Reregistration Eligibility
Decision (RED) for PHMB
September 30, 2004
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United States Prevention, Pesticides EPA739-R-05-003
Environmental Protection and Toxic Substances September 2005
Agency (751OC)
Reregistration Eligibility Decision
for PHMB
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the Environmental Protection Agency (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments
received related to the preliminary risk assessments for the antimicrobial
poly(hexamethylenebiguanide) hydrochloride (PHMB). The Reregistration Eligibility Decision
(RED) was approved in the form of a decision memorandum which summarized the regulatory
decision for PHMB on September 30, 2004. Public comments and additional data received were
considered in this decision.
Based on its review, EPA is now publishing its Reregistration Eligibility Decision (RED)
and risk management decision for PHMB and its associated human health and environmental
risks. A Notice of Availability will be published in the Federal Register announcing the
publication of the RED.
The RED and supporting risk assessments for PHMB are available to the public in EPA's
Pesticide Docket OPP-2004-0305 at: http://www.epa.gov/edockets.
The PHMB RED was developed through EPA's public participation process, published in
the Federal Register on September 10, 2004, which provides opportunities for public
involvement in the Agency's pesticide tolerance reassessment and reregistration programs.
Developed in partnership with USDA and with input from EPA's advisory committees and
others, the public participation process encourages robust public involvement starting early and
continuing throughout the pesticide risk assessment and risk mitigation decision making process.
The public participation process encompasses full, modified, and streamlined versions that
enable the Agency to tailor the level of review to the level of refinement of the risk assessments,
as well as to the amount of use, risk, public concern, and complexity associated with each
pesticide. Using the public participation process, EPA is attaining its strong commitment to both
involve the public and meet statutory deadlines.
Please note that the PHMB risk assessment and the attached RED document concern only
this particular pesticide. This RED presents the Agency's conclusions on the dietary, drinking
water, occupational and ecological risks posed by exposure to PHMB alone. This document also
contains both generic and product-specific data that the Agency intends to require in Data Call-
ins (DCIs). Note that DCIs, with all pertinent instructions, will be sent to registrants at a later
date. Additionally, for product-specific DCIs, the first set of required responses will be due 90
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days from the receipt of the DCI letter. The second set of required responses will be due eight
months from the receipt of the DCI letter.
As part of the RED, the Agency has determined that PHMB will be eligible for
reregistration provided that all the conditions identified in this document are satisfied, including
implementation of the risk mitigation measure outlined in Section IV of the document. Sections
IV and V of this RED document describe the labeling amendments for end-use products and data
requirements necessary to implement this mitigation measure. Instructions for registrants on
submitting the revised labeling can be found in the set of instructions for product-specific data
that accompanies this document.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by PHMB. Where
the Agency has identified any unreasonable adverse effect to human health and the environment,
the Agency may at any time initiate appropriate regulatory action to address this concern. At
that time, any affected person(s) may challenge the Agency's action.
If you have questions on this document or the label changes relevant to this reregistration
decision, please contact the Chemical Review Manager, Jennifer Slotnick, at (703) 305-0601.
For questions about product reregistration and/or the Product DCI that accompanies this
document, please contact Adam Heyward at (703) 308-6422.
Sincerely,
Frank T. Sanders
Director, Antimicrobials Division
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REREGISTRATION ELIGIBILITY
DECISION
for
PHMB
ListC
CASE 3122
Approved By:
Frank T. Sanders
Director, Antimicrobials Division
September 29, 2005
Attachment
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Table of Contents
PHMB Reregistration Team i
Glossary of Terms and Abbreviations ii
Executive Summary iv
I. Introduction 1
II. Chemical Overview 3
A. Regulatory History 3
B. Chemical Identification 3
C. Use Profile 4
III. Summary of PHMB Risk Assessments 7
A. Human Health Risk Assessment 7
1. Toxicity of PHMB 7
2. FQPA Safety Factor 10
3. Population Adjusted Dose (PAD) 10
a. Acute PAD 10
b. Chronic PAD 11
4. Exposure Assumptions 11
5. Dietary Risk Assessment 11
a. Dietary Risk from Food 11
b. Dietary Risk from Drinking Water 12
6. Residential Risk Assessment 12
a. Residential Toxicity 12
b. Residential Handlers 13
i. Exposure Assessment 13
ii. Risk Assessment 14
b. Residential Post-Application 14
i. Exposure Assessment 14
ii. Risk Assessment 15
7. Aggregate Risk 16
a. Short- and Intermediate-Term Aggregate Risk 16
b. Chronic Aggregate Risk 18
8. Occupational Risk 18
a. Occupational Toxicity 19
b. Occupational Handler Exposure 19
c. Occupational Handler Risk Summary 20
9. Human Incident Data 20
B. Environmental Risk Assessment 21
1. Environmental Fate and Transport 21
2. Ecological Risk 21
a. Toxicity (Hazard) Assessment 22
b. Exposure and Risk 22
c. Risk to Listed Species 23
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IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 24
A. Determination of Reregistration Eligibility 24
B. Public Comments and Responses 24
C. Regulatory Position 26
1. Food Quality Protection Act Findings 26
a. "Risk Cup" Determination 26
b. Determination of Safety to U.S. Population 26
c. Determination of Safety to Infants and Children 27
d. Endocrine Disrupter Effects 27
e. Cumulative Risks 28
2. Tolerance Summary 28
D. Regulatory Rationale 28
1. Human Health Risk Management 28
a. Dietary (Food) Risk Mitigation 28
b. Drinking Water Risk Mitigation 28
c. Residential Risk Mitigation 29
i. Handler Risk Mitigation 29
ii. Post-Application Risk Mitigation 29
d. Occupational Risk Mitigation 29
i. Handler Risk Mitigation 29
ii. Post-Application Risk Mitigation 29
2. Environmental Risk Management 29
3. Other Labeling Requirements 29
4. Listed Species Considerations 29
a. The Endangered Species Act 29
b. General Risk Mitigation 30
V. What Registrants Need to Do 31
A. Manufacturing-Use Products 33
1. Additional Generic Data Requirements 33
2. Labeling for Technical and Manufacturing-Use Products 34
B. End-Use Products 34
1. Additional Product-Specific Data Requirements 34
2. Labeling for End-Use Products 34
a. Label Changes Summary Table 35
VI. Appendices 39
A. Table of Use Patterns for PHMB 40
B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision 59
C. Technical Support Documents 65
D. Bibliography Citations 67
E. Generic Data Call-In 74
F. Product Specific Data Call-In 75
G. Batching of End-Use Products 76
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H. List of All Registrants Sent the Data Call-In 80
I. List of Available Forms 81
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PHMB Reregistration Team
Health Effects Risk Assessment
Jonathan Chen
Timothy Leighton
Tim McMahon
Najm Shamim
Cassi Walls
Ecological Risk Assessment
Kathryn Montague
Environmental Fate Risk Assessment
Najm Shamim
Registration Support
Adam Heyward
Lisa McKelvin
Risk Management
Jennifer Slotnick
Ben Chambliss
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
APHIS Animal and Plant Health Inspection Service
ARTF Agricultural Re-entry Task Force
BCF Bioconcentration Factor
CDC Centers for Disease Control
CDPR California Department of Pesticide Regulation
CFR Code of Federal Regulations
ChEI Cholinesterase Inhibition
CMBS Carbamate Market Basket Survey
cPAD Chronic Population Adjusted Dose
CSFII USDA Continuing Surveys for Food Intake by Individuals
CWS Community Water System
DCI Data Call-In
DEEM Dietary Exposure Evaluation Model
DL Double layer clothing {i.e., coveralls over SL}
DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EDSP Endocrine Disrupter Screening Program
ED STAC Endocrine Disrupter Screening and Testing Advisory Committee
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
EXAMS Tier II Surface Water Computer Model
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FOB Functional Observation Battery
FQPA Food Quality Protection Act
FR Federal Register
GL With gloves
GPS Global Positioning System
HIARC Hazard Identification Assessment Review Committee
IDFS Incident Data System
IGR Insect Growth Regulator
IPM Integrated Pest Management
RED Reregistration Eligibility Decision
LADD Lifetime Average Daily Dose
LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause
death in 50% of test animals, usually expressed as the weight of substance per weight or volume
of water, air or feed, e.g., mg/1, mg/kg or ppm.
LCO Lawn Care Operator
LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals
when administered by the route indicated (oral, dermal, inhalation), expressed as a weight of
substance per unit weight of animal, e.g., mg/kg.
LOAEC Lowest Observed Adverse Effect Concentration
LOAEL Lowest Observed Adverse Effect Level
LOG Level of Concern
LOEC Lowest Observed Effect Concentration
mg/kg/day Milligram Per Kilogram Per Day
MOE Margin of Exposure
MP Manufacturing-Use Product
MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
MRL Maximum Residue Level
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N/A Not Applicable
NASS National Agricultural Statistical Service
NAWQA USGS National Water Quality Assessment
NG No Gloves
NMFS National Marine Fisheries Service
NOAEC No Observed Adverse Effect Concentration
NOAEL No Observed Adverse Effect Level
NPIC National Pesticide Information Center
NR No respirator
OP Organophosphorus
OPP EPA Office of Pesticide Programs
ORETF Outdoor Residential Exposure Task Force
PAD Population Adjusted Dose
PCA Percent Crop Area
PDCI Product Specific Data Call-In
PDF USDA Pesticide Data Program
PF10 Protections factor 10 respirator
PF5 Protection factor 5 respirator
PHED Pesticide Handler's Exposure Data
PHI Pre-harvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
PRZM Pesticide Root Zone Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RID Reference Dose
RPA Reasonable and Prudent Alternatives
RPM Reasonable and Prudent Measures
RQ Risk Quotient
RTU (Ready-to-use)
RUP Restricted Use Pesticide
SCI-GROW Tier I Ground Water Computer Model
SF Safety Factor
SL Single layer clothing
SLN Special Local Need (Registrations Under Section 24C of FIFRA)
STORET Storage and Retrieval
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TRAC Tolerance Reassessment Advisory Committee
TTRS Transferable Turf Residues
UF Uncertainty Factor
USDA United States Department of Agriculture
USFWS United States Fish and Wildlife Service
USGS United States Geological Survey
WPS Worker Protection Standard
ill
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EXECUTIVE SUMMARY
The Environmental Protection Agency (hereafter referred to as EPA or the Agency) has
completed its review of public comments on the human health and environmental risk
assessments for PHMB and is issuing its risk management decision. The Agency has decided
PHMB is eligible for reregistration provided all measures outlined in this document are
implemented. PHMB is used as a fungicide, algicide, and sanitizer in swimming pools;
preservative for cut flowers; materials preservative; bacteriostat in industrial processes and water
systems; and hard surface disinfectant (food and non-food contact surfaces). End-use products
are formulated as soluble concentrates, as solids, as ready-to-use solutions, and in water-soluble
packaging. The product with the impregnated wipe formulation was cancelled in July 2005.
Overall Risk Summary
The Agency's human heath risk assessment indicates only one risk of concern for
occupational handlers. An acute dietary risk estimate was completed for females 13-50 years
old, the only population subgroup with an acute toxicity endpoint, and is below the Agency's
level of concern. Chronic dietary risk estimates were provided for the general U.S. population
and all population subgroups. All chronic dietary risk estimates are below the Agency's level of
concern. As none of the uses associated with PHMB are expected to impact either surface or
ground water resources, no drinking water assessment was performed. When considering
aggregate risk from dietary and residential exposures, risk estimates are below the Agency's
level of concern.
To address occupational exposure, dermal and inhalation risks were assessed for
handlers. Scenarios involving pour liquid for drilling muds and workover fluids showed a risk
above the Agency's level of concern. In order to achieve MOEs above the target level, these
scenarios must use mitigation measures such as metering pump systems. In addition, since the
inhalation MOE for this scenario falls below the MOE of 1,000, when the additional route-to-
route extrapolation uncertainty factor is applied, an inhalation study will be required to confirm
these findings.
An environmental risk assessment was also conducted for PHMB. Due to limited
potential for environmental exposure, environmental risks are below the Agency's level of
concern.
Dietary Risk
Acute and chronic dietary (food) risks are below EPA's level of concern for the general
U.S. population and all population subgroups. A screening-level acute dietary risk assessment
was conducted for PHMB food uses. Risk estimates are provided for females 13-50 years old,
the only population subgroup with an acute toxicity endpoint of concern. Risk estimates for the
use with the highest exposures were 9% of the aPAD and, therefore, were not of concern.
The chronic dietary risk assessment concludes that for all included use sites, the chronic
risk estimates are below the Agency's level of concern for the general U.S. population (<10% of
the cPAD) and all population subgroups (37% of the cPAD for children). Risks, therefore, are
not of concern and no mitigation measures are necessary.
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Drinking Water Risk
None of the uses associated with PHMB are expected to impact either surface or ground
water resources. Therefore, no drinking water assessment was performed.
Residential Risk
Residential handler and post-application exposure scenarios were assessed using
surrogate exposure data, maximum label rates, and standard assumptions. All margins of
exposure (MOEs) from dermal and inhalation exposure for residential handlers are above the
target MOE of 100 and, therefore, not of concern. For post-application dermal and incidental
ingestion (oral) exposures, MOEs were below the Agency's level of concern. No residential risk
mitigation is necessary.
Aggregate Risk
The aggregate risk assessment integrates the assessments conducted for dietary and
residential exposure. Using the Aggregate Risk Index (ARI) method, aggregate calculations
were performed for adults and children. The ARIs are greater than 1.2 for children and 5.4 for
adults. These risks are below the Agency's level of concern (ARI<1), and no mitigation
measures are necessary to reduce risks from aggregate exposures.
Occupational Risk
To address occupational exposure, dermal and inhalation risks were assessed for
handlers. Only one scenario for occupational handlers showed a risk above the Agency's level
of concern. The dermal MOE of 74 for scenarios involving pour liquid for drilling muds and
workover fluids is below the target MOE of 100 and, therefore, is of concern. In order to
achieve MOEs above the target level (i.e., greater than 100), scenarios involving drilling muds
and workover fluids must use mitigation measures such as metering pump systems. In addition,
since the inhalation MOE for this scenario falls below the MOE of 1,000, when the additional
route-to-route extrapolation uncertainty factor is applied, an inhalation study will be required to
confirm these findings. At this time, EPA does not foresee post-application exposures for the
occupational uses of PHMB.
Ecological Risk
The Agency conducted an environmental risk assessment to determine the potential
impact of PHMB use on non-target terrestrial and aquatic organisms. Environmental exposure
modeling was not conducted for PHMB because its uses are not likely to result in significant
outdoor exposure. The uses of PHMB make it unlikely that any appreciable exposure to
terrestrial or aquatic organisms would occur. The Agency expects no effects to listed species or
critical habitat and therefore makes a "No Effect" determination for PHMB. However, the high
toxicity of PHMB to fish and aquatic invertebrates is of concern in the event of a spill or misuse
of the product.
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Regulatory Decision
The Agency has completed its review and has determined that the data are sufficient to
support reregistration of all supported products containing PHMB. The Agency is issuing this
RED for PHMB, as announced in a Notice of Availability published in the Federal Register.
The RED and supporting risk assessment for PHMB are available to the public in EPA's
Pesticide Docket OPP-2004-0305 at ://www.epa.gov/edockets. This RED document includes
guidance and time frames for making any necessary label changes for products containing
PHMB.
Summary of Mitigation Measures
The Agency has determined that PHMB is eligible for reregistration provided the
mitigation measure described in this document and the label changes included in Table 12 in
Section V of the RED are implemented.
Occupational Risk
EPA determined that the greatest potential for exposure appears to be the inhalation and
dermal occupational scenarios involving pour liquid for drilling muds and workover fluids.
Using an open pour scenario, these risks are of concern to the Agency. In order for risks to drop
below the Agency's level of concern, scenarios involving drilling muds and workover fluids
must use mitigation measures such as metering pump systems.
Data Requirements
Additional confirmatory data is required to complete the reregistration of PHMB. A
complete list of data gaps is presented Section V and Appendix B (Table of Generic Data
Requirements). In addition, product-specific data is required for all products containing PHMB
as described in Section V of this document.
VI
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time
frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the
development and submission of data to support the reregistration of an active ingredient, as well
as a review of all submitted data by the U.S. Environmental Protection Agency (EPA or the
Agency). Reregistration involves a thorough review of the scientific database underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional
data on health and environmental effects; and to determine whether or not the pesticide meets the
"no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require tolerance reassessment. The Agency has decided that,
for those chemicals that have tolerances and are undergoing reregistration, the tolerance
reassessment will be initiated through this reregistration process. The Act also requires that by
2006, EPA must review all tolerances in effect on the day before the date of the enactment of the
FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require a
safety finding in tolerance reassessment based on factors including consideration of cumulative
effects of chemicals with a common mechanism of toxicity. This document presents the
Agency's revised human health and ecological risk assessments and the Reregistration Eligibility
Decision (RED) for poly(hexamethylenebiguanide) hydrochloride (PHMB).
PHMB is an antimicrobial used in several types of applications, including as a fungicide,
algicide, and sanitizer in swimming pools; preservative for cut flowers; materials preservative;
bacteriostat in industrial processes and water systems; and hard surface disinfectant. The
registrant for PHMB has indicated that about 95 percent of the use of this chemical is for pools
and spas. The hard surface disinfectant use may be on food and non-food contact surfaces in or
on agricultural premises and equipment; commercial, industrial, and institutional premises and
equipment; residential contents and premises; and medical premises and equipment.
The Agency has concluded that the FQPA Safety Factor for PHMB should be removed
(equivalent to IX) based on: (1) there is no concern for developmental neurotoxicity resulting
from exposure to PHMB because there is no evidence PHMB will induce neurotoxic effects; (2)
there is no quantitative or qualitative evidence of increased susceptibility to the fetus following
in utero exposure in the prenatal developmental toxicity studies or to the offspring when adults
are exposed in the two-generation reproductive study; and (3) the risk assessment does not
underestimate the potential exposure for infants and children.
Risks summarized in this document are those that result only from the use of the active
ingredients PHMB. The Food Quality Protection Act (FQPA) requires that the Agency consider
available information concerning the cumulative effects of a particular pesticide's residues and
other substances that have a common mechanism of toxicity. The reason for consideration of
other substances is due to the possibility that low-level exposures to multiple chemical
substances that cause a common toxic effect by a common toxic mechanism could lead to the
same adverse health effect that would occur at a higher level of exposure to any of the substances
1
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individually. 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 for PHMB and any other substances. PHMB does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this action, therefore, EPA has not
assumed that PHMB has a common mechanism of toxicity with other substances. For
information regarding EPA's efforts to determine which chemicals have a common mechanism
of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements
released by EPA's Office of Pesticide Programs concerning common mechanism determinations
and procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at httEiZ/www^ei^Lgo^
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of PFDVIB. In an effort to simplify the RED, the information presented herein
is summarized from more detailed information which can be found in the technical supporting
documents for PHMB referenced in this RED. The revised risk assessments and related addenda
are not included in this document, but are available in the Public Docket at
http ://www. epa. gov/edocket.
This document consists of six sections. Section I is the introduction. Section II provides
a chemical overview, a profile of the use and usage of PHMB, and its regulatory history. Section
III, Summary of PHMB Risk Assessments, gives an overview of the human health and
environmental assessments, based on the data available to the Agency. Section IV, Risk
Management, Reregistration, and Tolerance Reassessment Decision, presents the reregistration
eligibility and risk management decisions. Section V, What Registrants Need to Do, summarizes
the necessary label changes based on the risk mitigation measures outlined in Section IV.
Finally, the Appendices list all use patterns eligible for reregistration, bibliographic information,
related documents and how to access them, and Data Call-In (DCI) information.
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II. Chemical Overview
A. Regulatory History
PHMB was first registered in the United States in 1982 as an active ingredient.
Currently, there are 17 products containing PHMB (two technical products and 15 end-use
products) registered under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) for use as algaecides, bacteriocides/ bacteriostats, fungicides/fungistats,
microbicides/microbiostats, disinfectants, regulators, and sanitizers.
B.
Chemical Identification
Technical PHMB
Common name:
Chemical name:
X - ((CH2)3 - NH - C - NH - C - NH - (CH2)3)n - X
NH NH. HC1
where X = HC1. NH2 - (CH2)3
OR
X = - (CH2)3 - NH - C - NH - CN
NH
OR
X = - (CH2)3 - NH - C - NH2. HC1
NH
Figure 1. Molecular Structure of PHMB
Poly(hexamethylenebiguanide) hydrochloride
Poly(iminoimidocarbonyliminoimidocarbonyl-
iminohexamethylene) hydrochloride
Chemical family: Guanidine
Empirical formula: Cg HI? Ns HC1
CAS Registry No.: 32289-58-0
Case number: 3122
OPP Chemical Code: 111801
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Molecular weight:
Other names:
219.5
PHMB, Vantocil IB, Baquacil, Baquacil SB, Cosmoquil CQ
Basic manufacturers: Arch Chemicals, Inc.
Mareva, Inc.
Chemical properties: PHMB is a very faint yellow, mobile liquid. Since PHMB is a
liquid, it has no melting point. It has a boiling point of 100.2°C,
and decomposition begins at 205 - 210°C. PHMB has a specific
gravity of 1.04 at 20°C.
C.
Use Profile
The following is information on the uses of PHMB products, currently registered as of
September 30, 2004 , and an overview of use sites and application methods. A detailed table of
the uses of PHMB eligible for reregistration is contained in Appendix A.
Type of Pesticide:
Summary of Use:
Food:
Public Health:
Algicide, bacteriostat/bacteriocide, fungistat/fungicide,
microbiostat/microbiocide, disinfectant, regulator, and sanitizer
Hard surface disinfectant uses on kitchen countertops, high chairs,
refrigerators, and microwave ovens are indirect food uses, as there
surfaces have the potential to come into contact with food.
Hard surface disinfectant:
For use in residential, healthcare, industrial and institutional settings such
as hospitals, nursing homes, day care centers, nurseries, hotels, schools,
airplanes, boats, buses, campers, cars, railroad trains, taxicabs,
campgrounds, restaurants, animal laboratories, veterinary offices, kennels,
dental offices, health clubs, farm and livestock premises and mushroom
house premises. May be used on hard, non-porous surfaces such as tables,
countertops, stovetops, sinks, cabinets, refrigerators, microwave ovens,
high chairs, tubs, floors, glazed tiles, urinals, diaper pails and other
bathroom surfaces, garbage cans, walls, floors, stainless steel surfaces,
kennel runs, pet areas, sealed stones, glazed ceramics, playground
equipment, picnic tables and the coils of air conditioning units.
Aquatic non-food residential sanitizer:
For use in swimming pool, spa and hot tub water systems.
1 The impregnated wipe disinfectant, EPA Reg. No. 50096-1, was cancelled in July 2005. Its exclusion in the risk
assessment would not change the risk levels of concern; therefore, the document was not revised to remove it.
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Other Non-food:
Target Pests:
Terrestrial non-food microbiostat and preservative:
For use on ornamental flowering plants (cuttings or stored).
Indoor non-food materials preservative:
For use in the preservation of electrocoat resins in addition to aqueous
industrial chemicals such as reagents, oil-in-water emulsions, water-in-oil
emulsions, cellulose solutions, silicone emulsions and silicone dispersions,
aqueous mineral slurries such as calcium carbonate and titanium dioxide
as well as polymer latices such as polyvinyl acetate and polyvinyl alcohol.
For the preservation of textiles and cellulosic materials such as carpet,
curtains, mops, dishcloths, wipes, sponges, tissues and non-food contact
paper products.
For the preservation of leather, fresh animal hides and skins prior to or
during processing.
For the control of microorganisms in aqueous adhesives such as animal
glues, latex adhesives and other synthetic and protein based glues.
Terrestrial non-food bacteriostat:
For the control of microorganisms and bacteria in drilling muds and
packer fluids in addition to workover fluids.
Indoor non-food bacteriostat:
For the control of microorganisms and bacteria in oil field injection water
and tunnel pasteurization water.
Slime-forming bacteria, deterioration/spoilage bacteria, animal pathogenic
bacteria (G-and G+ vegetative), pseudomonas spp, animal pathogenic
fungi, mold/mildew, algae.
Formulation Types: Soluble concentrate/solid, impregnated wipes, ready-to-use solution, and
water-soluble packaging.
Method and Rates of Application:
Equipment: The end-use products are added during the manufacturing process of
treated articles and materials. Poly(hexamethylenebiguanide)
hydrochloride formulations are added directly to water in swimming
pools, spas, and cut flower applications, as well as in oil field injection
waters and workover fluids. Impregnated wipes are dampened with water
prior to use.
Application Rates: For details about specific use sites for PHMB, refer to Appendix A.
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Use 1 to 50 Ibs. of end use formulation to 10,000 Ibs. of product to
produce a 100 to 5000 ppm solution for the preservation of reagents,
oil-in-water emulsions, water-in-oil emulsions, cellulose solutions,
silicone emulsions and silicone dispersions.
Use 5 to 50 Ibs. of end use formulation to 10,000 Ibs. of product to
produce a 500 to 5000 ppm solution for the preservation of aqueous
mineral slurries such as calcium carbonate and titanium dioxide, as
well as polymer latices, such as polyvinyl acetate and polyvinyl
alcohol, and adhesives, such as animal glues, latex adhesives and other
synthetic and protein based glues.
Use 1 to 30 Ibs. of end use formulation to 10,000 Ibs. of product to
produce a 100 to 3000 ppm solution for the preservation of leather and
fresh animal hides and skins prior to or during processing.
Use 13 fl. oz. to 1 gal. of end use formulation to 1000 gals, of water
for the preservation of tunnel pasteurization waters.
For non-porous surface disinfection, spray end use product on surface
until wet. Surface must remain wet for 10 minutes before wiping dry.
Rinse food-contact surfaces with potable water prior to reuse.
For sanitizing pool water, use enough end-use product to give a
concentration of 50 ppm PHMB (58-64 oz. per 10,000 gals.) for
freshly filled pools. To maintain or raise level of end use product add
at a rate of one pint per 10,000 gals, of water. For pool water sanitizer
tablets, add one tablet per approximately 5500 gals, of water.
Use Classification: General use
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III. Summary of PHMB Risk Assessments
The purpose of this summary is to assist the reader by identifying the key features and
findings of these risk assessments and to help the reader better understand the conclusions
reached in the assessments. The human health and ecological risk assessment documents and
supporting information listed in Appendix C were used to formulate the safety finding and
regulatory decision for PHMB. While the risk assessments and related addenda are not included
in this document, they are available from the OPP Public Docket and may also be accessed on
the Agency's website at http://epa.gov/dockets. Hard copies of these documents may be found in
the OPP public docket under docket number OPP-2004-0220. The OPP public docket is located
in Room 119, Crystal Mall II, 1801 Bell Street, Arlington, VA, and is open Monday through
Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
A. Human Health Risk Assessment
1. ToxicityofPHMB
A brief overview of the toxicity studies used for determining endpoints in the risk
assessments are outlined below in Table 1. Further details on the toxicity of PHMB can be found
in the "PHMB Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision
Document," dated January 18, 2005; "Poly(hexamethylenebiguanide) Hydrochloride (PHMB)
Risk Assessment for the Reregistration Eligibility Decision," dated February 14, 2005; and
"PHMB - 2nd Report of the Hazard Identification Assessment Review Committee," dated April
9, 2003. These documents are available on Agency's website in the EPA Docket at
http ://www/epa. gov/edockets.
The Agency has reviewed all toxicity studies submitted for PHMB and has determined
that the toxicological database is sufficient for reregistration. The studies have been submitted to
support guideline requirements. Major features of the toxicology profile are presented below.
Table 1. Summary of Acute Toxicity Data for PHMB
Guideline
No.
Study Type
MMD #(s)
Results
Toxicity
Category
Acute Toxicity
870.1100
870.1200
870.1300
Acute Oral
Acute Dermal
Acute Inhalation
00030330
44940701
45916505
00065124
44940702
45916506
44970403
LD50 = 2747 mg/kg
LD50= 1831mg/kg(M)
LD50 = 1617mg/kg (F)
LD50 = 1049mg/kg (F)
LD50 > 2.0 ml/kg
LD50 > 2000mg/kg
LD50 > 5000mg/kg
LC50= 1.76mg/L
III
III
IV
III
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Guideline
No.
870.2400
870.2500
870.2600
Study Type
Primary Eye Irritation
Primary Skin Irritation
Dermal Sensitization
MRID #(s)
45916508
00046789
00065120
44963902
00046789
00065120
44949704
45916509
42674201
44940705
Results
Corrosive
Moderate irritant
Moderate irritant
Slight irritant
Moderate sensitizer
Mild sensitizer
Toxicity
Category
I
II
II
IV
NA
Notes: LC = Lethal Concentration; LD = Lethal Dose; NA = Not Applicable
The doses and toxicological endpoints selected for various exposure scenarios are
summarized in Table 2 below.
Table 2. Dietary Toxicological Endpoints for PHMB
Exposure
Scenario
Dose Used in Risk
Assessment, UF
Special FQPA SF*
and Level of
Concern for Risk
Assessment
Study and Toxicological Effects
Acute Dietary
(Females 13-50 years
of age)
NOAEL = 20
mg/kg/day
UF= 100
Acute RID = 0.2
mg/kg/day
FQPA SF = 1
aPAD = acute RID
FQPA SF
= 0.2 mg/kg/day
Rabbit Developmental Study
(MRID 42865901)
LOAEL = 40 mg/kg/day based on reduced
number of litters and skeletal abnormalities.
Acute Dietary
(General population
including infants and
children)
No Appropriate single dose effects can be selected for general population
Chronic Dietary
(All populations)
NOAEL=20
mg/kg/day
UF=100
Chronic RID =
0.2 mg/kg/day
FQPASF=1
cPAD =
chronic RID
FQPA SF
=0.2 mg/kg/day
Rabbit Developmental Study (MRID
42865901)
LOAEL = 40 mg/kg/day
Based on the increased mortality, reduced
food consumption, and clinical toxicity;
Mouse Developmental Study (Report No.
CTL/P/335, 1977 (cited in Report No.
003810, 1978. Section C-9))
LOAEL = 40 mg/kg/day;
Based on reduced body weight gain; and
Rat Developmental Study (Report No.
CTL/P/1262. 1976 (cited in Report No.
003810, 1978. Section C-ll))
LOAEL = 50 mg/kg/day
Based on reduced food consumption.
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Exposure
Scenario
Dose Used in Risk
Assessment, UF
Special FQPA SF*
and Level of
Concern for Risk
Assessment
Study and Toxicological Effects
Cancer (Oral,
dermal, inhalation)
The HED Cancer Assessment Review Committee (CARC) classified PHMB as
"Suggestive Evidence of Carcinogenicity, but not sufficient to Assess Human
Carcinogenic Potential" by the oral and dermal routes. Quantification of human cancer
risk is not required.
Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest
observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RiD = reference dose
General Toxicity Observations
Dietary
The acute RED is 0.2 mg/kg/day for females (13-50 years), based on adverse
developmental effects (reduced number of litters and skeletal abnormalities) at 40 mg/kg/day in a
rabbit developmental study. The chronic RfD is 0.2 mg/kg/day based on increased mortality,
reduced food consumption, and clinical toxicity at 40 mg/kg/day in a rabbit developmental study;
reduced body weight gain in a mouse developmental study at 40 mg/kg/day; and reduced food
consumption in a rat developmental study at 50 mg/kg/day. An uncertainty factor of 100 (10X
for interspecies extrapolation and 10X for intraspecies variability) was applied to the NOAEL to
obtain the acute and chronic RfDs.
Incidental Oral
The short- and intermediate-term incidental oral NOAEL is 20 mg/kg/day from the
rabbit, mouse, and rat developmental toxicity studies that noted increased mortality, reduced
food consumption, clinical toxicity, and/or reduced body weight gain. The target margin of
exposure (MOE) is 100.
Short-, Intermediate-, and Long-term Dermal
The short-, intermediate-, and long-term dermal NOAEL is 150 mg/kg/day, which is
based on decreased body weight and liver tumors identified at a dose of 750 mg/kg/day in an 80-week
dermal painting study in mice. The uncertainty factor or "target" MOE for PHMB dermal
exposures are 100 for occupational and residential scenarios.
Short- and Intermediate-term Inhalation
The short- and intermediate-term inhalation NOAEL is 20 mg/kg/day based on the oral
endpoint. In the absence of route-specific data, it was conservatively assumed that inhalation
absorption is equivalent to oral absorption (i.e., 100%). For inhalation exposures, the uncertainty
factor is 100 for occupational and residential scenarios. An additional lOx route-to-route
extrapolation is used to determine if a confirmatory inhalation toxicity study is warranted.
Carcinogenicity Classification
The Agency classified PHMB as "Suggestive Evidence of Carcinogenicity, but not
sufficient to Assess Human Carcinogenic Potential" by the oral and dermal routes.
Quantification of human cancer risk is not required.
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Mutagenicity Potential
The data base for mutagenicity is considered adequate based on EPA's mutagenic
guidelines and indicates that PHMB is not mutagenic or genotoxic.
Endocrine Disruption Potential
EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended
by FQPA, to develop a screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator
may designate." When the appropriate screening and/or testing protocols being considered under
the Agency's Endocrine Disrupting Screening Program (EDSP) have been developed, PFDVIB
may be subjected to additional screening and/or testing to better characterize effects related to
endocrine disruption.
2. FQPA Safety Factor
The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is
intended to provide an additional 10-fold safety factor (10X), to protect for special sensitivity in
infants and children to specific pesticide residues in food, drinking water, or residential
exposures, or to compensate for an incomplete database. The FQPA Safety Factor has been
removed (i.e., reduced to IX) for PFDVIB based on: (1) a lack of evidence that PFDVIB will induce
neurotoxic effects, (2) no quantitative or qualitative evidence of increased susceptibility to the
fetus following in utero exposure in the prenatal developmental toxicity studies, and (3) no
quantitative or qualitative evidence of increased susceptibility to the offspring when adults are
exposed in the two-generation reproductive study. The FQPA Safety Factor assumes that the
exposure databases (food, drinking water, and residential) are complete and that the risk
assessment does not underestimate the potential risk for infants and children. These criteria have
been met for PHMB. Based on the analysis of submitted developmental toxicity studies, the
Agency determined that no special FQPA Safety Factor was needed since there were no residual
uncertainties for pre- and/or postnatal toxicity.
3. Population Adjusted Dose (PAD)
Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which
reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for
the FQPA Safety Factor (SF). This calculation is performed for each population subgroup. A
risk estimate that is less than 100% of the acute or chronic PAD is not of concern.
a. Acute PAD
Acute dietary risk for PHMB is assessed by comparing acute dietary exposure estimates
(in mg/kg/day) to the acute Population Adjusted Dose (aPAD). Acute dietary risk is expressed
as a percent of the aPAD. The aPAD is the acute reference dose (0.2 mg/kg/day) modified by
the FQPA safety factor. The acute reference dose was derived from a developmental toxicity
study in rabbits in which both the NOAEL (20 mg/kg/day) and the LO AEL (40 mg/kg/day) were
determined. Acute dietary exposure was estimated only for females ages 13-50 because
available studies did not show a toxicity endpoint attributable to a single exposure for the general
10
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population. The PHMB aPAD is 0.2 mg/kg/day based on a reference dose of 0.2 mg/kg/day, and
the FQPA safety factor of IX.
b. Chronic PAD
Chronic dietary risk for PHMB is assessed by comparing chronic dietary exposure
estimates (in mg/kg/day) to the chronic Population Adjusted Dose (cPAD). Chronic dietary risk
is expressed as a percent of the cPAD. The cPAD is the chronic reference dose (0.2 mg/kg/day)
modified by the FQPA safety factor. The cPAD was derived from developmental studies in rats,
rabbits, and mice, in which both the NOAELs (20 mg/kg/day) and the LOAELs (40 mg/kg/day
in rats and rabbits and 50 mg/kg/day in mice) were determined. The PHMB cPAD is 0.2
mg/kg/day based on a reference dose of 0.2 mg/kg/day, which incorporates the FQPA safety
factor (IX) for the overall U.S. population or any population subgroups.
4. Exposure Assumptions
Acute and chronic dietary exposure assessments from PFDVIB use as a disinfectant on
indirect food-contact surfaces were conducted using an equation that considers application rates,
surface area, pesticide migration fraction, and body weight. This approach differs from the FDA
approach. However, in assessing dietary exposures from PHMB in latex adhesives, a number of
assumptions were made based on the FDA guidelines (FDA, 2003b) for the migration level,
consumption factor, total food intake, and amount of packaging required for food. As a
conservative assumption, it is assumed that latex adhesive represents 10% of the packaging.
Also, it is assumed that paper used in food packaging weighs 50 mg/in2.
5. Dietary Risk Assessment
Generally, a dietary risk estimate that is less than 100% of the acute or chronic PAD does
not exceed the Agency's risk concerns. A summary of acute and chronic risk estimates are
shown in Table 4. Based on a review of product labels containing PHMB, four uses have been
identified as having the potential to cause indirect dietary exposure due to indirect food contact:
1. Tunnel Pasteurization
2. Disinfectant on Countertops (representative of food-contact hard surfaces)
3. Latex Adhesives on Food Packaging
4. Disinfectant Cloths
Although tunnel pasteurization has the potential for causing indirect dietary exposure to
PHMB, an Estimated Daily Intake (EDI) has not been calculated for this use because the bottles
or cans are already sealed, and the possibility of infiltration of this product from tunnel
pasteurization water into the food appears to be minimal.
a. Dietary Risk from Food
A screening-level acute dietary risk assessment was conducted for three of the four
PHMB food uses, excluding tunnel pasteurization. Acute dietary risk estimates are provided for
females 13-49 years old, the only population subgroup for which an endpoint was selected. The
results showed risk estimates to be <10% of the aPAD for each use site and therefore were not of
concern. The chronic dietary assessment concluded that for all included uses, the chronic risk
11
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estimates are below the Agency's level of concern for the general U.S. population (<10% of the
cPAD) and all population subgroups (<40% of the cPAD for children, the most highly exposed
subgroup). Because the exposure associated with latex adhesives is several orders of magnitude
less than the exposure associated with the countertop disinfectant use, the combined dietary
exposure amounts are, for all practical purposes, the same as the exposure to the countertop
disinfectant, with the liquid disinfectant as a worst-case scenario.
Table 3. Summary of Dietary Exposure and Risk for PHMB
Population
Subgroup
Acute Dietary
Dietary Exposure
(mg/kg/day)a
%aPADb
Chronic Dietary
Dietary Exposure
(mg/kg/day)a
%cPADb
Liquid Disinfectant
Adult Male
Adult Female
Child
0.016
0.018
0.074
-
9
-
0.016
0.018
0.074
8
9
37
Wipe Disinfectant
Adult Male
Adult Female
Child
0.0045
0.0053
0.021
-
3
-
0.0045
0.0053
0.021
2
3
11
Latex Adhesive
Adult Male
Adult Female
Child
7.4xlO-10
8.6xlO-10
3.4xlO-10
-
4.3xlO'7
-
7.4xlO-10
8.6xlO-10
3.4xlO-10
5.69xlO'7
6.62xlO'7
2.62xlO'6
1 acute and chronic exposure analysis based on daily consumption associated with use of a liquid disinfectant on counter tops and
exposure to food packages using treated latex adhesive.
b %PAD = dietary exposure (mg/kg/day) / aPAD or cPAD, where aPAD= 0.2 mg/kg/day (for adult females only) and cPAD=0.2
mg/kg/day (for all populations)
b. Dietary Risk from Drinking Water
None of the uses associated with PHMB are expected to impact either surface or ground
water resources. Therefore, no drinking water assessment was performed.
6. Residential Risk Assessment
a. Residential Toxicity
The toxicological endpoints and associated uncertainty factors used for assessing the non-
dietary, residential risks for PHMB are listed in Table 4.
12
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Table 4. Residential Toxicological Endpoints for PHMB
Exposure
Scenario
Short-Term
Incidental Oral (1-30
days)
Intermediate-Term
Incidental Oral (1-6
months)
Short-Term,
Intermediate-Term,
and Long-Term
Dermal Exposure
Short-Term and
Intermediate-Term
Inhalation Exposure
Cancer (Oral,
dermal, inhalation)
Dose Used in Risk
Assessment, UF
NOAEL=20
mg/kg/day
UF= 100
NOAEL=20
mg/kg/day
UF= 100
Dermal (or oral)
study
NOAEL= 150
mg/kg/day
UF= 100
Level of Concern
for Risk Assessment
Residential LOC for
MOE = 100
Occupational = NA
Residential LOC for
MOE = 100
Occupational = NA
Residential LOC for
MOE =100
Occupational LOC
for MOE =100
Study and Toxicological Effects
Rabbit Developmental Study (MRID
42865901)
LOAEL = 40 mg/kg/day
Based on the increased mortality, reduced
food consumption, and clinical toxicity;
Mouse Developmental Study (Report No.
CTL/P/335, 1977 (cited in Report No.
003810, 1978. Section C-9))
LOAEL = 40 mg/kg/day;
Based on reduced body weight gain; and
Rat Developmental Study (Report No.
CTL/P/1262, 1976 (cited in Report No.
003810, 1978. Section C-ll))
LOAEL = 50 mg/kg/day
Based on reduced food consumption.
See Short-Term Incidental Oral Endpoint
80-Week Dermal Painting Study (MRIDs
00066475 and 00 104796)
LOAEL = 750 mg/kg/day based on
decreased body weight and liver tumors.
No appropriate route-specific study was available. The oral endpoint of 20 mg/kg with a
Margin of Exposure of 100 (lOx inter-species extrapolation, lOx intra-species variation) is
used. An additional lOx route-to-route extrapolation is used to determine if a confirmatory
inhalation toxicity study is warranted.
The HED Cancer Assessment Review Committee (CARC) classified PHMB as "Suggestive
Evidence of Carcinogenicity, but not sufficient to Assess Human Carcinogenic Potential"
by the oral and dermal routes. Quantification of human cancer risk is not required.
Notes: LTF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, LOC
= level of concern, MOE = margin of exposure
b.
Residential Handlers
i. Exposure Assessment
Based on the use patterns of PHMB, EPA has identified the four major exposure scenarios
for residential handlers including:
Open pouring for swimming pools/spas;
• Spraying (aerosol and/or trigger pump sprays) disinfectants;
• Mopping with disinfectants; and
13
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Wiping with disinfectants.
Using surrogate unit exposure data from the Pesticide Handlers Exposure Database
(PHED) and the Chemical Manufacturers Association (CMA) database, maximum application
rates from labels, and EPA estimates of daily amount handled, exposure to residential handlers
were assessed. PHMB is assessed using a typical residential swimming pool capacity of 20,000
gallons. For mopping, it is assumed that a 1-gallon bucket of solution is used by a homeowner to
mop the floor.
11.
Risk Assessment
All of the inhalation and dermal MOEs for residential handlers are above the target MOE
of 100 and, therefore, not of concern. In addition, the inhalation MOEs for each use are above
the MOE of 1,000, when the additional route-to-route extrapolation uncertainty factor is applied.
An inhalation study is not being required for the residential uses at this time. The MOEs for
handlers are summarized in Tables 5.
Table 5. Residential Handler Risk Summary
Exposure
Scenario
Open Pouring
Spraying
Mopping
Wiping
Use site
Residential Pool
Household Premises (hard surfaces)
Household Floors (hard surfaces)
Household Premises (hard surfaces)
Label Application
Rate (Ib a.i./day)
2.2
0.006
0.023
0.006
Baseline
Dermal MOE
35,000
8,000
6,400
610
Baseline
Inhalation MOE
180,000
180,000
26,000
3,400
c. Residential Post-Application
i. Exposure Assessment
Based on the use patterns, EPA has identified residential post-application exposure
scenarios for the swimming pool/spa use along with the hard surface cleaners. The exposure
scenarios (and assumptions used in the assessment) that are considered representative of the
high-end exposures associated with PHMB include:
• Dermal exposure and ingestion of PHMB via swimming in treated pools for adults and
children, both competitive and non-competitive. The SWIMODEL 3.0 default values and
chemical-specific values (MRIDs 44051301 and 44046301) were used in the calculations
for the assessment. Exposure time for non-competitive swimmers is based on data
provided in EPA's Exposure Factors Handbook (1997) whereas competitive swimmer
exposure time data are based on the Agency's review of the American Chemistry Council
(ACC) study "An Analysis of the Training Patterns and Practices of Competitive
Swimmers" (ACC, 2002).
• Dermal contact and incidental ingestion (i.e., hand-to-mouth residue transfer) resulting
14
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from toddlers crawling on treated floors after mopping. While other hard surfaces may
be treated (e.g., wiping counter tops/sinks), it is believed that the floor represents the high
end exposure scenario for children's contact. Residential SOP assumptions are used for
this assessment. Toddlers (3 years old) are used to represent the 1 to 6 year old age group
and are assumed to weigh 15 kg, the median for male and female toddlers (USEPA,
2000b). A body surface area of 0.657 m2 has been assumed, which is the median value.
It was also assumed that the diluted treatment solution is applied at a rate of 1000 sq. ft.
per gallon, as this was not provided on the label. As a conservative measure, it has been
assumed that 25% of the mop solution remains after the final mop. The Residential SOPs
estimate of 10% of the amount on the floor/hard surface available for dermal transfer is
used.
11.
Risk Assessment
The residential post-application risk assessment identifies short-term (1-30 days) and
intermediate-term (1-6 month) exposure doses based on the reported toxicology endpoints for
PHMB. Because of the shorter exposure durations of these toxicological endpoints, conservative
event-based exposure assumptions are used to calculate upper bound daily dose estimates. Doses
are not amortized over a lifetime. Additionally, since the permeability constant provides
estimates of an internal dose from the dermal route of exposure, the oral toxicity endpoint rather
than the dermal toxicity endpoint is used to assess the risks from the dermal swimming route.
Table 6 presents the estimated doses from the dermal and ingestion routes of exposure
and the corresponding MOEs based on the oral endpoint for the swimming scenarios for each
age group. The calculated results for short-, intermediate-, and long-term exposures and risks
indicate that the risks from the dermal and ingestion routes of exposure are not of concern
(MOE>100) for the post-application scenarios developed in this assessment.
Table 6. Residential Post-Application Risk Summary
Use Type
Swimming
Pool
Floors
Floors
Scenario Description
Adult Competitive
Adult Non-Competitive
Child (7-10 yrs) Competitive
Child (7-10 yrs) Non-Competitive
Child (11-14 yrs) Competitive
Child (11-14 yrs) Non-Competitive
Child, Short-Term Duration
Child, Intermediate-Term Duration
Dermal Dose
(mg/kg/day)
4.06E-5
6.76E-5
1.80E-5
9.01E-5
3.08E-5
4.62E-5
150
150
Incidental
Ingestion
Dose
(mg/kg/day)
0.0056
0.019
0.017
0.087
0.011
0.033
0.031
0.014
Dermal
MOEa
490,000
300,000
1,100,000
220,000
650,000
430,000
600
600
Inhalation
MOEa
3600
1100
1200
230
1800
620
660
1,400
aMOE = NOAEL (mg/kg/day)/Dose (mg/kg/day). The same oral NOAEL is used for dermal and ingestion risks.
Target MOE = 100; NA = Not Applicable
15
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7. Aggregate Risk
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic
Act (FFDCA, Section 408(b)(2)(A)(ii)) require "that there is a 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 will typically include exposures from food, drinking water, residential uses of a
pesticide, and other non-occupational sources of exposure.
In the case of PHMB, a cancer aggregate assessment is not needed, as the chemical has
been classified by the Agency's Cancer Assessment Review Committee as having "Suggestive
Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential." For
the non-cancer aggregate assessment, there is no need for an acute and chronic dietary aggregate
assessment, as the uses of PHMB have been determined to have no impact on surface or ground
water and the dietary risk calculations estimated will characterize the total dietary risk of PHMB.
In the case of short-, intermediate-, and long-term aggregate assessments, the following exposure
scenarios were aggregated for adults exposed to PHMB: dietary exposure, dermal and inhalation
exposure from liquid pouring of PHMB swimming pool product, and dermal and incidental oral
exposure from swimming. Aggregate exposures for children and toddlers included food
exposure and dermal and incidental oral exposure from swimming. Cleaning activities were not
included in the aggregate assessment as these activities were not felt to reasonably occur together
with the other exposure scenarios. As about 95% of PHMB is used in swimming pool products,
it is unlikely that residential users will be using PHMB both to sanitize their swimming pools and
clean their homes.
a. Short- and Intermediate-Term Aggregate Risk
The Agency has concluded that, although an oral toxicity study was selected for dietary,
inhalation, and incidental oral risk assessments and a dermal toxicity study was selected for
dermal risk assessments, the non-cancer effects occurring by the oral and dermal routes were
similar and that these exposures should be aggregated. The report describing this decision can be
found in OPP-2004-0305 at http://www.epa.gov/edockets. Inhalation exposures are currently
included in the aggregate assessment based on the use of the oral endpoint. Aggregate MOE
calculations for adults and children were performed using the Aggregate Risk Index method
(USEPA, 200la). As shown in Table 7, no aggregate risks of concern were identified for either
adults or children.
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Table 7. Short- and Intermediate-Term Aggregate Risks
Population
Subgroup
Males
Females 13-
50 years
Children 7-
10 years
Children 11-
14 years
Chronic Food
Exp
mg/kg/day/
(MOE)
0.016/
(1250)
0.018/
(1111)
0.074/
(270)
0.074
(270)
ST/IT Incidental
Oral Swimming
Exposure
(mg/kg/day)
(MOE)
0.0056 (comp.)
(3600)
0.019 (non-comp.)
(1100)
0.0056 (comp.)
(3600)
0.019 (non-comp.)
(1100)
0.017 (comp.)
(1200)
0.087 (non-comp.)
(230)
0.0 11 (comp.)
(1800)
0.033 (non-comp.)
(620)
ST/IT Dermal
Swimming Exposure
(mg/kg/day)
(MOE)
0.000044 (comp.)
(450000)
0.000015 (non-comp.)
(1,300000)
0.000044 (comp.)
(450000)
0.000015 (non-comp.)
(1,300000)
0.000018 (comp.)
(1,100,000)
0.00009 (non-comp.)
(220000)
0.00003 (comp.)
(650000)
0.000046 (non-comp.)
(430000)
Liquid Pouring
Dermal
Exposure
(mg/kg/day)
(MOE)
0.00424
(35,000)
0.00491
(31,000)
N/A
N/A
Liquid Pouring
Inhalation
Exposure
(mg/kg/day)
(MOE)
0.000113
(180,000)
0.000131
(153,000)
N/A
N/A
Aggregate Risk
Index
9.0
5.7
8.2
5.4
2.2
1.2
2.3
1.9
MOE = NOEL (mg/kg/day)/Dose(mg/kg/day). Oral NOAEL is 20 mg/kg/day for short- and intermediate-term. Dermal NOAEL is 150 mg/kg/day for short- and intermediate-
term. Inhalation NOAEL is 20 mg/kg/day for short-term. The target Margins of Exposure for all exposures are 100.
Aggregation was performed using the Aggregate Risk Index method. ARI =11 ((UF1/MOE1) + (UF'2/MOE2) + (UF3/MOE3) + ...). ARIs greater than 1 are not of concern.
17
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b. Chronic Aggregate Risk
A long-term aggregate risk assessment was not performed in this assessment. None of
the residential exposure scenarios are considered to be long-term and were, therefore, not
aggregated with the chronic dietary exposure.
8. Occupational Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites (post-application exposure). Occupational handlers of
PHMB include workers pouring or pumping PHMB preservatives into vats or tanks for several
uses (materials preservatives, tunnel pasteurization, and industrial processes and water systems);
pouring PHMB products into swimming pools and spas; and spraying, wiping, and moping
PHMB disinfectants on medical premises and equipment. Occupational risk for all of these
potentially exposed populations is measured by a Margin of Exposure (MOE) which determines
how close the occupational exposure comes to a No Observed Adverse Effect Level (NOAEL)
from toxicological studies. In the case of PHMB, MOEs greater than 100 are not of concern to
the Agency. This MOE includes the standard safety factors of 10X for intraspecies variability
(i.e. differences among humans) and 10X for interspecies variability (differences between
humans and animals). An additional lOx route-to-route extrapolation is used to determine if a
confirmatory inhalation toxicity study is warranted. At this time, EPA does not foresee post-
application exposures for the occupational uses of PHMB.
Occupational risk is assessed for exposure at the time of application (termed "handler"
exposure). Application parameters are generally defined by the physical nature of the
formulation (e.g., formula and packaging), by the equipment required to deliver the chemical to
the use site, and by the application rate required to achieve an efficacious dose. Occupational
risks were assessed for exposures from pouring liquid formulations, as well as spraying, wiping,
and mopping applications.
For more information on the assumptions and calculations of potential risk of PHMB to
workers, see the Occupational Exposure Assessment (Section 7.0) in the
"Poly(hexamethylenebiguanide) hydrochloride (PHMB): Risk Assessment for the Reregistration
Eligibility Decision," dated February 14, 2005 and the "PHMB Occupational/Residential
Exposure Assessment," dated February 3, 2005.
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a. Occupational Toxicity
The toxicological endpoints used in the assessment can be found in Table 8 below.
Table 8. Occupational Toxicological Endpoints for PHMB
Exposure
Scenario
Dose Used in Risk
Assessment, UF
Level of Concern for
Risk Assessment
Study and Toxicological
Effects
Short-Term, Intermediate-
Term, and Long-Term
Dermal Exposure
Dermal (or oral) study
NOAEL= 150
mg/kg/day
UF= 100
Residential LOC for MOE
= 100
Occupational LOC for
MOE =100
80-Week Dermal Painting
Study (MRIDs 00066475 and
00104796)
LOAEL = 750 mg/kg/day
based on decreased body
weight and liver tumors.
Short-Term and
Intermediate-Term
Inhalation Exposure
No appropriate route-specific study was available. The oral endpoint of 20 mg/kg
with a Margin of Exposure of 100 (1 Ox inter-species extrapolation, lOx intra-species
variation) is used. An additional lOx route-to-route extrapolation is used to
determine if a confirmatory inhalation toxicity study is warranted.
Cancer (Oral, dermal,
inhalation)
The HED Cancer Assessment Review Committee (CARC) classified PHMB as
"Suggestive Evidence of Carcinogenicity, but not sufficient to Assess Human
Carcinogenic Potential" by the oral and dermal routes. Quantification of human
cancer risk is not required.
Notes: LTF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, LOC
= level of concern, MOE = margin of exposure
b. Occupational Handler Exposure
Inhalation and dermal exposures to PHMB were addressed for occupational populations
using surrogate data from the Pesticide Handlers Exposure Database (PHED) (USEPA, 1997c),
the Chemical Manufacturers Association (MRID 42587501), and several studies which relate to
the use patterns of PHMB. Using surrogate dermal and inhalation unit exposure data, application
rates from labels, and EPA estimates of daily amount handled, exposure and risks to handlers
were assessed. A description of the surrogate data and calculations used are included in the
Occupational Exposure Assessment (Section 7.0) in the "Poly(hexamethylenebiguanide)
hydrochloride (PHMB): Risk Assessment for the Reregistration Eligibility Decision," dated
February 14, 2005 and the "PHMB Occupational/Residential Exposure Assessment," dated
Februarys, 2005.
The Agency has determined that there are potential exposures to individuals who mix,
load, apply, and otherwise handle PHMB during the usual use patterns associated with the
pesticide's use. Based on the use patterns, the exposure scenarios in Table 9 were assessed.
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Table 9. PHMB Handler Scenarios
Category
Material Preservatives
Food Handling/Storage
Establishments Premises and
Equipment
Industrial Processes and Water
Systems
Swimming Pools
Medical Premises and
Equipment
Scenario
Pouring PHMB industrial preservative into vats or tanks of slurry containing
leather processing fluids, silicones, adhesives, mineral slurries, textiles, etc.
Pouring PHMB preservative into vats or tanks for tunnel pasteurization.
Pouring or pumping PHMB preservative into vats or tanks for preservation of oil
well injection fluids, mud packer solutions, and workover solutions.
Pouring PHMB preservatives into pools or spas by commercial treaters.
PHMB is used in a spray, wipe and mop to sterilize surfaces as a hospital cleaner
disinfectant and medical equipment. Disinfectants are applied by spray,
mopping and wiping.
c. Occupational Handler Risk Summary
The occupational handler risk assessment included both inhalation and dermal exposures.
The target MOE for both is 100. Scenarios with an MOE less than 100 indicate a risk of
concern. After performing the exposure assessment, EPA determined that the greatest potential
for exposure appears to be the inhalation and dermal occupational scenarios involving pour
liquid for drilling muds and workover fluids, based on application rates of 1,052 Ibs. of active
ingredient per day (dermal MOE = 74 and inhalation MOE = 370, target MOEs of 100). In order
to achieve MOEs above the target level (i.e., greater than 100), scenarios involving drilling muds
and workover fluids must use mitigation measures such as metering pump systems. Calculated
MOEs using the pump liquid scenario (i.e., dermal MOE=1,600 and inhalation MOE 3,300) are
greater than the target MOE. As the mitigation measure brings the inhalation MOE above 1,000
(which includes the additional lOx route-to-route extrapolation), no confirmatory inhalation
toxicity study is needed.
Dermal and inhalation MOEs for the commercial exposure scenarios involving
commercial pool operators pouring PHMB liquid into multiple residential swimming pools and
spas are greater than the target MOE and, therefore, are not of concern. The commercial
handlers for the medical premises uses did not trigger risks of concern for the spray/mop/wipe
applications.
9. Human Incident Data
In evaluating incidents to humans, the Agency reviewed reports from the National Poison
Control Centers (PCC), the Agency's Office of Pesticide Program's Incident Data System (IDS),
California Department of Pesticide Regulation, and the National Pesticide Telecommunications
Network (NPTN). Incident reports were only found in IDS and PCC. Those found in PCC were
also in IDS. Therefore, all incidents are reported as found in IDS.
A total of 118 individual incident cases submitted to the EPA Office of Pesticide
Programs involving use of PHMB-containing swimming pool products were reviewed to
determine the effects of exposure to PHMB. All of the incident reports reviewed were for
residential use of the products by consumers. In 17 (14%) out of the 118 individual incident
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cases reviewed, it was determined that the exposure effects were the result of not using the
product as intended by the manufacturer. They included not following the instructions on the
label, accidental ingestion of the product, or splashing the concentrated product onto the skin or
into the eyes.
The reported routes for exposure of the 118 incident cases were dermal (58%), ocular
(30%), ingestion (9%), inhalation (7%), and unknown (<1%). In some cases more than one route
of exposure applied for an individual incident case (e.g., both dermal and ocular exposure). The
most common symptoms reported for each exposure route are as follows:
• Dermal exposure: skin irritation/burning, rash, hives/welts, itching, skin
discoloration/redness, allergic reaction, and blistering
• Ocular exposure: eye irritation/burning, eye pain, loss of vision, swelling of eyes, and
allergic reactions.
Ingestion/oral exposure: vomiting/nausea/abdominal pain, irritation to the mouth/throat,
respiratory irritation including coughing/choking, and diarrhea
• Inhalation exposure: respiratory irritation and coughing/choking
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. PHMB
has several registered use sites: swimming pools, cut flowers, materials preservatives, industrial
processes and water systems, and hard surfaces. The following risk characterization is intended
to describe the magnitude of the estimated environmental risks for PHMB use sites and any
associated uncertainties.
For detailed discussions of all aspects of the environmental risk assessment, see the
Environmental Risk Assessment (Section 8.0) in the "Poly(hexamethylenebiguanide)
hydrochloride (PHMB): Risk Assessment for the Reregistration Eligibility Decision," dated
February 14, 2005, the "Environmental Fate Assessment of PHMB for the Reregistration
Eligibility Decision (RED)," dated August 18, 2004, and the "Ecological Hazard and
Environmental Risk Assessment: Poly(hexamethlenebiguanide) hydrochloride (PHMB)," dated
August 4, 2004.
1. Environmental Fate and Transport
PHMB is stable hydrolytically in the environment and has a half-life of more than thirty
days. This may be of environmental concern for surface water contamination, in the event of
exposure to surface water. Studies for other fate processes are not required by and have not been
submitted to the Agency.
2. Ecological Risk
The Agency's ecological risk assessment compares toxicity endpoints from ecological
toxicity studies to estimated environmental concentrations based on environmental fate
characteristics and pesticide use data.
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a. Toxicity (Hazard) Assessment
PHMB demonstrates low toxicity to birds and mammals and high toxicity to freshwater
aquatic organisms. All submitted ecological toxicity studies were conducted with a 20% a.i.
solution of PHMB, which is the technical formulation, and values were adjusted to 100% a.i. to
classify the studies according to relative toxicity. Submission of data regarding toxicity to
marine/estuarine organisms, plants, or chronic effects was not required for the indoor uses of
PHMB. Limited additional data was found using EPA's ECOTOX database. A summary of
submitted data is provided in the table below.
Table 10. Summary of Submitted Acute Ecological Effects Toxicity Data for PHMB
Species
LD50/ LC50
NOAEL/
NOAEC
Toxicity category (based
on 100% AI)
Birds
Northern bobwhite (Colinus
virginianus)
Mallard duck (Anas
platyrhynchos)
Mallard (Anas
platyrhynchos)
LC50> 5620 (>1 124
ppm ai)
LC50> 5620 (>1 124
ppm ai)
LD50>2510(>502
mg ai/kg)
NOEC 5620 ppm (1124
ppm ai)
NOEC 5620 (1124 ppm
ai)
NOEL = 25 10 (502 mg
ai/kg)
Slightly toxic
Slightly toxic
Slightly toxic
Mammals
Laboratory rat
(Rattus norvegicus)
LD50 = 2747 mg/kg
N/A
Freshwater Fish
Rainbow trout
(Oncorhynchus mykiss)
Bluegill sunfish
(Lepomis macrochims)
96-hr. LC50 =
0.02545 ppm ai
96-hr. LC50 = 0.57
(0.114ppmai);
NOEC = 0.0098 ppm ai
NOEC = 0.17 (0.034
ppm ai)
Very highly toxic
Highly toxic
Freshwater Invertebrate
Waterflea
(Daphnia magna)
48-hr. EC50 =
0.18(0.12-0.30)
(0.036 ppm ai)
NOEC = 0.7 (0.14 ppm
ai)
Highly toxic
N/A = not available
NOAEC= No-observable adverse effect concentration
b. Exposure and Risk
Environmental exposure modeling was not conducted for PHMB. The only use pattern
likely to result in significant outdoor exposure is the oil recovery use; however, there is a label
statement prohibiting use over or near marine/estuarine (e.g., offshore) oil fields. The uses of
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PHMB considered in this RED make it unlikely that any appreciable exposure to terrestrial or
aquatic organisms would occur. Facilities using PHMB for indoor industrial applications are
required to have NPDES permits before discharging effluents into receiving waters.
c. Risk to Listed Species
Due to the low likelihood of exposure and low toxicity of PHMB, the Agency expects no
effects to listed species or critical habitat and, therefore, makes a "No Effect" determination for
this chemical.
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IV. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregistration. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support reregistration
of products containing PHMB as an active ingredient. The Agency has completed its review of
these generic data and has determined that the data are sufficient to support reregistration of all
supported products containing PFDVIB.
The Agency has completed its assessment of the dietary, occupational, drinking water,
and ecological risks associated with the use of pesticide products containing the active ingredient
PHMB. Based on a review of these data and on public comments on the Agency's assessments
for the active ingredient PFDVIB, the Agency has sufficient information on the human health and
ecological effects of PFDVIB to make decisions as part of the tolerance reassessment process
under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has
determined that PHMB-containing products are eligible for reregistration provided that: (i)
current data gaps and confirmatory data needs are addressed; (ii) the risk mitigation measure
outlined in this document is adopted; and (iii) label amendments are made to reflect this measure.
Label changes are described in Section V. Appendix A summarizes the uses of PFDVIB that are
eligible for reregistration. Appendix B identifies the generic data requirements that the Agency
reviewed as part of its determination of reregistration eligibility of PHMB and lists the submitted
studies that the Agency found acceptable. Data gaps are identified as generic data requirements
that have not been satisfied with acceptable data.
Based on its evaluation of PHMB, the Agency has determined that PHMB products,
unless labeled and used as specified in this document, would present risks inconsistent with
FIFRA. Accordingly, should a registrant fail to implement the risk mitigation measure identified
in this document, the Agency may take regulatory action to address the risk concerns from the
use of PHMB. If all changes outlined in this document are incorporated into the product labels,
then all current risks for PHMB will be substantially mitigated for the purposes of this
determination.
B. Public Comments and Responses
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decision for PHMB. During the public comment period on the
risk assessments, which closed on September 27, 2004, the Agency received numerous
comments that addressed human health and ecological concerns from one of the technical
registrants (Arch Chemicals, Inc.); state and local regulatory agencies (California Regional
Water Quality Control Board and San Francisco Department of the Environment); an
environmental group (Natural Resources Defense Council [NRDC]); water advocacy groups
(Sanitation Districts of Los Angeles County and California Stormwater Quality Association);
and one private citizen. Comments were received on the following topics:
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• Toxicology and Mode of Action of PHMB and Endpoints Chosen;
Ecological Risks of PHMB;
Exposure to PHMB;
• Occupational and Residential Exposure to and Risk from PHMB;
• Dietary Exposure and Risk Assessment;
• Efficacy of PHMB as a Swimming Pool Sanitizer; and
• Abbreviated Length of Public Comment Period.
These comments have been addressed and the assessments refined, as appropriate, by the
Agency. Response to Comments documents addressing these comments, and those received by
the registrants during Phase I of the RED process, are available in the public docket at
http ://www. epa. (OPP-2004-0305).
Comments that were received comments from the California Regional Water Quality
Control Board, San Francisco Department of the Environment, Sanitation Districts of Los
Angeles County, and California Stormwater Quality Association on the possible release of
PHMB to surface waters are being addressed in the RED as follows:
Comment: Two governmental and two advocacy groups submitted comments in late
September 2004 stating the following (exact language differed slightly among
comments): Despite uses that will inevitably discharge PHMB to surface waters,
the U.S. EPA re-registration risk assessment does not estimate surface water
concentrations. U.S. EPA incorrectly assumes that environmental exposure to
PHMB will not occur. Whether discharged to a storm drain or a wastewater
treatment plant, PHMB will flow to surface water. It provides no chronic toxicity
data for aquatic organisms and presents no estimates of PHMB's environmental
fate. The risk assessment provides no scientific basis for evaluating PHMB risks
to aquatic organisms. These risks must be assessed prior to reregistration.
Response: For certain use categories, such as indoor sanitizers or contained outdoor uses,
such as swimming pools, the environmental exposure will be limited in most
cases, due either to treatment of wastewaters discharged through municipal
sewers and/or Federal or Local restrictions on how wastewaters are to be handled.
For such uses, environmental modeling is not currently performed, 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 currently undergo a full screening-level risk assessment and are
considered to fall under a "no effect" determination. The indoor uses of PHMB,
as well as the swimming pool use, fall into this category.
While unauthorized discharges into storm sewers, into surrounding waters, or
onto the ground could occur, this would be considered a misuse of the pesticide.
Illegal uses, or "misuses," of pesticides are not considered in Office of Pesticide
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Program risk assessments; the assessments are based on the correct, labeled use of
the pesticide products. In addition, AD recognizes the possibility of some of
these pesticides entering into US waterways, which may pose exposure and
hazard concerns. We are in the process of developing and validating various
modeling programs, which will help us to ascertain that pesticides entering into
U.S. water ways, as well as into the municipal waste treatment plants, are not at
levels of concern.
As stated in the 40CFR§158, the Agency requires a standard set of environmental
fate and aquatic toxicity studies to be submitted for indoor uses, including
hydrolysis, acute avian oral toxicity, acute freshwater fish toxicity, and acute
freshwater invertebrate toxicity. These data requirements have been fulfilled for
PHMB, and the database is considered adequate for the purposes of this risk
assessment.
Due to the abbreviated nature of the comment period held on the risk assessments in
2004, the Agency is providing a 60-day public comment period on this RED. While all
comments are welcome, those with specific data or information bearing on the risk assessments
are most useful.
C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with PHMB. The Agency has concluded that the risk from dietary exposure is within the "risk
cup." An aggregate assessment was conducted for exposures through food and residential uses.
Dietary exposure from drinking water was not assessed, as the uses of PHMB have been
determined to have no impact on surface or ground water. The Agency has determined that the
human health risks from these combined exposures are within acceptable levels. In reaching this
determination, EPA has considered the available information on the special sensitivity of infants
and children, as well as aggregate exposure from food and residential uses.
b. Determination of Safety to U.S. Population
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with PHMB. The Agency has determined that food uses of PHMB, meet the safety standards
under the FQPA amendments to section 408(b)(2)(D) of the FFDCA, and that there is a
reasonable certainty no harm will result to the general population or any subgroup from the use
of PHMB. In reaching this conclusion, the Agency has considered all available information on
the toxicity, use practices and exposure scenarios, and the environmental behavior of PHMB.
Dietary risk assessments were conducted for adults and children, with the highest risk
(9% aPAD for adult females and 37%cPAD for children) being below the Agency's level of
concern. Aggregate assessments from dietary and residential exposures were also conducted.
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The Aggregate Risk Index was 1.2 for children ages 7-10 years, the subpopulation with the
greatest risk, which is above the Agency's level of concern (ARI 1).
c. Determination of Safety to Infants and Children
EPA has determined that the currently registered uses of PHMB, with changes as
specified in this document, meet the safety standards under the FQPA amendments to section
408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants and
children. The safety determination for infants and children considers factors of the toxicity, use
practices, and environmental behavior noted above for the general population, but also takes into
account the possibility of increased susceptibility to the toxic effects of PHMB residues in this
population subgroup.
No Special FQPA Safety Factor is necessary to protect the safety of infants and children.
In determining whether or not infants and children are particularly susceptible to toxic effects
from PHMB residues, the Agency considered the completeness of the database for
developmental and reproductive effects, the nature of the effects observed, and other
information. The FQPA Safety Factor has been removed (i.e., reduced to IX) for PHMB based
on: (1) there is no concern for developmental neurotoxicity resulting from exposure to PHMB
because there is no evidence PHMB will induce neurotoxic effects; (2) there is no quantitative or
qualitative evidence of increased susceptibility to the fetus following in utero exposure in the
prenatal developmental toxicity studies or to the offspring when adults are exposed in the two-
generation reproductive study; and (3) the risk assessment does not underestimate the potential
exposure for infants and children.
d. Endocrine Disrupter Effects
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 endocrine effects as the Administrator may designate." Following
recommendations of its Endocrine Disrupter Screening 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 EPA include evaluations of
potential effects in wildlife. For pesticides, 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 Disrupter Screening
Program (EDSP).
When the appropriate screening and/or testing protocols being considered under the
EDSP have been developed, PHMB may be subject to additional screening and/or testing to
better characterize effects related to endocrine disruption.
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e. Cumulative Risks
Risks summarized in this document are those that result only from the use of PHMB.
The Food Quality Protection Act (FQPA) requires that the Agency consider "available
information" concerning the cumulative effects of a particular pesticide's residues and "other
substances that have a common mechanism of toxicity." The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. 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 for PHMB.
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 htt^/wjywJ^ga^goy/pesticides/cujTiujatiy^/.
2. Tolerance Summary
There are no tolerances or exemptions from the requirement of a tolerance established for
residues of PHMB.
D. Regulatory Rationale
The Agency has determined that PHMB is eligible for reregistration provided that
additional required data confirm this decision, the risk mitigation measure outlined in this
document are adopted, and label amendments are made to reflect this measure.
The following is a summary of the rationale for managing risks associated with the use of
PHMB. Where labeling revisions are warranted, specific language is set forth in the summary
tables of Section V of this document.
1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
The acute and chronic dietary risks from PHMB residues on food, estimated using
conservative measures, are below the Agency's level of concern. Therefore, no mitigation
measures are necessary at this time.
b. Drinking Water Risk Mitigation
As none of the uses associated with PHMB are expected to impact either surface or
ground water resources, no drinking water mitigation measures are necessary at this time.
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c. Residential Risk Mitigation
i. Handler Risk Mitigation
Residential handler risks were considered for pouring PHMB into a single swimming
pool, spraying an all-purpose cleaner, mopping floors with an all-purpose cleaner, and wiping
hard surfaces with an all-purpose cleaner. No mitigation measures are needed at this time for
these uses, as none present a risk of concern.
ii. Post-Application Risk Mitigation
High-end exposures were assessed for residential exposure after application of PHMB
products in swimming pools and spas, as well as on hard surfaces. All risks were below the
Agency's level of concern, and no mitigation measures are presently required.
d. Occupational Risk Mitigation
i. Handler Risk Mitigation
EPA determined that the greatest potential for exposure appears to be the inhalation and
dermal occupational scenarios involving pour liquid for drilling muds and workover fluids.
Using an open pour scenario, these risks are of concern to the Agency. In order for risks to drop
below the Agency's level of concern, scenarios involving drilling muds and workover fluids
must use mitigation measures such as metering pump systems.
ii. Post-Application Risk Mitigation
At this time, EPA does not foresee post-application exposures for the occupational uses
of PHMB; therefore, no mitigation measures are necessary.
2. Environmental Risk Management
As the Agency considers the uses of PHMB assessed in this RED to be unlikely to result
in any appreciable exposure to terrestrial or aquatic organisms, no environmental risk mitigation
is required.
3. Other Labeling Requirements
In order to be eligible for reregistration, various use and safety information will be
included in the labeling of all end-use products containing PHMB. For the specific labeling
statements and a list of outstanding data, refer to Section V of this RED document.
4. Listed Species Considerations
a. The Endangered Species Act
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
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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
LOG 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, and are considered to fall under a "no effect" determination. Due to the low
likelihood of exposure and low toxicity of PHMB, the Agency expects no effects to listed species
or critical habitat and therefore makes a "No Effect" determination for this chemical.
b. General Risk Mitigation
PHMB end-use products (EPs) may also contain other registered pesticides. Although
the Agency is not proposing any mitigation measures for products containing PHMB specific to
federally listed species, the Agency needs to address potential risks from other end-use products.
Therefore, the Agency requires that users adopt all listed species risk mitigation measures for all
active ingredients in the product. If a product contains multiple active ingredients with
conflicting listed species risk mitigation measures, the more stringent measure(s) should be
adopted.
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V. What Registrants Need to Do
The Agency has determined that PHMB is eligible for reregistration provided that: (i)
additional data that the Agency intends to require confirm this decision; (ii) the risk mitigation
measure outlined in this document is adopted; and (iii) label amendments are made to reflect this
measure. To implement the risk mitigation measure, the registrants must amend their product
labeling to incorporate the label statement set forth in the Label Changes Summary Table in
Section B below (Table 13). The additional data requirements that the Agency intends to obtain
will include, among other things, submission of the following:
For PHMB technical grade active ingredient products, the registrant needs to submit the
following items:
Within 90 days from receipt of the generic data call-in (DCI):
1. completed response forms to the generic DCI (i.e., DCI response form and
requirements status and registrant's response form); and
2. submit any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI:
1. cite any existing generic data which address data requirements or submit new generic
data responding to the DCI.
Please contact Jennifer Slotnick at (703) 305-0601 with questions regarding generic
reregistration.
By US mail:
Document Processing Desk (DCI/SRRD)
Jennifer Slotnick
US EPA (75IOC)
1200 Pennsylvania Ave., NW
Washington, DC 20460
By express or courier service:
Document Processing Desk (DCI/SRRD)
Jennifer Slotnick
Office of Pesticide Programs (75 IOC)
Room 266A, Crystal Mall 2
1801 S. Bell Street
Arlington, VA 22202
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For end-use products containing the active ingredient PHMB, the registrant needs to submit the
following items for each product.
Within 90 days from the receipt of the product-specific data call-in (PDCI):
1. completed response forms to the PDCI (i.e., PDCI response form and requirements
status and registrant's response form); and
2. submit any time extension or waiver requests with a full written justification.
Within eight months from the receipt of the PDCI:
1. two copies of the confidential statement of formula (EPA Form 8570-4);
2. a completed original application for reregistration (EPA Form 8570-1). Indicate on
the form that it is an "application for reregistration";
3. five copies of the draft label incorporating all label amendments outlined in Table 23
of this document;
4. a completed form certifying compliance with data compensation requirements (EPA
Form 8570-34);
5. if applicable, a completed form certifying compliance with cost share offer
requirements (EPA Form 8570-32); and
6. the product-specific data responding to the PDCI.
Please contact Adam Heyward at (703) 308-6422 with questions regarding product
reregistration and/or the PDCI. All materials submitted in response to the PDCI should be
addressed as follows:
By US mail: By express or courier service:
Document Processing Desk (PDCI/PRB) Document Processing Desk (PDCI/PRB)
Adam Heyward Adam Heyward
US EPA (75 IOC) Office of Pesticide Programs (75 IOC)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 South Bell Street
Arlington, VA 22202
32
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A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of PHMB has been reviewed and
determined to be substantially complete. However, the following additional data requirements
have been identified by the Agency as confirmatory and included in the generic DCI for this
RED.
The Agency has established an interim two-tiered system for toxicology testing
requirements. Tier I toxicology data requirements would apply to all indirect food additives that
result in residue concentrations ranging from 0-200ppb which applies to PHMB. The
requirements would consist of an acute toxicity testing battery, subchronic toxicity study in the
rodent, a developmental toxicity study in the rat, and a mutagenicity testing battery. Each of
these data requirements has been fulfilled for PHMB. The Agency also conducts a literature
search and can also conduct a Structural Activity Relationship analysis (SAR) if appropriate.
The Agency also will hold in reserve a two-generation reproduction toxicity study in the rat and
a subchronic toxicity study in a non-rodent which would become data requirements if the
Agency's evaluation of the Tier 1 data warranted. A 2-generation reproduction study and a
subchronic toxicity study in a non-rodent species are available for PHMB.
Tier II studies would be triggered by the presence of significant (i.e. >200ppb) residues in
food or evidence of significant toxicity from the Tier I data set, which may include
developmental / reproductive, or other systemic toxicity such as presence of neoplastic growth or
significant target organ toxicity. In such cases, chronic toxicity and carcinogenicity testing would
be required.
The risk assessment noted deficiencies in the surrogate dermal and inhalation exposure
data available from the Chemical Manufacturers Association (CMA) data base. Therefore, the
Agency is requiring confirmatory data to support the uses assessed with the CMA exposure data
within this risk assessment. The risk assessment also noted that many of the use parameters
(e.g., amount handled and duration of use) were based on professional judgments. Therefore,
descriptions of human activities associated with the uses assessed are required as confirmatory.
Table 11. Confirmatory Data Requirements for Reregistration
Guideline Study Name
Dermal Indoor Exposure
Inhalation Indoor Exposure
Descriptions of Human Activity
Dietary-Residues in Food from Treating
Countertops with PHMB (FDA Wipe Study
Methodology) (FDA, 2003a and 2003b)
New OPPTS Guideline No.
875.1200,875.1600
875.1400,875.1600
875.2800
Non-Guideline
Old Guideline No.
233,236
234, 236
133-1
Non-Guideline
33
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2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing-use product (MP)
labeling should be revised to comply with all current EPA regulations, PR Notices and
applicable policies. The Technical and MP labeling should bear the labeling contained in Table
13, Label Changes Summary Table.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. The Registrant
must review previous data submissions to ensure that they meet current EPA acceptance criteria
and if not, commit to conduct new studies. If a registrant believes that previously submitted data
meet current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product.
A product-specific data call-in, outlining specific data requirements, will be sent to
registrants at a later date. The efficacy studies the Agency intends to call-in are listed in Table
12 below.
Table 12. Efficacy Data Requirements for Reregistration
Claim
Disinfectant
Sanitizer
Sanitizer
Use Pattern
Hard inanimate
surfaces
Non-food contact
surfaces (non-
residual)
Swimming
Pools/Spas
EPA Reg. Nos.
71661-1
5813-75
1258-1263
1258-1265
1258-1275
7124-105
69461-1
71864-2
81002-2
Guideline Study Name
AOAC Use Dilution Test (Hard
water and organic soil) or
AOAC Germicidal Spray Test or
AOAC Hard Surface Carrier Test
(Distilled water only)
Sanitizer Test for Hard Inanimate
Non-Food Contact Surfaces
AOAC Method for Water
Disinfectants for Swimming Pools
New OPPTS
Guideline
No.
810.2100
(c), (d), (e)
810.2100 (1)
810.2700 (d)
Old
Guideline
No.
91-2 (b),
(c), (d)
91-2 CD
91-8 (c)
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section IV above.
Specific language to incorporate these changes is specified in Table 13.
34
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Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision document.
Persons other than the registrant may generally distribute or sell such products for 52 months
from the approval of labels reflecting the mitigation described in this RED. However, existing
stocks time frames will be established case-by-case, depending on the number of products
involved, the number of label changes, and other factors. Refer to "Existing Stocks of Pesticide
Products; Statement of Policy," Federal Register, Volume 56, No. 123, June 26, 1991.
a. Label Changes Summary Table
In order to be eligible for reregistration, amend all product labels to incorporate the risk
mitigation measure outlined in Section IV. The following table describes how language on the
labels should be amended.
35
-------
Table 13. Labeling Changes Summary Table
Description
Amended Labeling Language
Placement on Label
For all Manufacturing Use
Products
"Only for formulation into algicides, bacteriostats^acteriocides, fungistats/fungicides,
microbiostats/microbiocides, disinfectants, regulators, and sanitizers for the following uses:
hard surfaces (food-contact and non food-contact); swimming pools and spas; cut ornamental
plants; materials preservatives; drilling muds, packer fluids, and workover fluids; oil field
injection water; and tunnel pasteurization water."
Directions for Use
Environmental Hazards
Statements Required by the
RED and Agency Label Policies
"This product is toxic to fish and aquatic invertebrates. 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 Pollution Discharge Elimination System (NPDES) permit
and the permitting authority has been 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."
Precautionary
Statements
End Use Products Intended for Occupational Use
PPE Requirements1
"Wear goggles or face shield when handling concentrate."
Immediately
following^elow
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Engineering Controls
for Formulations Used in
Drilling Muds and Workover
Fluids
"Scenarios involving drilling muds and workover fluids must use metering pump systems.'
Precautionary
Statements: Hazards to
Humans and Domestic
Animals (Immediately
Following User Safety
Requirements.)
36
-------
User Safety Recommendations
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the
toilet.
Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly
and put on clean clothing.
Users should remove PPE immediately after handling this product. Wash the outside of gloves
before removing*. As soon as possible, wash thoroughly and change into clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
(Immediately
Following Engineering
Controls
(Must be placed in a
box.)
Environmental Hazards -for
Labels with Oil Recovery Uses
"Not for use in oil recovery systems which employ holding ponds for spent liquids. Do not
apply in, over, or near marine and/or estuarine oil fields."
Directions for Use
End Use Products Intended for Residential Use
PPE Requirements1
"Wear goggles or face shield when handling concentrate."
Immediately
following^elow
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Application Restrictions-For
Products Used in Swimming
Pools/Spas
"Do not use with chlorine- or bromine-based pool products.
Directions for Use
under General
Precautions and
Restrictions
Application Restrictions-For
Products Used on Food-Contact
Surfaces
"Rinse food-contact surfaces with potable water prior to reuse. Do not use on glasses, dishes,
or utensils."
Directions for Use
under General
Precautions and
Restrictions
37
-------
Application Restrictions-For
Products Used in Animal/Pet
Areas
"Remove animals and feeds. Remove litter, droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances. Rinse all food-contact surfaces with potable
water prior to reuse. Ventilate buildings/closed spaces."
Directions for Use
under General
Precautions and
Restrictions
Application Restrictions-For
Products Used in Mushroom
Houses
"Do not apply directly to the mushroom crop, compost, or casing. Rinse treated surfaces with
potable water before they contact the crop, compost, or casing."
Directions for Use
under General
Precautions and
Restrictions
Entry Restrictions-For Products
Used in Animal/Pet Areas,
Veterinary Offices, and Pet
Kennels
"Wait for treatment to have dried to house animals or employ equipment.'
Directions for use
under General
Precautions and
Restrictions
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document. The more protective PPE must be
placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
38
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VI. APPENDICES
39
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Appendix A. Table of Use Patterns for PHMB
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Agricultural premises and equipment
Hog
Barns/Houses/Parlors/
Pens (Enclosed Premise
Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Farm Premises
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Farrowing Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
1 Application rate is given in terms of end-use product, not active ingredient.
40
-------
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Livestock Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Livestock Feeding
Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Livestock Premises
(Enclosed Premise
Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
41
-------
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Livestock Watering
Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Mushroom House
Premises
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Do not apply directly to the mushroom crop,
compost, or casing. Rinse treated surfaces with
potable water before they contact the crop,
compost, or casing.
Poultry Feeding
Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Poultry House Premises
(Enclosed Premise
Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
42
-------
Use Site
Poultry Watering
Equipment
Formulation
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Remove all animals/feed. Remove all litter and
manure. Empty feeding/watering appliances.
Ventilate buildings, vehicles, and other enclosed
spaces. Do not house animals or employ
equipment until treatment has been absorbed, set,
or dried. Thoroughly scrub all feeding/watering
appliances with soap or detergent and rinse with
potable water before reuse.
Food handling/storage establishments premises and equipment
Tunnel
Pasteurization/Cooling
(Bottle/Can Wash) Water
Eating Establishments
(Non-Food Contact
Surfaces, Premises, Food-
Contact Surfaces)
Aqueous
Solution
(Reg. 1258-
1253)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
100-1,000 ppm
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Commercial, institutional and industrial premises and equipment
Commercial Equipment
Commercial Premises
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
43
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Use Site
Commercial
Transportation Facilities
Industrial Equipment
Industrial Premises
Institutional Equipment
Institutional Premises
Athletic Facilities
Barber and Beauty Shop
Premises
Aircraft (NonFeed/Food)
Formulation
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
44
-------
Use Site
Buses
(Nonfeed/Nonfood)
Railroad Trains
Ships
Trucks
Animal Cages
Animal Equipment
Formulation
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
45
-------
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Animal Feeding/Watering
Equipment
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Catteries (Enclosed
Premise Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Horse Stables (Enclosed
Premise Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Research Animal
Facilities (Enclosed
Premise Treatment)/
Animal Laboratories
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
46
-------
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Veterinary Hospital
Premises
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Zoo Premises (Enclosed
Premise Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Laundry Premises
(Commercial)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Urinals
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Coils/Drain Pans (Air
Conditioning/
Refrigeration Equipment
and Heat Pumps)
(Commercial/
Institutional/Indu strial)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Playground Equipment
(Institutional)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
47
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Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Residential and public access premises
Automobiles
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Boat Premises
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Pet Kennels (Enclosed
Premise Treatment)
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Pet Sleeping Quarters
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
Pet Areas
Ready-to-Use
Solution
(Reg. 71661-1)
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Remove animals and feeds. Remove litter,
droppings, and manure from all floors and other
surfaces. Empty all feeding/watering appliances.
Rinse all food contact surfaces with potable water
prior to reuse. Ventilate buildings/closed spaces.
Wait for treatment to have dried to house animals
or employ equipment.
48
-------
Use Site
Campers
Garbage Containers
Laundry Premises
(Residential)
Sinks
Stovetops
Residential Food-Contact
Surfaces (Microwave
Ovens/Refrigerators/
High Chairs/Tables)
Formulation
Ready-to-Use
Solution
(Reg. 71661-1)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
49
-------
Use Site
Bathroom Premises
Whirlpool Bath Surfaces
Diaper Pails
Domestic Dwellings
(House Trailer)
Household Contents
Household Contents
(Nursery)
Formulation
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
50
-------
Use Site
Household Floors
Household Premises
Mobile Homes (Indoor)
Coils/Drain Pans (Air
Conditioning/
Refrigeration Equipment
and Heat Pumps)
(Residential)
Formulation
Ready-to-Use
Solution
(Mopping
System)
(Reg. 5813-75)
Ready-to-Use
Solution
(Reg. 71661-1)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
24 fl.oz. lasts about 2-3
months under "normal
use"-mop has trigger
to dispense solution
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
51
-------
Use Site
Ornamental Flowering
Plants (Cut)
Furniture (Outdoor)
Campgrounds
Playground Equipment
(Residential)
Formulation
Powder (Water
Soluble
Packaging)
(Reg. 72992-2;
72992-8)
Soluble
Concentrate
(Reg. 72992-3;
72992-7)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
lOg per 2.6 quarts of
water
0. 17 oz (5g) per pint
(!/2 qt) of water2
10,000 -15,000 ppm
solution
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
2 Although the application rate of product is different, the application rate of active ingredient (as calculated by multiplying the
product application rate by the concentration of active ingredient in the product) is approximately 0.96g PFDVIB per quart of water.
3The application rate for both products is 900 ppm of active ingredient due to differences in the concentration of the active
ingredient in the product formulations.
52
-------
Use Site
Formulation
Application Rate
(Range)1
No. of
Applications
Use Limitations
Medical premises and equipment
Hospital Materials
Hospital Premises
Human Nursery
Equipment
Human Nursery Premises
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Impregnated
Wipe
(Reg. 50096-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
1 wipe lasts 20 uses
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
53
-------
Use Site
Nursing Home Premises
Dental Offices
Formulation
Ready-to-Use
Solution
(Reg. 71661-1)
Ready-to-Use
Solution
(Reg. 71661-1)
Application Rate
(Range)1
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
Thoroughly wet
(saturate) all surfaces
for 10 minutes.
No. of
Applications
Use Limitations
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Rinse food contact surfaces with potable water
prior to reuse. Do not use on glasses, dishes, or
utensils.
Materials preservatives
Adhesives/Glues
(Aqueous-Based)
(Indirect Food Contact)
Aqueous Industrial
Chemicals (Reagents/Oil-
in-Water
Emulsions/Water-in-Oil
Emulsions/Textile Spin
Finish Lubricants/Wash
Water/Cellulose Solutions
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
500-5,000 ppm
100-5,000 ppm
54
-------
Use Site
Cellulosic Materials
Industrial Electrocoats
(Resins and Deposition
Systems)
Household Consumer
Products
Leather Products and
Hides/Skins (Fresh
Animal)
Polymer Latices
(Aqueous-Based) (i.e.
Polyvinyl
Acetate/Alcohol)
Formulation
Aqueous
Solution (Apply
by padding,
spraying,
soaking, or
exhaustion)
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Application Rate
(Range)1
0.025-2% on dry
weight of substrate
1,000-5,000 ppm
250-2,500 ppm
15 floz.-3 gal [1.0-2.6
Ibs product per 1,000
Ibs hides/skins]
500-5,000 ppm
No. of
Applications
Use Limitations
Use prior to or during processing
55
-------
Use Site
Silicone
Emulsions/Dispersions
Slurries (Aqueous)
(Indirect Food Contact)
Textiles
Formulation
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution (Apply
by padding,
spraying,
soaking, or
exhaustion)
(Reg. 1258-
1253)
Application Rate
(Range)1
100-5,000 ppm
500-5,000 ppm
0.025-2% on dry
weight of substrate
No. of
Applications
Use Limitations
(8) Industrial processes and water systems
Leather Processing
Liquors/Solutions
Aqueous
Solution
(Reg. 1258-
1253)
100-3,000 ppm
56
-------
Use Site
Oil Recovery Drilling
Muds/Packer Fluids
Workover Fluids
Secondary Oil Recovery
Injection Water
Formulation
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Aqueous
Solution
(Reg. 1258-
1253)
Application Rate
(Range)1
3,000 ppm
3,000 ppm
95 ppm
47 ppm
4-20 ppm
No. of
Applications
Slug
Weekly
Continuous
Use Limitations
Not for use in oil recovery systems which employ
holding ponds for spent liquids. Do not apply in,
over, or near marine and/or estuarine oil fields.
Not for use in oil recovery systems which employ
holding ponds for spent liquids. Do not apply in,
over, or near marine and/or estuarine oil fields.
Not for use in oil recovery systems which employ
holding ponds for spent liquids Do not apply in
over, or near marine and/or estuarine oil fields.
Apply slug treatment to a point where system will
be uniformly mixed. Weekly follows slug
treatment when microbial control is evident.
Before continuous treatment, apply a slug
treatment.
Swimming pools
Swimming Pool Water
Systems
Ready-to-Use
Solution
(Reg. 1258-
1263; 1258-
1265; 7124-105;
69461-1; 71864-
2; 81002-2)
Maintain
Concentration of 30-50
ppm
Weekly/As
Necessary
Cannot use with chlorine or bromine based pool
products.
57
-------
Use Site
Hot Tubs/Spas (Water
Treatment)
Formulation
Tablets (Soluble
Concentrate)
(Reg. 1258-
1275)
Ready-to-Use
Solution
(Reg. 1258-
1263; 1258-
1265; 69461-1;
71864-2)
Application Rate
(Range)1
Maintain
Concentration of 6- 1 0
ppm
Maintain
Concentration of 30-50
ppm
No. of
Applications
Weekly/As
Necessary
Weekly/As
Necessary
Use Limitations
Cannot use with chlorine or bromine based pool
products.
Cannot use with chlorine or bromine based pool
products.
58
-------
Appendix B. Table of Generic Data Requirements and Studies Used to Make the Reregistration Decision
Guide to Appendix B
Appendix B contains listing of data requirements which support the reregistration for active ingredients within case #3144
(PHMB) covered by this RED. It contains generic data requirements that apply to PHMB in all products, including data requirements
for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data Requirement (Column 1). The data requirements are listed in the order in which they appear in 40 CFR part 158.
The reference numbers accompanying each test refer to the test protocols set in the Pesticide Assessment Guidance, which are
available from the National technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703) 487-4650.
2. Use Pattern (Column 4). This column indicates the use patterns for which the data requirements apply. The following
letter designations are used for the given use patterns.
(1) Agricultural premises and equipment
(2) Food handling/ storage establishments premises and equipment
(3) Commercial, institutional and industrial premises and equipment
(4) Residential and public access premises
(5) Medical premises and equipment
(6) Human water systems
(7) Materials preservatives
(8) Industrial processes and water systems
(9) Antifouling coatings
(10) Wood preservatives
(11) Swimming pools
(12) Aquatic areas
3. Bibliographic Citation (Column 5). If the Agency has acceptable data in its files, this column list the identify number
of each study. This normally is the Master Record Identification (MRID) number, but may be a "GS" number if no MRID number has
been assigned. Refer to the Bibliography appendix for a complete citation of the study.
59
-------
DATA REQUIREMENT
New Guideline
Number
Old Guideline
Number
Study Title
Use Pattern
CITATION(S)
MRID Number
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.7050
830.7200
830.7220
830.7300
830.7840
830.7860
830.7950
830.7370
61-1
61-2a
61-2b
62-1
62-2
62-3
63-2
63-3
63-4
None
63-5
63-6
63-7
63-8
63-9
63-10
Product Identity and Composition
Starting Materials and Manufacturing Process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Color
Physical State
Odor
UV/Visible Absorption
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant in Water
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
41965401, 42728901
41894001,41930701
41965401, 42728903
41965401
42728902, 41965401
42728902, 41965401
41966401
41966401
41966401
Waived1
41966401
41966401
41966401
41966401
41966401
41966401
Study waived because the chemical structure shows that it will not absorb in the UV spectral region.
60
-------
DATA REQUIREMENT
New Guideline
Number
830.7550
830.7560
830.7570
830.7000
830.6313
830.6314
830.6315
830.6316
830.6317
830.7100
830.6319
830.6320
830.6321
Old Guideline
Number
63-11
63-12
63-13
63-14
63-15
63-16
63-17
63-18
63-19
63-20
63-21
Study Title
Partition Coefficient (Octanol/Water)
PH
Stability
Oxidizing/Reducing Action
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
Corrosion Characteristics
Dielectric breakdown voltage
Use Pattern
All
All
All
All
All
All
All
All
All
All
All
CITATION(S)
MRID Number
41687001
41966401
42728902
Not Applicable
Not Applicable
Not Applicable
42728902
Not Applicable
Not Applicable
Not Applicable
Not Applicable
ECOLOGICAL EFFECTS
850.2100
850.2200
850.1075
850.1010
850.1075
71-1
71-2
72-1
72-2
72-3a
Avian Acute Oral Toxicity Test
Avian Dietary Toxicity
Fish Acute Toxicity - Freshwater
Acute Aquatic Invertebrate Toxicity
Acute Estuarine/Marine Toxicity - Fish
All
All
All
All
8
27491(93191001)
41382(93191002)
ACC 234289 (MRID 77928 and
77929), 43949001
ACC 234289 (MRID 77929)
Waived2
' Label precludes use in, over, or near marine and/or estuarine environments. Therefore, Guidelines 850.1075 and 850.1025 are waived.
61
-------
DATA REQUIREMENT
New Guideline
Number
850.1025
Old Guideline
Number
72-3b
72-3c
Study Title
Acute Estuarine/Marine Toxicity - Invertebrate (Mollusk)
Estuarine/Marine Toxicity - Invertebrate (Shrimp)
Use Pattern
8
8
CITATION(S)
MRID Number
Waived2
Waived2
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3200
870.3250
870.3465
870.3700
870.3800
81-1
81-2
81-3
81-4
81-5
81-6
82-la
82-lb
82-2
82-3
82-4
83-3
83-4
Acute Oral - Rat
Acute Dermal - Rabbit
Acute Inhalation - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization
90-Day Feeding-Rodent
90-Day Feeding-Non-Rodent
21/28-Day Dermal Toxicity - Rat
90-day Dermal Toxicity - Rodent
90-Day Inhalation - Rat
Developmental Toxicity
Reproduction and Fertility Effects - 2 Generation Repro
All
All
All
All
All
All
All
All
All
All
All
All
All
30330 (93191005), 44940701,
45916505
65124, 44940702, 45916506
44970403
46789, 65120, 44963902, 45916508
46789, 65120, 44949704, 45916509
42674201, 44940705
Waived3
53461
43047701
Waived4
Data gap
65 131 (rodent), 42992 10 15
(rodent), 42865901 (non-rodent)
43617401
Study waived because Guideline 83-la (Chronic Toxicity-Rodent) satisfies this data requirement.
Study waived because 80-week dermal cancer study in mice submitted under Guideline 83-2b satisfies requirement.
1 MRID 42992101 is an upgrade to the original study, MRID 65131.
62
-------
DATA REQUIREMENT
New Guideline
Number
870.4100
870.4200
870.4300
870.5265
870.5385
870.5375
870.5550
870.7485
870.7600
Old Guideline
Number
83-la
83-lb
83 -2a
83 -2b
83-5
84-2
84-2
84-2
84-2
85-1
85-2
Study Title
Chronic Feeding Toxicity - Rodent
Chronic Feeding Toxicity - Non-Rodent (dog)
Oncogenicity - Rat
Oncogenicity - Mouse
Combined Chronic Toxicity/Carcinogenicity
Bacterial Reverse Mutation Assay
Micronucleus Assay
Cytogenic assay with human lymphocytes
UDS Assay
General Metabolism
Dermal Absorption
Use Pattern
2,3,4,5,7,11
2,3,4,5,7,11
11
11
11
All
All
All
All
2,3,4,5,7,11
11
CITATION(S)
MRID Number
44059301, 44042801
43620501
44059301, 44042801
44074201 (oral), 93191028 (dermal),
66475(dermal), 104796 (dermal)
44059301
41687004
41096901, 41404503
41404501, 42149905
41404502, 42149903
43599901, 43567001, 77926, 86363
Waived6
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.2800
875.2400
875.2900
875.2500
875.2900
875.1200
875.1600
875.1400
875.1600
133-1
133-3
133-4
233
234
Description of Human Activity
Dermal Passive Dosimetry
Inhalation Passive Dosimetry
Dermal Indoor Exposure
Inhalation Indoor Exposure
All
11
11
All
All
Data Gap
44051301
44051301
Data Gap
Data Gap
Study waived because 80-week dermal cancer study submitted under Guideline 83-2b in mice satisfies requirement.
63
-------
DATA REQUIREMENT
New Guideline
Number
Old Guideline
Number
Study Title
Use Pattern
CITATION(S)
MRID Number
ENVIRONMENTAL FATE
835.2120
161-1
Hydrolysis
All
43622301
OTHER DATA REQUIREMENTS
Non-Guideline
Non-Guideline
Dietary-Residues in Food from Treating Countertops with
PHMB (FDA Wipe Study Methodology7)
2,3,4,5
Data Gap
FDA, 2003a. "Guidance For Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry
Recommendations. Final Guidance." US Food and Drug Administration. April 2003. http://www.cfsan.fda.gov/~dms/opa2pmnc.html.
FDA, 2003b. "Sanitizing Solutions:Chemistry Guidelines for Food Additive Petitions." US Food and Drug Administration. January, 1993.
http://www.cfsan.fda.gov/~dms/opa-cg3a.html. 64
-------
Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP docket,
located in Room 119, Crystal Mall #2, 1801 Bell Street, Arlington, VA. It is open Monday
through Friday, excluding legal holidays, from 8:30 am to 4 pm.
The docket initially contained the August 26, 2004 preliminary risk assessment and the
related documents. EPA then considered comments on these risk assessments (which are posted
to the e-docket) and revised the risk assessments. The revised risk assessments will be posted in
the docket at the same time as the RED.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following sites:
http://www.epa.gov/pesticides/antimicrobials
http ://www. epa. gov/edockets
These documents include:
Poly(hexamethylenebiguanide) hydrochloride Preliminary Risk Assessment; Notice of
Availability, 9/10/04.
Poly(hexamethylenebiguanide) hydrochloride (PHMB) Summary, 8/30/04.
Overview of the PHMB Preliminary Risk Assessment, 8/24/04.
Preliminary Risk Assessment and Supporting Science Documents:
Poly(hexamethylenebiguanide) hydrochloride (PHMB): Preliminary Risk Assessment for
the Reregistration Eligibility Decision, PC Code 111801, Case 3122, Antimicrobials
Division, 8/26/04.
Product Chemistry Science Chapter on PHMB (20% Formulations of Vantocil P and
Vantocil IB). PC Code 111801, Case 3122, Antimicrobials Division, 8/4/04, A. Najm
Shamim, Ph.D.
PHMB - 2nd Report of the Hazard Identification Assessment Review Committee, TXR
No. 0051756, Health Effects Division, 4/9/03, Jonathan Chen, Ph.D.
Cancer Assessment Document: Evaluation of the Carcinogenic Potential of PHMB, PC
Code 111801, Case 3122, TXR No. 0052040, Health Effects Division, 7/16/03, Jessica
Kidwell, Executive Secretary, Cancer Assessment Review Committee.
Poly(hexamethylenebiguanide) hydrochloride (PHMB): Toxicology Disciplinary Chapter
for the Reregistration Eligibility Decision Document, PC Code 111801, Case 3122,
Antimicrobials Division, 8/26/04, Jonathan Chen, Ph.D. and Timothy F. McMahon,
Ph.D.
PHMB Dietary Exposure Assessments for the Reregistration Eligibility Decision. PC
Code 111801, Case 3122, Antimicrobials Division, 8/26/04, A. Najm Shamim, Ph.D.
PHMB Occupational/Residential Exposure Assessment. PC Code 111801, Case 3122,
Antimicrobials Division, 8/19/04, Timothy Leighton, Ph.D.
Health Effects of PHMB in Humans. PC Code 111801, Case 3122, Antimicrobials
65
-------
Division, 8/4/04, Jonathan Chen, Ph.D.
Environmental Fate Assessment of PHMB for the Reregistration Eligibility Decision
(RED). PC Code 111801, Case 3122, Antimicrobials Division, 8/18/04, A. Najm
Shamim, Ph.D.
Ecological Hazard and Environmental Risk Assessment: Poly(hexamethlenebiguanide)
hydrochloride (PHMB). PC Code 111801, Case 3122, Antimicrobials Division, 8/4/04,
Kathryn Montague, M.S.
Revised Risk Assessment and Supporting Science Documents (RED Supporting Documents):
Poly(hexamethylenebiguanide) hydrochloride (PHMB): Risk Assessment for the
Reregistration Eligibility Decision, PC Code 111801, Case 3122, Antimicrobials
Division, 2/14/05.
Product Chemistry Science Chapter on PHMB (20% Formulations of Vantocil P and
Vantocil IB). PC Code 111801, Case 3122, Antimicrobials Division, 8/4/04, A. Najm
Shamim, Ph.D.
PHMB - 2nd Report of the Hazard Identification Assessment Review Committee, TXR
No. 0051756, Health Effects Division, 4/9/03, Jonathan Chen, Ph.D.
Cancer Assessment Document: Evaluation of the Carcinogenic Potential of PHMB, PC
Code 111801, Case 3122, TXR No. 0052040, Health Effects Division, 7/16/03, Jessica
Kidwell, Executive Secretary, Cancer Assessment Review Committee.
Poly(hexamethylenebiguanide) hydrochloride (PHMB): Toxicology Disciplinary Chapter
for the Reregistration Eligibility Decision Document, PC Code 111801, Case 3122,
Antimicrobials Division, 1/18/05, Jonathan Chen, Ph.D. and Timothy F. McMahon,
Ph.D.
PHMB Dietary Exposure Assessments for the Reregistration Eligibility Decision. PC
Code 111801, Case 3122, Antimicrobials Division, 1/18/05, A. Najm Shamim, Ph.D.
PHMB Occupational/Residential Exposure Assessment. PC Code 111801, Case 3122,
Antimicrobials Division, 2/3/05, Timothy Leighton, Ph.D. and Cassi Walls, Ph.D.
Health Effects of PHMB in Humans. PC Code 111801, Case 3122, Antimicrobials
Division, 8/4/04, Jonathan Chen, Ph.D.
Environmental Fate Assessment of PHMB for the Reregistration Eligibility Decision
(RED). PC Code 111801, Case 3122, Antimicrobials Division, 8/18/04, A. Najm
Shamim, Ph.D.
Ecological Hazard and Environmental Risk Assessment: Poly(hexamethlenebiguanide)
hydrochloride (PHMB). PC Code 111801, Case 3122, Antimicrobials Division,
11/18/05, Kathryn Montague, M.S.
66
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Appendix D. Citations Considered to be Part of the Data Base Supporting the
Reregistration Decision (Bibliography)
1. MRID Studies
MRID# Citation
27491 Beavers, J.B.; Fink, R.; Brown, R. (1979) Final Report: Acute Oral LD50-
Mallard Duck: Project No. 123-131. (Unpublished study received Feb 14, 1980
under 10182-19; prepared by Wildlife International, Ltd. in cooperation with
Washington State College, submitted by ICI Americas, Inc., Wilmington, Del;
CDL:241792-A)
30330 Jackson, SJ. (1979) Acute Oral and Dermal Toxicity: Report No. CTL/T/1361:
Vantocil/P. (Unpublished study received Feb 14, 1980 under 10182-19; prepared
by Imperial Chemical Industries, Ltd., submitted by ICI Americas, Inc.,
Wilmington, Del; CDL: 241790-A)
41382 Beavers, J.B.; Fink, R.; Brown, R. (1979) Final Report: Eight-Day Dietary LC50-
-Bobwhite Quail: Project No. 123-129. (Unpublished study received Feb 14, 1980
under 10182-19; prepared by Wildlife International, Ltd. in cooperation with
Washington State College, submitted by ICI Americas, Inc., Wilmington, Del;
CDL: 241792-C)
45698 Brown, D.; Maddock, E.G. (1980) Determination of the Acute Toxicity of
Vantocil P to Rainbow Trout (-Salmo gairdneri-): BL/B/2031. (Unpublished
study received Aug 21, 1980 under 10182-19; prepared by Imperial Chemical
Industries, Ltd., submitted by ICI Americas, Inc., Wilmington, Del;
CDL:243099-B)
46789 Imperial Chemical Industries, Limited (1966) Antibacterial 9073: Toxicological
Properties: Report No. TR/558. (Unpublished study received Feb 6, 1969 under
OH2556; CDL:221701-I)
53460 Griffiths, D.; Hayes, M.J.; McElligott, T.F. (1966) Ninety-Day Oral Toxicity of
Antibacterial 9073--Albino Rats: Report No. IHR/199. (Unpublished study
received Feb 6, 1969 under OH2556; submitted by Imperial Chemical Industries,
Ltd., London, England; CDL: 2217101-J)
53461 Griffiths, D.; Hayes, M.J.; McElligott, T.F. (1966) Ninety-Day Oral Toxicity of
Antibacterial 9073-Beagle Dogs: Report No. IHR/202. (Unpublished study
received Feb 6, 1969 under OH2556; submitted by Imperial Chemical Industries,
Ltd., London, England; CDL:221701-K)
67
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65120 Conning, D.N. (1966) Antibacterial 9073: Toxicological Properties: Report No.
TR/558. (Unpublished study received Mar 10, 1978 under 10182-EX-ll;
prepared by Imperial Chemical Industries Ltd., England, submitted by ICI
Americas, Inc., Wilmington, Del; CDL:233267-B)
65124 Trueman, R.W.; Eaton, D. (1977) Baquacil SB: Acute Dermal Toxicity and Skin
Irritation Effects: Report No. CTL/T/1057. (Unpublished study received Mar 10,
1978 under 10182-EX-l 1; prepared by Imperial Chemical Industries Ltd.,
England, submitted by ICI Americas, Inc., Wilmington, Del; CDL:233267-F)
65131 Hodge, M.C.E.; Palmer, S. (1976) Baquacil SB: A Teratology Study in the Rat by
Dietary Administration: Report No. CTL/P/262. (Unpublished study received Mar
10, 1978 under 10182-EX-ll; submitted by ICI Americas, Inc., Wilmington, Del;
CDL:233267-M; 233268)
66475 Clapp, M.J.L.; Iswaran, T.J.; Major, P. (1977) Polyhexamethylene Biguanide: 80
Week Skin Painting Study in Mice: Report No. CTL/ P/331 (Amended).
(Unpublished study received Mar 10, 1978 under 10182-EX-l 1; submitted by ICI
Americas, Inc., Wilmington, Del; CDL:233269-A)
77926 Bratt, H. (1977) Vantocil IB: Absorption and Excretion Studies in the Rat: Report
No. CTL/P/163B. Interim rept. (Unpublished study received May 30, 1978 under
10182-19; submitted by ICI Americas, Inc., Wilmington, Del; CDL:234289-B)
77928 Hill, R.W.; Maddock, E.G.; Hart, B. (1975) Vantocil: Determination of the Acute
Toxicity to Rainbow Trout of Vantocil IB in Freshwater: BL/B/1631.
(Unpublished study received May 30, 1978 under ACC#234289; prepared by
Imperial Chemical Industries, Ltd., England, submitted by ICI Americas, Inc.,
Wilmington, Del; CDL:234289-D)
77929 Buccafusco, R.J.; LeBlanc, G.A. (1977) Acute Toxicity of VantocilA(R)I IB, Mix
No. 1857, to Bluegill (-Lepomis macrochirus-) and the Water Flea (-Daphnia
magna-). (Unpublished study received May 30, 1978 under ACC#234289;
prepared by EG & G, Bionomics, submitted by ICI Americas, Inc., Wilmington,
Del; CDL:234289-E)
86362 Trutter, J.A.; Patterson, D.R. (1977) 26-week Toxicity Study in Dogs: 20%
P.H.M.B. Final rept. (Unpublished study received Mar 10, 1978 under 10182-EX-
11; prepared by Hazleton Laboratories America, Inc., submitted by ICI Americas,
Inc., Wilmington, Del; CDL:233270-A)
86363 Bratt, H. (1975) Vantocil IB: Absorption and Excretion Studies in the Rat: Report
No. CTL/P/163B. Interim rept. (Unpublished study received Mar 10, 1978 under
10182-EX-ll; submitted by ICI Americas, Inc., Wilmington, Del; CDL:233270-
B)
68
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104796 ICI Americas, Inc. (1975) Polyhexamethylene Biguanide: 80 Week Skin Painting
Study in Mice: Appendix B: Pathology Individual Animal Data: Report No.
CTL/P/331. (Unpublished study received Sep 27, 1978 under 10182-EX-ll;
CDL:235604-A)
41096901 Randall, V.; Beck, S. (1989) Vantocil IB: An Evaluation in the Mouse
Micronucleus Test: Report No. CTL/P/2436. Unpublished study prepared by ICI
Ltd., Central Toxicology Laboratory. 37 p.
41404501 Howard, C. (1989) Vantocil IB: An Evaluation in the in vitro Cytogenetic Assay
in Human Lymphocytes: Lab Project ID: CTL/P/2582. Unpublished study
prepared by ICI Central Toxicology Laboratory. 28 p.
41404503 Randall, V.; Beck, S. (1989) Vantocil IB: An Evaluation in the Mouse
Micronucleus Test—Addendum: Lab Project ID: CTL/P/2436. Unpublished study
prepared by ICI Central Toxicology Laboratory. 7 p.
41687004 Callander, R. (1989) Vantocil IB: An Evaluation in the Salmonella Mutation
Assay: Lab Project Number: CTL/P/2406. Unpublished study prepared by ICI
Central Toxicology Laboratory. 39 p.
42587501 Popendorf, W.; Selim, M.; Kross, B. (1992) Chemical Manufacturers Association
Antimicrobial Exposure Assessment Study: Second Replacement to MRID
41761201: Lab Project Number: Q626. Unpublished study prepared by The
University of Iowa. 316 p.
42674201 Duerden, L. (1993) Polyhexamethylene Biguanide: Skin Sensitisation to the
Guinea Pig of a 20% Aqueous Solution: Lab Project Number: CTL/P/3889:
GG5741: GG5694. Unpublished study prepared by ZENECA Central Toxicology
Lab. 27 p.
42865901 Brammer, A. (1993) Polyhexamethylene Biguanide: Developmental Toxicity
Study in the Rabbit: Lab Project Number: CTL/P/3997: RB0614. Unpublished
study prepared by Zeneca Central Toxicology Lab. 352 p.
43567001 Lythgoe, R.; Howard, E.; Prescott, E. (1995) PHMB: Absorption, Distribution,
Metabolism and Excretion Following Single Oral Dosing (20mg/kg) in the Rat:
Lab Project Number: CTL/P/4537: UR0360. Unpublished study prepared by
Zeneca Central Toxicology Lab. 82 p.
43599901 Lythgoe, R.; Howard, E. (1995) PHMB: Bioavailability Following Dietary
Administration in the Rat: Lab Project Number: CTL/P/4595: UR0468.
Unpublished study prepared by Zeneca Central Toxicology Lab. 41 p.
69
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43617401 Milburn, G. (1995) Polyhexamethylene Biguanide: Multigeneration Study in the
Rat: Lab Project Number: CTL/P/4455: RR0621/FO: RR0621/F1. Unpublished
study prepared by Zeneca Central Toxicology Lab. 1985 p.
43620501 Horner, S. (1995) Polyhexamethylene Biguanide: 1 Year Dietary Toxicity Study
in Dogs: Lab Project Number: CTL/P/4488: PD0947. Unpublished study prepared
by Zeneca Central Toxicology Lab. 542 p.
43622301 Evans, K.; Beaumont, G.; Williams, D. (1995) PHMB Hydrolysis Study for EPA
Registration: Project 302: Lab Project Number: RD012064B. Unpublished study
prepared by Zeneca Specialties. 33 p.
43949001 Penwell, A.; Roberts, G. (1995) PHMB: Acute Toxicity to Rainbow Trout
Oncorhynchus mykiss: Lab Project Number: BL5506/B: X839/B. Unpublished
study prepared by Zeneca Ltd. 30 p.
44042801 Busey, W. (1996) Polyhexamethylene Biguanide (PHMB): Two Year Feeding
Study in Rats: Pathology Working Group Peer Review of Proliferative Vascular
Lesions in Male and Female Rats: Lab Project Number: PR0936: CTL/C/3172:
Y00156/008. Unpublished study prepared by Experimental Pathology Labs., Inc.
67 p. (Relates to L0000061}.
44046301 Dugard, P.; Mawdsley, S. (1982) (Carbon 14)-Polyhexamethylene Biguanide
(PHMB): Absorption Through Human Epidermis and Rat Skin in vitro: Lab
Project Number: CTL/R/579. Unpublished study prepared by Imperial Chemical
Industries Ltd., Central Toxicology Lab. 36 p.
44051301 Burt, M. (1996) Assessment of Worker and Postapplicator Exposure to PHMB
Used in Pools and Spas: Lab Project Number: JCS/1. Unpublished study prepared
by Zeneca Specialties. 41 p.
44059301 Horner, S. (1996) Polyhexamethylene Biguanide: Two Year Feeding Study in
Rats: Lab Project Number: CTL/P/4663: PR0936. Unpublished study prepared by
Zeneca Central Toxicology Lab. 3015 p. Relates to L0000061.
44074201 Milburn, G. (1996) Polyhexamethylene Biguanide: Two Year Oncogenic Study in
Mice: Lab Project Number: CTL/P/4649: PM0937. Unpublished study prepared
by Zeneca Central Toxicology Lab. 2348 p.
45187701 Backhouse, B. (2000) Health Risk Assessment for PHMB in 100% Cotton Textile
Applications-Systemic Toxicity by an Infant Sucking a Textile (Initially
Unwashed, Subsequently Washed): Lab Project Number: SENS10D. Unpublished
study prepared by Avecia Limited. 7 p.
70
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45710801
45710802
45710803
45710804
45710805
45710807
45710808
93191001
93191002
93191004
Piccirillo, V. (2002) Evaluation of the Weight-of-Evidence for the Carcinogenic
Potential of PHMB: Lab Project Number: VJP 7172-02-1. Unpublished study
prepared by Avecia, Inc. lip.
Mann, P. (2002) Polyhexamethylene Biguanide (PHMB): 2 Year Oncogenic
Study in Mice: Lab Project Number: PM0937: 698-001. Unpublished study
prepared by Experimental Pathology Laboratories, Inc. 63 p. (OPPTS 870.4300}
Freemantle, M. (2002) Polyhexamethylene Biguanide (PHMB): Two-Year
Oncogenic Study in Mice: Statistical Analysis of the Results from the Pathology
Working Group Peer Review of Vascular Lesions in Male and Female Mice: Lab
Project Number: AP-7. Unpublished study prepared by Syngenta Central
Toxicology Laboratory. 17 p.
Brown, E. (2002) Historical Control Data for Occurrence of Hemangiosarcoma
(Angiosarcoma) in C57BL/10J/CD-1 Alpk Mice: Lab Project Number: AP-1.
Unpublished study prepared by Syngenta Central Toxicology Laboratory. 7 p.
Brown, E. (2002) Exceedance of the Maximum Tolerated Dose at the Highest
Tested Dose of PHMB in Mice: Lab Project Number: AP-2. Unpublished study
prepared by ChemReg International, LLC. 5 p.
Brown, E. (2002) Potential Carcinogenicity from Dermal Applications of PHMB:
Lab Project Number: AP-4. Unpublished study prepared by ChemReg
International, LLC. 10 p.
Brown, E. (2002) Historical Control Data for Occurrence of Hemangiosarcoma
(Angiosarcoma) in Alpk: ApfSD Wistar Rats: Lab Project Number: AP-5.
Unpublished study prepared by Syngenta Central Toxicology Laboratory. 8 p.
Burt, M. (1990) ICI Americas Inc. Phase 3 Summary of MRID 00027491. Acute
Oral LD50 - Mallard Duck, Baquacil Mix #5889, Final Report: Project No. 123-
131. Prepared by Wildlife International Ltd. 10 p.
Burt, M. (1990) ICI Americas Inc. Phase 3 Summary of MRID 00041382. Eight
Day Dietary LC50 - Bobwhite Quail Baquacil Mix #5889, Final Report: Project
No. 123-129. Prepared by Wildlife International Ltd. 11 p.
Adams, D. (1990) ICI Americas Inc. Phase 3 Summary of MRID 00045698.
Vantocil P: Determination of the Acute Toxicity to Rainbow Trout Salmo
gairdneri: Report No. BL-B-2031; Study No. G184-B. Prepared by ICI Brixham
Laboratory. 14 p.
71
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2. Open Literature
American Chemistry Council (ACC). 2002. An Analysis of the Training Patterns and Practices
of Competitive Swimmers. Alexandria, Virginia: Prepared by Richard Reiss. Sciences
International, Inc.
Brunsman, L.L. 2002. PHMB Qualitative Risk Assessment Based On 1977 SPF Alderley Park
Mouse Dermal Study, and 1996 C57Bl/10JfCD-l/Alpk Mouse and 1996 Alpk:APfSD
Wistar Rat Dietary Studies. TXR No. 0051368.
Dykstra, W. 1978. Baquacil Swimming Pool Sanitizer (containing Poly (hexamethylene
biguanide hydrochloride). Experimental Use Permit Application for the Evaluation of
Baquacil in Recreational Swimming Pools. 10182-EUP-l 1. Caswell # 676. Report No.
003801.
IT Environmental Programs, Inc. 1991. Chemical Engineering Branch Manual for the
Preparation of Engineering Assessments. Contract No. 68-D8-0112. Work Assignment
P3-7. U.S. Environmental Protection Agency. Office of Toxic Substances.
McMahon, T. 1995. Polyhexamethylene Biguanide (PHMB, Baquacil): Review of a
Mutagenicity Study Submitted by the Registrant. Report No. 011380.
McMahon, T. 1997. Vantocil IB® (Baquacil): Review of Mutagenicity Data. DP Barcode:
D240678.
Megosh, LC, Hu, J, Geroge K, O'Brien TG. 2002. Genetic control of polyamine-dependent
susceptibility to skin carcinogenesis. Genomics 79:505-512.
Milovic V, Turchanowa L. 2003. Polyamines and colon cancer. Biochemical Society
Transactions 31:381-383.
Fletcher, J.M. 2002. Memorandum on Pathology Working Group Peer Review of Proliferative
Vascular Lesions in Male and Female Mice. October 28, 2002. TXR No. 0052033.
Fletcher, J.M. 2003. Memorandum on Pathology Working Group Peer Review of Proliferative
Vascular Lesions in Male and Female Rats. July 16, 2003. TXR No. 0052000.
US EPA. 1997a. Standard Operating Procedures (SOPs) for Residential Exposure Assessments.
Contract No. 68-W6-0030. Prepared by the Residential Exposure Assessment Work
Group. Office of Pesticide Programs, Health Effects Division and Versar. July 1997.
US EPA. 1997b. Exposure Factors Handbook. National Center for Environmental Assessment,
Office of Research and Development.
72
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US EPA. 1997'c. Surrogate Exposure Guide: Estimates of Worker Exposure from the Pesticide
Handler Exposure Database, Version 1.1. May 1997.
US EPA. 2000. Standard Operating Procedures (SOPs) for Residential Exposure Assessments.
Office of Pesticide Programs, Health Effects Division. April 2000.
US EPA 200 Ib. Review of a Health Risk Assessment for PHMB (Vantocil IB) used on 100%
Cotton Textile Application - Systemic Toxicity by an Infant Sucking Textile.
Memorandum for Siroos Mostaghimi, Ph.D. to Adam Heyward. January 3, 2001.
Versar. 2003. User's Manual Swimmer Exposure Assessment Model (SWIMODEL) Version
3.0. Prepared for the US EPA Antimicrobials Division. November 2003.
3. Website References
FDA, 2003 a. "Guidance For Industry: Preparation of Food Contact Notifications and Food
Additive Petitions for Food Contact Substances: Chemistry Recommendations. Final
Guidance." US Food and Drug Administration. April, 2003.
http://www.cfsan.fda.gov/~dms/opa2pmnc.html. Last accessed June 9, 2003.
FDA, 2003b. "Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions." US
Food and Drug Administration. January, 1993. http://www.cfsan.fda.gov/~dms/opa-
cg3a.html. Last accessed June 9, 2003.
USEPA, 1999. "Available Information on Assessing Exposure from Pesticides, A User's
Guide." US Environmental Protection Agency, Office of Pesticide Programs. June 21,
1999. http://www.epa.gov/fedrgstr/EP A-PEST/2000/Julv/Dav-12/6061 .pdf Last
accessed June 9, 2003.
USEPA, 200la. "General Principles for Performing Aggregate Exposure and Risk
Assessments." US Environmental Protection Agency, Office of Pesticide Programs.
November 28, 2001. http://www.epa.gov/pesticides/trac/science/aggregate.pdf
USEPA, 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide
Programs U.S. Environmental Protection Agency - Endangered and Threatened Species
Effects Determinations, Appendix A, Section IIB, pg.81. US Environmental Protection
Agency. January 24, 2004.
http://www.epa.gov/oppfeadl/endanger/consultation/ecorisk-overview.pdf
73
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Appendix E. Generic Data Call-In
The Agency intends to issue a Generic Data Call-In at a later date. See Chapter V of the PHMB
RED for a list of studies that the Agency plans to require.
74
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Appendix F. Product Specific Data Call-In
The Agency intends to issue a Product Specific Data Call-In at a later date.
75
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Appendix G. Batching of PHMB Products for Meeting Acute Toxicity Data Requirements
for Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregistration of products containing PHMB as an active
ingredient, the Agency has batched products which can be considered similar for purposes of
acute toxicity. Factors considered in the sorting process include each product's active and inert
ingredients (identity, percent composition and biological activity), type of formulation (e.g.,
emulsifiable concentrate, aerosol, wettable powder, granular), and labeling (e.g., signal word, use
classification, precautionary labeling). Note that the Agency is not describing batched products
as "substantially similar," since they may not have similar use patterns.
Using available information, batching has been accomplished by the process described in
the preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to
require, at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or
cite a single battery of six acute toxicological studies to represent all the products within that
batch. It is the registrants' option to participate in the process with all other registrants, only
some of the other registrants, or only their own products within a batch, or to generate all the
required acute toxicological studies for each of their own products. If a registrant chooses to
generate the data for a batch, he/she must use one of the products within the batch as the test
material. If a registrant chooses to rely upon previously submitted acute toxicity data, he/she
may do so provided that the data base is complete and valid by today's standards (see partial list
of acceptance criteria attached), the formulation tested is considered by EPA to be similar for
acute toxicity, and the formulation has not been significantly altered since submission and
acceptance of the acute toxicity data. The Agency must approve any new or canceled
formulations (that were presented to the Agency after the publication of the RED) before data
derived from them can be used to cover other products in a batch. Regardless of whether new
data is generated or existing data is referenced, registrants must clearly identify the test material
by EPA Registration Number. If more than one confidential statement of formula (CSF) exists
for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow
the directions given in the Data Call-In Notice and its attachments appended to the RED. The
DCI Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response," asks whether the registrant
will meet the data requirements for each product. The second form, "Requirements Status and
Registrant's Response," lists the product specific data required for each product, including the
standard six acute toxicity tests. A registrant who wishes to participate in a batch must decide
whether he/she will provide the data or depend on someone else to do so. If a registrant supplies
the data to support a batch of products, he/she must select one of the following options:
Developing Data (Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing
Study (Option 5) or Citing an Existing Study (Option 6). If a registrant depends on another's
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data, he/she must choose among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or
Citing an Existing Study (Option 6). If a registrant does not want to participate in a batch, the
choices are Options 1, 4, 5 or 6. However, a registrant should know that choosing not to
participate in a batch does not preclude other registrants in the batch from citing his/her studies
and offering to cost share (Option 3) those studies.
If a registrant would like to have the batching status of a product reconsidered, he/she
must submit detailed information on the product, including a detailed rationale for the inclusion
of the product into a batch. An MSDS for each "inert" ingredient should be included where
possible. A current version of the Confidential Statement of Formula (CSF) is to be included in
the submission. However, registrants and manufacturers should realize that the more unusual
their formulation is, the less likely it is to be able to batch that product.
Seventeen products were found which contain PHMB as an active ingredient. These
products have been placed into three batches and a "No Batch" category in accordance with the
active and inert ingredients and type of formulation. The following bridging strategies may be
employed:
Batch 3:
— For eye irritation and skin sensitization data, Registration Numbers 72992-
2 and 72992-8 may only cite their own studies or those of 72992-2.
— For eye irritation and skin sensitization data, Reg. No. 72992-3 and 72992-
7 may cite each other's studies but not 72992-2 or 72992-8 studies.
— For all other studies, each product must cite its own data or data from Reg.
No. 72992-2.
No Batch: Each product in this batch should generate its own data (or cite its own
pre-existing data if it exists and meets current Agency standards).
Table: PHMB Batching, Case 3122
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Please note that while products may have the same percent active ingredient as another product,
the composition of their inert ingredients may vary greatly.
78
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MINIMUM ACUTE TOXICITY ACCEPTANCE CRITERIA
Does the study report clearly identify the test material? That is, is the
test material identified by EPA Registration Number, product name,
or, is the product listed as technical grade?
Does the report state that the study was conducted in concurrence with
the (1984) 40 CFR §160.12?
3 Is the test species identified?
4 Are the test animals the proper weight? (Rats approximately 200-300
grams, rabbits approximately 2.0 - 3.0 kg.)
5 Acute oral, dermal and inhalation toxicity: Did the observation period
last for 14 days, or, until the test subjects appeared normal?
Primary eye irritation: Did the observation period continue for 21 days,
or, until all irritation subsided? Studies displaying excessive irritation
(toxicity category I) may be stopped before 21 days.
Primary skin irritation: Did the observation period continue for 14 days,
or, until all irritation subsided? Studies displaying excessive irritation
(toxicity category I) may be stopped before 14 days.
Acute inhalation toxicity: Were the test subjects exposed to the material
for at least 4 hours (if there was no mortality during the exposure)?
Acute inhalation toxicity: Was particle size determined at least twice
during the exposure? Was the MMAD between 1 and 4 microns
(micrometers)?
10 Acute inhalation toxicity: Was the particle concentration
determined at least twice during the study?
Studies that do not meet each (1-10) of the criteria listed above will be rejected. Please be
informed that EPA's guidelines change from year to year. A study that was accepted 25 or more
years ago may not be currently acceptable.
Please refer to the following documents for more information.
1. Health Effects Test Guidelines. Series 870. EPA 712-C-98-189, August 1998.
2. Conduct of Acute Toxicitv Studies. EPA 737-R-97-002, September 1997.
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Appendix H. List of All Registrants Sent the Data Call-In
A list of registrants sent the data call-in will be posted at a later date.
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Appendix I. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader)
Instructions
1 . Print out and complete the forms. (Note: Form numbers that are bolded can be
filled out on your computer then printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the
existing policy.
3. Mail the forms, along with any additional documents necessary to comply with
EPA regulations covering your request, to the address below for the Document
Processing Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or
'Sensitive Information.'
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-
5551 or by e-mail at williams.nicole@epamail.epa.gov.
The following Agency Pesticide Registration Forms are currently available via the
internet at the following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
Application for Pesticide Registration/ Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of Distribution of
a Registered Pesticide Product
Application for an Experimental Use Permit
Application for/Notification of State Registration of a
Pesticide To Meet a Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data Gap Procedures
Pesticide Registration Maintenance Fee Filing
Certification of Attempt to Enter into an Agreement
with other Registrants for Development of Data
Certification with Respect to Citations of Data (in PR
Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical Properties (in PR
Notice 98-1)
Self-Certification Statement for the Physical/Chemical
Properties (in PR Notice 98-1)
http://www.cpa.gov/opprd001/forms/8570-l.pdf
http://www.epa.KOv/opprd001/forms/8570-4.pdf
http://www.cpa.gov/opprd001/forms/8570-5.pdf
http://www.epa.KOv/opprd001/forms/8570-17.pdf
http://www.cpa.gov/opprd001/forms/8570-25.pdf
http://www.epa.KOv/opprd001/forms/8570-27.pdf
http://www.epa.KOv/opprd001/forms/8570-28.pdf
http://www.cpa.gov/opprd001/forms/8570-30.pdf
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http://www.epa.Kov/opppmsdl/PR Notices/pr98-
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Pesticide Registration Kit
www.epa.gov/pesticides/registrationkit/.
Dear Registrant:
For your convenience, we have assembled an online registration kit that contains the
following pertinent forms and information needed to register a pesticide product with the U.S.
Environmental Protection Agency's Office of Pesticide Programs (OPP):
1 . The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal
Food, Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality
Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program — Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through
Irrigation Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation
Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This
document is in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at
3. Pesticide Product Registration Application Forms (These forms are in PDF format
and will require the Acrobat reader.)
a. EPA Form No. 8570-1, Application for Pesticide
Regi stration/ Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
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4. General Pesticide Information (Some of these forms are in PDF format and will
require the Acrobat reader.)
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data
Requirements (PDF format)
e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f 40 CFR Part 158, Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27,
1985)
Before submitting your application for registration, you may wish to consult some
additional sources of information. These include:
1. The Office of Pesticide Programs' Web Site
2. The booklet "General Information on Applying for Registration of Pesticides in
the United States", PB92-221811, available through the National Technical
Information Service (NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000. Please note that EPA is currently in
the process of updating this booklet to reflect the changes in the registration program resulting
from the passage of the FQPA and the reorganization of the Office of Pesticide Programs. We
anticipate that this publication will become available during the Fall of 1998.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue
University's Center for Environmental and Regulatory Information Systems. This
service does charge a fee for subscriptions and custom searches. You can contact
NPIRS by telephone at (765) 494-6614 or through their Web site.
4. The National Pesticide Telecommunications Network (NPTN) can provide
information on active ingredients, uses, toxicology, and chemistry of pesticides.
You can contact NPTN by telephone at (800) 858-7378 or through their Web site:
ace. orst. edu/info/nptn.
The Agency will return a notice of receipt of an application for registration or amended
registration, experimental use permit, or amendment to a petition if the applicant or petitioner
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encloses with his submission a stamped, self-addressed postcard. The postcard must contain the
following entries to be completed by OPP:
Date of receipt
EPA identifying number
Product Manager assignment
Other identifying information may be included by the applicant to link the
acknowledgment of receipt to the specific application submitted. EPA will stamp the date of
receipt and provide the EPA identifying File Symbol or petition number for the new submission.
The identifying number should be used whenever you contact the Agency concerning an
application for registration, experimental use permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and
assigned to your company, please include a list of all synonyms, common and trade names,
company experimental codes, and other names which identify the chemical (including "blind"
codes used when a sample was submitted for testing by commercial or academic facilities).
Please provide a CAS number if one has been assigned.
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