PRO-
Reregistration Eligibility
Decision (RED) for 4-t-
Amylphenol
September 30, 2005
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United States Prevention, Pesticides EPA738-R-05-001
Environmental Protection and Toxic Substances January 2005
Agency (7508C)
Re registration
Eligibility Decision
for Para-Tertiary-
Amylphenol, Potassium
Sodium Salt (Case 3016)
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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, Para-Tertiary-
amylphenol (4-t-amylphenol). The enclosed Reregistration Eligibility Decision (RED) document
was approved on September 30, 2005. 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 4-t-amylphenol 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 4-t-amylphenol are available to the public
in EPA's Pesticide Docket OPP-2005-0181 at: http://www.epa.gov/edockets.
The 4-t-amylphenol RED was developed through EPA's public participation process,
published in the Federal Register on July 20, 2005, 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 4-t-amylphenol 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 4-t-amylphenol
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
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sent to registrants at a later date. Additionally, for product-specific DCIs, the first set of required
responses will be due 90 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 4-t-amylphenol will be eligible for
reregistration provided that all the conditions identified in this document are satisfied, including
implementation of the risk mitigation measures outlined in Section IV of the document. Sections
IV and V of this RED document describe labeling amendments for end-use products and data
requirements necessary to implement these mitigation measures. 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 4-t-amylphenol.
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 necessary for reregistration,
please contact the Chemical Review Manager, Killian Swift, at (703) 308-6346. For questions
about product reregistration and/or the Product DCI that accompanies this document, please
contact Adam Heyward at (703) 308-6422.
Sincerely,
Frank Sanders, Director
Antimicrobials Division (75IOC)
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REREGISTRATION ELIGIBILITY
DECISION
for
Para-tertiary-amylphenol
ListC
CASE 3016
Approved By:
Frank Sanders
Director, Antimicrobials Division
Date: September 30, 2005
Attachment
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Table of Contents
Glossary of Terms and Abbreviations xvi
4-t-amylphenol Reregistration Team xiv
Executive Summary xv
I. Introduction 1
II. Chemical Overview 3
A. Regulatory History 3
B. Chemical Identification 3
C. Use Profile 4
III. Summary of 4-t-amylphenol Risk Assessments 6
A. Human Health Risk Assessment 6
1. Toxicity of 4-t-amylphenol 6
2. FQPA Safety 8
3. Population Adjusted Dose (PAD) 9
a. Acute PAD 9
b. Chronic PAD 9
4. Exposure Assumptions 10
5. Dietary (Food) Risk Assessment 10
a. Acute Dietary Risk 10
b. Chronic (Non-Cancer) Dietary Risk 10
c. Dietary Risks from Drinking Water 11
6. Residential Exposure 11
a. Toxicity 12
b. Residential Handler 13
i. Exposure Scenarios, Data and Assumptions 13
ii. Residential Handler Risk Estimates 14
c. Residential Post-application 14
i. Exposure Scenarios, Data and Assumptions 14
ii. Residential Post-Application Risk Estimates.... 15
7. Aggregate Risk 16
a. Short and Intermediate Term Aggregate Risk 17
b. Long Term Aggregate Risk 18
8. Occupational Risk 18
a. Occupational Toxicity 19
b. Occupational Handler Exposure 19
c. Occupational Handler Risk Summary 19
d. Occupational Post-Application Risk Summary 21
e. Human Incident Data 21
B. Environmental Risk Assessment 21
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1. Environmental Fate and Transport 21
2. Ecological Risk 22
3. Endocrine Effects in Fish 23
4. Listed Species Consideration 24
a. The Endangered Species Act 24
b. General Risk Mitigation 25
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 26
A. Determination of Reregistration Eligibility 26
B. Public Comments and Responses 26
C. Regulatory Position 27
1. Food Quality Protection Act Considerations 27
a. "Risk Cup" Determination 27
b. Determination of Safety to U. S. Population 27
c. Determination of Safety to Infants and Children 28
d. Endocrine Disrupter Effects 28
e. Cumulative Risks 29
2. Tolerance Summary 29
a. Tolerances Currently Listed and Tolerance 29
Reassessment
b. Codex Harmonization 30
D. Regulatory Rationale 30
1. Human Health Risk Management 30
a. Dietary (Food) Risk Mitigation 30
b. Drinking Water Risk Mitigation 30
c. Residential Risk Mitigation 30
d. Occupational Risk Mitigation 31
i. Handler Exposure 31
ii. Post-Application Risk Mitigation 31
2. Environmental Risk Management 31
3. Other Labeling Requirements 31
4. Threatened and Endangered Species Considerations 32
a. The Endangered Species Program 32
b. General Risk Mitigation 32
V. What Registrants Need to Do 34
A. Manufacturing Use-Products 36
1. Additional Generic Data Requirements 36
2. Labeling for Technical and Manufacturing-Use Products 38
B. End-Use Products 38
1. Additional Product Specific Data Requirements 38
2. Labeling for End-Use Products 38
a. Label Changes Summary Table 39
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VI. Appendices 41
A. Table of Use Patterns for 4-t-amylphenol 43
B. Table of Generic Data Requirements and Studies Use to Make the
Reregistration Decision 68
C. Technical Support Documents 73
D. Bibliography Citations 74
E. Generic Data Call-In 79
F. Product Specific Data Call-In 80
G. Batching of End-Use Products 81
H. List of All Registrants Sent the Data Call-In 83
I. List of Available Forms 84
XI
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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
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MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
MRL Maximum Residue Level
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
PCCs Poison Control Centers
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
Xlll
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4Para-Tertiary-Amylphenol Reregistration Team
Office of Pesticide Programs
Environmental Fate and Effects Risk Assessment
Srinivas Gowda
David Bays
Health Effects Risk Assessment
Jonathan Chen
Timothy Leighton
Tim McMahon
Siroos Mostaghimi
Myron Ottley
Bob Quick
Najm Shamim
Deborah Smegal
Cassi Walls
Registration Support
Adam Heyward
Risk Management
Ben Chambliss
Killian Swift
ShaRon Carlisle
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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 para-tertiary-amylphenol (4-t-amylphenol) and its potassium and sodium salt and
is issuing its risk management decision. The Agency has determined 4-t-amylphenol and its
potassium and sodium salts are eligible for reregistration provided all measures outlined in this
document are implemented. 4-t-Amylphenol is a member of the phenolic class of antimicrobials.
4-t-Amylphenol is an active ingredient in disinfectant, food-contact sanitizer and deodorizer
products used in agricultural, food handling, commercial, institutional, industrial, residential,
public access, and medical settings, primarily on hard, non-porous surfaces. The majority of the
products are virucidal, fungicidal, tuberculocidal or bactericidal. Examples of registered uses for
4-t-amylphenol include application to hard surfaces (e.g., walls, floors, tables, fixtures), textiles
(e.g., clothing, diapers, mattresses, bedding), carpets, medical instruments, and agricultural
equipment. Additionally, there are registered uses for fogging in occupational settings and air
deodorization in both occupational and residential settings.
Overall Risk Summary
The Agency's human heath risk assessment indicates no risks of concern for dietary or
drinking water exposures. An acute dietary risk estimate was completed for females 13-49 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.
4-t-Amylphenol and its salts are not likely to contaminate surface and ground waters
based on its use patterns and fate characteristics. Thus, a drinking water assessment was not
conducted. Therefore, no risk mitigation measures are required to address 4-t-amylphenol
exposure from drinking water.
Residential risks from handler and post-application exposure were calculated for short-
and intermediate-term dermal, inhalation and incidental oral exposures. All exposure and risk
estimates for residential handler scenarios are below the Agency's level of concern. Risks of
concern have been identified for several post-application exposure scenarios including children's
dermal exposure to treated clothing and treated diapers and children's incidental oral exposure to
treated clothing. The Agency believes that adding clear instructions for washing and rinsing
textile items will result in the adequate removal of residues from the treated items and address
the Agency's concerns for this scenario. The MOE for dermal exposure to children to treated
surfaces in daycare centers slightly exceeds the Agency's level of concern (MOE = 940 with a
target MOE of 1,000). However, the Agency believes actual exposure from this pathway to not
exceed its level of concern when taking into account the conservative nature of the risk estimate
which is likely to overestimate potential exposures.
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Aggregate short and intermediate term risk assessments were conducted for this chemical
that includes incidental oral and inhalation risks only. Dermal risks are not included in the
aggregate risk estimates because they have a different toxicity endpoint. The aggregate oral and
inhalation risks are not of concern for adults, as the total aggregate MOE is greater than the
target of 3,000. For children, the aggregate risk estimates are also above the target MOE of
3,000 and thus are not of concern. However, incidental oral exposures to treated textiles are not
included in the aggregate assessment because the oral MOE is already of concern.
For the occupational handler dermal and inhalation risk assessment, the short- and
intermediate- term risks calculated at baseline exposure (no gloves and no respirators) were
above target MOEs for all scenarios. For most of the occupational scenarios, postapplication
dermal exposure is not expected to occur or is expected to be negligible based on the application
rates and chemical properties of the chemical. Postapplication/bystander inhalation exposures,
however, were assessed for entry into a building after a fogging application. The representative
building selected was a poultry barn. The calculated inhalation MOEs were above the target
MOE of 300 for all fogging postapplication scenarios with the exception of the scenario for 8-hr
exposure to the product with a 2-hr reentry interval (MOE = 86).
There is a concern about the possibility of endocrine disruption in fish, since 4-t-
amylphenol is considered an ecoestrogen. However, since this chemical is restricted to indoor
uses only, the possibility for exposure to fish to 4-t-amylphenol would be limited. The limited
exposure resulting from indoor uses of 4-t-amylphenol and its salts is not anticipated to cause
adverse effects to terrestrial or aquatic organisms.
Dietary Exposure Risk
An acute dietary risk assessment was conducted for 4-t-amylphenol indirect food uses.
Dietary risk estimates are provided for females 13-49 years old, the only population subgroup for
which an endpoint was selected. The result of this assessment showed the risk estimate to be
2.7% of the aPAD and therefore is not of concern
A chronic dietary risk assessment was conducted for 4-t-amylphenol food uses. The risk
analysis assumes daily exposure from the hard surface disinfection of counter tops. The result of
this assessment showed the risk estimates to be <42% of the cPAD and therefore are not of
concern.
Drinking Water Risk
4-t-Amylphenol and its salts are not likely to contaminate surface and ground waters
based on its use patterns and fate characteristics. There are no currently registered outdoor uses
of 4-t-amylphenol and its salts. Further, the estimated value for biodegradation indicates it may
biodegrade linearly within days in the aquatic environment, although ultimate biodegradation
(mineralization) may take months. It also is volatile based on its vapor pressure of 0.00116
mmHg, and has a moderate to slight mobility in soils based on its estimated Koc value of 3799.
The sodium and potassium salts of 4-t-amylphenol also are slightly to moderately mobile in
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soils, and are estimated to biodegrade within days to weeks. Because of the possibility of
biodegradation in water and soils and the lack of outdoor uses, 4-t-amylphenol and its salts are
not likely to contaminate surface and ground waters. Thus, a drinking water assessment was not
conducted.
Residential Handler Risk
For residential handlers that handle products containing 4-t-amylphenol and its salts,
short-term, and intermediate-term MOEs were above the target MOEs (i.e., >1,000 for dermal
and >3,000 for inhalation) for all scenarios evaluated and thus, do not exceed the Agency's level
of concern.
Residential Post-Application Risk
Risks of concern have been identified for several post-application exposure scenarios
including children's dermal exposure to treated clothing and treated diapers and children's
incidental oral exposure to treated clothing. The Agency believes that adding clear instructions
for washing and rinsing textile items will result in the adequate removal of residues from the
treated items and address the Agency's concerns for this scenario. The MOE for dermal
exposure to children to treated surfaces in daycare centers slightly exceeds the Agency's level of
concern (MOE = 940 with a target MOE of 1,000). However, the Agency believes actual
exposure from this pathway to not exceed its level of concern when taking into account the
conservative nature of the risk estimate which is likely to overestimate potential exposures.
Aggregate Risk
Short- and intermediate-term aggregate risks are considered together because the
exposure and toxicity endpoints are identical for incidental oral and inhalation residential
exposures for both durations. For children, the short- and intermediate-term aggregate
assessment includes average dietary exposure (food) and estimated incidental oral exposures to
children from residential uses such as hard surface disinfection. In addition, inhalation exposure
from post-application of an air deodorizer use was aggregated with the oral exposures since the
toxicity endpoint is the same. For adults, the aggregate assessment includes dietary (oral) and
residential inhalation exposures from wiping a hard surface disinfectant, in addition to post
application inhalation exposure from the air deodorizer.
Aggregate oral and inhalation risks are not of concern for adults, as the total aggregate
MOE is greater than the target of 3,000. For children, the aggregate risk estimates are also above
the target MOE of 3,000 and thus are not of concern. As noted previously, incidental oral
exposures to treated textiles are not included in the aggregate assessment because the oral MOE
is already of concern.
A dermal aggregate assessment was not conducted because the toxicity effects for the
dermal exposure route are not the same as the oral/inhalation exposure route. However, short-
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and intermediate dermal risks are already of concern for residents for the treated textile and
diaper use.
Occupational Risk
To assess the handler risks, the Agency used surrogate unit exposure data from both the
proprietary Chemical Manufacturers (CMA) antimicrobial exposure study and the Pesticide
Handlers Exposure Database (PHED). For the occupational handler dermal and inhalation risk
assessment, the short- and intermediate-term risks calculated at baseline exposure (no gloves and
no respirators) were above target MOEs for all scenarios (i.e., dermal MOEs > 100 and
inhalation MOEs were >300). Note, however, that high pressure spray application method in the
agricultural use site category was assessed using gloved data.
For most of the occupational scenarios, post-application dermal exposure is not expected
to occur and it is expected to be negligible based on the application rates and chemical properties
of the chemical. However, post-application/bystander inhalation exposures were assessed for
entry into a building after fogging application. The representative building selected was a
poultry barn. The Agency used MCCEM (Multi-Chamber Concentration and Exposure Model)
to estimate post-application/bystander exposures. The calculated inhalation MOEs were above
the target MOE of 300 for all fogging post-application scenarios with the exception of the
scenario for 8-hour exposure to the product with a 2-hour re-entry interval (MOE = 86).
The Agency does not believe that any mitigation is necessary to address the post-
application scenario with a 2-hr reentry interval at this time. The risk estimate was calculated
using the Agency's standard assumptions for air exchange rates. The Agency believes that in the
case of animal barns and facilities this assumption in very conservative given the relatively high
air exchange rates for such facilities.
Ecological Risk
There is a concern about the possibility of endocrine disruption in fish, since 4-t-
amylphenol is considered an ecoestrogen. This was documented in several studies on carp
(Cyprimus carpio). However, since this chemical is restricted to indoor uses only, the possibility
for exposure to fish to 4-t-amylphenol would be limited. The limited exposure resulting from
indoor uses of 4-t-amylphenol and its salts is not anticipated to cause adverse effects to terrestrial
or aquatic organisms.
Regulatory Decision
The Agency has completed its review and has determined that the data are sufficient to
support reregistration of all supported products containing 4-t-amylphenol. The Agency is
issuing this RED for 4-t-amylphenol, as announced in a Notice of Availability published in the
Federal Register. This RED document includes guidance and time frames for making any
necessary label changes for products containing 4-t-amylphenol.
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Summary of Mitigation Measures
The Agency has determined that 4-t-amylphenol and its salts (potassium and sodium) are
eligible for reregistration provided the mitigation measures described in this document and the
label changes included in Table 13 in Section V of the RED are implemented.
Residential Risk Mitigation
To reduce residential exposure, the Agency has determined that the following mitigation
and label changes for specific scenarios are appropriate and required for reregistration eligibility:
Delete all diaper uses
Delete all use on non-laundered textiles\items including mattresses, helmets,
headgear, headphones, facegear, and mouthpieces.
- All labels with laundered textile uses must have directions that indicate that items
must be treated prior to washing and rinsing.
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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 4-tertiary-amylphenol (4-t-amylphenol), and salts (potassium and
sodium).
4-t-Amylphenol and salts are active ingredients in disinfectant and food-contact
sanitizer products used in agricultural, food handling, commercial/institutional/industrial,
residential, public access, and medical settings - primarily on hard, non-porous surfaces. The
majority of the products are virucidal, fungicidal, bactericidal, pseudomonacidal, or
staphylocidal. Examples of registered uses for 4-t-amylphenol and salts include application to
hard surfaces (e.g., walls, floors, tables, and fixtures), textiles (e.g., clothing, diapers, mattresses,
and bedding), carpets, medical instruments, and agricultural equipment. Additionally, there are
registered uses for fogging in occupational settings and air deodorization in both occupational
and residential settings. Concentrations of 4-t-amylphenol and salts in products range from
0.0027% to 10%. The products are formulated as soluble concentrates, ready-to-use liquid
solutions, pressurized sprays, and impregnated wipes.
The Agency has concluded that the hazard based FQPA safety factor should be retained
at 10X. The toxicology data base is not complete with respect to assessing the increased
susceptibility to infants and children as required by FQPA for 4-t-amylphenol. The rat prenatal
developmental study showed no quantitative evidence of increased susceptibility (i.e.,
developmental NOAELs /LOAELs were higher than those for maternal effects). However, there
was qualitative evidence of increased susceptibility as the fetal effects (i.e., skeletal
abnormalities, decreased body weight gain) were considered to be more severe than maternal
toxicity (reversible clinical signs). In addition, there is an absence of developmental toxicity data
in the rabbit, and an absence of reproductive toxicity data. Furthermore, studies in the open
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literature suggest that 4-t-amylphenol may be an endocrine disrupter. It increased non-pregnant
uterine weight in rats and was associated with elevated blood levels of billirubin in children
exposed to 4-t-amylphenol and other phenols in disinfectants. These studies, while not
indicative, are suggestive of a basis for increased concern for reproductive and/or developmental
effects due to exposure to 4-t-amylphenol.
Risks summarized in this document are those that result only from the use of the active
ingredients 4-t-amyphenol and its salts (potassium and sodium). 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 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 4-t-amyphenol and its salts (potassium and
sodium) and any other substances. 4-t-Amyphenol and it salts (potassium and sodium) do not
appear to produce a toxic metabolite produced by other substances. For the purposes of this
action, therefore, EPA has not assumed that 4-t-amyphenol and it salts (potassium and sodium)
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
http://www.epa.gov/pesticides/cumulative .
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of 4-t-amyphenol and its salts (potassium and sodium). 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 4-t-amylphenol and
salts 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 (OPP-
2005-0181)
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 4-t-amylphenol and its salt (potassium and
sodium), and its regulatory history. Section III, Summary of 4-t-amylphenol and salts Risk
Assessment, 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
4-t-Amyphenol and its salts (potassium and sodium) have been registered for use since
1962. Currently, there are 35 products containing 4-t-amyphenol (one technical product and 34
end-use-products) registered under Section 3 of the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA).
B. Chemical Identification
1. Para-Tertiary-Amylphenol & its Potassium and Sodium Salts
CH
"Na
CH 3
P aratertiaryam yl Phenol, Sodium Salt
CH 3
P aratertiaryam yl Phneol, Potassium Salt
Common name: Para-Tertiary amylphenol
Chemical name: 4-tertiary-amylphenol, and salts
Chemical Family: Antimicrobial Disinfectant
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Empirical formula: C5H! 1C6H4OH (064101) C5H! 1C6H4Na+ (064111)
C5H11C6H4K+(064112)
CAS Registry No.: 064101: 80-46-6 (4-t-amylphenol)
064111: 53404-18-5 (sodium salt)
064112: 31366-95-7 (potassium salt)
Case number: 3016
OPP Chemical Code: 064101, 064111, 064112
Molecular weight: 164.25 (064111)
Trade name: Nipacide PTAP
Basic manufacturer: Clariant Corporation
Technical 4-t-amylphenol is a white solid. 4-t-Amylphenol has a melting point of 95 C.
The water solubility of 4-t-amylphenol is 113.4 ppm. 4-t-Amylphenol has a vapor pressure of
1.16xlO-3mmHgat25°C.
Sodium 4-tert-amylphenate is also a solid with an estimated melting point of 205 C,
water solubility of 4,595 ppm and an estimated vapor pressure of 7.7 xlO"10 at 25°C. Potassium
4-tert-amylphenate is also a sold with an estimated melting point of 206 C, water solubility of
-10
3,811 ppm and an estimated vapor pressure of 7.7 xlO" at 25 C.
C.
Use Profile
The following is information on the currently registered uses of 4-t-amylphenol and salts
products and an overview of use sites and application methods. A detailed table of the uses of
eligible for reregistration is contained in Occupational and Residential Exposure Assessment for
this RED.
Type of Pesticide:
Summary of Use:
Food:
Non-Food:
Antimicrobial
4-tert-amylphenol and its salts are applied to the following use sites, which
may result in indirect food contact: commercial egg washing, handling,
hatchery, and processing facilities; milking equipment; and mushroom
houses.
Farm and agricultural equipment and structures/premises; beverage
processing plants; eating establishment surfaces, equipment, and utensils;
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Residential:
food storage and distribution equipment and utensils; and food dispensing
equipment.
Air deodorizer in residential premises, hard surface disinfection, textiles,
and carpets.
Target Pests: Viruses, fungi, tuberculocidal microbes, bacteria, pseudomonacidal
microbes, and staphylocidal microbes.
Formulation Types: Soluble concentrates, ready-to-use liquid solutions, pressurized sprays,
and impregnated wipes
Method and Rates of Application:
Equipment: Mops, wipes, trigger-pump sprayer, aerosol.
Application Rates: Concentrations of 4-t-amylphenol and salts products range from 0.0027%
to 10%.
Timing:
Most labeling indicates product needs to remain on surface for at least a
10 second contact time before it is removed using a potable water rinse.
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III. Summary of 4-Tert-Amylphenol 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 4-t-amylphenol. 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. Toxicity of 4-tertiary-amylphenol
A brief overview of the toxicity studies used for determining the dietary endpoints in the
risk assessments are outlined in Table 2. Further details on the toxicity of 4-t-amylphenol can be
found in the "Toxicology Science Chapter for Reregistration Eligibility Decision Document",
September 2005; and "4-t-amylphenol Report of the Antimicrobial Division's Toxicology
Endpoint Selection Committee (ADTC)", July 2005. These documents are available on
Agency's website in the EPA Docket at http://www/epa.gov/edockets. (OPP-2005-0181)
The Agency has reviewed all toxicity studies submitted for 4-t-amylphenol and has
determined that the toxicological database is sufficient for reregistration. Major features of the
toxicology profile are presented below. The toxicology database for 4-t-amylphenol, in terms of
guideline studies, is largely incomplete. 4-t-amylphenol appears to be a primary dermal and eye
irritant (Category I), and it may be in Category III for acute oral dermal studies, according to
data from the open literature, and two registrant submitted studies. However, four acceptable
guideline acute studies are not available, and the literature data protocols were inadequate.
Table 1. Acute Toxicity of 4-t-amylphenol Technical
Guideline No./ Study Type
870. 1 100 Acute Oral Toxicity
870.1200 Acute Dermal Toxicity
870. 1300 Acute Inhalation Toxicity
870.2400 Acute Eye Irritation
870.2500 Acute Dermal Irritation
870.2600 Skin Sensitization
MRID
Number
46616601
Results
LD50 >2000 mg/kg
Toxicity
Category
III
Not available; required
Not available; required
Not available; required
46616602
Corrosive
I
Not available; required
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The doses and toxicological endpoints selected for the dietary exposure scenarios are
summarized in Table 2 below.
Table 2. Toxicological Endpoints for 4-t-amylphenol and salts (Dietary)
Exposure
Scenario
Acute Dietary
(Females 13-50
years of age)
Chronic Dietary
(All populations)
Dose for Risk
Assessment and
Uncertainty Factor
NOAEL = 200
mg/kg/day
UF= 100
Acute RfD = 0.67
mg/kg/day
NOAEL=50 mg/kg/day
UF= 100
Chronic RfD = 0.17
mg/kg/day
Special FQPA Safety
Factor and Population
Adjusted Dose
FQPA SF = lOx
aPAD = acute RfD
FQPA SF
= 0.6 mg/kg/day
FQPA SF = lOx
cPAD = chronic RfD
FQPA SF
= 0.17 mg/kg/day
Study and Toxicological Effects
Developmental Toxicity Study in Rats
LOAEL = 500 mg/kg/day based on
skeletal effects and decreased fetal body
weight.
Developmental toxicity study in the rat.
LOAEL = 200 mg/kg/day based on
clinical signs of toxicity, decreased body
weight and body weight gain, and
decreased food consumption.
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse
effect level, PAD = population adjusted dose, (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, N/A = Not Applicable
In short-term studies, 4-t-amylphenol produced clinical signs along with decreased food
consumption and body weight in a developmental toxicity study, but not systemic effects in a 13-
week dermal study. The structural abnormalities and developmental delays that occurred in the
developmental study occurred at higher dose levels than the maternal effects, suggesting that
increased quantitative susceptibility concerns are not warranted. However, the minimal maternal
effects (reversible clinical signs) seen in the presence of developmental effects increases concern
for qualitative susceptibility.
Available data suggest that 4-t-amylphenol has endocrine disrupter capabilities
(uterotrophic and estrogenic effects) and increased billirubin production in babies. When taken
with the lack of available developmental and reproductive toxicity data, concerns for FQPA
issues are heightened.
General Toxicity Observations
Dietary
The acute RfD is 0.67 mg/kg/day for females (13-50 years), based on adverse
developmental effects (skeletal effects and decreased fetal body weight) at 500 mg/kg/day in a
rat developmental study. The chronic RfD is 0.17 mg/kg/day based on clinical signs of toxicity
and decreased body weight and food consumption at 200 mg/kg/day in a rat developmental
study. An uncertainty factor of 300 (10X for interspecies extrapolation, 10X for intraspecies
variability, and 3X for database uncertainties) was applied to the NOAEL to obtain the acute and
chronic RfDs. A database uncertainty factor of 3x is applied to non-occupational risk
assessments for 4-t-amylphenol, due to the number and significance of the data gaps including
lack of repeated oral toxicity studies. An additional Food Quality Protection Factor (FQPA)
safety factor is applied, which is discussed below.
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Incidental Oral
The short- and intermediate-term incidental oral NOAEL is 50 mg/kg/day from a rat oral
developmental toxicity study that noted clinical signs, decreases in body weight and body weight
gain, coupled with decreased food consumption at 200 mg/kg/day. The target margin of
exposure (MOE) is 3,000 (includes 10X FQPA factor).
Short- and Intermediate-term Dermal
The short- and intermediate-term dermal NOAEL is 25 mg/kg/day, which is based on the
lack of systemic effects identified up to and including a dose of 25 mg/kg/day in a rat subchronic
dermal toxicity study. Uncertainty factors or "target" margins of exposure (MOE) for 4-t-
amylphenol dermal exposures are 100 for occupational scenarios and 1,000 for residential
scenario (includes 10X FQPA factor).
Short-, Intermediate- and Long-term Inhalation
The short-, intermediate- and long-term inhalation NOAEL is 50 mg/kg/day from a rat
oral developmental toxicity study that noted clinical signs, decreases in body weight and body
weight gain, coupled with decreased food consumption at 200 mg/kg/day. In the absence of
data, it was conservatively assumed that inhalation absorption is equivalent to oral absorption
(i.e., 100%). For inhalation exposures, the uncertainty factors are 300 for occupational scenarios
and 3,000 for residential scenarios (includes 10X FQPA factor). An additional 3X database
uncertainty factor was applied due to the absence of inhalation toxicity data, and studies that
address the sensitivity of infants and children. The 3,000 MOE represents the maximum
uncertainty that can be applied under Agency guidelines and applies to residential exposures.
Carcinogenicity Classification
There are no lifetime carcinogenicity studies available for 4-t-amylphenol.
Mutagenicity Potential
The data base for mutagenicity is considered adequate based on EPA's 1991 mutagenic
guidelines and indicates that 4-t-amylphenol 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." 4-t-Amylphenol has properties that could indicate Endocrine Disrupting
Chemical (EDC) properties given that available data suggest that 4-t-Amylphenol has endocrine
disrupter capabilities (uterotrophic and estrogenic effects) and increased billirubin production in
babies.
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
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retained (i.e., remains 10X) for 4-t-amylphenol based on the limited database, qualitative
evidence of sensitivity in the developmental toxicity study, and the suggestive evidence in the
open literature of possible endocrine effects.
The toxicology data base is not complete with respect to assessing that increased
susceptibility to infants and children as required by FQPA for 4-t-Amylphenol. The rat prenatal
developmental study showed no quantitative evidence of increased susceptibility (i.e.,
developmental NOAELs/LOAELs were higher than those for maternal effects). However, there
was qualitative evidence of increased susceptibility [i.e., fetal effects (skeletal abnormalities,
decreased body weight gain) were considered to be more severe than the maternal toxicity
(reversible clinical signs) observed at the same dose level]. In addition, there is an absence of
developmental toxicity data in the rabbit and an absence of reproductive toxicity data.
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 4-t-amylphenol 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 (0.67 mg/kg/day)
modified by the FQPA safety factor. The acute reference dose was derived from a
developmental toxicity study in rats in which both the NOAEL (200 mg/kg/day) and the LO AEL
(500 mg/kg/day) were determined. Acute dietary exposure was estimated only for females ages
13-49 because available studies did not show a toxicity endpoint attributable to a single exposure
for the general population. The 4-t-amylphenol aPAD is 0.067 mg/kg/day based on a reference
dose of 0.6 mg/kg/day, and incorporating the FQPA safety factor of 10X.
b. Chronic PAD
Chronic dietary risk for 4-t-Amylphenol 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 (0.17
mg/kg/day) modified by the FQPA safety factor. The cPAD was derived from a developmental
toxicity study in rats in which both the NOAEL (50 mg/kg/day) and the LOAEL (200
mg/kg/day) were determined. The 4-t-amylphenol cPAD is 0.017 mg/kg/day based on a
reference dose of 0.17 mg/kg/day, which includes the incorporation of the FQPA safety factor
(10X) for the overall U.S. population or any population subgroups.
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4. Exposure Assumptions
The use of antimicrobial chemicals on food or feed contact surfaces, agricultural
commodities, in animal premises and poultry premises including hatcheries and application to
food-grade eggs may result in pesticide residues in human food. The Agency must determine the
risk to human health that may occur from exposure to these chemicals.
Refrigerators, counter tops, sinks and stoves are use sites on registered labels. These
surfaces that have been treated with the 4-t-amylphenol products may bear small residues of the
4-t-amylphenol products after rinsing with potable water; i.e., rinsing with potable water may not
remove all residues deposited on the treated surfaces from the proposed uses. Residues from
treated surfaces can migrate to food coming into contact with the treated and rinsed surfaces and
can be ingested by humans.
In the absence of residue data for 4-t-amylphenol on treated food contact surfaces, the
Agency estimated residue levels that may occur in food using the highest application rate for
food contact surfaces. To estimate the Estimated Daily Intake (EDI), the Agency has used an
FDA model. The maximum ingredient percentage for 4-t-amylphenol in food handling
establishments from the various labeled ready-to-use products is 0.054 % a.i (540 ppm). The
Agency assumed that food can contact 2000 cm2 of treated surfaces, and that 10% of the
pesticide migrates to food based on the Agency Residential SOPs. The use of the 10% transfer
rate instead of the use of a 100% transfer rate that is used in the FDA Sanitizer Solution
Guidelines requires the submission of confirmatory data to establish the reliability of the use of
the 10% transfer rate. These daily estimates were conservatively used to assess both acute and
chronic dietary.
5. Dietary (Food) 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 3.
a. Acute Dietary Risk
An acute dietary risk assessment was conducted for 4-t-amylphenol food uses. Dietary
risk estimates are provided for females 13-49 years old, the only population subgroup for which
an endpoint was selected. The result of this assessment showed the risk estimate to be 2.7% of
the aPAD and therefore is not of concern
b. Chronic (Non-cancer) Dietary Risk
A chronic dietary risk assessment was conducted for 4-t-amylphenol food uses. The risk
analysis assumes daily exposure from the hard surface disinfection of counter tops. The result of
this assessment showed the risk estimates to be <42% of the cPAD and therefore are not of
10
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concern. However, since the Agency assumed 10% of the residues are transferred to foods it is
requiring confirmatory data for this transfer rate because 100% residue transfer indicates risks of
concern.
Table 3: Acute and Chronic Dietary Exposure and Risk
Population
Subgroup
adult male
females (13-50
years)
infants/children
Acute Dietary
Dietary Exposure
(mg/kg/day) a
0.0015
0.0018
0.0072
% aPAD b
NA
2.7
NA
Chronic Dietary
Dietary Exposure
(mg/kg/day) a
0.0015
0.0018
0.0072
% cPAD b
9
10.6
42
NA=not applicable
b. Dietary Risk from Drinking Water
4-t-Amylphenol and its salts are not likely to contaminate surface and ground waters
based on its use patterns and fate characteristics. There are no currently registered outdoor uses
of 4-t-amylphenol and its salts. Further, the estimated value for biodegradation indicates it may
biodegrade linearly within days in the aquatic environment, although ultimate biodegradation
(mineralization) may take months. It also is volatile based on its vapor pressure of 0.00116
mmHg, and has a moderate to slight mobility in soils based on its estimated Koc value of 3799.
The sodium and potassium salts of 4-t-amylphenol also are slightly to moderately mobile in
soils, and are estimated to biodegrade within days to weeks. Because of the possibility of
biodegradation in water and soils and the lack of outdoor uses, 4-t-amylphenol and its salts are
not likely to contaminate surface and ground waters. Thus, a drinking water assessment was not
conducted.
6. Residential Exposure
Residential exposure assessment considers all potential pesticide exposure, other than
exposure due to residues in food or in drinking water. Exposure may occur during and after
application as a hard surface disinfectant (e.g., walls, floors, tables, fixtures), to textiles (e.g.,
clothing, diapers, mattresses, bedding) and to carpets. Each route of exposure (oral, dermal,
inhalation) is assessed, where appropriate, and risk is expressed as a Margin of Exposure (MOE),
which is the ratio of estimated exposure to an appropriate NOAEL. Based on its use patterns, 4-
t-amylphenol has been assessed for the residential mixing/loading/applicator (or "handler")
exposure for applications by homeowners mopping, wiping and spraying hard surfaces. For
post-application exposure, 4-t-amylphenol has been assessed for adults and children contacting
treated hard surfaces/floors, wearing treated clothing, wearing treated diapers (children),
mouthing treated textiles (children) and bystander inhalation exposure.
11
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a. Toxicity
The toxicological endpoints and associated uncertainty factors used for assessing the non-
dietary risks for 4-t-amylphenol are listed in Table 4.
A MOE greater than or equal to 3,000 is considered adequately protective for the
residential exposure assessment for the incidental oral and inhalation routes of exposure. The
MOE of 3,000 includes lOx for interspecies extrapolation, lOx for intraspecies variation, 3x for
database uncertainty and the lOx FQPA factor. For the dermal route of exposure, a MOE greater
than or equal to 1,000 is considered adequately protective for the residential exposure
assessment. The MOE of 1,000 includes lOx for interspecies extrapolation, lOx for intraspecies
variation and the lOx FQPA factor.
Table 4: Toxicity Endpoints Selected for Assessing Occupational and Residential Risk for
4-t-Amylphenol
Exposure
Scenario
Incidental Oral,
Short- and
Intermediate-Term
Short-, and
Intermediate -Term
Dermal
Short-, Intermediate-,
and Long-Term
Inhalation
Cancer
Dose Used in
Risk Assessment
Maternal Oral
NOAEL = 50
mg/kg/day
Dermal NOAEL =
25
mg/kg/day for
systemic effects
Oral
NOAEL = 50
mg/kg/day
Level of Concern
for Risk
Assessment
Residential LOCfor
MOE = 3000
Occupational = NA
Residential LOCfor
MOE = 1000
Occupational = 100
Residential LOCfor
MOE = 3000
Occupational = 300
Study and Toxicological
Effects
Developmental toxicity study in
the rat
LOAEL = 200 mg/kg/day based
on clinical signs of toxicity,
decreased body weight and body
weight gain, and decreased food
consumption
Subchronic dermal toxicity study
in Rats
Systemic LOAEL = not
identified. No systemic effects
identified up to and including 25
mg/kg/day (HOT).
Dermal LOAEL= 10 mg/kg/day
for dermal effects and irritation.
Dermal NOAEL=2.5 mg/kg/day
Developmental toxicity study in
the rat
LOAEL = 200 mg/kg/day based
on clinical signs of toxicity,
decreased body weight and body
weight gain, and decreased food
consumption.
No cancer data available for 4-t-amylphenol
HDT= Highest dose tested
12
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b Residential Handler
i. Exposure Scenarios, Data and Assumptions
Residential exposure may occur during application of 4-t-amylphenol as a hard surface
disinfectant (e.g., walls, floors, tables, fixtures), to textiles (e.g., clothing, diapers, mattresses,
bedding) and to carpets. A number of assumptions, or estimates, such as adult body weight and
area treated per application, are made by the Agency for residential risk assessment. Also, note
that residential handlers are sometimes addressed somewhat differently than occupational
handlers in that homeowners are assumed to complete all elements of an application
(mix/load/apply) without the use of personal protective equipment.
The quantitative exposure/risk assessment developed for residential handlers is based on these
scenarios:
(1) mopping hard surfaces,
(2) wiping hard surfaces,
(3) using trigger pump equipment to treat hard surfaces and/or textiles, and
(4) application to air using an aerosol spray can
4-t-Amylphenol products are widely used disinfectants and have a large number of use
patterns that are difficult to completely capture in this assessment. As such, the Agency has
selected representative scenarios for each use site that are believed to be representative of the
vast majority of 4-t-amylphenol uses, based on end-use product application methods and use
amounts.
Surrogate data are available for mopping, wiping, trigger pump spray and aerosol can
application methods. Dermal and inhalation exposures were assessed for mopping and wiping
using proprietary Chemical Manufacturers Association (CMA) data (CMA 1992, USEPA 1999).
These data are based on individuals mopping floors and receiving exposure via contact with the
mop or with the bucket, or using a finger pump sprayer to apply the product and then wipe the
surfaces with a paper towel. Dermal and inhalation exposures were assessed for trigger pump
spray and aerosol application methods using PHED Version 1.1 values found in the Residential
Exposure SOPs (U.S. EPA, 1997a, 2001). The surrogate exposure data in PHED are based on
test subjects applying an aerosol insecticide to baseboards in kitchens. The dermal and
inhalation exposures from these techniques have been normalized by the amount of active
ingredient handled and reported as unit exposures (UE) expressed as mg/lb ai handled.
In addition, product label maximum application rates, related use information, and
Agency standard values were used to assess residential handler exposures. For example, it was
assumed that one gallon of diluted solution is used for mopping floors, while 0.5 liters (0.13
gallons) are used in the wiping and trigger pump spray scenario. For aerosol can spray, it was
assumed that one 16 oz can of product is used in a day. The residential handler scenarios are
assumed to be of short- and intermediate-term duration (1-30 days and 1-6 months)
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ii. Residential Handler Risk Estimates
Based on toxicological criteria and potential for exposure, the Agency has conducted
dermal and inhalation exposure assessments. As noted previously, MOEs greater than or equal to
3,000 for the inhalation route of exposure and 1,000 for dermal exposure are considered
adequately protective for the residential exposure assessment.
A summary of the residential handler exposures and risk are presented on Table 5. For
residential handlers that handle products containing 4-t-amylphenol and its salts, short-term, and
intermediate-term MOEs were above the target MOEs (i.e., >1000 for dermal and >3000 for
inhalation) for all scenarios evaluated and thus, do not exceed the Agency's level of concern.
Table 5: Estimates of Exposures and Risks to Residential Handlers of 4-t-Amylphenol
(Short- and Intermediate-Duration)
Scenario
(1) Mopping
(2) Wiping
(3) Trigger Pump Spray
(4) Aerosol Spray
Dermal
Dose
(mg/kg/day)
0.00128
0.00666
0.00198
0.00233
Inhalation
Dose
(mg/kg/day)
4.25x10°
1.56xlO'4
2.16xlO'5
2.54xlO'5
Dermal MOE
(Target
MOE>1000)
20,000
3,800
13,000
11,000
Inhalation MOE
(Target
MOE>3000)
1,200,000
320,000
2,300,000
2,000,000
c. Residential Post-Application
i. Exposure Scenarios, Data and Assumptions
Residential postapplication exposures result when bystanders (adults and children) come
in contact with 4-t-amylphenol in areas where pesticide end-use products have recently been
applied (e.g., treated hard surfaces/floors), or when children incidentally ingest the pesticide
residues through mouthing the treated end products/treated articles (i.e., hand-to-mouth or
object-to-mouth contact).
For the purposes of this screening level assessment, postapplication scenarios have been
developed that encompass multiple products, but still represent a high end exposure scenario for
all products represented. Representative postapplication scenarios assessed include:
contacting treated hard surfaces/floors (dermal and incidental oral exposure to
children),
• wearing treated clothing (dermal exposure to adults and children),
• wearing diapers treated with a trigger-pump spray (dermal exposure to children),
mouthing treated textiles such as clothing and blankets (incidental oral exposure
to children), and
14
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postapplication/bystander inhalation exposures from use of
disinfecting/deodorizing products (vapor exposure to adults and children).
Typically, most products used in a residential setting result in exposures occurring over
a short-term time duration (1 - 30 days). If the products are used on a routine basis (i.e., once a
week) and the active ingredient has a long indoor half-life, exposures may occur over an
intermediate-term time duration (30 days - 6 months). At this time, the Agency does not have
residue dissipation data or reliable use pattern data, including the frequency and duration of use
of antimicrobial products in the residential setting. Even though the Agency does not believe
that the use patterns of many residential products result in intermediate-term exposure, they are
assessed to provide an upper bound estimate of exposure. The Agency does believe, however,
that intermediate-term exposure to children may occur in day care centers where disinfecting
products are used more frequently.
A number of conservative assumptions were used in assessing postapplication risks
including maximum application rate from the label. In addition quantities handled/treated were
estimated based on information from various sources, including the Draft Standard Operating
Procedures (SOPs) for Residential Exposure Assessments (USEPA 2000, 2001) and the AD
Draft Residential SOP use table. In certain cases, no standard values were available for some
scenarios. Assumptions for these scenarios were based on AD estimates and could be further
refined from input from affected sectors. In the absence of data, for both the textile and diaper
scenarios, it was assumed that either 100% or 5% of 4-t-amylphenol could transfer and be
available for dermal contact. The Agency will require data to confirm the actual transfer factor
of 4-t-amylphenol.
No postapplication air concentration data have been submitted for 4-t-amylphenol to
determine potential vapor inhalation risk. Therefore, the Multi-Chamber Concentration and
Exposure Model (MCCEM vl.2) was used to present a screening-level estimate of the potential
inhalation risk to adults and children for the air deodorizer use. MCCEM estimates average and
peak indoor air concentrations of chemicals released from products or materials in houses,
apartments, townhouses, or other residences. The data libraries in MCCEM contain information
about residential settings. MCCEM estimates inhalation exposures to chemicals, calculated as
single day doses, chronic average daily doses, or lifetime average daily doses. All dose estimates
are potential doses; they do not account for actual absorption into the body.
ii. Residential Post-Application Risk Estimates
Based on toxicological criteria and potential for exposure, the Agency has conducted
dermal, incidental oral and inhalation exposure assessments. As noted previously, MOEs greater
than or equal to 3,000 for incidental oral and inhalation exposure and 1,000 for dermal exposure
are considered adequately protective for the residential exposure assessment. A summary of the
residential post-application exposures and risk are presented on Table 6.
The child short- and intermediate-term dermal MOEs for contact following hard surface
disinfection is above the target MOE of 1,000 for residential settings and slightly below the
MOE for daycare centers. The short- and intermediate-term MOEs for dermal contact with
15
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treated clothing is of concern for young children (MOEs are <1 assuming a 100% transfer factor;
MOE=17 assuming a 5% transfer factor). For adults, the dermal MOE is below the target MOE
of 1,000 using a 100% transfer factor (MOE = 140) and above the MOE using the 5% transfer
factor. The dermal MOE for children wearing treated diapers is only of concern (MOE=59)
using a transfer factor of 100%, but it not of concern when using a transfer factor of 5%. In
addition, it should be noted that 4-t-amylphenol caused dermal irritant effects following repeated
dermal exposure, and may also be a potential dermal sensitizer.
The short- and intermediate-term incidental oral MOEs following hard surface
disinfection are above the target MOE of 3,000 for residential settings and daycare centers, and
thus are not of concern. However, the oral MOE for children mouthing treated textiles exceeds
the Agency's level of concern (MOE=650 compared to target MOE>3,000).
For both adults and children, the calculated inhalation MOEs are greater than the target
MOE of 3,000 for inhalation exposures following use of an air deodorizer, and thus are not of
concern.
Table 6: Summary of Short- and Intermediate-Term Residential Post-Application
Exposures and Risks
Scenario
Dose
(mg/kg/day)
MOE
(Target MOE>1000 dermal;
>3000 oral and inhalation)
Dermal Exposure
Hard surface
Disinfection
Treated clothing
Treated Diapers
Residential Setting
Daycare center
Adults
Children
Children
0.0067
0.0267
0.0092 (5% transfer)
0.185 (100% transfer)
1.45 (5% transfer)
28.9 (100% transfer)
0.02 12 (5% transfer)
0.424 (100% transfer)
3,700
940
2,700
140
17
<1
1,200
59
Incidental Oral Exposure
Hard surface
Disinfection
Treated clothing
Residential Setting
Daycare center
Children
0.000817
0.00155
61,000
32,000
650
Inhalation Exposure
Air Deodorizer
Adults
Children
0.00186
0.00666
27,000
7,500
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. Since no drinking water estimates
16
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were developed for 4-t-amylphenol, aggregate assessments include exposure to food and as a
result of residential uses only.
Typically, aggregate risk assessments are conducted for acute (1 day), short-term (1-30
days), intermediate-term (1-6 months) and chronic (6 months to lifetime) exposures. However,
acute and chronic aggregate assessments were not conducted because there are no significant
impacts to drinking water sources, nor are there long-term residential uses. Thus, only short- and
intermediate-term aggregate assessments were conducted. Oral and inhalation exposure and risk
estimates were combined for the aggregate risk assessment because these endpoints are based on
the same toxicity study (oral developmental study) and effects of concern (clinical signs and
changes in body weight and food consumption). Dermal exposures were not aggregated with the
oral or inhalation exposures due to different toxicological endpoints for oral (clinical signs and
body weight changes), and dermal (no systemic effects at the highest dose tested).
a. Short- and Intermediate-Term Aggregate Risk
Aggregate short- and intermediate-term risk assessments are designed to provide
estimates of risk likely to result from exposures to the pesticide or pesticide residues in food,
water, and from residential (or other non-occupation) pesticide uses. Short- and intermediate-
term aggregate risks are considered together because the exposure and toxicity endpoints are
identical for incidental oral and inhalation residential exposures for both durations. For children,
the short- and intermediate-term aggregate assessment includes average dietary exposure (food)
and estimated incidental oral exposures to children from residential uses such as hard surface
disinfection. In addition, inhalation exposure from postapplication of an air deodorizer use was
aggregated with the oral exposures since the toxicity endpoint is the same. For adults, the
aggregate assessment includes dietary (oral) and residential inhalation exposures from wiping a
hard surface disinfectant, in addition to post application inhalation exposure from the air
deodorizer.
The results of the aggregate short- and intermediate-term risk assessments are presented
in Table 7. The aggregate oral and inhalation risks are not of concern for adults, as the total
aggregate MOE is greater than the target of 3,000. For children, the aggregate risk estimates are
also above the target MOE of 3,000 and thus are not of concern. As noted previously, incidental
oral exposures to treated textiles are not included in the aggregate assessment because the oral
MOE is already of concern.
A dermal aggregate assessment was not conducted because the toxicity effects for the
dermal exposure route are not the same as the oral/inhalation exposure route. However, as
shown previously on Table 6, short- and intermediate dermal risks are already of concern for
residents for the treated textile and diaper use.
17
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Table 7. Summary of Short- and Intermediate-Term Aggregate Risk Estimates
Exposure
Scenario
Oral Exposure
Dietary Exposure
Hard Surface
Disinfection -
Daycare Center
Inhalation Exposure
Handler of hard
surface
Disinfectant -
wiping
Air Deodorizer
Total Aggregate
Dose & MOE
DC
(mg/k
Child
0.0072
0.00155
NA
0.00666
0.0154
»se
?/day)
Adult
0.0018(a)
NA
0.000156
0.00186
0.00316
Total MOE (b)
(Target MOE>3000
Child
6940 (c)
32,000
NA
7,500
3,240
Adult
28,000 (c)
NA
320,000
27,000
13,000
NA: Not Applicable.
(a): Chronic Dietary Exposure for Females (13-50 years).
(b): MOE = NOAEL (mg/kg/day) / potential dose rate (mg/kg/day) [Where short- &
intermediate-term oral NOAEL = 50.
(c): Risk estimates are equivalent to percent of the PAD of 42% for child and 10.6% for adults.
b. Long-Term Aggregate Risk
A long-term (or chronic) aggregate assessment was not undertaken because the only
long-term residential use (diaper use) results in dermal exposure, which has a different
toxicological effect than the chronic dietary oral exposure.
8. Occupational Exposure and Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Occupational handlers of 4-t-amylphenol include workers
in a variety of occupational settings. Additionally, postapplication exposures are likely to occur
in these settings. The representative scenarios selected for assessment were evaluated using
maximum application rates as recommended on the product labels for 4-t-amylphenol.
Occupational risk is assessed for exposure at the time of application (termed "handler"
exposure) and is assessed for exposure following application, or post-application 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 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 4-t-
amylphenol, MOEs greater than 100 for dermal exposures and 300 for inhalation exposures are
not of concern to the Agency. For workers entering a treated site, MOEs are calculated for each
day after application to determine the minimum length of time required before workers can
safely re-enter.
18
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For more information on the assumptions and calculations of 4-t-amylphenol 's potential
risk to workers, see the Occupational Exposure Assessment (Section 8.0) in the "AD Risk
Assessment for the Reregistration Eligibility Decision (RED) Document"(Revised)," dated
September, 2005. 3
a. Occupational Toxicity
Table 4 provides a listing of the toxicological endpoints used in the occupational risk
assessment for 4-t-amylphenol.
b. Occupational Handler Exposure
Potential occupational handler exposure can occur at various use sites, including
agricultural premises, food handling, commercial/institutional/industrial premises, and medical
premises. MOEs are: > 100 for dermal exposure and; >300 for inhalation exposure. Only the
high pressure spray in the agricultural use scenario was evaluated using gloved data.
The Agency has determined that there is potential for dermal and inhalation worker
exposure to 4-t-amylphenol at various use sites including agricultural premises, food handling,
commercial/institutional/industrial premises, and medical premises. To assess handler risks, the
Agency used surrogate unit exposure data from both proprietary Chemical Manufacturers
(CMA) antimicrobial exposure study and the Pesticide Handlers Exposure Database (PHED).
c. Occupational Handler Risk Summary
For the occupational handler dermal and inhalation risk assessment, the short- and
intermediate- term risks calculated at baseline exposure (no gloves and no respirators) were
above target MOEs for all scenarios (i.e., dermal MOEs were >100 and inhalation MOEs were
>300). Note, however, that the high pressure spray application method in the agricultural use site
category was assessed using gloved data. A summary of the results of the occupational handler
assessment is provided in Table 8.
19
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Table 8: Short-, Intermediate-Term Risks for Occupational Handlers
Exposure
Scenario
Method of
Application
Application
Rate (Ibai/
gallon)
Quantity
Handled/
Treated per
day (gallons)
MOE
Baseline
Dermal (a)
(Target
MOE>100)
PPE Gloves
Dermal (b)
(Target
MOE>100)
Baseline
Inhalation
(Target
MOE>300)
Agricultural Premises and Equipment
Application
to hard
surfaces
Fogger
Low Pressure
Handwand
High Pressure
Handwand
Mopping
Wiping
Trigger Pump
Spray
Liquid Pour of
soluble
concentrate
0.0034
0.1631b
ai/gal/
6,000 ft2
10
40
2
0.26
0.26
15,000 ft2
270
No Data
3,600
690
10,000
120
No Data
5,100
No Data
No Data
24,000
No Data
150,000
210,000
220,000
59,000
3,000,000
4,500
Food Handling
Application
to indoor
hard surfaces
Low Pressure
Handwand
Mopping
Wiping
Trigger Pump
Spray
0.0025
2
2
0.26
0.26
1,800
4,900
940
7,300
No Data
No Data
No Data
17,000
1,000,000
290,000
80,000
2,100,000
Commercial/Institutional Premises
Application
to indoor
hard surfaces
Low Pressure
Handwand
Mopping
Wiping
Trigger Pump
Spray
Air Aerosol
Deodorization Spray
0.005
0.074% ai
by weight
2
2
0.26
0.26
3 16 oz cans
920
2,400
470
7,100
4,100
No Data
No Data
No Data
17,000
9,700
510,000
150,000
40,000
2,100,000
1.200,000
Medical Premises and Equipment
Application to
indoor hard
surfaces
Low Pressure
Handwand
Mopping
Wiping
Trigger Pump
Spray
Air Aerosol
Deodorization Spray
0.005
0.074% ai
by weight
2
45
0.26
0.26
3 16 oz cans
920
110
470
7,100
4,100
No Data
No Data
No Data
17,000
9,700
510,000
6,500
40,000
2,100,000
1,200,000
(a) Baseline Dermal: Long-sleeve shirt, long pants, no gloves.
(b) PPE Dermal with gloves: baseline dermal plus chemical-resistant gloves.
20
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d. Occupational Post-application Risk Summary
For most of the occupational scenarios, postapplication dermal exposure is not expected
to occur or is expected to be negligible based on the application rates and chemical properties of
the chemical. Postapplication/bystander inhalation exposures, however, were assessed for entry
into a building after a fogging application. The representative building selected was a poultry
barn. The Agency used the MCCEM (Multi- Chamber Concentration and Exposure Model) to
estimate postapplication/bystander exposures. The calculated inhalation MOEs were above the
target MOE of 300 for all fogging postapplication scenarios with the exception of the scenario
for 8-hr exposure to the product with a 2-hr reentry interval (MOE = 86).
The Agency does not believe that any mitigation is necessary to address the post-
application scenario with a 2-hr reentry interval at this time. The risk estimate was calculated
using the Agency's standard assumptions for air exchange rates. The Agency believes that in the
case of animal barns and facilities this assumption in very conservative given the relatively high
air exchange rates for such facilities.
e. Human Incident Data
There are some reported incidents associated with exposure to end-use products
containing 4-t-amylphenol. Dermal, ocular and inhalation are the primary routes of exposure.
Most of the incidents are related to irritation reaction. The most common symptoms reported for
cases of inhalation exposure were respiratory irritation/burning, irritation to mouth/throat/nose,
coughing/choking, shortness of breath, dizziness, flu-like symptoms, and headache. Eye pains,
burning of eyes, conjunctivivitis, blurring vision, and acute inflammation have been reported in
ocular incidents. Neurological effects, such as dizziness, headache and blurred vision also have
been reported.
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. The
following risk characterization is intended to describe the magnitude of the estimated
environmental risks for 4-t-amylphenol use sites and any associated uncertainties. A detailed
ecological hazard and environmental risk assessment for 4-t-amylphenol and its salts is presented
in "Ecological Hazard and Environmental Risk Assessment for 4-tert-amylphenol and salts to be
included in the RED", September 2005. A brief summary is presented below.
1. Environmental Fate and Transport
The environmental fate assessment for 4-t-amylphenol and its potassium and sodium salts
is based on US EPA s Estimation Programs Interface (EPI) Suite. EPI Suite provides estimations
of physical/chemical properties and environmental fate properties.
4-t-Amylphenol may be bioaccumlative (log K0w 3.91) and is likely to pose a concern
for aquatic organisms. It is expected to have moderate to slight mobility in soils based upon the
estimated Koc value of 3799. Estimated value for biodegradation probability indicates that it
21
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may biodegrade linearly within days in aquatic medium. However, ultimate biodegradation
(mineralization) may take months. It is volatile and may vaporize into the atmosphere. The
estimated half life in the air for 4-t-amylphenol is about three hours which indicates that it is not
persistent in air. Because of the possibility of biodegradation in water and soils, it is not likely to
contaminate surface and ground waters.
4-t-Amylphenol, potassium salt, is not likely to be bioaccumlative ( log KOW 1.23) and
may not pose a concern for bioconcentration in aquatic organisms. It may be expected to have
moderate to slight mobility in soils as its estimated Koc value is 3799. Estimated probability of
biodegradation of 4-t-amylphenol, potassium salt, in soils and water indicates that it is likely to
biodegrade within days to weeks. Therefore, it may be unlikely that soil and water
contamination would take place. It has low volatility and its estimated half life in air is about
4.68 hours and is not likely to be persistent in air.
4-t-Amylphenol, sodium salt, is not likely to be bioaccumlative (log KOW is 1.23) and
may not pose a concern for bioconcentration in aquatic organisms. It may be expected to have
moderate to slight mobility in soils as its estimated Koc value is the same as the parent molecule,
4-t-amylphenol. Probability for sodium 4-t-amylphenate biodegradation is the same as the
parent molecule, 4-t-amylphenol. Hence, it is not likely to persist in soils and water, and surface
and ground water contamination is not likely to occur. It has low volatility and its estimated
half life in air is about 4.68 hours and is not likely to be persistent in air.
2. Ecological Risk
Guideline ecological effects data has not submitted for 4-t-amylphenol. The only data
that was available was found in the peer-reviewed literature. None of these studies met current
guideline requirements and therefore, could not be used in a risk assessment. There is a concern
about the possibility of endocrine disruption in fish, since 4-t-amylphenol is considered an
ecoestrogen. This was documented in several studies on carp (Cyprimus carpio). However,
since this chemical is restricted to indoor uses only, the possibility for exposure to fish to 4-t-
amylphenol would be limited. The limited exposure resulting from indoor uses of 4-t-
amylphenol and its salts is not anticipated to cause adverse effects to terrestrial or aquatic
organisms.
The acute toxicity data for 4-t-amylphenol are summarized on Table 9. As shown in
Table 9, acute toxicity for freshwater fish ranged from 2.50 mg/L to 16 mg/L in the fathead
minnow. The first study was conducted using criteria similar to OPP/OPPTS guidelines and
would have more weight than the second study which did not provide any information on how
the study was conducted. Therefore, the data indicates that 4-t-amylphenol is moderately toxic
to coldwater species, such as the fathead minnow. The fathead minnow is considered to be less
sensitive than the bluegill. Also shown in Table 9, acute toxicity to shrimp was LC50 =1.7
mg/L. This indicated that 4-t-amylphenol was moderately toxic to shrimp. The study does not
meet current guideline requirements.
22
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Table 9. Acute Toxicity of 4-t-amylphenol and salts
Organism
Results - LC50
(mg/L) (95%
Confidence
Limit)
Toxicity
Category
Comments
Reference
Freshwater Fish
Fathead minnow
(Pimephales
promelas)
Fathead minnow
(Pimephales
promelas)
2.50(1.87-
3.34)
16
moderatel
y toxic
Slightly
toxic
- 96h test duration;
- flow-through bioassay
-caused necrosis in fish
- No information
available on the test
parameters
Holcombe, G W
et al. 1984
Environ Pollut
ser A Ecol Biol
35:367-81
Russon, C L et
al. 1997 Environ.
Toxicol. Chem
16:948
Marine/Estuarine Invertebrates
Shrimp (Crangon
septemspinosd)
96hLC50= 1.7
mg/L
Moderatel
y toxic
- 96h test duration;
- aerated gently and
changed at 49 hours
McLeese, D W
1981
Chemosphere
10(7): 723
3.
Endocrine Effects in Fish
As mentioned above, potential endocrine effects for 4-t-amylphenol have been identified.
Examples of the impacts of 4-t-amylphenol affecting the reproductive processes of carp have
been reported in the peer-reported literature. Since the use pattern for this chemical is restricted
to indoor uses, exposure to fish, such as carp, should be limited. Therefore, no additional testing
for endocrine disruption effects on fish is necessary.
23
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Table 10: Examples of 4-t-amylphenol Affecting the Endocrine System in Fish
Organism
Male common
carp (Cyprinus
carpio)
Male common
carp (Cyprinus
carpio)
Cultured
hepatocytes from
genetically-
uniform, all male,
Fl -hybrid
progenies of
common carp
(Cyprinus capio)
Male common
carp (Cyprinus
carpio)
Results
caused formation of
oviducts in male fish
and reduced the
number of primordial
germ cells in gonads
30-day EC50 for
oviduct formation =
63ug/L
NOEC for oviduct
formation = <36 ug/L
primordial germ cells
lower in treated fish
NOEC for
vitellogenin induction
=90-256 ug/L
vitellogenin induction
in carp hepatocytes
with LOEC ranging
from 5-50 uM,
cytotoxic at lOOuM
elevated levels of
vitellogenin,
inhibition of
spermatogenesis,
disappearance of
spermatozoa and
spermatogenic cysts,
reduced diameter of
seminiferous lobules,
reduced spermatocrit
values and early
appearance of ovo-
testes
LOAEL= 0.032 mg/L
Toxicity
Category
identified as an
ecoestrogen
identified as
causing
endocrine
disruption
effects
identified as
causing
endocrine
disruption
effects
identified as
causing
endocrine
disruption
effects and
no mortality or
growth effects
Comments
- test concentration 0. 14
mg/L
- exposed embryos and
fmgerlings at various
ages
- 120 male carp tested
- nominal concentrations
of 100, 320, & 1000
ug/L were tested
- 160 day test duration
- intermittent flow
through system
-six month old
hepatocytes with fully
mature testes containing
mature sperm
- 3 month test duration
- nominal concentrations
of 32, 100, 320 and
1000 ug/L were tested
Reference
Gimeno et al. 1997
Environ Sci Technol
3 1(10): 2884-2890.
Gimeno, S. et al.
1998a
Aquatic Toxicology
(Amsterdam) 43:77-
92.
Smeets, J. M. et al.
1999. Toxicol. Sci.
50(2): 206-213.
Gimeno et al. 1998b
Aquatic Toxicology
(Amsterdam) 43 : 93 -
109.
4. Listed Species Consideration
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
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
24
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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 form the indoor uses of 4-t-amylphenol, 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
4-t-Amylphenol end-use products (EPs) may also contain other registered pesticides.
Although the Agency is not proposing any mitigation measures for products containing 4-t-
amylphenol 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.
25
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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 4-t-amylphenol and its salts (potassium and sodium) as active ingredients.
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 4-t-amylphenol and salts,
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
ingredients 4-t-amylphenol. Based on a review of these data and on public comments on the
Agency's assessments for the active ingredients 4-t-amylphenol and its salts (potassium and
sodium), the Agency has sufficient information on the human health and ecological effects of 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 products
containing 4-t-amylphenol and its salts are eligible for reregistration provided that: (i) current
data gaps and confirmatory data needs are addressed; (ii) the risk mitigation measures outlined in
this document are adopted; and (iii) label amendments are made to reflect these measures. Label
changes are described in Section V. Appendix A summarizes the uses of 4-t-amylphenol and
salts 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 4-t-amylphenol
and salts, 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 4-t-amylphenol and salts, the Agency has determined that 4-t-
amylphenol and salts products, unless labeled and used as specified in this document, would
present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of
the risk mitigation measures identified in this document, the Agency may take regulatory action
to address the risk concerns from the use of 4-t-amylphenol and salts. If all changes outlined in
this document are incorporated into the product labels, then all current risks for 4-t-amylphenol
and salts (potassium and sodium) 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 decisions for 4-t-amylphenol. During the public comment
period on the risk assessments, which closed on September 19, 2005, the Agency received
comments from the Clariant Corporation regarding risk assessment assumptions and endocrine
disruption potential and from a private citizen concerned about the diaper use of this chemical.
These comments in their entirety are available in the public docket,
http://docket.epa.gov/edkpub/index.jsp. (OPP-2005-0181).
26
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C. Regulatory Position
1. Food Quality Protection Act (FQPA) Considerations
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with 4-t-amylphenol. The Agency has concluded that the tolerance exemption for 4-t-
amylphenol meets the FQPA safety standards and that the risk from dietary (food sources only)
exposure is within the "risk cup." An aggregate assessment was conducted for exposures
through food, drinking water and residential exposure. The Agency has determined that the
human health risks from these combined exposures are within acceptable levels provided that the
mitigation contained in this document is implemented. 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, water and residential exposures.
b. Determination of Safety to U.S. Population
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with 4-t-amylphenol and its salts (potassium and salts). The Agency has determined that the
established tolerance exemption for 4-t-amylphenol and its salts with amendments and changes
as specified in this document, 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 reregistered, labeled uses of 4-t-amylphenol and
salts. In reaching this conclusion, the Agency has considered all available information on the
toxicity, use practices and exposure scenarios, and the environmental behavior of 4-t-amylphenol
and its salts. Both the acute dietary (food alone) and chronic dietary risks from 4-t-amylphenol
are not of concern. 4-t-Amylphenol and its salts are not likely to contaminate surface and ground
waters based on its use patterns and fate characteristics. Thus, a drinking water assessment was
not conducted.
Short- and intermediate-term aggregate risk assessments were conducted for 4-t-
amylphenol. The aggregate oral and inhalation risks are not of concern for adults, as the total
aggregate MOE is greater than the target of 3,000. For children, the aggregate risk estimates are
also above the target MOE of 3,000 and thus are not of concern. As noted previously, incidental
oral exposures to treated textiles are not included in the aggregate assessment because the oral
MOE is already of concern.
A dermal aggregate assessment was not conducted because the toxicity effects for the
dermal exposure route are not the same as the oral/inhalation exposure route. However, as
shown previously on Table 6, short- and intermediate dermal risks are already of concern for the
treated textile and diaper uses.
27
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c. Determination of Safety to Infants and Children
EPA has determined that the established tolerance exemption for 4-t-amylphenol, with
amendments and changes as specified in this document, meets 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 dietary exposure due to the
specific consumption patterns of infants and children, as well as the possibility of increased
susceptibility to the toxic effects of 4-t-amylphenol residues in this population subgroup.
A 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 4-t-amylphenol 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 retained (i.e., remains 10X) for 4-t-amylphenol
based on a lack of guideline studies, qualitative evidence of sensitivity in the developmental
toxicity study, and the suggestive evidence in the open literature of possible endocrine effects.
The toxicology data base is not complete with respect to assessing that increased
susceptibility to infants and children as required by FQPA for 4-t-amylphenol. The rat prenatal
developmental study showed no quantitative evidence of increased susceptibility (i.e.,
developmental NOAELs/LOAELs were higher than those for maternal effects). However, there
was qualitative evidence of increased susceptibility (i.e., fetal effects (skeletal abnormalities,
decreased body weight gain) were considered to be more severe than the maternal toxicity
(reversible clinical signs) observed at the same dose level). In addition, there is an absence of
developmental toxicity data in the rabbit and an absence of reproductive toxicity data.
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).
28
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When the appropriate screening and/or testing protocols being considered under the
EDSP have been developed, 4-t-amylphenol may be subject to additional screening and/or
testing to better characterize effects related to endocrine disruption.
e.
Cumulative Risks
Risks summarized in this document are those that result only from the use of 4-t-
amylphenol and salts. 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 4-t-amylphenol. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects from substances
found to have a common mechanism on EPA's website at
http ://www. epa. gov/pesticides/cumulative/.
2. Tolerance Summary
4-t-amylphenol (also known as phenol, 4-1,1-dimethylpropyl) (CAS No. 80-46-6) has a
tolerance exception in 40CFR 180.940 (c) as a food-contact sanitizer for use in food-processing
equipment and utensils with a not to exceed limit of 80 ppm.
a. Tolerances Currently Listed Under 40 CFR §180.940(c) and
Tolerance Reassessment
Table 11. Tolerance Reassessment Summary for 4-t-amylphenol
Tolerance Exemption Listed Under 40 CFR § 180.940 (c)
Use Site
Food
processing
equipment and
utensils
Current
Limit (ppm)
80
Tolerance
Reassessment
(ppm)
540
Correct Definition/Comment
When ready for use, the end-use concentration is not to
exceed 540 ppm.
b. Codex Harmonization
Currently there are no Codex MRLs established for 4-t-amylphenol.
29
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D. Regulatory Rationale
The Agency has determined that 4-t-amylphenol is eligible for reregistration provided
that additional required data confirm this decision and that the risk mitigation measures outlined
in this document are adopted, and label amendments are made to reflect these measures.
The following is a summary of the rationale for managing risks associated with the use of
4-t-amylphenol. 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
For all supported uses, the acute and chronic dietary exposure estimates are below the
Agency's level of concern. Therefore, no risk mitigation measures are required to address
exposure to 4-t-amylphenol residues in food. Residue data are required to confirm the 10%
transfer assumption used in the risk assessment.
b. Drinking Water Risk Mitigation
4-t-Amylphenol and its salts are not likely to contaminate surface and ground waters
based on its use patterns and fate characteristics. Thus, a drinking water assessment was not
conducted. Therefore, no risk mitigation measures are required to address 4-t-amylphenol
exposure from drinking water.
c. Residential Risk Mitigation
Residential risks from handler and post-application exposure were calculated for short-
and intermediate-term dermal, inhalation and incidental oral exposures. All exposure and risk
estimates for residential handler scenarios are below the Agency's level of concern. Therefore,
no risk mitigation measures are required for these handler scenarios.
Risks of concern have been identified for several post-application exposure scenarios
including children's dermal exposure to treated clothing and treated diapers and children's
incidental oral exposure to treated clothing. The Agency believes that adding clear instructions
for washing and rinsing textile items will result in the adequate removal of residues from the
treated items and address the Agency's concerns for this scenario. The MOE for dermal
exposure to children to treated surfaces in daycare centers slightly exceeds the Agency's level of
concern (MOE = 940 with a target MOE of 1,000). However, the Agency believes actual
exposure from this pathway to not exceed its level of concern when taking into account the
conservative nature of the risk estimate which is likely to overestimate potential exposures.
30
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In summary, to reduce residential exposure, the Agency has determined that the
following mitigation and label changes for specific scenarios are appropriate and required for
reregistration eligibility:
- Delete all diaper uses
- Delete all use on non-laundered textiles\items including mattresses, helmets,
headgear, headphones, face gear, and mouthpieces.
All labels with laundered textile uses must have directions that indicate that items
must be treated prior to washing and rinsing.
d. Occupational Risk Mitigation
i. Handler Exposure
Occupational risks from handler and applicator exposures were calculated for short-term
and intermediate-term dermal and inhalation exposures. All exposure and risk estimates for
occupational handler scenarios are below the Agency's level of concern. Therefore, no risk
mitigation measures are required for these handler scenarios.
ii. Post-Application Risk Mitigation
Post-application exposure to re-entry workers is possible because 4-t-amylphenol can be
applied as a fogging application to animal buildings. The Agency used the MCCEM (Multi-
Chamber Concentration and Exposure Model) to estimate postapplication/bystander exposures.
The calculated inhalation MOEs were above the target MOE of 300 for all fogging
postapplication scenarios with the exception of the scenario for 8-hr exposure to the product with
a 2-hr reentry interval (MOE = 86).
The Agency does not believe that any mitigation is necessary to address the post-
application scenario with a 2-hr reentry interval at this time. The risk estimate was calculated
using the Agency's standard assumptions for air exchange rates. The Agency believes that in the
case of animal barns and facilities this assumption is very conservative given the relatively high
air exchange rates for such facilities.
2. Environmental Risk Management
As the uses of 4-t-amylphenol considered in this RED make it unlikely that any
appreciable exposure to terrestrial or aquatic organisms would occur, no risk mitigation measures
are required to address environmental exposure to 4-t-amylphenol.
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 4-t-amylphenol. For the specific
labeling statements and a list of outstanding data, refer to Section V of this RED document.
31
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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
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 of 4-t-amylphenol, 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
4-t-Amylphenol end use products (EPs) may also contain other registered pesticides.
Although the Agency is not proposing any mitigation measures for products containing 4-t-
amylphenol specific to federally listed threatened and endangered species, the Agency needs to
address potential risks from other end-use products. Therefore, the Agency requires that users
adopt all threatened and endangered species risk mitigation measures for all active ingredients in
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the product. If a product contains multiple active ingredients with conflicting threatened and
endangered species risk mitigation measures, the more stringent measure(s) should be adopted.
33
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V. What Registrants Need to Do
The Agency has determined that 4-t-amylphenol is eligible for reregistration provided
that: (i) additional data that the Agency intends to require confirm this decision; and (ii) the risk
mitigation measures outlined in this document are adopted, and (iii) label amendments are made
to reflect these measures. To implement the risk mitigation measures, the registrants must
amend their product labeling to incorporate the label statements 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 4-t-amylphenol 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 Killian Swift at (703) 308-6346 with questions regarding generic reregistration.
By US mail: By express or courier service:
Document Processing Desk (DCI/SRRD) Document Processing Desk (DCI/SRRD)
Killian Swift Killian Swift
US EPA (75 IOC) Office of Pesticide Programs (75 IOC)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 S. Bell Street
Arlington, VA 22202
34
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For end use products containing the active ingredient 4-t-amylphenol, 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 13
of this document;
4. a completed form certifying compliance with data compensation requirements (EPA
Form 8570-34); and
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
35
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A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of 4-t-amylphenol 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 4-t amylphenol. The
requirements would consist of an acute toxicity testing battery, subchronic toxicity studies in the
rodent, a developmental toxicity study in the rat, and a mutagenicity testing battery. The
developmental toxicity study in the rat, mutagenicity testing battery, the acute oral toxicity and
the acute dermal irritation data requirements has been fulfilled for 4-t amylphenol. 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 studies in a non-rodent which would become
data requirements if warranted by the Agency's evaluation of the Tier 1 data. A 2-generation
reproduction study and a subchronic toxicity study in a non-rodent are being held in reserve for
4-t amylphenol.
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.
As mentioned earlier, the Agency assumed that food can contact 2000 cm2 of treated
surfaces, and that 10% of the pesticide migrates to food based on the Agency Residential SOPs
in its dietary risk assessment. The use of the 10% transfer rate instead of the use of a 100%
transfer rate that is used in the FDA Sanitizer Solution Guidelines requires the submission of
confirmatory data to establish the reliability of the use of the 10% transfer rate.
The Agency is also holding in reserve a developmental toxicity study in rabbits based on
the potential endocrine disruption effects of this chemical. The need for this study will be
determined following the Agency's review of the 90-day oral study in rodents.
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
36
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(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.
A 28-day rat inhalation study for hazard considerations because 4-t-amylphenol is an air
deodorizer was considered, however, the Agency does not believe this study is necessary
because the MOEs are sufficiently high for this use, and thus not of concern. In addition, the
Agency believes the repeat dermal toxicity study with end use formulation product, and
confirmatory residue migration data are not necessary because the diaper and textile use are no
longer eligible for registration.
Table 12. Confirmatory Data Requirements for Registration
Guideline Study Name
90-day Oral Subchronic in Rats (including neurotoxicity
and endocrine endpoints)
Acute Dermal Toxicity
Acute Inhalation Toxicity
Acute Eye Irritation
Skin Sensitization
Dermal Indoor Exposure
Inhalation Indoor Exposure
Descriptions of Human Activity
Avian acute oral toxicity
Freshwater fish acute toxicity
Freshwater invertebrate acute toxicity
Dietary-Residues in Food from Treating Countertops with
4-t amylphenol (FDA Wipe Study Methodology) (FDA,
2003a and 2003b)
New OPPTS
Guideline No.
870-3100
870.1200
870.1300
870.2400
870.2600
875.1200,
875.1600
875.1400,
875.1600
875.2800
850.2100
850.1075
850.1010
Non-Guideline
Old Guideline No.
82-1
81-2
81-3
81-4
81-6
233 and 236
234 and 236
133-1
71-1
72-1
72-2
Non-Guideline
Studies Held in Reserve
2-Generation Reproduction
90-day Oral Subchronic in Non-Rodents
Developmental Toxicity in Rabbits
870.3800
870-3150
870.3700b
83-4
82-1
83-3b
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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 follow this
RED.
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.
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.
38
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a. Label Changes Summary Table
In order to be eligible for reregistration, amend all product labels to incorporate the risk mitigation measures outlined in
Section IV. The following table describes how language on the labels should be amended.
Table 13. Labeling Changes Summary Table
Summary of Labeling Changes for 4-t-Amylphenol and its Salts
Description
Delete use on diapers
Delete all use on non-
laundered textiles\items
including mattresses, helmets,
headgear, headphones,
facegear, and mouthpieces.
Laundry Use
Amended Labeling Language
Clarify language to ensure use requires washing and rinsing prior to wearing clothing
Placement on Label
Use Directions
Use Directions
Use Directions
39
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40
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VI. APPENDICES
41
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42
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Appendix A: Use Patterns Eligible for Reregistration
4-T-Amylphenol
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
(1) Agricultural premises and equipment
Mushroom houses-empty
premises/equipment
Soluble
concentrate:
Reg.211-36
Soluble
concentrate:
Reg. 1043-26
Reg.211-25
Reg.65020-7
Mop, cloth,
sponge or hand
trigger sprayer
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Use as a premises spray, do not apply to
the crop, compost, or casing.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Hard, non porous, non
food contact surfaces
Soluble
concentrate:
Reg.211-36
Reg.49403-6
Reg. 1043-118
Reg. 11725-9
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
43
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
minutes allow to air dry
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Agricultural/farm
equipment/shoe baths
Agricultural/farm
equipment/shoe baths
(continued)
Soluble
concentrate:
Reg.211-36
Reg.49403-6
Reg. 1043-118
Reg. 66171-1
Reg. 11725-9
Soluble
concentrate:
Reg. 11725-8
Reg. 1043-91
Reg. 11725-7
Reg. 1043-26
Reg.211-25
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
**Shoe bath sanitizer
containing one inch of
freshly made disinfectant
should be placed at all
entrances
Do not use in milking stalls. Milking
parlors, or milk houses. Do not apply to
crop, soil or growing media in which a crop
grows or will be growing
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Fogger (wet
misting)
l/2 oz per gallon of water
1:256 dilution
Set the automatic timer on
the fogger for 6 minutes for
lOOOcu.ft and leave the
room. Allow at least 2
hours before entering a
room that has been fogged
Treated food contact surfaces must be
thoroughly rinsed with potable water prior
to use. Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
44
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Reg.66171-1
Reg. 11725-7
Reg. 1043-26
Reg.211-25
Reg.65020-7
Ree.3862-180
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
**Shoe bath sanitizer
containing one inch of
freshly made disinfectant
should be placed at all
entrances
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
(2) Food handling/storage establishments premises and equipment
Hard, non porous, non
food contact surfaces
Hard, non porous, non
food contact surfaces
(continued)
Ready to use
solution:
Reg. 1270-237
Res. 1008-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
45
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Reg. 1043-92
Reg. 1043-91
Reg. 11725-7
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Meat processing plant
premises (nonfood)
Ready to use
solution:
Reg. 10088-105
Reg. 1270-237
Soluble
concentrate:
Reg. 11725-7
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
46
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Poultry processing plant
premises (nonfood)
Ready to use
solution:
Reg. 10088-105
Reg. 1270-237
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Soluble
concentrate:
Reg.49403-23
Reg.211-25
Mop, cloth,
sponge or hand
trigger sprayer
Poultry processing plant
premises (nonfood)
(continued)
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Processing/handling
equipment (nonfood)
Ready to use
solution:
Reg. 10088-105
Res. 1270-237
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
47
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Res. 11725-7
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
(3) Commercial, institutional and industrial premises and equipment
Institutional premises
Ready-to-use-
solution:
Reg. 104319,
Reg.44446-67
Reg. 10088-105
Reg. 1270-237
Reg.7405-51
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
48
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Institutional premises
(continued)
Soluble
concentrate:
Reg. 11725-8
Reg. 1043-91
Fogger (wet
misting)
Va oz per gallon of water
1:256 dilution
Set the automatic timer on
the fogger for 6 minutes for
lOOOcu.ft and leave the
room. Allow at least 2
hours before entering a
room that has been fogged
Treated food contact surfaces must be
thoroughly rinsed with potable water prior
to use. Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
Hard, non porous, non
food contact surfaces
Soluble
concentrate:
Reg.66171-1
Reg. 117258
Reg. 1043-91
Reg, 1043-92
Reg.66171-2
Reg. 211-25
Reg.3862-180
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
49
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Reg.211-36,
Reg. 1043-115
Reg. 1043-87
Reg.2212-5
Reg.49403-6
Reg. 1043-118
Reg. 11725-9
Ready-to-use-
solution
Reg. 1043-19
Reg.44446-67
Reg. 10088-105
Reg. 1270-237
Reg.7405-51
Reg.55195-3
Res.3862-104
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
50
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Hard, non porous, non
food contact surfaces
(continued)
Soluble
concentrate:
Reg. 11725-8
Reg. 1043-91
Fogger (wet
misting)
Va oz per gallon of water
1:256 dilution
Set the automatic timer on
the fogger for 6 minutes for
lOOOcu.ft and leave the
room. Allow at least 2
hours before entering a
room that has been fogged
Treated food contact surfaces must be
thoroughly rinsed with potable water prior
to use. Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
Bedside and office
furniture
Soluble
concentrate:
Reg.66171-1,
Reg. 11725-8,
Reg. 1043-92
Reg. 1043-91,
Reg.66171-2,
Reg.211-25
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
51
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Bedside and office
furniture (continued)
Soluble
concentrate:
Reg.211-36
Reg. 1043-115
Reg. 1043-87
Reg.2212-5
Reg.49403-6
Reg. 1043-118
Impregnated
material.:
Reg.55195-4
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67,
Reg. 10088-105
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Wipe
Thoroughly wet pre-
cleaned surface with a
wipe and allow to air dry
Do not reuse wipes
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Trash carts
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
52
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Reg. 10088-105
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Telephones
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Waste cans and laundry
hampers
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Sinks
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
53
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Reg. 10088-105
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Carpet cleaning
Soluble
concentrate:
Reg.70263-7
Hot water
extraction
1 oz per gallon of water
Inject and extract as you
would with other extraction
cleaners
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Soluble
concentrate:
Reg.70263-7
Spin bonnet
cleaning
(spray)
4 oz per gallon of water
Spray on at a rate of 200-
300 square feet per gallon,
scrub with rotary floor
machine equipped with
bonnet or pad
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Soluble
concentrate:
Reg.70263-7
Immersion
Mix 2 oz per gallon of
water in a cleaning tank.
Immerse rug in cleaning
solution.
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
(4)Residential and public access premises
Household/domestic
dwelling
Ready-to-use-
solution:
Reg. 1043-19
Reg.4444667
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
54
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Reg. 10088-105
Reg. 1008-104
Reg. 1270-237
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Carpet cleaning
Carpet cleaning
(continued)
Soluble
concentrate:
Reg.70263-7
Hot water
extraction
1 oz per gallon of water
Inject and extract as you
would with other extraction
cleaners
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Soluble
concentrate:
Reg.70263-7
Spin bonnet
cleaning
(spray)
4 oz per gallon of water
Spray on at a rate of 200-
300 square feet per gallon,
scrub with rotary floor
machine equipped with
bonnet or pad
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Soluble
concentrate:
Reg.70263-7
Immersion
Mix 2 oz per gallon of
water in a cleaning tank.
Immerse rug in cleaning
solution.
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Hard, non porous, non
food contact surfaces
Ready-to-use-
solution:
Reg. 1043-19,
Reg.44446-67
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
55
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Reg. 1008-104
Reg. 1270-237
Reg.3862-104
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Animals kennels/sleeping
quarters (commercial)
Soluble
concentrate:
Reg. 303-225
Soluble
concentrate:
Reg. 66171-2
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
(5) Medical premises and equipment
56
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Hospital non critical
items(bedpans/furniture
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Reg. 10088-105
Reg. 1270237
Reg. 10807-177
Reg. 10807-178
Reg.3862-104
Reg.706-69
Soluble
concentrate:
Reg.211-25
Soluble
concentrate:
Reg.675-21
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
40cc per 2 gallons of water
1:200 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
57
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Hospital non critical
items(bedpans/furniture
(continued)
Soluble
concentrate:
Reg.211-36
Reg.49403-6
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Hospital semi critical
items
Soluble
concentrate:
Reg.211-36
Reg.49403-6
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
**Prior to sterilization or
high level decontamination
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
58
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Hospital critical items
(surgical
instruments/pacemakers)
Soluble
concentrate:
Res. 1043-114
Immersion
2 oz per gallon of water
1:64 dilution
Soak for a minimum of 20
minutes to achieve interim
instrument
decontamination
**Prior to sterilization or
high level decontamination
Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
Soluble
concentrate:
Ree.675-21
Immersion
5oz per 2 gallons of water
2:100 dilution
Soak for 15 minutes to
achieve interim instrument
decontamination, then
immerse in 70% alcohol
for one minute
Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
59
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Res. 2212-170
Hospital critical items
(surgical
instruments/pacemakers)
(continued)
Ultra sonic
cleaning
system
1 oz per gallon of water
1:128 dilution
Fill the basket with pre
cleaned instruments, place
cover on machine and run
cycle for 10 minutes
**Prior to sterilization or
high level decontamination
Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Hospital/medical
institutions premises
(human/veterinary)
Ready to use
solution:
Reg.7405-51,
Reg.3862-104
Res.706-69
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
60
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Hospital/medical
institutions premises
(human/veterinary)
(continued)
Soluble
concentrate:
Res. 11725-8
Soluble
concentrate:
Reg.66171-1
Reg. 1043-92
Reg. 11725-8
Reg.66171-2
Reg. 49403-23
Reg.211-25
Soluble
concentrate:
Reg.211-36
Reg. 1043-87
Reg. 1043-115
Reg.49403-6
Reg. 1043-118
Reg. 11725-9
Fogger (wet
misting)
l/2 oz per gallon of water
1:256 dilution
Set the automatic timer on
the fogger for 6 minutes for
lOOOcu.ft and leave the
room. Allow at least 2
hours before entering a
room that has been fogged
Treated food contact surfaces must be
thoroughly rinsed with potable water prior
to use. Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
61
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Impregnated
material:.
Reg.55195-4
Wipe
Thoroughly wet pre-
cleaned surface with a
wipe and allow to air dry
Do not reuse wipes
Hard, non porous, non
food contact surfaces
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Reg. 1008-105
Reg. 12702-37
Reg. 10807-177
Reg. 10807-178
Reg.7405-51
Reg.55195-3
Reg.3862-104
Soluble
concentrate:
Reg. 11725-8
Reg.66171-2
Reg. 211-25
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Mop, cloth,
sponge or hand
trigger sprayer
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
62
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Reg. 11725-8
Impregnated
material:
Reg.55195-4
Soluble
concentrate:
Reg.211-36
Reg. 1043-87
Reg. 1043-115
Reg.49403-6
Reg. 1043-118
Reg. 11725-9
Fogger (wet
misting)
Va oz per gallon of water
1:256 dilution
Set the automatic timer on
the fogger for 6 minutes for
lOOOcu.ft and leave the
room. Allow at least 2
hours before entering a
room that has been fogged
Treated food contact surfaces must be
thoroughly rinsed with potable water prior
to use. Do not apply in a way that will contact
workers or any other persons, either directly
or through drift. Only protected handlers may
be in the area during the application. Do not
contaminate other materials (including
foods/drinks/feeds/ water)
Wipe
Thoroughly wet pre-
cleaned surface with a
wipe and allow to air dry
Do not reuse wipes
Mop, cloth,
sponge or hand
trigger sprayer
1 oz per gallon of water
1:128 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Household sickrooms
premi se s/content s/utensil s
Ready-to-use-
solution:
Reg. 1043-19
Reg.44446-67
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
63
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Reg.3862-104
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Morgues/mortuaries/autop
sy/embalming equipment
Ready to use
solution:
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Morgues/mortuaries/autop
sy/embalming room
premises
Ready to use
solution :
Reg. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
64
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Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Barber/beauty shop
instruments and
equipment
Ready to use
solution:
Res. 10088-105
Spray
To disinfect: Thoroughly
wet (saturate) all surfaces
for 10 minutes.
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Soluble
concentrate:
Res.66171-1
Immersion
1/2 oz per gallon of water
1:256 dilution
Thoroughly wet for 10
minutes allow to air dry
Following application as a spray, do not enter
or allow others to enter the treated area until
sprays have dries. Do not apply in a way that
will contact workers or any other persons,
either directly or through drift. Only protected
handlers may be in the area during the
application. Do not contaminate other
materials (including foods/drinks/feeds/
water)
Carpet cleaning
Soluble
concentrate:
Reg.70263-7
Hot water
extraction
1 oz per gallon of water
Inject and extract as you
would with other extraction
cleaners
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
65
-------
Use Site
Formulation
Method of
Application
Application Rate/ No. of
applications
Use Limitations
Soluble
concentrate:
Ree.70263-7
Spin bonnet
cleaning
(spray)
Carpet cleaning
(continued)
4 oz per gallon of water
Spray on at a rate of 200-
300 square feet per gallon,
scrub with rotary floor
machine equipped with
bonnet or pad
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
Soluble
concentrate:
Res.70263-7
Immersion
Mix 2 oz per gallon of
water in a cleaning tank.
Immerse rug in cleaning
solution.
Test fibers for colorfastness before use. Apply
diluted cleaner to inconspicuous area, and rub
with a white cloth. If color transfers to cloth
or changes, a water based cleaning system
should not be used.
66
-------
67
-------
APPENDIX B: Para-Tertiary Amylphenol Case 3016
Appendix B lists the generic (not product specific) data requirements which support the re-registration of Para-tertiary
Amylphenol. These requirements apply to Para-Tertiary Amylphenol in all products, including data requirements for which a
technical grade active ingredient is the test substance. The data table is organized in the following formats:
1. Data Requirement (Columns 1 and 2). The data requirements are listed by Guideline Number. The first column lists the new Part
158 Guideline numbers, and the second column lists the old Part 158 Guideline numbers. Each Guideline Number has an associated
test protocol set forth in the Pesticide Assessment Guidance, which are available on the EPA website.
2. Guideline Description (Column 3). Identifies the guideline type.
3. Use Pattern (Column 4). This column indicates the standard Antimicrobial Division use patterns categories for which the generic
(not product specific) data requirements apply. The number designations are used in Appendix B.
(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 data in its files to support a specific generic Guideline requirement, this
column will identity each study by a "Master Record Identification (MRID) number. The listed studies are considered "valid" and
acceptable for satisfying the Guideline requirement. Refer to the Bibliography appendix for a complete citation of each study.
68
-------
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
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Not Applicable
Data Gap
Data Gap
Not Applicable
Data Gap
Data Gap
Data Gap
Not Applicable
69
-------
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
Data Gap
Data Gap
Data Gap
Not Applicable
Data Gap
Not Applicable
Data Gap
Not Applicable
Data Gap
Not Applicable
Not Applicable
ECOLOGICAL EFFECTS
850.2100
850.1075
850.1010
71-1
72-1
72-2
Avian Acute Oral Toxicity Test (Quail/Duck)
Fish Acute Toxicity - Freshwater (Rainbow Trout)
Acute Aquatic Invertebrate Toxicity
All
All
All
Data Gap
Data Gap
Data Gap
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
81-1
81-2
81-3
81-4
81-5
Acute Oral - Rat
Acute Dermal - Rabbit
Acute Inhalation - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
All
All
All
All
All
46616601
Data Gap
Data Gap
Data Gap
46616602
70
-------
DATA REQUIREMENT
New Guideline
Number
870.2600
870.3100
870.3200
870.3250
870.3465
870.3700
870.3700a
870.5265
870.5300
870.5385
870.3150
870.3700b
870.3800
Old Guideline
Number
81-6
82-la
82-2
82-3
82-4
83-3
83-3a
84-2
84-2
84-2
82-lb
83-3b
83-4
Study Title
Dermal Sensitization
90-Day Feeding-Rodent, with modifications (See RED)
21/28-Day Dermal Toxicity - Rat
90-day Dermal Toxicity - Rodent
28/90-Day Inhalation - Rat
Developmental Toxicity -Rat
Prenatal Developmental in Rodents
Bacterial Reverse Mutation Assay
Detection of gene mutations in somatic cells (CHO)
Micronucleus Assay
Reserved Studies
90-Day Oral Subchronic in Non-Rodent
Developmental Toxicity -Rabbit
Reproduction and Fertility Effects - 2 Generation Repro
Use Pattern
All
All
All
All
All
All
All
All
All
All
CITATION(S)
MRID Number
Data Gap
Data Gap
Not Applicable
42470301
waived
Data Gap
41920002, 41920001, 42026801
41438401, 41572701, 41728801
41572701
41710801
Data Gap, Reserved Study
Data Gap, Reserved Study
Data Gap, Reserved Study
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.2800
875.1200
875.1600
875.1400
875.1600
133-1
233/236
234/236
Descriptions of Human Activity
Dermal Indoor Exposure
Inhalation Indoor Exposure
All
All
All
Data Gap
Data Gap
Data Gap
71
-------
DATA REQUIREMENT
New Guideline
Number
Old Guideline
Number
Study Title
Use Pattern
CITATION(S)
MRID Number
ENVIRONMENTAL FATE
835.2120
161-1
Hydrolysis
All
Required
OTHER DATA REQUIREMENTS
FDA Guideline
identified here
FDA
Guideline
identified here
Dietary-Residues in Food from Treating hard non-porous
surfaces with 4-t-Amylphenol (conducted according to
FDA guideline entitled "Recommendations for Chemistry
Data for Indirect Food Additive Petitions.")
All
Required
72
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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 St., Arlington, VA 22202. It is open Monday
through Friday, excluding legal holidays, from 8:30 AM to 4:00 PM.
The docket initially contained preliminary risk assessments and related documents as of
April 28, 2004. Sixty days later the first public comment period closed. The EPA then
considered comments and revised the risk assessments.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following site: http://www.epa.gov/edockets
These documents include:
1. 4-t-Amylphenol: Report of the Antimicrobials Divisions's Toxicology Endpoint
Selection Committee (ADTC), July 2005
2. Toxicology Science Chapter for the Reregistration Eligibility Decision Document, From
M. Ottley to K. Swift, July 2005 D316279
3. Occupational and Residential Exposure Assessment for t-Tert-Amylphenol and Salts. S.
Mostaghimi. May 2005. D316290
4 Product Chemistry of Para-Tertiary-Amylphenol, para-tertiary-amylphenol, sodium salt
and para-tertiary-amylphenol, potassium salt. From A. N. Shamim to T. McMahon.
D316275
5 Environmental Fate Assessment of 4-tert-Amylphenol and its Potassium and Sodium
salts for the Reregistration Eligibility Decision (RED) Document. From S. Gowda,
Microbiologist to M. Hartman. May 2005, D316277
6 Ecological Hazard and Environmental Risk Assessment for 4-tert-amylphenol and salts to
be included in the RED. D. Bays to A. Heyward and K. Swift. July 2005, D316278
7 Incident Reports Associated with 4-tert-amylphenol. J.Chen. May 2005, D3162
8 Dietary Exposure Assessments for the Reregistration Eligibility Decision. R. Quick.
July 2005. D316295.
73
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Appendix D. Citations Considered to be Part of the Data Base Supporting the 4-t-
amylphenol Reregistration Decision (Bibliography)
GUIDE TO APPENDIX D
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in the
4-t-amylphenol Reregistration Eligibility Document. Primary sources for studies in this
bibliography have been the body of data submitted to EPA and its predecessor agencies in
support of past regulatory decisions. Selections from other sources including the published
literature, in those instances where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study." In the
case of published materials, this corresponds closely to an article. In the case of unpublished
materials submitted to the Agency, the Agency has sought to identify documents at a level
parallel to the published article from within the typically larger volumes in which they were
submitted. The resulting "studies" generally have a distinct title (or at least a single subject), can
stand alone for purposes of review and can be described with a conventional bibliographic
citation. The Agency has also attempted to unite basic documents and commentaries upon them,
treating them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID" number. This number is unique to the
citation, and should be used whenever a specific reference is required. It is not related to the six-
digit "Accession Number" which has been used to identify volumes of submitted studies (see
paragraph 4(d)(4) below for further explanation). In a few cases, entries added to the
bibliography late in the review may be preceded by a nine character temporary identifier. These
entries are listed after all MRID entries. This temporary identifying number is also to be used
whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material submitted to
EPA, by a description of the earliest known submission. Bibliographic conventions used reflect
the standard of the American National Standards Institute (ANSI), expanded to provide for
certain special needs.
a. Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the Agency has shown an
74
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identifiable laboratory or testing facility as the author. When no author or laboratory could be
identified, the Agency has shown the first submitter as the author.
b. Document date. The date of the study is taken directly from the document. When
the date is followed by a question mark, the bibliographer has deduced the date from the
evidence contained in the document. When the date appears as (1999), the Agency was unable
to determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained between square
brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements describing
the earliest known submission:
(1) Submission date. The date of the earliest known submission appears immediately
following the word "received."
(2) Administrative number. The next element immediately following the word "under" is the
registration number, experimental use permit number, petition number, or other administrative
number associated with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to the
submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the original submission
of the study appears. The six-digit accession number follows the symbol "CDL," which stands
for "Company Data Library." This accession number is in turn followed by an alphabetic suffix
which shows the relative position of the study within the volume.
BIBRA, Working Group (1990): Para-tertiary-Amylphenol. Toxicity Profile BIBRA
Toxicology International. 3pp.
MRIDNo. 41710801
Edwards, C. N. 1990. Assessment of Clastogenic Action on Bone Marrow Erthrocytes in
the Micronucleus Test. Prepared by Life Science Research Ltd., Suffolk, UK. Study No. 907
NLL033.0533. Submitted by Nipa Laboratories, Inc. Wilmington, DE.
75
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MRID No. 41438401
May, K. 1990. Nipacide PTAP (para-tertiary amylphenol): Assessment of Mutagenic Potential
in Histidine Auxotrophs of Salmonella typhimurium. Prepared by Life Science Research Ltd.,
Suffolk, UK. Study No. 90/0109. Submitted by Nipa Laboratories, Inc. Wilmington, DE.
MRID No. 41572701
Lloyd, J. M. 1990. Investigation of Mutagenic Activity in the TK+/ - Mouse Lymphoma Cell
Mutation System. Prepared by Life Science Research Ltd., Suffolk, UK. Study No.
90/NLL034/0395. Submitted by Nipa Laboratories, Inc., Wilmington, DE.
MRID No. 41920002
Siglin, J. C. 1991. Nipacide PTAP, Teratology Study in Rats. Prepared by Springborn
Laboratories, Inc. Spencerville, OH. Study No. 3227.3. Submitted by Nipa Laboratories, Inc.,
Wilmington, DE.
MRID No. 46616601
Tufnell, P. P. 1992. Phenol, 4-(l,l-dimethylpropyl): Acute Oral Toxicity Test in the Rat.
Prepared by Safepharm Laboratories Ltd., Derby U.K., Laboratory Test No. 47/2097. Submitted
by Sandoz Chemicals Ltd.
MRID No. 46616602
Tufnell, P. P. 1992. Phenol, 4-(l,l-dimethylpropyl): Acute Dermal Irritation Test in the Rabbit.
Prepared by Safepharm Laboratories Ltd., Derby U.K., Laboratory Test No. 47/2098. Submitted
by Sandoz Chemicals Ltd.
Gimeno S., Komen, H., Venderbosch, P.W. and Bowner, T. (1997) Disruption of sexual
differentiation in genetic male carp (Cyprinus carpio) exposed to an alkylphenol during different
life stages. Enviro Sci. Technol. 31(10): 2884-2890.
Gimeno S., Komen H., Venderbosch, P. W. and Bowner, T. (1998a): Feminisation of young
males of the common carp, Cyprinus carpio, exposed to 4-ter-pentyphenol during sexual
differentiation. Aquatic Toxicology (Amsterdam) 43: 77-92.
Gimeno, S. Komen, H. Jobling S., Sumpter, J. and Bowner, T. (1998b): Demasculinisation of
sexually mature male carp, Cyprinus carpio, exposed to 4-tert-amylphenol during
Spermatogenesis. Aquatic Toxicology (Amsterdam) 43: 93-109.
Hazard Substances Databank (HSDB). A Database of the National Library of Medicine's
TOXNET System.
Helwig, D. (2003) Personal Communication between D. Helwig (Johnson Dirersey, Inc.) and K.
Riley (Versar, Inc., November 11, 2003.
76
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Holcombe, G. W., Phipps, G. L., Knuth, M. L. and Felhabert, T. (1984): The acute toxicity of
selected substituted phenols, benzenes and benzole acid ester to fathead minnows Pimephales
promelas. Environ. Pollut. Ser. A. Ecol. Biol. 35(4): 367-381.
McLeese, D.W. (1981). Lethality and accumulation of alkylphenols in aquatic fauna.
Chemosphere 10(7): 723.
Routledge, E. J. Sumpter, J. P. (1997) Structural features of alkylphenolic chemicals associated
with estrogenic activity. J. Biol. Chem. 272(6): 3280-3288.
Russon, C.L., Bradbury, S.P., Broderius S. J., Hammermeister, R. A. and Drummond, R. A.
(1997) [no title given] environ. Toxicol. Chem. 16:948.
Smeets, J. M., Van, H. I, Giesey, J. P., Seinen, W., and van den, B. M. (1999).\
Soto, et. al.(1995). The E-SCREEN assay tool to identify estrogens: An update on estrogenic
environmental pollutants. Environ. Health Perspect. 103 (Suppl. 7): 113-122.
Stevenson, CJ. (1984): Environmentally induced vitililigo (leukoderma) from depigmenting
agents and chemicals. J. Toxicol. Cutaneous Ocul. Toxicol. 3(3): 299-308.
USEPA. 1997. Exposure Factors Handbook. Volume I-II. Office of Research and Development.
Washington, D.C. EPA/600/P-995/002 Fa.
EPA, 1997. "Exposure Factors Handbook, Volume III: Activity Factors." EPA/600/P-
95/002Fe August 1997.
USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure from the
Pesticide Handler Exposure Database Version 1.1. Washington, DC: U.S. Environmental
Protection Agency.
USEPA. 1999. Evaluation of Chemical Manufacturers Association Antimicrobial Exposure
Assessment Study. Memorandum from Siroos Mostaghimi, Ph.D., USEPA, to Julie Fairfax,
USEPA. Dated November 4, 1999. DP Barcode D247642.
EPA, 1999. "Available Information on Assessing Exposure from Pesticides, A User's Guide."
U.S. Environmental Protection Agency (EPA) 2001. Residential SOPs Policy Update 12, EPA
Office of Pesticide Programs - Human Health Division. Dated April 5, 2000.
U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology
Database System. Version 3.0. Available: http://www.epa.gov/ecotox/
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USEPA. 2005. Product Chemistry of Para-Tertiary-Amylphenol (PC Code 064101), Para-
Tertiary- Amylphenol, Sodium Salt (PC Code 064112), and Para-Tertiary-Amylphenol,
Potassium Salt (PC Code 064111). Memorandum from A.Najm Shamim, Ph.D.,
USEPA.2005. the Estimation Programs Interface (EPI) Suite. Windows-based suite of
physical/chemical properties and environmental estimation models developed by the US EPA's
Office of Prevention, Pesticides and Toxic Substances (OPTS) and Syracuse Research Institute
(SRC) http://www.epa.gov/oppintr/exposure/docs/EPISuitedl.htm
USEPA's Estimation of P/Chem Properties Program, EPS Suite.
FDA, 2003 a. "Guidance For Industry: Preparation of Food Contact Notifications and Food
Additive Petitions for Food Contact Substances: Chemistry Recommendations. Final
Guidance."
FDA, 2003b. "Sanitizing Solutions: Chemistry Guidelines for Food Additive Petitions."
January, 1993. http://www.cfasan.fda.gov/~dms/opa-cg3a.html. Last accessed June 9, 2003.
Whatman, 2005. Whatman Absorbent Sinks.
http://www.whatman.com/products/?pageID=7.32.42, Accessed March 2005.
Wysowski, D.K. et. al. (1978) Epidemic neonatal Hyperbilirubinemia and use of phenolic
disinfectant detergent. Pediatrics 61: 165-170.
Yamasaki, K. et., al. (1978). Immature rat uterotrophic assay of 18 chemicals and Hershberger
assay of 30 chemicals. Toxicology 183: 93-115.
Zeiger, E., Anderson B., Haworth, S., Lawlor, T. and Mortelmans, K. (198): Salmonella
mutagenicity tests. 4. results from testing of 300 chemicals. Environ. Mol. Mutagen 11: 1-158.
78
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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 RED
for a list of studies that the Agency plans to require for 4-t-amylphenol.
79
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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.
80
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Appendix G. Batching of 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 4-t-amylphenol as the
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, etc.), and labeling (e.g., signal
word, use classification, precautionary labeling, etc.). Note that the Agency is not describing
batched products as "substantially similar" since some products within a batch may not be
considered chemically similar or have identical use patterns.
Using available information, batching has been accomplished by the process described in
the preceding paragraph. Not with-standing 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 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. 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.
The batching information will be provided with the product-specific DCI
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Appendix H. List of All Registrants To Be Sent the Generic Data Call-In
Clariant Corporation
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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:
http://www.epa.gov/opprd001/forms/
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.epa.sov/opprd001/forms/8570-l.pdf
http://www.epa.sov/opprd001/forms/8570-4.pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www.epa.sov/opprd001/forms/8570-32.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
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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 http://www.epa.gov/opppmsdl/PR_Notices.
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 Registration/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:
http://npic.orst.edu .
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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
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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