United States Prevention, Pesticides EPA738-R-97-016
Environmental Protection And Toxic Substances January 1998
Agency (7508W)
&EPA Reregistration
Eligibility Decision (RED)
Paranitrophenol
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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 Paranitrophenol. The enclosed
Reregi strati on Eligibility Decision (RED) contains the Agency's evaluation of the data base of
this chemical, its conclusions on the potential human health and environmental risks of the
current product uses, and decisions and conditions under which these uses and product can be
used. The RED includes the data and labeling requirements for the product reregi strati on
decision.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." The required response is due 90 days from the
receipt of this letter. Complete and timely responses will avoid the Agency taking the
enforcement action of suspension against your product.
If you have questions on the labeling language for Paranitrophenol-containing product
requirements or wish to meet with the Agency, please contact the Special Review and
Reregi strati on Division representative Veronica Dutch (703) 308-8585.
Sincerely yours,
Lois 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 APPLICATION FOR REREGISTRATION Decision-You must submit the following
items for each product within ninety days 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 and c below) to the address listed in item
3.
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 reregi strati on) separately. You may,
but are not required to, delete uses which the RED says are ineligible for reregi strati on. 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 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.
2 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.
3 WHERE TO SEND REREGISTRATION DECISION 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
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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
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REREGISTRATION ELIGIBILITY DECISION
PARANITROPHENOL
LISTB
CASE 2465
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
PARA-NITROPHENOL REREGISTRATION ELIGIBILITY DECISION TEAM i
ABSTRACT v
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Data Requirements 3
D. Regulatory History 3
III. SCIENCE ASSESSMENT 4
A. Physical Chemistry Assessment 4
1. Identification of Active Ingredient 4
B. Human Health Assessment 4
1. Toxicology Assessment 4
a. Acute Toxicity 4
b. Subchronic Toxicity 6
c. Chronic toxicity 6
d. Carcinogenicity 7
e. Developmental Toxicity 7
f. Reproductive Toxicity 8
g. Mutagenicity 8
h. Metabolism 10
i. Neurotoxicity 11
j. Other Toxicological Considerations 11
2. Toxicological Endpoints of Concern Identified for Use in Risk . . 12
a. Reference Dose (RfD) 12
b. Carcinogenic Classification 12
c. Other Toxicological Endpoints 12
3. Dietary Exposure and Risk AssessmenACharacterization 14
a. Dietary 14
4. Occupational Exposure and Risk Assessment/Characterization 14
a. Occupational Exposure 14
b. Occupational Risk Assessment 17
C. Environmental Assessment 19
1. Ecological Toxicity Data 19
a. Toxicity to Terrestrial Animals 19
b. Toxicity to Freshwater Aquatic Animals 20
2. Environmental Fate 22
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a. Environmental Fate Assessment 22
b. Environmental Fate and Transport 23
c. Water Resources 23
3. Exposure and Risk Characterization 24
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 24
A. Reregistration Decision 24
V. ACTIONS REQUIRED OF REGISTRANTS 26
A. Labeling Language for Paranitrophenol-Containing Products 26
VI. APPENDICES 29
APPENDIX A. Citations Considered to be Part of the Data Base Supporting
the Reregistration of Paranitrophenol 31
APPENDIX B. List of Available Related Documents 49
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PARA-NITROPHENOL REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Michele Cottrill
Ghulam All
Biological Analysis Branch
Economic Analysis Branch
Environmental Fate and Effects Risk Assessment
Mary Frankenberry
Gail Maske-Love
Paul Mastradone
Jim Goodyear
Health Effects Risk Assessment
Paula A. Deschamp
Arliene M Aikens
Linnea Hansen
Thomas Campbell
Registration Support
Wallace Powell
Sami Malak
Risk Management
Veronica Dutch
Barbara Briscoe
Linda S. Propst
Science Analysis and Coordination Staff
Environmental Fate and Groundwater Branch
Environmental Fate and Groundwater Branch
Ecological Effects Branch
Risk Characterization and Analysis Branch
Risk Characterization and Analysis Branch
Toxicology Branch I
Occupational and Residential Exposure Branch
Antimicrobial Program Branch
Registration Support Branch
Product Reregi strati on Branch
Product Reregi strati on Branch
Product Reregi strati on Branch
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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 D WEL 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
FQPA Food Quality Protection 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 i s
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 Micrograms per liter
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.
Ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
N/A Not Applicable
NOEC No Observable 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
Pa pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
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.
WP Wettable Powder
WPS Worker Protection Standard
IV
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ABSTRACT
The U.S. Environmental Protection Agency has completed its reregi strati on eligibility
decision for the pesticide paranitrophenol (case 2465).
Paranitrophenol, a nitrated benzene, is a nonfood use chemical that is registered for use
as a fungicide for controlling fungal mold on leather and specialty industrial products used by the
military. The treatment process is for protection of military leather shoes, leather combat boots
and other leather items while in storage in the field, and for specified cork insulations on Air
Force equipment. Paranitrophenol-treated cork is used in missile silo construction. There is a
single registered paranitrophenol product, the 99.5% technical which is formulated as a flaked
solid.
Paranitrophenol is acutely toxic (toxicity category II) via the oral route and is moderately
toxic (toxicity category III) via the dermal route. Paranitrophenol is a corrosive eye irritant and
a potential dermal irritant.
The Agency has some concerns about paranitrophenol relating to the potential for handler
dermal and inhalation exposure associated with the registered uses of paranitrophenol (i.e.,
leather and cork treatment applied by military contractors to products used by military workers).
Lacking adequate exposure and toxicity data, the Agency is unable to conduct a quantitative risk
assessment. In order to assess the risk, the following data would be required to support the
continued registration of paranitrophenol:
EPA Guideline Study
81-3 Rat acute inhalation toxicity
81-5 Primary dermal irritation study in rabbit
81-6 Dermal sensitization potential study in guinea pig
83-3(b) Rabbit developmental toxicity study
84-4 in vivo bone marrow cytogenetics
231 Dermal exposure
232 Inhalation exposure
Based on the Agency's contact with the sole registrant of paranitrophenol, the United
States Department of the Army, regarding the data necessary to support the continued registration
of paranitrophenol, the Agency received a request to cancel the registration of the product
containing paranitrophenol. The cancellation will become effective on May 30, 2002.
The Agency has decided to accept the voluntary cancellation request to be effective on
May 30, 2002. The Agency is basing this decision on:
v
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1. The weight of evidence from all available toxicological data does not suggest a potent
threat from dermal and inhalation exposure.
2. Exposure to paranitrophenol is believed to be very limited. It's uses are confined to
leather and cork treatment applied by military contractors to few products used by military
workers. The worker population exposed during treatment is likely to be small. The only large
population potentially exposed is military personnel wearing treated footwear. The Agency was
able to quantitatively estimate their risk and found it to be acceptably low even using the
protective assumptions.
3. During the five year phase-out period, workers using and handling paranitrophenol
solutions and freshly treated products are required to wear chemical resistant aprons and attached
full sleeve gloves.
Revised label language as set forth in Section V of this document is required. Several
of the label revisions pertain to handler safety requirements that must be established due to the
acute and other adverse effects associated with paranitrophenol. Due to concerns about
potentially high dermal exposures during the introduction and removal of leather or cork by hand
from dip vats, and handlers participating in such hands-on operations, workers must wear
chemical-resistant full-front aprons with attached full-sleeve gloves. Other required label
changes address application restrictions and user safety requirements, and are found in Part V of
this document.
VI
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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 reregistration process. The first four phases of the process
focus on identification of data requirements to support the reregistration 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 reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for reregistration" before calling
in data on products and either reregistering products or taking "other appropriate regulatory
action." Thus, reregistration involves a thorough review of the scientific database underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional
data on health and environmental effects; and to determine whether the pesticide meets the "no
unreasonable adverse effects" criterion of FIFRA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of paranitrophenol. The document consists of six sections. Section I is the
introduction. Section II describes paranitrophenol, 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 reregistration decision for paranitrophenol.
Section V discusses the reregistration requirements for paranitrophenol . Finally, Section VI is
the Appendices which support this Reregistration 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: Phenol, 4-Nitrophenol
• Chemical Name: p-Nitrophenol
• Chemical Family: Nitrated benzene
• CAS Registry Number: 100-02-7
• OPP Chemical Code: 056301
• Empirical Formula: C6H5NO3
• Trade and Other Names: PNP
• Basic Manufacturer: Army Nattick RD & F Center
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 these uses of paranitrophenol is in
Appendix A.
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For Paranitrophenol:
TYPE OF PESTICIDE:
Fungici de/Fungi stat
USE SITES:
INDOOR NON-FOOD:
INDUSTRIAL PRESERVATIVE
* Leather/Leather Products
* Speciality Industrial Products (cork
insulation)
TARGET PESTS: Fungi associated with leather products and cork
insulation.
FORMULATION TYPES REGISTERED:
TYPE: End use product 99.5000%
FORM: CRYSTALLINE [99.5000%]
METHOD AND RATES OF APPLICATION:
Equipment - Mixer (mechanical); Not specified on label; Tank
Types of Treatment - Industrial preservative treatment
Rates of Application - 6965 ppm active ingredient by weight
Timing - During manufacture; Not specified on label
C. Data Requirements
The Agency issued a Data Call-In Notice (DCI) to the registrant of
paranitrophenol February 12, 1991 under Phase IV of the reregi strati on program and
required submission of environmental fate and toxicity data.
D. Regulatory History
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The active ingredient paranitrophenol was first registered in the United States in
1963 as a fungicide. It was used at the time as a fungicidal product for preservative
incorporation in leather products and hides. A second fungicidal product received
registration in 1967. Both products contained a second active ingredient, salicylanilide.
However, the registrations for all registered products containing salicylanilide as an active
ingredient have since been canceled.
There is currently one product registered by the Agency containing
paranitrophenol active ingredient. Registration for paranitrophenol was granted in 1980
for use as a fungicide for incorporation into leather for military use, at a concentration not
to exceed 0.7% on a basis of dry finished leather weight. In 1983 this registration was
amended to add the use of the product for incorporation into cork insulation for military
use.
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
1. Identification of Active Ingredient
Paranitrophenol is a solid at room temperature. The melting point and vapor pressure of
the solid is 114°C and 0.60 mm Hg at 120°C, respectively. A 30°C the vapor pressure is 3 x 10~4
mmHg.
PC Code: 056301
Chemical Formula: C6H5NO3
CAS Registry No.: 100-02-7
B. Human Health Assessment
1. Toxicology Assessment
Additional toxicity studies or information are needed to support the reregi strati on of
paranitrophenol. The required studies include: rat acute inhalation toxicity (81-3); primary
dermal irritation study in rabbit (81-5); dermal sensitization potential study in guinea pig (81-6);
rabbit developmental toxicity study (83-3b) (exposure via dermal route is required); and in vivo
bone marrow cytogenetics assay (84-4). These studies should be conducted using the technical
material. In addition, an acute inhalation toxicity study in rats on the formulated end-use product
at the minimum dilution specified on product labels, is required.
a. Acute Toxicity
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Acute toxicity data for paranitrophenol is listed below.
Table 1. Acute Toxicity Data for Paranitrophenol (TGAI).
TEST
Oral LD50 in rats
Dermal LD50 in rabbits
Inhalation LC50 in rats
Eye irritation in rabbits
Dermal irritation in rabbits
Dermal sensitization in guinea pigs
MRID NO.
42539601
42539701
NA
42539801
NA
NA
RESULT
LD50 Males =191 mg/kg (95%
confidence limits 131 - 303 mg/kg)
Females = 170 mg/kg (95%
confidence limits 129 - 225 mg/kg)
LD50 (males) = 3.69 g/kg (95%
confidence limits 2.03 - 6.71 g/kg)1
Data gap2
Corrosive - persistent severe
conjunctival irritation, irritation and
damage to iris, corneal opacity
Data gap3
Data gap4
Toxicity
Category
II
III
--
I
--
--
1 Females were not evaluated in this study.
2 A 28-day inhalation toxicity study was submitted but does not satisfy this data requirement (MRID
42538701). Although no mortality or signs of toxicity were observed from exposure to 0.03 mg
paranitrophenol/L; particle size was larger (>5 /^m) than guideline requirements.
3 A primary dermal irritation study was submitted but was not considered acceptable (MRID 42539901).
Although no dermal irritation was observed, test material was not moistened or pulverized before
application.
4 A dermal sensitization potential study was submitted but was not considered acceptable (MRID 42540001).
There was no evidence of sensitization; however, an insufficient number of animals were tested and th e
challenge dose was too low.
Clinical signs seen in the acute oral toxicity study cited above included ataxia, convulsions
and diarrhea at 200 mg/kg or higher in females (signs did not show dose-response). In the acute
dermal toxicity study cited above, all treated animals showed signs of dermal irritation at the
application site.
Additional information on acute toxicity of paranitrophenol in the "Toxicology Profile for
nitrophenols" of the Agency for Toxic Substances and Disease Registry (ATSDR; TP-91/23,
7/92) provides oral LD50 values consistent with the submitted study. Other reported oral LD;0
values in albino rats are 230 mg/kg (propylene glycol vehicle; same vehicle as submitted acute
oral toxicity study cited above) and 620 mg/kg (corn oil vehicle). An LD50 of 470 mg/kg was
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determined in mice (corn oil vehicle). Reported symptoms of acute toxicity include
hyperthermia, respiratory depression, central nervous system (CNS) depression and
methemoglobinemia. No mortality or significant toxicity was reported in rats following
inhalation exposure up to 4 mg/L paranitrophenol (dust atmosphere) for 4 hrs. Exposures to 2.1
mg/L (dust atmosphere) to rats for 2 weeks (5 days/week) also caused no mortality (clinical signs
observed in this study included methemoglobinemia, slightly increased SGOT levels and corneal
opacities, probably due to direct effect of dust on the eye).
b. Subchronic Toxicity
The database for subchronic toxicity (Series 82) is adequate. Oral Study in Rats: In a
subchronic toxicity study (MRID 42788801), paranitrophenol (tech., 99.81% ai) was
administered for 13 weeks to 20 Sprague-Dawley Crl:CD®BR rats/sex/dose in water by gavage
(volume of 10 ml/kg) at dose levels of 0, 25, 70 or 140 mg/kg/day. At 70 mg/kg/day, 1 male and
1 female died and females showed increased incidence of urine staining between weeks 7-9.
At 140 mg/kg/day, 14 males and 6 females died and urine staining was observed in females.
Clinical signs preceding death included wheezing, dyspnea, pallor, prostration and languid
behavior. Death of 1 female at 25 mg/kg/day was not considered treatment-related. There were
no compound related effects on body weight, food consumption, hematology, clinical chemistry
or organ weight. The LOEL is 70 mg/kg/day, based on increased incidence of acute mortality
and associated clinical signs and pathology, and possibly urine staining in females. The NOEL
is 25 mg/kg/day.
Dermal Study in Mice: In a subchronic dermal toxicity study (range-finding study for the
NTP 18-month dermal mouse cancer bioassay, summarized in MRID 43766201), paranitrophenol
(tech., 97.5% ai) at doses of 0, 21.9, 43.8, 87.5, 175 or 350 mg/kg in acetone was applied to the
interscapular skin of 10 Swiss-Webster mice/sex/ dose 3 times per week for 13 weeks. At 350
mg/kg, all males and 8 females died before termination; at 175 mg/kg, 3 males and 1 female died.
All deaths except 1 were attributed to treatment. Statistically significantly increased incidence
of epidermal inflammation (marked to severe), hyperplasia and hyperkeratosis were observed in
both sexes at 175 and 350 mg/kg and dermal necrosis was observed in 2-3 males. Based on
mortality and dermal irritation, a LOEL of 175 mg/kg is identified for this study. The NOEL is
87.5 mg/kg. However, the study report did not indicate whether other parameters such as body
weight, clinical chemistry/hematology or clinical signs other than dermal lesions were evaluated.
c. Chronic toxicity
A chronic toxicity study which was not acceptable was submitted by the registrant. The
18-month mouse dermal carcinogenicity study provided some information on chronic toxicity
and did not identify any treatment-related effects on clinical signs, body weight or
gross/microscopic pathology at doses up to and including 160 mg/kg applied 3X/week.
However, chronic toxicity could not be conclusively evaluated due to lack of evaluation of
hematology, clinical chemistry/urinalysis parameters and microscopic examination of some
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tissues.
d. Carcinogenicity
In a dermal carcinogen!city study (MRID 43766201), paranitrophenol (tech., 97.5% a.i.)
was administered to 60 Swiss-Webster mice/sex/dose 3 times/week (Monday, Wednesday,
Friday) at levels of 0, 40, 80 or 160 mg/kg in 100 //I acetone to the shaved interscapular skin, for
18 months (equivalent to amortized daily doses of 0, 17.1, 34.3 or 68.6 mg/kg/day). Clinical
signs, body weight and gross/microscopic pathology were evaluated.
No treatment-related systemic toxicity was observed. Animals were sacrificed at 18
months due to reduced survival from amyloidosis, observed at high incidence in all groups. The
NOEL for systemic toxicity is >160 mg/kg and the LOEL is > 160 mg/kg.
At the doses tested, there was no treatment-related increase in tumor incidence compared
to controls. Dosing was considered adequate based on a mouse 13 week dermal toxicity study
in which excessive local dermal irritation at >175 mg/kg and mortality at 350 mg/kg were
observed.
e. Developmental Toxicity
A dermal developmental toxicity study in the rabbit (83-3b) is required to support the
reregi strati on of paranitrophenol. Previously, the Agency indicated that oral administration
would also be acceptable for this study (RfD/Peer Review meeting of 3/21/96). However, it is
requested that the study be conducted using dermal exposure because it is more appropriate.
Evaluation of dermal developmental toxicity studies for other chemicals submitted to the Agency
indicates that well-designed studies have been successful and able to minimize local dermal
irritation (e.g., by rotating the application site).
Although there are study deficiencies, a new rat developmental toxicity study is not
required. In the developmental toxicity study which was submitted, (MRID 42788601),
paranitrophenol (tech., 99.1% a.i.) was administered to 20 pre-mated female Sprague-Dawley
rats/dose in propylene glycol, by gavage at dose levels of 0, 1.4, 13.8 or 27.6 mg/kg/day from
days 6 through 16 of gestation. In addition a positive control group (aspirin, 250 mg/kg/day) was
included. At 27.6 mg/kg/day, decreased maternal body weight and weight gain (-12%/-45%)
were observed during the dosing period. No treatment-related effects on mortality, clinical signs,
food consumption or cesarean parameters were reported. Food consumption was not measured.
The maternal LOEL is 27.6 mg/kg/day, based on decreased body weight/body weight gain. The
maternal NOEL is 13.8 mg/kg/day.
No treatment-related developmental toxicity was observed. However, the small number
of litters (10) available for examination at high dose and lack of some experimental details
compromised interpretation of the results. The developmental NOEL is tentatively 27.6
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mg/kg/day. A developmental LOEL was not established. The developmental toxicity study in
the rat is classified as supplementary (not upgradable).
f. Reproductive Toxicity
The database for reproductive toxicity is considered to be adequate. Although there are
study deficiencies, a new rat two-generation reproductive toxicity study is not required. The
submitted data are considered acceptable for regulatory purposes because no evidence of
potential reproductive toxicity was observed. New studies are not expected to add significant
information for risk assessment purposes.
In a two-generation reproduction toxicity study (MRIDs 00146455 and 40529701),
paranitrophenol (tech., 99.1% a.i.) was administered dermally in ethanol vehicle to 12 male and
24 female Crl:COBS-CD(SD) rats/dose group at doses of 0 (saline vehicle), 0 (ethanol vehicle),
50, 100 or 250 mg/kg/day (5 days/week application for about 23 - 24 weeks to the FO adults and
about 36 weeks to Fl adults). Each parental generation was bred once.
There were no indications of maternal systemic toxicity at any dose tested. However,
dermal irritation at the site of treatment was observed in all treated groups (increased incidence
of eschar formation, ballooning degeneration, chronic inflammation, acanthosis and/or sebaceous
hypertrophy were observed microscopically). The LOEL for local dermal irritation is <50
mg/kg/day. A NOEL for local dermal irritation was not determined. The NOEL for maternal
systemic toxicity is tentatively >250 mg/kg/day. A LOEL for maternal systemic toxicity was not
determined.
No reproductive toxicity was observed at any dose based on the parameters evaluated.
However, the conclusions regarding reproductive toxicity are considered tentative due to several
study deficiencies (low pregnancy rate, resulting in low numbers of litters for evaluation in most
test groups; no analysis of dosing solutions provided; errors in study reporting and data
presentation). Although the reproductive toxicity NOEL is tentatively >250 mg/kg/day, and a
reproductive toxicity LOEL was not determined, the study is considered adequate because there
were no indications of reproductive toxicity at any dose tested in either the Fl or F2 matings.
g. Mutagenicity
The database for mutagenicity is not complete. Since an in vivo cytogenetic assay has not
been submitted, it is not known whether the test material can express genotoxic activity in the
whole animal. Without this information, the genetic toxicology profile for paranitrophenol is
considered incomplete. It is, therefore, required that paranitrophenol be evaluated in an in vivo
bone marrow cytogenetic assay which is required to satisfy the NEW mutagenicity initial testing
battery guidelines.
(1) In a Salmonella typhimurium reverse gene mutation assay (MRID 42174801), strains
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TA1535, TA1537, TA1538, TA98 and TA100 were exposed for 72 hours to paranitrophenol
(technical, 99.7% a.i.) at concentrations of 0.01, 0.05, 0.10, 0.50 or 1.00 mg/plate in the presence
or absence of S9 metabolic activation. In strain TA1535 a weakly increased frequency in
revertants was observed (up to 2.7-fold above vehicle controls) at 0.5, 5.0 and 10.0 mg/plate in
the presence of metabolic activation and in the absence of significant cytotoxicity.
(2) In an in vitro mammalian gene mutation assay (MRID 42271001), mouse L5178Y
lymphoma TK+/- cells were exposed for 4 hours to 0, 32, 42, 56, 75, 100, 133, 178, 237, 316 or
422 //g paranitrophenol (tech., 99.7% a.i.)/ml culture media in the absence of S9 and 0, 18, 24,
32, 42, 56, 75, 100, 133, 178 or 237 //g/ml in the presence of S9. No evidence of an increased
forward mutation rate at the thymidine kinase locus was observed under the conditions of these
assays, including doses producing cytotoxicity (>100//g/ml).
(3) In an in vitro chromosomal aberrations assay (MRID 42270901), Chinese hamster
ovary (CHO) cells were exposed to 0, 75, 100, 250, 500 or 750 //g paranitrophenol (tech., 99.7%
ai)/ml culture media for 22 hours (absence of S9) or 4 hours (presence of S9). At doses >250
//g/ml and in the apparent absence of significant cytotoxicity, increased incidence of
chromosomal aberrations was observed in the absence, but not presence, of S9 (lower doses not
tested for mutagenicity).
In addition to the submitted studies described above, the following mutagenicity studies,
conducted as part of the National Toxicology Program (NTP) 18-month mouse dermal cancer
bioassay of paranitrophenol (MRID 43766201), were considered in assessing the genotoxicity
of paranitrophenol:
(4) Salmonella typhimurium reverse gene mutation preincubation assay. Paranitrophenol
(10-1000 jig/plate) was assayed in the absence and presence of 10% rat and hamster S9. The test
was negative in all strains up to the HTD in two independent trials.
(5) Sex-linked recessive lethal assay in Drosophila melanogaster. Paranitrophenol was
found to be negative when administered in feed up to levels (>6000 ppm) that caused »50%
mortality but no sterility and negative by injection up to doses (>1000 ppm) that caused »40%
mortality and »12% sterility.
(6) In vitro cytogenetics in Chinese hamster ovary (CHO) cells—structural chromosomal
aberrations/sister chromatid exchange (SCE). Paranitrophenol was found to be negative for
structural chromosome damage up to severely cytotoxic concentrations (>750 |ig/ml-S9) and
negative for SCE induction up to doses that cause severe cell cycle delay (25 ng/ml -S9; 1700
|ig/ml+S9). However, reproducible, dose-related and significant increases in cells with structural
chromosomal aberrations were seen at levels (1500 and 1700 |ig/ml +S9) that induced severe cell
cycle delay.
Additional information of mutagenicitv and conclusions on mutagenicitv of oaranitroohenol:
-------
Paranitrophenol has been tested extensively in bacterial mutagenicity assays; the results
are summarized in NTP Technical Report (Series No. 417; NIH Publication No. 93-3148, 4/93)
as well as in the Agency for Toxic Substances and Disease Registry (ATSDR) "Toxicology
Profile for nitrophenols" (TP-91/23, 7/92). Overall the data presented in both documents indicate
that while the aromatic nitro group on paranitrophenol is a structural alert for DNA reactivity, the
test substance is not a mutagen for bacteria. In light of the sizable body of evidence suggesting
that paranitrophenol is not a mutagen for microbial systems, the unconfirmed positive result in
the S. typhimurium assay listed above (MRID 42174801) appears to be an anomalous finding.
Similarly, neither the ortho-isomer nor the metabolite, para-aminophenol are microbial mutagens.
Paranitrophenol was also not mutagenic in mouse lymphoma cells or active in microbial or
mammalian cell DNA repair assays.
There is also a lack of agreement between the submitted (MRID 42270901) and the NTP-
sponsored in vitro chromosome aberration assays. Although both studies showed evidence of
clastogenicity, the response was only seen in the absence of exogenous metabolic activation in
MRID 42270901 but only in the presence of S9-activation in the NTP-sponsored study.
Repeating the assay would likely resolve this inconsistency, however, the available data are
considered sufficient to conclude that paranitrophenol is an in vitro clastogen for mammalian
cells.
h. Metabolism
The database for metabolism is considered adequate and no additional metabolism studies
on paranitrophenol are required, despite study deficiencies in the submitted dermal
penetration/metabolism study. Additional information on metabolism and identification of
metabolites contained in the NTP and ATSDR reports, together with the submitted metabolism
study, allow adequate characterization of the metabolism of paranitrophenol. A new study would
not be expected to provide significant additional useful information for risk assessment purposes.
The dermal absorption values in the study below are not considered reliable for risk assessment
purposes, but new data were not required since dermal toxicity studies were available for
characterization of toxicity from dermal exposure.
(1) In a dermal penetration/metabolism study (MRID 42539501), single doses of 14C-
paranitrophenol (tech., radiochemical purity 98.5%, Sp. Act. 3.9 mci/mmol) were administered
to two groups of 3 male New Zealand white rabbits (1) dermally at 40.1 //g/cm2 on 8.9 cm2 of
skin in ethanol (357 //g/animal) or (2) intravenously at 357 //g/animal in saline infusion; and to
two groups of 3 male beagle dogs (1) dermally at 40.1 //g/cm2 on 17.8 cm2 skin in ethanol (714
//g/animal) or (2) intravenously at 714 //g/animal. Blood was collected from animals given
intravenous doses at 9 intervals up to 24 hours post-dosing to evaluate plasma clearance and half
life. Urine and feces were collected at 24 hrs and daily for 7 days post-dosing. Tissues were
evaluated at sacrifice (day 7) for radioactivity.
Thirty-five percent of the administered dose in rabbits and 11% in dogs was estimated to
10
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be absorbed. Paranitrophenol was rapidly cleared from the plasma following IV injection (half
life estimated at 15 min). The majority of absorbed radioactivity was excreted in the urine within
1 day (IV) to 2-3 days (dermal) and no detectable radioactivity was identified in tissues except
for the skin application site. Metabolites were not characterized.
The dermal penetration/metabolism study is unacceptable due to several study deficiencies
including small number of animals tested, large amount of applied dose retained in the patch
covering application site and lack of identification and quantitation of metabolites.
(2) Additional information on the metabolism of paranitrophenol was summarized in the
literature review of the NTP mouse dermal cancer bioassay and in Chapter 2 (Health Effects) of
the "Toxicological Profile for nitrophenols" prepared by the Agency for Toxic Substances and
Disease Registry (ATSDR). Paranitrophenol is rapidly metabolized in the liver, primarily into
conjugated glucuronide and sulfate esters; little unchanged parent compound is excreted. Small
amounts of parent compound may also be reduced to 4-aminophenol or hydroxylated to 4-
nitrocatechol. As seen in the submitted study, metabolites are excreted primarily in urine and to
a very small extent in feces. Conjugation mechanisms are reportedly similar in male and female
rats.
i. Neurotoxicity
Neurotoxicity study data are not required.
j. Other Toxicological Considerations
Methemoglobinemia is an established systemic toxic effect of nitrophenols. Animal
studies and reports of human poisonings summarized briefly in the NTP and ATSDR documents
indicate that paranitrophenol can induce methemoglobinemia. Reports of toxicity in humans
following accidental ingestion include respiratory depression with cyanosis, along with
headaches, drowsiness and nausea. Rats given inhalation exposures to paranitrophenol sodium
salts for 2 weeks developed methemoglobinemia at 0.112 mg/L or higher and showed at least
partial recovery 2 weeks after termination of exposures. In the rat subchronic gavage study
(MRID 42788801), data on methemoglobinemia are not available. Although methemoglobin
levels were measured at week 7, the results were not considered reliable due to unusually high
control values (and no increases in treated groups were observed).
Although methemoglobinemia was observed in the inhalation studies, no clinical
indications of methemoglobinemia were observed in the rat subchronic gavage study (e.g.,
cyanosis) at lethal dose levels or in dermal studies in mouse and rat at dose levels causing
significant dermal irritation (rats and mice) or lethality (mice). The available toxicity data is
therefore considered adequate for assessment of systemic toxicity from dermal exposure to
paranitrophenol, despite the lack of methemoglobin data via the oral or dermal route.
11
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2. Toxicological Endpoints of Concern Identified for Use in Risk
Assessment
a. Reference Dose (RfD)
A Reference Dose has not been established for paranitrophenol because it is registered for
non-food use applications only.
b. Carcinogenic Classification
The Health Effects Division RfD/Peer Review Committee evaluated paranitrophenol on
March 21, 1996 and determined that it should be classified as Group D (inadequate information
to determine cancer classification). There was no evidence of carcinogenicity in the National
Toxicology Program (NTP) mouse dermal carcinogenicity study; however, a cancer study in a
second species is not available. A second species study is not required at this time.
c. Other Toxicological Endpoints
The Health Effects Division Toxicology Endpoint Selection Committee considered the
toxicity data available for this chemical at a meeting held on March 26, 1996 (report date
4/10/96). Based on a review of the toxicology database for paranitrophenol, toxicology endpoints
and dose levels of concern have been identified for use in occupational and residential risk
characterization; they are listed in Table 2.
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TABLE 2. Summary of Toxicological Endpoints for Paranitrophenol.
EXPOSURE DURATION
EXPOSURE
ROUTE
NOEL and ENDPOINT
Acute Dietary
ORAL
This risk assessment is not required since PNP has no
food uses.
Short-Term (1 to 7 days)
Occupational/Residential
DERMAL
This risk assessment is not required since no overt
systemic toxicity was observed in the available
studies within 7 days of exposure.
Intermediate-Term
(1 week to several months)
Occupational/Residential
DERMAL
NOEL: 87.5 mg/kg/day based on mortality at 175
mg/kg/day from a dermal toxicity study in mice.
All Duration Periods
Short/Intermediate/Chronic
Occupational/Residential
INHALATION
This risk assessment cannot be completed at this time
due to lack of toxicity data. This will be further
evaluated for potential inhalation risk concerns upon
receipt and evaluation of the required inhalation
toxicity data.
Chronic Exposure
Occupational
DERMAL
NOEL: 87.5 mg/kg/day based on mortality at 175
mg/kg/day from a dermal toxicity study in mice.
Detailed Discussion of Short- and Intermediate-Term Endpoints
Dermal Absorption: A dermal absorption factor is not applicable since a subchronic
dermal toxicity study was used as the basis for risk assessments of intermediate- and long-term
occupational exposures.
Inhalation Occupational Exposure (all durations): This risk assessment cannot be
completed at this time due to lack of toxicity and exposure data.
Short-Term Occupational Dermal Exposure (1 to 7 days): No acute toxic effects were
seen either in a 13-week dermal toxicity study in mice, in a dermal two-generation reproduction
study in rats (doses of 8, 50, 100 or 250 mg/kg/day for several months) or in a 90-day study in
rats given 0, 25, 70 or 140 mg/kg/day by gavage; the LOEL was 70 mg/kg/day based on mortality
and associated clinical signs and pathology, which did not occur until week 7. This risk
assessment is not required.
Intermediate-Term Occupational Dermal Exposure (1 week to several months):
The NOEL is 87.5 mg/kg/day based on mortality at 175 mg/kg/day in the previously
described subchronic dermal toxicity range-finding study in Swiss-Webster mice.
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Comparison of oral and dermal LD50 values for paranitrophenol suggest that toxicity from
dermal exposure is significantly lower than by the oral route. Use of available oral toxicity studies
was considered inappropriate for dermal exposure risk assessment since dermal toxicity studies
were available. The dermal studies did not thoroughly evaluate some parameters, but no overt
toxicity was observed in the 90-day gavage study until immediately prior to death. Although a
NOEL of 160 mg/kg for systemic toxicity was observed in the 18-month mouse dermal
carcinogen!city study, this value was not used for risk assessment since mortality was observed
in the 13-week study at 175 mg/kg. The dose of 87.5 mg/kg/day was not amortized for 3x/week
application because the endpoint was considered adequately conservative, based on comparisons
withNOELs from the oral toxicity studies, and because the applied doses were not later washed
off.
Chronic Occupational Dermal Exposure: The NOEL for chronic dermal exposure is 87.5
mg/kg/day based on mortality at 175 mg/kg/day. See details above under intermediate-term
exposure. A chronic dermal risk assessment is required.
d. Potential Risks to Infants and Children
Paranitrophenol is not registered for food uses nor is it available for use by homeowners
in the residential setting. However, personnel in the military and in boot manufacturing settings
could be exposed to paranitrophenol-treated leather. EPA has evaluated developmental and
reproduction studies for purposes of assessing the pre- and post-natal toxicity of paranitrophenol.
Neither the developmental or the reproduction study indicate pre-natal effects. This conclusion
would need to be confirmed by the results of a new rabbit developmental study.
3. Dietary Exposure and Risk AssessmenACharacterization
a. Dietary
There are currently no registered food-uses of paranitrophenol; therefore, a dietary
exposure and risk assessment/characterization is not required.
4. Occupational Exposure and Risk Assessment/Characterization
a. Occupational Exposure
An occupational exposure assessment is required for an active ingredient if (1) certain
toxicological criteria are triggered and (2) there is potential exposure to handlers (mixers, loaders,
applicators, etc.) during use or to persons entering treated sites after application is complete.
Summary of Use Patterns and Formulations
Paranitrophenol is a non-food use chemical that is registered for use as a
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fungicide/biocide. Paranitrophenol is incorporated into leather or cork insulation for military use.
Paranitrophenol may be added to 1) a running drum or mixer during or immediately after the re-
tanning, coloring, and fat liquoring operation; 2) the soaking tanks containing cut insoles during
the chrome re-tanning of vegetable tanned insoles; 3) a butyl impregnating solution which is used
to treat vegetable tanned cut outsoles. Paranitrophenol treated leather is then used in the
manufacture of boots and shoes used by military personnel. Paranitrophenol-treated cork is used
in missile silo construction. There is a single registered paranitrophenol product, the 99.5%
technical which is formulated as a flaked solid.
All products containing paranitrophenol are intended for occupational use when handled
directly; currently there are no uses of paranitrophenol intended for homeowner use.
The following table summarizes the occupational handler and post-application exposure
scenarios.
TYPE OF EXPOSURE
Handler Exposure
Post-Application
Exposure
Primary
Secondary
Primary
Secondary
OCCUPATIONAL SETTINGS - Examples
Adding paranitrophenol to a vat solution to preserve or
rehydrate hides/cut insoles or outsoles/cork; handling wet
hides/soles/cork to which paranitrophenol has been added
Handling dry hides/cut insoles or outsoles/cork to which
paranitrophenol has been added
Working near a vat where paranitrophenol was added
Wearing treated military boots and shoes
Handler Exposures & Assumptions
The Agency establishes handler safety requirements when risk assessments or general
concerns suggest such requirements are appropriate. The Agency is developing standardized
requirements for occupational handlers of industrial biocides, based on the acute toxicity
characteristics of each end-use product. As described below, several exposure scenarios of
concern are identified. The Agency is requesting additional exposure information as confirmatory
data to validate these standardized requirements.
EPA has determined that there is a potential for dermal and inhalation exposures to
handlers during usual use-patterns associated with paranitrophenol in commercial/industrial
settings. The Agency has identified two levels of handler exposures:
• primary handlers — persons handling aqueous solutions containing
paranitrophenol as an active ingredient.
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• secondary handlers — persons handling products, such as leather products and
cork insulation, to which paranitrophenol has been added.
At this time, EPA lacks information about probable dermal and inhalation exposures to
primary handlers (mixers/loaders and applicators) engaged in treating leather or cork with
paranitrophenol. Specifically, the Agency has insufficient information about:
(1) the amount of paranitrophenol likely to be handled in a day;
(2) how frequently (daily, weekly, monthly) paranitrophenol is likely to be handled in the
occupational setting;
(3) what methods (open-pouring, meter-pump, etc.) are likely to be used to introduce the
paranitrophenol into the processing water; and
(4) what methods (hand, machine, etc.) are likely to be used to remove the leather or cork
from the processing water.
Therefore, at this time, EPA is unable to determine a reasonable worst-case scenario for
primary handlers engaged in treating leather and cork with paranitrophenol.
EPA, lacks information about probable dermal and inhalation exposures to secondary
handlers engaged in handling products, such as leather products and cork insulation, to which
paranitrophenol has been added. Specifically, the Agency has insufficient information about:
(1) the amount of paranitrophenol-treated leather or cork likely to be handled in a day;
(2) how frequently (daily, weekly, monthly) paranitrophenol-treated leather or cork is
likely to be handled in the occupational setting;
(3) what methods are likely to be used in handling the treated leather or cork (frequent
hand contact, mostly mechanized, etc.); and
(4) how soon following treatment with paranitrophenol will workers be handling the
treated leather or cork while still wet.
Therefore, at this time, EPA is unable to determine a reasonable worst-case scenario for
secondary handlers engaged in processing or handling treating leather and cork. However, EPA
does believe, based on the limited use information available, that dermal and inhalation exposures
to secondary handlers handling dry hides/cork/insoles or outsoles would be much less than
handling wet hides/cork/insoles or outsoles. EPA believes that inhalation and ocular exposures
for secondary handlers (handling dry materials) are minimal.
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Post-Application Exposures & Assumptions
As stated in the handler exposures and assumptions section, the Agency established
handler safety requirements when risk assessments or general concerns suggest such requirements
are appropriate. The Agency is developing standardized requirements for occupational handlers
of industrial biocides, based on the acute toxicity characteristics of each end-use product. As
described below several exposure scenarios of concern are identified. The Agency is requesting
additional exposure information as confirmatory data to validate these standardized requirements.
EPA has determined that there are potential intermediate and chronic primary post-
application dermal and inhalation occupational exposures to persons in and near treatment sites
during use of paranitrophenol end-use products in occupational (commercial and industrial)
settings. However, as explained above under "Handler Exposures & Assumptions," the Agency
lacks information about probable exposures to persons in or near treatment sites during the use
of paranitrophenol to treat leather or cork products. Therefore at this time, the Agency is unable
to determine a reasonable worst-case scenario for primary post-application exposures.
EPA also has determined that there are potential intermediate-term and chronic secondary
post-application dermal exposures to military personnel from wearing the treated leather
products. Based on the use information available, a plausible worst-case post-application
secondary exposure scenario would entail the wearing of treated military footwear. EPA believes
that potential inhalation and ocular secondary post-application exposure (wearing treated
footwear) is not significant.
b. Occupational Risk Assessment
Risk from Handler Exposures
Dermal Risk Concerns
Based on the available toxicity data and exposure scenarios for paranitrophenol, EPA has
determined that a quantitative risk assessment for primary and secondary handlers is appropriate
for intermediate- and chronic-term dermal exposures. However, at this time, EPA is unable to
perform a quantitative risk assessment for dermal exposures to primary and secondary handlers
due to the lack of information about: 1) the probable exposures to primary handlers engaged in
treating leather and cork with paranitrophenol; and 2) the probable exposures to primary handlers
engaged in processing or handling treated leather and cork while it is still wet. EPA does believe
dermal exposure to secondary handlers handling dry hides would be much less than handling wet
hides. Exposure data for primary handlers are required.
Inhalation Risk Concerns
At this time, EPA has no data upon which to conduct a quantitative exposure or risk
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assessment for primary and secondary handler inhalation concerns. At the present time, a risk
assessment for inhalation exposure cannot be completed due to lack of adequate toxicity and
exposure data. Acute inhalation toxicity data are required. In addition, the Agency requests
information about the vapor pressure and the acute inhalation toxicity of paranitrophenol after
being introduced to aqueous solution. The need for inhalation exposure data will be further
evaluated upon receipt and evaluation of the required inhalation toxicity data.
Additional Dermal and Ocular Risk Concerns: EPA is also concerned about potential
dermal and ocular exposures to primary handlers from paranitrophenol, since it is classified as
toxicity category I for eye irritation potential and there is a data gap for skin irritation potential.
The Agency believes that risk reduction measures may be appropriate for persons who are
dermally or ocularly exposed to paranitrophenol. Such persons should wear personal protective
equipment (such as chemical-resistant gloves, a chemical-resistant apron, and protective eyewear)
in addition to the basic attire of long-sleeve shirt, long pants, shoes, and socks (refer to Section
V for details). Depending on the probable dermal and ocular exposure, the Agency may impose
engineering controls, such as meter pumps, instead of or in addition to PPE. However, such a
decision cannot be made until the Agency receives further information about primary and
secondary handler exposures to paranitrophenol in the commercial/industrial setting.
Risk From Post-Application Exposures
Primary Post-application Dermal Risk Concerns: At this time, EPA is unable to perform
a quantitative risk assessment for primary post-application dermal exposures due to the lack of
information about probable exposures to persons in commercial/industrial sites during the use of
paranitrophenol to treat leather or cork products. However, the Agency believes that dermal
exposures incurred during primary handler application are likely to be much higher than dermal
exposures incurred during primary post-application.
Primary Post-application Inhalation Risk Concerns: EPA is unable to perform a
quantitative risk assessment for primary post-application inhalation exposures due to the lack of
information about paranitrophenol's inhalation toxicity and about probable inhalation exposures
to persons in commercial/industrial sites during the use of paranitrophenol to treat leather or cork
products. At this time, primary post-application inhalation risk concerns are considered
equivalent to primary handler risk concerns which will be assessed upon receipt and evaluation
of the required acute toxicity data. The need for primary post-application inhalation exposure
data will be further evaluated upon receipt and evaluation of the required inhalation toxicity data.
Secondary Post-application Dermal Risk Concerns: In assessing the potential risk from
secondary dermal exposures to military personnel from wearing treated leather products, EPA
considered information provided in a leather leaching/efficacy study (MRID 41896801). The
data from this study were found to be insufficient, but have been utilized for worst case exposure
assumptions. The study indicated that 80% ai PNP leached out of treated leather after 24 hours
of soaking in a tank of water where the water was exchanged five times per hour. A more
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realistic, but still conservative percentage of leaching would be 10% ai PNP available in the first
24 hour period. Taking into consideration this worst case exposure estimate, the unique route of
exposure (total contact skin area of feet only) and the permeability coefficient for paranitrophenol
adjusted for factors of skin thickness, pH, and temperature, the total dermal absorption exposure
for the average 60 or 70 kg military worker is 3-fold less than the level considered to be a
potential risk concern.
Secondary Post-application Inhalation Risk Concerns: At this time, EPA does not believe
that possible risks from inhalation exposures to paranitrophenol would be of concern for
secondary post-application exposures (military personnel wearing treated leather items, such as
boots), since inhalation exposures in these situations are likely to be minimal.
C. Environmental Assessment
1. Ecological Toxicity Data
a. Toxicity to Terrestrial Animals
Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is
required to establish the toxicity of paranitrophenol to birds. The preferred test species is either
the mallard duck (a waterfowl) or bobwhite quail (an upland gamebird). Results of this test are
tabulated below.
Table 4. Avian Acute Oral Toxicity
Species % ai
Northern bobwhite quail ?
(Colinus virginianus)
LD50 in mg/kg
(C.I.)
577(464-719)
Toxicity Category
Slightly toxic
MRID No.
Author/Year
Unknown
Beavers, 1979
Study
Classification1
Core
1 Core (study satisfies guideline). Supplemental (study is scientifically sound, but does not satisfy guideline)
Since the LD50 falls in the range of 501-2000 mg/kg, paranitrophenol is slightly toxic to
avian species on an acute oral basis. The guideline (71-1) is fulfilled.
Two subacute dietary studies using the TGAI are required to establish the toxicity of 4-
nitrophenol to birds. The preferred test species are mallard duck and bobwhite quail. Results of
these tests are tabulated below.
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Table 5. Avian Subacute Dietary Toxicity
5-Day LC50 MRID No. Study
Species % ai (ppm)1 Toxicity Category Author/Year Classification
Northern bobwhite quail ? >5620 Practically nontoxic 31682 Core
(Colinus virginianus) Beavers, 1979
Mallard duck ? >5260 Practically nontoxic 31683 Core
(Anas platyrhynchos) Beavers, 1979
1 Test organisms observed an additional three days while on untreated feed.
Since the LC50 is greater than 5260 ppm, paranitrophenol is practically nontoxic toxic to
avian species on a subacute dietary basis. The guideline (71-2) is fulfilled (MRID 31682 and
31683).
Birds, Acute and Subacute
Birds, Chronic
Avian reproduction studies using the TGAI are not required for paranitrophenol because
birds are not expected to be subject to repeated or continuous exposure to the pesticide, especially
preceding or during the breeding season, and the pesticide is not expected to be stable in the
environment to the extent that potentially toxic amounts may persist in animal feed.
Mammals
Acute laboratory mammalian studies (submitted to the Agency's Health Effects Division,
MRID 42539601) found an LD50 of 191 (131-303) mg/kg for male rats and an LD50 of 170 (129-
225) for female rats. Therefore, paranitrophenol is characterized as being moderately toxic to
mammals on an acute basis.
b. Toxicity to Freshwater Aquatic Animals
Freshwater Fish, Acute
Two freshwater fish toxicity studies using the TGAI are required to establish the toxicity
of paranitrophenol to fish. The preferred test species are rainbow trout (a coldwater fish) and
bluegill sunfish (a warmwater fish). Results of these tests are tabulated below.
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Table 6. Freshwater Fish Acute Toxicity
Species/
(Flow-through or Static) % ai
Warm water fish 99. 1
Bluegill sunfish
(Lepomis macrochirus)
static 99.7
Cold water fish 99. 1
Rainbow trout
(Oncorhynchus mykiss)
static 99.7
Fathead minnow 98
(Pimephales promelas)
96-hour
LC50 (ppm)
(measured/nominal)
5.9
(Adjusted Nominal)
19.7(19-27)
(Adjusted Nominal)
4.0
(Adjusted Nominal)
11.6(9-16)
(Adjusted Nominal)
53.4(50-55)
36.7 (34-40), &
33.3 (30-37)
(Adjusted Nominal)
Toxicity Category
Moderately to
slightly toxic
Moderately to
slightly toxic
Slightly toxic
MRID No. Study
Author/Year Classification
94659 Core
Wyatt, 1979
42382601 Core
Bowman, 1981
94659 Core
Wyatt, 1979
42382601 Core
Bowman, 1981
4403601 Supplemental
Geiger, 1985
Supplemental (study is scientifically sound, but does not satisfy guideline)
All of the first three studies reviewed above were performed in 1977 to 1980 and do not
have measured concentrations. The minnow study (1985) measured the concentration at 24, 48,
and 72 hours (but not at 96 hours). The Agency used the measured concentrations from this
study to calculate a 96-hour degradation constant and applied it to the other aquatic studies. Its
use did not change the results substantially. Toxicity was, therefore, characterized with nominal
values. New studies with measured endpoints will not be required.
Since the LC50 falls in the range of 10-100 ppm, paranitrophenol is slightly toxic to
freshwater fish on an acute basis. The guideline (72-1) is fulfilled (MRIDs 94659, 4403601 and
42382501).
Freshwater Fish, Chronic
A freshwater fish early life-stage test using the TGAI was not required for
paranitrophenol.
Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the
toxicity of paranitrophenol to aquatic invertebrates. The preferred test species is Daphnia magna.
Results of this test are tabulated below.
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Table 7. Freshwater Invertebrate Toxicity
48-hour LC50/
Species/(Static or Flow- EC50 (ppm) MRID No. Study
through) % ai (measured/nominal) Toxicity Category Author/Year Classification
Waterflea 99.1 5, 19, and 15 (Adjusted Moderately toxic 94659 Core
(Daphnia magna) Nominal) Wyatt, 1979
Ostracod
(Cyprinotus incongruens)
Waterflea
(Daphnia magna)
99.1
99.5
28 and 25
(Adjusted Nominal)
34(17-53)
NOEC 17
(Adjusted Nominal)
Slightly toxic
Slightly toxic
94659
Wyatt, 1979
42382501
Bowman, 1981
Core
Core
Since the LC50/EC50 falls in the range of 10-100 ppm, paranitrophenol is slightly toxic to
aquatic invertebrates on an acute basis. The guideline (72-2) is fulfilled (MRIDs 94659 and
42382501).
Freshwater Invertebrate, Chronic
A freshwater aquatic invertebrate life-cycle test using the TGAI was not required for
paranitrophenol.
2. Environmental Fate
a. Environmental Fate Assessment
Since paranitrophenol has only been registered for indoor uses, there are limited
environmental fate data available. No guideline environmental fate studies are available.
However, based on available literature data (for which the study methodology has not been
evaluated), the major route of dissipation appears to be microbial mediated processes (literature
reported half-life =16 days for aerobic soil metabolism). Under anaerobic conditions,
paranitrophenol appears to undergo nitroreduction (no half-life reported). In addition, when
exposed to sunlight or an artificial light source, paranitrophenol appears to degrade (no half-life
reported). However, the sterility of the treated river water was not reported in the photolysis
study.
There are no mobility data available except for a Koc of 214. Paranitrophenol has been
detected in ground water monitoring wells (EPA Pesticides in Ground Water Database, 1971-
1991). In addition, based on the reported vapor pressure (1 X 10"3 mm Hg at 25°C), the log Kow
(1.91), and Henry's Law Constant (3.0 X 10'5 atm-m3/mol @ 20°C), 4-nitrophenol appears to have
low volatility and is not expected to accumulate in fish.
There is limited data on the persistence and mobility of the paranitrophenol metabolites.
However, the nitroreduction compound produced under anaerobic conditions was identified as
p-aminophenol. The degradates identified in the photodegradation studies were hydroquinone,
22
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4-nitrocatechol, and 4-aminophenol. Quantitation data for the degradates were not furnished.
Therefore, it is difficult to do any quantitative or qualitative assessment of paranitrophenol
residues.
Again it should be noted that this environmental fate assessment is tentative. The data are
from sources that have not been internally reviewed by EPA. In addition, except for hydrolysis
data no guideline environmental fate studies have been required. Unless guideline environmental
fate data are submitted, an environmental fate assessment of paranitrophenol with supporting data
cannot be made. Given the use patterns of this chemical, however, the present assessment is
considered to be sufficient.
b. Environmental Fate and Transport
For indoor non-food use patterns, only hydrolysis data (161-1) are required. The
guideline requirement is not fulfilled.
c. Water Resources
Ground Water
Paranitrophenol is an environmental breakdown product of several natural and synthetic
compounds. Therefore, detections of paranitrophenol in ground water may not have resulted
from its uses as a fungicide, and the source of contamination is difficult to determine. In the EPA
Pesticides in Ground Water Database - A compilation of Monitoring Studies: 1971-1991 National
Summary, there were three detections (all in Mississippi) in ground water out of 344 monitoring
wells tested in MS and WA. The source(s) of these detections was not discussed in the data.
However, based on the limited use pattern, the Agency believes that these detections were not
from the present fungicide use pattern. It should be noted that even though there are no guideline
mobility studies available for paranitrophenol, its chemical properties (Koc=214) and the data in
the literature indicate that paranitrophenol may move in the soil profile.
Surface Water
Paranitrophenol has been discernible in surface water at low concentrations (at or near
detection limits). The Agency believes these paranitrophenol detections are not due to the present
fungicide use pattern (limited to military leather clothing and cork insulation for missle
equipment). Paranitrophenol is an environmental breakdown product of several natural and
synthetic compounds; therefore, the source of surface water contamination is difficult to
determine. There are no guideline adsorption/desorption data requirements for indoor uses.
Therefore, no adsorption/desorption data are available for paranitrophenol. However, based on
the chemical properties reported (Koc of 214 and solubility in water = 1.6 g/100 ml),
paranitrophenol contamination of surface water is believed to be due to dissolved
paranitrophenol rather than soil bound paranitrophenol in runoff.
23
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3. Exposure and Risk Characterization
Paranitrophenol is used as a fungicide in cork insulation and leather for military uses. It
is applied at a concentration that may not exceed 0.7% of the treated material's weight. It is
moderately to slightly toxic to birds and aquatic animals. Since it is not applied outside of a
factory, it is not expected that any wild animals or plants will be exposed to it. Therefore,
paranitrophenol is not expected to pose a risk to nontarget organisms.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Reregistration Decision
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 ingredient
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 paranitrophenol. The Agency has completed its review of these generic data, and has
made a reregistration decision. Appendix B identifies the generic data requirements that the
Agency reviewed as part of its decision on paranitrophenol, and lists the submitted studies that
the Agency found acceptable.
The Agency based its reregistration decision upon the target data 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.
Based on the reviews of the generic data for the active ingredient paranitrophenol, the
Agency has some concerns about paranitrophenol relating to the potential for handler dermal and
inhalation exposure associated with the registered uses of paranitrophenol (i.e., leather and cork
treatment applied by military contractors to products used by military workers). Lacking
adequate exposure and toxicity data, the Agency is unable to conduct a quantitative risk
assessment. In order to assess the risk, the following data would be required to support the
continued registration of paranitrophenol:
24
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EPA Guideline Study
81-3 Rat acute inhalation toxicity
81-5 Primary dermal irritation study in rabbit
81-6 Dermal sensitization potential study in guinea pig
83-3(b) Rabbit developmental toxicity study
84-4 in vivo bone marrow cytogenetics
231 Dermal exposure
232 Inhalation exposure
The Agency contacted the sole registrant of paranitrophenol, the United States Department
of the Army, regarding the data necessary to support the continued registration of
paranitrophenol. Subsequently, the Agency received a request to cancel the registration of the
sole product containing paranitrophenol from the Department of the Army to take effect on May
30, 2002. In the letter submitted requesting cancellation of the registration, the registrant stated
the following: there are no supplies of PNP in stock; the product would only be used in a
national security emergency situation; a commitment to rely on available alternative fungicides
registered for use to treat leather and cork products and to pursue efficacy testing of these
alternative products.
The Agency has decided to accept the voluntary cancellation request to be effective on
May 30, 2002. The Agency is basing this decision on:
1. The weight of evidence from all available toxicological data does not suggest a potent
threat from dermal and inhalation exposure.
2. Exposure to paranitrophenol is believed to be very limited. It's uses are confined to
leather and cork treatment applied by military contractors to few products used by military
workers. The worker population exposed during treatment is likely to be small. The only large
population potentially exposed is military personnel wearing treated footwear. The Agency was
able to quantitatively estimate their risk and found it to be acceptably low even using the
protective assumptions.
3. During the five year phase-out period, workers using and handling paranitrophenol
solutions and freshly treated products are required to wear chemical resistant aprons and with
attached full sleeve gloves.
Revised label language as set forth in Section V of this document is required. Several
of the label revisions pertain to handler safety requirements that must be established due to the
acute and other adverse effects associated with paranitrophenol. Due to concerns about
potentially high dermal exposures during the introduction and removal of leather or cork by hand
25
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from dip vats, and handlers participating in such hands-on operations, workers must wear
chemical-resistant full-front aprons with attached full-sleeve gloves. Other required label
changes address application restrictions and user safety requirements, and are found in Part V of
this document.
V. ACTIONS REQUIRED OF REGISTRANTS
A. Labeling Language for Paranitrophenol-Containing Products
1. Personal Protective Equipment Label statements
a.The personal protective equipment requirements must be placed on the end-use
product labeling in the format and language as specified and must be placed in the
"Hazards to Humans" section of the pesticide labeling. The label language is
indicated in quotation marks.
"Mixers, loaders, applicators and other handlers must wear:
— Long-sleeve shirt and long pants,
— Shoes plus socks."
— "Protective eyewear."
— "Chemical-resistant apron, and attached full sleeve
— Chemical-resistant gloves*."
*For the glove statement, use the statement established for PNP through
the instructions in Supplement Three of PR Notice 93-7. In addition, the
concentrated PNP product, the corrosiveness and penetration of PNP
must be considered. Appropriate chemical-resistant materials must be
listed on the product labeling.
b. Since this product is toxicity category II for acute inhalation toxicity, a
respirator requirement must be added. The type of respirator must be specified
in the statement and is based on the acute toxicity category and the vapor pressure.
EPA will assist the registrant in determining the appropriate type of respirator.
c. In addition to the minimum PPE specified above, the following specific PPE
requirements must be added to labels:
"Handlers participating in hands-on operations, including introduction of
materials to and removal from the dip, and handling leather or cork still
wet with the treatment, must wear chemical-resistant full-front aprons with
attached full-sleeve gloves."
26
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2. Application Restrictions
"Do not use this product in a way that will contact workers or other persons."
3. Restrictions For Use Statement
"This product can not be used after May 30, 2002."
4. User Safety Requirements
"Follow manufacturer"s instructions for cleaning/maintaining PPE. If no such
instructions for washables, use detergent and hot water. Keep and wash PPE
separately from other laundry."
5. 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. As soon as possible wash thoroughly."
27
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28
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VI. APPENDICES
29
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30
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GUIDE TO APPENDIX A
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 Reregi strati on 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.
31
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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.
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.
32
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BIBLIOGRAPHY
MRID CITATION
00031651 U.S. Army, Natick R & D Command (1978) Paranitrophenol: Study No.
51-0047-78 (Unpublished study received Sep 19, 1979 under 40510-2;
CDL:241879-A)
00031652 U.S. Army, Natick R & D Command (1978) Protocol: Sp Study No.
7551-0045-79, Parti. (Unpublished study received Sep 19, 1979 under 40510-2;
CDL:241874-A)
00031653 U.S. Army, Natick R & D Command (1978) Protocol-Primary Skin Irritation: Sp
Study No. 75-51-0045-79, Part I. (Unpublished study received Sep 19, 1979
under 40510-2; CDL:241873-A)
00031654 U.S. Army, Natick R & D Command (1978) Paranitrophenol: Prenatal Toxicity:
Study No. 51-0047-78. (Unpublished study received Sep 19, 1979 under
40510-2; CDL:241882-A)
00031656 U.S. Army, Natick R & D Command (1979) Paranitrophenol: Study No.
51-0047-78. (Unpublished study received Sep 19, 1979 under 40510-2;
CDL:241880-A)
00031657 U.S. Army, Natick R & D Command (1978) Protocol Guinea Pig Sensitization
Test: Sp Study No. 75-51-0045-79, Part I. (Unpublished study received Sep 19,
1979 under 40510-2; CDL:241876-A)
00031658 U.S. Army, Natick R & D Command (1979) Protocol LDaeSO- Determinations:
Sp Study No. 75-51-0045-79, Parti. (Unpublished study received Sep 19, 1979
under 40510-2; CDL:241875-A)
00031677 U.S. Army, Natick R & D Command (1978) Paranitrophenol: Prenatal Toxicity:
Study No. 51-0047-78. (Unpublished study received Sep 19, 1979 under
40510-2; CDL:241883-A)
00031678 U.S. Army, Natick R & D Command (1978) Paranitrophenol: Prenatal Toxicity:
Study No. 51-0047-78. (Unpublished study received Sep 19, 1979 under
40510-2; CDL:241884-A)
33
-------
BIBLIOGRAPHY
MRID CITATION
00031679 U.S. Army, Natick R & D Command (1978) Paranitrophenol: Prenatal Toxicity:
Study No. 51-0047-78. (Unpublished study received Sep 19, 1979 under
40510-2; CDL:241885-A)
00031680 Weisburger, E.; Donahoe, R.; Shores, R.; et al. (1979) Test for Carcinogenicity of
Chlorinated Dioxanes by Pulmonary Tumor Response in Strain A Mice: Protocol:
Technical Guide Paranitrophenol: Sp Study No. 75-51-0047-79, Part I. (Appendix
J; unpublished study received Sep 19, 1979 under 40510-2; prepared by
Microbiological Associates, submitted by U.S. Army, Natick R & D Command,
Natick, Mass.; CDL:241889-A)
00031681 Jagannath, D.R. (1978) Mutagencity Evaluation of Paranitrophenol Lot # 777A
in the Ames-Salmonella- ,/Microsome Plate Test. Final rept. (Unpublished study
received Sep 19, 1979 under 40510-2; prepared by Litton Bionetics, Inc.,
submitted by U.S. Army, Natick R & D Command, Natick, Mass.;
CDL:241886-A)
00031682 Beavers, J.B.; Fink, R.; Brown, R.; et al. (1979) Final Report: Eight-Day Dietary
LC50--Bobwhite Quail: Project No. 167-101. (Unpublished study received Sep
19, 1979 under 40510-2; prepared by Wildlife International, Ltd. in cooperation
with Washington College, submitted by U.S. Army, Natick R & D Command,
Natick, Mass.; CDL:241888-A)
00031683 Beavers, J.B.; Fink, R.; Brown, R.; et al. (1979) Final Report: Eight-Day Dietary
LC50~Mallard Duck: Project No. 167-101. (Unpublished study received Sep 19,
1979 under 40510-2; prepared by Wildlife International, Ltd. in cooperation with
Washington College, submitted by U.S. Army, Natick R & D Command, Natick,
Mass.; CDL:241888-B)
00031690 U.S. Army, Natick R & D Command (1967) Effect of Paranitrophenol on the
Embryonic Development of Rats: Sp Study No. 75-51-0045-79. (Appendix F;
unpublished study received Sep 19, 1979 under 40510-2; CDL:241878-A)
00031691 U.S. Army, Natick R & D Command (1978) Enzyme Induction: Sp Study No.
75-51-0045-79, Part I. (Appendix F; unpublished study received Sep 19, 1979
under 40510-2; CDL:241877-A)
34
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BIBLIOGRAPHY
MRID
CITATION
00037268 Dewaide, J.H. (1971) Comparison of N-demethylation, P-hydroxylation and
glucuronidation in various animal species, particularly in species offish. Pages
83-89,~In~Metabolism of Xenobiotics: Comparative and Kinetic Studies as a
Basis for Environmental Pharmacology. Doctoral dissertation, Katholieke Univ.,
Wiskunde en Natuurwetenschappen. Nijmegen, ^Netherlands*: Drukkerij Leijn.
(Also~In~unpublished submission received Apr 5, 1974 under IF 1074; submitted
by Thompson-Hayward Chemical Co., Kansas City, Kans.; CDL:093384-C)
00041783 Lichtenstein, E.P. (1969) Pesticide residues in soils, water, and crops. Annals of
New York Academy of Sciences 160(1):155-161. (Also~In~unpublished
submission received Nov 1, 1970 under unknown admin, no.; submitted by
Hercules, Inc., Agricultural Chemicals, Wilmington, Del.; CDL:005104-BJ)
00060768 Simpson, J.R.; Evans, W.C. (1953) The metabolism of Nitrophenols by certain
bacteria. Journal of Biochemistry 55:XXIV. (Also ,-In-unpublished submission
received Jun 10, 1968 under 8F0712; submitted by Dow Chemical U.S.A.,
Midland, Mich.; CDL:091234-V)
00061486 E.I. du Pont de Nemours & Company (1971) Inert ingredient Technical.
Unpublished study; 1 p.
00061487 U.S. Department of the Army, Natick Research and Development Command
(19??) Para-Nitrophenol Manufacture Process. (Unpublished study;
CDL:230416-B)
00061488 E.I. du Pont de Nemours and Company (1960) Inert ingredient Technical:
Determination of Purity. Orchem method 21-6-9-1 dated Jun 21, 1960.
Unpublished study; 4 p.
00061489 McCarthy, J.R.; Bryant, W.M., III (1972) p-Nitrophenol: Determination of Color
and Scum. Orchem method 21-3-13-1C dated May 22, 1972. Unpublished study;
4 p.
35
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BIBLIOGRAPHY
MRID
CITATION
00061490 Fentin, A. (1958) General Procedure: Determination of Ash on Nonvolatile Matter
by Direct Ignition. Procedure 6-5-2. (Unpublished study received May 4, 1977
under 40510-2; submitted by U.S. Dept. of the Army, Natick Research and
Development Command, Natick, Mass.; CDL:230416-E)
00061491 Williams, L.A.; Brandenberger, E.G. (1970) Iron: Spectrophotometric
Determination of Small Amounts in Organic Matter (1,10-Phenanthroline
Method). Undated Orchem method 6-11-5B. (Unpublished study received May
4, 1977 under 40510-2; prepared by E.I. du Pont de Nemours and Co., submitted
by U.S. Dept. of the Army, Natick Research and Development Command, Natick,
Mass.; CDL:230416-F)
00061492 Lollar, R.M. (1954) Para-Nitrophenol as a fungicide for leather. Journal of the
American Leather Chemists Association XL1X(9): 605-624. (Also In unpublished
submission received May 4, 1977 under 40510-2; submitted by U.S. Dept. of the
Army, Natick Research and Development Command, Natick, Mass.;
CDL:230416-G)
00061493 Graham, R.C. (1977) (Properties of para-Nitrophenol). (Unpublished study
received May 4, 1977 under 40510-2; prepared by E.I. du Pont de Nemours and
Co., submitted by U.S. Dept. of the Army, Natick Research and Development
Command, Natick, Mass.; CDL: 230416-H)
00061494 Smithsonian Science Information Exchange, Incorporated (1977) Inert ingredient:
SSIENo. AO-18208-1. Unpublished compilation; 19 p.
00061495 Miller, C.Q. (1962) Determination of Moisture by the Karl Fischer Method Using
the Beckman Aquameter, Model KF-3; Operation and Maintenance of the
Beckman Aquameter, Model KF-3. Orchem method 2-14-3A dated Jan 16, 1962.
(Unpublished study received May 4, 1977 under 40510-2; prepared by E.I. du
Pont de Nemours and Co., submitted by U.S. Dept. of the Army, Natick Research
and Development Command, Natick, Mass.; CDL:230416-J)
00061496 Lollar, R.M. (1974) Report on a study and the development of a mold resistant
treatment for leather. Journal of American Leather Chemists Association
39(May): 12-24. (Also In unpublished submission received May 4, 1977 under
40510-2; submitted by U.S. Dept. of the Army, Natick Research and Development
Command, Natick, Mass.; CDL:230416-K)
36
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BIBLIOGRAPHY
MRID
CITATION
00061497 Lollar, R.M. (1974) Report on mold resistant treatments for leather. Journal of
American Leather Chemists Association 39(May): 179-190. (Also In unpublished
submission received May 4, 1977 under 40510-2; submitted by U.S. Dept. of the
Army, Natick Research and Development Command, Natick, Mass.;
CDL:230416-L)
00061498 Lollar, R.M. (1944) Report on toxicity studies on preservative bearing leather.
Journal of the American Leather Chemists Association 39(5):203-209. (Also In
unpublished submission received May 4, 1977 under 40510-2; submitted by U.S.
Dept. of the Army, Natick Research and Development Command, Natick, Mass.;
CDL:230416-M)
00061499 Riley, B.C. (1944) Letter sent to the Director, AIHL dated May 2, 1944: Results
of patch tests performed at Federal Security Agency, Social Security Office,
Candler Bldg., Baltimore, Md. (U.S. Army Service Forces, Army Industrial
Hygiene Laboratory; unpublished study; CDL:230416-N)
00061500 McNary, R.R.; Hussey, R. (1944) Letter sent to Commanding Officer, Army
Service Forces, Army Industrial Hygiene Laboratory dated Aug 18, 1944: Request
for Analysis of Spray Compound, Type II. (U.S. Army Service Forces,
Headquarters First Service Command; unpublished study; CDL:230416-O)
00061501 Riley, B.C. (1944) Letter sent to the Director, AIHL dated Aug 9, 1944: Result of
2nd series of patch tests performed at Federal Security Agency, Social Security
Office, Candler Bldg., Baltimore, Md. (U.S. Army Service Forces, Army
Industrial Hygiene Laboratory; unpublished study; CDL:230416-P)
00061502 Alters, W.D. (1944) Letter sent to the Director, AIHL dated Nov 20, 1944
(Various tests with p-Nitrophenol). (U.S. Army Service Forces, Army Industrial
Hygiene Laboratory; unpublished study; CDL:230416-Q)
37
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BIBLIOGRAPHY
MRID
CITATION
00061503 U.S. Department of the Army, Natick Research and Development Command
(19??) Protocol for Paranitrophenol Use Test in Shoes. (Unpublished study;
CDL:230416-S)
00061504 U.S. Department of the Army, Natick Research and Development Command
(19??) p-Nitrophenol. Undated method. (Unpublished study; CDL:230416-T)
00061505 Ambrose, A.M. (1957) Determination of para-Nitrophenol and Metabolites
Thereof in Urine: MEDEI 2214T234-55. Method dated Nov 1957. (U.S. Dept.
of the Army, Natick Research and Development Command; unpublished study;
CDL:230416-U)
00061506 Duguid, R.H. (1958) Report of Paranitrophenol-Treated Combat-BootWearing
Test: Project No. 2214T234-56/59: MEDEI-M 400.112. (U.S. Army Medical
Service, Environmental Health Laboratory; unpublished study; CDL:230416-V)
00061507 Ambrose, A.M. (1958) Report of Study on Toxicologic Effects from Wearing of
Boots Treated with Nitrophenol: Project No. 2214T23455: MEDEI-T 400.112.
(U.S. Army Medical Service, Environmental Health Laboratory; unpublished
study; CDL:230416-W)
00061508 Wands, R.C. (1967) Letter sent to Chief, Preventive Medicine Division, Office of
the Surgeon General dated Jan 13, 1967 (Toxicity of Paranitrophenol when used
as a fungicide on shoe leather). (Unpublished study received May 4, 1977 under
40510-2; submitted by U.S. Dept. of the Army, Natick Research and Development
Command, Natick, Mass.; CDL:230416-X)
00061509 U.S. Department of the Army, Natick Research and Development Command
(1966) Annotated Bibliography of Skin Sensitization Studies Using
Paranitrophenol. (Unpublished study; CDL:230416-Y)
00061510 Kaminer, AJ. (19??) Letter sent to the Record circa Dec 1965 High PNP content
of shoes (Gardiner Shoe Company): USAEHA-MM. (U.S. Dept. of the Army,
Environmental Hygiene Agency, unpublished study; CDL:230416-Z)
38
-------
BIBLIOGRAPHY
MRID
CITATION
00061511 U.S. Department of the Army, Natick Research and Development Command
(1960) Effectiveness. (Reports by various sources; unpublished study including
published data, received May 4, 1977 under 40510-2; CDL:230416-AA)
00065407 Ciba Agrochemical Company (1960?) Full Reports of Investigations Made with
Respect to the Safety of the Pesticide Chemical, C-6989. Summary of studies
091635-B through 091635-D. (Unpublished study received Apr 3, 1970 under
OF0958; CDL:091635-A)
00065409 Mastri, C. (1970) Report to ...: Acute Oral Toxicity Study on Technical Preforan
and Ten Metabolites of Preforan in White Mice: IBT No. A8018; Research Report
CF-6822. (Unpublished study received Apr 3, 1970 under OF0958; prepared by
Industrial Bio-Test Laboratories, Inc., submitted by Ciba Agrochemical Co.,
Summit, N.J.; CDL:091635-C)
00065412 Ciba Agrochemical Company (1970) Gas Chromatographic Analysis of
Conjugated~p—Nitrophenol Residues in Soybean Seed and Foliage ^Provisional
Method for Preforan-'(R)ae(C-6989)*. Vero Beach, Fla.: Ciba. (Research bulletin
no. 59; also~In~unpublished submission received Apr 3, 1970 under OF0958;
CDL:091635-F)
00065416 Katz, S.E.; Winnett, G. (1970) Preforan-(R)cE Analytical Method Trial According
to Research Bulletin No. 58 for Analysis of Free ,~p—Nitrophenol in Soybean
Seed: Research Report CF-7026. (Unpublished study received Apr 3, 1970 under
OF0958; prepared by Rutgers Univ., Dept. of Agricultural Chemistry, submitted
by Ciba Agrochemical Co., Summit, N.J.; CDL:091635-J)
00065418 Katz, S.E. (1970) Letter sent to V. Frank Boyd dated Feb 10, 1970: Method trial
of procedure for determining~p—nitrophenol conjugates according to research
bulletin no. 59: Research Report CF-7050. (Unpublished study received Apr 3,
1970 under OF0958; prepared by Rutgers Univ., Dept. of Agricultural Chemistry,
submitted by Ciba Agrochemical Co., Summit, N.J.; CDL:091635-L)
39
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00065423 Ciba Agrochemical Company (1970) Method Development for Conjugated
,~p~-Nitrophenol Analysis: Research Report CF-7082. (Unpublished study
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00068906 E.I. du Pont de Nemours & Company (1977?) Mutagenicity: Summary. Summary
of studies 234119-1 through 234119-J. (Unpublished study received Jun 15, 1978
under unknown admin, no.; CDL: 234119-H)
00068907 Koops, A. (1975)~In vitro-Microbiol Mutagenicity Studies of pNitrophenol:
Haskell Laboratory Report No. 193-75. (Unpublished study received Jun 15, 1978
under unknown admin, no.; submitted by E.I. du Pont de Nemours & Co.,
Wilmington, Del.; CDL: 234119-J)
00078015 Duguid, R.H. (1958) Report of Paranitrophenol-treated Combat-bootwearing Test:
Project No. 2214T234-56/59. (U.S. Army Medical Service, Environmental Health
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00078016 Ambrose, A.M. (1958) Report of Study on Toxicologic Effects from Wearing of
Boots Treated with Nitrophenol: Project No. 22MT23455. (U.S. Army Medical
Service, Environmental Health Laboratory; unpublished study; CDL:233979-B)
00078017 Ambrose, A.M. (1957) Determination of Para-Nitrophenol and Metabolites
Thereof in Urine: MEDEI 22MT234-55. (Unpublished study received Oct 11,
1977 under 40510-2; submitted by U.S. Dept. of the Army, Natick Research &
Development Command, Natick, Mass.; CDL:233979-D)
00078018 Waldman, R.K.; Krouse, L.A. (1952) A rapid routine method for determination
of paranitrophenol in urine. Occupational Health 12(3):37-38. (Also In
40
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00078019 Mountain, J.T.; Zlotolow, H.; O'Conor, G.T. (1951) Determination of
paranitrophenol in urine in parathion poisoning cases. Industrial Health Monthly
ll(6):88-89. (Also In unpublished submission received Oct 11, 1977 under
40510-2; submitted by U.S. Dept. of the Army, Natick Research & Development
Command, Natick, Mass.; CDL:233979-F)
00094659 Wyatt, J.T.; Fianu, P. (1979) Static Bioassays of Technical Grade Paranitrophenol
with Aquatic Organisms: 1 June-30 November 1979: Water Quality Bioassay No.
32-24-0215-80. Final rept. (U.S. Environmental Hygiene Agency; unpublished
study, including undated letter from R.L. Hanson to Arthur Kaplan;
CDL:246725-A)
00127232 Barnes, J.; Denz, F. (1951) The chronic toxicity of p-nitrophenyl diethyl
thiophosphate (E. 605): A long-term feeding experiment with rats. Journal of
Hygiene 49(4):430-441. (Also In unpublished submission received Feb 12, 1982
under unknown admin, no.; submitted by Stauffer Chemical Co., Richmond, CA;
CDL: 247779-C)
00139876 Davis, J.H.; Davies, I.E.; Fisk, AJ. (1969) Occurence, diagnosis, and treatment
of organophosphate pesticide poisoning in man. Annals of New York Academy
of Sciences 160:383-392. (Also~In~ unpublished submission received Apr 6,
1976 under 4715-352; submitted by Colorado International Corp., Lakewood,
Colo.; CDL: 230814-O)
00144773 Chaiyarach, S.; Ratananun, V.; Harrel, R. (1975) Acute toxicity of the insecticides
toxaphene and carbaryl and the herbicides propanil and molinate to four species
of aquatic organisms. Bulletin of Environmental Contamination & Toxicology
14(3):281-284.
41
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00146455 Angerhofer, R. (1985) Applications of Paranitrophenol on the Reproductive
Functions on Rats, Study No. 75-51-0047-85, September 1980-March 1985.
Prepared by U.S. Army Environmental Hygiene Agency. 38 p.
00160272 Izmirova, N.; Petkova, V.; Beraha, R. (1981) Sanitary and hygiene studies in case
of mechanized pesticide application. Khig Zdraveopaz 24(6):537-542.
05009237 Propping, P.; Buselmaier, W.; Roehrborn, G. (1973) Kritische Betrachtung ueber
die intra-animale Kultur von Mikroorganismen, eine Methode zum Nachweis
chemisch induzierter Mutationen_ ^Critical notes on intra-animal culture of
microorganisms, a method for detecting chemically induced mutations_*
Arzneimittel-Forschung23(6):746-749.
40529700 USAEHA (1987) Submission of Data To Support the Registration of
Paranitrophenol: Toxicology Study. Transmittal of 1 study.
40529701 USAEHA (1985) Effect of Dermal Applications of Paranitrophenol on the
Reproductive Functions of Rats: 75-51-0047-85. 1583 p.
41343700 A/S Cheminova (1990) Submission of data in support of Ethyl Parathion
registration standard: Residue method study. Transmittal of 1 study.
41343701 Szorik, M. (1989) Accountability Study of the Proposed Enforcement Method for
the Determination of Ethyl Parathion (EP), Ethyl Paraoxon (EPOX), and
p-Nitrophenol (PNP) in Raw Agricultural Commodities or Processed Raw
Agricultural Commodities: Final Report: Lab Project No. HLA 6012-259; Method
MP-EPHY-MA. Unpublished study prepared by Hazleton Laboratories America,
Inc. 64 p.
41576600 Department of the Army (1990) Submission of Chemistry Data in Support of
Paranitrophenol Phase 3 Response Data Call-in. Transmittal of 1 study.
41576601 Rogers, M. (1990) Paranitrophenol: Product Chemistry Studies. Unpublished
study prepared by Monsanto Chemical Co. 35 p.
42
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BIBLIOGRAPHY
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41896800 Rogers, M.; Greenberger, M. (1979) Submission of Data To Support
4-Nitrophenol Reregi strati on Phase 4: Leather Leaching Study. Transmittal of 1
study.
41896801 Rogers, M.; Greenberger, M. (1979) 4-Nitrophenol Leather Leaching Study: Lab
Project Number: 1L162723AH98. Unpublished study prepared by US Army
Natick Research, Development and Engineering Center. 28 p.
41934800 Dept. of the Army (1991) Submission of residue data on paranitrophenol in
response to Phase III data requirements. Transmittal of 1 study.
41934801 Duguid, R. (1958) Report of Paranitrophenol-Treated Combat BootWearing Test:
Lab Project Number: 2214T234-56/59. Unpublished study prepared by U.S.
Army, Environmental Health Agency. 16 p.
42174600 Department of the Army (1992) Submission of toxicity data in support of a phase
4 data call-in for 4-Nitrophenol. Transmittal of 1 study.
42174601 Pedersen, C.; Helsten, B. (1991) Para-Nitrophenol: 8-Day Acute Dietary LC50
Study in Mallard Ducklings: Lab Project Number: BLAL 90 DC 152.
Unpublished study prepared by Bio-Life Associates, Ltd. 28 p.
42174700 Department of the Army (1992) Submission of toxicity data in support of a phase
4 data call-in for 4-Nitrophenol. Transmittal of 1 study.
42174701 Pedersen, C.; Helsten, B. (1991) Para-Nitrophenol: 21-Day Acute Oral LD50
Study in Bobwhite Quail: Lab Project Number: BLAL 90 QD 159. Unpublished
study prepared by Bio-Life Associates, Ltd. 40 p.
42174800 Department of the Army (1992) Submission of toxicity data in support of a phase
4 data call-in for 4-Nitrophenol. Transmittal of 1 study.
42174801 Andrews, P. (1990) In vitro Mutagenicity Tests on p-Nitrophenol and CIC4
Employing the Salmonella/Ames Plate Assay Test System: Lab Project Number:
DAAD05-90-C001: ILS A043. Unpublished study prepared by Integrated Lab
Systems. 25 p.
43
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BIBLIOGRAPHY
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42174900 Department of the Army (1992) Submission of toxicity data in support of a phase
4 data call-in for 4-Nitrophenol. Transmittal of 1 study.
42174901 Pedersen, C.; Helsten, B. (1991) Para-Nitrophenol: 8-Day Acute Dietary LC50
Study in Bobwhite Quail: Lab Project Number: BLAL 90 QC 156. Unpublished
study prepared by Bio-Life Aassociates, Ltd. 31 p.
42270900 US Army Natick R.D. & E Center (1992) Submission of Data in Response to
4-Nitrophenol (PNP) Phase 4 Data Call-in: Toxicology Study. Transmittal of 1
study.
42270901 Andrews, P. (1990) In vitro Cytogenetic Testing on p-Nitrophenol Employing the
Chromosome Aberration Assay in Chinese Hamster Ovary Cells: Contract No.
DAAD05-90-C-0001: Lab Project Number: 90/22. Unpublished study prepared
by Integrated Lab Systems. 18 p.
42271000 US Army Natick R. D. & E. Center (1991) Submission of Data in Resposne to
4-Nitrophenol (PNP) Phase 4 Data Call-in : Toxicology Study. Transmittal of 1
study.
42271001 Andrews, P. (1990) Mouse Lymphoma Mutagenesis Assay on p-Nitrophenol (ILS
#90-22): Contract No. DAAD05-90-C001: Lab Project Number: ILS A043.
Unpublished study prepared by Integrated Lab Systems. 39 p.
42382400 U.S.Army, Natick (1992) Submission of toxicity data for Paranitrophenol in
accordance with Phase IV DCI. Transmittal of 1 study.
42382401 Bowman, J. (1991) Acute Toxicity of Paranitrophenol to Rainbow Trout
(Oncorrhynchus mykiss): Lab Project Number: 38994. Unpublished study
prepared by ABC Labs, Inc. 77 p.
42382500 U.S. Army, Natick (1992) Submission of toxicity data to support the Phase IV
requirements for Paranitrophenol. Transmittal of 1 study.
44
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BIBLIOGRAPHY
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42382501 Blasberg, I; Butzlaff, T. (1991) Acute Toxicity of Paranitrophenol to Daphnia
magna: Lab Project Number: 38996: DAAD05-89P-2152. Unpublished study
prepared by ABC Labs, Inc. 62 p.
42382600 U.S. Army, Natick (1992) Submission of product chemistry data to support the
Phase IV registration requirements paranitrophenol. Transmittal of 1 study.
42382601 Bowman, J. (1991) Acute Toxicity of Paranitrophenol to Bluegill (Lepomis
macrochirus): Lab Project Number: 38995. Unpublished study prepared by ABC
Labs, Inc. 70 p.
42538700 Department of the Army (1992) Submission of toxicity data in support of the data
call-in for p-Nitrophenol. Transmittal of 1 study.
42538701 Coate, W. (1992) Subacute Dust Inhalation Toxicity Study in Rats-p-Nitrophenol:
Lab Project Number: 241-139. Unpublished study prepared by Hazelton
Laboratories America, Inc. 243 p.
42539500 US Army Aviation and Troop Command (1992) Submission of toxicity data to
support reregi strati on of PNP. Transmittal of 1 study.
42539501 Snodgrass, H. (1983) Dermal Penetration and Distribution of 0carbon 14-labeled
Paranitrophenol (PNP): Lab Project Number: 75-51-0047-84-H. Unpublished
study prepared by US Army Environmental Hygiene Agency. 28 p.
42539600 US Army Aviation and Troop Command. (1992) Submission of toxicity data to
support PNP reregi strati on. Transmittal of 1 study.
42539601 Weeks, M. (1979) Acute Oral Toxicity in Rats: PNP: Lab Project Number:
75-51-0047-79-C. Unpublished study prepared by US Army Environmental
Hygiene Agency. 38 p.
42539700 US Army Natick RD&E Center (1992) Submission of Toxicity Data in Support
for 4-Nitrophenol (PNP) Phase 4 Data Call-In. Transmittal of 1 study.
45
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BIBLIOGRAPHY
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42539701 Weeks, M. (1992) Dermal LD50 in Rabbits: 4-Nitrophenol (PNP): Lab Project
Number: 75-51-0047-79-G: SPONSOR. Unpublished study prepared by U.S.
Army Environmental Hygiene Agency. 20 p.
42539800 U.S. Army Natick RD&E Center (1992) Submission of Toxicity Data in Support
for 4-Nitrophenol (PNP) Phase 4 Data Call-In. Transmittal of 1 study.
42539801 Weeks, M. (1992) Primary Eye Irritation of Paranitrophenol in Rabbits:
4-Nitrophenol (PNP): Lab Project Number: 75-51-0047-79-B. Unpublished study
prepared by U.S.Army Environmental Hygiene Agency. 10 p.
42539900 U.S. Army Natick RD&E Center (1992) Submission of Toxicity Data in Support
for 4-Nitrophenol (PNP) Phase 4 Data Call-In. Transmittal of 1 study.
42539901 Weeks, M. (1992) Primary Dermal Irritation of Paranitrophenol in Rabbits:
4-Nitrophenol (PNP): Lab Project Number: 75-51-0047-79-A: SPONSOR.
Unpublished study prepared by U. S. Army Environmental Hygiene Agency. 10
P-
42540000 U.S. Army Natick RD&E Center (1992) Submission of Toxicity Data in Support
for 4-Nitrophenol (PNP) Phase 4 Data Call-In. Transmittal of 1 study.
42540001 Weeks, M. (1992) Dermal Sensitization Guinea Pig Test: 4-Nitrophenol (PNP):
Lab Project Number: 75-51-0047-79-D: SPONSOR. Unpublished study prepared
by U. S. Army Environmental Hygiene Agency. 17 p.
42788600 US Army Natick RD&E Center (1993) Submission of toxicity data in support of
the Phase 4 reregi strati on for 4-Nitrophenol (PNP). Transmittal of 1 study.
42788601 Angerhofer, R.; Weeks, M. (1992) Effect of Paranitrophenol on the Embryonic
Development of Rats: Lab Project Number: 75-51-0047-79-F. Unpublished study
prepared by U.S. Army Environmental Hygiene Agency. 44 p.
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Data Call-In for 4-Nitrophenol. Transmittal of 1 study.
46
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42788801 Schulze, G. (1992) Subchronic Toxicity Study in Rats with paraNitrophenol: Lab
Project Number: 241-221. Unpublished study prepared by Hazleton Laboratories
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43766200 U.S. Army Soldier Systems Command (1995) Submission of toxicity data in
support of data call-in for Paranitrophenol. Transmittal of 1 study.
43766201 Alden, C. (1988) Toxicology and carcinogenesis studies of p-nitrophenol in
Swiss-Webster mice (dermal studies): (Includes raw data). Prepared by National
Toxicology Program; available from the National Technical Information Service.
270 p.
44036800 US EPA (1996) Submission of Hazard to Aquatic Organisms Data in Support of
4-Nitrophenol. Transmittal of 1 Study.
44036801 Anderson, C.; Brooke, L.; Call, D.; et al. (1988) Acute toxicities of organic
chemicals to fathead minnows (Pimephales promelas): Volumes I through IV.
Prepared by and Available from Center for Lake Superior Environmental Studies,
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Nitrophenol.
92131999 U. s. Army Natick R & D Command (1990) Reregi strati on Phase 3 Response:
Nitrophenol. Correspondence and Supporting Material.
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APPENDIX B - LIST OF AVAILABLE RELATED DOCUMENTS
The following is a list of available documents for PARANITROPHENOL 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 Veronica Dutch at (703)-308-8585.
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 PARANITROPHENOL.
The following documents are part of the Administrative Record for
PARANITROPHENOL 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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