United States Prevention, Pesticides EPA-738-R-96-008
Environmental Protection And Toxic Substances January 1997
Agency (7508W)
&EPA Reregistration
Eligibility Decision (RED)
p-Chloro-m-cresol
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregi strati on eligibility review and decisions on the pesticide chemical case 3046 which
includes the active ingredient p-chloro-m-cresol. The enclosed Reregistration Eligibility
Decision (RED) contains the Agency's evaluation of the data base of this chemical, its
conclusions of the potential human health and environmental risks of the current product uses,
and its decisions and conditions under which these uses and products will be eligible for
reregi strati on. The RED includes the data and labeling requirements for products for
reregi strati on. It may also include requirements for additional data (generic) on the active
ingredient to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses is due 90 days from the
receipt of this letter. The second set of required responses is due 8 months from the date
of this letter. Complete and timely responses will avoid the Agency taking the enforcement
action of suspension against your products.
Please note that this RED was finalized and signed prior to August 3, 1996. On that
date, the Food Quality Protection Act of 1996 ("FQPA") became effective, amending portions
of both the pesticide law (FIFRA) and the food and drug law (FFDCA). This RED does not
address any issues raised by FQPA, and any tolerance-related statements in the RED did not
take into account any changes in tolerance assessment procedures required under FQPA. To
the extent that this RED indicates that a change in any tolerance is necessary, that
determination will be reassessed by the Agency under the standards set forth in FQPA before
a proposed tolerance is issued. To the extent that the RED does not indicate that a change in a
tolerance is necessary, that tolerance too will be reassessed in the future pursuant to the
requirements of FQPA.
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If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregi strati on Division representative,
Emily Mitchell at (703) 308-8583. Address any questions on required generic data to the
Special Review and Reregi strati on Division representative, Tom Luminello at (703) 308-
8075.
Sincerely yours,
Lois A. Rossi, Director
Special Review
and Reregi strati on Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCI) OR "90-DAY RESPONSE"-If generic data are required for
reregi strati on, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and
product specific data are required, a combined Generic and Product Specific DCI letter will
be enclosed describing such data. However, if you are an end-use product registrant only and
have been granted a generic data exemption (GDE) by EPA, you are being sent only the
product specific response forms (2 forms) with the RED. Registrants responsible for generic
data are being sent response forms for both generic and product specific data requirements (4
forms). You must submit the appropriate response forms (following the instructions
provided) within 90 days of the receipt of this RED/DCI letter; otherwise, your product
may be suspended.
2. TIME EXTENSIONS AND DATA WAIVER REQUESTS No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data
should be submitted in the 90-day response. Requests for data waivers must be submitted as
part of the 90-day response. All data waiver and time extension requests must be accompanied
by a full justification. All waivers and time extensions must be granted by EPA in order to go
into effect.
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE" You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further
labeling guidance, refer to the labeling section of the EPA publication "General Information
on Applying for Registration in the U.S., Second Edition, August 1992" (available from the
National Technical Information Service, publication #PB92-221811; telephone number 703-
487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI).
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d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
concentration. You have two options for submitting a CSF: (1) accept the standard certified
limits (see 40 CFR §158.175) or (2) provide certified limits that are supported by the analysis
of five batches. If you choose the second option, you must submit or cite the data for the five
batches along with a certification statement as described in 40 CFR §158.175(e). A copy of
the CSF is enclosed; follow the instructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA form 8570-31 for each product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data
waiver and time extension requests within 60 days. EPA will also try to respond to all 8-
month submissions with a final reregistration determination within 14 months after the RED
has been issued.
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REREGISTRATION ELIGIBILITY DECISION
P-CHLORO-M-CRESOL
LISTC
CASE 3046
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
P-CHLORO-M-CRESOL REREGISTRATION ELIGIBILITY DECISION TEAM . . . i
EXECUTIVE SUMMARY v
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Data Requirements 4
D. Regulatory History 4
III. SCIENCE ASSESSMENT 5
A. Physical Chemistry Assessment 5
B. Human Health Assessment 6
1. Toxicology Assessment 6
a. Acute Toxicity 6
b. Subchronic Toxicity 7
c. Chronic toxicity 7
d. Carcinogenicity 8
e. Developmental Toxicity 9
f. Reproductive Toxicity 9
g. Mutagenicity 10
h. Metabolism 11
i. Toxicological Endpoints of Concern 12
2. Exposure Assessment 12
a. Dietary Exposure 12
b. Occupational and Residential Exposures 13
3. Risk Assessment 16
a. Dietary 16
b. Occupational and Residential 16
C. Environmental Assessment 18
1. Ecological Toxicity Data 18
a. Toxicity to Terrestrial Animals 18
b. Toxicity to Aquatic Animals 19
2. Environmental Fate 20
3. Exposure and Risk Characterization 20
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IV. RISK MANAGEMENT AND REREGISTRATION DECISION 21
A. Determination of Eligibility 21
B. Determination of Eligibility Decision 22
1. Eligibility Decision 22
2. Eligible and Ineligible Uses 22
C. Regulatory Position 22
1. Occupational and Residential Labeling Rationale/Risk Mitigation
Measures; Personal Protective Equipment (PPE)/Engineering
Controls for Handlers 22
2. Reduction in Percentage of Active Ingredient 23
3. Other Labeling Requirements 23
V. ACTIONS REQUIRED OF REGISTRANTS 23
A. Manufacturing-Use Products 23
1. Additional Generic Data Requirements 23
2. Labeling Requirements for Manufacturing-Use Products 23
B. End-Use Products 24
1. Additional Product-Specific Data Requirements 24
2. Labeling Requirements for p-Chloro-m-cresol Products 24
C. Existing Stocks 28
VI. APPENDICES 29
APPENDIX A. Table of Use Patterns Subject to Reregistration 30
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision 35
APPENDIX C. Citations Considered to be Part of the Data Base Supporting
the Reregistration of p-Chloro-m-cresol 41
APPENDIX D. Product Specific Data Call-In 47
Attachment 1. Chemical Status Sheets 61
Attachment 2. Product Specific Data Call-In Response Forms (Form
A inserts) Plus Instructions 63
Attachment 3. Product Specific Requirement Status and Registrant's
Response Forms (Form B inserts) and Instructions
67
Attachment 4. EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration 75
Attachment 5. List of All Registrants Sent This Data Call-In (insert)
Notice 77
Attachment 6. Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions 79
APPENDIX E. List of Available Related Documents 87
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P-CHLORO-M-CRESOL REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Assessment
Margaret Cogdell-Ervin
Tom Harris
Frank Hernandez
Rafael Prieto
Biological Analysis Branch
Biological Analysis Branch
Economic Analysis Branch
Biological Analysis Branch
Environmental Fate and Effects Assessment
Karen Angulo
Joanne Edwards
Hank Jacoby
Health Effects Assessment
Winston Dang
Pamela M. Hurley
Tom Myers
Registration Assessment
Marianne Clark
Tina Levine
Shyam Mathur
Risk Management
Kathy Davis
Tom Luminello
Emily Mitchell
Field Operations Division
Science Analysis and Coordination Staff
Ecological Effects Branch
Environmental Fate and Groundwater Branch
Occupational and Residential Exposure Branch
Toxicology Branch I
Risk Characterization and Analysis Branch
Antimicrobial Program Branch
Registration Support Branch
Registration Support Branch
Accelerated Reregi strati on Branch
Accelerated Reregi strati on Branch
Planning and Reregi strati on Branch
Steve Shapiro
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11
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific (i.e.
drinking water) lifetime exposure at which adverse, non carcinogenic health effects are not
anticipated to occur.
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
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and
other organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of
substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in
50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It
is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
LOD Limit of Detection
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
Hg/g Micrograms Per Gram
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
N/A Not Applicable
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GLOSSARY OF TERMS AND ABBREVIATIONS
NOEC No effect concentration
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
Q*! The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RS Registration Standard
RUP Restricted Use Pesticide
SLN Special Local Need (Registrations Under Section 24 (c) of FIFRA)
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
ug/L Micrograms per liter
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency has completed its reregi strati on eligibility
decision (RED) for the pesticide p-chloro-m-cresol, case 3046, which includes the active
ingredient para-chloro-meta-cresol. This decision includes a comprehensive reassessment of
the required target data and the use patterns of currently registered products. p-Chloro-m-
cresol is an antimicrobial preservative used to control bacteria and fungi in the formulation of
industrial materials. The Agency has concluded that all uses, as described in this document,
will not cause unreasonable risks to humans or the environment and therefore, all products are
eligible for reregi strati on.
To mitigate risks of potential toxicity to occupational handlers, the Agency is requiring
use of personal protective equipment and reductions of application concentrations of p-
chloro-m-cresol in the manufacture of paints. The Agency is also requiring revisions to
product labels to clarify use sites, application instructions, and user safety recommendations.
Revised labeling, product chemistry, and acute toxicology studies must be submitted to
achieve product reregi strati on.
v
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was
amended to accelerate the reregi strati on of products with active ingredients registered prior to
November 1, 1984. The amended Act provides a schedule for the reregi strati on process to be
completed in nine years. There are five phases to the reregi strati on process. The first four
phases of the process focus on identification of data requirements to support the reregi strati on
of an active ingredient and the generation and submission of data to fulfill the requirements.
The fifth phase is a review by the U.S. Environmental Protection Agency (referred to as "the
Agency") of all data submitted to support reregi strati on.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for reregi strati on" before
calling in data on products and either reregistering products or taking "other appropriate
regulatory action." Thus, reregi strati on involves a thorough review of the scientific data base
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 the
pesticide meets the "no unreasonable adverse effects" criterion of FIFRA.
This document presents the Agency's decision regarding the reregi strati on eligibility of
the registered uses of p-chloro-m-cresol. The document consists of six sections. Section I is
the introduction. Section II describes p-chloro-m-cresol, its uses, data requirements and
regulatory history. Section III discusses the human health and environmental assessment
based on the data available to the Agency. Section IV presents the reregi strati on decision for
p-chloro-m-cresol. Section V discusses the reregi strati on requirements for p-chloro-m-cresol.
Finally, Section VI is the Appendices which support this Reregi strati on Eligibility Decision.
Additional details concerning the Agency's review of applicable data are available on request.
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II. CASE OVERVIEW
A. Chemical Overview
The following active ingredient is covered by this Reregi strati on Eligibility
Decision:
• Common Name: p-chloro-m-cresol (PCMC)
• Chemical Name: para-chloro-meta-cresol
• Chemical Family: phenol
• CAS Registry Number: 59-50-7
• OPP Chemical Code: 064206
• Empirical Formula: C7H7OC1
• Trade and Other Names: Preventol
• Basic Manufacturer: Bayer AG
B. Use Profile
The following is information on the currently registered uses with an overview
of use sites and application methods. A detailed table of the uses of p-chloro-m-cresol
is in Appendix A.
Type of Pesticide: Fungicide; Microbiocide/Microbiostat (Slime-Forming
Bacteria); Microbiocide/Microbiostat (Slime Forming Fungi)
Use Sites: Terrestrial Non-food
Industrial Preservatives:
Oil Recovery Drilling Muds/Packer Fluids
Aquatic Non-Food Industrial
Industrial Preservatives:
Oil Recovery Drilling Muds/Packer Fluids
Indoor Non-Food
Industrial Preservatives:
Adhesives, Industrial
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Coatings, Industrial
Emulsions, Resin/Latex/Polymer
Leather Processing Liquors
Leather/Leather Products
Metalworking Cutting Fluids
Paints (In-Can)
Specialty Industrial Products
Wet-end Additives/Industrial Processing Chemicals
Target Pests:
Bacteria: Formaldehyde-resistant bacteria, Aeromonaspunctata, Bacillus
subtilis, Escherichia coli, Leuconostoc mesenteroides, Proteus
vulgaris, Pseudomonas aeruginosa, Pseudomonasfluorescens,
Staphylococcus aureus, Desulfovibrio desulfuricans
Yeasts: Candida albicans, Torula rubra
Fungi: Aspergillus flavus, Aspergillus niger, Aureobasidiumpullulans,
Chaetomium globosum, Cladosporium herbarum, Coniophora
puteana, Paecilomyces variotti, Penicillium citrinum,
Penicillium glaucum, Trichophyton pedis, Trichoderma viride
Formulation Types Registered: End use, manufacturing use; crystalline
Method and Rates of Application:
Types of Treatment - Hides and skins treatment; Industrial preservative
treatment; Preservative treatment; Not on label (registrant
must specify on label)
Equipment - Not on label (registrant must specify on label)
Timing - During manufacture; Not on label (registrant must specify on label)
Surface Type - Not Applicable
Application Rate -
Terrestrial non-food crop: From 500 to 1998 ppm of active ingredient.
Aquatic non-food industrial: From 500 to 1998 ppm of active
ingredient.
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Indoor non-food: From 500 to 29970 ppm of active ingredient.
Use Practice Limitations: (that apply to all uses on all products)
Do not discharge effluent containing this pesticide into sewage systems without
notifying the sewage treatment plant authority (POTW).
Do not discharge effluent containing this product into lakes, streams, ponds, estuaries,
oceans, or public water (NPDES license restriction).
C. Data Requirements
The Agency applied the data requirements specified in 40 CFR Section 158 and
the Phase II Requirements to active ingredients in this chemical case. Studies were
generated and submitted for these requirements to the Agency. The data from these
studies along with other available information form the basis for the Agency's
scientific assessment and regulatory decisions. Appendix B includes all data
requirements identified by the Agency needed to support reregi strati on for currently
registered uses.
D. Regulatory History
p-Chloro-m-cresol was initially registered as a pesticide in the United States in
1968 for use as an industrial preservative. There are currently three products
registered with p-chloro-m-cresol as an active ingredient. Each product is at least
99.9% p-chloro-m-cresol.
Data to support the continued registration of p-chloro-m-cresol were required
under the Antimicrobial Data Call-In of 1987 and the Phase IV Data Call-In of 1991.
These data have been submitted and are part of the data base considered in this
Reregi strati on Eligibility Decision.
Uses of p-chloro-m-cresol include application to systems which may result in
residues of p-chloro-m-cresol in paper coatings and adhesives. Tolerances for food
grade adhesives and paper coatings which may contact foods are cited in the 21 CFR.
The FDA has jurisdiction for establishing these tolerances.
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III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
Chemical Name: p-chloro-m-cresol
Molecular Weight: 142.58
Color: white/colorless
Physical State: crystalline solid
Odor: phenolic
Melting Point: 63-65°C
Boiling Point: approximately 239°C
Bulk Density: 49.93 Ibs/ft3 (800 g/kg/m3)
Solubility: Water 4 g/L
Ethanol 500 g/L
Toluene 300 g/L
10% aqueous NaOH solution 320 g/L
Vapor Pressure: 0.25 mm Hg at 25°C
Dissociation constant: 9.4 ± 0.1 at 20°C
Log K0/,/or log P): 3.02
pH: 5.6 (saturated aqueous solution) at 20°C
Flash Point: 244.4°F (118°C)
p-Chloro-m-cresol is corrosive to metals and forms complex compounds with
transition metal ions. Slow discoloration of the chemical occurs in the presence of
sunlight.
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B.
Human Health Assessment
1. Toxicology Assessment
At present, the toxicological data base for p-chloro-m-cresol meets the
requirements for antimicrobial pesticides. The data are adequate and will
support a reregi strati on eligibility determination for the currently registered
non-food uses.
a. Acute Toxicity
Results of the acute toxicity studies conducted with technical p-
chloro-m-cresol are summarized below in Table 1:
Table 1. Acute Toxicity Values of Technical p-Chloro-m-cresol
Route
Oral
Dermal
Inhalation
Eye Irritation1
Skin Irritation1
Dermal Sensitization1
Species
Rat
Rat
Rat
Rabbit
Rabbit
Guinea Pig
Results
LD50:
Males 5129mg/kg
Females 3636 mg/kg
LD,0 >5000 mg/kg
Waived
Corrosive
Corrosive
Not a sensitizer
Toxicity Category
III
IV
..
I
I
N/A
Not required for TGAI, however, presented here for informational purpose.
The acute oral LD50 in rats is 5129 mg/kg for males and 3636
mg/kg for females placing p-chloro-m-cresol in Toxicity Category III
(MRID 00071335). The acute dermal LD50 in rats is >5000 mg/kg
placing p-chloro-m-cresol in Toxicity Category IV (MRID 00075492).
The rat acute inhalation study was waived because p-chloro-m-
cresol is a chunky solid and respirable particles will not be formed.
p-Chloro-m-cresol is a Toxicity Category I primary eye irritant
in rabbits. The study resulted in corneal cauterization, conjunctivitis,
conjunctival ulceration, iritis, and corneal opacity and ulceration. The
results were not reversible in 21 days (MRIDs 00109649 and
00048548). p-Chloro-m-cresol is a Toxicity Category I primary dermal
irritant in rabbits. This study demonstrated that p-chloro-m-cresol was
very irritating and cauterizing at the site of administration (MRID
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00109649). However, p-chloro-m-cresol is not a skin sensitizer in
guinea pigs (MRID 00078837).
b. Subchronic Toxicity
Preventol CMK (technical 99.9% p-chloro-m-cresol) was tested
in a subchronic feeding study in 20/sex male and female Wistar rats at
dose levels of 0, 150, 500 or 1500 ppm for 13 weeks (0, 12, 41, or 120
mg/kg/day for males and 0, 17, 54, or 167 mg/kg/day for females).
Clinical signs, body weights, food consumption, clinical biochemistry,
urinalysis, organs weights, gross pathology and microscopic pathology
were examined. At 500 and 1500 ppm, a decrease in body weight gain
was observed in males but not females (5-6% less than controls). No
other effects were observed. The decreases in body weight gain are not
of toxicological significance. The NOEL is greater than 1500 ppm
which was the highest dose tested (MRID 124844).
Preventol CMK (technical 99.9% p-chloro-m-cresol) was tested
in a 21-day dermal study in New Zealand White rabbits (10/sex/dose
group) at the following dose levels: 0, 10, 40 or 160 mg/kg/day. The
animals were dosed 5 days/week for a total of 15 applications. It
appears that the test material was applied without a vehicle. Dermal
irritation was observed in all treated groups, which ranged from slight
erythema and very slight edema (10 mg/kg/day) to severe erythema and
slight edema (160 mg/kg/day). Other dermal effects included skin
thickening, scaling, blanching, raw areas, necrosis, brown scab-like
areas, and sloughing. Fissuring occurred in one mid-dose female and in
two high dose males. The NOEL for dermal irritation is less than 10
mg/kg/day lowest dose tested. No systemic effects were observed at
either 10 mg/kg/day or 40 mg/kg/day. At 160 mg/kg/day, a compound-
related enhancing effect on nonsupporative pericholangitis (both sexes)
and bile duct proliferation (females) in the liver were observed. The
systemic NOEL is 40 mg/kg/day and the LOEL is 160 mg/kg/day based
on enhanced liver pathology in both sexes (MRID 62905).
c. Chronic toxicity
Technical p-chloro-m-cresol (99.90 - 99.97%) was tested in a
chronic feeding/carcinogenicity study in male and female Wistar rats for
24 months. Fifty/sex were tested per dose level with an additional
ten/sex scheduled to be sacrificed at 53 weeks. The following dose
levels were administered: 0, 400, 2000, or 10,000 ppm (0, 21.0, 103.1,
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or 558.9 mg/kg/day for males and 0, 27.7, 134.3, or 743.5 mg/kg/day
for females).
At some intervals, the concentration analyses were somewhat
low for all dose groups. At 10,000 ppm, the following systemic effects
were observed when compared to controls: an increase in the frequency
of poor general condition in females; a decrease in body weight (8%
males, 21% females, p < 0.01); a decrease in food efficiency in females
(29%); an increase in water intake (14% in males, 16% in females); a
decrease in urinary total protein in females (25-40%, p< 0.01); a
decrease in brain weight in females (88.6-94.4%, p < 0.01); an increase
in relative kidney weights (both sexes 8%, p< 0.05); an increase in
papillary necroses in males (eight vs. two in controls, p < 0.05 for
trend); an increase in cortical dilation and fibrosis in the kidney of males
(p < 0.05); an increase in unilateral and combined unilateral and
bilateral degeneration of seminiferous tubules in males; an increase in
unilateral and combined unilateral and bilateral reduced spermatozoa in
epididymides in males and an increase in brain compression in females.
At 2000 ppm, the same effects in seminiferous tubules, epididymides
and brain were observed. At 400 ppm, the same effects were observed
in the brain. The systemic NOEL is less than 400 ppm and the systemic
LOEL is 400 ppm based on poor general condition, decreased body
weight and food efficiency, increased water intake, decreased urinary
protein, changes in organ weights and histopathology of the kidney,
brain (400 ppm and above), testes and epididymides (2000 ppm and
above) (MRID 42784801). Conclusions on carcinogenicity in this study
are reported below.
d. Carcinogenicity
From the above chronic toxicity study (MRID 42784801),
female rats had a statistically significant increase in pituitary adenomas
and adenomas and/or carcinomas combined in the mid-dose group
(2000 ppm, p=0.042) but not in the high dose group in pairwise
comparisons with the control group. There was no significant increase
in the trend for these tumors. In addition, the incidences of these tumors
were within the historical control range. A statistically significant
increase in pituitary adenomas was also observed in low dose males, but
not in the mid- or high dose males. There was a statistically significant
decreasing trend for these tumors (p <0.05). Again, the incidences of
these tumors were within the historical control range.
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In addition to the pituitary tumors in females, male rats had a
significant increasing trend in testicular interstitial cell tumors (p <0.05).
The incidences of these tumors, however, were within the historical
control range. Therefore, the increased incidence of tumors seen in this
study were not related to treatment with p-chloro-m-cresol. Based on
the Agency's conclusions of this study and because there is no mouse
study, the Agency has determined that p-chloro-m-cresol is not
classifiable as a human carcinogen, Group D. This determination is also
discussed in subsection], Toxicological Endpoints of Concern.
e. Developmental Toxicity
p-Chloro-m-cresol was tested by gavage in a developmental
toxicity study in rats at the following dose levels: 0, 30, 100, or 300
mg/kg/day during gestation days 6-15 inclusive. At 300 mg/kg, six
dams died. Treatment-related clinical signs of toxicity included audible
breathing sounds, gasping breathing, reduced motility and high stepping
gait; and after dosing: lying on side, somnolence, abdominal position,
spastic convulsions, rough coat, sunken flanks and bloody muzzle.
Statistically significant decreases in body weight gain were observed
during the dosing period and significant decreases in the corrected body
weight gain were also observed during the entire gestation period. In
addition, the decreased food consumption was also considered to be
biologically significant. Finally, two dams totally resorbed their litters.
At 100 mg/kg/day, labored breathing was observed in two animals.
Statistically significant decreases in body weight gain during the dosing
period were observed in addition to significant decreases in the
corrected body weight gain during the entire gestation period. The
NOEL for maternal toxicity is 30 mg/kg/day and the LOEL is 100
mg/kg/day based on clinical signs of toxicity and decreases in body
weight gain (100 mg/kg/day and above) and death, decreases in food
consumption and increases in total resorptions (300 mg/kg/day). The
NOEL for developmental toxicity is 100 mg/kg/day and the LOEL is
300 mg/kg/day based on a significant decrease in the mean fetal weight
per litter at 300 mg/kg/day when compared to the control group and a
slight increase in the number of microphthalmias or anophthalmias at
this dose level (MRID 42292901).
f. Reproductive Toxicity
A reproduction study is required for antimicrobials if it is
determined that developmental toxicity and/or adverse effects on the
reproductive organs were observed in a 90-day dermal or inhalation
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study. From the available subchronic studies (developmental, a 90-day
subchronic feeding, and 21-day dermal studies) no adverse effects on
the reproductive organs were observed in either of the 21-day dermal or
the 90-day feeding studies. The developmental toxicity study indicated
that developmental effects in the rat were only observed at maternally
toxic levels. In addition, there was no indication of any mutagenic
effects for p-chloro-m-cresol under the conditions of the studies.
Although p-chloro-m-cresol was considered to have induced effects in
the testes and epididymides in the chronic feeding study, a closer
examination of the data indicated that these effects appeared late in the
study in older rats at terminal sacrifice. Therefore, it is unlikely that
these effects would be observed in a reproduction study, and one is not
required.
g. Mutagenicity
The four acceptable studies satisfy the guideline requirements for
mutagenicity studies for p-chloro-m-cresol. All of these studies indicate
that p-chloro-m-cresol was not found to be mutagenic.
Technical p-chloro-m-cresol was tested for potential to induce
reverse mutations in Salmonella typhimurium strains TA 1535, TA
1537, TA 100 and TA 98. Metabolic activation was provided by an S-9
mix prepared from the livers of adult male Sprague-Dawley rats,
induced with an injection of Aroclor 1254. Five dose levels, ranging
from 20 to 12,500 jig/plate, were used. All dose groups were tested
with S-9 mix; the highest dose was also tested in the absence of the S-9
mix. Endoxan® and Trypaflavin were used as positive controls. The
two highest dose levels, 2500 and 12,500 jig/plate were toxic to the
cells. p-Chloro-m-cresol failed to induce a mutagenic response at any
of the three lowest dose levels (20, 100, or 500 jig/plate) with all four
tester strains (MRID 00078838).
Technical p-chloro-m-cresol was tested for potential to induce
reverse mutations in Salmonella typhimurium strains TA1535, TA1537,
TA100 and TA98. Metabolic activation was provided by an S-9 mix
prepared from the livers of adult male rats, induced with an injection of
Aroclor 1254. The initial assay was conducted with five dose levels
ranging from 8 to 5000 jig/plate, evaluated both with and without
metabolic activation. The repeat assay was conducted with six dose
levels ranging from 30 to 960 jig/plate, evaluation both with and
without metabolic activation. Positive control chemicals were sodium
azide, nitrofurantoin, 4-nitro-l,2-phenylene diamine and 2-
10
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aminoanthracene. In the initial assay, no revertant colonies were
observed on plates containing 5000 jig/plate with and without S-9.
Cytotoxicity was observed in all strains at 1000 jig/plate with and
without S-9. At the other dose levels, no increase in revertants were
observed. In the repeat assay, cytotoxicity was observed in all strains at
960 jig/plate with and without activation. Reduced bacterial
populations were observed for all strains at 480 jig/plate and for strain
TA100 at 240 jig/plate with S-9. p-Chloro-m-cresol was not found to
be mutagenic under the conditions of the assay (MRID 42199901).
p-chloro-m-cresol was tested in a CHO-HGPRT assay for
potential to induce forward mutations. The dose levels tested were 50,
100, 150, 200, 250, or 300 |ig/ml, either with or without metabolic
activation. Both the 250 and 300 |ig/ml doses were cytotoxic, with and
without activation. For the remaining dose levels, p-chloro-m-cresol did
not induce an increase in mutations over the controls, either with or
without metabolic activation (MRID 41548601).
p-Chloro-m-cresol was tested for the potential to induce
chromosomal aberrations in a micronucleus assay in the mouse. It was
administered as a single i.p. injection at a dose level of 125 mg/kg. The
animals were sacrificed and the bone marrow was isolated and prepared
at 24, 48, and 72 hours after administration of the test chemical. No
increases in micronuclei in the polychromatic erythrocytes were
observed under the conditions of the study. In addition, the ratio of
normochromatic and polychromatic erythrocytes were unaffected by
treatment at any time point. The positive control, cyclophosphamide,
induced a statistically significant positive response. There were clear
signs of toxicity to the animals. Therefore, the dose level used was
acceptable (MRID 41598101 or 42005201).
p-Chloro-m-cresol was tested in a rat primary hepatocyte
unscheduled DNA synthesis (UDS) assay. The following dose levels
were tested: 0.25, 0.5, 2.5, 7.5, 10 or 20 |ig/ml and 2.53, 5.06, 7.58,
10.1, 15.2 or 20.2 |ig/ml. The positive control used was 2-
acetylaminofluorene (2-AAF). p-Chloro-m-cresol did not cause any
DNA damage or inducible repair under the conditions of the studies
(MRIDs 41548602 and 42163201).
h. Metabolism
A metabolism study is not required at this time for p-chloro-m-
cresol based on the Agency's requirements for antimicrobials.
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Metabolism studies are required only if the Agency determines that
additional information on the metabolism of the chemical is necessary
to clarify unusual effects observed in chronic or reproduction studies or
to clarify issues concerning structural activity relationships. For
p-chloro-m-cresol, the Agency has not identified any such issues that
warrant the need for metabolism data.
i. Toxicological Endpoints of Concern
For short term (1 to 7 days) and intermediate term (one week to
several months) occupational or residential exposure, the NOEL of 30
mg/kg/day and the LOEL of 100 mg/kg/day for maternal toxicity
(developmental toxicity study in the rat) is appropriate for risk
assessment. For chronic occupational or residential exposures, a LOEL
of 28 mg/kg/day for brain weight depression in females should be used
for risk assessment. This LOEL was observed in the two-year feeding
study in rats (MRID 42784801). Due to the lack of dermal absorption
data for p-chloro-m-cresol, 100% absorption is assumed for these risk
assessments.
The Agency (OPP's Health Effects Division's Carcinogenicity
Peer Review Committee) has classified p-chloro-m-cresol as Group D,
not classifiable as to human carcinogenicity. This determination is
further discussed in subsection d., Carcinogenicity, above. In addition,
there was no concern for mutagenicity. Several distant analogues tested
negatively in NTP bioassays. p-Chloro-m-cresol was not tested in the
mouse. However, since p-chloro-m-cresol is intended for non-food use,
a mouse carcinogenicity study is not required.
2. Exposure Assessment
a. Dietary Exposure
p-Chloro-m-cresol current uses include applications to
adhesives, glues, and paper which can be used in food processing,
packaging, and transportation. FDA has established tolerances for these
uses, as specified above in Section II, and is responsible for assuring
that any potential dietary exposures attributable to these uses are
acceptable in terms of toxicological risk. Therefore, EPA has not
addressed dietary exposure.
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b. Occupational and Residential Exposures
All current product formulations contain 99.9% p-chloro-m-
cresol as a crystalline solid. As specified above in Section II and in
Appendix A, the use sites include industrial adhesives, general
preservatives for leather, paper products, textiles, fibers and cordage,
metal-working fluids, industrial oil drilling muds and packer fluids,
industrial coatings, paints, and resin/latex/polymer emulsions. The
range of application rates for p-chloro-m-cresol is 0.05 to 2.0% in
adhesives, coatings, emulsions, dye pigments, and materials in the
paper, photo and textile industries and 0.02 to 5.0% in metal-working
fluids based on the total weight of product. All products containing p-
chloro-m-cresol are intended primarily for occupational use. However,
people in residential settings may use or handle products, such as
adhesives, leather, or paper products, which have been treated with p-
chloro-m-cresol.
An occupational and/or residential exposure assessment is
required for a pesticide if certain toxicological criteria are triggered and
there is potential exposure to handlers (mixers, loaders, and/or
applicators) during use, or to persons entering treated sites after
application is complete. As discussed above, the Agency believes there
are toxicological endpoints of concern for p-chloro-m-cresol and it is
reasonable to assume there is occupational and residential exposure
from the use of p-chloro-m-cresol products. Therefore, exposure
assessments are appropriate. To estimate exposures of primary
occupational handlers (workers) to this chemical the Agency used the
CMA Antimicrobial Exposure Assessment Study (MRID 42587501)
and a complete set of product application rates for primary occupational
handler exposure. Because current p-chloro-m-cresol end-use products
are formulated as solids, the pour-solid data from this study were used.
For secondary occupational handlers (painters) the Agency used the
Pesticide Handlers Exposure Data base (PHED) to estimate the
exposure.
Handler (Mixers. Loaders. Applicators) Exposures and Assumptions
There are potential exposures from handling p-chloro-m-cresol
end-use products or products to which p-chloro-m-cresol has been
added in commercial, industrial, and residential settings. The Agency
calculated daily exposure estimates using the following formula:
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Actual Daily Exposure (ADE) (mg/kg/day)
= ADE (//g/day) - Body Weight (BW) (kg) X 1 mg/1000 //g
Where the body weight is 60 kg based on the average weight of an adult
female, since the selected toxicological endpoint is a developmental
effect, and dermal absorption is assumed to be 100%.
Occupational Handler Exposures
Primary Exposures to Occupational Handlers: EPA estimated
exposures of p-chloro-m-cresol to handlers (mixers, loaders, and
applicators) who open-pour end use products into tanks of metal
working fluids and for other general industrial preservative uses. Short-
term and intermediate-term average daily doses for these handlers are
presented in Table 2. These uses are considered reasonable worst-case
exposures.
Table 2. Exposure Estimates for Short- and Intermediate-Term Worker Exposures for
p-Chloro-m-cresol
Use Scenario
Metal-working
Fluids
Mineral Oil based
(cone.)3
Non-Mineral Oil
based (cutting
fluids)4
General
Preservative5
UE1
(Hg/lb ai)
479
479
479
Ib/ai
used
5
6.5
3
Actual Daily
Exposure
(Hg/kg/day)
40.00
52
24.00
MOE2
751.00
578
1,253.00
'UE = Unit Exposure (dermal and inhalation) was derived from CMA Study. All handlers in these exposure studies
wore chemical-resistant gloves, long sleeves, and long pants.
2 Margin of Exposure (MOE) for short and intermediate term exposures.
3 Exposure calculation for metal-working fluid (mineral oil) tank side additives. Preventol CMK Preservative (EPA
Reg. 39967-12, 99.9% a.i.), is added at concentrations of approximately 0.5 pounds of preservative per gallon of
mineral oil. Assuming 10 gallons of mineral oil are treated before further dilution then, a total of 5 pounds of active
ingredient is used by handler per day.
4 Exposure calculation for metal-working fluids (non-mineral oil) tank side additives. Preventol CMK Preservative
(EPA Reg. 39967-12, 99.9% a.i.), is added at concentrations of approximately 1.3 pounds of preservative per gallon
of substrate. Assuming 5 gallons of mineral oil are treated everyday then, a total of 6.5 Ibs of active ingredient is
used by handler per day.
5 Exposure calculation for the general preservative use of p-chloro-m-cresol in adhesives.
1000 pounds of the material being treated at a labeled maximum rate of 0.3% by weight. Assuming 1000 pounds is
treated then, a total of 3 pounds of active ingredient is used by handler per day.
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Secondary Occupational and Residential Exposures: Based on the
use patterns, the Agency has identified three secondary exposure
scenarios for occupational handlers likely to represent reasonable worst-
case scenarios. These are exposures while handling paints, adhesives
and metal-working fluids treated with p-chloro-m-cresol.
The Pesticide Handler's Exposure Database (PHED) was used to
calculate risks to painters using p-chloro-m-cresol treated paints at the
currently labeled range of concentration (0.05 to 0.40%). Exposures to
homeowners using paints are expected to be of short or intermediate
term, but are not expected to be significant bcause of infrequent use.
Commercial painters, however, may experience significant short and
intermediate term and chronic exposures.
Currently, the Agency has no specific data upon which to
estimate exposures from adhesive and metal-working/cutting fluids.
However, the Agency assumes that such secondary occupational
exposures, whether occupational or residential, are not greater than
primary occupational exposures (open-pouring the 99.9% p-chloro-m-
cresol product). EPA makes this assumption of relatively low exposure
because: 1) p-chloro-m-cresol is in a diluted concentration (0.02 to
5.0%) in treated products like adhesive paper coatings, textiles and
leather; and 2) the length of contact time with treated products in
residential settings is usually of short duration.
Secondary occupational handler exposures and risks to
machinists handling metal-working/cutting fluids containing p-chloro-
m-cresol are not addressed in detail in this document. Agency
representatives continue to discuss with the Occupational Safety and
Health Administration (OSHA) the roles and responsibilities of
regulating the uses of metal-working fluids, and other products in
industrial settings. Currently, OSHA is responsible for regulating
machinists safety and exposure. EPA has made available this document
to OSHA for their regulatory use.
Post-Application Exposures
Primary and Secondary Occupational Post-Application
Exposures: Based on the use patterns, the Agency has identified two
reasonable worst-case primary occupational post-application exposure
scenarios: (1) exposures following applications of p-chloro-m-cresol to
open vats of liquids, such as adhesives, coatings, paints, or emulsions in
a commercial/industrial setting, and (2) exposures to persons
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maintaining equipment, such as industrial equipment, which contains
product treated with p-chloro-m-cresol. Exposures to persons
occupying work areas where p-chloro-m-cresol containing adhesives
have recently been applied, exposures in areas where p-chloro-m-cresol
containing products are being manufactured, and exposures to p-chloro-
m-cresol treated products are secondary occupational post-application
exposure. These exposures include both dermal and inhalation
exposures.
Primary and Secondary Residential Post-Application
Exposures: Because currently there are no end-use products containing
p-chloro-m-cresol intended for residential use, any exposures in these
settings would be limited to those after application of a p-chloro-m-
cresol treated product. Reasonable worst-case secondary residential
post-application exposure scenarios are exposures while occupying
areas where p-chloro-m-cresol containing adhesives and paints have
recently been applied and exposures to p-chloro-m-cresol treated
products, such as leather, paper or textile products. For the reasons
stated above, the Agency assumes secondary post-application exposures
in residential settings would be lower than primary exposures to
workers in industrial settings.
3. Risk Assessment
a. Dietary
The Agency did not conduct a dietary risk assessment for p-
chloro-m-cresol because of the non-food use patterns of current
products and FDA's responsibility for the tolerances for food-grade
adhesives and paper, as explained above.
b. Occupational and Residential
The Margin of Exposure (MOE) is a measure of how closely the
estimated exposure is to the NOEL (NOEL/exposure = MOE). For
substances whose NOEL is based on animal studies, the Agency's
policy has been that MOEs of 100 or greater represent a negligible risk
from that toxicological endpoint, that is, there is an adequate margin of
the exposure from the toxicological endpoint. However, for p-chloro-
m-cresol an additional factor of 3 is included in the margin of exposure
for chronic exposure to account for a lack of an NOEL from the chronic
rat study. For reasons given in subsection l.j, Toxicological Endpoints
of Concern, 30 mg/kg/day is the selected toxicological endpoint
16
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(NOEL) for short- and intermediate-term risk assessments of
occupational exposures. For chronic risk assessment, the toxicological
endpoint is the LOEL (no NOEL) of 28 mg/kg/day from the chronic rat
study. This increases the MOE threshold for chronic risk assessment
from 100 to 300 because of the additional uncertainty factor of 3. For
the exposure component the Agency used the calculated ADEs (Table 2
above) to calculate the MOEs for the primary occupational scenarios.
Risk from Occupational Handler Exposures
Primary Occupational Handler Exposures: The Agency estimated
risks (MOEs) to occupational handlers who have primary exposures of
short- and/or intermediate-term duration to p-chloro-m-cresol from the
application of p-chloro-m-cresol products to metal-working/ cutting
fluids and as general preservatives. In addition, the chronic risk was
estimated for the primary occupational exposures from the general
preservative use of p-chloro-m-cresol. The results (for the short- and
intermediate-term exposures) are presented in Table 2, above. MOEs
for chronic exposure would be similar to those calculated for short- and
intermediate-term exposure since the LOEL (no NOEL) selected for
chronic risk assessment is 28 mg/kg/day (brain weight depression in
female rats) versus a NOEL of 30 mg/kg/day for short- and
intermediate-term risks. MOEs are greater than 300 for all use settings
and thus are not of concern to the Agency.
Secondary Occupational Handler Exposures: The Agency believes
that exposures to painters using p-chloro-m-cresol treated paints
represents one of the worst-case scenarios for secondary occupational
handlers. To estimate these exposures, the Agency used the maximum
application concentration of 0.40% and assumed that 5 gallons of paint
are applied per day. In the absence of dermal absorption data, 100 %
dermal absorption is assumed. Using the PHED exposure database, the
short- and intermediate-term NOEL of 30 mg/kg/day, and the chronic
LOEL of 28 mg/kg/day resulted in low MOEs of approximately 30 for
the three terms of exposures. These compare against the Agency's
acceptable risk level of 100 (300 for p-chloro-m-cresol chronic
exposure as explained above). However, using the lowest application
concentration (0.05%) the estimated MOEs are 247 for short- and
intermediate-term and 269 for chronic exposure. While the chronic
MOE for painters is 269 as compared to the Agency's regulatory
standard of 300, the Agency is comfortable with this MOE because this
risk estimate includes conservative assumptions. These conservative
assumptions include 100% dermal absorption of p-chloro-m-cresol,
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chronic exposure to occupational painters, and that all paint is treated
with p-chloro-m-cresol. Therefore, this MOE may actually be greater
than 269.
The Agency has assumed that secondary occupational handler
exposures from handling adhesives containing p-chloro-m-cresol are not
greater than the exposures of the primary occupational handler from
open pouring the solid formulation of p-chloro-m-cresol in the industrial
preservative use scenario. Therefore, the risks from secondary
occupational exposures are assumed to be equal to or less (MOE >
1,253) than that for primary occupational exposure in the industrial
preservative use.
Using the assumption of 100% dermal absorption and the
potentially worst-case dermal and inhalation exposures to machinists
handling metal-working fluids containing p-chloro-m-cresol, the
Agency has some risk concerns for these secondary occupational
handlers. Metal-working machinists may experience high exposure
from splashing of the metal-working cutting fluids. The Agency will
notify OSHA of its concerns and will provide that Agency with a copy
of this document and supporting information.
Risk for All Other Occupational and Residential Scenarios
As discussed above, the Agency assumes that all other primary
and secondary exposures in occupational and residential settings, as
described above, including post-application exposures, are expected to
be no greater than, and more likely less than, estimated exposures
associated with the general preservative use (Table 2). Thus, the risks
associated with the other exposure scenarios are likely to be no greater,
or less, than those estimated, for the general preservative use (MOE =
1,253).
C. Environmental Assessment
1. Ecological Toxicity Data
a. Toxicity to Terrestrial Animals
(1) Acute Toxicity to Birds
In order to establish the acute toxicity of p-chloro-m-cresol to
birds, the following test was performed using the technical grade
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material: one avian single-dose oral (LD50) study on one species of
waterfowl or upland game bird (preferably mallard duck or bobwhite
quail).
TABLE 3: Avian Acute Oral Toxicity Findings
Species
Bobwhite Quail
% A.I.
99.97%
LD50 (ppm)
1,540
MRID
42692401
Toxicity Category
Slightly toxic
There is sufficient information to characterize p-chloro-m-cresol
as slightly toxic to avian species on an acute oral basis (Table 3). The
guideline requirement is satisfied (MRID 42692401).
(2) Subacute Toxicity to Birds
In order to establish the subacute toxicity of p-chloro-m-cresol to
birds, the following test was performed using the technical grade
material: one avian dietary study (LC50) on one species of waterfowl or
upland game bird (preferably the mallard duck or bobwhite quail).
TABLE 4: Avian Subacute Dietary Toxicity Findings
Species
Bobwhite Quail
% A.I.
99.97%
LC50(ppm)
>3,180
MRID
42692402
Toxicity Category
Slightly toxic
There is sufficient information to characterize p-chloro-m-cresol
as slightly toxic to practically non-toxic to avian species on a subacute
dietary basis (Table 4). The guideline requirement is satisfied (MRID
42692402).
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
In order to establish the toxicity of p-chloro-m-cresol to
freshwater fish, the minimum data required on the technical grade of the
active ingredient is a single 96-hour LC50 fish toxicity study using either
a warmwater fish (preferably bluegill sunfish) or a coldwater fish
(preferably rainbow trout).
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TABLE 5: Freshwater Fish Acute Toxicity Findings
Species
Rainbow trout
% A.I.
99.97%
LC50 (ppm)
0.9
MRID
42692403
Toxicity Category
Highly toxic
There is sufficient information to characterize p-chloro-m-cresol
as highly toxic to freshwater fish (Table 5). The guideline requirement
for freshwater fish acute toxicity is fulfilled (MRID 42692403).
(2) Freshwater Invertebrates
The minimum testing required to assess the acute toxicity of p-
chloro-m-cresol to freshwater invertebrates is a single 48-hour LC50 test.
TABLE 6: Freshwater Invertebrate Acute Toxicity Findings
Species
Daphnid (Daphnia magna)
% A.I.
99.97%
LC50 (ppm)
2.3
MRID
42692404
Toxicity Category
Moderately toxic
2.
There is sufficient information to characterize p-chloro-m-cresol
as moderately toxic to freshwater invertebrates (Table 6). The guideline
requirement is satisfied (MRID 42692404).
Environmental Fate
The Agency has not required data on the dissipation of p-chloro-m-
cresol in the environment. However, the currently registered uses are of such a
nature that little or no environmental exposure is likely to occur and no further
information is currently necessary. Based on the very limited information
available, it appears that this chemical may be relatively stable in the
environment. Eventual degradation would depend on the solubilization of the
chemical and microbial-aided degradation. Solubility in water is reported in
the Ninth Edition of The Merck Index as 1 gram of p-chloro-m-cresol in 260
milliliters of water at 20° C with solubility increasing with temperature.
3. Exposure and Risk Characterization
Acceptable laboratory studies demonstrate that p-chloro-m-cresol is
slightly toxic to birds, highly toxic to fish, and moderately toxic to aquatic
invertebrates. The oil recovery drilling mud (aquatic and terrestrial) uses are
expected to result in minimal to no exposure if proper procedures are employed
in the disposal of contaminated drilling muds.
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While the hazard to aquatic organisms from p-chloro-m-cresol has been
characterized, a quantitative risk assessment has not been conducted. The risks
to aquatic environments from this use are regulated under the NPDES
permitting program of EPA's Office of Water. The labels for all p-chloro-m-
cresol products must require that discharges to aquatic environments comply
with an NPDES permit.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after
submission of relevant data concerning an active ingredient, whether products
containing the active ingredients are eligible for reregi strati on. The Agency has
previously identified and required the submission of the generic (i.e. active ingredient
specific) data required to support reregi strati on of products containing p-chloro-m-
cresol active ingredients. The Agency has completed its review of these generic data,
and has determined that the data are sufficient to support reregi strati on of all current
products containing p-chloro-m-cresol. Appendix B identifies the generic data
requirements that the Agency reviewed as part of its determination of reregi strati on
eligibility of p-chloro-m-cresol, and lists the submitted studies that the Agency found
acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess
the registered uses of p-chloro-m-cresol and to determine that p-chloro-m-cresol can
be used without resulting in unreasonable adverse effects to humans and the
environment. The Agency therefore finds that all products containing p-chloro-m-
cresol as the active ingredient, and as specified in this document, are eligible for
reregi strati on. The reregi strati on of particular products is addressed in Section V of
this document.
The Agency made its reregi strati on eligibility determination based upon the
target data base required for reregistration, the current guidelines for conducting
acceptable studies to generate such data, published scientific literature, etc. and the
data identified in Appendix B. Although the Agency has found that all uses of p-
chloro-m-cresol are eligible for reregistration, it should be understood that the Agency
may take appropriate regulatory action, and/or require the submission of additional
data to support the registration of products containing p-chloro-m-cresol, if new
information comes to the Agency's attention or if the data requirements for registration
(or the guidelines for generating such data) change.
21
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B. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredients p-
chloro-m-cresol, the Agency has sufficient information on the health effects of
p-chloro-m-cresol and on its potential for causing adverse effects in fish and
wildlife and the environment. The Agency has determined that p-chloro-m-
cresol products, labeled and used as specified in this Reregi strati on Eligibility
Decision, will not pose unreasonable risks or adverse effects to humans or the
environment. Therefore, the Agency concludes that products containing p-
chloro-m-cresol for all uses are eligible for reregi strati on.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of p-chloro-m-cresol are
eligible for reregi strati on.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for p-
chloro-m-cresol. Where labeling revisions are imposed, specific language is set forth
in Section V of this document.
1. Occupational and Residential Labeling Rationale/Risk Mitigation
Measures; Personal Protective Equipment (PPE)/Engineering Controls for
Handlers
Occupational-Use Products
The Agency has determined that regulatory action regarding the
establishment of active-ingredient-based minimum PPE requirements for
primary occupational handlers is necessary for products containing p-chloro-m-
cresol. Because data from the CMA study were collected with the handlers
wearing long sleeved shirt, long pants, shoes, socks and chemical-resistant
gloves, the Agency is requiring these PPE as active-ingredient based minimum
(baseline) PPE for primary handlers of p-chloro-m-cresol.
The Agency has determined that for the other occupational and
residential exposure scenarios (except machinists using p-chloro-m-cresol
treated metal-working fluids and painters using p-chloro-m-cresol treated
paint), including post-application exposure, concerns for toxicological risks are
unwarranted. For this reason, active ingredient-based minimum PPE
22
-------
requirements, or entry restrictions are not being imposed. The Agency notes,
however, that there are possible concerns about secondary occupational
handlers who are machinists handling p-chloro-m-cresol treated metal-working
fluids. These concerns will be conveyed to OSHA for their consideration of
regulatory measures to protect these workers.
2. Reduction in Percentage of Active Ingredient
Also the Agency notes that short- and intermediate- term and chronic
toxicity risks to painters may be unacceptable when paints are formulated at
higher application concentration of p-chloro-m-cresol. At the lowest
application concentrations (0.05%) these risks are significantly reduced. The
sole registrant with products for use in paint, Bayer, has agreed to reduce the
concentration to 0.05% in paints.
3. Other Labeling Requirements
The Agency is also requiring other use and safety information to be
placed on the labeling of all end-use products containing p-chloro-m-cresol.
For the specific labeling statements, refer to Section V of this document.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the
reregi strati on of all p-chloro-m-cresol products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of p-chloro-m-cresol
for the above eligible uses has been reviewed and determined to be
substantially complete.
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP)
labeling must be revised to comply with all current EPA regulations, PR
Notices and applicable policies. The MP labeling must bear the following
statement under Directions for Use:
"Only for formulation into a microbiocide for the following use(s): industrial
adhesives, general preservatives for leather, paper products, textiles, fibers and
23
-------
cordage, metalworking (cutting) fluids, industrial oil/ gas drilling muds and
packer fluids, industrial coatings, and resin/latex/ polymer emulsions."
An MP registrant may, at his/her discretion, add one of the following
statements to an MP label under:
"Directions for Use" to permit the reformulation of the product
for a specific use or all additional uses supported by a formulator
or user group:
(a) "This product may be used to formulate products for specific
use(s) not listed on the MP label if the formulator, user group, or
grower has complied with U.S. EPA submission requirements
regarding support of such use(s)."
(b) "This product may be used to formulate products for any
additional use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U.S.
EPA submission requirements regarding support of such
use(s)."
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 product specific data requirements are listed in Appendix
G, the Product Specific Data Call-In Notice.
Registrants must review previous data submissions to ensure that they
meet current EPA acceptance criteria (Appendix F; Attachment E) and if not,
commit to conduct new studies. If a registrant believes that previously
submitted data meet current testing standards, then study MRID numbers
should be cited according to the instructions in the Requirement Status and
Registrants Response Form provided for each product.
2. Labeling Requirements for p-Chloro-m-cresol Products
a. Environmental Hazards
The following statement is required to appear in the
Environmental Hazards section of the label, in accordance with 40 CFR
156.10:
24
-------
"This pesticide is highly toxic to fish."
b. Directions for Use Clarification
Registrants must specify on labeling the complete directions for
use for each use pattern: site of application, type of application, timing
of application, equipment used for application, and the rate of
application (dosage).
The labeling must be amended to specify a maximum application
rate to achieve a concentration of 0.05% of p-chloro-m-cresol in paints.
The following statement must be added to the precautionary labeling:
"Do not apply in marine and/or estuarine oil fields."
The following statement must be added to the labels for aquatic
non-food industrial oil drilling muds and packer fluids:
"For use in offshore wells only."
For use in both terrestrial and offshore oil drilling muds and
packer fluids, the following statement must be added:
"This product may be used for terrestrial and off-shore oil/gas
drilling muds and packer fluids."
Clarification of Oil Drilling Mud Use
To clarify the intent of the oil recovery drilling muds/packer
fluids use (as an aquatic or terrestiral non-food use pattern), the
following statement must be added to the labels for terrestrial non-food
oil drilling muds and packer fluids:
"For use in terrestrial wells only."
c. Worker Protection Labeling
PPE/Engineering Control Requirements for Pesticide Handlers
For sole active-ingredient end-use products that contain p-
chloro-m-cresol, the product labeling must be revised to adopt the
handler personal protective equipment/engineering control requirements
25
-------
set forth in this section. Any conflicting PPE requirements on the
current labeling must be removed.
For multiple active-ingredient end-use products that contain p-
chloro-m-cresol, the handler personal protective equipment/engineering
control requirements set forth in this section must be compared to the
requirements on the current labeling and the more protective must be
retained. For guidance on which requirements are considered more
protective, see PR Notice 93-7.
Minimum (Baseline) PPE/Engineering Control Requirements
The Agency is establishing active-ingredient-based minimum
(baseline) PPE/engineering control requirements for p-chloro-m-cresol
end-use products that are intended primarily for occupational use. The
minimum (baseline) PPE for all occupational uses of p-chloro-m-cresol
end-use products is:
Applicators and other handlers must wear:
—long-sleeved shirt, long pants, socks and shoes, and
—chemical-resistant gloves.
For the glove statement, use the statement established through the
instructions in Supplement Three of PR Notice 93-7. Although this PR
Notice addresses products within the scope Worker Protection Standard
(WPS), that is products are generally of agricultural use, the certain
parts of the guidance are applicable to all pesticide products.
Determining PPE Requirements for End-use Product Labels
1. Any necessary PPE for each p-chloro-m-cresol occupational end-use
product will be established on the basis of the end-use product's acute
toxicity category. NOTE: All end-use products will also be required to
specify minimum work attire for all handlers. If the end-use product is
classified as toxicity category I or II for eye irritation potential,
protective eyewear is also required for all handlers. If the end-use
product is classified as toxicity category I or II for skin irritation
potential or acute dermal toxicity, a chemical-resistant apron is also
required for all handlers.
2. The PPE that would be established on the basis of the acute toxicity
category of the end-use product must be compared to the active
26
-------
ingredient-based minimum (baseline) personal protective equipment
specified above. The more protective PPE must be placed on the
product labeling. For guidance on which PPE is considered more
protective, see PR Notice 93-7.
Placement in Labeling
The personal protective equipment requirements must be placed
on the end-use product labeling in the location specified in PR Notice
93-7, and the format and language of the PPE requirements must be the
same as is specified in PR Notice 93-7.
d. Other Labeling Requirements
The Agency is requiring the following labeling statements to be
located on all end-use products containing p-chloro-m-cresol:
Application Restrictions
"Do not apply this product in a way that will contact workers or other
persons."
User Safety Requirements
Add the following statement to all end-use product labeling:
"Follow manufacturer's instructions for cleaning/maintaining personal
protection equipment (PPE). If no such instructions for washables, use
detergent and hot water. Keep and wash PPE separately from other
laundry."
User Safety Recommendations
• "Users should wash hands before eating, drinking, chewing gum,
using tobacco, or using the toilet."
• "Users should remove clothing immediately if pesticide gets
inside. Then wash thoroughly and put on clean clothing."
• "Users should remove PPE immediately after handling this
product. Wash the outside of gloves before removing."
27
-------
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/
labeling for 26 months from the date of the issuance of this RED. Persons other than
the registrant may generally distribute or sell such products for 50 months from the
data of the issuance of 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.
The Agency has determined that registrants may distribute and sell p-chloro-m-
cresol products bearing old labels/labeling for 26 months from the date of issuance of
this RED. Persons other than the registrant may distribute or sell such products for 50
months from the date of issuance of this RED. Registrants and persons other than
registrants remain obligated to meet pre-existing Agency imposed label changes and
existing stocks requirements applicable to your products.
28
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VI. APPENDICES
29
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30
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Report Run Date: 03/14/96 ) Time 11:20 LUIS 3.0 - Page:
PRD Report Date: 06/07/95
APPENDIX A REPORT
Case 3046[p-Chloro-m-cresol] Chemical 064206[4-Chloro-m-cresol]
44444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444444,
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Restr. Geographic Limitations Use
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/A] (days) Interv Codes
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year [day(s)]
cycle
))))))
The uses in Appendix A were evaluated for reregistration. These do NOT include changes in application rates, deletion of uses, frequency or timing of applications, restricted entry intervals,
etc. that may have been mandated in this document.
NON- FOOD/NON- FEED
ADHESIVES, INDUSTRIAL
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
COATINGS, INDUSTRIAL
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
EMULSIONS, RESIN/LATEX/POLYMER
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
LEATHER PROCESSING LIQUORS
Preservative treatment, Not on label, Not P/T
on label, Not Applicable, Not applicable
for this use
W 500
W 500
Use Group: INDOOR NON-FOOD
W 19980 * NS NS NS
Use Group: INDOOR NON-FOOD
W 3996 * NS NS NS
Use Group: INDOOR NON-FOOD
W 1998 * NS NS NS
Use Group: INDOOR NON-FOOD
W 2498 * NS NS NS
CIS, C24
CIS, C24
CIS, C24
CIS, C24
LEATHER/LEATHER PRODUCTS
Hides and skins treatment, Not on label, P/T
Not on label, Not Applicable, Not
applicable for this use
METALWORKING CUTTING FLUIDS
Preservative treatment, Not on label, Not P/T
on label, Not Applicable, Not applicable
for this use
OIL RECOVERY DRILLING MUDS/PACKER FLUIDS
Preservative treatment, Not on label, Not P/T
on label, Not Applicable, Not applicable
for this use
W 500
W 500
Use Group: INDOOR NON-FOOD
W 3996 * NS NS NS NS NS NS
Use Group: INDOOR NON-FOOD
W 29970 * NS NS NS NS NS NS
Use Group: AQUATIC NON-FOOD INDUSTRIAL
W 1998 * NS NS NS NS NS NS
CIS, C24
CIS, C24
CIS, C24
Preservative treatment, Not on label, Not P/T
on label, Not Applicable, Not applicable
for this use
W 1998 * NS NS
NS NS NS NS
CIS, C24
OIL RECOVERY DRILLING MUDS/PACKER FLUIDS
Preservative treatment, Not on label, Not P/T
on label, Not Applicable, Not applicable
for this use
W 500
Use Group: TERRESTRIAL NON-FOOD CROP
W 1998 * NS NS NS NS NS NS
CIS, C24
-------
Report Run Date: 03/14/96 ) Time 11:20
PRD Report Date: 06/07/95
APPENDIX A REPORT
Case 3046[p-Chloro-m-cresol] Chemical 064206[4-Chloro-m-cresol]
1444444,
SITE Application Type, Application Form(s) Min. Appl.
Timing, Application Equipment ) Rate (AI un-
Surface Type (Antimicrobial only) & Effica- less noted
cy Influencing Factor (Antimicrobial only) otherwise)
LUIS 3.0 - Page:
Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Restr. Geographic Limitations Use
Rate (AI Tex. @ Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
unless noted Max. /crop /year otherwise)/A] (days) Interv Codes
otherwise) Dose cycle /crop /year [day(s)]
cycle
The uses in Appendix A were evaluated for reregistration. These do NOT include changes in application rates, deletion of uses, frequency or timing of applications, restricted entry intervals,
etc. that may have been mandated in this document.
NON-FOOD/NON-FEED (continued)
OIL RECOVERY DRILLING MUDS/PACKER FLUIDS (continued)
Preservative treatment, Not on label, Not P/T W
on label, Not Applicable, Not applicable
for this use
PAINTS (IN-CAN)
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
SPECIALITY INDUSTRIAL PRODUCTS
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
WET-END ADDITIVES/INDUSTRIAL PROCESSING CHEMICALS
Industrial preservative treatment, During P/T
manufacture, Not on label, Not
Applicable, Not applicable for this use
W 500
W 500
Use Group: TERRESTRIAL NON-FOOD CROP
W 1998 * NS NS NS NS NS NS
Use Group: INDOOR NON-FOOD
W 3996 * NS NS NS NS NS NS
Use Group: INDOOR NON-FOOD
W 19980 * NS NS NS NS NS NS
Use Group: INDOOR NON-FOOD
W 2997 * NS NS NS NS NS NS
CIS, C24
CIS, C24
CIS, C24
CIS, C24
32
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Report Run Date: 03/14/96 ) Time 11:20
PRD Report Date: 06/07/95
APPENDIX A REPORT
Case 3046[p-Chloro-m-cresol] Chemical 064206[4-Chloro-m-cresol]
LUIS 3.0 - Page:
LEGEND
444444
Sort: Uses Eligible or Ineligible for Re-registration, Food/Feed or Non-Food/Non-Feed Uses, Alpha Site Name, Use Group Name, Alpha Application Type/Timing/Equipment
Description, Formulation, Maximum Application Rate Unit/Area Quantity, Minimum Application Rate, Maximum Number of Applications at Maximum Rate, Maximum Dose per Crop
Cycle or per Year, Minimum Interval Between Applications (Days), Restricted Entry Interval (Days), Allowed/Disallowed Geographical Areas, Use Limitations Codes.
HEADER ABBREVIATIONS
Min. Appl. Rate (AI unless : Minimum dose for a single application to a single site. System calculated. Microbial claims only.
noted otherwise)
Max. Appl. Rate (AI unless : Maximum dose for a single application to a single site. System calculated.
noted otherwise)
Soil Tex. Max. Dose : Maximum dose for a single application to a single site as related to soil texture (Herbicide claims only).
Max. # Apps @ Max. Rate : Maximum number of Applications at Maximum Dosage Rate. Example: "4 applications per year" is expressed as "4/1 yr"; "4 applications per 3
years" is expressed as "4/3 yr"
Max. Dose [(AI unless : Maximum dose applied to a site over a single crop cycle or year. System calculated.
noted otherwise)/A]
Min. Interv (days) : Minimum Interval between Applications (days)
Restr. Entry Interv (days) : Restricted Entry Interval (days)
PRD Report Date : LUIS contains all products that were active or suspended (and that were available from OPP Document Center) as of this date. Some products
registered after this date may have data included in this report, but LUIS does not guarantee that all products registered after this date have
data that has been captured.
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
FORMULATION CODES
P/T : PELLETED/TABLETED
ABBREVIATIONS
AN : As Needed
NA : Not Applicable
NS : Not Specified (on label)
UC : Unconverted due to lack of data (on label), or with one of following units: bag, bait, bait block, bait pack, bait station, bait station(s), block, briquet,
briquets, bursts, cake, can, canister, capsule, cartridges, coil, collar, container, dispenser, drop, eartag, grains, lure, pack, packet, packets, pad, part,
parts, pellets, piece, pieces, pill, pumps, sec, sec burst, sheet, spike, stake, stick, strip, tab, tablet, tablets, tag, tape, towelette, tray, unit, --
APPLICATION RATE
DCNC : Dosage Can Not be Calculated
No Calc : No Calculation can be made
W : PPM calculated by weight
V : PPM Calculated by volume
U : Unknown whether PPM is given by weight or by volume
cwt : Hundred Weight
nnE-xx : nn times (10 power -xx); for instance, "1.234E-04" is equivalent to ".0001234"
USE LIMITATIONS CODES
CIS : Do not discharge effluent containing this pesticide into sewage systems without notifying the sewage treatment plant authority (POTW).
C24 : Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or public water. (NPDES license restriction)
* NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
-------
34
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregi strati on for
active ingredients within the case p-Chloro-m-cresol covered by this Reregi strati on Eligibility
Decision Document. It contains generic data requirements that apply to p-Chloro-m-cresol in
all products, including data requirements for which a "typical formulation" is the test
substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in
which they appear in 40 CFR Part 158. the reference numbers accompanying each test refer
to the test protocols set in the Pesticide Assessment Guidelines, which are available from the
National Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703)
487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files,
this column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
35
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36
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of p-Choloro-m-cresol
REQUIREMENT
USE PATTERN
CITATION(S)
PRODUCT CHEMISTRY
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
63-14
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
pH
Stability
Oxidizing/Reducing Action
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
41962601
37
-------
Data Supporting Guideline Requirements for the Reregistration of p-Choloro-m-cresol
REQUIREMENT USE PATTERN
63-15
63-16
63-17
63-18
63-19
63-20
63-21
64-1
Flammability
Explodability
Storage stability
Viscosity
Miscibility
Corrosion characteristics
Dielectric breakdown volt
Submittal of Samples
CITATION(S)
ECOLOGICAL EFFECTS
71-1A
71-2A
72-1C
72-2A
Acute Avian Oral - Quail/Duck C,F,M
Avian Dietary - Quail C,F,M
Fish Toxicity Rainbow Trout C,F,M
Invertebrate Toxicity C,F,M
42692401
42692402
42692403
42692404
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
Acute Oral Toxicity - Rat C,F,M
Acute Dermal Toxicity - C,F,M
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit C,F,M
Primary Dermal Irritation - C,F,M
Rabbit
Dermal Sensitization - Guinea Pig C,F,M
38
71335
75492
48548, 109649
48548, 109649
78837
-------
Data Supporting Guideline Requirements for the Reregistration of p-Choloro-m-cresol
REQUIREMENT
82-1A
82-2
83-1A
83-2A
83-3A
84-2A
84-2B
90-Day Feeding - Rodent
21-Day Dermal - Rabbit/Rat
Chronic Feeding Toxicity - Rodent
Oncogenicity - Rat
Developmental Toxicity - Rat
Gene Mutation (Ames Test)
Structural Chromosomal
USE PATTERN
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
C,F,M
CITATION(S)
124844
62905
42784801
42784801
42292901
42199901,41548601
42005201,41598101
84-4
Aberration
Other Genotoxic Effects
C,F,M
OCCUPATIONAL/RESIDENTIAL EXPOSURE
233
234
Estimation of Dermal Exposure at
Indoor Sites
Estimation of Inhalation Exposure
at Indoor Sites
C,F,M
C,F,M
42163201,41548602
41412201,42587501
41412201,42587501
39
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40
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GUIDE TO APPENDIX C
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 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 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 (19??), the Agency was unable to determine or estimate the date of the
document.
41
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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.
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BIBLIOGRAPHY
MRID
CITATION
00062905 Rutter, H.A., Jr.; Dewey, J.M.; Wolfe, G.W.; et al. (1980) Subchronic Dermal
Study in Rabbits: Preventol CMK: Toxicology Report No. 109. Rev. final rept.
(Unpublished study received Dec 4, 1980 under 39967-1; prepared by Hazleton
Laboratories Ameriknown admin, no.; CDL:223571-A)
00048548 Lamb, D.W.; Matzkanin, C.S. (1976) The Eye and Dermal Irritancy of Mobay
Sample, p-Chloro-m-cresol: Report No. 50847. (Unpublished study received
Jan 24, 1977 under 39967-1; submitted by Mobay Chemical Corp., Pittsburgh,
Pa.; CDL:227654-C)
00071335 Hixson, E.J.; Lamb, D.W.; English, T.D.; et al. (1981) Acute Oral Toxicity of
PCMC (p-Chloro-m-cresol) to Rats: Study No. 80-011-14. (Unpublished study
received Jan 26, 1981 under 39967-1; submitted by Mobay Chemical Corp.,
Pittsburgh, Pa.; CDL:244164-A)
00075492 Hazleton Laboratories America, Incorporated (1979) Final Report: Acute
Dermal Administration in Male and Female Rabbits: Project No. 339-108.
(Unpublished study received Mar 16, 1981 under 39967-1; submitted by
Mobay Chemical Corp., Pittsburgh, Pa.; CDL:244849-A)
00078837 Bomhard, E.; Loeser, E.; Lorke, D. (1981) Preventol CMK: Evaluation To
Determine the Sensitization Effect by Means of the Open Epicutaneous Test:
Report # 9447. A translation of: Preventol CMK: Untersuchungen auf
sensibilisierende Wirkung im offenen Epikutan-Test. (Unpublished study,
including German text, received Jul 1, 1981 under 39967-1; prepared by Bayer,
AG, West Germany, submitted by Mobay Chemical Corp., Pittsburgh, Pa.;
CDL: 245551-B)
00078838 Herbold, B.; Lorke, D. (1980) Preventol CMK: Salmonella/Microsome Test for
Detection of Point Mutagenic Effects: Report No. 9122. A translation of:
Preventol CMK: Salmonella/Mikrosomen-test zur Untersuchung auf
Punktmutagen Wirkung. (Unpublished study, including German text, received
Jul 1, 1981 under 39967-1; prepared by Bayer, AG, West Germany, submitted
by Mobay Chemical Corp., Pittsburgh, Pa.; CDL:245551-C)
00109649 Thyssen, J. (1978) Tests Regarding Skin and Mucosa Tolerance: Preventol
CMK. (Unpublished study received Jun 13, 1979 under 39967-1; Submitted by
Mobay Chemical Corp., Pittsburgh, PA; CDL: 238740-E) 00124844 Eiben,
R.; Bomhard, E.; Loeser, E.; et al. 1981 (Preventol CMK: Subchronic
Toxicological Tests on Rats: 3-month Feeding Test: Report # 10283.
(Unpublished study received Sep 20, 1982 under 39967-1; prepared by Bayer
Toxicological Institute, W Ger., submitted by Mobay Chem. Corp. Pittsburgh,
PA. CDL: 248361-A)
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BIBLIOGRAPHY
MRID
CITATION
41548601 Lehn, H. (1989) Parachlorometacresol (Preventol CMK): Mutagenicity Study
for the Detection of Induced Forward Mutations in the CHO-HGPRT Assay in
vitro: Lab Report No.: T1029785; 17755. Unpublished study prepared by
Bayer AG, Dept. of Toxicology. 36 p.
41548602 Cifone, M. (1988) Parachlorometacresol (Preventol CMK) in the Rat Primary
Hepatocyte Unscheduled DNA Synthesis Assay: HLA Study No.:
10285-0-447: Sponsor Study No.: T3027707. Unpublished study prepared by
Hazleton Laboratories America, Inc. 30 p.
41598101 Herbold, B. (1990) Preventol CMK: Micronucleus Test on the Mouse: Lab
Project Number: T 3033061. Unpublished study prepared by Bayer Ag. 45 p.
42005201 Herbold, B. (1991) Preventol CMK: Micronucleus Test on the Mouse:
Supplement to: Lab Proj ect Number: 18686A: T 3033061. Unpublished study
prepared by Bayer Ag. 12 p.
42163201 Van Goethem, D. (1991) Mutagenicity Test on Preventol CMK in the in the
Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: Lab Project
Number: 10285-0-447: T3027707. Unpublished study prepared by Hazleton
Labs America, Inc. 6 p.
42199901 Herbold, B. (1991) Preventol CMK: Salmonella/Microsome Test: Lab Project
Number: T 4038030. Unpublished study prepared by Bayer AG. 45 p.
42292901 Bartman, K. (1991) Parachlorometacresol (Preventol CMK); Study for
Embryonic Effects in the Rats after Oral Administration: Lab Project Number:
T3038066: 20869. Unpublished study prepared by Bayer AG, Wuppertal. 250
P-
42587501 Popendorf, W.; Selim, M. Kross, B. (1992) Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study: Second Replacement
to MRID 41761201: Lab Project Number: Q626. Unpublished study prepared
by the University of Iowa. 316 p.
42692401 Hancock, G. (1993) Preventol CMK: An Acute Oral LD50 with Bobwhite
Quail: Lab Proj ect Number: PR711701: 105005. Unpublished study prepared
by Miles Inc. 24 p.
42692402 Hancock, G. (1993) Preventol CMK: A Subacute Dietary LC50 with Bobwhite
Quail: Lab Proj ect Number: PR721701: 105006. Unpublished study prepared
by Miles Inc. 44 p.
44
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BIBLIOGRAPHY
MRID
CITATION
42692403 Gagliano, G.; Bowers, L. (1993) Acute Toxicity of Preventol CMK Technical
to the Rainbow Trout (Oncorhynchus mykiss) Under Static Renewal
Conditions: Lab Project Number: PR812201: 105020. Unpublished study
prepared by Miles Inc. 48 p.
42692404 Gagliano, G.; Bowers, L. (1993) Acute Toxicity of Preventol CMK Technical
to the Waterflea (Daphnia magna) Under Static Conditions: Lab Project
Number: PR820701: 105021. Unpublished study prepared by Miles Inc. 45 p.
42784801 Leser, K. (1993) Preventol CMK: Chronic Toxicity and Carcinogenicity Study
in Wistar Rats: Lab Project Number: T9030673: 22168. Unpublished study
prepared by Bayer Ag Institute of Industrial Toxicology. 1359 p.
The Merck Index. Ninth Edition
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet
to submit certain product specific data as noted herein to the U.S. Environmental Protection
Agency (EPA, the Agency). These data are necessary to maintain the continued registration
of your product(s) containing this active ingredient. Within 90 days after you receive this
Notice you must respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 6; or
2. Why you believe you are exempt from the requirements listed in this Notice
and in Attachment 3, Requirements Status and Registrant's Response Form.
(see section III-B); or
3. Why you believe EPA should not require your submission of product specific
data in the manner specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list
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of all of your products subject to this Notice in Attachment 2, Data Call-In Response Form, as
well as a list of all registrants who were sent this Notice (Attachment 6).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-
0107 and 2070-0057 (expiration date 03-31-99).
This Notice is divided into six sections and six Attachments. The Notice itself
contains information and instructions applicable to all Data Call-In Notices. The Attachments
contain specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable
Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregi strati on
5 - List of Registrants Receiving This Notice
6 - Cost Share and Data Compensation Forms
SECTION! WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the
data needed to support continued registration of the subject active ingredient. The Agency
has concluded that the only additional data necessary are product specific data. No additional
generic data requirements are being imposed. You have been sent this Notice because you
have product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment 3,
Requirements Status and Registrant's Response Form. Depending on the results of the studies
required in this Notice, additional testing may be required.
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II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment 3, Requirements Status and Registrant's Response Form, within the time frames
provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD-recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the study
will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend deadlines
for complying with data requirements when the studies were not conducted in accordance with
acceptable standards. The OECD protocols are available from OECD, 2001 L Street, N.W.,
Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone number 202-785-
0350).
All new studies and proposed protocols submitted in response to this Data Call-In Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICESISSUED BY
THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change
the requirements of any previous Data Call-In(s). or any other agreements entered into with the
Agency pertaining to such prior Notice. Registrants must comply with the requirements of all
Notices to avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for product specific data must
be submitted to the Agency within 90 days after your receipt of this Notice. Failure to
adequately respond to this Notice within 90 days of your receipt will be a basis for issuing a
Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for issuance of
NOIS due to failure to comply with this Notice are presented in Section IV-A and IV-B.
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III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice or
(c) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product specific
data requirements of this Notice is contained in Section III-C. A discussion of options relating to
requests for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your
response, one or both must be used in your response to the Agency. These forms are the Data-
Call-in Response Form, and the Requirements Status and Registrant's Response Form.
Attachment 2 and Attachment 3. The Data Call-In Response Form must be submitted as part of
every response to this Notice. In addition, one copy of the Requirements Status and Registrant's
Response Form must be submitted for each product listed on the Data Call-In Response Form
unless the voluntary cancellation option is selected or unless the product is identical to another
(refer to the instructions for completing the Data Call-In Response Form in Attachment 2).
Please note that the company's authorized representative is required to sign the first page of the
Data Call-In Response Form and Requirements Status and Registrant's Response Form (if this
form is required) and initial any subsequent pages. The forms contain separate detailed
instructions on the response options. Do not alter the printed material. If you have questions or
need assistance in preparing your response, call or write the contact person(s) identified in
Attachment 1.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by requesting
voluntary cancellation of your product(s) containing the active ingredient that is the subject of
this Notice. If you wish to voluntarily cancel your product, you must submit a completed Data
Call-In Response Form, indicating your election of this option. Voluntary cancellation is item
number 5 on the Data Call-In Response Form. If you choose this option, this is the only form
that you are required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this Notice There are various
options available to satisfy the product specific data requirements of this Notice. These options
are discussed in Section III-C of this Notice and comprise options 1 through 6 on the
Requirements Status and Registrant's Response Form and item numbers 7a and 7b on the Data
Call-in Response Form. Deletion of a use(s) and the low volume/minor use option are not valid
options for fulfilling product specific data requirements.
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3. Request for Product Specific Data Waivers. Waivers for product specific data are
discussed in Section III-D of this Notice and are covered by option 7 on the Requirements Status
and Registrant's Response Form. If you choose one of these options, you must submit both
forms as well as any other information/data pertaining to the option chosen to address the data
requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form that you agree to satisfy the
product specific data requirements (i.e. you select item number 7a or 7b), then you must select
one of the six options on the Requirements Status and Registrant's Response Form related to data
production for each data requirement. Your option selection should be entered under item
number 9, "Registrant Response." The six options related to data production are the first six
options discussed under item 9 in the instructions for completing the Requirements Status and
Registrant's Response Form. These six options are listed immediately below with information in
parentheses to guide registrants to additional instructions provided in this Section. The options
are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data — If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced herein
and in the attachments. All data generated and submitted must comply with the Good
Laboratory Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide
Assessment Guidelines (PAG), and be in conformance with the requirements of PR Notice 86-5.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports. The noted
deadlines run from the date of the receipt of this Notice by the registrant. If the data are not
submitted by the deadline, each registrant is subject to receipt of a Notice of Intent to Suspend
the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to the
Agency which includes: (1) a detailed description of the expected difficulty and (2) a proposed
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schedule including alternative dates for meeting such requirements on a step-by-step basis. You
must explain any technical or laboratory difficulties and provide documentation from the
laboratory performing the testing. While EPA is considering your request, the original deadline
remains. The Agency will respond to your request in writing. If EPA does not grant your
request, the original deadline remains. Normally, extensions can be requested only in cases of
extraordinary testing problems beyond the expectation or control of the registrant. Extensions
will not be given in submitting the 90-day responses. Extensions will not be considered if the
request for extension is not made in a timely fashion; in no event shall an extension request be
considered if it is submitted at or after the lapse of the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data — Registrants may only choose
this option for acute toxicity data and certain efficacy data and only if EPA has indicated in the
attached data tables that your product and at least one other product are similar for purposes of
depending on the same data. If this is the case, data may be generated for just one of the
products in the group. The registration number of the product for which data will be submitted
must be noted in the agreement to cost share by the registrant selecting this option. If you
choose to enter into an agreement to share in the cost of producing the required data but will not
be submitting the data yourself, you must provide the name of the registrant who will be
submitting the data. You must also provide EPA with documentary evidence that an agreement
has been formed. Such evidence may be your letter offering to join in an agreement and the
other registrant's acceptance of your offer, or a written statement by the parties that an agreement
exists. The agreement to produce the data need not specify all of the terms of the final
arrangement between the parties or the mechanism to resolve the terms. Section 3(c)(2)(B)
provides that if the parties cannot resolve the terms of the agreement they may resolve their
differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development — This option only applies to
acute toxicity and certain efficacy data as described in option 2 above. If you have made an
offer to pay in an attempt to enter into an agreement or amend an existing agreement to meet the
requirements of this Notice and have been unsuccessful, you may request EPA (by selecting this
option) to exercise its discretion not to suspend your registration(s), although you do not comply
with the data submission requirements of this Notice. EPA has determined that as a general
policy, absent other relevant considerations, it will not suspend the registration of a product of a
registrant who has in good faith sought and continues to seek to enter into a joint data
development/cost sharing program, but the other registrant(s) developing the data has refused to
accept your offer. To qualify for this option, you must submit documentation to the Agency
proving that you have made an offer to another registrant (who has an obligation to submit data)
to share in the burden of developing that data. You must also submit to the Agency a completed
EPA Form 8570-32, Certification of Offer to Cost Share in the Development of Data,
Attachment 7. In addition, you must demonstrate that the other registrant to whom the offer was
made has not accepted your offer to enter into a cost sharing agreement by including a copy of
your offer and proof of the other registrant's receipt of that offer (such as a certified mail receipt).
Your offer must, in addition to anything else, offer to share in the burden of producing the data
upon terms to be agreed or failing agreement to be bound by binding arbitration as provided by
FIFRA section 3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also
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inform EPA of its election of an option to develop and submit the data required by this Notice by
submitting a Data Call-In Response Form and a Requirements Status and Registrant's Response
Form committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your offer
to share in the burdens of developing the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this Notice. If the other registrant
fails to develop the data or for some other reason is subject to suspension, your registration as
well as that of the other registrant will normally be subject to initiation of suspension
proceedings, unless you commit to submit, and do submit the required data in the specified time
frame. In such cases, the Agency generally will not grant a time extension for submitting the
data.
Option 4. Submitting an Existing Study — If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed by
this Notice. You may only submit a study that has not been previously submitted to the Agency
or previously cited by anyone. Existing studies are studies which predate issuance of this
Notice. Do not use this option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid and
needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw data
and specimens from the study are available for audit and review and you must
identify where they are available. This must be done in accordance with the
requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR Part 160.
As stated in 40 CFR 160.3(j) " 'raw data' means any laboratory worksheets,
records, memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts of raw
data have been prepared (e.g., tapes which have been transcribed verbatim, dated,
and verified accurate by signature), the exact copy or exact transcript may be
substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments."
The term "specimens", according to 40 CFR 160.3(k), means "any material
derived from a test system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all GLP-
required quality assurance and quality control information, pursuant to the
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requirements of 40 CFR Part 160. Registrants must also certify at the time of
submitting the existing study that such GLP information is available for post-May
1984 studies by including an appropriate statement on or attached to the study
signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregi strati on Phase 3
Technical Guidance and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
available from NTIS). A study not conducted according to the PAG may be
submitted to the Agency for consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is referred to 40 CFR 158.70
which states the Agency's policy regarding acceptable protocols. If you wish to
submit the study, you must, in addition to certifying that the purposes of the PAG
are met by the study, clearly articulate the rationale why you believe the study
meets the purpose of the PAG, including copies of any supporting information or
data. It has been the Agency's experience that studies completed prior to January
1970 rarely satisfied the purpose of the PAG and that necessary raw data are
usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements of
the criteria outlined above.
If you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable adverse
effects, you must notify the Agency of such a study. If such study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study — If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement is
not satisfied, you may still be required to submit new data normally without any time extension.
Deficient, but upgradeable studies will normally be classified as supplemental. However, it is
important to note that not all studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a study may be upgraded, call or
write the contact person listed in Attachment 1. If you submit data to upgrade an existing study
you must satisfy or supply information to correct all deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA. Your submission must also
specify the MRID number(s) of the study which you are attempting to upgrade and must be in
conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
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This option should also be used to cite data that has been previously submitted to upgrade
a study, but has not yet been reviewed by the Agency. You must provide the MRID number of
the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those
criteria as well as a certification regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies — If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it
must be a study which has not yet been reviewed by the Agency. Acceptable toxicology studies
generally will have been classified as "core-guideline" or "core minimum." For all other
disciplines the classification would be "acceptable." With respect to any studies for which you
wish to select this option you must provide the MRID number of the study you are citing and, if
the study has been reviewed by the Agency, you must provide the Agency's classification of the
study.
If you are citing a study of which you are not the original data submitter, you must submit
a completed copy of EPA Form 8570-31, Certification with Respect to Data Compensation
Requirements.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form, as appropriate.
III-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies. (Note: any
supplemental data must be submitted in the format required by PR Notice 86-5). This will be the
only opportunity to state the reasons or provide information in support of your request. If the
Agency approves your waiver request, you will not be required to supply the data pursuant to
section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver request, you must choose an
option for meeting the data requirements of this Notice within 30 days of the receipt of the
Agency's decision. You must indicate and submit the option chosen on the Requirements Status
and Registrant's Response Form. Product specific data requirements for product chemistry,
acute toxicity and efficacy (where appropriate) are required for all products and the Agency
would grant a waiver only under extraordinary circumstances. You should also be aware that
submitting a waiver request will not automatically extend the due date for the study in question.
Waiver requests submitted without adequate supporting rationale will be denied and the original
due date will remain in force.
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IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due
to failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final
protocol when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study
as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration concerning
joint data development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or
failure of a registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this
Notice on a Data Call-In Response Form and a Requirements Status and
Registrant's Response Form:
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
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c. otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in the
specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds
for suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines)
regarding the design, conduct, and reporting of required studies. Such requirements
include, but are not limited to, those relating to test material, test procedures, selection of
species, number of animals, sex and distribution of animals, dose and effect levels to be
tested or attained, duration of test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation
of any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or included in this Notice or
contained in PR 86-5. All studies must be submitted in the form of a final report; a
preliminary report will not be considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not
be consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may
be suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act.
You must also explain why an "existing stocks" provision is necessary, including a statement of
the quantity of existing stocks and your estimate of the time required for their sale, distribution,
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and use. Unless you meet this burden the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use such
existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required by
this Notice will not result in the Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due unless you demonstrate
to the Agency that you are in full compliance with all Agency requirements, including the
requirements of this Notice. For example, if you decide to voluntarily cancel your registration
six months before a 3 year study is scheduled to be submitted, all progress reports and other
information necessary to establish that you have been conducting the study in an acceptable and
good faith manner must have been submitted to the Agency, before EPA will consider granting
an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the information to
the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies, regarding
unreasonable adverse effects on man or the environment. This requirement continues as long as
the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic data
exemption claims) must include a completed Data Call-In Response Form and a completed
Requirements Status and Registrant's Response Form (Attachment 2 and Attachment 3 for
product specific data) and any other documents required by this Notice, and should be submitted
to the contact person(s) identified in Attachment 1. If the voluntary cancellation or generic data
exemption option is chosen, only the Data Call-In Response Form need be submitted.
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The Office of Compliance Monitoring (OCM) of the Office of Pesticides and Toxic
Substances (OPTS), EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois Rossi, Division Director
Special Review and
Reregi strati on Division
Attachments
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregi strati on
5 - List of Registrants Receiving This Notice
6 - Cost Share and Data Compensation Forms and the Confidential Statement of
Formula Form
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P-CHLORO-M-CRESOL DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have
product(s) containing p-Chloro-m-cresol.
This Product Specific Data Call-In Chemical Status Sheet contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregi strati on of p-
Chloro-m-cresol. This attachment is to be used in conjunction with (1) the Product Specific Data
Call-In Notice, (2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the
Requirements Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5) the EPA
Acceptance Criteria (Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6)
and (7) the Cost Share and Data Compensation Forms in replying to this p-Chloro-m-cresol
Product Specific Data Call-In (Attachment 7). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for p-Chloro-m-cresol
are contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency
has concluded that additional data on p-Chloro-m-cresol are needed for specific products. These
data are required to be submitted to the Agency within the time frame listed. These data are
needed to fully complete the reregi strati on of all eligible p-Chloro-m-cresol products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and
procedures established by this Notice, please contact Emily Mitchell at (703) 308-8583.
All responses to this Notice for the Product Specific data requirements should be
submitted to:
Emily Mitchell
Chemical Review Manager Team 81
Product Reregi strati on Branch
Special Review and Reregi strati on Branch 7508W
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: p-Chloro-m-cresol
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer "yes." If you choose this
option, you will not have to provide the data required by the Data Call-In Notice
and you will not have to complete any other forms. Further sale and distribution
of your product after the effective date of cancellation must be in accordance with
the Existing Stocks provision of the Data Call-In Notice (Section IV-C).
Item 6. Not applicable since this form calls in product specific data only. However, if
your product is identical to another product and you qualify for a data
exemption, you must respond with "yes" to Item 7a (MUP) or 7B (EUP) on this
form, provide the EPA registration numbers of your source(s); you would not
complete the "Requirements Status and Registrant's Response" form. Examples
of such products include repackaged products and Special Local Needs (Section
24c) products which are identical to federally registered products.
Item 7a. For each manufacturing use product (MUP) for which you wish to maintain
registration, you must agree to satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes." If you are
requesting a data waiver, answer "yes" here; in addition, on the "Requirements
Status and Registrant's Response" form under Item 9, you must respond with
Option 7 (Waiver Request) for each study for which you are requesting a waiver.
See Item 6 with regard to identical products and data exemptions.
Items 8-11. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a
signed letter that accompanies this form. For example, you may wish to report
that your product has already been transferred to another company or that you
have already voluntarily canceled this product. For these cases, please supply all
relevant details so that EPA can ensure that its records are correct.
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INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number assigned by EPA in
Item 3 This number must be used in the transmittal document for any data
submissions in response to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to support the product's
continued registration are identified. These guidelines, in addition to the
requirements specified in the Notice, govern the conduct of the required studies.
Note that series 61 and 62 in product chemistry are now listed under 40 CFR
158.155 through 158.180, Subpart C.
Item 5. The study title associated with the guideline reference number is identified.
Item 6. The use pattern(s) of the pesticide associated with the product specific
requirements is (are) identified. For most product specific data requirements, all
use patterns are covered by the data requirements. In the case of efficacy data, the
required studies only pertain to products which have the use sites and/or pests
indicated.
Item 7. The substance to be tested is identified by EPA. For product specific data, the
product as formulated for sale and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified. It is normally based on 8
months after issuance of the Reregistration Eligibility Document unless EPA
determines that a longer time period is necessary.
Item 9. Enter only one of the following response codes for each data requirement to
show how you intend to comply with the data requirements listed in this
table. Fuller descriptions of each option are contained in the Data Call-In Notice.
1. I will generate and submit data by the specified due date (Developing Data). By
indicating that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as outlined in
the Data Call-In Notice. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4)
2. I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing). I am submitting a copy of this agreement. I understand
that this option is available only for acute toxicity or certain efficacy data and
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only if EPA indicates in an attachment to this Notice that my product is similar
enough to another product to qualify for this option. I certify that another party in
the agreement is committing to submit or provide the required data; if the required
study is not submitted on time, my product may be subject to suspension. By the
specified due date, I will also submit: (1) a completed "Certification With
Respect To Data Compensation Requirements" form (EPA Form 8570-29)
and (2) two completed and signed copies of the Confidential Statement of
Formula (EPA Form 8570-4)
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I
understand that this option is available only for acute toxicity or certain efficacy
data and only if EPA indicates in an attachment to this Data Call-in Notice that
my product is similar enough to another product to qualify for this option. I am
submitting evidence that I have made an offer to another registrant (who has an
obligation to submit data) to share in the cost of that data. I am also submitting a
completed "Certification of Offer to Cost Share in the Development Data"
form. I am including a copy of my offer and proof of the other registrant's receipt
of that offer. I am identifying the party which is committing to submit or provide
the required data; if the required study is not submitted on time, my product may
be subject to suspension. I understand that other terms under Option 3 in the Data
Call-In Notice (Section III-C.l.) apply as well. By the specified due date, I will
also submit: (1) a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA
Form 8570-4)
4. By the specified due date, I will submit an existing study that has not been
submitted previously to the Agency by anyone (Submitting an Existing Study).
I certify that this study will meet all the requirements for submittal of existing data
outlined in Option 4 in the Data Call-In Notice (Section III-C.l.) and will meet the
attached acceptance criteria (for acute toxicity and product chemistry data). I will
attach the needed supporting information along with this response. I also certify
that I have determined that this study will fill the data requirement for which I
have indicated this choice. By the specified due date, I will also submit a
completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) to show what data compensation
option I have chosen. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4)
5. By the specified due date, I will submit or cite data to upgrade a study classified
by the Agency as partially acceptable and upgradable (Upgrading a Study). I
will submit evidence of the Agency's review indicating that the study may be
upgraded and what information is required to do so. I will provide the MRID or
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Accession number of the study at the due date. I understand that the conditions
for this option outlined Option 5 in the Data Call-In Notice (Section III-C.l.)
apply. By the specified due date, I will also submit: (1) a completed
"Certification With Respect To Data Compensation Requirements" form
(EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4)
6. By the specified due date, I will cite an existing study that the Agency has
classified as acceptable or an existing study that has been submitted but not
reviewed by the Agency (Citing an Existing Study). If I am citing another
registrant's study, I understand that this option is available only for acute toxicity
or certain efficacy data and only if the cited study was conducted on my product,
an identical product or a product which EPA has "grouped" with one or more
other products for purposes of depending on the same data. I may also choose this
option if I am citing my own data. In either case, I will provide the MRID or
Accession number(s) for the cited data on a "Product Specific Data Report" form
or in a similar format. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4)
7. I request a waiver for this study because it is inappropriate for my product
(Waiver Request). I am attaching a complete justification for this request,
including technical reasons, data and references to relevant EPA regulations,
guidelines or policies. [Note: any supplemental data must be submitted in the
format required by P.R. Notice 86-5]. I understand that this is my only
opportunity to state the reasons or provide information in support of my request.
If the Agency approves my waiver request, I will not be required to supply the
data pursuant to Section 3(c)(2)(B) of FIFRA. If the Agency denies my waiver
request, I must choose a method of meeting the data requirements of this Notice
by the due date stated by this Notice. In this case, I must, within 30 days of my
receipt of the Agency's written decision, submit a revised "Requirements Status
and Registrant's Response" Form indicating the option chosen. I also understand
that the deadline for submission of data as specified by the original data call-in
notice will not change. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed
copies of the Confidential Statement of Formula (EPA Form 8570-4)
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a
signed letter that accompanies this form. For example, you may wish to report
that your product has already been transferred to another company or that you
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have already voluntarily canceled this product. For these cases, please supply all
relevant details so that EPA can ensure that its records are correct.
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71
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72
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EPA'S BATCHING OF P-CHLORO-M-CRESOL 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 reregi strati on of products containing p-chloro-m-cresol 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. Notwith-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
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
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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.
Three active products containing p-chloro-m-cresol have been identified, Registration
Nos. 39967-8, 39967-12 and 49403-19. All three products contain greater than 99% p-chloro-
m-cresol; two are identified as technicals and one is identified as a ready-to-use solution. They
are all considered to be in the same batch. The data reviewed and considered acceptable in the
RED chapter will support all three products. However, as noted in the chapter, and acute
inhalation study, or an acceptable data waiver request is still required.
Table 1
Batch
1
EPA Reg. No.
13808-7
35975-4
35978-8
39508-2
46779-1
56228-22
% Active Ingredient
1.0
1.0
1.0
1.0
1.0
1.0
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
The following table lists a product that was either considered not to be similar or the
Agency lacked sufficient information for decision making and were not placed in any batch. The
registrant of this product is responsible for meeting the acute toxicity data requirements
separately.
Table 2 (No Batch)
EPA Reg. No.
56228-26
% Active Ingredient
90.0
Formulation Type
Solid
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Attachment 5. List of All Registrants Sent This Data Call-In (insert) Notice
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible, signed
copies of the form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF must be signed, dated and the telephone number of the responsible party
must be provided.
d. All applicable information which is on the product specific data submission must
also be reported on the CSF.
e. All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
f Flashpoint must be in degrees Fahrenheit and flame extension in inches.
g. For all active ingredients, the EPA Registration Numbers for the currently
registered source products must be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
common names for the trade names must be reported.
i. For the active ingredients, the percent purity of the source products must be
reported under column 10 and must be exactly the same as on the source product's
label.
j. All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or
grams. In no case will volumes be accepted. Do not mix English and metric
system units (i.e., pounds and kilograms).
k. All the items under column 13.b. must total 100 percent.
1. All items under columns 14.a. and 14.b. for the active ingredients must represent
pure active form.
m. The upper and lower certified limits for ail active and inert ingredients must
follow the 40 CFR 158.175 instructions. An explanation must be provided if the
proposed limits are different than standard certified limits.
n. When new CSFs are submitted and approved, all previously submitted CSFs
become obsolete for that specific formulation.
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United States Environmental Protection Agency
Washington, B.C. 20460
Certification of Offer to Cost
Share in the Development of Data
Form Approved
OMB No. 2070-0106,
2070-0057
Approval Expires
3-31-99
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden to, Chief Information Policy
Branch, PM-233, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of
Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill in blanks below:
Company Name
Company Number
Product Name
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
an offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firms on the following
date(s):
Name of Firm (s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative
Date
Name and Title (Please Type or Print)
EPA Form 8570-32 (5/91) Replaces EPA form 8580 which is obselete
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United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
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Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-99
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including time for
reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect of this collection of information,
including suggestions for reducing this burden to, Chief Information Policy Branch, PM-233, U.S. Environmental Protection
Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project
(2070-0106), Washington, DC 20503.
Please fill in blanks below.
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
data submitter to cite that study.
2. That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
original data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
company(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
3(c)(1 )(F) and 3(c)(2)(D) of FIFRA; and (b) Commence negotiation to determine which data are subject to the compensation
requirement of FIFRA and the amount of compensation due, if any. The companies I have notified are. (check one)
[ ] The companies who have submitted the studies listed on the back of this form or attached sheets, or indicated on the attached
"Requirements Status and Registrants' Response Form,"
3. That I have previously complied with section 3(c)(1)(F) of FIFRA for the studies I have cited in support of registration or
reregistration under FIFRA.
Signature
Date
Name and Title (Please Type or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or
reregistration of my products, to the extent required by FIFRA section 3(c)(1)(F) and 3(c)(2)(D).
Signature
Date
Name and Title (Please Type or Print)
EPA Form 8570-31 (4-96)
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The following is a list of available documents for p-Chloro-m-cresol that my further assist
you in responding to this Reregi strati on Eligibility Decision document. These documents
may be obtained by the following methods:
Electronic
File format: Portable Document Format (.PDF) Requires Adobe® Acrobat or compatible
reader. Electronic copies can be downloaded from the Pesticide Special
Review and Reregi strati on Information System at 703-308-7224. They also are
available on the Internet on EPA's gopher server, GOPHER.EPA.GOV, or
using ftp on FTP.EPA.GOV, or using WWW (World Wide Web) on
WWW.EPA.GOV., or contact Emily Mitchell at (703)-308-8583.
1. PR Notice 86-5.
2. PR Notice 91-2 (pertains to the Label Ingredient Statement).
3. A full copy of this RED document.
4. A copy of the fact sheet for p-Chloro-m-cresol.
The following documents are part of the Administrative Record for p-Chloro-m-cresol
and may included in the EPA's Office of Pesticide Programs Public Docket. Copies of these
documents are not available electronically, but may be obtained by contacting the person
listed on the Chemical Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
The following Agency reference documents are not available electronically, but may be
obtained by contacting the person listed on the Chemical Status Sheet of this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
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