r/EPA
United State*
Environmental Protection
Agency
Office of
Penteidee and Toxic Subetancee
Washington OC 20460
540/RS-88-117
Peeticidee
Guidance for the
Reregistration of
Pesticide Products
Containing Metalaxyl
as the Active Ingredient
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OMB Control No. 2070-0057
Expires 11/89
GUIDANCE FOR THE
REREGISTRATION OF PESTICIDE PRODUCTS
CONTAINING
N-(2,6-DIMETHYLPHENYL)-N-(METHOXYACETYL)
ALANINE, METHYL ESTER
(REFERRED TO AS METALAXYL)
AS THE ACTIVE INGREDIENT
CASE NUMBER: 0081
CAS (DOCKET) NUMBER 57837-19-1
EPA SHAUGHNESSY CODE: 113501
. SŁETEŁ[BER 1988
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
WASHINGTON, D.C. 20460
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TABLE OF CONTENTS
GLOSSARY OF TERMS AND ABBREVIATIONS
I. INTRODUCTION 1
II. CHEMICAL(s) COVERED BY THIS STANDARD 4
A. Description of Chemical
B. Use Profile
C. History
III. AGENCY ASSESSMENT 6
A. Summary
t B. Risk Assessment
C. Other Science Findings
D. Tolerance Reassessment
IV. REGULATORY POSITION AND RATIONALE 22
A. Regulatory Positions and Rationales
B. Criteria for Registration
C. Acceptable Ranges and Limits
D. Required Labeling
V. PRODUCTS SUBJECT TO THIS STANDARD—--—- 31
A. Manufacturing Use Products Containing This
Pesticide As The Sole Active Ingredient
B. Manufacturing Use Products Containing This
Pesticide As One of Multiple Active Ingredients
C. End Use Products Containing This Product As
The Sole Active Ingredient
D. End Use Products Containing This Pesticide As
One Of Multiple Active Ingredients
VI. REQUIREMENT FOR SUBMISSION OF GENERIC DATA 33
A. What are Generic Data?
B. Who Must Submit Generic Data?
C. What Generic Data Must be Submitted?
D. How to Comply with DCI Requirements
E. Registrant Requests Regarding Data Requirements
and Agency Responses
F. Test Protocols and Standards
G. Procedures for Requesting A Change in Test Protocol
H. Procedures for Requesting Extensions of Time
I. Data Format and Reporting Requirements
J. Existing Stocks Provision upon Suspension
or Cancellations
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VII. REQUIREMENT FOR SUBMISSION OF PRODUCT-SPECIFIC DATA . 39
VIII. REQUIREMENT FOR SUBMISSION OF REVISED LABELING .... 40
IX. INSTRUCTIONS FOR SUBMITTAL 40
A. Manufacturing-Use Products (sole active)
B. Manufacturing-Use Products (multiple active)
C. End-Use Products (Sole active)
D. End-Use Products (Multiple active)
E. Intrastate Products
-11-
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APPENDICES
I. DATA APPENDICES 44
Guide to Tables
Table A
Table B
II. LABELING APPENDICES 80
Summary of Label Requirements and Table
* 40 CFR 156.10 Labeling Requirements
Physical/Chemical Hazards Labeling Statements
Storage Instructions
Pesticide Disposal Instructions
Container Disposal Instructions
III. BIBLIOGRAPHY APPENDICES . . . . , -r-t—-.——--. .... 144
Guide to Bibliography
Bibliography
IV. FORMS APPENDICES 161
EPA Form'8580-1 FIFRA S3(c)(2)(B) Summary Sheet
EPA Form 8580-6 Certification of Attempt to Enter Into
an Agreement with Other Registrants for
Development of Data
EPA Form 8580-4 Product Specific Data Report
EPA Form 8570-27 Formulator's Exemption Statement
-HIT
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GLOSSARY OF TERMS AND ABBREVIATIONS
The following terms are used throughout this Registration
Standard and are defined here for the convenience of the reader.
ADI: (Acceptable Daily Intake) An acceptable daily intake of
pesticide residue based on a complete data base.
ai: Active ingredient
CAS: Chemical Abstract Service (number)
EEC: (Estimated Environmental Concentration) Estimated pesticide
concentration in the environment (terrestrial or aquatic
ecosystem).
t
EP: End-use Product
EPA: The Environmental Protection Agency, also "the Agency"
FIFRA: The Federal Insecticide, Fungicide, and Rodenticide Act
HOT: Highest dose tested
(median lethal concentration): a statistically derived
concentration of a substance that can be _expjected.-to cause
death in 50 percent of test animals, expressed as weight
or volume of test substance per volume of air or water
or per weight of feed (e.g., mg/L or ppm).
(median lethal dose): a statistically derived single dose
that can be expected to cause death in 50 percent of animals
when administered by the route indicated, expressed as
weight of substance per unit weight of test animal (e.g.,
mg/kg).
LEL: Lowest Effect Level
MOS: Margin of Safety -
MPI: Maximum Permissible Intake
MRID: Master Record Identification (number)—EPA's system of
tracking studies used in support of registrations
MP: Manufacturing-use product
NPDES: National Pollution Discharge Elimination System
NOEL: No Observed Effect Level—the maximum dose used in a
test which produces no observed adverse effects.
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OPP: The Office of Pesticide Programs (EPA)
OM: Organic matter (used to describe soils)
ppm: Parts per million
PADI: (Provisional Acceptable Daily Intake) An acceptable daily
intake of pesticide residue based on a limited data base.
PAI: Pure active ingredient
Technical: Active ingredient as manufactured
TMRC: (Theoretical Maximum Residue Contribution)
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1• INTRODUCTION
EPA has established the Registration Standards program
in order to provide an orderly mechanism by which pesticide
products containing the same active ingredient can be reviewed
and standards set for compliance with FIFRA. The standards
are applicable to reregistration and future applications for
registration of products containing the same active ingredient.
Each registrant of a product containing an active ingredient
subject to this Standard who wishes to continue to sell or
distribute that product must bring his product and labeling
into compliance with FIFRA, as instructed by this Standard.
The Registration Standards program involves a thorough
review of the scientific data base underlying a pesticide's
registration. The purpose of the Agency's review is to
reassess the potential hazards arising from the currently
registered uses of the pesticide; to determine the need for
additional data on health and environmental effects; and to
determine whether the pesticide meets the "no unreasonable
adverse effects" criteria of FIFRA. In its review EPA identifies
1. Studies that are acceptable to support the data
requirements for the currently registered uses of the pesticide.
2. Additional studies necessary to support continued _
registration. The additional studies may not have been
required when the product was initially registered or may be
needed to replace studies that are now considered inadequate.
3. Labeling revisions needed to ensure that the product
is not misbranded and that the labeling is adequate to protect
man and the environment.
The detailed scientific review and use index which are
not contained in this document, but is available upon request1,
focuses on the pesticide active ingredient. The scientific
review primarily discusses the Agency's evaluation of and
conclusions from available data in its files pertaining to
the pesticide active ingredient. However, during the review
of these data the Agency is also looking for potential hazards
that may be associated with the end use products that contain
the active ingredient. The Agency will apply the provisions
of this Registration Standard to end use products if necessary
to protect man and the environment.
scientific reviews and use index are available from the
National Technical Information Service, 5285 Port Royal Road,
Springfield, Va. 22161 or from the Order Desk (703) 487-4650,
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EPA's reassessment results in the development of a
regulatory position, contained in this Registration Standard,
on the pesticide and each of its registered uses. See
Section IV - Regulatory Position and Rationale. Based on its
regulatory position, the Agency may prescribe a variety of
steps to be taken by registrants to maintain their registrations
in compliance with FIFRA. These steps may include:
1. Submission of data in support of product registration;
2. Modification of product labels;
3. Modifications to the manufacturing process of the
pesticide to reduce the levels of impurities or contaminants;
4. Restriction of the use of the pesticide to certified
applicators or other specially trained individuals;
5. Modification of uses or formulation types; or
6. Specification of packaging limitations.
Failure to comply with the data submission requirements
may result in the issuance of a Notice of Intent to Suspend.
Failure to comply with the other requirements in this Standard
may result is the issuance of a Notice of Intent to Cancel.
In addition, in cases in which hazards to man or the
environment are identified, the Agency may initiate a special
review of the pesticide in accordance with 40 CFR Part 154
to examine in depth the risks and benefits of use of the
pesticide. If the Agency determines that the risks of the
pesticide's use outweigh the benefits of use, the Agency
may propose additional regulatory actions, such as cancellation
of uses of the pesticide which have been determined to cause
unreasonable adverse effects on the environment.
EPA has authority under the Data Call-in (DCI) provisions
of FIFRA sec. 3(c)(2)(B) to require that registrants submit
data to answer our questions regarding the chemical, toxicological,
and environmental characteristics and fate of a pesticide.
This Registration Standard lists the data EPA believes are
necessary to resolve our concerns about this pesticide.
These data are listed in the Tables A, and B in Appendix I.
Failure to comply with the DCI requirements enumerated in
this Registration Standard may result in issuance by EPA of a
Notice of Intent to Suspend the affected product registrations.
Registrants are reminded that FIFRA sec. 6(a)(2) requires
them to submit factual information concerning possible unreason-
able adverse effects of a pesticide at any time that they
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become aware of such information. Registrants must notify
the Agency of any information, including interim or preliminary
results of studies, if that information suggests possible
adverse effects on man or the environment. This requirement
is independent of the specific time requirements imposed by
EPA for submission of completed studies called in by .the
Agency and continues as long as the products are registered
under FIFRA.
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II. CHEMICAL COVERED BY THIS STANDARD
A. Description of Chemical
The following chemical is covered by this Registration
Standard:
Common Name: METALAXYL
Chemical Name: N-(2,6-Dimethylphenyl)-N-(methoxyacetyl)
alanine methyl ester
CAS Number: 57837-19-1
OPP Shaughnessy Number: 113501
Year of Initial Registration: 1979
Date of Initial Registration Standard: December 1981
Empirical Formula: Ci5H2iNOA
Trade Name: Ridomil, Subdue
Description of Physical
Characteristics of Chemical:
Apron, Proturf
Metalaxyl is a white to
odorless crystal with a
bility in water (at 20
beige i
solu-
°C) of
7100 ppm, 65% in
55% in benzene.
methanol and
B. Use Profile
Type of Pesticide: Systemic fungicide
Pests Controlled:
Registered Uses:
Principal Uses;
Soil borne diseases caused by Pythium and
Phytophthpra and against foliar diseases
caused by Phycomycetes (downy mildews).
Metalaxyl is registered for use on over 100
agricultural crops (including more than 37
seed treatment uses). Metalaxyl is also
registered for ornamental and turf uses.
Some of the principal uses are: Ridomil® 2E
registered in the United States for soil use
for apples, avocados, citrus, conifers,
cotton, tobacco and tomatoes; Ridomil* 5G
for avocados and cotton; Subdue 2E for
ornamentals and turf; Apron® 25 WP and Apron®
Flowable (2.65 Ib/gal) for use as a seed
dressing on numerous crops. More than 90%
of the total poundage of metalaxyl used
domestically is used in the following 10
crops/sites: tobacco, turf, potatoes, orna-
mentals, soybean (seed treatment), onions,
citrus, cucurbits, tomatoes, and cotton.
Mode of Activity: Unknown.
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Types Registered: Single active ingredient products containing
metalaxyl are formulated as a granular (G),
pelleted/tableted (P/T) (in fertilizer
spikes)/ wettable powder (WP), emulsif-iable
concentrate (EC) and flowable liquid con-
centrate (FlC), as well as a 90% technical
product. The granular, wettable powder and
emulsifiable concentrate formulations are
also formulated as multiple active ingredient
products. In addition, metalaxyl is sold
in combination with mancozeb, chlorotha-
lonil, pentachloronitrobenzene, captan, and
triadimefon.
Methods of
'Applications: Foliar application; soil application by incor-
poration, surface spraying (broadcast or band),
drenching, sprinkler or drip irrigation; soil
mixing; trunk spraying. For agricultural seed
treatment metalaxyl is applied with conventional
slurry or mist seed treating equipment.
C. History
Metalaxyl was first registered in 1979. Ciba-Geigy Corpora-
tion, Agricultural Division, is the sole producer and principal
supplier of metalaxyl products sold in the United States.
Granular formulations, emulsifiable concentrate formulations,
and flowable liquid concentrate formulations are also distributed
by O.M. Scott and Son Company, Wilbur-Ellis, and Gustafson.
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III. AGENCY ASSESSMENT
A. Summary
This review of metalaxyl is the second intensive evaluation
of the compound. A Registration Standard was developed in 1981
in conjunction with its initial registration. At that time
metalaxyl was registered for non-food uses on tobacco, conifers,
ornamentals, and turf and was not registered for any food or feed
uses. The only additional data needed to support the registered
non-food uses in 1981 were groundwater monitoring, subchronic
inhalation toxicity, phytotoxicity and storage stability. Since
the issuance of the 1981 Registration Standard, registrations
have been approved for use on over 100 agricultural crops. These
registrations were granted based on adequate supporting data
(including residue, acute and chronic data) at the time of
application for registration.
In 1984, the Agency promulgated general rules at 40 CFR Part
158, which set forth the range of data which must be submitted to
EPA to support the registration or reregistration of each pesticide
under FIFRA. Based on these revised and expanded data requirements,
the toxicity data base for metalaxyl is still virtually complete -
and in most cases is adequate to support continued registration
of existing uses. However, some data determined to support
registration in the past only partially fullfill current data
requirements. As a result, several studies primarily in the
disciplines of residue chemistry and environmental fate, must be
conducted and submitted to the Agency. In addition, several new
data requirements are being imposed to characterize potential
adverse effects to marine/estuarine species. A more detailed
discussion is contained in the remainder of this Chapter.
o Metalaxyl has moderate acute oral and dermal toxicity
(toxicity category III), is slightly irritating to the
eye (toxicity category II), and is a mild dermal irritant
(toxicity category IV). Metalaxyl does not cause
dermal sensitization. There is no information on its
acute inhalation toxicity; these data are required.
o Data from rat and mouse long-term studies are sufficient
to indicate that metalaxyl did not show an oncogenic poten-
tial in those animals even though the Maximum Tolerated
Dose (MTD) was not tested.
o The teratology study indicated no teratogenic effects or
embryotoxicity in any of the treated groups of rats.
Metalaxyl also did not cause embryotoxic, fetotoxic, or
teratogenic effects in treated rabbits.
o In a multigeneration reproduction study with rats, no dose-
related effects were observed throughout the three gener-
ations with respect to toxicity or reproductive parameters.
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o Metalaxyl did not induce gene mutations in bacteria, yeast
and mouse lymphoma cells in vitro with or without metabolic
activation. The fungicide also caused no structural or
numerical chromosomal aberrations in tests with yeast,
hamsters, and mice.
o Metabolism studies in rats indicated that single oral
doses of metalaxyl are readily absorbed. Approximately
65% of the administered radioactivity is recovered in the
urine and feces within 24 hours after dosing, and 96% is
recovered during the 48 hours after dosing.
o Metalaxyl was found to be practically non-toxic acutely
and subacutely to avian species and to present no adverse
effects to avian and mammalian populations.
t
o Because metalaxyl may affect marine/estuarine species
such as oysters and shrimp, the Agency is requesting
additional data.
o Metalaxyl does not present a hazard to endangered
terrestrial or aquatic animal species, or plant species.
o Metalaxyl was found to be moderately stable (to hydrol-
ysis) under normal environmental conditions. The rota-
tional crop data demonstrated the need for a 12-month ro-
tational crop restriction because some crops will take up
metalaxyl residues of concern when planted 12 months or
more after treatment of a prior crop.
o Previously submitted ground water monitoring studies in-
dicated that some parent residues of metalaxyl reached
ground water, but these studies were found to be inade-
quate and inconclusive. The laboratory adsorption/de-
sorption studies indicated that the parent compound can
readily leach in sand, silt loam and sandy clay loam
soils. Additional monitoring studies are being required.
• Based on the current requirements the following data are
now required to support the continued registration of metalaxyl:*
40CFR§158.120 - Product Chemistry
o Description of Beginning Materials and
Manufacturing Process
o Discussion of Formation of Impurities
o Preliminary Analysis
o Certification of Ingredient Limits
o Analytical Methods to Verify Certified Limits
* Note that this is only a summary and complete details can be
obtained by referring to the tables in Appendix I.
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40CFRS158.125 - Residue Chemistry
o Nature of the Residue in Livestock
o Residue Analytical Method
o Storage Stability Data
o Magnitude of the Residue (potatoes; sugar beet
roots; soybeans; cereal grains; forage, fodder
and straw of cereal grains; cottonseed; hops;
peanuts; pineapples; sunflower seed)
40CFRS158.130 - Environmental Fate
o Photodegradation Studies in Water
o Terrestrial Field Dissipation Studies
o Confined Accumulation Studies on Rotational
Crops
o Ground Water Monitoring and Laboratory Leaching
Studies
40CFRS158.135 - Toxicology
o Acute Inhalation Toxicity
o Metabolism Studies
40CFRS158.145 - Ecological Effects
o Acute LCso Estuarine/Marine Organisms
(shrimp and oyster)
B- Risk Assessment
The Agency has conducted a thorough review of the scientific
data base for metalaxyl. The conclusions and requirements
imposed as a result of this review and evaluation are summarized
in Section IH-A. A discussion of the results of the review of
the data base is presented below.
1. Acute Toxicity
Adequate data are available to determine the acute toxicity
of metalaxyl. Technical metalaxyl is classified in Toxicity
Category II based on eye irritation. Metalaxyl has a moderate
acute oral and dermal toxicity (toxicity category III) and is a
mild dermal irritant (toxicity category IV). However, metalaxyl
does not cause dermal sensitization.
The acute oral LDsg for rats is 669 mg/kg, for mice is 788
mg/kg, and for hamsters is 7120 mg/kg. The acute dermal LDso
for rabbits is greater than 6000 mg/kg with the acute dermal
in rats greater than 3170 mg/kg.
8
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No additional acute oral and dermal toxicity studies are
required. A study on the acute inhalation toxicity of technical
grade metalaxyl is required if the technical grade material is in
a respirable form.
A primary eye irritation study in rabbits indicated that
metalaxyl is a moderate eye irritant. Corneal opacity cleared
after 3 days following treatment, and no other signs of irritation
were observed. No additional eye irritation studies are required.
Studies indicate that technical grade metalaxyl is a slight
irritant when applied to the skin of rabbits. However, no addi-
tional skin irritation studies are required.
No sensitization reactions were observed in guinea pigs
treated with metalaxyl. Consequently, no additional dermal
sensitization studies are required.
2. Subchronic Toxicity
a. Subchronic Feeding
1) Rats
Metalaxyl was fed to groups of male and female rats at doses
of 0, 50, 250, or 1250 ppm for 90 days. Observed effects included
minimal hepatocellular hypertrophy in 25% of the female rats at
the highest dose level. No other treatment related changes were
observed, and the NOEL was 250 ppm (12.5 mg/kg/day).
2) Mice
Four groups, each consisting of 85 male and female weanling
CFLP (ICI Strain 1 origin) mice, were fed diets of metalaxyl
containing 0, 1250, 2500, or 5000 ppm. Subsequently, some of the
test animals were given control diets for an additional 30 days
in a recovery phase of the experiment. There were minimal liver
effects at the 2500 and 5000 ppm levels in males. Effects observed
after 3 months of treatment included changes in glycogen content,
fatty vacuolization, and hypertrophy of hepatocytes. Liver
weights were elevated in all treated animals after 90 days on the
test diets, but no histopathological effects were reported in
livers of females or in low-dose group males. Absolute liver
weights for test groups in the recovery phase of the study were
comparable with those of the control group at termination. The
NOEL in this study was < 1250 ppm (187.5 mg/kg/day) with an LOEL
of 1250 ppm.
3) Dogs
Technical metalaxyl was administered to groups of male and
female beagle dogs at dietary concentrations of 0, 50, 250, or
1250 ppm for 91 days. No mortality or treatment-related changes
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in animal behavior, hematology, clinical chemistry, urine analysis,
or gross and microscopic observations were noted. The NOEL is
greater than 1250 ppm. This study is classified as Supplementary
and a new 3-month study is not required because an acceptable
6-month dog study is available.
No additional subchronic oral studies are required.
b. Subchronic Dermal
In a 21-day dermal toxicity study, metalaxyl was applied to
shaved intact or abraded skin of rabbits under impervious bindings.
The dosages tested were 0, 10, 100, or 1000 mg/kg/day. Only one
animal died during the study. There were no significant differ-
ences between the control group and treatment groups with respect
to food consumption, body weight, hematology, clinical chemistry,
organ weights, and organ to body weight ratios. There were also
no effects observed at necropsy either macro- or microscopically.
The NOEL is greater than 1000 mg/kg/day (HOT). No additional
subchronic dermal studies are required.
c. Subchronic Inhalation
A 90-day smoke inhalation study is required if pesticide
residues in the smoke of treated tobacco are greater than
0.1 ppm.
In a preliminary study, groups of male and female rats were
exposed to the smoke from 16 cigarettes per day. Three of the
groups were exposed to smoke from tobacco spiked with 130, 3900,
and 13,000 ppm metalaxyl (by weight), and the fourth group was
exposed to untreated smoke for 28 days. There were no signifi-
cant differences between treated and control groups with respect
to toxic signs, hematology, body weight, organ weight or organ-
to-body weight ratios, and gross pathology observations. These
results indicated that a NOEL for exposure of rats to metalaxyl-
spiked tobacco smoke was greater than 13,000 ppm (HOT).
In a second study, groups of male and female rats were exposed
to smoke from standard cigarettes spiked with 0, 130, 3900, or
13,000 ppm metalaxyl for 90 days. Exposures were approximately
4 hours per day, 5 days per week for 13 weeks, and the animals
were exposed to the smoke of 18 cigarettes during each 252 minute
exposure. A few animals exhibited eye irritation, but no effects
could be associated with the addition of metalaxyl to the ciga-
rettes' tobacco. The highest concentration of metalaxyl reported
in the air during exposure was 5 ug/L, and the NOEL in this study
is greater than that level (HOT). No additional subchronic inha-
lation toxicity studies are required.
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3. Chronic Feeding/Oncogenicity Studies
a. Chronic Feeding
1) Rats
Groups of male and female Sprague-Dawley rats were fed diets
containing 0, 50, 250, or 1250 ppm metalaxyl for 2 years. No
effects were noted with respect to toxic signs, mortality, body
weight, food consumption, ophthalmologic examination, hematology,
urinalysis or the incidence of palpable masses.
The only effects on clinical chemistry parameters included
decreased SCOT and SGPT values at weeks 12, 25, and 51 of the
2-year feeding period in treated females. At 78 weeks of treat-
ment there was an increase in SCOT and SGPT values in females
receiving the 250 and 1250 ppm diets, and after 104 weeks of
treatment SCOT values were comparable for treated and control
groups of both sexes. Relative liver weight was increased in
females fed 1250 ppm at 55 weeks, and in males fed 250 or 1250
ppm at 105 weeks. Females fed 1250 ppm also had increased
relative liver weights at 105 weeks.
The changes in SCOT and SGPT are not toxicologically signif-
icant in view of the minor microscopic changes (periacinar vacuo-
lation of hepatocytes) and increase in relative liver weights
without a concurrent increase in absolute liver weights observed
at the highest dietary level tested. However, the NOEL estab-
lished in this study is 250 ppm (12.5 mg/kg/day), and the LOEL
is 1250 ppm (62.5 mg/kg/day) for rats treated for 2 years.
2) Dogs
Technical metalaxyl was fed to groups of six male and six
female beagle dogs at dietary levels of 50 or 250 ppm for 6
months. Two additional diets containing 0 or 1000 ppm were fed
to groups containing eight animals of each sex for the same
period, and two dogs 'of each sex from those two groups were given
the 0 ppm diet for an additional 30 days (recovery phase).
There were no mortalities or signs of toxicity observed in
the experiment, and no gross or microscopic lesions were observed
to occur in a dose- or treatment-related manner. There were also
no effects on hematology, urinalysis, or opthalmological parameters.
Increased alkaline phosphatase, observed in animals given the 1000
ppm diet, was the only biochemical change noted. In addition, the
absolute liver weights and brain/ liver weight ratios for dogs
given the highest dose level were increased. Based on these
results the LOEL was established at 1000 ppm (25 mg/kg/day), and
the NOEL was 250 ppm (6.25 mg/kg/day).
At the time this study was submitted a 6-month dog study
satisfied Agency requirements for a long-term nonrodent study.
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Although the Agency now requires a 12-month dog study, the Agency
is accepting the submitted study to satisfy this requirement for
metalaxyl. No additional chronic feeding studies in rodent and
nonrodent species are required.
b. Oncogenicity Studies
1) Rats
In the 2-year study with rats described in the preceding sec-
tion, no tumors were observed to be increased by treatment with
metalaxyl, but the minimal nature of the compound related effects
(increased relative liver weights and periacinar vacuolation of
hepatocytes) suggests that an MTD was not achieved in this study.
However, this study is considered acceptable for a rat oncogenicity
study.
2) Mice
Diets containing 0, 50, 250, or 1250 ppm metalaxyl were given
to groups of male and female Swiss mice for 104 weeks. There
were no compound-related signs of toxicity observed in the study,
and mice given the highest dose level exhibited only slight
temporary reductions in body weight gain with mean body weights
less than 10 percent below those for control group animals. There
were no dose-related incidences of neoplastic or non-neoplastic
lesions observed in the study, with the exception of fatty infil-
tration of the liver. Results of this study are similar to those
of the rat study in that they indicated no MTD was achieved. How-
ever this study is considered acceptable for a mouse oncogenicity
study.
Although the Agency concluded that neither of the long-term
studies evaluated an MTD, the two studies are sufficient to
indicate that metalaxyl did not show an oncogenic potential in
rats and mice for the following reasons.
o Doses tested in the rat and mouse studies were high enough
to produce compound-related changes in liver weight and/
or histology, probably representing a pharmacologic
response.
o Metalaxyl is not structurally related to known carcinogens.
o Available mutagenicity studies indicated no potential
genotoxic activity which is consistent with the negative
oncogenic potential demonstrated in long-term testing.
o Under the conditions of the long-term feeding studies
in rats and mice, there was no indication of oncogeni-
city in either species or sex, at any dose level tested.
No additional oncogenicity studies with metalaxyl in rats
and mice are required.
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4. Teratology
1) Rats
A study in rats evaluated doses of 0, 20, 60, and 120 mg/kg/
day. The doses were administered to groups of pregnant rats on
gestation days 6 through 15. There were no teratogenic effects
noted in the study, and the HOT did not clearly cause maternal
toxicity. There were no corpora lutea counts reported and groups
of animals were sacrificed on different days of gestation at the
end of the experiment which limited the ability of the study to
detect developmental toxicity. NOELs for maternal and develop-
mental toxicity could not be established in this study, and
another study with rats was conducted.
In the second study, groups of pregnant rats were given
metalaxyl in daily doses of 0, 50, 250, or 400 mg/kg/body weight
on gestation days 6 through 15. Doses were administered by
gavage. Maternal toxicity was observed in dams given the 250 and
400 mg/kg/day doses as indicated by convulsions and ataxia during
the treatment period. Fetotoxicity was indicated by an increase
in the incidence of unossified sternebrae in fetuses from the two
highest dosed groups; no teratogenicity or embryotoxicity was
observed in any of the treated groups. Based on these results
NOELs for maternal and developmental toxicity were established at
50 mg/kg/day, and LOELs for both types of toxicity were established
at 250 mg/kg/day. The adult-to-developmental toxicity ratio
(A/D ratio; ratio of the adult toxicity NOEL to fetal toxicity
NOEL) is eaual to one.
2) Rabbits
Metalaxyl was given to groups of pregnant rabbits on gestation
days 6 through 18. Doses of 0, 5, 10, or 20 mg/kg/day were admin-
istered by oral intubation. No maternal or fetal"effects associ-
ated with treatment were observed in the study. On that basis,
the study could not be used to fully assess the potential develop-
mental toxicity of metalaxyl in rabbits, and the study was repeated.
The range-finding study preceding the second definitive experi-
ment with rabbits was conducted with doses of 0, 30, 100, 250, 500,
and 1000 mg/kg/day. These doses were administered by gavage on
gestation days 6 through 18 to groups of Dutch belted rabbits.
The HOT caused 100 percent mortality (5 of the 5 treated does),
and the 500 mg/kg/day dose caused decreased group mean body weight
(7.4% below that for control animals). Based on these results,
the highest dose selected for the main study was 300 mg/kg/day.
The second definitive study evaluated metalaxyl at doses of
0, 30, 150, and 300 mg/kg/day administered to groups of pregnant
rabbits on gestation days 6 through 18. Slight maternal toxicity
was noted at 300 mg/kg/day as shown by a small decrease in body
weight (2.3%) during the 13-day treatment period. There were no
embryotoxic, fetotoxic, or teratogenic effects associated with
13
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treatment in this experiment. Based on these results and those
from the range-finding study, the NOEL for maternal toxicity was
300 to 500 mg/kg/day, and that for developmental toxicity was
greater than 300 mg/kg/day (HDT in the main study). The A/D
ratio suggested by these results is less than one.
No additional teratology studies in rats or rabbits are
required.
5* Reproductive Toxicity Study
In a multigeneration reproduction study, four groups of rats
were given diets containing 0, 50, 250, or 1250 ppm metalaxyl.
No dose-related effects were observed throughout the three genera-
tions with respect to signs of toxicity, mortality, body weights,
food and water consumption, mating, fertility, duration of gesta-
tion, or necropsy findings. In addition, there were no effects
on pre- and post-implantation losses, litter size, mean litter and
fetal weights, or the incidence of fetal variations and malforma-
tions in the teratology phase of the study. The NOEL for repro-
duction and developmental toxicity is greater than 1250 ppm based
on these observations.
No additional reproduction toxicity studies are required. -
6* Mutagenicity Studies
a. Gene Mutation
Three studies were conducted in Salmonella typhimurium and one
study in Escherichia cqli at concentrations rangingfrom 10 to
5000 ug metalaxyl per plate with or without metabolic activation.
No mutagenic activity was observed in these assays.
Two assays in Saccharomyce_s cerevisiae were conducted with
concentrations of 40 to 10,000 ug/mL, and no increase in the
frequency of gene mutations for treated yeast cultures was ob-
served. However, no response to the positive control substance,
absence of toxicity in metalaxyl treated cultures, and low solu-
bility of the test substance in growth medium suggested that the
sensitivity of these assays was limited.
An assay in vitro with mouse lymphoma cells also found no in-
creases in gene mutations in treated cells at concentrations
ranging from 0.125 to 1.0 mg/mL without metabolic activation or
0.0625 to 0.5 mg/mL with metabolic activation.
«
b. Structural and Numerical Chromosomal Aberrations
The two yeast assays described above indicated that metalaxyl
did not induce mitotic gene conversion or recombination at the
concentrations tested, but those assays are considered limited
with respect to their sensitivity. A third assay in S_. cerevisiae
also suggests that metalaxyl did not induce nondisjunction. The
14
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third study also has the same limitations mentioned above for the
other two assays.
In an in vitro assay with Chinese hamster ovary cells exposed
to concentrations of metalaxyl ranging from 150 to 1200 ug/mL, an
increase in the number of cells with chromosomal aberrations was
observed at the HOT without liver microsomal enzyme activation
of the test substance. There was no increase in the frequency
of cells with chromosomal aberrations when metalaxyl was added
to cultures after being treated with liver microsomal enzymes.
However, the results are inconclusive because there is not enough
enough information in the report to indicate whether metalaxyl is
detoxified by the microsomal enzymes or the exposure period in
that portion of the assay (2 hours) is too short in comparison to
that of the other phase of the experiment (17.5 hours).
t
Two in vivo assays were conducted with hamsters and mice. In
the first experiment, males and females were administered metalaxyl
in two consecutive daily oral doses of 0, 595, 1190, or 2380 mg/kg/
body weight (bwt). These doses did not increase the incidence of
bone marrow cells with nuclear anomalies (single Jolly bodies,
fragments or nuclei in erythrocytes, micronuclei in erythroblasts,
micronuclei in leucopoietic cells, and polyploid cells). The
second assay was a dominant lethal study in which no genetic
effects were observed after administration of single oral doses
of 0, 65, or 195 mg/kg/bwt metalaxyl to male mice. Acute oral
toxicity studies in hamsters and mice suggest that the doses
tested in the genetic toxicity assays were approximately 1/3 of
the LD5Q value for hamsters and mice.
c. DNA Damage
Metalaxyl did not cause DNA damage in Bacillus subtil is (Rec
assay) at levels from 20 to 5000 ug/disk, and the fungicide did
not induce unscheduled DNA synthesis in rat primary hepatocytes
at concentrations of 0 to 2000 ug/mL in two other experiments or
in human fibroblasts at concentrations of 0 to 500 ug/mL.
No additional data are necessary on any of the three required
mutagenicity studies: gene mutation; structural and chromosomal
aberrations, and DNA damage.
7. Metabolism in Rats
Available metabolism studies in rats more than adequately
characterize the absorption and excretion of metalaxyl in male
and female rats at low- and high-dose levels, as well as clearly
describe the metabolism of the fungicide in female rats for single
dose administration. However, an additional study to characterize
the absorption, distribution, and excretion of metalaxyl after
repeated dosing is needed.
There were three metabolism studies in rats available for
review.
15
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In the first study, groups of male and female rats were given
single doses of 0.5 or 25 mg/kg radiolabeled metalaxyl (orally by
gavage). Urine, feces, and expired air were sampled at 24-hour
intervals for 6 days following dosing. At the end of that time
the animals were sacrificed and tissue samples were collected.
During the first 24 hours after dosing with either the high
or low doses, male and female rats excreted 62 to 65 percent of
the administered radioactivity. Over the 6-day observation
period the majority of the excreted radioactivity in males was
recovered from the feces (63 to 66% of the administered dose),
while the majority of residues in females was found in the urine
(55 to 63% of the dose). Although no metabolites were identified
in this study, their chromatographic patterns did not appear to
vary with dose or sex, and the tissue distribution observed 6 days
after dosing did not indicate that metalaxyl residues were stored
in tissues.
The second and third studies indicated that metalaxyl is
readily absorbed by females after a single 28 mg/kg oral dose.
The second study showed that nearly all of the administered
radioactivity (96.3%) was excreted in the urine and feces duriag
the 48 hours following treatment. The majority (63.5% of the.
dose) was recovered in the urine which was used in identification
of metabolites; approximately 20 percent of the residues were
identified by chromatographic and spectroscopic methods. Those
results indicated that ether and ester bonds of metalaxyl [N-(2,
6-dimethylphenyl)-N-(methoxyacetyl)-alanine methyl ester] are
hydrolyzed first to form N-(2,6-dimethylphenyl)-N-(methoxyacetyl)
alanine, N-(2,6-dimethylphenyl)-hydroxyacetamide, and N-(2,6-
dimethylphenyl)-hydroxyacetamide (only in free form). Thin layer
chromatography of urine fractions treated with glucuronidase
showed similar patterns to those for urine not treated with the
enzyme indicating that the metabolites are excreted as uncon-
jugated or glucuronide conjugate products. The fecal metabolites
were not characterized in this study beyond comparison of chroma-
tograms for urine and feces.
Similar results were obtained in the third study which also
indicated that metalaxyl is metabolized in rats first by hydro-
lysis of the ester and ether bonds, by oxidation of methyl groups
of the phenyl moiety, and oxidation of the phenyl moiety itself.
Secondary metabolic pathways led to the formation of products
such as N-(2carboxy-6-methylphenyl)-N-(methoxyacetyl)-alanine
methyl ester and 4-(2,6-dimethylphenyl)-3-morpholine-2,5-dione
isomeric lactone form of the N-(2,6-dimethylphenyl)-N-(hydroxy-
acetyl) alanine as well as glucuronic acid conjugates of these
products. Approximately 38 percent of the administered radio-
label was unidentified.
16
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8. Dermal Absorption Studies
Male and female rats received dermal applications of 1 or
10 mg/kg/bwt metalaxyl dissolved in tetrahydrofuran (THF).
During the first 8 hours after treatment, approximately 30
percent of the dose was absorbed. Only 1 percent of the applied
test substance was in the skin of the application site. Based
on radioassay of skin washings, the absorption T]_/2 values for
males receiving the low and high doses were 12 and 20 hours,
respectively, while those for females were 13 hours for both
doses. Residues were cleared from tissues by 72 hours following
dosing with 70 to 80 percent of the applied radioactivity being
excreted during that time. The major route of excretion in
females was the urine, and that for males was the feces. The
Tl/2 for excretion in males was 36 hours at the low dose and
49'hours at the high dose level, and those respective values for
females were 42 and 44 hours for low and high-dose groups.
No additional studies on dermal absorption are required.
C. Other Science Findings
1. Ecological Effects
Metalaxyl has been found to be practically nontoxic acutely
and subacutely to avian species and to present no potential for
adverse effects to avian and mammalian populations. Phytotoxicity
studies on green alga and duckweed indicate no detrimental effect
on aquatic plant species. The available data demonstrate that
the technical pesticide is practically nontoxic to freshwater
aquatic species while one formulated product, Ridomil 27.9% ai EC,
is slightly toxic. This toxicity may be due to the inherent
toxicity of the inerts in the formulation or a synergistic effect
making the active ingredient more available. The most sensitive
organism appears to be Daphnia magna having LC5QS of 28 and 12.5
ppm on technical and formulated products, respectively.
Chronic toxicity assays on aquatic species and fish accumula-
tion testing do not suggest that metalaxyl presents a long-term
risk in the aquatic environment (acute testing on marine fish is
waived because the LC$Q on freshwater fish is >100 ppm). It
appears very unlikely that metalaxyl could accumulate in water or
sediments to concentrations that would pose a risk to aquatic
populations (primarily due to the low toxicity of the pesticide).
Even though it is apparent that the use of metalaxyl presents
little risk to freshwater populations, it cannot be assumed that
the same holds true for marine/estuarine species such as oysters
and shrimp. Several of the registered uses (citrus, cotton,
etc.) of the pesticide may result in exposure to marine/estuarine
environments. Data on oysters and shrimp are required.
17
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2. Endangered Species
The registered uses of technical metalaxyl and a widely used
formulation, Ridomil® 27.9% ai EC (which appears more toxic to
aquatic organisms than the technical) do not present a hazard to
endangered terrestrial or aquatic animal species, or plant species.
This is primarily due to metalaxyl's very low toxicity to fish and
wildlife. Data from phytotoxicity studies on Lemma gibba and
Selena strum c a. pr i c o r n u t u m indicate no detrimental effect to aquatic
plant species from technical metalaxyl. The EECs resulting from
currently registered uses are considerably below the LC$Q of the
most sensitive species tested. At this time the threatened/en-
dangered species triggers have not been exceeded (EEC greater than
1/20 of the LCso for aquatic or 1/10 the LC^Q for terrestrial
species).
i
3. Environmental Fate
Metalaxyl was found to be moderately stable under normal envi-
ronmental conditions. At 20°C the calculated half-life was 200
days at pH 5 and 7, and was 115 days at pH 9. Studies also
indicated that metalaxyl was stable to photodegradation on soil.
Test results indicated no difference between the irradiated sample
and the control sample. The aerobic soil metabolism half-life was
determined to be about 40 days. While other experiments demons-
trated that less than 0.5 percent of the applied metalaxyl would
be lost to volatilization, field dissipation studies showed that
metalaxyl's half-life was about 2 weeks.
Fish accumulation was found not to exceed 7X when fish were
exposed to metalaxyl at 1 ppm in water, and residues were found
to accumulate in the nonedible portions over the edible portions
in a ratio range of 4:1 to 15:1. Residues declined rapidly during
depuration. In addition, a separate fish accumulation study using
catfish showed accumulation of IX and rapid depuration.
The rotational crop data demonstrated the need for a 12-month
rotational crop restriction because some crops will take up
metalaxyl residues of concern when planted 12 months or more after
treatment of a prior crop. Confined studies are needed to identify
all residues of concern plus field tests to determine the need
for additional inadvertent tolerances.
Ground water monitoring studies were determined to be inade-
quate. The results from a Florida test site do not address the
issue of metalaxyl leaching to shallow first-encountered aquifers,
but rather the possibility of leaching to deep aquifers at >200
feet. Of the 67 samples extracted, two showed positive results:
3.1 and 4.7 ppb. In addition, on test sites located in North
Carolina and Oregon, two years of approximately monthly samples
from three wells at each location showed no positive results,
supporting the hypothesis that metalaxyl may not be traversing
off-site at these locations. However, wells were inadequately
18
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described, and water table depths described at 40 to 140 feet in
Oregon are at the far end of the definition of "shallow" water
tables.
Surface water monitoring in the Sacramento River, California,
showed seasonal concentrations of metalaxyl in two of the three
years of bi-monthly sampling. Seasonal, in this context, refers
to spring, summer and fall when runoff typically transports
residues of pesticide from the treated field to the surface water.
In one year, 61% of seasonal samples were positive with a range
of 0.97 to 3.5 ppb, while in the other year of positive results,
50% of seasonal samples showed positive, with a range of 0.25 to
0.43 ppb. Samples from tap water obtained from the Sacramento
River showed no positive residues in three years of sampling.
In conclusion, surface and ground water monitoring results from
these studies were considered inconclusive and additional moni-
toring data are required.
D• Tolerance Reassessment
Tolerances have been published in 40 CFR 180.408 for residues
of metalaxyl on the following raw agricultural commodities (RACS):
apples, avocados, beets, beet tops, brassica (cole) leafy vege- -
tables group [except broccoli, cabbage, and cauliflower], broccoli,
cabbage, cattle fat, cattle kidney, cattle meat, cattle meat
byproducts (except kidney and liver), cauliflower, citrus fruit,
cottonseed, cucurbit vegetables group, eggs, fruiting vegetables
(except cucurbits) group [except tomatoes], goat fat, goat kidney,
goat liver, goat meat, goat meat byproducts (except kidney and
liver), grain crops, grass forage, hog fat, hog kidney, hog
liver, hogs meat, hog meat byproducts (except kidney and liver),
hops green, horse fat, horse kidney, horse liver, horse meat,
horses meat byproducts (except kidney and liver), leafy vegetables
(except brassica) group, legume vegetable foliage, legume vegetable
group (dry or succulent), lettuce head, milk, onions (dry bulb),
onions (green), peanut hay, peanut vines, peanut nuts, peanut
shells, pineapples, pineapple fodder, pineapple forage, poultry
fat, poultry kidney, poultry liver, poultry meat, poultry meat
byproducts (except kidney and liver), potatoes, raspberries,
sheep fat, sheep kidney, sheep liver, sheep meat, sheep meat
byproducts, soybean grain, spinach, sunflowers, sunflower forage,
and tomatoes.
In addition, tolerances are established for indirect or inad-
vertant residues of metalaxyl in or on the following RACs when
present as a result of the application of metalaxyl to growing
crops: wheat, fodder; wheat, forage; wheat, grain; wheat, straw;
and, wheat, milling fraction.
Tolerances have also been published in 21 CFR 193.277 permit-
ting the combined residues of the fungicide metalaxyl [N-(2,6-
dimethylphenyl)-N-(methoxyacetyl) alanine methyl ester] and its
metabolites containing the 2,6-dimethylaniline moiety, and
N-(2-hydroxy methyl-6-methyl)-N-methoxyacetyl)-alanine methyl
19
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ester, each expressed as metalaxyl, in or on the following food
commodities: citrus, oil; potatoes, processed (including potato
chips); and tomatoes, processed.
There are also indirect or inadvertant tolerances for those
residues of metalaxyl in the food commodities when present therein
as a result of the application of metalaxyl to growing crops
listed in 40 CFR 180.408(a).
A regulation is also established under 21 CFR 561.273
permitting the combined residues of the fungicide metalaxyl in
the following feed commodities: apple, pomace (dry); apple,
pomace (wet); citrus, molasses; citrus, pulp; hops, dry; legume
vegetable, cannery waste; peanut, meal; peanut, soapstock;
potato waste, dried processed; soybean, hulls; soybean, meal;
soybean soapstock; tomato pomace, dry; and tomato pomace, wet.
In addition, indirect or inadvertant tolerances are established
for indirect residues of metalaxyl in the food commodities when
present therein as a result of the application of metalaxyl to
growing crops listed in 40 CFR 180.408(a).
There are no Codex tolerances for metalaxyl. EPA has eval-
uated the following residue and toxicology data supporting the .
tolerances:
1. A 3-month dietary study in rats with a NOEL at 12.5
mg/kg bwt/day (250 ppm).
2. A teratology study in rats with a NOEL to 400 mg/kg bwt
(HOT). Metalaxyl was not teratogenic, even in the
presence of maternal toxicity.
3. A teratology study in rabbits with a NOEL of 300 mg/kg
bwt (HOT). Metalaxyl was not teratogenic, even in the
presence of maternal toxicity.
4. A Salmonella mutagenicity study that was negative for
reverse mutations with and without mammalian microsome
activation.
5. A mouse dominant lethal study that was negative for
rautagenicity.
6. A 3-generation rat reproduction study with a NOEL of
62.5 mg/kg bwt/day (1250 ppm).
7. A 6-month dog feeding study with a NOEL of 6.3 mg/kg
bwt (250 ppm).
8. A 2-year rat chronic feeding/oncogenicity study with no
compound-related oncogenic effects under the conditions
of the study at dietary levels up to 1250 ppm. The NOEL
is 12.5 mg/kg bwt/day (250 ppm) based upon slight in-
creases in liver weight to body weight ratios at 1250 ppm.
20
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9. A 2-year mouse oncogenicity study with no compound-related
oncogenic effects under the conditions of the study at
dietary levels up to 1250 ppm.
The ADI, based on the 6-month dog feeding study (NOEL of 6.3
mg/kg bwt/day) and a hundredfold safety factor, is calculated to
be 0.063 mg/kg/day. The MPI for a 60kg human is calculated to
be 3.8 mg/day.
The nature of the residue in plants is adequately understood
and analytical methodology is available in the Pesticide Analytical
Manual II (PAM II) for enforcement purposes. The PAM II method
involves gas-liquid chromatography (GLC) with alkali flame ioniza-
tion detection (AFID), and with mass spectrometry for samples that
sh6w interference in the GLC/AFID. A newer analytical method which
involves capillary gas chromatography using a nitrogen/ phosphorus
detector operating in the nitrogen-specific mode will be included
in PAM II.
21
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IV. REGULATORY POSITION AND RATIONALE
A. Regulatory Positions and Rationales
This review of metalaxyl is the second intensive evaluation
of the compound. A Registration Standard was developed in 1981
in conjunction with its initial registration. At that time
metalaxyl was registered for non-food uses on tobacco, conifers,
ornamentals, and turf and was not registered for any food or feed
uses. The only additional data needed to support the registered
non-food uses in 1981 were groundwater monitoring, subchronic
inhalation toxicity, phytotoxicity and storage stability. Since
the issuance of the 1981 Registration Standard, registrations
have been approved for use on over 100 agricultural crops. These
registrations were granted based on adequate supporting data
(including residue, acute and chronic data) at the time of
application for registration.
In 1984, the Agency promulgated general rules at 40 CFR Part
158, which set forth the range of data which must be submitted to
EPA to support the registration or reregistration of each pesticide
under FIFRA. Based on these revised and expanded data requirements,
the toxicity data base for metalaxyl is still virtually complete ~
and in most cases is adequate to support continued registration
of existing uses. However, some data determined to support
registration in the past only partially fullfill current data
requirements. As a result, several studies primarily in the
disciplines of residue chemistry and environmental fate, must be
conducted and submitted to the Agency. In addition, several new
data requirements are being imposed to characterize potential
adverse effects to marine/estuarine species. A more detailed
discussion is contained in the remainder of this Chapter.
(1) None of the risk criteria listed in 40 CFR 154.7 prescri-
bing a Special Review have been met. Therefore, metalaxyl is not
being placed in Special Review at this time.
Rationale; After consideration of available toxicology data,
the Agency has determined that no reason exists for placement of
metalaxyl in Special Review at this time.
The original reviews of a chronic rat and a mouse oncogenicity
study indicated apparent dose-related oncogenic effects by meta-
laxyl. While this gave rise to regulatory concern, subsequent
reevaluation of the histopathology and other aspects of the study
led the Agency to conclude that the results of these studies were
negative, even though the MTD may not have been tested. Further
testing is not warranted because the doses tested were high enough
to produce toxicity in the liver. Metalaxyl is not structurally
related to known oncogens and available mutagenicity studies
indicate no potential genotoxic activity. Adequate evidence thus
provides no basis for further concern over the oncogenicity of
metalaxyl.
22
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(2) The Agency is requesting rotational crop studies and,
in order to meet the statutory standard for continued registra-
tion, product labeling must bear a 12-month rotational crop
restriction as an interim measure.
Rationale; Available rotational crop studies indicate that
some crops will take up metalaxyl residues of concern when planted
12 months or more after treatment of a prior crop. Confined
studies are needed to identify all residues of concern plus field
tests are necessary to determine the need for additional inadver-
tent tolerances. As an interim measure, a 12-month rotational
crop interval is be required for all crops for which tolerances
have not been established.
(3) Additional ground water monitoring and laboratory
leaching studies are being required.
Rationale; The Agency determined that data submitted on
ground water monitoring are inadequate to determine leaching
potential. The results of submitted monitoring data indicate
that some parent residues reached ground water. Laboratory
adsorption/desorption studies indicate that parent compound can
readily leach in sand, silt loam and sandy clay loam soils. In-
a laboratory column leaching study, parent metalaxyl plus its.
degradates leached in sand and silt loam soils. Also, both
parent and degradates were shown to be sufficiently persistent
in laboratory studies to have potential to reach ground water.
Existing data, however, are inadequate to conclude whether
metalaxyl has the potential to reach groundwater. Therefore,
new monitoring studies and laboratory leaching studies that
conform to current testing standards are needed.
(4) Ground water monitoring data will receive immediate
review when submitted.
Rationale; Because of the potential for metalaxyl to reach
ground water, it is essential that these data be reviewed as they
are received. This will allow the Agency to determine whether
regulatory action is warranted based on this concern.
(5) The Agency is requiring further data on potential adverse
effects to marine/estuarine species.
Rationale; Based on available toxicity studies, no adverse
effects to either endangered or nonendangered avian, mammalian,
or freshwater aquatic animal species are expected from currently
registered uses of metalaxyl. However, further testing is
required on marine/estuarine species to determine if currently
registered uses will result in exposure levels of concern to
these populations.
23
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(6) While data gaps are being filled, currently registered
manufacturing-use products (MP's) and end-use products (EP's)
containing metalaxyl as the sole active ingredient may be sold,
distributed, formulated, and used, subject to the terms and
conditions specified in this Standard. Registrants must provide
or agree to develop additional data, as specified in the Data
Appendices, in order to maintain existing registrations.
Rationale; Under FIFRA, the Agency may elect not to cancel
or withhold registration even though data are missing or are
inadequate (see FIFRA section 3(c)(2)(B) and 3(c)(7)). Issuance
of this Standard provides a mechanism for identifying data needs.
These data will be reviewed and evaluated, after which the Agency
will determine if additional regulatory actions are necessary.
The Agency wll consider registration of any significant new use
on a* case-by-case basis while data gaps are being filled and data
evaluated.
B. Criteria for Registration
To be registered or reregistered under this Standard, products
must contain metalaxyl as the sole active ingredient, bear required
labeling, and conform to the product composition, acute toxicity ~
limits, and use pattern requirements listed in this section.
C. Acceptable Ranges and Limits
1. Product Composition Standard
To be registered or reregistered under this Standard, MPs
must contained metalaxyl as the sole active ingredient. Each MP
formulation proposed for registration must be fully described
with an appropriate certification of limits, stating maximum and
minimum amounts of the active ingredient and inert ingredients
which are present in products, as well as impurities found at
greater than 0.1 percent.
2. Acute Toxicity Limits
The Agency will consider registration of technical grade
and EPs containing metalaxyl provided that the product labeling
bears appropriate precautionary statements for the acute toxicity
category in which each product is placed.
3. Use Patterns
To be registered under this Standard, manufacturing-use
products must be labeled for formulation into end-use products
only for the uses listed below. The EPA Index to pesticide
chemicals lists all registered uses, as well as approved maximum
application rates and frequencies.
Terrestrial, food and non-food uses
24
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Metalaxyl is registered for use on at least 100 agricul-
tural crops, as well as ornamental and turf sites. About 37 uses
are for agricultural seed treatments.
The following table lists the ten major crops/sites using
metalaxyl on food, non-food and ornamental crops.
25
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USE OF METALAXYL ON TERRESTRIAL FOOD, NONFOOD AND ORNAMENTAL CROPS
•~— -— —— • '- ——r*" *
Use Site
Tobacco
Turf
Potatoes
Ornamentals
Target Pest
Blue mold
Black shank
Pythium damp-
ing-of f
Downy mildew
Pythium blight
Pythium damp-
ing-of f
• Yellow tuft
Phytophthora
and Pythium
tuber and
storage rot
Late blight
Pythium and
Pythophthora
diseases
Formulation
& EPA Reg. No.
SAI 2 Ib/gal EC
(100-607)
SAI 2 Ib/gal EC,
(100-619), 1.21% G
(538-185), and 5% G
(100-646), and
MAI 16% EC (538-
203)
SAI 9% WP (100-658)
MAI 10% WP (100-629)
SAI 2 Ib/gal EC
(100-607) and (100-
619), 5% G (100-
646), 1.21% G (538-
185), 0.1%, 0.3%,
and 0.5% P/T
(46260-26, 46260-
27 and 46260-28)
Application
Rate
0.25 to 3.0 Ib/A
0.25-0.5 oz/1000 sq
ft for soil or
foliar application
or 0.33 to 0.66 Ib/A
for foliar applica-
tion.
0.135 to 0.2 Ib/A
0.3 to 1.5 oz/1000
sq ft of treated
soil surface.
Application
Method
Soil and foliar
applications.
Soil and foliar
application.
Foliar appli-
cation
Soil application
by granules or
spray applied to
soil surface or
drenches applied
near plants.
Foliar applied
to azalea.
Application
Timing
Soil applications
are preplant or at-
planting. Foliar
applications are to
begin 70 days after
planting or after
initial preplant
treatment, and
repeat every 7 days.
Apply to soil or
foliage and repeat
every 5 to 21 days.
Foliar repeated
every 14 days as
needed.
Preplanting or at-
planting or before
growth begins and
repeat at 2- to 6-
month intervals.
Remarks
Limit is
3 Ib per
season
except
for black
shank
(4 Ib/
season).
Treated
foliage
not for
livestock
consump-
tion.
Tolerance
0.5 ppm
with 7-
day pre-
harvest
interval.
Nonfood
crop use.
Higher
levels
produce
phytotox-
icity to
some
plants.
-------
USE OF METALAXYL ON TERRESTRIAL FOOD, NONFOOD AND ORNAMENTAL CROPS
Use Site
Soybeans
(seed
treatment )
Soybeans
( field
application)
Onions
(dry bulb,
green and
grown for
seed)
Citrus
Target Pest
Pythium damp-
ing-of f
Phytophthora
(early season
control )
Phthium damp-
ing-off and
root rot
Pythium damp-
ing-off and
downy mildew
Phytphthora
foot rot/
root rot
Formulation
& EPA Reg. No.
SAI 25% WP (100-
639), 2.65 Ib/gal
F1C (2935-427 and
7501-42), 2 Ib/gal
EC (100-626)
SAI 2 Ib/gal
EC (100-607)
5% G (100-628)
SAI 2 Ib/gal EC
(100-607)
MAI 9% WP (100-658)
& 10% WP (100-629)
SAI 2 Ib/gal EC
(100-607)
SAI 5% G (100-628)
Application
Rate
0.25 to 0.5 oz/100
Ib seed
0.6875 to 1.375 Ib/
treated acre
or
0.25 lb/13,000
linear ft of row
0.15 to 0.3 oz per
1,000 ft of row
0.135 to 0.2 Ib/A
2.0-4.0 Ib/ 'treated
acre
Application
Method
Seed treatment
Soil application
in the seed fur-
row or a 7- inch
band over the
row, or broadcast
to seed furrow or
7-inch band over
the row.
Foliar appli-
cation
Soil treatment
Application
Timing
Preplant seed
application
At-planting
At-planting
Begin when disease
threatens and con-
tinue at 14-day
intervals as needed.
Begin early season
application to soil
under canopy of
tree. Make 2 addi-
tional applications
as needed.
Remarks
Tolerance :
3 ppm dry
bulb, 10
ppm green
7-day pre-
harvest
interval.
Tolerance :
1.0 ppm
fruit, 7.0
ppm for
molasses,
oil pulp.
27
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USE OF METALAXYL ON TERRESTRIAL FOOD, NONFOOD AND ORNAMENTAL CROPS
Use Site
Cucurbits
Tomatoes
Cotton
(seed
treatment)
Target Pest
Downy mildew
Pythium damp-
ing-off
cottony leak
(Pythium)
Late blight
Pythium damp-
ing-off
Pythium damp-
ing-off, seed
and seedling
rot
Pythium damp-
ing-off
Formulation
& EPA Reg. No.
MAI 9% WP (100-658),
10% WP (100-629)
SAI 2 Ib/gal EC
(100-607)
MAI 9% WP (100-658),
10% WP (100-629)
SAI 2 Ib/gal EC
(100-619) and
(100-607), 5% G
(100-646)
SAI 2 Ib/gal EC
(100-607), 5% G
(100-628) MAI 1% G
(100-664)
SAI 25% WP (100-
639), 2.65 Ib/gal
F1C (2935-427 and
7501-42)
Application
Rate
0.135 to 0.2 Ib/A
1.0 to 2.0 lb/ trea-
ted acre.
0.135 to 0.2 Ib/A
0.5 to 2.0 Ib/A
0.0625 to 0.125 lb/
13,000 linear ft of
row.
0.25 to 0.5 oz per
100 lb seed.
Application
Method
Foliar
Soil, broadcast
or banded on a
7-inch band.
Foliar
Soil
Soil application
at-planting in
seed furrow.
Seed treatment
Application
Timing
Begin when plants
are in two-leaf
stage, repeat at
14-day intervals
as needed.
One application at-
planting.
Begin application
when disease threat-
ens; repeat at 14-
day intervals as
needed.
Apply ' immediately
before or at-plant-
ing to soil surface.
Incorporate or
apply irrigation
water.
At-planting only
Preplanting
Remarks
Tolerance :
1 ppm
5 day pre-
harvest
interval .
Tolerance :
1.0 ppm
3 Ib/A/
season
maximum.
Tolerance :
0. 1 ppm in
cotton
seed.
28
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D. Required Labeling
All metalaxyl products must bear appropriate labeling as
specified in 40 CFR 162.10. Appendix II contains information
on label requirements.
In order to remain in compliance with FIFRA, no pesticide
product containing metalaxyl may be released for shipment by
the registrant after October 30, 1989, unless the product bears
amended labeling which complies with the specifications in this
Standard.
In order to remain in compliance with FIFRA, no pesticide
product containing metalaxyl may be distributed, sold, offered
for sale, held for sale, shipped, delivered for shipment, or
recedved and (having been so received) delivered or offered to
be delivered by any person after October 30, 1990, unless the
product bears amended labeling which complies with the speci-
fications in this Standard.
In addition to the above, in order to remain in compliance
with FIFRA, the following information must appear on the
labeling:
1. All MP's and EP's must bear the following statements;
A. Ingredient Statement. The ingredient statement
for MP's and EP's must list the active ingredient
as:
Metalaxyl ( % ai)
2. Maufacturinq-Use Products
A. Use Pattern Statement. All manufacturing-use prod-
ucts must state that they are intended for formula-
tion into end-use products for acceptable use
patterns. However, no use may be included on the
label where the registrant fails to agree to comply
with the data requirements in Table A for that use
pattern.
B. Disposal Statements. Because metalaxyl has not
been designated as an acute or toxic hazardous
waste under the Resource Conservation and Recovery
Act (RCRA), the following is the appropriate pest-
icide disposal statement for metalaxyl products:
"Wastes resulting from the use of this product
may be disposed of on site or at an approved
waste disposal facility."
The labels of all products must bear the appropriate
container disposal statement (See Appendix III).
29
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C. All MP's must bear the following statement:
"Do not discharge effluent containing this product
into lakes, streams, ponds, estuaries, oceans, or
public waters unless this product is specifically
identified and addressed in an NPDES permit. Do
not discharge effluent containing this product to
sewer systems without previously, notifying the
sewege treatment plant authority. For guidance
contact your State Water Board or Regional Office
of the EPA."
3. End-Use Pro-duets. All End-Use products are to bear
"the following statements on the label:
"Do not apply directly to water or wetlands (swamps,
bogs, marshes, and potholes). Do not contaminate
water when disposing of equipment washwaters."
"Do not plant any crop which is not registered for
use with metalaxyl in metalaxyl treated soil for a
period of 12 months."
30
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V. PRODUCTS SUBJECT TO THIS STANDARD
All products containing one or more of the pesticides
identified in Section II.A. are subject to certain requirements
for data submittal or changes in composition, labeling or
packaging of the product. The applicable requirements depend
on whether the product is a manufacturing or end use product
and whether the pesticide is the sole active ingredient or
one of multiple active ingredients.
Products are subject to this Registration Standard as
follows:
A. Manufacturing use products containing this pesticide as
the sc^le active ingredient are subject to:
1. The restrictions (if any) upon use, composition, or
packaging listed in Section IV, if they pertain to the
manufacturing use product.
2. The data requirements listed in Tables A and B2
3. The labeling requirements specified for manufacturing
use products in Section IV.
4. Administrative requirements (application forms, Confiden-
tial Statement of Formula, data compensation provisions)
associated with reregistration.
2 Data requirements are listed in the three Tables in
Appendix I of this Registration Standard. The Guide to
Tables in that Appendix explains how to read the Tables.
Table A lists generic data requirements applicable to all
products containing the pesticide subject to this Registra-
tion Standard. Table B lists product-specific data applicable
to manufacturing use products. The data in Tables A and B
need not be submitted by an end use producer who is eligible
for the generic data exemption for that active ingredient.
Table C lists product-specific data applicable to end use
products. The Agency has decided that, in most cases, it
will not require the submittal of product-specific data for
end use products at this time. Therefore most Registration
Standards do not contain a Table C.
31
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B. Manufacturing use products containing this pesticide
as one of multiple active ingredients are subject to:
1. The data requirements listed in Table A.
2. The labeling requirements specified for manufacturing
use products in Section IV.
C. End use products containing this pesticide as the
sole active ingredient are subject to:
1. The restrictions (if any) upon use, composition, or
packaging listed in Section IV if they pertain to the
end use product.
2. If eligible for the generic data exemption^, the
data requirements listed in Table C.
3. If not eligible for the generic data exemption, the
data requirements listed in Table A and the data require-
ments listed in Table C.
4. The labeling requirements specified for end use
products in Section IV.
D. End use products containing this pesticide as one of
multiple active ingredients are subject to:
1. If not eligible for the generic data exemption,
the data requirements listed in Tables A and C.
3 if you purchase from another producer and use as the
source of your active ingredient only EPA-registered products,
you are eligible for the generic data exemption for generic
data concerning that active ingredient (Table A) and product-
specific data for the registered manufacturing use product
you purchase (Table B).
Two circumstances nullify this exemption:
1) If you change sources of active ingredient to an
unregistered product, formulate your own active ingredient,
or acquire your active ingredient from a firm with ownership
in common with yours, you individually lose the exemption
and become subject to the data requirements in Table A.
2) If no producer subject to the generic data requirements
in Table A agrees to submit the required data, all end use
producers lose the exemption, and become subject to the data
requirements in Table A.
32
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2. If eligible for the generic data exemption, the
data requirements listed in Table C.
3. The labeling requirements specified for end use
products in Section IV.
VI. REQUIREMENT FOR SUBMISSION OF GENERIC DATA
This portion of the Registration Standard is a notice
issued under the authority of FIFRA sec. 3(c)(2)(B). It
refers to the data listed in Table A, which are required to
be submitted by registrants to maintain in effect the regis-
tration of products containing this active ingredient.4
A. what are generic data?
Generic data pertain to the properties or effects of a
particular active ingredient. Such data are relevant to an
evaluation of all products containing that active ingredient
regardless of whether the product contains other ingredients
(unless the product bears labeling that would make the data
requirement inapplicable).
Generic data may also be data on a "typical formulation"
of a product. "Typical formulation" testing is often required
for ecological effects studies and applies to all products
having that formulation type. These are classed as generic
data, and are contained in Table A.
B. Who must submit generic data?
All current registrants are responsible for submitting
generic data in response to a data request under FIFRA sec.
3(c)(2)(B) (DCI Notice). EPA has decided, however, not to
require a registrant who qualifies for the formulator's
exemption (FIFRA sec. 3(c)(2)(D) and S 152.85) to submit
generic data in response to a DCI notice if the registrant
who supplies the active ingredient in his product is complying
with the data request.
If you are granted a generic data exemption, you rely on
the efforts of other persons to provide the Agency with the
required data. If the registrants who have committed to
generate and submit the required data fail to take appropriate
steps to meet the requirements or are no longer in compliance
with this data requirements notice, the Agency will consider
4 Registrations granted after issuance of this Standard will
be conditioned upon submittal or citation of the data listed
in this Registration Standard.
33
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that both they and you are not in compliance and will normally
initiate proceedings to suspend the registrations of both
your product(s) and their product(s) unless you commit to submit
and submit the required data in the specified timeframe. In
such cases, the Agency generally will not grant a time extension
for submitting the data.
If you are not now eligible for a generic data exemption,
you may qualify for one if you change your source of supply
to a registered source that does not share ownership in
common with your firm. If you choose to change sources of
supply, the Confidential Statement of Formula must identify
the new source(s) and you must submit a Generic Data Exemption
Statement.
\
If you apply for a new registration for products containing
this active ingredient after the issuance of this Registration
Standard, you will be required to submit or cite generic data
relevant to the uses of your product if, at the time the
application is submitted, the data have been submitted to the
Agency by current registrants. If the required data have not
yet been submitted, any new registration will be conditioned
upon the new registrant's submittal or citation of the
required data not later than the date upon which current
registrants of similar products are required to provide such
data. See FIFRA sec. 3(c)(7)(A). If you thereafter fail to
comply with the condition of that registration to provide
data, the registration may be cancelled (FIFRA sec. 6(e)).
C. What generic data must be submitted?
You may determine which generic data you must submit by
consulting Table A. That table lists the generic data needed
to evaluate current uses of all products containing this
active ingredient, the uses for which such data are required,
and the dates by which the data must be submitted to the
Agency.
D. How to comply with PCI requirements.
Within 90 days of your receipt of this Registration
Standard, you must submit to EPA a completed copy of the form
entitled "FIFRA Section 3(c)(2)(B) Summary Sheet" (EPA Form
8580-1, enclosed) for each of your products. On that form
you must state which of the following six methods you will
use to comply with the DCI requirements:
1. You will submit the data yourself.
2. You have entered into an agreement with one or more
registrants to jointly develop (or share in the cost of
developing) the data, but will not be submitting the data
yourself. If you use this method, you must state who will
34
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submit the data on which you will rely. You must also provide
EPA with documentary evidence that an agreement has been
formed which allows you to rely upon the data to be submitted.
Such evidence may be: (1) your letter offering to join in
an agreement and the other registrant's acceptance of your
offer, (2) a written statement by the parties that an agreement
exists, or (3) a written statement by the person who will be
submitting the data that you may rely upon its submittal.
The Agency will also require adequate assurance that the
person whom you state will provide the data is taking appropriate
steps to secure it. The agreement to produce the data need
not specify all of the terms of the final arrangement between
the parties or a mechanism to resolve the terms.
If you and other registrants together are generating or
submitting requested data as a task force or consortium, a
representative of the group should request a Joint Data
Submitter Number, as part of your 90-day response. The
request must include the following information:
a. A list of the members of the consortium;
b. The name and address of the designated representative
of the consortium, with whom EPA will correspond
concerning the data;
c. Identity of the Registration Standard containing
the data requirement;
d. A list of the products affected (from all members
of the consortium); and
e. Identification of the specific data that the con-
sortium will be generating or submitting.
The Agency will assign a number to the consortium, which
should be used on all data submittals by the consortium.
3. You have attempted to enter into an agreement to
jointly develop dataf but no other registrant has accepted
your offer. You request that EPA not suspend your registration
for non-compliance with the PCI. EPA has determined that,
as a general policy, it will not suspend the registration of
a product when the registrant has in good faith sought and
continues to seek to enter into a data development/cost
sharing program, but the other registrants developing the
data have refused to accept its offer. [If your offer is
accepted, you may qualify for Option 2 above by entering
into an agreement to supply the data.]
In order to qualify for this method, you must:
1. File with EPA a completed "Certification of Attempt
to Enter into an Agreement with other Registrants for Develop-
ment of Data" (EPA Form 8580-6, enclosed).
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2. Provide us with a copy of your offer to the other
registrant and proof of the other registrant's receipt of your
offer (such as a certified mail receipt). Your offer must,
at a minimum, contain the following language or its equivalent:
[Your company name] offers to share in the burden of
producing the data required pursuant to FIFRA sec.
3(c)(2)(B) in the [name of active ingredient] Registration
Standard upon terms to be agreed or failing agreement
to be bound by binding arbitration as provided by FIFRA
section 3(c)(2)(B)(iii) .
The remainder of your offer may not in any way attempt to
limit this commitment. If the other registrant to whom your
offer is made does not accept your offer, and if the other
registrant informs us on a DCI Summary sheet that he will
develop and submit the data required under the DCI, then you
may qualify for this option. In order for you to avoid
suspension under this method, you may not later withdraw or
limit your offer to share in the burden of developing the
data.
In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice in a timely manner. If the other registrant fails to
develop the data or for some other reason would be subject to
suspension, your registration as well as that of the other
registrant will normally be subject to initiation of suspension
proceedings, unless you commit to submit and submit the required
data in the specified timeframe. In such cases, the Agency
generally will not grant a time extension for submitting the data.
4. You request a waiver of the data requirement. If
you believe that a data requirement does not (or should not)
apply to your product or its uses, you must provide EPA with
a statement of the reasons why you believe this is so. Your
statement must address the specific composition or use factors
that lead you to believe that a requirement does not apply.
Since the Agency has carefully considered the composition and
uses of pesticide products in determining that a data require-
ment applies, EPA does not anticipate that many waivers will
be granted. A request for waiver does not extend the time-
frames for developing required data, and if your waiver
request is denied, your registration may be suspended if you
fail to submit the data. The Agency will respond in writing
to your request for a waiver.
5. You request that EPA amend your registration by deleting
the uses for which the data are needed. You are not required
to submit data for uses which are no longer on your label.
36
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6. You request voluntary cancellation of the registration
of your product(s) for which the data are needed.
E. Registrant Requests Regarding Data Requirements and Agency
Responses
All requests for modification of data requirements
(inapplicability, waiver), approval of protocols or protocol
changes, or time extensions must be submitted in writing.
The original requirement remains in effect unless the Agency
has notified you in writing that it has agreed to a change in
the requirement. While being considered by the Agency, such
requests for changes in the requirements do not alter the
original requirements or extend the time allowed for meeting
the requirement.
F. Test Protocols and Standards
All studies required under this Notice must be conducted
in accordance with test standards outlined in the Pesticide
Assessment Guidelines, unless other protocol or standards are
approved for use by the Agency in writing. All testing must
be conducted in accordance with applicable Good Laboratory
Practices regulations in 40 CFR Part 160.
The Pesticide Assessment Guidelines, which are referenced
in the Data Tables, are available from the National Technical
Information Service (NTIS), Attn: Order Desk, 5285 Port Royal
Road, Springfield, VA 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic
Cooperation and Development (OECD) are also acceptable if
the OECD-recommended test standards conform to those specified
in the Pesticide Data Requirements regulation (Part 158.70).
Please note, however, that certain OECD standards (such as
test duration, selection of test species, and degradate
identification which are environmental fate requirements) are
less restrictive than those in the EPA Assessment Guidelines
listed above. When using the OECD protocols, they should be
be modified as appropriate so that the data generated by the
study will satisfy the requirements of Part 158. Normally,
the Agency will not extend deadlines for complying with data
requirements when the studies were not conducted in accord
with acceptable standards. The OECD protocols are available
from OECD, 1750 Pennsylvania Avenue, N.W., Washington, D.C.
20006.
37
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G. Procedures for requesting a change in test protocol.
If you will generate the required data and plan to use
test procedures which deviate from EPA's Pesticide Assessment
Guidelines or the Reports of Expert Groups to the Chemicals
Group, Organization for Economic Cooperation and Development
(OECD) Chemicals Testing Programme, you must submit for EPA
approval the protocols you propose to use.
You should submit your protocols before beginning testing,
because the Agency will not ordinarily accept as sufficient
studies using unapproved protocols. A request for protocol
approval will not extend the timeframe for submittal of the
data, nor will extensions generally be given to conduct
studies due to submittal of inappropriate protocols. The
Agency* will respond in writing to your request for protocol
approval or change.
H. Procedures for requesting extensions of time.
If you think that you will need more time to generate
the data than is allowed by EPA's schedule, you may submit a
request for an extension of time.
EPA will view failure to request an extension before
the data submittal response deadline as a waiver of any
future claim that there was insufficient time to submit the
data. While EPA considers your request, you must strive to
meet the deadline for submitting the data.
The extension request should state the reasons why you
believe that an extension is necessary and the steps you
have taken to meet the testing deadline. Time extensions
normally will not be granted due to problems with laboratory
capacity or adequacy of funding, since the Agency believes
that with proper planning these can be overcome. The Agency
will respond in writing to any requests for extension of time.
I. Data Format and Reporting Requirements
All data submitted in response to this Notice must comply
with EPA requirements regarding the reporting of data,
including the manner of reporting, the completeness of results,
and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or
included in this Notice or contained in PR Notice 86-5 (issued
July 29, 1986). All studies must be submitted in the form of
a final report; a preliminary report will not be considered
to fulfill the submittal requirement.
38
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J. Existing stocks provision upon suspension or cancellation.
The Agency has determined that if a registration is
suspended for failure to respond to a DCI request under
FIFRA sec. 3(c)(2)(B), an existing stocks provision for the
registrant is not consistent with the Act. Accordingly, the
Agency does not anticipate granting permission to sell or
distribute existing stocks of suspended product except in
rare circumstances. If you believe that your product will be
suspended or cancelled and that an existing stocks provision
should be granted, you have the burden of clearly demonstrating
to EPA that granting such permission would be consistent with
the Act. The following information must be included in any
request for an existing stocks provision:
1. Explanation of why an existing stocks provision is
necessary, including a statement of the quantity of
existing stocks and your estimate of the time required
for their sale or distribution; and
2. Demonstration that such a provision would be consis-
tent with the provisions of FIFRA.
VII. REQUIREMENT FOR SUBMISSION OF PRODUCT-SPECIFIC DATA
Under its DCI authority, EPA has determined that certain
product-specific data are required to maintain your registrations
in effect. Product-specific data are derived from testing
using a specific formulated product, and, unlike generic
data, generally support only the registration of that product.
All such data must be submitted by the dates specified in
this Registration Standard.
If you have a manufacturing use product, these data are
listed in Table B. If you have an end use product, the data
are listed in Table C. As noted earlier, the Agency has
decided that it will not routinely require product-specific
data for end use products at this time. Therefore, Table C
may not be contained in this Registration Standard; if there
is no Table C, you are not required to submit the data at
this time.
In order to comply with the product specific data require-
ments, you must follow the same procedures as for generic data.
See Section VI.D through J. You should note, however, that
product chemistry data are required for every product, and the
only acceptable responses are options VI.D.I. (submit data)
or VI.D.6.(cancellation of registration).
Failure to comply with the product-specific data require-
ments for your products will result in suspension of the
product's registration.
39
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VIII. REQUIREMENT FOR SJBMITTAL OF REVISED LABELING
FIFRA requires each product to be labeled with accurate,
complete and sufficient instructions and precautions, reflecting
the Agency's assessment of the data supporting the product
and its uses. General labeling requirements are set out in
40 CFR 156.10 (see Appendix II - LABELING and SUMMARY). In
addition, labeling language specific to products containing
this pesticide is specified in Section IV.D of this Registra-
tion Standard. Responses to this Registration Standard must
include draft labeling for Agency review.
Labeling must be either typewritten text on 8-1/2 x 11
inch paper or a mockup of the labeling suitable for storage
in 8-1/2 x 11 files. Draft labeling must indicate the intended
colors of the final label, clear indication of the front
panel of the label, and the intended type sizes of the text.
If you fail to submit revised labeling as required,
which complies with 40 CFR 156.10 and the specific instructions
in Section IV.D., EPA may seek to cancel the registration of
your product under FIFRA sec. 6.
IX. INSTRUCTIONS FOR SUBMITTAL
All submittals in response to this Registration Standard
must be sent to the following address:
Office of Pesticide Programs
OPP Mailroom (TS-767C)
Environmental Protection Agency
401 M St., SW
Washington, D.C. 20460
Attn: Metalaxyl Registration Standard
All submittals in response to this Registration Standard
are non-fee items, including 90-day responses, protocols and
waiver requests, data, and revised labeling. Submittals must
be clearly identified as being in response to the Registration
Standard. Under no circumstances may Registration Standard
responses be combined with other types of filings for which
fees are required.
A. ManufacturingJJse Products (MUPs) containing the subject
pesticide as sole active ingredient.
1. Within 90 days from receipt of this document, you
must submit for each product subject to this Registration
Standard:
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a. -Generic Data Exemption Statement (EPA Form 8580-3)/
if applicable, or the "FIFRA Section 3(c)(2)(B) Summary
Sheet" (EPA Form 8580-1), with appropriate attachments.
b. Confidential Statement of Formula (EPA Form 8570-4).
c. Evidence of compliance with data compensation
requirements of FIFRA sec. 3(c)(l)(D). Refer to 40 CFR
152.80-152.99.
2. Within 9 months from receipt of this document you
must submit:
a. Application for Pesticide Registration (EPA
Form 8570-1).
( b. Two copies of any required product-specific data
(See Table B).
c. Three copies of draft labeling, including the
container label and any associated supplemental labeling.
d. Product Specific Data Report (EPA Form 8580-4).
3. Within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
B. Manufacturing Use Products containing the subject pesticide
in combination with other active ingredients.
1. Within 90 days from receipt of this document, you
must submit:
a. Generic Data Exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA sec. 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4)
2. Within 9 months of receipt of this document, you must
submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
3. Within the time frames set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
41
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notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
C. End Use Products containing the subject pesticide as sole
active ingredient.
1. Within 90 days from receipt of this document, you
must submit:
a. Generic data exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA Section 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
2.* Within ^ months from receipt of this document you
must submit:
a. Two copies of any product-specific data, if required
by Table C.
b. Product Specific Data Report (EPA Form 8580-4),
if Table C lists required product-specific data.
c. Three copies of draft labeling, including the
container label and any associated supplemental labeling.
3. Within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
D. End Use Products containing the subject active ingredient
as one of multiple active ingredients
1. Within 90 days from receipt of this document, you
must submit:
a. Generic data exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA Section 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
2. Within 9 months from the receipt of this document, you
must submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
42
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3. Within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
E. Intrastate Products
Applications for full Federal registration of intrastate
products were required to be submitted no later than July 31,
1988. Unless an application for registration was submitted
by that date, no product may be released for shipment by the
producer after July 31, 1988.
43
-------
-------
APPENDIX I
DATA APPENDICES
44
-------
-------
TGUIDE-1
GUIDE TO TABLES
Tables A and B contain listings of data requirements
for the pesticides covered by this Registration Standard.
Table A contains generic data requirements that apply to
the pesticide in all products, including data requirements
for which a "typical formulation" is the test substance.
Table B contains product-specific data requirements that
apply only to a manufacturing use product.
The data tables are generally organized according to the
following format:
1. Data Requirement (Column 1). The data requirements are
listed in the order in which they appear in 40 CFR Part 158.
The reference numbers accompanying each test refer to the
test protocols set out in the Pesticide Assessment Guidelines,
which are available from the National Technical Information -
Service, 5285 Port Royal Road, Springfield, VA 22161.
2. Test Substance (Column 2). This column lists the composition
of the test substance required to be used for the test, as
follows:
TGAI = Technical grade of the active ingredient
PAI = Pure active ingredient
PAIRA = Pure active ingredient, radio labeled
TEP = Typical end use formulation
MP = Manufacturing use product
EP = End use product
Any other test substances, such as metabolites, will be
specifically named in Column 2 or in footnotes to the table.
3. Use pattern (Column 3). This column indicates the use
patterns to which the data requirement applies. Use patterns
are the same as those given in 40 CFR Part 158. The following
letter designations are used for the given use patterns:
A * Terrestrial, food
B a Terrestrial, non-food
C = Aquatic, food
D = Aquatic, non-food
E = Greenhouse, food
F = Greenhouse, non-food >- .
G » Forestry
H = Domestic outdoor
I = Indoor
Any other designations will be defined in a footnote to the table.
45
-------
TGUIDE-2
4. Does EPA have data? (Column 4). This column indicates one
of three answers:
YES - EPA has data in its files that satisfy this data
requirement. These data may be cited by other registrants
in accordance with data compensation requirements of
Part 152, Subpart E.
PARTIALLY - EPA has some data in its files, but such data
do not fully satisfy the data requirement. In some cases,
the Agency may possess data on one of two required species,
or may possess data on one test substance but not all.
The term may also indicate that the data available to
EPA are incomplete. In this case, when the data are
clarified, or additional details of the testing submitted
by the original data submitter, the data may be determined
^ to be acceptable. If this is the case, a footnote to
the table will usually say so.
NO - EPA either possesses no data which are sufficient
to fulfill the data requirement, or the data which EPA
does possess are flawed scientifically in a manner that
cannot be remedied by clarification or additional infor-r.
mation.
5. Bibliographic citation (Column 5). If the Agency has
acceptable data in its files, this column lists the identifying
"number of each study. This normally is the Master Record
Identification (MRID) number, but may be a GS number if no
MRID number has been assigned. Refer to the Bibliography
Appendices for a complete citation of the study.
6. Must additional data be submitted? (Column 6). This
column indicates whether the data must be submitted to the
Agency. If column 3 indicates that the Agency already has
data, this column will usually indicate NO. If column 3
indicates that the Agency has only partial data or no data,
this column will usually indicate YES. In some cases, even
though the Agency does not have the data, EPA will not require
its submission because of the unique characteristics of the
chemical; because data on another chemical can be used to
fulfill the data requirement; or because the data requirement
has been waived or reserved. Any such unusual situations
will be explained in a footnote to the table.
7. Tiaefraae for submission (Column 7). If column 5 requires
that data be submitted,this column indicates when the data
are to be submitted, based on the issuance date of the Regis-
tration Standard. The timeframes are those established either
as a result of a previous Data Call-in letter, >or.,. standardized
timeframes established by PR Notice 85-5 (August 22, 1985).
8. Footnotes (at the end of each table). Self-explanatory.
46
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Composition1 Pattern
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No Bibliographic
or Partially) Citation
-Must Additional
Data Be Submitted
Time Period
After EPA
Notification
Under FIFRA Section to Report
3(c)(2)(B)?
Data3
§158.120 Product Chemistry
Product Identity and Composition
61-1 - Product Identity
and Disclosure of
Ingredients
TGAI
61-2 - Description of Beginning TGAI
Materials and Manufac-
turing Process
61-3 - Discussion of Formation TGAI
of Impurities
Analysis and Certification of
Product Ingredients
62-1 - Preliminary Analysis TGAI
of Product Samples
62-2 - Certification of TGAI
Ingredient Limits
62-3 - Analytical Methods TGAI
to Verify Certified
Limits
All
All
All
All
All
All
Yes
Partially
00104498 4
00104498
Partially 00104498
00104483
Partially
No
Partially
No
Yes-
Yes6
6 Months
6 Months
00104483
40435001
00104498
Yes?
Yes8,9
YeslO
12 Months
12 Months
12 Months
47,
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Use2
Compositionl Pattern
Does EPA Have
Data to Satisfy
This Require-
nent? (Yes, No
or Partially)
Bibliographic
Citation
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?
Time Period
After EPA
Notification
to Report
Data3
§158. 120 Product Chemistry (continued)
Physical and Chemical Characteristics
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
- Color
- Physical State
- Odor
- Melting Point
- Boiling Point
- Density, Bulk Density,
or Specific Gravity
- Solubility
- Vapor Pressure
- Dissociation Constant
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI or PAI
PAI
TGAI or PAI
- Octanol/Water Partition TGAI
Coefficient
- PH
- Storage Stability
TGAI
TGAI
All Yes
All Yes
All Yes
All Yes
All N/AH
All Yes
All Yes
All Yes
All Yes
All Yes
All Yes
All Yes
00104483
00104483
00104483
00104483
00104483
00104483
00104483
00104483
40435001
40435001
00104483
No
No
No
No
No
No
No
No
No
No
No
No
48
-------
TABLE A
GENERIC DATA REQUIREMENTS FDR METALAXYL
Does EPA Have Time Period
Data to Satisfy * Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 nent? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Composition1 Pattern or Partially) Citation 3(c)(2)(B)? Data3
§158.120 Product Chemistry (continued)
Other Requirements;
64-1 - Submittal of Samples N/A N/A N/A N/A12 No N/A
49
-------
FOOTNOTES FDR PREVIOUS TABLE A
I/ The 90% technical is the only registered metalaxyl manufacturing-use product. Composition: TGAI = technical grade
~~ of the active ingredient; PAI = pure active ingredient.
2/ The use patterns are coded as follows: "A" for Terrestrial, Food Crop; "B" for-Terrestrial, Non-Foods,; "C" for
Aquatic, Food Crop, "D" for Aquatic, Non-Food; "E" for Greenhouse, Food Crop; "F" for Greenhouse, Non-Food;
"G" for Forestry; "H" for Domestic Outdoor; and "I" for Indoor.
3/ Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
4/ Information obtained from desk references.
5/ Complete information must be provided regarding the nature of the process (batch or continuous), the relative
amounts of beginning material and the order in which they are added, the chemical equations for each intended
reaction, equipment used to produce each intermediate and the final product, reaction conditions, the duration
of each step of the process, purification procedures, and quality control measures. In addition, the name and
address of the manufacturer, producer, or supplier of each beginning material must be provided, along with in-
formation regarding the properties of each beginning material used to manufacture each product. In order to
assess the potential for contamination with nitrosamines, a{description of manufacturing process conditions
favoring formation of nitrosamines must be provided. |
6/ A detailed discussion of all impurities that are or may be present at >^ 0.1%, based on knowledge of the beginning
materials, chemical reactions (intended and side) in the manufacturing process, and any contamination during and
after production must be submitted. This discussion must also address the possible formation of nitrosamines
from metalaxyl and its impurities.
7/ Five or more representative samples must be analyzed for the amount of active ingredient and each impurity for
which a certified limit is required. Complete validation data (accuracy, precision) must be submitted for each
analytical method used.
8/ Available data do not meet the requirements of 40 CFR 158.120, Part 62-2.
9/ Upper and lower limits for metalaxyl must be provided, certified, and validated by sample analysis using
analytical procedures for which accuracy and precision data have been provided. Upper limits for each impurity
present at ^0.1% (w/w), and for each "toxicologically significant" impurity present at < 0.1% (w/w) must be
provided, certified, and validated by sample analysis using analytical procedures for which accuracy and
precision data have been provided. All nitrosamines must be identified and quantified in six samples of each
product; two samples of each must be analyzed shortly after production and 6 months after production. A method
sensitive to 1 ppm of N-nitroso contaminants must be used. An upper limit must be provided (and certified) for all
nitrosamines found. Certifications should be submitted on EPA Form 8570 (Rev. 2-85).
lO/ Analytical methods must be provided to determine the active ingredient and each toxicologically significant
impurity (including nitrosamines) for which a certified limit is required. Each method must be accompanied
by validation studies indicating its accuracy and precision. These methods must be suitable for enforcement
of certified limits.
ll/ Not required; a solid at room temperature.
12/ N/A = Not applicable.
50 '
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Composition^
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
§158.125 Residue Chemistry
171-2 - Chemical Identity4
171-3 - Directions for Use
171-4 - Nature of Residue25
(metabolism)
- Plants
- Livestock
171-4 - Residue Analytical
Method
- Plant and Animal
TGAI
PAIRA
PAIRA
TGAI and
Metabolites
(See Index)
Yes
No
Partially
Bibliographic
Citation
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?2
Time Period
After EPA
Notification
to Report
Data3
00071603,00071604,
00071605,00071606
00071607,00071608,
00071609,00071610,
00114379,00128102
00071622,00071623,
00071676,00104656,
00148440,00157740,
Yes5
6 Months
No
Yes
18 Months
Yes'
15 Months
171-4 - Storage Stability
PAI or TEP, Partially
and Metabolites
00148440
18 Months
51
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TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Composition-1
§158.125 Residue Chemistry
171-4 - Magnitude of the25
Residue—Residue
Studies for Each
Food Use
- Crop Field Trials
- Crop Group #1 - Root
Tuber Vegetables
Group
o Beets
o Potatoes
o Sugar Beet Roots
- Crop Group #2 - Leaves
of Root and Tuber
Vegetables Group
o Beet Greens
o Sugar Beet Tops
TEP
TEP
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Yes
Partially
No
Yes
No
Bibliographic
Citation
00128102
00071616
00128102
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?2
Time Period
After EPA
Notification
to Report,
Data3
No
Yes11
24 Months
24 Months
No
No12
52
-------
TABLE A
GENERIC DATA REQUIREMENTS FDR METALAXYL
Data Requirement
Composition1
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Bibliographic
Citation
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?2
Time Period
After EPA
Notification
to Report
Data3
§158.125 Residue Chemistry (con't)
171-4 - Magnitude of the
Residue—Residue
Studies for Each
Food Use (cont'd)
- Crop Group #3 - Bulb
Vegetables Group
o Onions
- Crop Group #4 - Leafy
Vegetables Group
o Lettuce
o Spinach
Crop Group #5 - Brassica
Leafy Vegetables Group
o Broccoli
o Cabbage
o Cauliflower
Yes
Yes
Yes
Yes
Yes
Yes
00071615,00098428
00130694,00148103
00071615,00097511
00114377,00130695
00071672,00114378
00130695
00071615,00130773
00071615,00130773
00071615,00130773
No
No
No
No
No
No
53
-------
TABLE A
GENERIC DATA REQUIREMENTS EDR METALAXYL
Data Requirement
Composition*
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Bibliographic
Citation
Must Additional
Data Be Submitted
Under FTFRA Section
3(c)(2)(B)?2
Tine Period
After EPA
Notification
to Report
Data3
§158.125 Residue Chemistry (cpnt'd)
171-4 - Magnitude of the
Residue—Residue
Studies for Each
Food Use (cont'd)
- Crop Group #6 - Legume
Vegetables Group
Soybeans
Crop Group #7 - Foliage
of the Legume
Vegetables Group
Crop Group #8 - Fruiting
Vegetables Group
Crop Group #9 - Curcubit
Vegetables Group
Crop Group #10 - Citrus
Fruits Group
Crop Group #11 - Pome
Fruits Group
o Apples
TEP
Yes
Partially
Yes
Yes
Yes
Yes
00129003
00071672,00104390
00148440
00129003
00148103,00148440
00157480
00071615,00098428
00130693,00148103
00117969,00133020
00148440
No
Yes13
No
No
No
No
18 Months
Yes
00126315,00141519
i
No
54
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
[—
I
{
I -1
Data Requirement Composition1
§158.125 Residue Chemistry (cont'd)
171-4 - Magnitude of the
Re s idue — Res idue
Studies for Each
Food Use (cont'd)
- Crop Group #12 - Small TEP
Fruits and Berries
Group
o Raspberries
- Crop Group #13 - Cereal TEP
Grains Group
- Crop Group #14 - Forage, TEP
Fodder, and Straw of
Cereal Grains Group
- Miscellaneous Commodities
o Avocados
o Cottonseed TEP
o Hops TEP
o Peanuts TEP
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Yes
Partially
Partially
Yes
Partially
Partially
Partially
Time Period
Must Additional After EPA
Data Be Submitted Notification
Bibliographic Under FIFRA Section to Report
Citation 3(c)(2)(B)?2 Data3
00127769 No
00128102,00071672 Yes 18 Months14
00104387,00114376 24 Months1^
00128102 Yes 18 MonthsIS
6 Months17
00074488 No
00109402 Yes18 24 Months
00079433 Yes19 24 Months
00128738 Yes20 24 Months
55
-------
TABLE A
GENERIC DATA REQUIREMENTS FDR METALAXYL
Data Requirement
Composition-^
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Bibliographic
Citation
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?2
Time Period
After EPA
Notification
to Report
Data3
§158.12J5 Residue Chemistry (cont*d)
171-4 - Magnitude of the
Residue—Residue
Studies for Each
Food Use (cont'd)
- Miscellaneous Commodities (cont'd)
o Pineapples TEP
o Sunflower Seed TEP
o Tobacco
- Nonbearing Orchard Groups
o Pome Fruit TEP
o Stone Fruit TEP
o Tree Nuts TEP
- Meat/Milk/Poultry/Eggs
Partially
Partially
No
No
No
Yes
00109472 Yes^1
00128102 Yes22
00148440 No
No2 3
No23
No23
00071674,00114376, Reserved24
24 Month
24 Month
00100753,00071673
56
-------
TABLE A
GENERIC DATA REQUIREMENTS EDR METALAXYL
FOOTNOTES:
I/ Test Substance: TGAI = Technical grade of the active ingredient; PAIRA = Pure active ingredient, radiolabeled;
TEP = Typical end-use product; EP = End-use product.
2/ The use patterns are coded as follows: "A" for Terrestrial, Food Crop; "B" for Terrestrial, Non-Foods,; "C" for
Aquatic, Food Crop; "D" for [Aquatic, Non-Food; "E" for Greenhouse, Food Crop; "F" for Greenhouse, Non-Food;
"G" for Forestry; "H" for Domestic Outdoor; and "I" for Indoor.
V Timeframe for submission is from date of registrants receipt of registration standard.
4/ Refer to Product Chemistry Data Requirement tables.
5/ The registrant must propose (i) a label amendment that specifies a maximum seasonal use rate or maximum number of
applications per season for dry bulb onions (based on the available data, we recommend a maximum of four applica-
tions per season); and (ii) a preharvest interval following registered/proposed use of metalaxyl on members of
the Fruiting Vegetables (except Curcurbits) Groups (based on the available data, we recommend a 7-day preharvest
interval). Also, refer to footnote 17 for additional required label amendments for wheat as a rotational crop.
_§/ Metabolism studies must be submitted utilizing ruminants and poultry in which animals must be dosed for a minimum
of 3 days with -l^c] metalaxyl at a level sufficient to make residue identification and quantification possible.
Milk and eggs must be collected twice daily during the dosing period. Animals must be sacrificed within 24 hours
of the final dose. The distribution and characterization of residues must be determined in milk, eggs, liver,
kidney, and muscle and also skin and gizzard for hen. If the metabolism of metalaxyl in ruminants or_ poultry is
found to differ from that in rats, or with each other, then swine metabolism data may be required. Data reflecting
solvent extraction of residues are also required. Representative samples from the above described tests must also
be analyzed by current enforcement methods to ascertain the validity of these methods.
7/ Metalaxyl metabolites containing the 2,6-dimethylaniline moiety and CGA-94689 in or on crop samples must be
subjected to analysis by multiresidue protocols. Protocols for Methods I, II, III, and IV are available from
the National Technical Information Service under Order No. PB-203734/AS.
8/ The storage intervals and conditions of samples used to support all established tolerances for residues must be
submitted. These data must be accompanied by data depicting the percent decline in residues at the times and under
the conditions specified. (No additional stability studies are required for plant commodities stored at 5 °F
[-15 °C] for up to 12 months.) On receipt of these data, the adequacy of the aforementioned tolerances will be
evaluated.
9_/ All residue data requested in this Standard must be accompanied by data regarding storage length and conditions
of storage of samples analyzed. These data must be accompanied by data depicting the stability of residues under
the conditions and for the time intervals specified, with the exception of plant commodities stored at 5 °F
(-15 °C) for up to 12 months.
10/ Data must be submitted depicting metalaxyl residues of concern in chips, granules or flakes, and wet and dry potato
peel processed from potatoes bearing measurable, weathered residues. If residues concentrate in any of these
processed commodities, appropriate food/feed additive tolerances must be proposed.
i
57
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
FOOTNOTES (cont'd):
ll/ Data must be submitted depicting total metalaxyl residues of concern in molasses processed from sugar beets bearing
measurable, weathered residues to support the established tolerance of 1.0 ppm in molasses. In addition, data must
be submitted depicting metalaxyl residues of concern in dehydrated pulp and refined sugar processed from sugar
beets bearing measurable, weathered residues. If residues are found to concentrate in either of these processed
commodities, appropriate food/feed additive tolerances must be proposed.
12_/ Data from garden beets are adequate to support sugar beets.
13/ The registrant must propose tolerances for total metalaxyl residues in or on soybean forage, hay, and straw.
We recommend a tolerance of 8 ppm, toxicological considerations permitting, based on the available data.
14/ Data must be submitted depicting metalaxyl residues of concern in or on the grain of field corn harvested from
seed treated with the 25% WP formulation at 0.5 oz ai/100 Ib of seed.
15/ Data must be submitted depicting metalaxyl residues of concern in milled products and grain dust from the milling
process of: field corn (starch, crude and refined oils from wet milling, and grits, meal, flour, crude and refined
oils from dry milling); rice (hulls, bran, polished rich); and sorghum (flour, starch) grains bearing measurable,
weathered residues. If residues concentrate during processing in any of these commodities, then appropriate food/
feed additive tolerances must be proposed.
16/ Data must be submitted depicting metalaxyl residues of concern in or on field corn forage and fodder grown from
seed treated with the 25% WP formulation at 0.5 oz ai/100 Ib of seed.
IT/ The registrant must propose specific time restrictions with respect to the last application of the 2 Ib/gal
EC formulation to the primary crops and planting of the rotational wheat crop. Based on the available data, we
recommend an interval of 14 days.
18_/ Data must be submitted depicting concentration of metalaxyl residues of concern during processing of cottonseed
hulls, meal, crude oil, refined oil, and soapstock derived from cottonseed bearing measurable, weathered residues.
(Exaggerated application rates may be necessary to obtain these levels on the cottonseed.) If concentration occurs
during processing, the registrant must propose appropriate food/feed additive tolerances.
19_/ The Agency has established interim tolerances for metalaxyl in dried and spent hops at 50.0 ppm with an expiration
date of October 28, 1988. Additional residue data have been submitted and are currently under review. Based
on these data revised tolerances may need to be proposed and established.
20_/ Data must be submitted depicting metalaxyl residues of concern in or on nuts, hulls, hay, and vines from soil
applications of a G formulation at 0.25 Ib ai/A (at-planting) and 1.0 Ib ai/13,000 linear ft of row (at pegging).
Tests must be conducted in AL (15%), GA (49%), NC (10%), OK (4%), and VA (6%), States which collectively produced
ca. 84% of 1984 U.S. peanut product.
21/ Data must be submitted from a processing study depicting metalaxyl residues of concern in pineapple juice and
pineapple bran (chopped, dehydrated pineapple tops and shells) processed from pineapple fruit bearing measurable,
weathered residues. If residues concentrate in any of these processed commodities, then appropriate food/feed
additive tolerances must be proposed.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
FOOTNOTES (ccnt'd):
22/ Data must be submitted depicting metalaxyl residues of concern in meal, hulls, crude oil and refined oil processed
from sunflower seed bearing measurable, weathered residues. If residues concentrate in any of these commodities
then appropriate food/feed additive tolerances must be proposed.
23/ Considered "non-food use."
24/ Presently, the nature of the residue in animals is not adequately understood. On receipt of the data requested in
the section entitled "Nature of the Residue in Animals," the appropriate nature of tolerances for residues in animal
products will be determined and, with consideration for any newly found metabolites of toxicological concern, the
adequacy of the available data regarding the magnitude of the residue in animal commodities (milk, poultry, eggs,
fat, meat, liver, and kidney) will be determined.
25/ For nature of the residue in plants and magnitude of the residue in crops, the timeframes for submitting data are 18
or 24 months, as appropriate, commencing with the first planting season following the receipt of the Registration
Standard.
-------
TABLE A
GENERIC DATA REQUIREMENTS FDR METALAXYL
Data Requirement Composition^
§158.135 Toxicology
ACUTE TESTING:
81-1 - Acute Oral - Rat TGAI
81-2 - Acute Dermal - Rabbit TGAI
81-3 - Acute Inhalation - Rat TGAI
81-4 - Eye Irritation - Rabbit TGAI
81-5 - Dermal Irritation - TGAI
Rabbit
81-6 - Dermal Sensitization - TGAI
Guinea Pig
81-7 - Delayed Neurotoxicity - TGAI
Hen
SUBCHRONIC TESTING:
82-1 - 90-Day Feeding
- Rodent TGAI
- Non-rodent TGAI
Does EPA Have
Data to Satisfy
This Require-
Use2 rrent? (Yes, No
Pattern or Partially)
A,B Yes
A,B Yes
A,B No
A,B Yes
A,B Yes
A,B Yes
A,B No
A,B Yes
A,B Yes
Time Perkx
Must Additional After EPA
Data Be Submitted Notificati<
Bibliographic Under FIFRA Section to Report
Citation 3(c)(2)(B)? Data3 ,
00063990,00063991 No
00154308
00063993,00063994 No
Yes 9 Months
00084108 No
00084107 No
00084109 No
No4
00084110,00148087 No
00084111 No
60
-------
TABLE A
GENERIC DATA REQUIREMENTS FDR METALAXYL
Does EPA Have Time Period
Data to Satisfy * Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 nent? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Composition1 Pattern or Partially) Citation 3(c)(2)(B)? Data3
§158.135 Toxicology (cont'd)
SUBCHRONIC TESTING (cont'd):
82-2 - 21-Day Dermal
82-3 - 90-Day Dermal
82-4 - 90-Day Inhalation
82-5 - 90-Day Neurotoxicity
CHRONIC TESTING:
83-1 - Chronic Toxicity
2 Species:
- Rodent, and
- Nonrodent
83-2 - Oncogenicity Study
2 Species:
- Rat, and
- Mouse
TGAI A,B Yes 00072394 No
TGAI A,B No No5
TGAI A,B Yes 00109471,00103564 No
TGAI A,B No No6
TGAI A,B Yes 00098481 No
TGAI A,B Yes 00071598 No
TGAI A,B Yes 00098481,00013209 No
TGAI A,B Yes 00103354,00150094 No
61
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Composition^- Pattern
Does EPA Have ^ Time Period
Data to Satisfy Must Additional After EPA
This Require- Data Be Submitted Notification
ment? (Yes, No Bibliographic Under FIFRA Section to Report
or Partially) Citation 3(c)(2)(B)? Data3
§158.135 Toxicology (cent1d)
CHRONIC TESTING (cont'd):
83-3 - Teratogenicity
2 Species:
- Rat, and
- Rabbit
TGAI
TGAI
83-4 - Reproduction - Rat TGAI
MUTAGENICITY TESTING;
84-2 - Gene Mutation (Ames Test) TGAI
84-2 - Structural Chromosomal TGAI
Aberration
A,B
A,B
A,B
A,B
A,B
A,B
Yes
Yes
Yes
Yes
Yes
Yes
84-2 - Other Mechanisms of TGAI
Mutagenicity
SPECIAL TESTING:
85-1 - General Metabolism PAIR OR PAIRA A,B Partially
00161405,00144423 No
00161404,00144372 No
00144371
0071600 No
00084113,00154301, No
00154302,00103362
00103361,0084114 No
00154302,00154306, No
00154663,00103363
00071613,00071614, Yes?
00098084
24 Months
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
FOOTNOTES:
j/ Composition: TGAI = Technical grade active ingredient; PAI = Pure active ingredient; PAIRA = Pure active ingredient,
radiolabeled; Choice = Choice of several test substances determined on a case-by-case basis.
2/ The use patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, NonFoods,; C = Aquatic, Food Crop;
D = Aquatic, Nonfood; E = Greenhouse, Food Crop; F = Greenhouse, Nonfood; G = Forestry; H = Domestic Outdoor; I =.
Indoor; IP = Industrial Preservative.
V Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
4/ Metalaxyl is not an organophosphate or a metabolite or degradation product thereof, so a study is not required.
V The study is not required because the 21 day dermal study showed no significant toxicological effects.
6/ Since an acute neurotoxicity study is not required for this compound and there is no evidence of neurotoxicity in
mammalian species, this study is not required.
7/ A repeated dose study of the absorption, distribution, and excretion and a study identifying metabolites in male
rats is needed.
63
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Use2
Data Requirement Composition1 Pattern
§158.145 Wildlife and
Aquatic Organisms
AVIAN AND MAMMALIAN TESTING
71-1 - Acute Avian Oral TGAI A,B
Toxicity
71-2 - Avian Subacute Dietary
Toxicity
- Upland Game Bird, and TGAI A,B
- Waterfowl TGAI A,B
71-3 - Wild Mammal Toxicity TGAI A,B
71-4 - Avian Reproduction TGAI A,B
71-5 - Simulated and Actual
Field Testing
- Mammal TEP A,B
- Birds TEP A,B
Does EPA Have
Data to Satisfy Must Additional
This Require- Data Be Submitted
ment? (Yes, No Bibliographic Under FIFRA Section
or Partially) Citation 3(c)(2)(B)?
Yes 00077334 No
Yes 00077335 No
Yes 00063989 No
No No
No No4
No No
No No
Time Period
After EPA
Notification
to Report
Data3
64
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Use2
Composition! Pattern
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3(c)(2)(B)?
Time Period
After EPA
Notification
to Report
Data3
S158.145 Wildlife and
Aquatic Organisms (cont'd)
AQUATIC ORGANISM TESTING
72-1 - Freshwater Fish Toxicity
- Coldwater Fish Species
(Trout) and
(2
- Warmwater Fish Species
(Bluegill)
(2
72-2 - Acute Toxicity to Fresh-
water Invertebrates
(2
72-3 - Acute LCso Estuarine and
Marine Organisms
- Fish
(2
- Oyster
TGAI
TEP
Ib/gal
TGAI
TEP
Ib/gal
TGAI
TEP
Ib/gal
i
|
TGAI
'TEP
Ib/gal
TGAI
TEP
A,B
A,B
EC)
A,B
A,B
EC)
A,B
A,B
EC)
A,B
A,B
EC)
A,B
A,B
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
NO
00071303,00100447 No
00072396 No
00071302,00100446 No
00071301 No
00100448,00071306 No
0071304 No
No5
No5
Yes6 12 Months
Yes? 12 Months
(2 Ib/gal EC)
65
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
S158
Use2
Data Requirement Compositionl Pattern
.145 Wildlife and
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3(c)(2)(B)?
Time Period
After EPA
Notification
to Report
Data3
Aquatic Organisms (cont'd)
AQUATIC ORGANISM TESTING (cont'd)
72-3
72-4
- Acute Toxicity to Estuarine
and Marine Organisms
- Shrimp TGAI A,B
TEP A,B
(2 Ib/gal EC)
- Fish Early Life Stage
- Freshwater TGAI A,B
- Estuarine TGAI A,B
- Aquatic Invertebrate
Life Cycle
- Freshwater TGAI A,B
- Estuarine TGAI A,B
No
No
Yes
No
Yes
No
Yes6
Yes?
00071308 No
No
00071307 No
ReservedS
12 Months
12 Months
72-5 - Fish Live Cycle
- Freshwater and
Estuarine
TGAI
A,B
No
No
66
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Does EPA Have Time Period
Data to Satisfy Must Additional After EPA
This Reouire- Data Be Submitted Notification
Use2 ment? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Compositionl Pattern or Partially) Citation 3(c)(2)(B)? Data3
S158.145 Wildlife and
Aquatic Organisms (cont'd)
AQUATIC ORGANISM TESTING (cont'd)
72-6 - Aquatic Organism TGAI A,B Yes9 No
Accumulation
72-7 - Simulated or Actual Field
Testing
- Aquatic Organisms TEP A,B No No
I/ Composition: TGAI = Technical grade of the active ingredient; TEP = Typical end-use product.
2/ The use patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, Nonfood Crop; C = Aquatic,
Food Crop; D = Aquatic, Nonfood; E = Greenhouse, Food Crop; F = Greenhouse, Nonfood; G = Forestry; H = Domestic
Outdoor; I = Indoor.
V Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
4/ Avian reproduction studies are not required due to the very low acute toxicity, no evidence of bioaccumulation,
and the lack of persistence in field dissipation studies.
J>/ Waived due to LC^QS on freshwater fish {> 100 ppm).
6/ Required to support citrus and; cotton uses.
7/ Acute freshwater testing indicates this formulated product is more toxic to aquatic organisms than the
technical grade.
J3/ Reserved pending results of acute estuarine testing on the technical and formulated products.
9/ Refer to Science EAB chapter which can be obtained. Please refer to page 1 of this document for instructions.
! i
67
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Use2
Compositionl Pattern
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3(c)(2)(B)?
Time Period
After EPA
Notification
to Report
Data3
§158.155 Nontarqet Insect
NONTARGET INSECT TESTING - POLLINATORS;
141-1 - Honey Bee Acute TGAI
Contact LD5Q
141-2 - Honey Bee - Toxicity TEP
of Residues on
Foliage
141-4 - Honey Bee Subacute TEP
Feeding Study
141-5 - Field Testing for TEP
Pollinators
NONTARGET INSECT TESTING -
AQUATIC INSECTS;
142-1 - Acute Toxicity to (Reserved)5
Aquatic Insects
142-2 - Aquatic Insect Live (Reserved)5
Cycle Study
142-3 - Simulated or Acutal (Reserved)5
Field Testing for
Aquatic Insects
Yes
No
No
No
40276701
No
No*
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Does EPA Have _ Time Period
Data to Satisfy Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 ment? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Composition* Pattern or Partially) Citation 3(c)(2)(B)? Data3
S158.155 Nontarget Insect (cont'd)
143-1 - NONTARGET INSECT (Reserved)5
thru TESTING - PREDATORS
143-3 - AND PARASITES
I/ Composition: TGAI = Technical grade of the active ingredient; TEP = Typical end-use product.
2/ The use patterns are coded asjfollows: A = Terrestrial, Food Crop; B = Terrestrial, Nonfood; C = Aquatic,
Food Crop; D = Aquatic, Nonfood; E = Greenhouse, Food Crop; F = Greenhouse, Nonfood; G = Forestry; H = Domestic
Outdoor; I = Indoor. ;
3/ Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
4/ The results of the Honey Bee acute contact LDso study shows that metalaxyl is practically non-toxic to
honey bees and further testing is not required.
5/ Reserved pending Agency decision as to whether the data requirement should be established.
69
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Does EPA Have - Time Period
Data to Satisfy Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 ment? (Yes, No Bibliographic Under FIFRA Section to Report
Compositionl Pattern or Partially) Citation 3(c)(2)(B)? Data3
§158.130 Environmental Fate
DEGRADATION STUDIES-LAB:
161-1 - Hydrolysis
Photodeqradat ion
161-2 - In Water
161-3 - On Soil
161-4 - In Air
METABOLISM STUDIES-LAB:
162-1 - Anerobic Soil
162-2 - Anaerobic Soil
162-3 - Anaerobic Aquatic
163-4 - Aerobic Aquatic
MOBILITY STUDIES:
TGAI or PAIRA A,B Yes 00104493 No
TGAI or PAIRA A,B NO Yes 9 Months
TGAI or PAIRA A Yes 00100456 No
TGAI or PAIRA N/A No No4
TGAI or PAIRA A,B Yes 00104494 No
TGAI or PAIRA A Yes 00104494 No
TGAI or PAIRA N/A NO No4
TGAI or PAIRA N/A NO NO4
163-1 - Leaching and
Adsorption/
Desorption
TGAI or PAIRA A,B
Yes
00100464,00100465,
00100466
No
70
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TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
§158.130 Environmental Fate
MOBILITY STUDIES (cont'd):
163-2 - Volatility (Lab)
164-3 - Volatility (Field)
DISSIPATION STUDIES-FIELD:
164-1 - Soil
164-2 - Aquatic (Sediment)
164-3 - Forestry
164-4 - Combination and
Tank Mixes
165-5 - Soil, Long-Term
ACCUMULATION STUDIES:
165-1 - Rotational Crops
(Confined)
165-2 - Rotational Crops
Composition^-
(cont'd)
TEP
TEP
TEP
TEP
TEP
TEP
1
!
| TEP
i
i
f>AIRA
TEP
Use2
Pattern
A
N/A
A,B
N/A
N/A
A
A
A
A
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Yes
No
No
No
No
No
No
No
Partially
Time Period
Must Additional After EPA
Data Be Submitted Notification
Bibliographic Under FIFRA Section to Report
Citation 3(c)(2)(B)? Data3
00100455 No
No4
Yes 27 Months
No4
No4
No5
No6
Yes 39 Months
00104376,00104381, Reserved7
(Field)
00104382,00104383,
00104384,00104385
71
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Use2
Composition! Pattern
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No
or Partially)
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3{c)(2)(B)?
Time Period
After EPA
Notification
to Report
Data3
S158.130 Environmental Fate (cont'd)
ACCUMULATION STUDIES (cont'd);
165-3 - Irrigated Crops TEP
165-4 - In Fish TGAI or PAIRA
165-5 - In Aquatic Nontarget TEP
Organisms
N/A
A,B
N/A
NO
Yes
No
00100468,00100470
No
72
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
Data Requirement
Use2
Composition1 Pattern
Does EPA Have
Data to Satisfy
This Require-
Must Additional
Data Be Submitted
ment? (Yes, No Bibliographic Under FIFRA Section
or Partially)
Citation
3(c)(2)(B)?
Ground Water Monitoring
Studies
NO
Time Period
After EPA
Notification
to Report
Data3
§158.140 Reentry Protection
132-1 - Foliar Dissipation
132-1 - Soil Dissipation
133-3 - Dermal Exposure
133-4 - Inhalation Exposure
§158.142 Spray Drift
201-1 - Droplet Size Spectrum
202-1 - Drift Field Evaluation
Monitoring Studies
TEP
TEP
TEP
TEP
TEP
TEP
A,B
A,B
A,B
A,B
A,B
A,B
NO
NO
NO
NO
NO
NO
NO
NO
Conditional8
Conditional8
No9
NO*
27 Months
27 Months
6 Months/
24 Months
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METALAXYL
FOOTNOTES:
I/ Composition: TGAI = Technical grade of the active ingredient; PAIRA = Pure active ingredient, radiolabeled;
TEP = Typical end-use product.
2/ The use patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, NonFood,; C = Aquatic, Food
Crop; D = Aquatic, Nonfood; E = Greenhouse, Food Crop; F = Greenhouse, Nonfood; G = Forestry; H = Domestic Outdoor;
I = Indoor.
V Data must be submitted within the indicated timeframes, which begin upon receipt of the Guidance Document.
4_/ Not required based on the use pattern of metalaxyl.
V Tank mix data requirements are not being imposed by this Standard.
6/ Soil long-term study is not required because of the dissipation rate of metalaxyl.
7/ Data are reserved pending the results of the confined rotational crop study.
8/ Human-exposure monitoring data may be submitted at the registrant's option. If dermal exposure data are submitted,
inhalation exposure data must also be submitted.
9/ Data are not required based on the moderate acute inhalation toxicity of metalaxyl.
IS/ A small-scale retrospective ground-water study is required. The registrant must submit a protocol for Agency
approval six months after receipt of the Guidance Document. The timeframe for submission of the study will be
24 months after Agency approval of the protocol.
74
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING METALAXYL
Data Requirement
Composition-'
Use2
Pattern
Does EPA Have
Data to Satisfy
This Require-
ment? (Yes, No Bibliographic
or Partially) Citation
§158.120 Product Chemistry
Product Identity and Composition
61-1 - Product Identity MP
and Disclosure of
Ingredients
61-2 - Description of Beginning MP
Materials and Manufac-
turing Process
61-3 - Discussion of Formation MP
of Impurities
Analysis and Certification of
Product Ingredients
62-1 - Preliminary Analysis MP
of Product Samples
62-2 - Certification of MP
Ingredient Limits
62-3 - Analytical Methods MP
to Verify Certified
Limits
All
All
All
All
All
Yes
Partially
Partially
No
00104498 4
00104498 4
All Partially 00104498
00104483
00104483
40435001
Partially 00104498
Must Additional
Data Be Submitted
Under FIFRA Section
3(c)(2)(B)?
No
Yes5
Yese
Yes
Yes
10
Time Period
After EPA
Notification
to Report
Data3
6 Months
6 Months
12 Months
6 Months
12 Months
75
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING METALAXYL
Use2
Data Requirement Composition1 Pattern
Does EPA Have Tine Period
Data to Satisfy __ Must Additional After EPA
This Require- Data Be Submitted Notification
ment? (Yes, No Bibliographic Under FIFRA Section to Report
or Partially) Citation 3(c)(2)(B)? Data3
§158. 120 Product Chemistry (continued)
Physical and Chemical Characteristics
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
- Color
- Physical State
- Odor
- Melting Point
- Boiling Point
- Density, Bulk Density,
or Specific Gravity
- Solubility
- Vapor Pressure
- Dissociation Constant
- Octanol/Water Partition
Coefficient
- pH
- Storage Stability
MP
MP
MP
MP
MP
MP
MP
MP
MP
MP
MP
MP
All
All
All
All
All
All
All
All
All
All
All
All
Yes
Yes
Yes
Yes
N/A11
Yes
Yes
Yes
Yes
Yes
Yes
Yes
00104483
00104483
00104483
00104483
00104483
00104483
00104483
00104483
40435001
40435001
00104483
No
No
No
No
No
No
No
No
No
No
No
No
76
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TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING METALAXYL
Does EPA Have ' Time Period
Data to Satisfy Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 ment? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Composition* Pattern or Partially) Citation 3(c)(2)(B)? Data3
§158.120 Product Chemistry (continued)
Other Requirements;
64-1 - Submittal of Samples MP N/A N/A N/A12 No N/A
77
-------
FOOTNOTES FOR PREVIOUS TABLE B
I/ The 90% technical is the only registered metalaxyl manufacturing-use product. Composition: TGAI = technical grade
of the active ingredient; PAI = pure active ingredient.
2/ The use patterns are coded as follows: "A" for Terrestrial, Food Crop; "B" for Terrestrial, Non-Foods,; "C" for
Aquatic, Food Crop, "D" for Aquatic, Non-Food; "E" for Greenhouse, Food Crop; "F" for Greenhouse, Non-Food;
"G" for Forestry; "H" for Domestic Outdoor; and "I" for Indoor.
3/ Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
4/ Information obtained from desk references.
5/ Complete information must be provided regarding the nature of the process (batch or continuous), the relative
amounts of beginning material and the order in which they are added, the chemical equations for each intended
reaction, equipment used to produce each intermediate and the final product, reaction conditions, the duration
of each step of the process, purification procedures, and quality control measures. In addition, the name and
address of the manufacturer, producer, or supplier of each beginning material must be provided, along with in-
formation regarding the properties of each beginning material used to manufacture each product. In order to
assess the potential for contamination with nitrosamines, a description of manufacturing process conditions
favoring formation of nitrosamines must be provided.
6/ A detailed discussion of all impurities that are or may be present at >^ 0.1%, based on knowledge of the beginning
materials, chemical reactions (intended and side) in the manufacturing process, and any contamination during and
after production must be submitted. This discussion must also address the possible formation of nitrosamines
from metalaxyl and its impurities.
7/ Five or more representative samples must be analyzed for the amount of active ingredient and each impurity for
which a certified limit is required. Complete validation data (accuracy, precision) must be submitted for each
analytical method used.
8/ Available data do not meet the requirements of 40 CFR 158.120, Part 62-2.
9/ Upper and lower limits for metalaxyl must be provided, certified, and validated by sample analysis using
analytical procedures for which accuracy and precision data have been provided. Upper limits for each impurity
present at >^ 0.1% (w/w), and for each "toxicologically significant" impurity present at < 0.1% (w/w) must be
provided, certified, and validated by sample analysis using analytical procedures for which accuracy and
precision data have been provided. All nitrosamines must be identified and quantified in six samples of each
product; two samples of each must be analyzed shortly after production, 3 months after production and 6 months
after production. A method sensitive to 1 ppm of N-nitroso contaminants must be used. An upper limit must be
provided (and certified) for all nitrosamines found. Certifications should be submitted on EPA Form 8570
(Rev. 2-85).
10/ Analytical methods must be provided to determine the active ingredient and each toxicologically significant
impurity (including nitrosamines) for which a certified limit is required. Each method must be accompanied
by validation studies indicating its accuracy and precision. These methods must be suitable for enforcement
of certified limits.
ll/ Not reauired; a solid at room temperature.
12/ N/A = Not applicable.
78
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING METALAXYL
Does EPA Have - Time Period
Data to Satisfy Must Additional After EPA
This Require- Data Be Submitted Notification
Use2 ment? (Yes, No Bibliographic Under FIFRA Section to Report
Data Requirement Compositionl Pattern or Partially) Citation 3(c)(2)(B)? Data3
§158.
ACUTE
81-1
81-2
81-3
81-4
81-5
81-6
135 Toxicology
TESTING:
- Acute Oral - Rat MP A,B No
- Acute Dermal MP A,B No
- Acute Inhalation
- Rat MP A,B No
- Primary Eye Irritation
- Rabbit MP A,B No
- Primary Dermal Irritation
- Rabbit MP A,B No
- Dermal Sensitization MP A,B No
Yes 6 Months
Yes 6 Months
Yes 6 Months
Yes 6 Months
Yes 6 Months
Yes 6 Months
Guinea Pig
I/ Composition: MP = Manufacturing-use product.
2/ The use patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, NonFood, C = Aquatic, Food
Crop; D = Aquatic, Nonfood; E = Greenhouse, Food Crop; F = Greenhouse, Nonfood; G = Forestry; H = Domestic Outdoor;
I = Indoor.
3/ Data must be submitted within the indicated time frames which begin upon receipt of the Guidance Document.
79
-------
-------
APPENDIX II
LABELING APPENDICES
80
-------
-------
SUMMARY-1
LABEL CONTENTS
HO CPR 162.10 requires that certain specific labeling
statements appear at certain locations on the label. This
Is referred to as format labeling. Specific label items listed
below are keyed to the table at the end of this Appendix.
Item 1. PRODUCT NAME - The name, brand or trademark is
required to be located on the front panel, preferably centered
in the upper part of the panel. The name of a product will
not be accepted if it is false or misleading.
Item 2. COMPANY NAME AND ADDRESS - The name and address
of the registrant or distributor Is required on the label.
The name and address should preferably be located at the
bottom of the front panel or at the end of the label text.
(
Item 3. NET CONTENTS - A net contents statement is
required on all labels or on the container of the pesticide.
The preferred location is the bottom of the front panel
immediately above the company name and address, or at the end
of the label text. The net contents must be expressed in the
largest suitable unit, e.g., "1 pound 10 ounces" rather than
"26 ounces." In addition to English units, net contents may
be expressed in metric units. [40 CPR I62.10(d)]
Item 4. EPA REGISTRATION NUMBER - The registration
number assigned to the pesticide product must appear on the
label, preceded by the phrase "EPA Registration No.," or "EPA
Reg. No." The registration number must be set in type of a
size and style similar to other print on that part of the
labej. on which it appears and must run parallel to it. The
registration number and the required identifying phrase must
not appear in such a manner as to suggest or imply recommendation
or endorsement of the product by the Agency.
[40 CPR I62.10(e)]
Item 5. EPA ESTABLISHMENT NUMBER - The EPA establishment
number, preceded by the phrase "EPA Est.n is the final" estab-
lishment at which the product was produced, and may appear
In any suitable location on the label or Immediate container.
It must also appear on the wrapper or outside container of
the package if the EPA establishment number on the Immediate
container cannot be clearly read through such wrapper or container.
[40 CPR I62.10(f)]
Item 6A. INGREDIENTS STATEMENT - An Ingredients statement
Is required on the front panel. The Ingredients statement must
contain the name and percentage by weight of each active ingredient
and the total percentage by weight.of all Inert ingredients.
The preferred location is immediately below the product name.
The Ingredients statement must run parallel with, and be clearly
distinguished from, other text on the panel. It must not be
placed in the body of other text. [40 CPR I62.10(g)3
81
-------
SUMMARY-2
Item 6B. POUNDS PER GALLON STATEMENT - For liquid agricul-
tural formulations, the pounds per gallon of active Ingredient
must be indicated on the label.
Item 7. FRONT LABEL PRECAUTIONARY STATEMENTS - Front panel
precautionary statements must be grouped together, preferably
within a block outline. The table below shows the minimum type
size requirements for various size labels.
Size of Label Signal Word "Keep Out of Reach
on Front Panel Minimum Type Size of Children"
in Square Inches All Capitals Minimum Type Size
5 and under 6 point 6 point
above 5 to 10 10 point • . 6 point
above 10 to 15 12 point 8 point
above 15 to 30 14 point 10 point
30 18 point 12 point
Item 7A. CHILD HAZARD WARNING STATEMENT - The statement
"Keep Out of Reach of Children" must be located on the front
panel above the signal word except where contact with children
during distribution or use is unlikely. [40 CFR I62.10(h) (1) ( 11)]
Item 7B. SIGNAL WORD - The signal word (DANGER, WARNING,
or CAUTION) is required on the front panel immediately below
the child hazard warning statement. [40 CFR 162.10 (h)(l)(i)]
Item 7C. SKULL & CROSSBONES AND WORD "POISON" - On products
assigned a toxicity Category I on the basis of oral, dermal,
or Inhalation toxicity, the word "Poison" shall appear on the
label in red on a background of distinctly contrasting color and
the skull and crossbones shall appear in immediate proximity to
the word POISON. [40 CFR 162. 10(h) (1) (1) ]
Item 7D. STATEMENT OF PRACTICAL' TREATMENT - A statement
of practical treatment (first aid or other) shall appear on
the label of pesticide products in toxicity Categories I,
II, and III. [40 CFR I62.10(h) (1) (ill)]
Item 7E. REFERRAL STATEMENT - The statement "See Side
(or uack) Panel for Additional Precautionary Statements" is
required on the front panel for all products, unless all
required precautionary statements appear on the front panel.
[40 CFR I62.10(h)(l)(iil)]
Item 8. SIDE/BACK PANEL PRECAUTIONARY LABELING - The
precautionary statements listed below must appear together
on the label under the heading "PRECAUTIONARY STATEMENTS."
The preferred location is at the top of the side or back
panel preceding the directions for use, and It Is preferred
that these statements be surrounded by a block outline. Each
of the three hazard warning statements must be headed by the
appropriate hazard title. [40 CFR I62.10(h)(2)].
82
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SUMMARY-3
Item 8A. HAZARD TO HUMANS AND DOMESTIC ANIMALS - Where a
hazard exists to humans or domestic animals, precautionary
statements are required Indicating the particular hazard, the
route(s) of exposure and the precautions to be taken to avoid
accident, injury or damage. [HO CPR I62.10(h)(2)(1)3
Item 8B. ENVIRONMENTAL HAZARD - Where a hazard exists to
non-target organisms excluding humans and domestic animals,
precautionary statements are required stating the nature of
the hazard and the appropriate precautions to avoid potential
accident, injury, or damage. [*40 CPR I62.10(h) (2) (ii)]
Item 8C. PHYSICAL OR CHEMICAL HAZARD - PLAMMABILITY
Precautionary statements relating to flammability of a product
are required to appear on the label if it meets the criteria
in the PHYS/CHEM Labeling Appendix. The requirement is
based on the results of the flashpoint determinations and
flame extension tests required to be submitted for all products.
These statements are to be located in the aide/back panel
precautionary statements section, preceded by the heading
"Physical/Chemical Hazards." Note that no signal word is
used in conjunction with the flammability statements.
Item 9A. RESTRICTED USE CLASSIFICATION - PIPRA sec. 3(d)
requires that all pesticide formulations/uses be classified
for either general or restricted use. Products classified
for restricted use may be limited to use by certified applicators
j>r persons under their direct supervision (or may be subject
to other restrictions that may be imposed by regulation).
In the Registration Standard, the Agency has (1) indicated
certain formulations/uses are to be restricted (Section IV
indicates why the product has been classified for restricted
use); or (2) reserved any classification deci'slon until
appropriate data are submitted.
The Regulatory Position and Rationale states whether
products containing this active ingredient are classified
for restricted use. If they are restricted the draft label(s)
submitted to the Agency as part of your application must
reflect this determination (see below).
If you do not believe that your product should be classified
for restricted use, you must submit any Information and
rationale with your application for reregiatratlon. During
the Agency*s review of your application, your proposed classi-
fication determination will be evaluated In accordance with
the provisions of 40 CPR I62.11(e). You will be notified of
the Agency's classification decision.
83
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SUMMARY -4
Classification Labeling Requirements
If your product has been classified for restricted use,
the following label requirements apply:
1. All uses restricted.
a. The statement "Restricted Use Pesticide" must
appear at the top of the front panel of the label. The
statement must be set in type of the same minimum size
as required for human hazard signal word (see table in 40
CFR
b. Directly below this statement on the front panel,
a summary statement of the terms of .restriction must
t appear (including the reasons for restriction if specified
in Section I). If use is restricted to certified applicators,
the following statement is required: "For retail sale
to and use only by Certified Applicators or persons
under their direct supervision and only for those uses
covered by the Certified Applicator's Certification."
2. Some but not all uses restricted. If the Regulatory ' .
Position and Rationale states that some uses are classified
for restricted use, and some are unclassified, several courses
of action are available:
a. You may label the product for Restricted use.
If you do so, you may include on the label uses that
are unrestricted, but you may not distinguish them
or. the label as being unrestricted.
b. You may delete all restricted uses from your
label and submit draft labeling bearing only unrestricted
uses .
c. You may "split" your registration, i.e., register
two separate products with Identical formulations, one
bearing only unrestricted uses, and the other bearing
restricted uses. To do so, submit two applications for
reregistratlon, each containing all forms and necessary
labels. Both applications should be submitted simul-
taneously. Note that the products will be assigned
separate registration numbers.
Item 9B. MISUSE STATEMENT - All products must bear the
misuse statement, "It is a violation of Federal law to use
this product in a manner Inconsistent with its labeling."
This statement appears at the beginning of the directions
for use, directly beneath the heading of that section.
84
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SUMMARY-5
Item 10A. REENTRY STATEMENT - If a reentry interval
has been established by the Agency, it must be included on
the label. Additional worker protection statements may be
required in accordance with PR Notice 83-2, March 29, 1983.
Item 10B. STORAGE AND DISPOSAL BLOCK - All labels are
required to bear storage and disposal statements. These
statements are developed for specific containers, sizes, and
chemical content. These instructions must be grouped and
appear under the heading "Storage and Disposal" in the directions
for use. This heading must be set In the same type sizes as
required for the child hazard warning. Refer to Appendix II,
STOR, PEST/DIS, and CONT/DIS to determine the storage and
disposal instructions appropriate for your products.
Item IOC. DIRECTIONS FOR USE - Directions for use must
be stated in terms which can be easily read and understood by
the average person likely to use or to supervise the use of
the pesticide. When followed, directions must be adequate to
protect the public from fraud and from personal injury and to
prevent unreasonable adverse effects on the environment.
[40 CFR 162.10]
COLLATERAL LABELING
Bulletins, leaflets, circulars, brochures, data sheets,
flyers, or other written or graphic printed matter which is
referred To on the label or which is to accompany the product
are termed collateral labeling. Such labeling may not bear
claims or representations that differ In substance from those
accepted in connection with registration of the product. It
should be made part of the response to this notice and submitted
for review.
85
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PRECAUTIONARY ITATEMEMT8
HAZARDS TO HUMANS
d OOMEBTC ANMAtS)
OANOCJI
ENMRONMENTAl HAZARDS
PHYSCAL Off CHtMCAL
HAZARDS
pntOTONt POR UM
Ik* ttoMM * H«rt tar
Ml n*u* k • Mmv
M-fiMTNV STATEMENT
STORAGE AND
r DISPOSAL
STOAAOf'
CHOP:
RESTRICTED USE
PESTICIDE
(reason for clasnlfyinp.)
1HCIR OI«BCt «UPe«VUION MO OMLT K* TOOBE
oveno IT me comneo APPUCATCM>I cnmncATicw
CM
PRODUCT
NAME
ACTMI NOMEOCNT:
MCKT NOREOCNT8:
TOTAL:
10000%
TWO MOOUCT CONTAM8 LM Of PW OAUON
KEEP OUT OF REACH OF CHILDREN
DANGER —POISON
STATEMENT OF PfUCTCAL TREATMENT
F8WAOOWEO:
f M EYE8
SEE SOE PANEL POM AOOmONAL PMCAUTDNANV STATEMENTS
MfOBY! -
TOWN. IT ATE
ISTABU8HMENT NO.
NET r-QMt»MT«
C«OP:
CHOP:
CROP:
CMOP:
WAMANTY STATEMENT
n x
-------
I
!':
!>!i
• a
11!
I;
A
>
*«
5
i
SSSf
> sIS
''
M
00
"~ 4b
2 i
?
>
C
H
X
m
9
5
3)
m
I
I
3
M
TJ
'X
mo
-------
SUMMARY-6
LABELING REQUIREMENTS OP THE PIFRA, AS AMENDED
ITEM
1
2
3
li
5
6A
6B
7
7A
7B
LABEL ELEMENT
Product name
Company name
and address
Net contents
EPA Reg. No.
EPA Eat. ta.
Ingredients
statement
Pounds/gallon
* statement
Front panel
precautionary
statements
Keep Out of Reach
of Children
(Child hazard
Naming)
Signal word
TROBmCltY'"
Of REQUIREMENT
products
products
All products
All products
All products
All products
Liquid products
where dosage
given as IDS.
al/unit area
All products
All products
All products
PLACEMENT 6N LABEL 1
REQUIRED
Front panel
None
None
None
None
Front panel
Front panel
Front panel
Front panel
Front panel
tTOFEHHEU
Center front
panel
Bottom front
panel or end
of label text
Bottom front
panel or end
of label text
Front panel
Front panel,
Immed lately
before or
following
Reg. No.
immediately
following
product name
Directly below
the main
Ingredients
statement
Above signal
word
Immediately
below child
hazard
warning
COMMENTS
If registrant is not the producer, mur.t
be qualified by "Packed for . . .,"
•'Distributed by. . .."etc.
May be in metric units in addition to
U.S. units
Must be in similar type size and run
parallel to other type.
May appear on the container Instead o.
the label.
Text must run parallel with other texi.
on the panel.
All front panel precautionary statement/I
must be grouped together, preferably
blocked. •
Note type size requirements.
Note type size requirements.
88
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SUMMARY-?
ITEM
••s
7C
TD
7E
b
HA
8B
LABEL ELEMENT
Skull & cross-
booea and word
POISON (In red)
Statement or
Practical
Treatment or
Plrat Aid
Referral
statement
V
Side/back panel
precautionary
statements
Hazards to
humans and
domestic
animals
Environmental
hazards
APPLICABILITY —
OP REQUIREMENT
products
which are Cat-
egory I based
on oral, der-
mal , or Inhala-
tion toxlclty
products
In Categories
I, II, and III
All products
where pre-
cautionary
labeling
appears on
other than
front panel.
All products
All products
In Categories
I, II, and III
All products
I PLACEMENT ON LABEL 1
RETIRED
Front panel
Category I:
Front panel
unless refer-
ral statement
Is used.
Others;
Grouped with
side panel
precautionary
statements.
Front panel
None
None
None
FK&KERRED
Both In close
proximity to
signal word
Front panel
for all.
1
Tbp or side
of back panel
preceding
directions
for use
Same as above
Same as above
COMMENTS
*
Must be grouped under the headings In
8A, 8B, and 8C; preferably blocked.
Must be preceded by appropriate signal
word.
Environmental hazards Include bee
caution where applicable.
89
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SUMMARY-8
ITEM
86
9A
9B
10A
10B
IdC
LABEL ELEMENT
Physical or
chemical
hazards
Restricted
block
Misuse
statement
Reentry
statement
Storage and
disposal block
s,
Directions
for use
APPLICABILITY
OP REQUIREMENT
All pressurized
products, others
with flash
points under
150°P
All restricted
products
All products
Fft Notice B3-2
or as determined
by the Agency
All products
All products
PLACEMENT ON LABEL
REQUIRED
None
Top center
of front
panel
Inmediately
following
heading of
directions
for use
In the
directions
for use
In the
directions
for use
None
FHEMSHHKL)
Same as above
Preferably
blocked
Immediately
after misuse
statement
Inmediately
before
specific
directions
for use or
at the end of
directions
for use
None
COMMENTS
Refer to Appendix II guide
PHYS/CHEM
Includes a statement of the terms of
restriction. The words "RESTOICTED U
PESTICIDE" must be same type size as
signal word.
Required statement is:
"It is a violation of Federal law
to use this product in a manner
inconsistent with its labeling."
Must be set apart and clearly distin-
guishable from from other directions
for use.
Refer to Appendix II guides STOR.
CONT/DIS, and PEST/DIS for further
information and required statements.
May be In metric as well as U.S. unit..
90
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fi 162.10 Labeling requirement*.
(a) General—<1) Content* of the
label Every pesticide products «h*Mi
bear a label containing the informa-
tion specified by the Act and the regu-
lations in this Part. The contents of a
label must show clearly and promi-
nently the following:
.it) The name, brand, or trademark
under which the product Is sold as pre-.
scribed In paragraph (b) of this sec-
tion;
(U) The name and address of the
producer, registrant, or person for
whom produced as prescribed In para-
graph (c) of this section:
(111) The net contents as prescribed
in paragraph (d) of this section;
(iv) The product registration
number as prescribed in paragraph (e)
of this section:
-------
Environmental Protection Agency
§ 162.10
(v) The producing establishment
number as prescribed in paragraph g statement
concerning the composition of the
product;
(11) A false or nti«i*«ai»tŁ statement
concerning the effectiveness of the
product as a pesticide or device;
(ill) A false or tn1«l**'*<"g statement
about the value of the product for
purposes other than as a pesticide or
device;
(iv) A false or "•<*i*«"«"y comparison
with other pesticide* or devices;
(v) Any «*-Vftrr~*t directly or indi-
rectly implying that the pesticide or
device is r^oofnin^TKtf*^ or endorsed by
any agency of the Federal Govern-
ment;
(vi) The name of a pesticide which
contains two or more principal active
92
-------
§ 162.10
40 CFR Ch. I (7-1-35 Edition)
ingredients if -the name suggests one
or more but not all such principal
active ingredients even though the
names of the other ingredients are
stated elsewhere in the labeling;
(vii) A 'true statement used in such a
way as to give a false or misleading im-
pression to the purchaser;
(viii) Label disclaimers which negate
or detract from labeling statements re-
quired under the Act and these regula-
tions;
(ix) Claims as to the safety of the
pesticide or its ingredients, including
statements such as "safe," "nonpoison-
ous," "noninjurious," "harmless" or
"nontoxic to_Jiumans and pets" with
or without such a qualifying phrase as
"when used as directed"; and
(x) Non-numerical and/or compara-
tive statements on the safety of the
product, including but not limited to:
(A) "Contains all natural Ingredi-
ents":
(B) "Among the least toxic chemi-
cals known"
(C) "Pollution approved"
(6) Final printed labeling, (i) Except
as provided in paragraph (aX6)(ii) of
this section, final printed labeling
must be submitted and accepted prior
to registration. However, final printed
labeling need not be submitted until
draft label texts have been provision-
ally accepted by the Agency.
(II) Clearly legible reproductions or
photo reductions will be accepted for
unusual labels such as those silk-
screened directly onto glass or metal
containers or large bag or drum labels.
Such reproductions must be of micro-
film reproduction quality.
(b) A'arn*, brand, or trademark. (1)
The name, brand, or trademark under
which the pesticide product la sold
shall appear on the front panel of the
label
(2) No name, brand, or trademark
may appear on the label which:
(1) Is false or miilfailfnc. or
(11) Has not been approved by the
Administrator through registration or
supplemental registration at an addi-
tional name pursuant to f 16X6(bX4).
(c) Name and address of producer.
registrant, or penon for whom pro-
duced. An unqualified "«*TH* myj ad-
dress given on the label shall be con-
sidered as the name and address of the
producer. If the registrant's name ap-
pears on the label and the registrant is
not the producer, or if the name of the
person for whom the pesticide was
produced appears on the label, it must
be qualified by appropriate wording
such as "Packed for ' • V "Distribut-
ed by • • V or "Sold by • • •" to show
that the name is not that of the pro-
ducer.
(d) Net leeight or measure of con-
tents. (1) The net weight or measure
of content shall be exclusive of wrap-
pers or other materials and shall be
the average content unless explicitly
stated as a mtnimutn quantity.
<2) If the pesticide Is a liquid, the
net content statement shall be in
terms of liquid measure at 68* P <20*C>,
and shall be expressed in conventional
American units of fluid ounces, pints.
quarts, and gallons.
(3) If the pesticide is solid or semi-
solid, viscous or pressurized, or is a
mixture of liquid and solid, the net
content statement shall be in terms of
weight expressed as avoirdupois
pounds and ounces.
(4) In all cases, net content shall be
stated in terms of the largest suitable
units. Le., "1 pound 10 ounces" rather
than "26 ounces."
(5) In addition to the required units
specified, net content may be ex-
pressed in metric units.,
(6) Variation above minimum con-
tent or around an average is permissi-
ble only to the extent that it repre-
sents deviation unavoidable in good
manufacturing practice. Variation
below a stated minimum is not permit-
ted. In no case shall., the average con-
tent of the packages in a «hipm*>*it fall
below the stated average content.
(e) Product registration number.
The registration number ««««g™** to
the pesttdde product at the time of
registration «H«J| appear on ttw IV**?.
preceded by the phrase "EPA Regis-
tration No.," or the phrase "EPA Reg,
No." The registration «m»*^n' thfiM be
set in type of a ate *rvi style •fa*» to
other print on that put of the label
on which It appears and shall run par-
allel to It. The registration number
and the required identifying phrase
shall not appear in such a manner as
to suggest or imply recommendation
93
-------
Environmental Protection Agency
§ 162.10
or endorsement of the product by the
Agency.
(f) Producing establishments regis-
tration number. The producing estab-
lishment registration number preced-
ed by the .phrase "EPA Est.". of the
final establishment at which the prod-
uct was produced may appear in any
suitable location on the label or imme-
diate container. It must appear on the
wrapper or outside container of the
package if the EPA establishment reg-
istration number on the immediate
container cannot be clearly read
through such wrapper or container.
(g) Ingredient statement— <1) Gener-
aL The label of each pesticide product
must bear a statement which contains
the name and percentage by weight of
each active Ingredient, the total per-
centage by weight of all Inert ingredi-
ents: and if the pesticide contains ar-
senic In any form, a statement of the
percentages of total and water-soluble
arsenic calculated as elemental ar-
senic. The active Ingredients must be
designated by the term "active Ingredi-
ents" and the inert Ingredients by the
term "inert Ingredients." or the singu-
lar forms of these terms when appro-
priate. Both terms shall be In the
same type size, be aligned to the same
margin and be equally prominent. The
statement "Inert Ingredients, none" is
not required for pesticides which con-
tain 100 percent active ingredients.
Unless the ingredient statement is a
complete analysis of the pesticide, the
term "analysis" shall not be used as a
heading for the ingredient statement.
(2) Position of ingredient statement
(i) The ingredient statement Is nor*
mally required on the front panel of
the label. If there is an outride con-
tainer or wrapper through which the
ingredient statement cannot be dearly
read, the ingredient ff*fltfrnCTft
also appear on such outside ~*
or wrapper. If the ste or form of the
package makes it impracticahle to
place the ingredient fftntfrnifot on the
front panel of the label, permission
may be granted for the ingredient
statement to appear elsewhere,
(11) The text of the ingredient state-
ment must run parallel with other
text on the panel oh which it appears,
and must be clearly distinguishable
from and must not be placed in the
body of other text.
(3) Names to be used in ingredient
statement. The name used for each in-
gredient shall be the accepted
common name, if there is one. fol-
lowed by the chemical name. The
common name may be used alone only
if it is well known. If no common name
has been established, the chemical
name alone shall be used. In no case
will the use of-a trademark or proprie-
tary name be permitted unless such
name has been accepted as a common
name by the Administrator under the
authority of Section 25
-------
§ 162.10
(h) Warnings and precautionary
statements. Required warnings and
precautionary statements concerning
the general areas of toxicological
hazard Including hazard to children.
environmental hazard.'and physical or
chemical hazard fall Into two groups;
those required on the front panel of
the labeling and those which may
appear elsewhere. Specific require-
ments concerning content, placement.
40 CFR Ch. I (7-1-85 Edition)
type size, and prominence are given
below.
(1) Required front panel statements.
With the exception of the child
hazard warning statement, the text re- ,
quired on the front panel of the label
is determined by the Toxicity Categor
ry of the pesticide. The category is as-
signed on the basis of the highest
hazard shown by any of the indicators
in the table below:
H&zard jnrirrtnm
\
\
lfc» Bfl «WVf SWfcMfrM 5O
me/kg.
IMTto MV< kviutai 3
mg/ste.
1 w fc. ^*4 htr^jnij 4rm
»"»*»
GOtTMAM! CORMHV
TT ahaH besur on ^fr*
front panel the alfnal word "Warn-
ing."
(C) TbzieUy Cattoory OL AH pe*O-
cide prodncti maednc *t» criteria of
Toxldty Category HZ atufl bear on
the front panel the sicnal word •Cau-
tion,'*
Toxictt* Category 17. AH peKt-
dde products nvrttrn the criteria of
Toxlctty Catecory 17 shall bear on the
front panel the a1«nal word -Caatton,-
(E) Cfce o/ ti&uU vords, Use of any
signal woroXs) associated with a higher
Toxicity Category to not permitted
except when the Agency determines
vent unreasonable adverse effects on
man or the environment. In no case
shall more than one human hazard
signal word appear on the front panel
of a label.
(U) Child hazard warning. Every pes-
ticide product label shall bear on the
front panel the statement "keep out of
reach of children." Only in cases
where the likelihood of contact with
children during distribution. market-
Ing. storage or use is demonstrated by
the applicant to be extremely remote.
or if the natters of the pesticide is such
that it is approved for-use on infants
or *™*+fi ***'flT1, *T**r fch* Administra-
tor waive this reqiiirement.
(ill) Statement of practical treat*
Toxicity Category L A
of practical treatment OQnt
aid or other) shall appear on the front
panel of the label of afl pesticides fan-
ing Into Toxicity Category I on the
baste of oral, tnhtlsftnn or dermal tox-
ktty. Tne Agency mar, "howerer«
permit rfamniMa rmriations in the
cal treatment to tome icfqqice
as "See statement of practical treat-
ment on back panel'* appears on the
95
-------
Environmental Protection Agency
§ 162.10
front panel near the word "Poison"
and the skull and crossbones.
(B) Other toxicity categories. The
statement of practical treatment is not
required on the front panel except as
described in paragraph
-------
§ 162.10
40 CFR Ch. I (7-1-35 Edition)
stances under which they are required
follow:
(A) If a pesticide intended for out-
door use contains an active ingredient
with a mammalian acute oral LD« of
100 or less, the statement "This Pesti-
cide is Toxic to Wildlife" is required.
-------
Environmental Protection Ag«ncy
for use only by manufacturers of prod-
ucts other than pesticide products in
their regular manufacturing processes.
provided that:
U) The label clearly shows that the
product Is intended for use only in
manufacturing processes and specifies
the type**Mng of pesti-
cide products which are intended for
use only by fonnulators in preparing
pesticides for sale to the public, pro-
vided that:
(J) There is information readily
available to the formulators on the
composition, toxictty. *n*ttnH> of use,
applicable restrictions or
and effectiveness of the product for
pesttdde purposes;
(2) The label dearly states that the
product is intended for use only in
manufacturinc* formulating;
or repacking for use as a pesticide and
specifies the type(s) of pesticide prod-
ucts involved:
(J) The product as finally manufac-
tured. formulated, y*M"*gd, or repack-
aged is registered: and
§ 162.10
The Administrator determines
that such directions are not necessary
to prevent unreasonable adverse ef-
fects on man or the environment.
(2) Contents of Directions for Use.
The directions for use shall include
the following, under the headings "Di-
rections for Use":
(i) The statement of use classifica-
tion as prescribed in 162.KKJ) immedi-
ately under the heading "Directions
for Use,"
(ii) Immediately below the state-
ment of use classification, the state-
ment "It Is a violation of Federal law
to use this product in a manner incon-
sistent with its labeling/1 •.
(ill) The site
-------
(E) For restricted use pesticides, a
statement that the pesticide may be
applied under the direct supervision of
a certified applicator who is not phys-
ically present at the site of application
but nonetheless available to the
person applying the pesticide, unless
the Agency has determined that the
pesticide may only be applied under
the direct supervision of a certified ap-
plicator who is physically present.
(F) Other pertinent information
which the Administrator determines
to be necessary for the protection of
man and the environment.
(j) Statement of Use Classification.
By October 22. 1976. all pesticide prod-
ucts must bear on their labels a state-
ment of use classification as described
in paragraphs (J) (1) and (2) of this
section. Any pesticide 'product for
which some uses are classified for gen-
eral use and others for restricted use
shall be separately labeled according
to the labeling standards set forth in
this subsection, and shall be marketed
as separate products. with differen-
registration numbers, one bearing di-
rections only for general use
-------
PHYS/CHEM-1
PHYSICAL/CHEMICAL HAZARDS
Criteria
I. Pressurized Containers
A.
Flashpoint at or below
20°P; or if there is a
flashback at any valve
opening.
B.
Flashpoint above 20°F
and not over 80°F; or
if the flame extension
is more than 18 inches
long at a distance of
6 inches from the
valve opening.
All Other Pressurized
Containers
II. Non-Pressurized Containers
A. Flashpoint at or below
20°F.
B. Flashpoint above 20°F
and not over 80°F.
C. Flashpoint over 80°F
and not over 150°F.
D. Flashpoint above
150°F.
Required Label Statement
Extremely flammable.
Contents under pressure.
Keep away from fire, sparks,
and heated surfaces. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Flammable. 'Contents under
pressure. Keep away from
heat, sparks, and flame. Do
not puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Contents under pressure.
Do not use or store near
heat or open flame. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Extreme-ly flammable. Keep
away from fire, sparks, and
heated surfaces.
Flammable. Keep away from
heat and open flame.
Do not use or store near
heat and open flame.
None required.
too
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STOR-1
STORAGE INSTRUCTIONS FOR PESTICIDES
Heading:
All products are required to bear specific label instructions
about storage and disposal. Storage and disposal instructions
must be grouped together in the directions for use portion of
the label under the heading STORAGE AND DISPOSAL. Products
intended solely for domestic use need not include the heading
"STORAGE AND DISPOSAL."
Storage Instructions;
All product labels are required to have appropriate storage
instructions. Specific storage instructions are not prescribed.
Each registrant must develop his own storage instructions,
considering, when applicable, the following factors:
1. Conditions of storage that might alter the composition or
usefulness of the pesticide. Examples could be temperature
extremes, excessive moisture or humidity, heat, sunlight,
friction, or contaminating substances or media.
2. Physical requirements of storage.which might adversely ' _
affect the container of the product and Its ability to
continue to function properly. Requirements might include
positioning of the container in storage, storage or damage
due to stacking, penetration of moisture, and ability to
withstand shock or friction.
3. Specifications for handling the pesticide container,
Including movement of container within the storage area,
proper opening and closing procedures (particularly for
opened containers), and measures to minimize exposure
while opening or closing container.
K. Instructions on what to do if the container Is damaged in
any way, or If the pesticide is leaking or has been
spilled, and precautions to minimize exposure If damage occurs
5. General precautions concerning locked storage, storage In
original container only, and separation of pesticides
during storage to prevent cross-contamination of other
pesticides, fertilizer, food, and feed.
6. General storage instructions for household products should
emphasize storage In original container and placement In
locked storage areas.
101
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PEST/DIS-1
PESTICIDE DISPOSAL INSTRUCTIONS
The label of all products, except those Intended solely for domestic
use, must bear explicit instructions about pesticide disposal. The
statements listed below contain the exact wording that must appear on
the label of these products:
1. The labels of all products, except domestic use, must contain the
statement, "Do not contaminate water, food, or feed by storage or disposal.
2. Except those products Intended solely for domestic use, the labels
of all products that contain active Ingredients that are Acute Hazardous
Wastes or are assigned to Toxicity Category I on the basis of oral or
dermal toxicity, or Toxicity Category I or n on the basis of acute
inhalation toxicity must bear the following pesticide disposal statement:
* "Pesticide wastes are acutely hazardous. Improper disposal of
excess pesticide, spray mixture, or rlnsate is a violation of Federal
Law. If these wastes cannot be disposed of by use according to
label instructions, contact your State Pesticide or Environmental
Control Agency, or the Hazardous Waste representative at the nearest
EPA Regional Office for guidance."
3. Tiie labels of all products, except those intended for domestic use,
containing active or inert ingredients that are Toxic Hazardous Wastes
or meet any of the criteria in 40 CPR 261, Subpart C for a hazardous
waste must bear the following pesticide disposal statement:.
"Pesticide wastes are toxic. Improper disposal of excess pesticide,
spray mixture, or rlnsate is a violation of Federal Law. If these
wastes cannot be disposed of by use according to label Instructions,
contact your State Pesticide or Environmental Control Agency, or the
Hazardous Waste representative at the nearest EPA-.Regional Office
for guidance."
1». Labels for all other products, except those Intended for domestic
use, must bear the following pesticide disposal statement:
"Wastes resulting from the use of this product may be disposed of on
site or at an approved waste disposal facility."
5. Products Intended for domestic use only must bear the following
disposal statement: "Securely wrap original container In several layers
of newspaper and discard In trash."
102
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CONT/DIS-1
CONTAINER DISPOSAL INSTRUCTIONS
The label of each product must bear container disposal
instructions appropriate to the type of container.
1. Domestic use products must bear one of the following
container disposal statements:
Container Type
Statement
Non-aerosol products
(bottles, cans, Jars)
Non-aerosol products
(bans)
Aerosol products
Do not reuse container (bottle, can, Jar).
Rinse thoroughly before discarding in trash.
Do not reuse bag. Discard bag in trash.
Replace cap and discard containers in
trash. Do not incinerate or puncture.
i 2. All other products must bear container disposal instructions,
based on container type, listed below:
Container Type
Statement
Metal
containers
(non-aerosol)
Plastic containers
Glass containers
Fiber drums
with liners
Paper and
plastic bags
Compressed gas
cylinders
Triple rinse (or equivalent). Then offer
for recycling or reconditioning, or puncture
and dispose of in a sanitary landfill, or i>y
other procedures approved by state and local
authorities.
Triple rinse (or equivalent). Then offer
for .recycling or reconditioning, or puncture
and dispose of in a sanitary landfill, or
incineration, or, If allowed by state and
local authorities, by burning. If burned,
stay out of smoke.
Triple rinse (or equivalent). Then dispose
of in a sanitary landfill or by other
approved state and local procedures.
Completely empty liner by shaking and
tapping aides and bottom to loosen clinging
particles. Empty residue into application
equipment. Then dispose of liner in a
sanitary landfill or by incineration if
allowed by state and local authorities.
If drum Is contaminated and cannot be
reused1, dispose of In the same manner.
Completely empty bag into application
equipment. Then dispose of empty bag in
a sanitary landfill or by incineration,
or, if allowed by State and local
authorities, by burning. If burned, stay
out of smoke.
Return empty cylinder for reuse (or
similar wording)
Manufacturer may replace this phrase with one Indicating
whether and how fiber drum may be reused.
103
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APPENDIX III
BIBLIOGRAPHIC APPENDICES
104
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BIBGUIDE-1
GUIDE TO USE OF THIS BIBLIOGRAPHY
CONTENT OF BIBLIOGRAPHY. This bibliography contains
citations of all studies considered relevant by EPA in
arriving at the positions and conclusions stated elsewhere
in the Standard. 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, will be included.
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
uripublished 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 attempted also to unite basic
documents and commentaries upon them, treating them as a
single study.
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 at any time 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 a further explana-
tion. 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 identifier number is
also to be used whenever specific reference is needed.
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
standards of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
105
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BIBGUIDE-2
a. Author. Whenever the Agency could confidently identify
one, 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 author. As a last resort, the Agency has shown
the first submitter as author.
b. Document Date. When the date appears as four digits
with no question marks, the Agency took it directly
from the document. When a four-digit date is followed
by a question mark, the bibliographer deduced the
date from evidence in the document. When the date
appears as (19??), the Agency was unable to determine
or estimate the date of the document.
t
c. Title. In some cases, it has been necessary for
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 fol-
lowing 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,
following the phrase "submitted by." 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," standing 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.
For example, within accession number 123456, the
first study would be 123456-A; the second, 123456-
B; the 26th, 123456-Z; and the 27th, 123456-AA.
106
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BIBLIOGRAPHY OF STUDIES CONSIDERED IN SUPPORT
OF REGISTRATION UNDER THE STANDARD
Registration Standards Case Number 0081: Metalaxyl
All studies in this bibliography are usable only with the
permission of their submitter under the provisions of FIFRA
§3(c)(1)(D)(i), for the ten-year period beginning with the date
of the first product registration under this standard.
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00063989 Fink, R.; Beavers, J.B.; Brown, R. (1977) Final Report: Eight-Day
Dietary LC50—Mallard Duck: Project No. 108-148. (Unpublished
study received Jul 13, 1978 under 100-EX-62; prepared by Wild-
life International, Ltd. and Washington College, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:234439-H)
00063990 Sachsse, K. ; Bathe, R. (1976) Acute Oral LD50 in the Rat of Tech-
nical CGA 48988: Project No. Siss 5388. (Unpublished study re-
ceived Jul 13, 1978 under 100-EX-62; prepared by Ciba-Geigy,
Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:234439-1)
00063991 Sachsse, K.; Bathe, R. (1976) Acute Oral LD50 in the Mouse of
Technical CGA 48988: Project No. Siss 5388. (Unpublished study
received Jul 13, 1978 under 100-EX-62; prepared by Ciba-Geigy,
Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL-.234439-J)
00063993 Sachsse, K.; Ullmann, L. (1978) Acute Dermal LD50 in the Rabbit
of Technical CGA 48988: Project No. 408378—Siss 6547. (Unpub- '
lished study received Jul 13, 1978 under 100-EX-62; prepared by
Ciba-Geigy, Ltd., Switzerland, submitted by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:234439-L)
00063994 Sachsse, K.; Bathe, R. (1976) Acute Dermal LD50 in the Rat of
Technical CGA 48988: Project No. Siss 5388. (Unpublished study
received Jul 13, 1978 under 100-EX-62; prepared by Ciba-Geigy,
Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:234439-M)
00071301 U.S. Environmental Protection Agency, Animal Biology Laboratory
(1979) Ridomil 2%: Bluegill (Lepomis macrochirus): Test #
2411. (Unpublished study; CDL:244183-B)
00071302 U.S. Environmental Protection Agency, Terrestrial & Aquatic Biology
Laboratory (1979) Ridomil Tech: Bluegill (Lepomis macro-
chirus): Test ft 2413. (Unpublished study; CDL:244183-E)
00071303 U.S. Environmental Protection Agency, Terrestrial & Aquatic Biology
Laboratory (1979) Ridomil Tech: Rainbow Trout (Salmo gaird-
neri): Test # 2414. (Unpublished study; CDL:244183-F)
00071304 U.S. Environmental Protection Agency, Terrestrial & Aquatic Biology
Laboratory (1979) Ridomil 2%: Daphnia magna: Test # 2416.
(Unpublished study; CDL:244183-G)
00071306 U.S. Environmental Protection Agency, Terrestrial & Aquatic Biology
Laboratory (1979) Ridomil Tech: Daphnia magna: Test # 2415.
(Unpublished study; CDL:244183-1)
1D8
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00071307 LeBlanc, G.A.; Mastone, J.; Altshul, L.; et al. (1980) The Chronic
Toxicity of CGA-48988 to the Water Flea (Daphnia magna): Re-
port | BW-80-5-668. (Unpublished study received Jan 23, 1981
under 100-607; prepared by EG & G, Bionomics, submitted by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:244183-J; 244782)
00071308 LeBlanc, G.A.; Mastone, J.; Wilson, B.F.; et al. (1980) The Toxic-
ity of CGA-48988 to Fathead Minnow (Pimephales promelas)
Eggs and Fry: Report f BW-80-4-642. (Unpublished study received
Jan 23, 1981 under 100-607; prepared by EG & G, Bionomics, sub-
mitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:244183-K;
244782)
(
00071598 Beck, L.S. ; DeWard, J.; Kitchen, D.N.; et al. (1981) Six Month
Chronic Oral Toxicity Study with CGA-48988 Technical in Beagle
Dogs: Project No. 1545. (Unpublished study received Apr 15,
1981 under 100-607; prepared by Elars Bioresearch Laboratories,
Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:
070016-A)
00071600 Cozens, D.D.; Allen, P.A.; Clark, R.; et al. (1980) Effect of CGA
48-988 on Reproductive Function of Multiple Generations in the
Rat: CBG 181/80254. (Unpublished study received Apr 15, 1981
under 100-607; prepared by Huntingdon Research Centre, England,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:070015-A)
00071603 Honeycutt, R.C.; Fischer, W.C.; Madrid, S.; et al. (1980) Uptake,
Balance and Metabolism of Phenyl-14C-CGA-48988 in Field
Grown Potatoes: M11-69-14P, 14S; Report No. ABR-80042. (Unpub-
lished study received Apr 15, 1981 under 100-607; submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:070018-C)
00071604 Honeycutt, R.C.; Cassidy, J.E. (1980) Translocation of Phenyl-
14C-CGA-48988 and Metabolites from Leaves into Potato Tubers:
M11-69-12P, 12S; Report No. ABR-80048. (Unpublished study re-
ceived Apr 15, 1981 under 100-607; submitted by Ciba-Geigy
Corp., Greensboro, N.C.; CDL:070018-D)
00071605 Gross, D. (1977) Metabolism of CGA 48 988 in Field Grown Potato
Plants: Project Report 30/77. (Unpublished study received Apr
15, 1981 under 100-607; prepared by Ciba-Geigy Ltd., Switzer-
land, submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:070018-F)
00071606 Gross, D. (1978) Metabolism of CGA 48 988 in Grapevine: Project Re-
port 11/78. (Unpublished study received Apr 15, 1981 under 100-
607; prepared by Ciba-Geigy Ltd., Switzerland, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:070018-F)
109
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00071607 Gross, D. (1979) Identification of Metabolites of CGA 48 988 (Ri-
domil in Grapevine: Project Report 06/79. (Unpublished
study received Apr 15, 1981 under 100-607; prepared by Ciba-
Geigy Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greens-
boro, N.C. ; CDL: 070018-<3)
00071608 Gross, D. (1979) Fate of CGA 48 988 in Lettuce: Project Report 38/
79. (Unpublished study received Apr 15, 1981 under 100-607;
prepared by Ciba-Geigy Ltd., Switzerland, submitted by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:070018-H)
00071609 Gross, D. (1979) Identification of Metabolites of CGA 48 988 (Ri-
1 domil) in Field Grown Potato Plants: Project Report 39/79.
(Unpublished study received Apr 15, 1981 under 100-607; prepared
by Ciba-Geigy Ltd., Switzerland, submitted by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:070018-1)
00071610 Gross, D. (1980) Identification of Degradation Products of CGA
48988 (Ridomil) in Lettuce: Project Report 38/80. (Unpub-
lished study received Apr 15, 1981 under 100-607; prepared by
Ciba-Geigy Ltd., Switzerland, submitted by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:070018-J)
00071613 Hanfoock, H. (1977) Distribution, Degradation and Excretion of CGA
48 988 in the Rat: Project Report 18/77. (Unpublished study
received Apr 15, 1981 under 100-607; prepared by Ciba-Geigy
Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:070018-M)
00071614 Hambock, H. (1978) Metabolism of CGA 48 988 in the Rat: Project Re-
port 26/78. (Unpublished study received Apr 15, 1981 under
100-607; prepared by Ciba-Geigy Ltd., Switzerland, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:070018-N)
00071615 Ciba-Geigy Corporation (1980) Study of Metalaxyl (Ridomil 2E) Res-
idue Tolerances in Cottonseed, Soybeans, Wheat, and Certain Veg-
etable Crops: AG-A 5457 I. (Compilation; unpublished study,
including AG-A 5725, 5456 I, 5545 I, II..., received Apr 15,
1981 under 100-607; CDL:070019-A)
00071616 Ciba-Geigy Corporation (1981) Study of Various Compounds for Res-
idue Tolerances in Potatoes: AG-A 4601. (Compilation; unpub-
lished study/ including AG-A 4614, 4615, 4903..., received Apr
15, 1981 under 100-607; CDL:070020-A)
00071622 Balasubramanian, K. (1980) Analytical method for the Determination
of Total Residues of Metalaxyl in Animal Tissues, Milk and Eggs
as 2,6-Dimethylaniline. Method no. AG-349 dated Nov 25, 1980.
(Unpublished study received Apr 15, 1981 under 100-607; submit-
ted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:070022-L)
110
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00071623 Balasubramanian, K. (1980) Analytical Method for the Determination
of Total Residues of Metalaxyl in Oil Seed Fractions as 2,6-Di-
methylaniline. Method no. AG-350 dated Dec 18, 1980. (Unpub-
lished study received Apr 15, 1981 under 100-607; submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:070022-M)
00071672 Ciba-Geigy Corporation (1981) Series of Tests Performed with
Metalaxyl on Various Crops: AG-A 5638. (Compilation; unpub-
lished study, including AG-A nos. 5639 I,II, 5754 I,II, 5805
I,II, ..., received Apr 15, 1981 under 100-607; CDL:070021-A)
00071673 Seim, V.W.; Thomas, W.A. (1980) Biological Report For CGA-48988:
' Residue Test in Laying Hens: Report No. Biol-80009. (Unpub-
lished study received Apr 15, 1981 under 100-607; submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:070021-B)
00071674 Seim, V.; Thomas, W.; Brown, G. (1980) Biological Report for CGA-
48988: Residue Test in Lactating Cows: Report No. Biol-79009.
(Unpublished study received Apr 15, 1981 under 100-607; submit-
ted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:070021-C)
00071676 Balasubramanian, K.; Ross, J.A. (1981) Comparison of Analyses of
Potato Tubers Treated with Metalaxyl Using the Parent Method
AG-325 and the Total Method AG-348: Report No. ABR-80056. (Un-
published study received Apr 15, 1981 under 100-607; submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:070021-E)
00072394 Calkins, J.E.; Morgan, J.M.; Casey, H.W.; et al. (1980) A 21-day
Subacute Dermal Toxicity Study in Albino Rabbits with CGA-48988
Technical: Study No. 410-0226. Rev. (Unpublished study re-
ceived Jan 23, 1981 under 100-607; prepared by Whitaker Corp.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:244182-A)
00072396 U.S. Environmental Protection Agency, Terrestrial & Aquatic Biology
Laboratory (1979) Ridomil 2%: Rainbow Trout (Salmo gaird-
neri): Test # 2417. (Unpublished study; CDL:244183-C)
00074488 Ciba-Geigy Corporation (1981) Residues of Metalaxyl in Avocados
Resulting from Soil Surface Granular, Soil Drench, and Drip
Fungigation Applications: Report No. ABR-81016. (Compilation;
unpublished study received Jun 9, 1981 under 100-607; CDL:
070151-A)
00077334 Fink, R.; Beavers, J.B.; Brown, R. (1977) Final Report: Acute Oral
LD50—Mallard Duck: Project No. 108-149. (Unpublished study re-
ceived Jul 13, 1978 under 100-EX-62? prepared by Wildlife Inter-
national, Ltd. in cooperation with Washington College, submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234439-D)
111
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00077335 Fink, R.; Beavers, J.B.; Brown, R. (1977) Final Report: Eight-Day
Dietary LC50—Bobwhite Quail: Project No. 108-147. (Unpublished
study received Jul 13, 1978 under 100-EX-62; prepared by Wild-
life International, Ltd. and Washington College, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:234439-F)
00079433 Kahrs, R.A. (1981) Residues of Metalaxyl in Hops Resulting from
Soil Drench Applications: Report No. ABR-81024. (Unpublished
study received Jul 15, 1981 under 100-607; submitted by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:070188-A)
00084107 Sachsse, K.; Ullmann, L. (1976) Skin Irritation in the Rabbit af-
t ter Single Application of Technical CGA 48988: Project No. Siss
5388. (Unpublished study received Jul 13, 1978 under 100-EX-
62; prepared by Ciba-Geigy, Ltd., Switzerland, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:234428-E)
00084108 Sachsse, K.; Ullmann, L. (1975) Eye Irritation in the Rabbit of
Technical CGA 48988: Project No. Siss 5388. (Unpublished study
received Jul 13, 1978 under 100-EX-62; prepared by Ciba-Geigy, -
Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:234428-F)
00084109 Sachsse, K.; Ullmann, L. (1976) Skin Sensitizing (Contact Aller-
genic) Effect in Guinea Pigs of Technical CGA 48988: Project
No. Siss 5388. (Unpublished study received Jul 13, 1978 under
100-EX-62; prepared by Ciba-Geigy, Ltd., Switzerland, submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234428-G)
00084110 Drake, J.C. (1977) 3 Months Dietary Study in Rats in Compound CGA
48 988. (Unpublished study received Jul 13, 1978 under 100-
EX-62; prepared by Ciba-Geigy, Ltd., Switzerland, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:234428-H)
00084111 Finn, J.P.; Rider, L.; Briggs, K.; et al. (1977) CGA 48.988: 91 Day
Dietary Toxicity Study in Beagle Dogs: Report No. 653/380/4.
(Unpublished study received Jul 13, 1978 under 100-EX-62; pre-
pared by Hazleton Laboratories Europe, Ltd., submitted by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:234428-1)
00084113 Ami, P.; Muller, D. (1978) Salmonella/Mammalian-microsome Muta-
genicity Test with CGA 48 988: (Test for Mutagenicity Properties
in Bacteria). (Unpublished study received Jul 13, 1978 under
100-EX-62; prepared by Ciba-Geigy, Ltd., Switzerland, submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234428-K)
00084114 Fritz, H. (1978) Dominant Lethal Study—CGA 48 988 Tech.: Mouse:
(Test for Cytotoxic or Mutagenic Effects on Male Germinal
Cells). (Unpublished study received Jul 13, 1978 under 100-
EX-62; prepared by Ciba-Geigy, Ltd., Switzerland, submitted by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:234428-L)
112
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00097511 Ciba-Geigy Corporation (1981) Residues of Ridomil in Lettuce.
(Compilation; unpublished study received Apr 1, 1982 under
100-EX-71; CDL:070732-A)
00098084 Clair, M.; Fouillet, X. (1977) RU 22974: Formulation: Decis EC 2.5;
Formulation: Decis ULV: Acute Toxicity in the Rabbit by Percu-
taneous Administration: IFREB—R 770258/A. (Translation; unpub-
lished study received Mar 25, 1982 under 2E2663; prepared by
Institut Francais de Recherches et Essais Biologiques, France,
submitted by American Hoechst Corp., Somerville, N.J.; CDL:
070734-J)
00098428 Kahrs, R.A. (1982) Metalaxyl—Melons, Cucumbers, Squash, Green
Onions, Bulb Onions, Potatoes—Supportive Data Requested by EPA:
Report No. ABR-82014. (Unpublished study received Apr 7, 1982
under 1F2500; submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:070765-A)
00098481 Ashby, R.; Whitney, J.C.; Bhatt, A.; et al. (1980) Cga 48 988:
Toxicity and Oncogenicity in Dietary Administration to Rats for -
Two Years: 80/CIA009/315. Final rept. (Unpublished study
received Apr 15, 1982 under 1F2500; prepared by Life Science Re-
search, England, submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:070767-A; 070768; 070769)
00100446 Buccafusco, R.; Stiefel, C.; Fratus, G.; et al. (1978) Acute
Toxicity of CGA-48988 Technical to Bluegill (Lepomis macro-
chirus): Report #BW-78-12-381. (Unpublished study received Feb
21, 1979 under 100-601; prepared by EG & G, Bionomics, submitted
by Ciba-Geigy Corp., Greensboro, NC; CDL:236854-A)
00100447 Buccafusco, R.; Stiefel, C.; Fratus, G.; et al. (1978) Acute
Toxicity of CGA-48988 Technical to Rainbow Trout (Salmo gaird-
neri): Report #BW-78-12-376. (Unpublished study received Jan
25, 1979 under 100-601; prepared by EG & G, Bionomics, submitted
by Ciba-Geigy Corp., Greensboro, NC; CDL:236854-B)
00100448 Suprenant, D. (1978) Acute Toxicity of CGA-48988 to the Water Flea
(Daphnia magna): Report IBW-78-12-364. (Unpublished study re-
ceived Jan 25, 1979 under 100-601; prepared by EG & G, Biono-
mics, submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:
236854-C)
00100455 Burkhard, N. (1977) Volatilization of CGA-48988 from Soil under
Laboratory Conditions: Project Report 29/77. (Unpublished
study received Apr 26, 1979 under 100-600; prepared by Ciba-
Geigy, Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greens-
boro, NC; CDL:238231-D)
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00100464 Guth, J. (1976) Leaching Model Study with the Fungicide CGA-48988
in Four Standard Soils: Project Report 30/76. (Unpublished
study received Apr 26, 1979 under 100-600; prepared by Ciba-
Geigy, Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greens-
boro, NC; CDL:238232-A)
00100465 Guth, J. (1978) Leaching Characteristics of Aged 14C-CGA 48988
(Ridomil) Residues in Two Standard Soils: Project Report 33/78.
(Unpublished study received Apr 26, 1979 under 100-600; pre-
pared by Ciba-Geigy, Ltd., Switzerland, submitted by Ciba-Geigy
Corp., Greensboro, NC; CDL:238232-B)
00100466 Guth, J. (1978) Adsorption and Desorption of CGA 48988 (Ridomil)
in Various Soil Types: Project Report 35/78. (Unpublished
study received Apr 26, 1979 under 100-600; prepared by Ciba-
Geigy, Ltd., Switzerland, submitted by Ciba-Geigy Corp., Greens-
boro, NC; CDL:238232-C)
00100468 Ladd, S.; Wilson, W. (1979) Accumulation and Elimination of 14C-
residues by Bluegill Sunfish ... Exposed to 0-14C-CGA-48988:
Report #BW-78-10-328. (Unpublished study received Apr 26, 1979
under 100-600; prepared by EG & G, Bionomics; submitted by
Ciba-Geigy Corp., Greensboro, NC; CDL:238232-E)
00100470 Ladd, S.; Enos, J. (1979) Kinetics of Phenyl-14C-CGA in a Model
Aquatic Ecosystem: Report #BW-79-2-401. (Unpublished study
received Apr 26, 1979 under 100-600; prepared by EG & G, Bio-
nomics, submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:
238232^3)
00100753 Ciba-Geigy Corp. (1982) Residues of Metalaxyl in Cattle and
Goats. (Compilation; unpublished study received May 11, 1982
under 1F2500; CDL:070836-A)
00103354 McSheehy, T.; Macrae, S.; Whitney, J. (1981) CGA 48 988: Oncogen-
icity in Dietary Administration to Mice for Two Years: LSR Re-
port No.: 80/CIA008/442. (Unpublished study received Jun 11,
1982 under 100-607; prepared by Life Science Research, Eng.,
submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:247660-B)
00103361 Langauer, M.; Muller, D. (1979) Nucleus Anomaly Test in Somatic
Interphase Nuclei: CGA 48 988: Chinese Hampster (Test for
Mutagenic Effects on Bone Marrow Cells): No. of Experiment 78-
3007. (Unpublished study received Jun 11, 1982 under 100-607;
prepared by Ciba-Geigy, Ltd., Switz., submitted by Ciba-Geigy
Corp., Greensboro, NC; CDL:247661-D)
114
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00103362 Strasser, F. (1982) L5178Y/TK+/-Mouse Lymphoma Mutagenicity Test:
CGA 48 988 (In vitro Test for Mutagenic Properties of Chemical
Substances in Mammalian Cells): No. of Experiment 811258. (Un-
published study received Jun 11, 1982 under 100-607; prepared
by Ciba-Geigy, Ltd., Switz., submitted by Ciba-Geigy Corp.,
Greensboro, NC; CDL:247661-E)
00103363 Puri, E. (1982) Autoradiographic DNA Repair Test on Rat Hepato-
cytes: CGA 48 988 (In vitro Test for DNA-damaging Properties):
No. of Experiment 811259. (Unpublished study received Jun 11,
1982 under 100-607; prepared by Ciba-Geigy, Ltd., Switz., sub-
mitted by Ciba-Geigy Corp., Greensboro, NC; CDL:247661-F)
t
00103564 Modin, J. (1969) Residues in fish, wildlife, and estuaries. Pesti-
cides Monitoring Journal 3(1):1-7. (Available from: Superin-
tendent of documents, U.S. Government Printing Office, Washing-
ton, DC 20402; published study; CDL:091969-AX)
00104376 Ballantine, L. (1979) Rotational Crop Data Submitted in Support of
Conditional Registration for Ridomil (Metalaxyl) Use on Tobacco:
Report No. ABR-79099. (Unpublished study received Oct 31, 1979
under 100-607; submitted by Ciba-Geigy Corp., Greensboro, NC;
CDL.-241243-A)
00104381 Fischer, W.; Cassidy, J. (1978) Uptake and Characterization of
Phenyl-14C-CGA-48988 and Its Soil Metabolites in Rotation Let-
tuce, M6-69-8PR, 8SR: Report No. ABR-78078. (Unpublished study
received Oct 31, 1979 under 100-607; submitted by Ciba-Geigy
Corp., Greensboro, NC; CDL:241243-G)
00104382 Fischer, W.; Cassidy, J. (1979) Uptake and Characterization of
Phenyl-14C-CGA-48988 and Its Soil Metabolites in Field Rota-
tion Spring Oats, M6-69-4PR, 4SR: Report No. ABR-79002. (Unpub-
lished study received Oct 31, 1979 under 100-607; submitted by
Ciba-Geigy Corp., Greensboro, NC; CDL:241243-H)
00104383 Fischer, W.; Cassidy, J. (1979) Uptake and Characterization of
Phenyl-14C-CGA-48988 and Its Soil Metabolites in Field Rota-
tion Corn, M6-69-6PR, 6SR: Report No. ABR-79004. (Unpublished
study received Oct 31, 1979 under 100-607; submitted by Ciba-
Geigy Corp., Greensboro, NC; CDL:241243-1)
00104384 Hamilton, T.; Fischer, W.; Cassidy, J. (1979) Uptake and Character-
ization of Phenyl-14C-CGA-48988 and Its Soil Metabolites in
Field Rotation Soybeans, M6-69-7PR, 7SR: Report No. ABR-79003.
(Unpublished study received Oct 31, 1979 under 100-607; sub-
mitted by Ciba-Geigy Corp., Greensboro, NC; CDL:241243-K)
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00104385 Hamilton, T.; Fischer, W.; Cassidy, J. (1979) Uptake and Character-
ization of Phenyl-14C-CGA-48988 and Its Soil Metabolites in
Field Rotation Sugar Beets, M6-69-5PR, 5SR: Report No. ABR-
79005. (Unpublished study received Oct 31, 1979 under 100-607;
submitted by Ciba-Geigy Corp., Greensboro, NC; CDL-.241243-L)
00104387 Ciba-Geigy Corp. (1979) Residues of CGA-48988 on Wheat, Rye, For-
age and Other Crops. (Compilation; unpublished study received
Oct 31, 1979 under 100-607; CDL:241243-N)
00104390 Ciba-Geigy Corp. (1979) Residue Studies of CGA-48988 on Soybeans
and Other Crops. (Compilation; unpublished study received Oct
31, 1979 under 100-607; CDL:241243-Q)
00104483 Ciba-Geigy Corp. (1978) [Chemical Data on the Fungicide Ridomil].
(Compilation; unpublished study received Jul 13, 1978 under
100-EX-63; CDL:234427-A)
00104493 Burkhard, N. (1976) Hydrolysis of CGA-48988 under Laboratory Con-
ditions: Project Report 26/76. (Unpublished study received
Jul 13, 1978 under 100-EX-62; prepared by Ciba-Geigy, Ltd.,
Switz., submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:
234438-C)
00104494 Ellgehausen, H. (1977) Distribution of the Non-extractable Radio-
activity between Different Soil Organic Matter Fractions of a
Field Soil Treated with 14C-labeled CGA 48988 (Addendum to
Project Report 55/77): Project Report 56/77. (Unpublished
study received Jul 13, 1978 under 100-EX-62; prepared by Ciba-
Geigy, Ltd., Switz., submitted by Ciba-Geigy Corp., Greensboro,
NC; CDL:234438-G)
00104498 Ciba-Geigy Corp. (1978) Chemistry of CGA-48988 Technical. (Com-
pilation; unpublished study received Sep 5, 1978 under 100-601;
CDL:235062-A)
00104656 Ciba-Geigy Corp. (1978) Ridomil 2E Fungicide Residue Study—
Potatoes. (Compilation; unpublished study received Sep 5, 1978
under 100-EX-l; CDL-.097389-A)
00109402 Ciba-Geigy Corp. (1981) Metalaxyl—Cotton In-furrow Applications of
Ridomil 2E and 5G Including Mixtures with PCNB: Report No. ABR-
81046. (Compilation; unpublished study received Jul 28, 1982
under 100-607; CDL.-247934-A)
00109471 Coate, W. (1982) Correction Pages and Addendum: Subchronic Inhala-
tion Study in Rats: CGA-48988: Project No. 483-202. (Unpublished
study received Aug 12, 1982 under 1F2500; prepared by Hazleton
Laboratories America, Inc., submitted by Ciba-Geigy Corp.,
Greensboro, NC; CDL:071032-A)
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00109472 Ciba-Geigy Corp. (1982) Metalaxyl Residues in Pineapple Resulting
from a Preplant Dip Application of Ridomil 2E. (Compilation;
unpublished study received Aug 12, 1982 under 100-607; CDL:
071034-A)
00114376 Ciba-Geigy Corp. (1982) Metalaxyl—Rotational Wheat: Report # ABR-
82061. (Compilation; unpublished study received Sep 23, 1982
under 100-607; CDL:071104-A)
00114377 Ciba-Geigy Corp. (1982) Metalaxyl—Lettuce: Report # ABR-82060.
(Compilation; unpublished study received Sep 23, 1982 under 100-
607; CDL:071106-A)
00114378 Ciba-Geigy Corp. (1982) Metalaxyl—Spinach: Report # ABR-82050.
(Compilation; unpublished study received Sep 23, 1982 under 100-
607; CDL:071107-A)
00114379 Collins, P.; Williams, S.; Cassidy, J. (1982) Metabolism of Phen-
yl-14C-CGA-48988 in Greenhouse Head Lettuce: Report No. ABR-
82054. (Unpublished study received Sep 23, 1982 under 100-607;.
submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:071108-A)
00117969 Cheung, M.; Manuli, P. (1982) Metalaxyl—Citrus: Residues Resulting
from Soil or Trunk-spray Applications of Ridomil 2E: Report
No. ABR-82069. (Unpublished study received Nov 16, 1982 under
100-607; submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:
071238-A)
00126315 Ciba-Geigy Corp. (1983) Summary of Section D: Metalaxyl—Ap-
ples. (Compilation; unpublished study received Mar 7, 1983
under 100-607; CDL:071476-A)
00127769 Ciba-Geigy Corp. (1983) Metalaxyl—Red Raspberries: Residues
Resulting from Soil Application of Ridomil 2E or 5G. (Compi-
lation; unpublished study received Mar 7, 1983 under 100-607;
CDL:071478-A)
00128102 Ciba-Geigy Corp. (1982) Metalaxyl (Apron 2E) Seed Treatments.
(Compilation; unpublished study received Feb 3, 1983 under
100-626; CDL:071388-A)
00128738 Ciba-Geigy Corp. (1983) Summary of Section D: Metalaxyl—Peanuts:
Residue Reports. (Compilation; unpublished study received Jun
29, 1983 under 100-607; CDL:071718-A)
00129003 Ciba-Geigy Corp. (1983) Summary of Section D: Metalaxyl—Pod Vege-
tables. (Compilation; unpublished study received Jun 23, 1983
under 3F2918; CDL:071711-A)
137
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00130693 Ciba-Geigy Corp. (1983) Residue Summary: Metalaxyl—Cucumbers,
Melons, and Squash. (Compilation; unpublished study received
Aug 19, 1983 under 100-607; CDL:251019-A)
00130694 Ciba-Geigy Corp. (1983) Residue Summary: Metalaxyl—Green and Dry
Bulb Onions. (Compilation; unpublished study received Aug 19,
1983 under 100-607; CDL:251020-A)
00130695 Ciba-Geigy Corp. (1983) Residue Summary: Metalaxyl—Lettuce and
Spinach. (Compilation; unpublished study received Aug 19, 1983
under 100-607; CDL-.251021-A)
001,30773 Ciba-Geigy Corp. (1983) Residue Summary: Metalaxyl—Broccoli, Cab-
bage and Cauliflower. (Compilation; unpublished study received
Aug 26, 1983 under 100-607; CDL:071918-A)
00132009 Hardisty, J. (1983) Toxicity and Oncogencity Dietary Administration
of GGA 48988 to Rats for Two Years: Part 1. (Unpublished study
received Oct 12, 1983 under 100-607; prepared by Experimental
Pathology Laboratories, Inc. Submitted by Ciba-Geigy Corp.
Greensboro, N.C.; CDL:251487-A)
00133020 Ciba-Geigy Corp. (1983) Metalaxyl—Citrus Residues Resulting from
Soil Applications of Ridomil 5G. (Compilation; unpublished
study received Dec 8, 1983 under 100-628; CDL:251988-A)
00141519 Ciba-Geigy Corp. (1984) Metalaxyl—Apples: [Residue Chemistry
Data]. Unpublished compilation. 77 p.
00144371 Laughlin, K. (1984) Range-finding Teratology Study in Rabbits:
[Metalaxyl]: 382-097. Unpublished study prepared by Interna-
tional Research and Development Corp. 52 p.
00144372 Laughlin, K. (1984) Teratology Study in Rabbits: [Metalaxyl]:
382-098. Unpublished study prepared by International Research
and Development Corp. 78 p.
00144423 Leng, J. (1985) Teratology Study in Rats:[Metalaxyl]: Study No.
382-100. Unpublished study prepared by International Research
and Development Corp. 94 p.
00148087 Ashby, R.; Fowler, J.; Finn, J. (1985) Metalaxyl Technical : Com-
bination 30-day to 90-day Subchronic Dietary Toxicity Study
in Albino Mice: Final Report: Addendum 1 : Supplementary Cli-
nical -, Macro- and Micro- Pathology: Report No. 85/CIA064/180.
Unpublished study prepared by Life Science Research Limited.
733 p.
Mb-
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
00148103 Ciba-Geigy Corp. (1985) Metalaxyl (Ridomil 2E and Ridomil MZ58) in
All Crops: Comparison Studies on Ground Vs. Aerial Treatments:
[Residue Data]. Unpublished compilation. 88 p.
00148440 Ciba-Geigy Corp. (1985) Metalaxyl (Ridomil 5G) in All Crops: Cross-
over Comparison Studies of Ridomil 2E and 5G. Unpublished com-
pilation. 577 p.
00150094 Hardisty, J. (1985) Metalaxyl: Oncogenicity in Dietary Administra-
tion to Mice for Two Years: Pathology Report Study Number
CIA/008/48988. Unpublished study prepared by Experimental
Pathology Laboratories, Inc. 946 p.
i
00154301 Deparade, E. (1985) SalmDnella/Mammalian-microsome Mutagenicity
Test: Test No.: 851007. Unpublished study prepared by Ciba-
Geigy Ltd. 18 p.
00154302 Moriya, M.; Ohta, T.; Shirasu, Y. (1981) Report on Mutagenicity
Study with CG-48988 in a Microbial System. Unpublished study
prepared by Institute of Environmental Toxicology. 6 p.
00154306 Puri, E. (1985) Autoradiographic DNA Repair Test on Rat Hepato-
cytes: Test Material: CGA 48 988: Supplement to the Report
(dated January 19, 1982): Test No.: 811259. Unpublished study
prepared by Ciba-Geigy Ltd. 37 p.
00154308 Thomann, P.; Pericin, C. (1977) Acute Oral LD50 in the Chinese
Hamster of CGH4A 48 988: No.. PH 2.634. Unpublished study pre-
pared by Ciba-Geigy Ltd. 3 p.
00154663 Puri, E. (1982) Autoradiographic DNA Repair Test on Human Fibro-
blasts: CGA 48 988: (In vitro Test for DNA-damaging Proper-
ties): No. of Experiment: 811660. Unpublished study prepared by
Ciba-Geigy Ltd. 23 p.
00157480 Ciba-Geigy Corp. (1984) [Residue Chemistry: Methods and Summary of
Results: Metalaxyl]. Unpublished compilation. 280 p.
00157740 Rohm and Haas Co. (1986) Product Chemistry of: Kerb 3.3F Flowable
Agricultural Herbicide:. Unpublished study. 4p.
00161404 Fritz, P. (1984) Expanded Report on a Segment II Reproduction
Study in the Rabbit with CGA-48988 Technical (Test for Terato-
genic or Embryotoxic Effects): Study No. 784868. Unpublished
study prepared by Ciba-Geigy, Corp. 459 p.
00161405 Fritz, P. (1984) Expanded Report on the Segment II Reproduction
Study with CGA-48988 Technical in the Rat (Test for Teratogenic
or Embryotoxic Effects): Study No. 227716. Unpublished study
prepared by Ciba-Geigy Corp. 359 p.
119
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metalaxyl Standard
MRID CITATION
40276701 Hoxter, K.; Jaber, M. (1987) An Acute Contact Toxicity Study with
the Honey Bee: Metalaxyl: Study No. 108-282. Unpublished study
prepared by Wildlife International, Ltd. 18p.
40435001 Ciba-Geigy Corp. (1982) Product Chemistry for Product Containing
Metalaxyl. Unpublished study. 4p.
120
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APPENDIX IV
FORMS APPENDICES
121
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OMB Aporovil No. 20OO-0468 (Expires 12-31-83) -
FIFHA SECTION 3(C)(2)(B) SUMMARY SHEET
EPA REGISTRATION NO.
PRODUCT NAME
APPLICANT'S NAME
DATE GUIDANCE DOCUMENT ISSUED
With retptct to tht roquiremtnt to lubmit "gtntric" data impoad by tht FIFRA action 3(C)(2)(B) notict containtd in tht rtfrrtnetd
Guidanct Oocumtm. I tm rttpondirtf in tht following mtflntr.
Q1. I will lubmit dra in t tuntty mmntf to atofy tht following nquirtmtnu. If flit Mt proctdum I will ua dtviatt from (or tri not
tptcifitd in) tht fltaatrat'on Guidtlina or tht Protocols rantaintd in tht Rtpora of Exptn Group* to tht Chtmicals Group, OECD
Cntmicats Tating Programme, I tndea tht protocol! thtt I will ua:
Q 2. I htvt tntwrtd into tn torttmtnt with ont or mort othtr rtfittnmn undtr FIFRA action 3(C)(2)(BHii) to satisfy tht following data
rtquirimtnts. Tht ttm, and tny rtquirtd protocols, will bi submintd to EPA by:
NAME OF OTHER REGISTRANT
CD 3. I mdoa t compltttd "Ctnifwrtion of Attempt to Enttr Into in Agntmtnt with Othtr Rtgistrinu for Otvtlopmtnt of Data" with
resptct to tht following dra rtquiramtno:
D 4. I nquat thtt you ummd my rtfiftration by otltting flu following UOM (this option • not mittolt to applicants for ntw products):
O 5. I rtquon voluntory ctncolwlion of ttM raoittretJon of thit product fTlw option is not ntjitoMt to applicants for ntw products.)
REGISTRANT'S AUTHORIZED RIPRCSCNTATIVC
SPA r-v rsao-i n»."r)
SIGNATURE
DATE
^ 122
-------
OMB Appro*,/ No. XO&O4GS
CERTIFICATION OF ATTEMPT TO ENTER
INTO AN AGREEMENT WITH OTHER REGISTRANTS
(To ««//r>. aftlfyALL *»»•«*»*) FOR DEVELOPMENT OF DATA
1. 1 am duly authorized to represent the following firm(s) who ara subiact to tha require-
mams of a Notica undor FIFRA Saction 3(c)(2)(B) containad in a Guidanca Oocumtnt
to submit data concarning tha active ingradiant:
NAME OP FIRM
OUIOANCf DOCUMENT OATI
ACTIVE INOMEOIENT
IPA COMPANY NUMBER
(This firm or group of firms is referred to balow as "my firm".)
2. My firm is willing to davolop and submit tha data as raquirad by that Notica, if necessary. However, my firm would prafer to ft
into an agreement with ona or mort othtr rtgistrants to davalop jointly, or to sharo in tha cost of developing, the following rtqu
Kams or data:
X My firm has offtrad In writing to afflar into audi an agreement Capias of tha offan an attached. That offor was Imuacabls and inctodad an offer n
Mimd by an arbitration decision undar FIF BA Saction 3(e)(2)(B)(i« If final agnamant on oN farms could not ba raacnad otharwiss. This offar was w
to tha following firmis) on tha (oOowing dao
-------
EPA Reg. No.
PRODUCT SPECIFIC DATA EEPORT
Date
Guidance Document for
Registration
Guideline No.
$158.120
FRQDXT
CHEMISTRY
61-1
61-2
61-3
62-1
62-2
62-3
63-2
63-3
63-4
6: -5
63-6
63-,'
63-8
63-9
63-10 -
63-11
63-12
Name of Test
Identity of
Ingredients
Statement of
composition
Discussion of
formation of
Ingredients
Preliminary
analysis
Certification of
limits
Analytical methods
for enforcement
limits
Color
Physical state
Odor
Melting point
Boiling point
Density* bulk-
density, or
specific gravity
solubility
Vapor pressure
Dissociation
constant
Octanol/water
partition
coefficient
PH
lest not
required
for my
product
listed
above
(check
below)
I am complying with
data requirements by
Citing MRLD
Number or
EPA Accession
Number
Submit-
ting
Data .
(At-
tached)
(For EPA Use Cnly)
Accession Numbers
Assigned
124
-------
Registration
Guideline No.
63-13
63-14
63-15
63-16
63rl7
63-18
63-19
. 63-20
63-21
515^.135
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
Name of Test
Stability
Oxidizing/reducing
reaction
Flannabillty
Explodablllty
Storage stability
Viscosity
Mlscibility
Corrosion
characteristics
Dielectric break-
down voltage
Acute oral
toxlclty, rat
Acute dermal
toxlcity, rabbit
Acute inhalation,
toxlcity, rat
Prljnary eye
irritation, rabbit
Primary dermal
irritation
Dermal sensitiza-
tlon
Test not
required
for my
product
listed
above
(check
below)
I am complying with
data requirements by
Citing MRID
Number or
EPA Accession
Number
'
Submit-
ting
Data
(At-
tached)
(For EPA Use Oily)
Accession Numbers
Assigned
• -
125
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CMB Approval No. 2070-0057
Expiration Date 11/30/89
GENERIC DATA EXEMPTION STATEMENT
EPA Product Registration Number:
Registrant's Name and Address:
As an authorized representative of the registrant of the product identified
above, I certify that:
(1) I have read and am familiar with the terms of the Notice from EPA dated
concerning a requirement for submission of "generic" data on the
active Ingredient ______________ named under FIFRA Section 3(c)(2)(B).
(2) Jfy firm requests that EPA" not suspend the registration of our product,
despite our lack of Intent to submit the generic data in question, on the grounds
that the product contains the active ingredient solely aa the result of the
incorporation Into the product of another product which contains that active
ingredient, which is registered under PIPRA Section 3, and which Is purchased by
us from another producer.
(3) An accurate Confidental Statement of Fonnula(CSF) for the above-identlfiea
product is attached to this statement. That formula statement indicates, by
company name, registration number, and product name, the source of the subject
active ingredient in my firm's product, or
The CSP dated _ on file with EPA is complete, current and accurate and
contains the information requested on the current CSP Fora No. 857CM. The
registered source(s) of the above named active Ingredient in my product(s) is/are
_ and their registration number(s) Is/are _ .
My firm will apply for an amendment to the registration prior to changing
the source of the active ingredient in our product.
I understand, and agree on behalf of my firm, that if at any time any
portion of this Statement is no longer true, or If my firm fails to comply with
the undertakings made in this Statement, my firm's product's registration may be
suspended under FIFRA Section 3(c)(2)(B).
(5) I further understand that If my firm is granted a generic data exemption
for the product, my firm relies on the efforts of other persons to provide the
Agency with the required generic data. If the registrant(s) who have committed
to generate and submit the required data fall to take appropriate steps to meet
requirements or are no longer In compliance with this Notice's data requirements,
the Agency will consider that both they and my firm are not In compliance and
will normally initiate proceedings to suspend the registrations of my firm's
product (a) and their product(s), unless my firm ccmndta to submit and submits
the required data in the specified time frame. I understand that, In such cases,
the Agency generally will not grant a time extension for submitting the data.
Registrant's authorized representative:
(signature)
Dated:
(Typed)
EPA Ponfl 8570-27 | 26
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