LOAEL = 700 mg/kg/day (increased mortality)

Incidental Oral

Intermediate-Term

(1 - 6 Months)

 	

NOAEL = 221 mg/kg/day

MOE = 100	

	

Subchronic toxicity in Rats

LOAEL = 752 mg/kg/day

Based on renal tubular mineralization

Non-Dietary Risk Assessments

Dermal

Short-Term	

NOAEL = 10 mg/kg/day

(125 µg/cm2)

MOE = 100	

	

 90-day dermal toxicity study in rats

MRID 40170601

LOAEL = 100 mg/kg/day, based on dermal irritation. 

Dermal

Intermediate and Long-Term

 

	 

No endpoint identified in the database. 

Inhalation

Short-Term

(1 - 30 Days)	

MOE = 1000	

	

See short-term incidental oral endpoint

Inhalation

Intermediate-Term

(1 - 6 Months)	

MOE = 1000	

	

See intermediate-term incidental oral endpoint

Inhalation

Long-Term

(> 6 Months)	

MOE = 1000	

	

See chronic RfD endpoint

Cancer	

Group “D” based on increased thyroid C-cell adenomas by ad hoc
committee.  Referred to the full HED CARC for evaluation of carcinogenic
potential.

	For Busan 77, the target MOE is 100 for all routes and duration of
exposure.  It should be noted that since the inhalation NOAEL is based
on an oral study that an additional 10X (i.e., MOE = 1,000) may be
warranted to request that an inhalation-specific study be conducted.   

3.3   FQPA Considerations

	Under the Food Quality Protection Act (FQPA), P.L. 104-170, which was
promulgated in 1996 as an amendment to the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and
Cosmetic Act (FFDCA), the Agency was directed to "ensure that there is a
reasonable certainty that no harm will result to infants and children"
from aggregate exposure to a pesticide chemical residue.  The law
further states that in the case of threshold effects, for purposes of
providing this reasonable certainty of no harm, "an additional tenfold
margin of safety for the pesticide chemical residue and other sources of
exposure shall be applied for infants and children to take into account
potential pre- and post-natal toxicity and completeness of the data with
respect to exposure and toxicity to infants and children. 
Notwithstanding such requirement for an additional margin of safety, the
Administrator may use a different margin of safety for the pesticide
residue only if, on the basis of reliable data, such margin will be safe
for infants and children."

	The toxicology database is considered to be complete with respect to
assessing the increased susceptibility to infants and children as
required by FQPA for Busan 77 because this chemical is not used in food.
 The ADTC report has recommended that the special hazard-based FQPA
safety factor for Busan 77 be removed (please see Busan 77 Revised
Report of the Antimicrobials Division’s Toxicology Endpoint Selection
Committee (ADTC). From T. McMahon, Dated July 26, 2007, PC Code 069183).
This conclusion is based upon the availability of acceptable
developmental and reproductive toxicity studies with Busan 77 that
adequately characterize the dose-response of this compound and the lack
of evidence for any sensitivity of offspring to the adverse effects of
Busan 77.

3.4	Endocrine Disruption

	  SEQ CHAPTER \h \r 1 EPA is required under the 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).

4.0	INCIDENCE REPORTS

	 tc "8.0	INCIDENTS" The Agency consulted the following databases for
poisoning incident data for Busan 77:  OPP Incident Data System (IDS),
Poison Control Centers, National Pesticide Information Center (NPIC) and
California Department of Pesticide Regulation (1982-2004). These
databases are summarized in more detail in the supporting incident
report chapter (J. Chen, August 2007).  

Although limited incidents reported in OPP IDS support that exposure to
Busan 77 may have some irritation concern through dermal, inhalation,
and/or ocular exposure, most of the symptoms are consider minor.  There
are no reported severe incidences associated with Busan 77 exposure in
the remaining databases and scientific literature that was consulted.  

5.0	EXPOSURE ASSESSMENT AND CHARACTERIZATION tc "4.0	EXPOSURE ASSESSMENT
AND CHARACTERIZATION" 

5.1 Summary of Registered Uses  tc "4.1 Summary of Registered Uses " \l
2 

	Busan 77 is only registered as an active ingredient in pesticide
products in which it serves as a algaecide, bacteriostat, fungicide,
microbiocide/microbiostat and molluscicide.  This active ingredient is
found in products that can be used in residential and occupational
settings.  Examples of the specific use sites in which products
containing Busan 77 can be applied include: swimming pools, spas,
whirlpools, hot tubs, metalworking fluids, fire water protection
systems, cooling water towers, petroleum secondary recovery systems,
paper mill process water, air washer water systems, ornamental ponds,
and aquariums.  In addition, various sorts of fibers can be preserved
with Busan 77.  The concentrations of Busan 77 as an active ingredient
in the registered end-use products range from 1.7% – 60%.  These
products are formulated as soluble concentrates, ready-to-use solutions
or granular pellets/tablets.  The application rates used in this
assessment were the maximum application rates as recommended on the
product labels (Tables A-1 and A-2  in Appendix A).

5.2 	Dietary Exposure and Risk

	For a complete dietary assessment please refer to the memorandum from
A.N Shamim, dated September 2007.  Upon considering all of the
registered labels for Busan 77, three labels: Bio/TEC 112 ( EPA Reg#
55137-1),  Bioguard Algae All 60 (EPA Reg# 5185-339), and BUSAN 77 (EPA
Reg# 1448-42) could potentially result in dietary exposures since they
are directed to be used in the paper manufacturing processes.  For the
BUSAN 77 label that includes the pulp and paper mill use, the active
ingredient is intended to serve as a slimicide for the machine parts
contacted by fresh water.  It is not recommended for use as the primary
microbiocide for pulp and paper mill slime control.  In addition, AD has
conducted dietary risk assessments on various REDs for application rates
in the range of 1,000 to 1,200 ppm levels.  In all such application
rates AD did not find any dietary risks to any set of population groups.
 With this information along with such a low application rate of 10 ppm,
the active ingredient assessed in this risk assessment is not considered
to result in dietary risks for any group or subgroup of the US
population. 

	

	All three of the labels have use direction for starch preservation, and
this could entail a possible migration of Busan 77 to the food
indirectly.  However, per an email received by the Agency from Dr. Carl
Waston of Buckman Laboratories (7/19/07), the registrant has decided to
no longer support the use of the chemical Busan 77 for starch
preservation.   This use is subject to removal from the label at the
close of the review process, and ultimately there are no dietary
exposures anticipated from the remaining supported uses of Busan 77. 

5.3   Drinking Water Exposure and Risk for Active Ingredient Uses 

	

	There are no registered outdoor uses for Busan 77, and the chemical
adsorbs strongly to soils, such that a drinking water exposure
assessment was not warranted. 

5.4 	Residential Exposure/Risk Pathway tc "4.4 	Residential
Exposure/Risk Pathway " \l 2 

	Details of the residential exposure assessment can be found within the
companion memorandum that contains the comprehensive residential and
occupational exposure assessment (C. Walls, July 2007).   In summary,
all of the potential exposures to Busan 77 that were able to be assessed
for residential users; both handler and post-application exposures, are
not of a concern.  It is important to make note that the
post-application exposures and risks were not able to be assessed for
individuals coming into contact with treated textiles.  A textile
residue study for the fresh water microbiocide use in textile
manufacturing facilities is needed to conduct the post-application
residential dermal and incidental oral exposure assessment. 

	In order to conduct the comprehensive risk assessment, AD used standard
assumptions, surrogate unit exposure data from the Chemical
Manufacturers Association (CMA) antimicrobial exposure study, EPA’s
Health Effects Division’s (HED) Standard Operating Procedures (SOPs)
for Residential Exposure Assessments, and EPA’s SWIMODEL. The specific
input parameters and assumptions are discussed in the supplementary
exposure assessment.  It is important to note that most of the CMA data
are of poor quality therefore, AD requests that confirmatory monitoring
data be generated to support the values used in these assessments.   In
addition, the values utilized for the quantities handled/treated were
estimated based on information from various sources and these can be
further refined from input from registrants.  

	A summary of the residential handler exposure and risk estimates that
were calculated are provided in Table 4.   A summary of the residential
post-application exposures and risk estimates are provided in Table 5. 
In addition, the post-application inhalation exposures (vapor) were not
assessed due to the extremely low vapor pressure of Busan 77.   A
thorough discussion of the parameters utilized is provided in the
companion memorandum.Table 4: Residential Handler Exposures and MOEs
for Busan 77

Exposure Scenario	Application Method	Unit Exposure	Amount treated

(gal/day)	Use Ratea	Amount ai handled (lb ai/day)b	ST/IT Exposure	ST
MOEsf

Target MOE = 100	IT MOEsf

Target MOE = 100

Dermal  (mg/lb ai/cm2)	Inhal (mg/lb ai)

Dermal (mg/cm2)c	Inhalation (mg/kg/day)d	Dermal	Inhalation	Inhalation

Swimming pools	Open pour - liquid	0.00023	0.00346	20,000	0.0012	fl oz
ai/gal	1.6	3.6E-04	7.7E-05	350	6,500,000	2,900,000

	Open pour - solid	NA	0.0119	20,000	0.0012	oz ai/gal	1.5	NA	2.6E-04	NA
2,000,000	870,000

Spas/whirlpools/

ponds	Open pour - liquid	0.00023	0.00346	1,000	0.0012	fl oz ai/gal	0.086
2.0E-05	4.2E-06	6,400	120,000,000	52,000,000

Aquariums	Open pour - liquid	0.00023	0.00346	100	0.00023	fl oz ai/gal
0.0015	3.4E-07	7.4E-08	360,000	6,800,000,000	3,000,000,000

Waterbed mattress	Open pour - liquid	0.00023	0.00346	180	0.0044	fl oz
ai/gal	0.053	1.2E-05	2.6E-06	10,000	190,000,000	84,000,000

a: Please see Table 4.1 of the Occupational and Residential Exposure
Chapter for a discussion of how the rates were calculated.

b: Liquid Amt ai handled (lb ai/day) = use rate (fl oz ai/gal) x
gal/128oz x product density (lb/gal) x amt treated (gal treated/day)

    Solid Amt ai handled (lb ai/day) = use rate (oz ai/gal) x lb/16oz x
amt treated (gal treated/day)

c: Dermal exposure (mg/cm2) = Dermal unit exposure (mg/lb ai/cm2) x Amt
ai handled (lb ai/day) 

e: Inhalation exposure (mg/kg/day) = Inhalation unit exposure (mg/lb ai)
x Amt ai handled (lb ai/day)/70 kg

f: MOE = NOAEL / Exposure; where ST dermal NOAEL = 125 µg/cm2 (or 0.125
mg/cm2);  ST inhalation NOAEL = 500 mg/kg/day; IT inhalation NOAEL = 221
mg/kg/day

Table 5: Short-term Adult and Child Dermal Exposures and MOEs for Busan
77 used in Swimming Pools and Spas

Scenario	

Dose

(µg/cm2)	

MOEa

ST Adult and Child Dermal Exposures and MOEs From the Use of Pools and
Spasa	0.046	2,700

Child (7-10 years)  Incidental Ingestion exposures for both competitive
and non-competitive swimmers in poolsb	0.016	32,0000 (ST) and 14,000
(IT)

ST Child (11-14 years)  Incidental Ingestion exposures for both
competitive and non-competitive swimmers in poolsb	0.0097	52,000 (ST)
and 23,000 (IT)

ST Adult competitive swimmers in pools; Incidental Ingestion Exposureb
0.0050	100,000 (ST) and 44,000 (IT)

ST Adult non-competitive swimmers in pools; Incidental Ingestion
Exposureb	0.0030	150,000 (ST) and 66,000 (IT)

a: MOE = NOAEL mg/kg/day/ Dose (mg/kg/day).  ST Oral NOAEL = 500
mg/kg/day, IT Oral NOAEL = 221 mg/kg/day; ST and IT Target MOE = 100

6.0 	AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION tc "5.0 
AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION" 

	In order for a pesticide registration to continue, it must be shown
that the use does not result in “unreasonable adverse effects on the
environment”.  Section 2 (bb) of FIFRA defines this term to include
“a human dietary risk from residues that result from a use of a
pesticide in or on any food inconsistent with standard under section
408...” of FFDCA.  As mandated by the FQPA amendments to FIFRA and the
Federal Food, Drug and Cosmetic Act (FFDCA), the Agency must consider
total potential exposure to Busan 77 (or its residues) that may occur
from dietary (i.e., food and drinking water), residential, and other
non-occupational sources, and from all known or plausible exposure
routes (oral, dermal, and inhalation).  

	In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at    
HYPERLINK "http://www.epa.gov/pesticides/trac/science/aggregate.pdf" 
http://www.epa.gov/pesticides/trac/science/aggregate.pdf ).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk.  

Short- and intermediate-term aggregate exposures and risks were
considered for adults and children that could be exposed to Busan 77
from the use of products in non-occupational environments.  The use
patterns of Busan 77 products and probability of co-occurrence were
addressed when selecting scenarios for incorporation in the aggregate
assessment.  The exposure scenarios that were considered for the
aggregate assessment are summarized in Table 6, and it is important to
note that there are no identified routes of dietary exposures to Busan
77.  

 

Table 6.  Short-term Aggregate

Adults 	Dermal:

Applying Busan 77 to swimming pools

Applying Busan 77 to spas/whirlpools

Applying Busan 77 to ornamental ponds/fountains

Applying Busan 77 to aquariums

Exposures to swimming pool water residues

Exposure to textile residues

Children	Exposures to swimming pool water residues

Exposure to textile residues

	It was determined that an aggregate assessment could not be conducted
at this time due to the lack of textile residue data.  The aggregate
assessment will need to include post-application exposures to swimming
pool water residues along with post-application exposure to textile
residues.

7.0	CUMULATIVE EXPOSURE AND RISK

		Another standard of section 408 of the FFDCA which must be considered
in making an unreasonable adverse effect determination is that the
Agency considers "available information” concerning the cumulative
effects of a particular pesticide's residues and "other substances that
have a common mechanism of toxicity.” 

		Unlike other pesticides 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 Busan 77 and any other
substances and Busan 77 does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA has assumed that Busan 77 does not have 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 http://www.epa.gov/pesticides/cumulative/.

8.0	OCCUPATIONAL EXPOSURE AND RISK tc "7.0	OCCUPATIONAL EXPOSURE AND
RISK"  

The Agency has assessed the exposures and risks to occupational workers
that handle Busan 77 (memorandum from C. Walls, July 2007).  Potential
occupational handler exposures can occur during the application of Busan
77 through either liquid/solid pour or liquid pump methods. 
Liquid/solid pour refers to transferring the antimicrobial product from
a small container to an open vat.  Liquid pump refers to transferring
the preservative by connecting/disconnecting a chemical metering pump
from a tote or by gravity flow.  For these routes of exposures,
short-term dermal exposures were not assessed because the endpoint is
based on dermal irritation.  Instead, dermal irritation exposures and
risks will be mitigated using default personal protective equipment
requirements based on the toxicity of the end-use product.  To minimize
dermal exposures, the minimum PPE required for mixers, loaders, and
others exposed to end-use products that result in classification of
category I, II, or III for skin irritation potential will be a
long-sleeve shirt, long pants, shoes, socks, chemical-resistant gloves,
and a chemical-resistant apron.  Note that chemical-resistant eyewear
will be required if the end-use product is classified as category I or
II for eye irritation potential. Most of the labels currently do not
require PPE; based on this assessment all of these labels will need to
be updated to reflect the PPE requirement.

	There are also potential dermal and inhalation exposures for a
machinist working with Busan 77 treated metalworking fluids.  Since
gloves are also not a viable mitigation option for a machinist using
biocide treated metalworking fluids, the short-term dermal exposure was
assessed for this scenario.  This is presented separately from the
occupational handler assessment because of the specific input parameters
and assumptions.  The parameters utilized for the occupational exposure
assessment are identified in Table 7, and a complete discussion of the
standard AD assumptions and unit exposure values utilized is provided in
the supporting exposure assessment chapter.  All of the MOEs for
occupational handlers assessed and reported in Table 7 are greater than
the target MOE of 100 and therefore are not of a concern.

Table 7: Occupational Handler Exposures and MOEs for Busan 77

Exposure Scenario	Application Method	Unit Exposure	Amount handled/

treated

(gal/day)	Use Ratea	Amount ai handled

 (lb ai/day)b	ST/IT Exposure	ST MOEsd

Target MOE = 100	IT MOEsd

Target MOE = 100

Inhalation 

(mg/lb ai)

Inhalation (mg/kg/day)c	Inhalation	Inhalation

Residential Premises

Swimming pools	Open pour - liquid	0.00346	200,000	0.0012	fl oz ai/gal
15.5	7.7E-04	650,000	290,000

	Open pour - solid	0.0119	200,000	0.0012	oz ai/gal	15.0	2.6E-03	200,000
87,000

Materials Preservative

Metal working fluid	Open pour - liquid	0.00854	300	0.06%	%ai	1.73
2.1E-04	2,400,000	1,000,000

	Metering pump	0.00348	300	0.06%	%ai	1.73	5.2E-08	9,700,000,000
4,300,000,000

Industrial Processes and Water Systems

Paper/Textile Mills	Metering pump	0.000265	20,000	0.0007	fl oz ai/gal
0.99	2.5E-09	200,000,000,000	90,000,000,000

Oil Field:

Water-based drilling fluids	Open pour - liquid	0.00346	5.6 (ST)

2.8 (IT)	0.0056	fl oz ai/gal	0.0021 (ST)

0.0011 (IT)	1.0E-07 (ST)

5.2E-08 (IT)	4,800,000,000	4,200,000,000

Oil Field:

Secondary recovery	Metering pump	0.000265	420,000	0.0056	fl oz ai/gal
158.9	6.02E-04	830,000	370,000

Recirculating Cooling Water	Open pour - liquid	0.45	10	0.0042	fl oz
ai/gal	0.0028	1.8E-05	27,000,000	12,000,000

	Metering pump	0.00432	20,000	0.0042 (ST)

0.0021 (IT)	fl oz ai/gal	5.68 (ST)

2.84 (IT)	3.5E-04 (ST)

1.8E-04 (IT)	1,400,000	1,300,000

	Metering pump	0.000265	50,000,000	0.0042 (ST)

0.0021 (IT)	fl oz ai/gal	14192 (ST)

7096 (IT)	5.4E-02 (ST)

2.7E-02 (IT)	9,300	8,200

Once-through Cooling Water	Open pour - liquid	0.45	10	0.0012%	%ai	0.0010
6.7E-06	75,000,000	33,000,000

	Metering pump	0.000265	2,000,000	0.0012%	%ai	208.56	7.9E-04	630,000
280,000

	Metering pump	0.000265	83,000,000	0.0012%	%ai	8655.24	3.3E-02	15,000
6,700

Air washer systems	Open pour - liquid	0.00346	10,000	0.0042	fl oz ai/gal
2.73	1.4E-04	3,700,000	1,600,000

	Metering pump	0.000403	10,000	0.0042	fl oz ai/gal	2.73	1.6E-05
32,000,000	14,000,000

Fire water protection systems	Open pour - liquid	0.00346	50,000	0.0056
fl oz ai/gal	18.92	9.4E-04	530,000	240,000

	Metering pump	0.000403	50,000	0.0056	fl oz ai/gal	18.92	1.1E-04
4,600,000	2,000,000

a: see Table 6.1 of the Occupational and Residential Exposure
Assessment 

b: Liquid Amt ai handled (lb ai/day) = use rate (fl oz ai/gal) x
gal/128oz x product density (lb/gal) x amt treated (gal treated/day)

    Solid Amt ai handled (lb ai/day) = use rate (oz ai/gal) x lb/16oz x
amt treated (gal treated/day)

c: Inhalation exposure (mg/kg/day) = Inhalation unit exposure (mg/lb ai)
x Amt ai handled (lb ai/day)/70 kg

d: MOE = NOAEL / Exposure; where ST inhalation NOAEL = 500 mg/kg/day; IT
inhalation NOAEL = 221 mg/kg/day

	The results for the risks posed to a machinist handling Busan 77
treated metalworking fluids are provided in Tables 8 and 9.  The
inhalation MOEs are greater than the target MOE of 100.  However, for
the short term dermal exposures, risks were evaluated at the maximum and
minimum application rates.  The MOE at the maximum application rate is
less than the target MOE of 100 and is therefore of a concern.

Table 8:  Short- term Dermal Exposures and MOEs for Machinist Exposure
to Metalworking Fluids

Exposure Scenario	

% aic	Film thickness (mg/cm2)	Exposure a

(mg ai/cm2)	Dermal MOE

 (Target MOE = 100) b

Machinist - two hand immersion	0.006	10.3	6.2E-04	200

	0.06	10.3	6.2E-03	20

a	For ST, exposures are calculated as a.i. per area of skin exposed
(mg/cm2) =  (% active ingredient x film thickness mg/cm2 (10.3 for ST
exposure).  

b	MOE = NOAEL (mg/cm2) / exposure (mg/cm2), Where: short-term NOAEL =
0.125 mg/cm2

c	The percent active ingredient in the treated fluid was assumed to be
the highest use rate for metalworking use scenarios (60 -600 ppm ai, or
0.006 - 0.06%, a.i. in treated metalworking fluid; Reg. No. 1448-217).

Table 9  Short-, Intermediate- and Long-Term Inhalation Exposures and
MOEs Associated with Metalworking Fluids Treated with Busan 77
(Machinist)

Exposure Scenario	% a.i.	OSHA PEL (mg/m3)	Inhalation rate

(m3/hr)	Exposure Duration (hrs/day)	Exposure (mg/kg/day)	

Inhalation MOEs

(Target MOE is 100) b

	

ST/IT/LT	

ST	

IT/LT

Machinist	

0.06%	

5	

1.25	

8	

4.3E-04	

1,200,000	

520,000

a Exposure (mg/kg/day) = % ai x OSHA PEL (mg/m3) x Inhalation rate
(m3/hr) x exposure duration (hr/day) / body weight (70 kg)

b  MOE = NOAEL (mg/kg/day) / exposure (mg/kg/day) [Where: ST NOAEL = 500
mg/kg/day and IT/LT NOAEL = 221 mg/kg/day] 

There are several data limitations and uncertainties associated with the
occupational assessment of Busan 77.  These are summarized in the
supporting chapter as well as below:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary CMA antimicrobial exposure study (US EPA 1999: DP Barcode
D247642). Most of the CMA data are of poor quality therefore, AD
requests that confirmatory monitoring data be generated to support the
values used in these assessments.  

The CMA unit exposure data used for the secondary recovery in oilfields
and water cooling tower operations are based on metering pump
applications made in a pulp and paper facilities.  Since the volume of
water being treated in secondary recovery and cooling water tower
operations is so large, the available CMA data can not be reliably
extrapolated because they are based on activities that handle much lower
volumes and possibly different techniques.  Therefore, it was assumed
that pulp and paper chemical metering applications, which are typically
large operations, can be representative of other large operations. 
Additional exposure data should be collected to confirm the estimates
for large scale applications 

The once through cooling water flow volumes for power generation are
large (e.g., 500 million gallons assessed).  It is unknown if these
utilities actually use Busan 77 but there are not label restrictions on
flow volumes.  Nonetheless, this screening-level assessment and the
inhalation risks are not of concern at these higher flows.

The use information for the pulp and paper/textile processing, materials
preservation, oil-well uses, and cooling water tower uses are based on
personal communication with the registrants.  The individuals contacted
have experience in these operations and their estimates are believed to
be the best available without undertaking a statistical survey of the
uses. 

9.0.	ENVIRONMENTAL FATE

Detailed information on the environmental fate of Busan 77 is presented
in the attached memo from J. Breithaupt (September 2007).  A brief
summary is provided below and the environmental fate database is
considered to be complete.  The various studies that were considered for
the environmental fate assessment are identified and summarized in Table
10.

.  

Table 10:  Environmental Fate Properties of Busan 77

Guideline No./

Study Type	Results	Reference Information

835.2110

Hydrolysis	Mean: 103-137mg/L over 30 day period

The hydrolytic stability of aqueous solutions of Busan 77 was tested at
pH 5, 7 and 9. No degradation was observed at any tested pH over a 30
day period at 25 °C in the dark. The following table summarizes the
measured concentrations of Busan 77 during the study.	41407401/93062026

Smith, A. (1990) Determination of Aqueous Hydrolysis Rate Constant and
half-life of Busan 77: Final Report: Lab Project Number:
995-1089-6116-715: Lab Report Number 90-2-3216. Unpublished study
prepared by Springborn Laboratories, Inc. 32 p.

Acceptable

835.2210

Direct photolysis rate in water by sunlight	Avg. mean recovery: 79.5 ±
3.5%

Under the aseptic test conditions employed with a solution temperature
of 25.6 ± 1.6 °C for the pH 5 and 7 phase of this study and 25.7 ±
1.7 °C for the pH 9 phase of this study, Susan 77 is photolytically
stable. Definitive testing was performed over a 30 day period with no
appreciable degradation observed, within experimental error, in any
solution at any of the pHs tested. Busan 77 is considered photolytically
stable (EPA Standard Evaluation Procedure, 1985).	41420901/93062027

Smith, A. (1990) Determination of Aqueous Photolysis Rate Constant and
half-life of Busan 77: Lab Project Number: 995-1089-6117-720; 90-3-3251.
Unpublished study prepared by Springborn Laboratories, Inc. 37 p.

Acceptable

835.3100

Aerobic aquatic biodegradation 	First Experiment. Under aerobic aquatic
conditions, 14C-Busan 77 (5.07 ppm) rapidly became sediment-bound. In
this experiment, sediment bound residues increased from approximately
11% at Day 0 to 53% at Day 2 and retained in the range of 52% to 70% for
the 30-day study. Approximately 4.0% of the total dose was trapped as
CO2 and 0.1% of the applied radioactivity was trapped as organic
volatiles by Day 30. Total recoveries averaged approximately 63% for the
experiment, which resulted from strong adsorption of the test material
to laboratory glassware during sale extraction.

Second Experiment. In the second experiment, 14C Busan 77 (4.77 ppm)
rapidly because sediment bound in aerobic aquatic samples. This sediment
bound radioactivity increased from approximately 31% at Day 0 to 94% at
Day 1, and then remained fairly constant for the 31 day study.
Approximately 5% of the total applied radioactivity was trapped as CO2.
No radioactivity was detected as organic volatiles. Total recoveries
averaged 100.0% for the experiment.	MRID 40334101

Obrist, J. (1987) Aerobic Aquatic Metabolism of Busan 77: Laboratory
Project ID: HLA 6015-251: Final Report. Unpublished study prepared by
Hazleton Laboratories America, Inc. 69 p.

Acceptable

835.3300

Anaerobic biodegradability of organic chemicals	Under laboratory
conditions at 25°C ±2°. Busan 77 rapidly became sediment-bound in an
anaerobic aquatic system (Lake Mendota water and sediment) following
treatment at 4.75 ppm. Sediment bound residues accounted for more than
90% of the total applied dose at all sampling points (except Day 0)
through 365 days. The majority of the sediment bound radioactivity was
associated with the humic fraction after treatment with a sodium
hydroxide solution. Approximately 0.7% of the total applied dose was
detected in the carbon dioxide trap, and less than 0.1% of the applied
radioactivity was found in the organic volatiles trap.	40165201

Obrist, J.  1987.  Anaerobic Aquatic Metabolism of Busan 77.  Hazelton #
6015-250.  Unpublished study prepared by Hazelton Laboratories Inc. 50
p.

Acceptable

835.3300

Aerobic Soil Metabolism	Under laboratory conditions at 23-25oC ± 1 oC,
Busan 77 was stable to aerobic soil metabolism.  Good material balance
was observed   	40165202

Das, Y. (1987) Aerobic Soil Metabolism of WSCP: Biospheric No. 84E-301A.
Unpublished study prepared by Biospheric Inc. 50 p.

No record review, based on material balance it appears to be valid.

835.1220

Soil Column Leaching	Busan 77 was found almost exclusively (96 %) in the
top 2 inches of 12-inch columns (average).  <1 % was found in the
leachate of the columns.   	00157906

Cargile, N. (1986).  Soil column leaching of 14C-WSCP.  Final Report
Project No. 84E-303L.   Study conducted by Biospherics, Inc.

00157907

Cargile, N.  Leaching characteristics of Aged 14C-WSCP.  Final Report
Project No. 34E-303AL.  Study conducted by Biospherics, Inc.

Acceptable

850.1730

Bioconcentration in Fish 	Busan 77 did not bioconcentrate (BCF=2) in
channel catfish.  	00159308

Barrows, B.A.  1985.  Bioconcentration of 14C-Radiolabeled WSCP in the
Channel Catfish, Ictalurus punctatus, in a Static Test System.  Study
conducted by Biospherics, Inc., and submitted by Buckman Laboratories.

Unacceptable

	In summary, Busan 77 is considered to be extremely stable
(hydrolytically, photolytically, stable to aerobic soil metabolism, and
stable under aerobic aquatic conditions).  Lastly, the results form the
study on the bioconcentration in fish, the BCF values did not exceed 2
during the study, indicating that bioconcentration is not likely to
occur.  This conclusion is consistent with the fact that Busan 77 is a
cation that will not concentrate in fat. However, it is important to
recognize that the nitrite levels in the water were high, which in turn
caused stress on the fish.  Also, the mortality was higher in the
treatment tank which indicates that in some conditions the presence of
Busan 77 in the water may cause some acute risk to fish.  

	

10.0 	ENVIRONMENTAL RISK

	A detailed ecological hazard and environmental risk assessment for
once-through cooling water of Busan 77 is presented in supporting
ecological risk assessment (memorandum from G. Angle, September 2007). 
A summary of the analysis and findings are presented, and all of the
other registered uses for Busan 77 are considered indoor and have
minimal to no environmental exposure potential following use.  

10.1	Summary of Ecological Toxicity Data Conclusions

	Acute and subacute toxicity to terrestrial organisms: The two acute
oral toxicity studies are considered acceptable and indicate that Busan
77 is moderately toxic to slightly toxic to birds on an acute oral
basis.  The results of the two acceptable subacute dietary studies
indicate that Busan 77 is slightly toxic to relatively nontoxic to avian
species.

	Acute toxicity to aquatic organisms:  Freshwater acute toxicity tests
indicate that Busan 77 is very highly toxic to highly toxic to fish on
an acute basis.  These studies fulfill guideline requirement OPPTS
850.1075 (72-1a&b), however because acute toxicity to fish is <1.0 mg/L,
the environmental hazard section of Busan 77 labels must state: “This
pesticide is toxic to fish.”

	Acute toxicity to estuarine/marine organisms: All of the three studies
available to the agency are acceptable.  These indicate that Busan 77 is
highly toxic to moderately toxic to estuarine/marine invertebrates on an
acute basis and relatively nontoxic to estuarine/marine fish on an acute
basis.  The Quahog clam study (403342-01) fulfills the guideline
requirement OPPTS 850.1055/(72-3b) for an acute estuarine/marine mollusk
study, however because the estuarine/marine acute toxicity values are <
1.0 mg/L, the environmental hazard section of Busan 77 labels must
state:  “This pesticide is toxic to clams.”

	Chronic toxicity to aquatic organisms:  The Agency requires chronic
toxicity testing and the preferred freshwater fish test species is the
fathead minnow, and the preferred freshwater invertebrate is Daphinia
magna.  There has not been any fathead minnow study submitted to date,
and the study on the waterflea does not fulfill the guideline
requirements for a chronic aquatic invertebrate study.  Neither
guideline, OPPTS 850.1300 nor 850.1400 are fulfilled. 

	Toxicity to Plants:  Testing has been conducted with Busan 77 on
several aquatic and terrestrial plant species.  The guideline
requirement for an algal toxicity test (850.5400, 123-2) is partially
fulfilled.  Two additional algal toxicity tests under 850.5400 are
outstanding because they do not meet guideline requirements; which
require a test with the freshwater green alga, Selenastrum
capricornutum, and a test with the marine diatom, Skeletonema costatum. 
The other non-target aquatic plant toxicity requirement, floating
freshwater aquatic macrophyte duckweed (Lemna gibba) – guideline
850.4400 - is not satisfied.  A study on the rooted freshwater
macrophyte rice (Oryza sativa) – 850.4225 (seedling emergence test) -
has not been submitted.

10.2	Environmental Risk Assessment

	This section summarizes the environmental exposure and risk assessment
for releases of Busan 77 when it used for the control of mollusks in
once-through cooling water systems.  The Probabilistic Distribution
Model (version 4) was used to estimate the number and percentage of days
per year that Busan 77 concentrations exceed ecotoxicity concentrations
of concern (COCs) .  The treatment scenarios that were utilized for the
analyses of Busan 77 were derived from product label information.  The
approach used to generate the ecological risk assessment is based on the
methodology developed in support of the environmental exposure
assessment for bromonitrostyrene. The comprehensive discussion of the
parameters, calculations, model output conclusions and data limitations
and uncertainties are all available in the supporting ecological risk
chapter along with the environmental exposure assessment chapter (G.
Angle and S. Mostaghimi, September 2007).

PDM is a screening-level exposure assessment tool developed by EPA to
model chemical releases from point sources to flowing surface waters. 
For this analysis, the PDM component within EPA’s Exposure and Fate
Assessment Screening Tool Version 2.0 (E-FAST2) was used.   Please see
For a modeling period of a given number of days, PDM calculates the
probability distribution of the chemical concentration in the receiving
stream, and then estimates the number of days during which the in-stream
chemical concentration is expected to exceed a COC.  The COC’s
identified and selected from the ecological effects information for
Busan 77 are provided in Table 11.

Table 11: Concentrations of Concern Selected for the Environmental
Exposure Assessment of Busan 77

COC	Test Species	Endpoint Type	Study Type	Reference (MRID)

12 µg/La	Waterflea (Daphnia magna)	NOEC	Life-cycle toxicity to
freshwater invertebrates	

42479601

130 µg/L	Waterflea (Daphnia magna)	NOEC	Acute toxicity to freshwater
invertebrates	

41352003

140 µg/L	Quahog clam (Mercenaria mercenaria)	NOEC	Acute toxicity to
estuarine and marine organisms	

40334201

260 µg/La	Rainbow trout (Oncorhynchus mykiss)	LC50	Acute toxicity to
freshwater fish	

00107207

7,800 µg/L	Mysid shrimp (Mysidopsis bahia)	NOEC	Acute toxicity to
estuarine and marine organisms	

40139203

360,000 µg/L	Sheepshead minnow (Cyprinodon varigates)	NOEC	Acute
toxicity to estuarine and marine organisms	

40139202

a COC is based on a study that does not fulfill the guideline
requirements.

Upon execution of the model, the number of days exceeding each COC were
provided and the averages and standard deviations were calculated.  In
addition, the percent of days per year above the COCs was calculated
along with the percent of days during the release period above COCs
(maximum 100 percent).   The results are provided in Table 12 and the
percentage of facilities that had exceedences at least once (i.e., on at
least one day) for each COC are provided in Table 13.  If the number of
days a COC is exceeded is greater than the number of days used to
determine the endpoint in toxicity testing, risk is assumed.  This
assumes that the number of days exceeded are consecutive, a conservative
but not impossible assumption.  Based on this assumption, Table 12 shows
there will be risk at the average number of days exceeded to freshwater
fish, freshwater invertebrates (both acute and chronic), and
estuarine/marine invertebrates.

Table 12: Number and Percent of Days with Downstream Busan 77
Concentrations Exceeding COCs

COC

(µg/L)	Number of Days With Exceedences	Percent of Days with Exceedences
per Year	Percent of Release Days with Exceedences

	Average Days COC Exceeded	Standard Deviation	Average Days COC Exceeded
Standard Deviation	Average Days COC Exceeded	Standard Deviation

12 µg/La	207	72	57%	20%	83%	29%

130 µg/L	152	94	42%	26%	61%	37%

140 µg/L	149	94	41%	26%	60%	37%

260 µg/La	129	92	35%	25%	51%	37%

7,800 µg/L	12	18	3%	5%	5%	7%

360,000 µg/L	1	5	<1%	2%	<1%	2%

a COC is based on a study that does not fulfill the guideline
requirements.

Table 13:  Percent of Facilities with Downstream Busan 77 Concentrations
Exceeding COCs on at Least One Day (n = 30)

COC

(µg/L)	Percent of Facilities with at Least One Day with an Exceedence 

12 µg/La	97%

130 µg/L	87%

140 µg/L	87%

260 µg/La	87%

7,800 µg/L	57%

360,000 µg/L	10%

                                  a COC is based on a study that does
not fulfill the guideline requirements

Endangered Species Considerations

	Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 C.F.R. ( 402.02.

	To facilitate compliance with the requirements of the Endangered
Species Act subsection (a)(2) the Environmental Protection Agency,
Office of Pesticide Programs has established procedures to evaluate
whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

	For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment.

	This preliminary analysis for the once-through cooling water uses of
Busan 77 indicates that there is a potential for Busan 77 use to overlap
with listed species and that a more refined assessment is warranted, to
include direct, indirect and habitat effects.  The more refined
assessment should involve clear delineation of the action area
associated with proposed once-through use of Busan 77 and best available
information on the temporal and spatial co-location of listed species
with respect to the action area.  This analysis has not been conducted
for this action and an endangered species effect determination is unable
to be made at this time.  

Label Hazard Statements/Use Recommendations:

Busan 77 labels must state:  

(A)  “This pesticide is toxic to fish, aquatic invertebrates and
clams.”

(B)  "Do not discharge effluent containing this product into lakes,
streams, ponds, estuaries, oceans, or other waters unless in accordance
with the requirements of a National Pollutant Discharge Elimination
System (NPDES) permit and the permitting authorities are notified in
writing prior to discharge.  Do not discharge effluent containing this
product to sewer systems without previously notifying the local sewage
treatment plant authority.  For guidance contact your State Water Board
or Regional Office of the EPA."

(C) All of the labels need to be updated to require PPE for occupational
handlers for the protection from dermal irritation effects.

11.0	DEFICIENCIES/DATA NEEDS

There are no identified hazard data gaps, environmental fate data gaps
or product chemistry data gaps. 

Ecological Effects:  

1)  850.1300: Aquatic invertebrate life-cycle study (using TGAI and most
sensitive species -                        freshwater or
estuarine/marine)

2)  850.1400: Fish early-life stage study (using TGAI and most sensitive
species - freshwater     or estuarine/marine)

3)  850.4225: Seedling emergence study - dose response using rice (Oryza
sativa)

4)  850.4400: Freshwater floating macrophyte duckweed study

5)  850.5400: Aquatic plant growth (algal toxicity) – 2 studies
outstanding (marine diatom -                         Skeletonema
costatum and green algae - Selenastrum capricornutum); Tier II          
                (using TGAI or TEP)

6)  850.1735: Whole sediment, acute invertebrates (freshwater) (using
TGAI)

7)  850.1740: Whole sediment, acute invertebrates (estuarine/marine)
(using TGAI)

	8)  Depending on the results of the whole sediment, acute invertebrate
studies, the following data may be required: Whole sediment - chronic
invertebrates (freshwater and/or estuarine/marine) (using TGAI or TEP)

Residential/Occupational Data Gaps :

A textile residue study for the fresh water microbiocide use in textile
manufacturing facilities is needed to conduct the post-application
residential dermal and incidental oral exposure assessment. 

12.0	REFERENCES 

Toxicology Disciplinary Chapter 

00151205	McCarroll, N. (1985) Drosophila Sex-linked Recessive Lethal
Assay [with WSCP (Busan 77)]: Final Report: Project No. 197-183.
Unpublished study prepared by Hazleton Laboratories. 20 p.

00151206	Cortina, T. (1984) In vivo Micronucleus Assay in Mice: WSCP:
Final Report: Project No. 197-182. Unpublished study prepared by
Hazleton Laboratories America, Inc. 38 p.

40025001	Tisdel, M. (1986) Busan 77-Thirteen-week Subchronic Toxicity
Study in Rats: Project ID: Study No. 6176-106. Unpublished study
prepared by Hazleton Laboratories of America, Inc. 285 p.

40139201	Bosch, A. (1987) Dermal Absorption of [Carbon 14]-Busan 77
(WSCP) in Male Rats: HLA Study No. 6176-117: Final Report. Unpublished
study prepared by Hazleton Laboratories America, Inc. 52 p.

40170601	Spindler, M. (1987) 13-Week Dermal Toxicity Study with Busan 77
in Rabbits: Laboratory Project ID: HLA 6176-118. Unpublished study
prepared by Hazleton Laboratories America, Inc. 290 p.

40268601	Puhl, R. (1987) Metabolism Study with Busan 77 (WSCP) in Rats:
Final Report: Laboratory Project ID: HLA 6176-115. Unpublished study
prepared by Hazleton Laboratories America, Inc. 98 p.

40578201	MacKenzie, K. (1988) Two-Generation Reproduction Study with
Busan 77 in Rats (One Litter per Generation): Project ID: HLA 6176-104.
Unpublished study prepared by Hazleton Laboratories America, Inc. 952 p.

40750301	Glaza, S. (1987) Dermal Sensitization Study in Guinea Pigs with
WSCP: Proj. ID 70303995. Unpublished study prepared by Hazleton
Laboratories America, Inc. 30 p.

40978701	Cifone, M. (1989) Mutagenicity Test on Busan 77 in the in
vivo/in vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay:
Project ID: HLA Study No. 10280-0-494. Unpublished study prepared by
Hazleton Laboratories America, Inc. 26 p.	

41234501	Kehoe, D. (1989) One-Year Chronic Toxicity Study with Busan 77
in Dogs: Laboratory Project ID: HLA 6176-111. Unpublished study prepared
by Hazleton Laboratories America, Inc. 301 p.

41248001	Rodwell, D. (1989) Teratology Study in rabbits with Buan 77:
SLS Study No. 3138.29. Unpublished study prepared by Springborn Life
Sciences, Inc. 229 p

41298601	Rush, R. (1989) Primary Skin Irritation Study in Rabbits with
Busan 77: SLS Study No. 3138.49. Unpublished study prepared by
Springborn Laboratories, Inc. 19 p.

41327101	Rush, R. (1989) Acute Dermal Toxicity Study in Rabbits with
Busan 77: Lab Project Number: 3138.50. Unpublished study prepared by
Springborn Laboratories, Inc. 26 p.

41361701	Rush, R. (1989) Primary Eye Irritation Study in Rabbits with
Busan 77 (EPA-FIFRA): Lab Project Number: 3138/52. Unpublished study
prepared by Springborn Laboratories, Inc. 25 p.	

41373401	Rush, R. (1990) Acute Oral Toxicity Study in Rats with Busan
77: SLS Study No. 3138.51. Unpublished study prepared by Springborn
Laboratories, Inc. 65 p.

41423001	Nemec, M. (1987) A Teratology Study in Rats with Busan 77:
Final Report: Lab Project Number: WIL-94020. Unpublished study prepared
by WIL Research Laboratories, Inc. 281 p.

41494301	Kehoe, D. (1990) 18-Month Study with Busan 77 in Mice: Lab
Project Number: HLA 6176-109. Unpublished study prepared by Hazleton
Labs America, Inc. 924 p.	

41561301	Kehoe, D. (1990) Combined Chronic Toxicity and Carcinogenicity
Study with Busan 77 in Rats: Draft Report: Lab Project Number: HLA
6176-107. Unpublished study prepared by Hazleton Laboratories America,
Inc. 1511 p.

41573701	Lawlor, T.; DaCosta, K. (1990) Mutagenicity Test on Busan 77 in
the Salmonella/Mammalian-Microsome Reverse Mutation Assay (Ames Test)
with Confirmatory Assay: Lab Project Number: 12144-0-401R. Unpublished
study prepared by Hazleton Laboratories America, Inc. 33 p.

41809101	Kehoe, D. (1991) Combined Chronic Toxicity and Carcinogenicity
Study with Busan 77 in Rats: Final Report (Supplement to MRID 41561301):
Lab Project Number 6176-107. Unpublished study prepared by Hazleton Labs
America, Inc. 1511 p.

41877501	Hoffman, G. (1991) An Acute Inhalation Toxicity Study of Busan
77 in the Rat: Lab Project Number: 90-8305. Unpublished study prepared
by Bio/dynamics, Inc. 105 p.

93062009	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41373401. Busan 77- Acute Oral Toxicity Study in Rats: Laboratory ID:
313851. Prepared by Springborn Laboratories, Inc. 9 p.

93062010	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41327101. Busan 77- Acute Dermal Toxicity Study in Rabbits: Laboratory
ID: 313850. Prepared by Springborn Laboratories, Inc. 6 p.

93062011	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41361701. Busan 77- Primary Eye Irritation in the Rabbit: Laboratory ID:
313852. Prepared by Springborn Laboratories, Inc. 7 p.

93062012	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41298601. Busan 77- Primary Dermal Irritation in the Rabbit: Laboratory
ID: 313849. Prepared by Springborn Laboratories, Inc. 6 p.

93062013	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40750301. Busan 77- Dermal Sensitization in the Guinea Pig (Closed Patch
Technique) Laboratory ID: 70303995. Prepared by Hazleton Laboratories
America, Inc. 6 p.

93062014	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40025001. Busan 77- Thirteen Week Subchronic Toxicity Study in Rats
Laboratory ID: HLA 6176-106. Prepared by Hazleton Laboratories America,
Inc. 12 p.

93062015	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40170601. Busan 77- 13 Week Dermal Toxicity Study in Rabbits: Laboratory
ID: 6176-118. Prepared by Hazleton Laboratories America, Inc. 6 p.

93062016	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41234501. Busan 77- One Year Chronic Toxicity Study in Dogs: Laboratory
ID: HLA 6176-111. Prepared by Hazleton Laboratories America, Inc. 8 p.

93062017	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41494301. Busan 77- 18 Month Study in Mice: Laboratory ID: HLA 6176-109.
Prepared by Hazleton Laboratories America, Inc. 10 p.

93062019	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41248001. Busan 77- Teratology Study in Rabbits: Laboratory ID: SLS
Study No. 3138-29. Prepared by Springborn Laboratories, Inc. 9 p.

93062020	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40578201. Busan 77- Two Generation Reproduction Study in Rats:
Laboratory ID: HLA 6176-104. Prepared by Hazleton Laboratories America,
Inc. 9 p.

93062021	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
00151206. Busan 77- in Vivo Mouse Micronucleus Assay: Laboratory ID:
197-182. Prepared by Hazleton Biotechnologies Corporation. 8 p.

93062022	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40978701. Busan 77- in Vivo/In Vitro Rat Primary Hepatocyte Unscheduled
DNA Synthesis Assay: Laboratory ID: 10280-0-494. Prepared by Hazleton
Laboratories America, Inc. 8 p.	

93062024	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40268601. Busan 77- Metabolism Study in Rats: Laboratory ID: HLA
6176-115. Prepared by Hazleton Laboratories America, Inc. 17 p.	

93062025	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40139201. Busan 77- Dermal Absorption: Laboratory ID: HLA 6176-117.
Prepared by Hazleton Laboratories America, Inc. 11 p.

Dietary Exposure Assessment

FDA, 2003, A Guidance For Industry: Preparations of food Contact
Notifications and Food Additive Petitions for Food Contact Substances,
Chemistry Recommendations. Final Guidance, April 2003.   HYPERLINK
"http://www.cfsan.fda.gov"  http://www.cfsan.fda.gov 

FDA, 2003.  Sanitizing  Solutions: Chemistry Guidance for Food Additive
Petitions, January 2003.   HYPERLINK "Http://www.cfsan.fda.gov" 
Http://www.cfsan.fda.gov 

Environmental Fate Science Chapter 

157906	Cargile, N. (1986) Soil Column Leaching of [Carbon-14]- WSCP:
Final Report: Project No. 84E-303L. Unpublished study prepared by
Biospherics Inc. 13 p.

157907	Cargile, N. (1986) Leaching Characteristics of Aged [Carbon-14]-
WSCP:Final Report: Project No. 84E-303AL. Unpublished study prepared by
Biospherics Inc. 9 p.

159308	Barrows, B. (1985) Bioconcentration of [Carbon 14]-radiolabelled
WSCP in the Channel Catfish, Ictalurus punctatus, in a Static Test
System: Biospherics Project No. 84E-301. Unpublished study prepared by
Biospherics Inc. 18 p.

159309	Martinson, J. (1985) Solution Hydrolysis of WSCP: Final Report:
Biospherics Project No. 83-E-605H. Unpublished study prepared by
Biospherics Inc. 58 p.

159310	Martinson, J. (1985) Photodegradation of WSCP in Water: Final
Report: Project No. 83-E-605P. Unpublished study prepared by Biospherics
Inc. 28 p.

159311	Biospherics, Inc. (1986) Summary of [Carbon 14]-WSCP Soil Column
Leaching Study Conditions: Project No. 84E-303L. Un-published study. 6
p.

159312	Cargile, N. (1986) Leaching Characteristics of Aged [Carbon 14]-
WSCP: Draft Final Report: Project No. 84E-303AL. Un-published study
prepared by Biospherics Inc. 8 p.

40165201 	Obrist, J. (1987) Anaerobic Aquatic Metabolism of Busan 77:
Final Report: Laboratory Project Identification: HLA 6015-250.
Unpublished study prepared by Hazleton Laboratories America, Inc. 50 p.

40165202	Das, Y. (1987) Aerobic Soil Metabolism of WSCP: Biospheric No.
84E-301A. Unpublished study prepared by Biospheric Inc. 50 p.

40334101	Obrist, J. (1987) Aerobic Aquatic Metabolism of Busan 77:
Laboratory Project ID: HLA 6015-251: Final Report. Unpublished study
prepared by Hazleton Laboratories America, Inc. 69 p.

41407401	 Smith, A. (1990) Determination of Aqueous Hydrolysis Rate
Constant and Half-life of Busan 77: Final Report: Lab Project Number:
995-1089-6116-715: Lab Report Number 90-2-3216. Unpublished study
prepared by Springborn Laboratories, Inc. 32 p.

41420901	Smith, A. (1990) Determination of Aqueous Photolysis Rate
Constant and Half-life of Busan 77: Lab Project Number:
995-1089-6117-720; 90-3-3251. Unpublished study prepared by Springborn
Laboratories, Inc. 37 p.

46276202	Watson, C.; Eickhoff, J. (2004) Bubond 60 Tolerance Exemption
Petition: Data Evaluation Records (DERs) for Ecotoxicology,
Environmental Fate and Plant Protection Studies Submitted in Support of
Busan 77 and WSCP. Project Number: BUBOND/2004/3. Unpublished study
prepared by Toxcel LLC. 253 p.

93062026  	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41407401. Busan 77- Determination of Aqueous Hydrolysis Rate Constant
and Half-Life: Laboratory ID: 90-2-3216. Prepared by Springborn
Laboratories, Inc. 11 p.

93062027	Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
41420901. Busan 77- Determination of Aqueous Photolysis Rate Constant
and Half-Life: Laboratory ID: 90-3-3251. Prepared by Springborn
Laboratories, Inc. 17 p.

93062028	 Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40165201. Busan 77- Anaerobic Aquatic Metabolism: Laboratory ID: HLA
6015-250. Prepared by Hazleton Laboratories America, Inc. 10 p.

93062029	 Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
40334101. Busan 77- Aerobic Aquatic Metabolism: Laboratory ID: HLA
6015-251. Prepared by Hazleton Laboratories America, Inc. 10 p.

93062030	 Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID
00157906 and Related MRIDs 00157907. Busan 77 - Soil Leaching:
Laboratory ID. 84E-303-L. Prepared by Biospherics, Inc. 13 p.

Occupational and Residential Exposure Assessment of Octhilinone :

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U.S. Environmental Protection Agency (US EPA).  1996.  Office of
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EPA/600/R-96/148, July.   Data Collection Period October 1992 -
September 1994.  

U.S. Environmental Protection Agency (US EPA).  1997a. Standard
Operating Procedures (SOPs) for Residential Exposure Assessments.  EPA
Office of Pesticide Programs Human Health Effects Division (HED). 
December 18, 1997.

U.S. Environmental Protection Agency (US EPA).  1997b. Exposure Factors
Handbook. Volume I-II.  Office of Research and Development.  Washington,
D.C.  EPA/600/P-95/002Fa.

U.S. Environmental Protection Agency (US EPA).  1999.  Evaluation of
Chemical Manufacturers Association Antimicrobial Exposure Assessment
Study.  Memorandum from Siroos Mostaghimi, Ph.D., USEPA, to Julie
Fairfax.

U.S. Environmental Protection Agency (US EPA).  2007. Exposure and Fate
Assessment Screening Tool (E-FAST) Version 2.0. Demonstration Manual.
Office of Pollution Prevention and Toxics Exposure Assessment Branch.
March 2007.

Versar. 2003.  User's Manual Swimmer Exposure Assessment Model
(SWIMODEL) Version 3.0. Prepared for US EPA Antimicrobials Division.
November 2003. 

Product Chemistry Science Chapter of Octhilinone 

418984-01 	Summers, W. (1991) Product Chemistry for WSCP: Lab Project
Number: 105.01. Unpublished study prepared by Buckman Labs, Int. 31 p.

418984-03 	Bowles, D. (1991) Product Chemistry for WSCP: Lab Project
Number: 20/90-BUC.8: NA 90 9218/1. Unpublished study prepared by Twin
City Testing Corp. and Natec...GmbH. 88 p.

423724-01	Bowles, D. (1991) Product Chemistry for WSCP: Lab Project
Number: NA 909218/1. Unpublished study prepared by Twin City Testing
Corp. and NATEC Institut fur Naturwissenschaftlich-technische Dienste
GmbH. 88 p.

42615901 	Whetzel, J. (1992) Determination of Storage Stability and
Corrosion Characteristics of WSCP: A Supplement: Lab Project Number:
71/91-BUC.2. Unpublished study prepared by Twin City Testing Corp. 29 p.

46832601  	Wo, C. (2006) Physical and Chemical Characteristics: Color,
Physical State, Odor, Oxidation/Reduction, Flammability, pH, Viscosity,
and Density/Relative Density. Project Number: 19425, P801. Unpublished
study prepared by Product Safety Laboratories. 17 p.		

46915602  	Wo, C. (2006) Physical and Chemical Characteristis (830
Series, Group B): Algae Clean Out W. Unpublished study prepared by
Product Safety Laboratories. 6 p.

47120304 	Tillman, A. (2007) Waiver Request for Certain Data
Requirements for WSCP MUP. Project Number: KT/200704. Unpublished study
prepared by Kerley Trading, Inc. 7 p.

Ecological Hazard and Environmental Risk Assessment

00107207	Knott, W.B. 1970.  Busan 77 (WSCP) - Evaluation of Acute LC50
for Rainbow Trout.  Study performed by Woodward Research Corporation for
Buckman Laboratories, Inc., Memphis, TN.

00159307	Beaver, J.B.  1985.  Busan 77 - A Dietary LC50 Study with the
Bobwhite.  Project No. 210-104. Study performed by Wildlife
International, Ltd. for Buckman Laboratories, Inc., Memphis, TN.

052201020	WARF Institute, Inc.  1971.  Report on Acute Oral LD50 in
Bobwhite Quail.  Prepared for Buckman Laboratories, Inc., Memphis, TN.

40139202	Surprenant, D.C. 1987a.  Acute Toxicity of Busan 77 to
Sheepshead Minnow (Cyprinodon varigatus).  Report No. BW-87-2-2294. 
Study performed by Springborn Bionomics, Inc. for Buckman Laboratories,
Inc., Memphis, TN.

40139203	Surprenant, D.C. 1987b.  Acute Toxicity of Busan 77 to Mysid
Shrimp (Mysidopsis bahia).  Report No. BW-87-3-2346.  Study performed by
Springborn Bionomics, Inc. for Buckman Laboratories, Inc., Memphis, TN.

40334201	Surprenant, D.C. 1987c.  Acute Toxicity of Busan 77 to
Embryos-Larvae of the Quahog Clam (Mercenaria mercenaria).  Report No.
BW-87-8-2459.  Study performed by Springborn Bionomics, Inc. for Buckman
Laboratories, Inc., Memphis, TN.

41352001	LeLievre, M.K. et al. 1990c.  (Busan 77) - Acute Toxicity to
Rainbow Trout (Oncorhynchus mykiss) Under Static Conditions.  Report No.
89-12-3182.  Study performed by Springborn Laboratories, Inc. for
Buckman Laboratories, Inc., Memphis, TN.

41352002	LeLievre, M.K. et al. 1990a. (Busan 77) - Acute Toxicity to
Bluegill (Lepomis macrochirus) Under Static Conditions.  Report No.
89-12-3176.  Study performed by Springborn Laboratories, Inc. for
Buckman Laboratories, Inc., Memphis, TN.

41352003	LeLievre, M.K. et al.  1990b.  (Busan 77) - Acute Toxicity to
Daphnids (Daphnia magna) Under Static Conditions.  Report No.
89-11-3181.  Study performed by Springborn Laboratories, Inc. for
Buckman Laboratories, Inc., Memphis, TN.

41411501	Bodden, R.M.  1974.  Busan 77 - Acute Avian Dietary Toxicity
Study in Mallard Ducks.  Report No. 4043621.  Study performed by the
WARF Institute, Inc. for Buckman Laboratories, Inc., Memphis, TN.

41654801	Campbell, S. et al.  1990.  Busan 77: An Acute Oral Toxicity
Study with the Mallard. Project No. 210-114A.  Study performed by
Wildlife International, Ltd. for Buckman Laboratories, Inc., Memphis,
TN.

42013301	Hoberg, J.R.  1991a.  Busan 77 - Toxicity to the Duckweed Lemna
gibba G3.  Report No. 91-5-3749.  Study performed by Springborn
Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN. 

42013302	Hoberg, J.R.  1991b.  Busan 77 - Toxicity to the Marine Diatom
Skeletonema costatum. Report No. 91-9-3864.  Study performed by
Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis,
TN.

42013303	Hoberg, J.R. 1991c.  Busan 77 - Toxicity to the Freshwater
Diatom Navicula pelliculosa.  Report No. 91-4-3728.  Study performed by
Springborn Laboratories, Inc. for Buckman Laboratories, Inc., Memphis,
TN.

42013304	Hoberg, J.R. et al.  1991d.  Busan 77 - Toxicity to the
Freshwater Bluegreen Algae Anabaena flos-aquae.  Report No. 91-4-3726. 
Study performed by Springborn Laboratories, Inc. for Buckman
Laboratories, Inc., Memphis, TN.

42013305	Hoberg, J.R. 1991e.  Busan 77 - Toxicity to the Freshwater
Green Algae Selenastrum capricornutum.  Report No. 91-4-3732.  Study
performed by Springborn Laboratories, Inc. for Buckman Laboratories,
Inc., Memphis, TN.

42038101	Hoberg, J.R.  1991f.  Busan 77 - Determination of Effects on
Seed Germination, Seedling Emergence, and Vegetative Vigor of Ten Plant
Species.  Report No. 91-3-3695.  Study performed by Springborn
Laboratories, Inc. for Buckman Laboratories, Inc., Memphis, TN.

42479601	Putt, A.E. et al. 1992.  Busan 77 – Chronic Toxicity to
Daphnids (Daphnia magna) Under Static Renewal Conditions.  Report No.
92-7-4343.  Study performed by Springborn Laboratories, Inc. for Buckman
Laboratories, Inc., Memphis, TN.



Appendix A: Residential and Occupational Uses and Rates 





A-1. Representative Uses Associated with Residential Exposure 

Representative Use	

Exposure Scenario	

Application Method	

Reg. #	

Application Rate

Swimming Pool 	ST handler: dermal (irritation) and inhalation (aerosol) 
Open pour

(solid)1

Open pour (liquid)	3432-28

57787-11

	0.0012 fl oz ai/gal

(30 oz/5,000 gal x 20%ai)

0.0012 oz ai/gal

(117 fl oz/10,000 gal x 10%ai)

(product density = 8.5lb/gal)

	ST and IT post-app: incidental oral and dermal2	NA	57787-11

	9.3 mg ai/L

(117 fl oz/10,000 gal x 10%ai x gal/128oz x 8.5 lb/gal x 4.54E5 mg/lb x
0.264 gal/L)

Spa/whirlpool/hot tub/ornamental ponds	ST handler: dermal (irritation)
and inhalation (aerosol)	Open pour (liquid)	1448-346

	0.0012 fl oz ai/gal

(3 fl oz/1000 gal x 40%ai)

(product density =9.12lb/gal)

Aquarium	ST handler: dermal (irritation) and inhalation (aerosol)	Open
pour (liquid)	14802-8

	0.00023 fl oz ai/gal

(5ml/40 gal x 5.4%ai x fl oz/29.57ml)

(product density = 8.4lb/gal)

Waterbed mattress water	ST handler: dermal (irritation) and inhalation
(aerosol)	Open pour (liquid)	42373-6

	0.0044 fl oz ai/gal

(8 fl oz/180 gal x 10%ai)

(product density = 8.5lb/gal)

1 Note: since the application rates are the same, the dermal irritation
exposure from the open solid pour scenario was represented by the open
pour liquid scenario.  Furthermore, the open liquid pour scenario is
considered worst-case as compared to the solid pour for dermal
irritation due to physical nature of the product and its potential to
contact skin during the application.

2 Note: post-application exposure to swimming pool residues is
representative for post-application exposure to spa/whirlpool residues
since the application rates are the same for both uses

Table A-2.  Representative Exposure Scenarios Associated with
Occupational Exposures to Busan 77

Representative Use	Method of Application	Exposure Scenario	Registration
#	Application Rate

Residential Premises

Swimming Pools	Liquid pour 

Solid pour	Handler: ST and IT inhalation	3432-28

57787-11

	0.0012 fl oz ai/gal

(30 oz/5,000 gal x 20%ai)

0.0012 oz ai/gal

(117 fl oz/10,000 gal x 10%ai)

Product density = 8.5lb/gal

Material Preservatives

Metalworking fluid	Liquid pour 

Liquid pump

Use of treated metalworking fluid	Handler (worker pouring preservative
into fluid being treated): ST and IT inhalation

Machinist:  ST dermal and 

ST and IT inhalation	1448-42

	0.006% to 0.06% ai

(or 60 to 600 ppm ai)

(0.01 to 0.1% product based on total weight of fluid x 60% ai)

Product density = 9.6 lb/gal

Industrial Processes and Water Systems

Pulp/paper and textile water systems	Liquid pump	Handler: ST and IT
inhalation	1448-42	0.0007 fl oz ai/gal

(11 fl oz/10,000 gal x 60% ai)

Product density = 9.6 lb/gal

Cooling tower waters (recirculating)	Liquid pour 

Liquid pump	Handler: ST and IT inhalation

	1448-398

	Initial dose: 

0.0042 fl oz ai/gal

(69.6 fl oz/1,000 gal x 6%ai)

Maintenance dose:

0.0021 fl oz ai/gal

(34.8 fl oz/1,000 gal x 6%ai)

Product density = 8.7 lb/gal

Cooling tower waters 

(once-through)	Liquid pour 

Liquid pump	Handler: ST and IT inhalation

	55137-1

	0.0012% ai

(60 ppm x 20%ai)

Product density = 8.69 lb/gal

Air washer water systems

	Liquid pour 

Liquid pump	Handler: ST and IT inhalation

	402-123

	0.0042 fl oz ai/gal

(83.25 fl oz/1,000 gal x5%ai)

Product density = 8.4 lb/gal

Fire protection systems

	Liquid pour 

Liquid pump	Handler: ST and IT inhalation	1448-398

	0.0056 fl oz ai/gal

(92.8 fl oz/1,000 gal x 6%ai)

Product density = 8.7 lb/gal

Petroleum secondary recovery systems	Liquid pour 

Liquid pump	Handler: ST and IT inhalation	1448-398

	0.0056 fl oz ai/gal

(92.8 fl oz/1,000 gal x 6%ai)

Product density = 8.7 lb/gal

Note: inhalation exposure refers to exposure to the aerosols not the
vapor

Appendix B:  Subchronic, Chronic and Other Toxicity Profiles 



Table B-1: Subchronic, Chronic, and other Toxicity Profiles for Busan 77

Guideline Number/

Study Type

Test Substance (% a.i.)	MRID Number (Year) /Citation/

Classification/ Doses	Results

870.3050

28-day oral (mice)

Purity:  not reported	MRID 40362601

Kehoe, D.F. (1987). Four-Week Toxicity Study with Busan 77 in Mice.
Buckman Labs, Inc., Memphis, TN. Study #: 6176-108

Not reviewed

Busan 77 administered orally in the diet at 0, 2500, 5000, 10000, 20000
ppm for 28 days

5  rats/sex/dose

	

NOAEL = 10, 000 ppm

Body weights, food consumptions, and antemortem observations were
recorded at initiation and then weekly for at least 4 weeks. At the end
of the study, all surviving mice were bled for hematology and clinical
chemistry tests. The mice were then anesthetized, exsanguinated, and
necropsied. A female mouse that died on test was also necropsied and
representative tissues were collected. At the scheduled necropsies,
macroscopic observations were recorded, selected organs were weighed,
and representative tissues were collected as required by the protocol.
Specified tissues from mice given  0 or 20,000 ppm were examined
microscopically. Representative samples of gross lesions and rectums
were also examined microscopically from all groups.

No treatment-related antemortem observations were seen in animals fed
Busan 77; and no treatment-related changes occurred in body weight or
food consumption the cumulative body weight gains were significantly
lower during Week 1, 2 and 4 in males fed 20,000 ppm Busan 77. Although
females fed 20,000 ppm had a lower body weight when compared with the
control group, there were no statistically significant differences.

There were no treatment-related effects on the clinical pathology data,
organ weight data, or microscopic observations. The only microscopic
lesions that may have been treatment related were small foci of
neutrophils at the anorectal junction of mice given 20,000 ppm Busan 77.

870.3100

90-day oral (rat)

Purity:  not reported

	MRID 40025001/93662014

Tisdel, Merrill (1986). Thirteen Week Subchronic Toxicity Study With
Busan 77 in Rats. Buckman Labs, Inc. Memphis, TN. Study #: 6176-106.

Core-Minimum

Busan 77 administered orally in the diet at 0, 3000, 10,000, 30,000 and
40,000ppm (0, 300 1000, 3000, and 4000 mg/kg ) for 13 weeks

10  rats/sex/dose

	

NOAEL = 3,000 ppm(2000 mg/kg) 

LOAEL  = 10,000 ppm (752 mg/kg) 

Mineralization of renal tubules. At 30,000 ppm and 40,000 ppm (approx.
2554 and 3685 mg/kg/d, resp.) the following were observed: 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-supportive inflammation in the choroid plexus of
the brain; death.

The occurrence of increased kidney weight and mineralization at 10,000
ppm and above suggests a treatment—related response. Severity of
mineralization was not discussed. Chronic inflammation of the choroid
plexus was observed at the two highest dose levels only, suggesting a
treatment—related response in this parameter. The decrease in actual
numbers of animals affected at the highest dose level (40,000 ppm) is a
function of the mortality that was observed at that level (8 males, 2
females).

870.3250

90-day dermal (rabbit)

Purity:60%	MRID 40170601/93062015

Spindler, M. (1987).  13-Week Dermal Toxicity Study with Busan 77 in
Rabbits. Buckman Laboratories, Inc. Memphis, TN.

Study #: 6176-118

Acceptable

Guideline

Busan 77 applied dermally at 0, 10, 100, 1000 mg/kg for 13 weeks

10 rabbits/sex/dose

	

Systemic Toxicity

NOAEL > 1000 mg/kg/day (HDT)

Dermal Toxicity

NOAEL = 10 mg/kg/day

LOAEL = 100 mg/kg/day, Based on treatment related dermatological changes
consistent with chronic irritation/inflammation. 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. 

Following the dermal application of Busan 77 to male and female rabbits
at dose levels of 0, 10, 100 and 1,000 mg/kg/day, 6 hours/day, 5
days/week for 13 weeks, there were no treatment-related changes in the
body weights, food consumption, hematology, clinical chemistry, organ
weights and organ—to-body weight ratios and gross and/or
histopathological changes of internal organs of males and females.
However, there was 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. The doses tested did not establish the MTD, however, the
highest dose tested reached Limit Dose.

870.3700a

Developmental Toxicity – oral gavage (rat)

Purity:  61.2%                                                          
                                                                        
                                                                

	MRID 41423001/93062018

Nemec, Marc D. (1987). A Teratology Study in Rats with Busan 77. Buckman
Laboratories, Inc. Study #: WIL-94020.

Core-Minimum

Guideline

Busan 77 administered orally at 0, 70, 350 500 mg/kg/day on GD 6-15

25 rats/dose group

	

Maternal Toxicity

NOAEL = 70 mg/kg/day 

LOAEL = 350 mg/kg/day, based on decreased food consumption and body
weight gain.  Mortality observed at 700 mg/kg/day

Developmental Toxicity

NOAEL = 500 mg/kg/day LOAEL > 500 mg/kg/day (HDT)

Busan 77 was toxic to rat dams, causing decreases in food consumption
and (non-statistically significant) decreases in body weight gains at
350 mg/kg/d and 500 mg/kg/d, and death and morbidity at 700 mg/kg/d. The
dose response curve appears to be inordinately steep, since 1) none of
the toxicity (convulsions, lethargy and pathological changes in lung,
brain, stomach and intestines) observed at 700 mg/kg/d was observed at
500 mg/kg/d, which is only of a log dose lower; and 2) the profile of
other adverse effects such as decrease food consumption (Table 2)
suggests a more gradual slope. However, absence of effects at lower dose
levels cannot be adequately verified from the data submitted with this
study (see Deficiencies Section above). It is also remarkable that liver
and/or kidney effects were not reported as being observed, even at
levels that killed 25% of the dams.

Busan 77 appears to cause a dose-related increase in embryonal death, as
manifested by a statistically significant increase in early resorptions,
at 500 mg/kg/d.

870.3700b

Developmental Toxicity – oral gavage (rabbit)

Purity:  60.8%	MRID 41248001/93062019

Rodwell, Dean E. (1989). Teratology Study in Rabbits with Busan 77.
Buckman Laboratories, Inc. Study #: 3138.29

Core

Guideline

Busan 77 administered via gavage at 0, 15, 45 and 125 mg/kg on GD 6-18
inclusive

20 rabbits/dose group

	

Maternal Toxicity

NOAEL = 45 mg/kg/day 

LOAEL = 125 mg/kg/day, based upon increased incidence of abortions,
clinical signs including reduced defecation and emaciation,
significantly reduced feed consumption and body weight gain during
treatment.

Developmental Toxicity

NOAEL = 45 mg/kg/day 

LOAEL = 125 mg/kg/day

based upon increased incidence of 13th rudimentary ribs and unossified
sternebrae #5 and #6.

The data reporting was thorough and the summary means that were
validated were supported by the individual animal data, except for minor
discrepancy in reporting the mean body weight gain of 80 instead of 183
for the high dose dams during gestation Day 24 - 29 (Report summary
Table 4). The error had been factored in, in the calculation of body
weight gain of dams and will not alter the conclusions of the study.

It was reported that the doses were selected based upon a range finding
study, but no details were provided. While this information should have
been included in the report, the deficiency is not a factor since
results of current study indicate maternal toxicity at 125 mg/kg/day.

a. Maternal Toxicity: At 125 mg/kg/day, increased incidence of
abortions, clinical signs including reduced defecation and emaciation,
significantly reduced feed consumption and body weight gain occurred
during treatment.

b. Developmental Toxicity: At 125 mg/kg/day, the incidence of 13th
rudimentary ribs and unossified sternebrae #5 and #6 was increased
significantly (P 0.05). The litter incidences for 13th rudimentary rib
(93.3 vs. 89.5 of historical controls) and unossified sternebrae #5
and/or #6 (40.0 vs. 36.8 of historical controls) are slightly above the
corresponding historical controls values. Although, the incidence lacked
a trend or dose- relationship and occurred at a maternally toxic dose,
the increases are considered treatment-related. 

870.3800

Reproduction and fertility effects (rat)

Purity: not reported	MRID 40578201/93062020

MacKenzie, K.M. (1988). Two-Generation Reproduction Study with Busan 77
in Rats (One Litter per Generation).  Buckman Laboratories, Inc.,
Memphis, TN.  Study #: HLA 6176-104.

Core-Minimum

Guideline

Busan 77 administered in the diet at 0, 6000, 12000 and 18000 (0, 300,
600 and 900 mg/kg/day) for two generations

25 rats/sex/dose

	

Maternal Toxicity

NOAEL: not established

LOAEL: 300 mg/kg/day, based on decr. Body weight, inflammation of
choroid plexus, tubular mineralization of the kidney.

Reproductive Toxicity:

NOAEL = 600 mg/kg/day

LOAEL = 900 mg/kg/day, based on decreased live pups.

870.4100

Chronic Toxicity (dog)

Purity: not reported	MRID 41234501/93062016

Kehoe, Daniel F. (1989). One-Year Chronic Toxicity Study with Busan 77
in Dogs.  Buckman Laboratories, Inc. Memphis, TN. Study #: HLA 6176-111

Supplementary

Busan 77 administered  orally at 0, 10000, 20000 and 40000 ppm (0, 250,
500, 1000 mg/kg)for 52 weeks

4 dogs/sex/dose

	

NOAEL: 250 mg/kg/day (M); 500 mg/kg/day (F)

LOAEL = 500 mg/kg/day (M), based on testicular hypoplasia,
atrophy/degeneration, aspermia, dysplasia and cellular debris of
testicular origin in epididymis.

LOAEL = 1,000 mg/kg/day (F), based on G-I disturbances, weight loss and
nervous symptoms (bloody stools, emaciation and ataxia, respectively).

Administration of Busan 77 in the feed for up to 52 weeks had no affect
on mortality. However, an increased incidence of vomits and abnormal
stools (soft and bloody) was observed with increasing dose. In the KTD
group, all males and females exhibited bloody stools at 12 (1) and 26
(2) weeks, respectively. Probably this is related to treatment. At
necropsy, thickened wall of duodenum (3 males and 2 females), jejunum (2
males) and ileum (1 male) were observed in the 40,000 ppm group.
Microscopic examination of these tissues did not reveal any changes
associated with the treatment and is probably of no toxicological
significance. In addition, microscopic examination of rectum or colon of
all HDT males revealed changes associated with chronic inflammatory
processes and was probably treatment related. Body weight gain of males
and females in the 40,000 ppm group decreased significantly when
compared to controls. Body weight gain of males and females was reduced
by 39 and 42%, respectively, at 12 weeks when compared to controls. In
the 20,000 ppm group, the mean body weight gain decreased
non-significantly in males and females 17 and 6%, respectively, at 12
weeks when compared to controls; and decreased in males and females 30
and 14%, respectively, at termination (52 weeks) when compared to
controls and it may not be related to treatment. Food consumption was
significantly decreased in the males and females in the 40,000 ppm group
at several intervals. At week 13, food consumption of males and females
in the 40,000 ppm group decreased 46 and 53%, respectively, when
compared to controls.

At 26 weeks, males and females in the 40,000 ppm group had a significant
increase in Hct, MCV, MCH and platelets, and in females a significant
increase in Hb was observed. Also, a significant decrease in RBC was
seen in males and females at the 26 week time interval. The low RBC and
increased MCV may signal mild anemia; however, histopathology of bone
marrow smears and bone sections did not correspond to morphological
changes. These changes in the HTD group may be in part/whole related to
mild anemia, emaciation and dehydration. Significant increases in MCV in
the 10,000 and 20,000 groups in males/females are of questionable
biological significance because of the sporadic nature of occurrence.

Total protein, albumin and creatinine were significantly decreased in
males and females in the 40,000 ppm group at 26 weeks, probably due to
anemia and emaciation and may be treatment related. Also, a significant
decrease in K, glucose in males and P(inorganic), Na and Cl in females
were also observed at this interval. This is probably due to
dehydration, associated with vomition/diarrhea. Changes noticed in the
10,000 ppm group and in the 20,000 ppm group for K, and P(i) at 26
weeks, are of sporadic nature and have no toxicological significance.
The significant (slight) increase of SGPT in males at 26 weeks, in the
40,000 ppm group and of SCOT at 52 weeks, in the 10,000 and in the
20,000 ppm groups at 52 weeks, is probably of no toxicological
significance, since the histopathology revealed no treatment related
affects. At 52 weeks, males and females had significantly reduced
cholesterol in the 20,000 ppm group; the toxicological significance of
this is uncertain.

urine pH in males was significantly reduced in the 40,000 ppm group at
26 weeks and in the 10,000 and in the 20,000 ppm groups at 52 weeks.
Also, higher urinary blood pigment was noticed in the 40,000 ppm group.
The significance of low urine pH and higher urinary blood pigment on the
urinary tract is of questionable values, since there was no
corresponding histopathological changes.

Organ to body weight ratios for brain, liver and kidney increased
(significantly) 52, 19 and 47%, respectively for males in the 20,000 ppm
group at termination, when compared to controls. The actual weights of
the brain, liver, and kidney in males were 1, -18 and -13 %,
respectively, when compared to controls. Females exhibited significant
increases of 4 and 47 %, respectively, in the body weight ratio of
kidney and liver. The apparent increase in the organ to body weight
ratios, and actual decrease in the absolute organ weights without
corresponding histopathological changes, suggest that the changes seen
grossly may be due to in part/whole to body weight loss, especially
water loss from vomition and diarrhea. In addition, testes relative
organ weights were not affected, where as actual weights decreased 27,
20 and 58 % in the LTD, MTD, and NW, respectively, when compared to
controls. Reduced testicular weights corresponded to testicular
hypoplasia on histopathology, evidenced by atrophy/degeneration,
aspermia, dysplasia and presence of cellular debris of testicular origin
in the epididymis of all males in the 40,000 ppm group and 2 males in
the 20,000 ppm group.

870.4200

Carcinogenicity (mice)

Purity: 60.8%	MRID 41494301/93062017

Kehoe, Daniel F. (1989). One-Year Chronic Toxicity Study with Busan 77
in Dogs.  Buckman Laboratories, Inc. Memphis, TN. Study #: HLA 6176-111

Core-Minimum

Guideline

Busan 77 administered  orally at 0, 4000, 8000 and 16000 ppm (0, 600,
1200, and 2400 mg/kg)for 18 months

50 mice/sex/dose

	

NOAEL= not established

LOAEL <600 mg/kg/day, based on enlarged kidney pelvis, diffuse rough
kidney I females; dose-related increase in proteinaceous casts in males,
and pelvic and tubular dilation in males and females.

It could not be definitively determined whether increase incidence of
rough hair coat, bloody crusts and red ears in males and convulsions in
females had a LEL of 4,000 or 16,000 ppm.

At the 8000 and above, all of the above findings and including
convulsions (M & F), urine scams (M & F), rough hair coat (F), bloody
crusts (F) swollen abdomen (M & F), swollen anus (M), red tails (H & F),
red ears (F), reduced body weight gains (H & F), diffuse rough kidneys
(H & F), large kidney pelvis (H & F), relative kidney weights (high dose
males, and mid and high dose females), proteinaceous casts (F), cortical
fibrosis/scarring (F) and cysts (F), were observed.

870.4300

Combined chronic toxicity/carcinogenicity (rat)

Purity: 60%	MRID 41809101/41561301

Kehoe, Daniel F. (1991). Combined Chronic Toxicity Study and
Carcinogenicity Study with Busan 77.  Buckman Laboratories, Inc.
Memphis, TN. Study #: HLA 6176-107.

Core-Minimum

Guideline

Busan 77 administered orally at 0, 2000, 6000 and 18,000 ppm (0, 100,
300 and 900 mg/kg./day)

50 rats/sex/dose

	

Chronic:

NOAEL = 100 mg/kg/day

LOAEL = 300 mg/kg/day, based on reduced body weight gain (F), reduced
albumin (M), reduced total protein (M), reduced Pi (M&F), increased
urine pH(F) and a dose related-related increase. In blood crusts.

Carcinogenicity:

I females, possible increased incidence of thyroid C-cell adenoma at 300
and 900 mg/kg/day, and positive trend for this tumor in both sexes.

RfD comm.. considered the data in this study; classified Busan Group D.

Mutagenicity

870.5100

Reverse mutation assay – salmonella typh.

Purity: not reported	MRID 41573701

Lawler, T.L. and  DaCosta, K. (1990). Mutagenicity Test on Busan 77 in
the Salmonella/Mammalian-Microsome Reverse Mutation Assay with
Confirmatory Assay. Buckman Laboratories, Inc. Study #: 12144-0-401R.

Acceptable

Guideline

Busan 77 doses of 66.7, 100, 333, 667, 1000 and  3330µg/plate

Strains: salmonella (TA1535, TA1537, TA1538, TA98 and TA100

	

Negative

In the initial mutagenic assay (Table 3), using strains TA1535, TA1537,
TA1538, TA100 and TA98 in the presence and absence of S9 activating
system, at doses of 66.7, 100, 333, 667, 1,000 and 3,330 mg/plate, did
not increase in the number of histidine revertants were observed, either
in the presence or absence of S9 system. The experiment was repeated and
all data were acceptable except for strain TA9B for which the means were
outside the acceptable range both in the presence and absence of S9. The
TA98 strain was retested both in the presence/absence of activation
system and the results were acceptable (Table 4). Revertants frequencies
for all doses of Busan 77 in all strains approximated or were less than
those observed in the concurrent negative controls (Tables 1 and 2). All
positive controls produced positive responses expected of the chemicals.

Based on the results of the Salmonella Reverse Mutation Assay the test
article Busan 77 did not cause a positive increase in the number of
histidine revertants per plate.

870.5275

Sex-linked recessive lethal test

Purity: 100%	MRID 00151205

McCarroll, N. (1985). Drosophila Sex-linked Recessive Lethal Assay [with
WSCP (Busan 77)]: Hazelton Laboratories, Inc. Project #: 197-183.
Unpublished

Acceptable 

Busan 77 administered at 0.08, 0.3 and 0.8 mg/ml

Test strain: Flies	

Negative

A dose-related increase in sterility was observed in the mated P1 males
to increasing concentration of the test material when compared to the
solvent control. 

870.5300

In vivo micronucleus assay (mice)

Purity: 100%

	MRID 00151206/93062021

Drake, K. (1990) Buckman Labs Inc Phase 3 Summary of MRID 00151206.
Busan 77- in Vivo Mouse Micronucleus Assay: Laboratory ID 197-182.
Prepared by Hazleton Biotechnologies Corporation. 8 p.

Acceptable

Guideline

Busan 77 administered via gavage at 0.08, 0.3 and 0.8 mg/ml

15 mice/sex/dose

	

Negative

The test compound WSCP (Busan 77) is considered non-mutagenic in mice
under the condition of this assay.

The test compound WSCP (Busan 77) did not induce a significant increase
of the PCE containing micronuclei in the treated mice when compared to
that of the vehicle control value.

The positive control compound cyclophosphamide induced a significant
increase of the PCE containing micronuclei, which indicated the
sensitivity of the assay system

(p < 0.0001).

870.5550

Unscheduled DNA synthesis in mammalian cells in culture (rat)

Purity: not reported

	MRID 40978701/93062022

Cifone, M. (1989) Mutagenicity Test on Busan 77 in the in vivo/in vitro
Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: Project ID: HLA
Study No. 10280-0-494. Unpublished study pre- pared by Hazleton
Laboratories America, Inc. 26 p.

Acceptable

Guideline

Busan 77 administered at 188, 375, 750 and 1500 mg/kg 

3 rats/group 

	

Negative

Hepatocyte viability/attachment efficiency ranged from 85.4 to
95.2%/66.2 to 81.5%. Busan at a concentration of 188, 375, 750 and 1,500
mg/kg resulted in hepatocyte viability (attached cells) of  93.9, 93.2,
94.9 and 93.3%, respectively; i.e., no toxicity (see Appendix 2).  None
of the treatments with Busan resulted in a significant increase in
nuclear labeling, when compared to the controls and did not meet the
minimum criteria for UDS assay for mean net nuclear grain count
exceeding 6, or at least 10% of the nuclei containing 6 or more grains,
or at least 2% of the nuclei containing 20 or more grains, to conclude a
positive response (see Appendix 1). Furthermore, there was no
dose-related trend observed. Positive control treated cultures exhibited
greatly exceeded all three criteria used to indicate UDS. 

870.7485

Metabolism and pharmacokinetics (rat)

Purity: 60%	MRID 40268601/93062024

Puhl, R. (1987) Metabolism Study with Busan 77 (WSCP) in Rats: Final
Report: Laboratory Project ID: HLA 6176-115. Unpublished study prepared
by Hazleton Laboratories America, Inc. 98 p.

Acceptable

14C-labeled Busan 77 administered oral and i.v. single of 10 mg/kg;
single oral dose of 1000 mg/kg; repeated oral dose of 10 mg/kg

5 rats/sex/dose

	

Intravenous excretion at 10 mg/kg; urine, 38-44% feces, 11-14%.  Tissue
contained 43-55% of the dose.  Single and repeated oral dose excretion:
urine, 3% of dose, feces 85-105% of dose.  Tissue levels low in these
groups (0.14% highest levels in any tissue)

Oral 1000 mg/kg dose: urine, 14-17%; feces 68-71% of dose.

Expired CO2 was not detected. In the intravenous dose group, the major
routes of excretion of radioactivity were via urine and feces. Over a
7-day period, approximately 52-55% of the test material administered was
excreted in the urine (38-44%) and feces (11-14%); 43-55% was, found in
the tissues. In a single repeated oral dosed groups 88-106% of the test
compound administered was excreted in the urine (3%) and feces
(85-105%); kidneys, liver, and spleen had a highest residue level. In
these

groups, tissue residue levels were low in all tissues, except kidneys.
Not more than 0.14% of the administered dose was recovered in tissues.
Potential for bioaccumulation at the single or repeated oral is minimal.
At the highest oral dose, 85% of the administered dose was recovered in
urine (14-17%) and feces (68-71%).  The information provided by the
sponsor explains that almost the entire administered dose was excreted
in the feces unchanged and remaining 40% of the composition of the
technical or radiolabeled material was water.

870.7600

Dermal penetration (rat)

Purity: 60%	MRID 40139201/93062025

Bosch, A. (1987) Dermal Absorption of [Carbon 14]-Busan 77 (WSCP) in
Male Rats: HLA Study No. 6176-117: Final Report. Unpublished study
prepared by Hazleton Laboratories America, Inc. 52 p.

Acceptable

Guideline

single dermal administration to male rats at 2, 20, or 200 mg/rat (0.16,
1.59, or 15.97 mg/cm2, respectively)

24 rats/group	

The total amount of Busan 77 absorbed (expressed as percent of 14C-dose)
from rats at various times following dermal administration of 14C-Busan
77 at 2, 20 or 200 mg/animal is negligible (less than 0.2% of the dose).
Also, no radioactivity was found in carcass and blood of all treated
animals indicating no dermal absorption of Busan 77.

Only less than 0.2% of the Busan  77was absorbed. Mean % recovery of
radioactive dose ranged from 74.5 - 92.7%. Majority of the dose was
recovered in the skin rinse (65.5% - 88.6%) and at the skin site (0.4% -
13.7%). 

  “Environmental Exposure Assessment for Releases of Bromonitrostyrene
from Once-through Cooling Water Systems,” memorandum to David Bays,
EPA OPP/AD, from Joshua Cleland and Keith Drewes, ICF International,
April 26, 2007.   Also, see “Environmental Exposure Assessment for
Releases of Busan 77 From Once-through Cooling Water Systems,”
memorandum to Norm Cook, EPA OPP/AD, from Siroos Mostaghimi, EPA OPP/AD,
July 27, 2007.

 The E-FAST2 model is available from EPA at   HYPERLINK
"http://www.epa.gov/opptintr/exposure/pubs/efastdl.htm" 
http://www.epa.gov/opptintr/exposure/pubs/efastdl.htm  and documentation
is available at   HYPERLINK
"http://www.epa.gov/opptintr/exposure/pubs/efast2man.pdf" 
http://www.epa.gov/opptintr/exposure/pubs/efast2man.pdf .

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