United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-96-031
November 1996
R.E.D. FACTS
Amitraz
Pesticide
Re registration
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered before November 1, 1984, be
reregistered to ensure that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
each pesticide's risks. EPA then reregisters pesticides that can be used
without posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregistration case 0234, amitraz.
*
Amitraz or BAAM is an insecticide and acaricide used primarily to
control the pear psylla on Oregon pear crops. It also is used to control
whiteflies and mites on cotton and pear crops; livestock ticks, lice, and
mange mites on beef and dairy cattle and swine; and ticks on dogs.
Formulations include a wettable powder, emulsifiable concentrate, soluble
concentrate/liquid, and impregnated collar (for dogs). Amitraz is applied as
an airblast and concentrate spray to pears; by ground boom or aircraft to
cotton; as a dip or low pressure hand spray to cattle and swine; and through
collars on dogs.
Reg Ulatory Amitraz was registered as a technical grade pesticide in 1975; EPA
H iStO ry received an application for registration of an end-use product for apples and
pears in 1976. Before a registration decision was made, however, in 1977,
the pesticide went into Special Review (then called Rebuttable Presumption
Against Registration or RPAR) because it met the risk criteria for cancer
effects-it was shown to cause cancerous tumors in mouse lymph systems.
Use Profile
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Human Health
Assessment
At the end of the RPAR process in 1979, EPA concluded that there
was "weakly positive evidence" that amitraz is a possible human
carcinogen. The Agency conditionally registered the pear use in 1980 since
there were no alternatives for controlling pear psylla, but rejected the apple
use since alternative pesticides were available.
Part of the conditional registration requirements were satisfied by
submission of a new mouse cancer study, which the Agency's Cancer
Assessment Group (CAG) evaluated in 1986. CAG classified amitraz as a
Group C, possible human carcinogen, a classification that still stands. In ,
1986, EPA registered amitraz to control ticks on cattle and lice on hogs.
Toxicity
In acute toxicity studies, amitraz is moderately toxic by the dermal
route, and has been placed in Toxicity Category II (the second highest of
four categories) for this effect. It is slightly toxic by the oral and inhalation
routes, and has been placed in Toxicity Category HI for these effects.
Amitraz is non-irritating to the eyes and skin and has been placed in
Toxicity Category TV for these effects. Amitraz does not cause skin
sensitization or cholinesterase inhibition.
In a subchronic toxicity study using mice, amitraz caused reduced
body weight gain and liver toxicity at the higher doses. A study using
Beagle dogs resulted in liver, kidney, and central nervous system effects.
A study using rabbits resulted in skin reactions, anorexia, hyperglycemia,
degeneration of the testes, and effects to the lymph nodes and various
organs. A chronic toxicity study using dogs resulted in central nervous
system depression, increased blood glucose levels, and hypothermia.
In a carcinogenicity feeding study using mice, amitraz produced
lymphoreticular tumors in females at the highest dose level. In another
study using mice, amitraz produced liver and lung tumors at the highest
level studied. Based on these studies, EPA has classified amitraz as a
Group C (possible human) carcinogen. Carcinogenic effects were not
observed in a study using rats. , .
Amitraz caused both maternal and developmental effects at the
highest dose level in a developmental toxicity study using rabbits. A multi-
generation reproduction study using rats is unacceptable and must be
replaced by confirmatory data regarding develo ontal neurotoxicity and
reproductive toxicity. Amitraz is not mutagenic
Data from an acute neurotoxicity study and a metabolism study using
volunteer human subjects were used to establish the NOEL, and LOEL.
Neurotoxic signs were observed in chronic oral tcxicity studies in rodents,
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as well as in subchronic and chronic oral toxicity studies in non-rodents
(dogs). Related acute signs also were observed in human volunteers.
Amitraz is rapidly metabolized iii several species, including humans,
to form six metabolites which are excreted primarily in the urine. EPA has
established a Reference Dose (RfD) for amitraz at 0.0025 mg/kg/day based
on .results of the chronic oral toxicity study in dogs.
Dietary Exposure
Tolerances or maximum residue limits are established for residues of
amitraz in or on apples, pears, cotton seed, honey and comb, eggs, milk,
and the meat, fat, and meat byproducts of cattle, hogs, horses, and poultry..
These tolerances have been reassessed and most were found to be adequate.
The 3.0 ppm tolerance for pears is being lowered to 2.0 ppm. Tolerances of
0.0 ppm for amitraz residues in apples and in horse fat, meat, and meat
byproducts are being revoked. A tolerance for imported hops was proposed
recently. No food/feed additive tolerances are established.
Adequate methods are available .to enforce amitraz tolerances.
Residues of amitraz and two of its metabolites are stable in several food
commodities tested. Existing crop rotation restrictions for amitraz1 cotton
use are adequate. >
A number of international Codex maximum residue limits (MRLs) are
established for amitraz. However, compatibility between the Codex MRLs
and U.S. tolerances cannot be achieved at present due to differences in
tolerance definition/expression and analytical enforcement methods.
EPA assessed the chronic, carcinogenic, and acute dietary risks posed
by amitraz. Most exposure to amitraz is attributed to one commodity,
pears, which accounts for 58% of total exposure based on a 14-day
preharvest interval (PHI). -
EPA's chronic dietary risk assessment for amitraz indicates that with a
14-day PHI for pears, the Anticipated Residue Concentration,(ARC) for the
overall U.S. population is 1.1% of the Reference Dose (RfD) or amount
believed not to cause adverse effects if consumed daily over a 70-year
lifetime. The ARC for non-nursing infants less than one year old, the most
highly exposed subgroup, is 4.5% of the RfD. In view of these low ARCs,
it appears that chronic, non-cancer dietary risk from exposure to amitraz is
minimal.
The upper bound cancer risk for the overall U.S. population is
estimated at 1.4 x 10"6, or 1.4 extra incidences of cancer per 1 ,QOO,000.
This degree of risk is considered acceptable by the Agency.
Because neurotoxicity is the endpoint of concern, acute exposure and
risk were calculated for all U.S. population subgroups. The Margins of
Exposure (MOEs) are greater than 10 for all of these groups, whichjs'
considered acceptable.
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Occupational and Residential Exposure
Workers may be exposed to amitraz during mixing, loading, and
application of the pesticide, especially when liquid (emulsifiable
concentrate) and wettable powder formulations are used! In addition,
potential exposure risk exists for workers entering treated sites after
application is complete, especially pear orchards and cotton fields.
A dermal and inhalation exposure assessment was conducted for the
pear, cotton, and livestock uses of amitraz. Pear use is associated with the
highest total exposure, followed by cotton use and, finally, livestock use
Pear handlers' exposure is highest when mixing/loading is accomplished
using an open system and the application is by open cab/airblast. Post-
application exposure is greatest during tasks requiring substantial derrr
contact with treated foliage.
Handlers using amitraz to treat pear orchards, cotton fields, and
livestock on a long-term basis may be at risk for carcinogenic effects. Pear
use is associated with the highest cancer risk, followed by cotton use, and
finally, livestock use. These handlers' upper bound cancer risks range from
2.7 x 10'8 to 1.2 x 10~5; however, these risk levels are less than 1 x 10/4
which EPA finds acceptable. .
In addition, certain handlers face neurotoxic risks from short-term
exposure to amitraz. Margins of Exposure (MOEs) are less than 10, the
margin generally considered acceptable, for three use scenarios in which
wettable powder or liquid formulations of amitraz are mixed/loaded via
open bag or open pour methods, and are applied to pear orchards or cotton
crops using open cab/air blast or ground boom equipment.
Reentry workers involved on a long-term basis with post-application
tasks requiring dermal contact with treated pear foliage also may be at risk
for cancer effects, though these risks are considered acceptable. Pear and
cotton reentry workers also encounter neurotoxicity risks from short-term
exposure to amitraz residues. Post-application neurotoxicity risks resulting
from use of amitraz on livestock and in pet collars are considered
negligible.
Human Risk Assessment
Amitraz is of relatively low acute toxicity, but has been demonstrated
to cause cancer in mice and is classified as a Group C "possible" human
carcinogen. People may be exposed to residues of amitraz in pears and
other foods. However, chronic exposure to amitraz in the diet is at a low
level (only a small percent of the RfD), and is not a cause for concern at this
time.
EPA is concerned that amitraz has the potential to cause reproductive,
developmental, and neurological toxicity risks to the general population.
The Agency also is concerned that handlers applying amitraz to pear
orchards, cotton fields, and livestock on a long-term basis may be at risk for
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Environmental
Assessment.
cancer effects. Both handlers and reentry workers in pear orchards and
cotton fields also may be at risk for acute neurotoxic effects.
To reduce risks of cancer and rieurotoxicity to the general public and
amitraz handlers, EPA is taking a number of risk mitigation measures
described in greater detail below. For example, the Agency is requiring an
increase in the interval between amitraz applications to pears; an increase in
the restricted-entry interval (REI) for pears and cotton; and engineering
controls for the pear and cotton uses. EPA also is specifying minimum,
baseline personal protective equipment (PPE) for workers, and is requiring
the registrant to submit a new combined developmental, neurological, and
reproductive toxicity study as confirmatory data.
Environmental Fate
The Agency has performed a comprehensive quantitative
environmental fate assessment for parent amitraz. The review of available
studies submitted indicates that parent amitraz rapidly degrades in the
environment to form two primary transformaton products BTS 27271, BTS
27919 and a secondary transformation product BTS 24868. Because of its
rapdi degration in the environment, parent amitraz is not expected to pose a
concern for ground or surface waters. In contrast to parent amitraz, amitraz
transformation products have been shown to be moderately persistent in
aquatic and terrestrial environments and appear to be relative immobile in
soil column and field dissipation studies. An accurate quantitative
assessment of these products in ground and surface water, though, cannot
be made until additonal mobility studies (batch equilibrium) are completed.
Ecological Effects
In acute toxicity studies, amitraz is slightly toxic to mallard ducks.
BTS-27271 is moderately toxic and BTS-27919 is slightly toxic to the
bobwhite quail. In subacute dietary studies, parent amitraz is practically
nontoxic to the mallard duck and slightly toxic to the bobwhite quail. Its
two primary degradates are practically nontoxic to the mallard duck.
BTS-27271 is slightly toxic and BTS-27919 is practically nontoxic to the
bobwhite quail. Parent amitraz causes effects on avian reproduction
including eggshell cracking and reductions in the number of viable
embryos, embryos that survive to hatching, and 14-day old survivors.
Parent amitraz is highly toxic to freshwater fish while BTS-27271 and
BTS-27919 are slightly toxic to practically nontoxic, respectively. Parent
amitraz also is very highly toxic to aquatic invertebrates while BTS-27271
and BTS-27919 are moderately toxic and practically nontoxic, respectively.
Parent amitraz is highly toxic to oysters, moderately toxic to the sheepshead
minnow, and slightly toxic to grass shrimp. BTS-27271 is slightly toxic
and BTS-27919 is practically nontoxic to the sheepshead minnow and
eastern oyster; both are moderately toxic to the mysid shrimp. -
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Risk Mitigation
Amitraz is slightly toxic to small mammals on an acute oral basis, and
is practically nontoxic to bees.
Ecological Effects Risk Assessment
Regarding acute risks, parent amitraz does not appear to pose a risk to
endangered or non-endangered terrestrial organisms from either the cotton
or pear uses. However, BTS-27271 may pose an acute hazard to birds since
it is more acutely toxic and more persistent in the environment than the
parent. Due to the presence of BTS-27271, use of amitraz on cotton and
pears may pose an acute risk to endangered birds feeding on insects or short
grass. Since parent amitraz dissipates rapidly in the environment, it should
pose minimal acute risk to aquatic organisms.
Regarding chronic effects, use of amitraz on cotton and pears may
adversely affect avian reproduction. In addition, endangered small :
mammals may be affected when amitraz is used on cotton. Because parent
amitraz is short-lived in the environment, the potential for chronic effects to
nontarget aquatic organisms is expected to be minimal. However, the
chronic toxicity of amitraz degradates is of concern because they are more
persistent in aquatic environments than parent amitraz. While the cotton
use pattern does not appear to pose a chronic risk to aquatic organisms, the
pear use pattern is of concern since it involves a higher application rate.
Chronic adverse effects to aquatic invertebrates may be expected from the
use of amitraz on pears. ฐ
Use of amitraz on cattle and swine is expected to result in minimal
exposure to aquatic organisms.
EPA has determined that amitraz is a valuable tool to control pear
psylla, whiteflies, and mites. Considering the limited acreage involved in
its use on pears and cotton, and the risk mitigation measures required,
amitraz1 risk potential is reduced.
The following risk mitigation measures, combined with generic
worker protection labeling, should mitigate the unacceptable neurotoxicity
risks to amitraz handlers:
' ' ' f
For the Pear Use:
Closed system mixing and loading;
Applications from within an enclosed cab; and
Minimal (baseline) personal protective equipment (PPE).
For the Cotton Use:
Closed system mixing and loading;
Mechanical flagging; and
. Minimal (baseline) PPE.
For the Livestock Spray/Dip Use: ;
Minimal (baseline) PPE. ;
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The following risk mitigation measures, combined with generic
worker protection labeling, should mitigate the unacceptable neurotoxicity
and cancer risks to post-application workers (those exposed to amitraz
residues after application is complete).
For the Pear Use:
' . . ^ . -
Minimum of 35 days between applications; and
Restricted-entry interval of 28 days (increased from 24 hours).
For the Cotton Use:
. ' Mechanical harvesting; and '
Restricted-entry interval of 48 hours (increased from 24 hours).
The following risk mitigation measures are required to reduce
: exposure to birds and small mammals:
For the Pear Use:
Deletion of pre-bloom use; and
Limit use to two applications per season.
Additional Data EPA is requiring the following additional generic data for amitraz to
Required confirm its regulatory assessments and conclusions:
. ' , .- ป Life-Cycle Aquatic Invertebrate study for the pear use;
Concurrent Dislodgeable Foliar Residue and Dermal Exposure data;
Batch Equilibrium studies for BTS 27271 and BTS 27919;
Droplet Size Spectrum and Field Drift studies;
Dermal Exposure and Inhalation Exposure studies for spray/dip
treatment of livestock.
An additional confirmatory study not part of the target database for amitraz
is also required:
Combined Developmental/Neurological/Reproduction Toxicity study
in rats. -
EPA also is requiring product-specific data including product
chemistry and acute toxicity studies, as well as revised Confidential
Statements of Formula (CSFs) and revised labeling for reregistration. '
Product Labeling ' All amitraz end-use products must comply with EPA's current
Changes pesticide product labeling requirements and those summarized below. For
Req U1 red a comP^ete description of amitraz labeling requirements, please refer to the
RED document.
Personal Protective Equipment (PPE) Requirements
For Occupational Use Products - Minimum/baseline PPE requirements are-
For Pear Uses - Applicators and other handlers must wear:
- Coveralls over long-sleeved shirt and long pants;
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Chemical-resistant footwear plus socks;
Chemical-resistant gloves;
Chemical-resistant headgear for overhead exposure;
Chemical-resistant apron when cleaning equipment, mixing, or
loading.
For Cotton Uses - Mixers, loaders and others exposed to the
concentrate must wear:
- Coveralls over long-sleeved shirt and long pants;
Chemical-resistant footwear plus socks;
Chemical-resistant gloves;
Chemical-resistant headgear for overhead exposure;
Chemical-resistant apron.
Applicators and other handlers exposed to the dilute must wear:
Long-sleeved shirt and long pants;
Chemical-resistant gloves;
Shoes plus socks.
For Livestock Spray or Dip Uses - Applicators and other handlers
must wear:
Coveralls over long-sleeved shirt and long pants;
Chemical-resistant footwear plus socks;
Chemical-resistant gloves;
Chemical-resistant headgear for overhead exposure;
Chemical-resistant apron when cleaning equipment, mixing, or
loading.
For Livestock Impregnated Collar Uses - Applicators and other
handlers must wear:
Long-sleeved shirt and long pants;
Chemical-resistant gloves;
Shoes plus socks.
For Homeowner Use Products - The Agency is not establishing
minimum/baseline PPE for end-use products intended primarily for
homeowner use. PPE requirements, if any, will be established based on the
acute toxicity of the end-use product.
Entry Restrictions
For Occupational Use Products:
Restricted-Entry Interval (RED - An REI is specified for uses within the
scope of the Worker Protection Standard (WPS) for all end-use products.
For Pear Uses- The REI is 28 days.
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For Cotton Uses - The REI requirement must state:
"Do not enter of allow workers entry into the treated area during the
restricted-entry interval of 48 hours. Note: mechanical harvesting
may be performed during the restricted-entry interval ONLY if the
harvesters will have no dermal or inhalation contact with treated
surfaces, including both the treated foliage and the residues in
airborne dusts generated by the mechanical harvesting. Crop advisors
may enter if they are wearing full early entry personal protective
equipment (PPE) as described below." -
Early-Entry Personal Protective Equipment (PPE)
For Pear and Cotton Uses-The PPE is:
Coveralls over long-sleeved shirt and long pants;
Chemical-resistant gloves;
Chemical-resistant footwear plus socks;
Chemical-resistant headgear for overhead exposures.
For Home Use Products - No restrictions are being established for products
intended primarily for home use.
Other Labeling Requirements
Application Restrictions:
"Do not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may
be in the area during application."
"For livestock spray or dip applications in enclosed areas: Apply only
in well-ventilated areas."
"For pear applications, allow a minimum of 35 days between
applications."
"Do not rotate to root and leafy vegetables for 44 days or to small
grains and other crops for 60 days following application."
Engineering Controls:, .
"When handlers use closed systems, enclosed cabs, or aircraft in a
manner that meets the requirements listed in the Worker Protection
Standard (WPS) for Agricultural Pesticides, ...the handler PPE
requirements may be reduced or modified as specified in the WPS."
"No human fiaggers allowed. Mechanical flaggers are required."
"Cotton must be harvested mechanically. No hand harvesting is
. allowed."
"For pear uses, this product must be mixed and loaded using a closed
system, and the applicator must be inside an enclosed cab during
application. The closed mixing/loading system and enclosed cab
must meet the requirements listed in the Worker Protection Standard
(WPS) for agricultural pesticides... When these engineering controls
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are used correctly, the handler PPE requirements may be reduced or
modified as specified in the WPS."
"For cotton uses, this product must be mixed and loaded using a
closed system (water-soluble bags are considered a closed
mixing/loading system). The closed mixing/loading system must
meet the requirements listed in the Worker Protection Standard
(WPS) for agricultural pesticides..
When these engineering controls are used correctly, the handler PPE
requirements may be reduced or modified as specified in the WPS."
User Safety Requirements:
"Follow manufacturer's instructions for cleaning/ maintaining PPE. If
no such instructions exist for washables, use detergent and hot water.
Keep and wash PPE separately from other laundry."
User Safety Recommendations:
"Users should wash hands before eating, drinking, chewing gum,
using tobacco, or using the toilet."
"Users should remove clothing immediately if pesticide gets inside.
Then wash thoroughly and put on clean clothing."
"Users should remove PPE immediately after handling this product.
Wash the outside of gloves before removing. As soon as possible,
wash thoroughly and change into clean clothing."
Notification Requirement for WPS Uses:
"Notify workers of the application by warning them orally and by
posting warning signs at entrances to treated areas."
Fish and Wildlife Hazard Statements: Amitraz labels must bear the
following Precautionary Statements under the subheading Environmental
Hazards:
Emulsifiable Concentrate and Wettable Powder Formulations:
"This pesticide is toxic to fish and aquatic invertebrates. Do not apply
directly to water, or to areas where surface water is present or to
intertidal areas below the mean water mark. Drift and runoff from
treated areas may be hazardous to aquatic organisms in adjacent sites.
Do not contaminate water when disposing of equipment washwaters
or rinsate."
Products Other than Those Described Above, and the 10% A.I. Dairy
Collar: . ' .
"This pesticide is toxic to fish and aquatic invertebrates. Do not
contaminate water when disposing of equipment washwaters or
rinsate."
10
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Regulatory
Conclusion
For More
Information
The MITAC WP label's Use Directions should be revised to include the
following restrictions:
"PEAR PS YLLA: Apply a maximum or 1 1/2 pounds MITAC WP
per acre. Do not exceed 3 Ibs of MITAC WP per acre per season. Do
not make more than two applications of MITAC WP per season."
The use of currently registered products containing amitraz in
accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products are eligible for reregistration.
Amitraz products will be reregistered once the required confimatory
generic data, product specific data, revised Confidential Statements of
Formula (CSFs) and revised labeling are revised and accepted by EPA.
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for [name] during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register. To
obtain a copy of the RED document or to submit written comments, please
contact the Pesticide Docket, Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide Programs
(OPP), US EPA, Washington, DC 20460, telephone 703-305-5805.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System
at 703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER.EPA.GOV, or using ftp on FTREPA.GOV, or using
WWW (World Wide Web) on WWW.EPA.GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489^8190, fax 513-489-8695.
Following the comment period, the [name] RED document also will
be available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
For more information about EPA's pesticide reregistration program,
the [name] RED, or reregistration of individual products containing [name],
please contact the Special Review and Reregistration Division (7508W),
OPP, US EPA, Washington, DC 20460, telephone 703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
11
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C: 20460
OFFICE OF
PREVENTION. PESTICIDES
AND TOXIC SUBSTANCES
NOV 2 2 1996
CERTIFIED MATT:
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case amitraz. This
RED was initially approved by the Agency in March 1995. Subsequently, the RED was
circulated for review and comment in connection with an international harmonization project.
The enclosed Reregistration Eligibility Decision (RED) document contains the Agency's
evaluation of the data base of these chemicals, its conclusions of the potential human health
and environmental risks of the current product uses, and its decisions and conditions under
which these uses and products will be eligible for reregistration. The RED includes the data
and labeling requirements for products for reregistration. It also includes requirements for
additional data (generic) on the active ingredient to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses are due 90 days from
the date of your receipt of this letter. The second set of required responses are due 8
months from the date of your receipt of this letter. Complete and timely responses will
avoid the Agency taking the enforcement action of suspension against your products.
Please note that this RED was finalized and signed prior to August 3, 1996. On that
date, the Food Quality Protection Act of 1996 ("FQPA") became effective, amending portions
of both the pesticide law (FIFRA) and the food and drug law (FFDCA). This RED does not
address any issues raised by FQPA, and any tolerance-related statements in the RED did not
take into account any changes in tolerance assessment procedures required under FQPA. To
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the extent that this RED indicates that a change in any tolerance is necessary, that
determination will be reassessed by the Agency under the standards set forth in FQPA before
a proposed tolerance is issued. To the extent that the RED does not indicate that a change in
a tolerance is necessary, that tolerance too will be reassessed in the future pursuant to the
requirements of FQPA.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Special Review and Reregistration Division representative
CP Moran (703) 308-8590. Address any questions on required generic data to the Special
Review and Reregistration Division representative Mario F. Fiol at (703) 308-8049.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Enclosures:
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SUMMARY OF DESTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION CRETH
1 DATA CALL-IN fDCD OR "90-DAY RESPONSE" - If generic data are
for reregistration, a DCI letter will be enclosed describing such date. If product specific data
are required, another DCI letter will be enclosed listing such requirements. Complete the two
response forms provided with each DCI letter by following the instructions contained in each
DCI. You must submit the response forms for each product and for each DCI within 90
days of the date you receive the RED; otherwise, your product may be suspended.
2 TIME EXTENSIONS AND DATA WAIVER REQUESTS - No time extension
requests will be granted for the 90-day response. Time extension requests may be submitted
only with respect to actual data submissions. Requests for data waivers must be submitted as
part of the 90-day response. Requests for time extensions should be submitted in the 90-day
response, but certainly no later than the 8-month response date. All data waiver and time
extension requests must be accompanied by a full justification. All waivers and time
extensions must be granted by EPA in order to go into effect.
3 APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"
You must submit the following items for each product within eight months of the
RED issuance date (the cover letter date).
a. Application for Reregistration (EPA Form 8570-1 V TTse only an
application form. Mark it "Application for Reregistration." Send your Application for
Reregistration (along with the other forms listed in b-e below) to the address listed in
itemS. ,
You may request an original EPA Form 8570-1 from:
b. Five copies of draft labeling which complies with the RED and current
regulations and requirements. Only make labeling changes which are required by the
RED and current regulations (40 CFR 156.10) and policies. Submit any other
amendments (such as formulation changes, or labeling changes not related to
reregistration) separately. You may delete uses which the RED says are ineligible for
reregistration. For further labeling guidance, refer the labeling section of the EPA
publication "General Information on Applying for Registration in the U,S., Second
Edition, August" 1992" (available from the National Technical Information Service,
publication #PB92-221811;703r487-4650).
c- Generic or Product Specific Data. Submit all data in a format which
complies with PR Notice 86-5, and/or submit citations of data already submitted and
give the EPA identifier (MRID) numbers. Before citing these studies, you must make
sure that they meet the Agency's acceptance criteria (attached to the DCI).
~ s - - '
d Two copies of the Confidential Statement of Formula (CSF) for each basic
and each alternate formulation. The labeling and CSF which you submit for each
product must comply with P.R. Notice 91-2 by declaring the active ingredient as the
nominal concentration. You have two options for submitting a CSF: (1) accept the
standard certified limits (see 40 CFR ง 1 5 8 . 1 75) or (2) provide certified limits that are
supported by the analysis of five batches. . If you choose the second option, you must
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submit or cite the data for the five batches along with a certification statement as
described in 40 CFRง158.175(e). A copy of the CSF is enclosed; follow the
instructions on its back.
e. ' Certification With Respect to Citation of Data. Complete and sign this form
(EPA form 8570-29) for each product. Cite-all is not a valid option for
reregistration.
ป
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE
Comments pertaining to the content of the RED may be submitted to the address
.. own in the Federal Register Notice which announces the availability of this RED.
5. WHERE TO SEND ALL PCI RESPONSES (90-DAY) AND APPLICATIONS
FOR REREGISTRATION (8-MONTH RESPONSES!
Bv U.S. Mail:
Document Processing Desk (RED-SRRb-0234)*
Office of Pesticide Programs (H7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001 ' .
Bv express;
Document Processing Desk (RED-SRRD-0234)*
Office of Pesticide Programs (H7504C)
, Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
* the case code for this RED (see front cover of document).
6. EPA'S REVIEWS-EPA .will screen all submissions for completeness; those which
are not complete will be returned with a request for corrections. EPA will try to respond to
data waiver and time extension requests within 60 days. EPA will also try to respond to all
8-month submissions with a final reregistration determination within 14 months after the RED
has been issued. .>-.'
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REREGISTRATION ELIGIBILITY DECISION
AMITRAZ
LISTA
CASE 0234
ENVIRONMENTAL PROTECTION AGENCY
. OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
AMITRAZ REREGISTRATION ELIGIBILITY DECISION TEAM .1
EXECUTIVE SUMMARY ........\. v
L INTRODUCTION ..., ..'......... .. 1
H. CASE OVERVIEW . ... .-. 2
A. Chemical Overview 2
B. Use Profile .2
C. Estimated Usage of Pesticide . 4
D. Data Requirements .....' .-.' , -.; 5
E. Regulatory History .-.... .:......., .5
SCIENCE ASSESSMENT . ....'.......- 7
A. Physical Chemistry Assessment 7
B. Human Health Assessment...... ;. 7
1. Toxicology Assessment '. 7
a. Acute Toxicity '...'... 8
b. Subchronic Toxicity . . : . 8
c. Chronic Toxicity .9
d. Carcinogenicity 9
e. Developmental Toxicity , 10
f. Reproductive Toxicity ;...-'............. 10
g.. Mutagenicity .11
h. Metabolism .11
i. Dermal Adsorption . 12
'. j. Special Studies ................... 12
k. Other Toxicological Considerations 13
1. Reference Dose (RfD) . . . . - 13
2. Exposure Assessment .........:................. 13
a. Dietary Exposure 13
b. Occupational and Residential Exposure 15
3. Risk Assessment. ....-..' 23
a. Dietary Risk " ;... ; 23
b. Occupational/Residential Risk .'...' , . 26
C. Environmental Assessment .. .30
1. Environmental Fate 31
a. Environmental Chemistry, Fate and Transport Data ....31
b. Environmental Fate Assessment 33
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2. Ecological Effects 33
a. Ecological Effects Data 33
(1) Terrestrial Data .; 34
(2) Aquatic Data , .36
(3) Non-Target Insects Data .40
(4) Non-Target Plants Data 41
b. Ecological Effects Risk Assessment 41
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 51
A. Determination of Eligibility '....''. .51
1. Eligibility Decision 52
2. Eligible and Ineligible Uses 52
B. Regulatory Position 52
1. Tolerance Reassessment 52
2. Codex Harmonization .54
3. Reference Dose 55
4: Risk Mitigation Measures .55
5. Endangered Species ...... 56
6. Labeling Rationale and Requirements 57
V. ACTIONS REQUIRED BY REGISTRANTS .,...'.... ... 61
A. Manufacturing-Use Products 61
1. Additional Generic Data Requirements 61
2. Labeling Requirements for Manufacturing-Use Products ...... 62
B. End-Use Products 63
1. Additional Product-Specific Data Requirements 63
2. Labeling Requirements for End-Use Products 63
a. Occupational/Residential Labeling 63
b. Other Labeling Requirements 66
C. Existing Stocks 69
VI. APPENDICES .....:. 71
APPENDIX A. Table of Use Patterns Subject to Refegistration .73
APPENDIX B. Table of the Generic Data Requirements and Studies
Used to Make the Reregistration Decision 77
APPENDIX C. Citations Considered to be Part of the Data Base
Supporting the Reregistration of Amitraz 87
APPENDIX D. Combined Generic and Product Specific Data Call-In ... 111
Attachment 1. Chemical Status Sheets 133
Attachment 2. Combined Generic and Product Specific Data
Call-in Response Forms (Form A inserts)
Plus Instructions : 135
Attachment 3. Generic and Product Specific Requirement Status
and Registrant's Response Forms (Form B inserts)
and Instructions ,..'..' 139
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Attachment 4.
Attachment 5.
Attachment 6.
APPENDIX E.
EPA Batching of End-Use Products for Meeting
Data Requirements for Reregistration 147
List of Registrants Sent this Data Call-in Notice .. 149
Cost Share, Data Compensation Forms,
Confidential Statement of Formula Form
and Instructions ...:........... 151
List of Available Related Documents 161
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AMITRAZ REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
*.
Biological and Economic Assessment
Paul Guillebeau
Gabe Patrick
YNg -
GhulamAli
Environmental Fate and Effects Assessment
Sharlene R. Matten
Harry Craven
Tracy L. Perry
James A. Hettrick
Health Effects Assessment
Debra Edwards
Flora Chow
John Redden
Nguyen B. Thoa
Patricia McLaughlin
JefFEvans .
Christina B. Swartz
Freshteh Toghrol
Stephen A. Schaible
Registration Support
Dennis H. Edwards
Meredith Johnson
Ian Blackwell
Risk Management
Lois A. Rossi
Esther Saito
Linda S. Propst
Mario F.Fiol
Carol Stangel
Biological Analysis Branch
LUIS, Biological Analysis Branch
Biological Analysis Branch
Biological Analysis Branch
Science Analysis and Coordination Staff
Ecological Effects Branch
Ecological Effects Branch
Fate and Groundwater Branch
Risk Characterization & Analysis Branch
Risk Characterization & Analysis Branch
Risk Characterization & Analysis Branch
Risk Characterization & Analysis Branch
Toxicology Branch U
Occupational and Residential Exposure
Branch
Chemistry Branch JJ
Chemistry Branch JJ
Science Analysis Branch
Insecticide-Rodenticide Branch
Insecticide-Rodenticide Branch
Registration Support Branch
Reregistration Branch
Reregistration Branch
Reregistration Branch
Reregistration Branch
Planning and Reregistration Branch
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ADI
AE
a.i.
ARC
CAS
CI
CNS
CSF
DFR
DRES
DWEL
EEC
EP
EPA
FAO/WHO
FDA
FIFRA
FFDCA
FOB
GLC
GM
GRAS
HA
HDT
LC,n
LD50
LD10
LEL
LOG
LOD
LOEL
MATC
MCLG
mg/L
MOE
MP
MPI "
MRE>
N/A
GLOSSARY OF TERMS AND ABBREVIATIONS
Acceptable Daily Intake. A now defunct term for reference dose (RfD). \
Acid Equivalent ,
Active Ingredient
Anticipated Residue Contribution
Chemical Abstracts Service
Cation
Central Nervous System .
Confidential Statement of Formula
Dislodgeable Foliar Residue .
Dietary Risk Evaluation System '
Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific (i.e.
drinking water) lifetime exposure at which adverse, non carcinogenic health effects are not
anticipated to occur.
Estimated Environmental Concentration., The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
End-Use Product .
U.S. Environmental Protection Agency .
Food and Agriculture Organization/World Health Organization
Food and Drug Administration .
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act ,
Functional Observation Battery
Gas Liquid Chromatography ,
Geometric Mean
Generally Recognized as Safe as Designated by FDA,
Health Advisory (HA). The HA values are used as informal guidance to municipalities and
other organizations when emergency spills or contamination situations occur.
Highest Dose Tested
Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of
substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg of ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to cause death in
50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It
is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
Lethal Dose-low. Lowest Dose at which lethality occurs.
Lowest Effect Level
Level of. Concern
Limit of Detection '
Lowest Observed Effect Level .
Maximum Acceptable Toxicant Concentration . .'
Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
Micrograms Per Gram .-,''.'
Milligrams Per Liter
. Margin of Exposure . ' ,
Manufacturing-Use Product
Maximum Permissible Intake
Master Record Identification (number). EPA's system of recording and tracking studies
submitted. .
Not Applicable .
ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
NOEC No effect concentration
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method .
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion ,
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
Q"j The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC , RedBloodCell . .
RED Reregistration Eligibih'ty Decision
REI Restricted Entry Interval
RfD Reference Dose =
RS Registration Standard
RUP Restricted Use Pesticide
SLN Special Local Need (Registrations Under Section 24(c) of FIFRA)
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
ug/L Micrograms per liter
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
Reregistration Decision
. This Reregistration Eligibility Decision (RED) Document addresses the reregistration
eligibility of the pesticide amitraz,
Based on the reviews of the generic data for the active ingredient amitraz, the Agency
has sufficient information, to make a reregistration eligibility decision on the health effects of
amitraz and on its potential for causing adverse effects in humans, fish and wildlife and the
environment. Based on this information, the Agency concludes that products containing
amitraz for all registered uses are eligible for reregistration, provided certain risk mitigation
measures required in this document are implemented.
The Agency, however, is concerned with the potential for the developmental/
neurological/ reproductive toxicity of amitraz to the general population, the acute neurotoxic
effect on certain categories of workers, and the possible significant risk to terrestrial and
aquatic species. In order to reduce these risks, the Agency is requiring an increase in the
interval between amitraz application to pears (minimum of 35 days between applications); an
increase in the restricted-entry interval (REI) for pears to 28 days, and for cotton an increase
to 48 hours; specifying minimum (baseline) personal protective equipment (PPE) for all
occupational uses, and requiring engineering controls for the pear use. Additionally, the
Agency is requiring the submission of a confirmatory developmental/neurological/
reproductive study and confirmatory dislodgeable foliar residue (DFR) and exposure data.
In order to reduce the potential risk for chronic reproductive effects to avian species,
risk mitigating measures were developed by the registrant, AgrEvo Co., and the Agency for
amitraz use on pears. The label deletion of the pre-blopm use on pears will reduce the
possible risk posed to on-site terrestrial animal species. In order to alleviate any concerns the
Agency may have for the neurotoxiciry effect of amitraz resulting from acute dietary
exposure, the registrant must provide label amendments that will limit the use on pears to two
applications of a WP formulation. .
The scientific data base is adequate to support the reregistration of all registered uses
of amitraz. The Agency is, however, requiring a life-cycle aquatic invertebrate study
(Guideline 72-4(b)) with BTS-27271, one of the three amitraz degradates; concurrent
dislodgeable foliar residue (DFR) data (Guideline 132-1 (a)) and dermal exposure data
(Guideline 133-3); batch equilibrium studies (Guideline 163-1) conducted with the amitraz
degradates BTS-27271 and BTS-27919; droplet size spectrum (Guideline 201-1) and field
drift studies (Guideline 202-1) which the registrant may elect to satisfy through the Spray
Drift Task Force; dermal exposure data (Guideline 231); and inhalation exposure data
(Guideline 232).
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Background Information
Amitraz is a formamidine insecticide/acaricide used to control pear psylla on pears,
whitefly and mites on cotton and pears; lice, livestock ticks, and mange mites on beef and
dairy cattle and swine; and ticks on dogs. Currently, there are six active amitraz products.
Bee mite strip and cattle collar uses were recently voluntarily canceled. Formulated amitraz
products include an emulsifiable concentrate, wettable powder, soluble concentrate, and
impregnated material. The registered formulations include an unspecified solid formulation
for manufacturing (97%), three emulsifiable concentrates (12.5% and two 19.8%); a wettable
powder (50%); and an impregnated dog collar/tag (9%). Currently maximum application ,
rates range from 0.2 lb/50 gal of water to 3 Ib ai/acre per season. Amitraz products can be
applied with aerial and ground equipment, including airblast sprayers and hand sprayers,
using dilute and concentrated solutions. There is also the 3-month dog collar.
Amitraz was first registered in 1975 as a technical to be used in the preparation of
experimental miticide/insecticide formulations. In 1976, an application for registration for an
end-use formulation to be used on apples and pears was submitted. In 1977, prior to any
registration decision, the Agency published a notice in the Federal Register of a rebuttable
presumption against reg. : oration (RPAR, now referred to as Special Review) on the basis that
amitraz met the risk criteria for carcinogenic effects. It was concluded that amitraz was a
possible human carcinogen and the proposed pear use would pose a risk of cancer, albeit very
small, to certain exposed groups. It was further concluded that the benefits for use on pears
outweighed the risks. The Agency conditionally registered amitraz on pears for four years.
Since alternative products were available for apples, the benefits for apples did not outweigh
the risks and apples were not registered. . '', ,
One of the conditions of registration was the generation of a new mouse
carcinogenicity study. This study was submitted mid evaluated by the Agency's Cancer
Assessment Group (CAG). Using both mouse studies, the CAG classified amitraz as a Group
C (possible human) carcinogen. This cancer classification decision was reaffirmed by the
Agency's Peer Review Committee in October 1990. .
The Agency issued a Registration Standard for amitraz in October 1987
(PB-88-128665). The Registration Standard required product and residue chemistry,
environmental fate and ecological effects data. No additional toxicology studies were
required.
A Data Call-in issued September 30, 1991 required additional data for product
chemistry, ecological effects, reentry protection, environmental fate, and nature of the residue
in livestock. The Agency has now completed its review of the target data base for amitraz,
including data submitted in response to the 1987 Registration Standard and the subsequent
Data Call-in.
VI
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Supporting Rationales for Reregistration Decision
Acute toxicity studies indicate that amitraz is slightly toxic by the oral and inhalation
routes (Toxicity Category HI) and moderately toxic by the dermal route (Toxicity Category
IT). Amitraz is not a dermal irritant and only a slight irritant to the eyes (Toxicity Category
IV) for both and is not a dermal sensitizer.
In a human study, acute exposure to amitraz was associated with central nervous
system (CNS) toxicity symptoms of sedation, disorientatibn, and hypothermia. The Agency
considers the NOEL for acute neurotoxicity in the human study, 0.125 mg/kg/day, to
represent the toxicological endpoint for short-term occupational risk assessment and considers
the Qj* of 5 x 1(T2 (mg/kg/day)"1 to represent the toxicological endpoint for occupational
carcinogenic risk assessment.
Amitraz may pose a concern for potential carcinogenic risks to certain categories of
workers. Amitraz is classified as a Group C (possible human) carcinogen, based on findings
of combined liver adenomas/carcinomas in female B6C3F1 mice. Estimates of human risk
may be calculated from the unit risk, Qj*, which is 5 x 10'2 (mg/kg/day)'1, based on findings
of combined hepatocellular adenbmas and carcinomas in female mice. Additionally, there
may also be a potential for a developmental, neurological and/of reproductive risk, based on
available toxicology information. These issues will be assessed after a confirmatory
combined developmental/neurological/reproductive study in rats is submitted and evaluated.
Dietary exposure due to published uses of amitraz may be associated with an estimated
excess upper bound carcinogenic risk of 1.4 x W6. The bulk of exposure was attributed to
pears (58% of total exposure based on 14 days PHI). Except for honey, for which 100% crop
treated value was used, the exposure estimates for all other published uses reflect all presently
available refinements in both residue and percent crop treated information.
Using anticipated residues and percent treated crop data, chronic exposure to amitraz
in the diet is only a small fraction of the RfD (1.1% of RfD for the overall U.S. population
and 4.5% of RfD for "non-nursing infants <1 year old", the most highly exposed ORES
subgroup) and does not appear to be a cause for concern. Based on the low % RfD's, it
appears that chronic non-cancer dietary risk from exposure to aniitraz is minimal.
Additionally, using tolerance level residues for all commodities except pears, acute exposure
to amitraz in the diet does not appear to be a cause for concern (MOE > 10, based on the
human study). The acute anticipated residue used for amitraz and BTS-27271 is 0.42 ppm.
At the 98th percentile of pear consumption, no population subgroup has acute dietary risk
MOEsof<10.
Handlers using amitraz to treat pear orchards, cotton fields, and livestock on a long-
term basis may be at risk from its carcinogenic effects. Estimated excess carcinogenic risks
for handlers are 2.7 x 10'8 to 1.2 x 10'5. MOEs were based on the NOEL from the human ..
vn
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study; handlers' exposure data for the pear use; and available PHED data for cotton and
livestock use and foliar residue data for pear use.
The Agency has performed a comprehensive qualitative environmental fate assessment
for parent amitraz. The available studies submitted and reviewed by the Agency show that
parent amitraz rapidly degrades in the environment to form two primary transformation
products BTS-27271 and BTS-27919 and a secondary transformation product BTS^24868.
Because of its rapid degradation in the environment, amitraz is not expected to pose a concern
for ground or surface waters. In contrast to parent amitraz, amitraz transformation products
have been shown-to be moderately persistent in aquatic and terrestrial environments and
appear to be relatively immobile in soil column and field dissipation studies. An accurate
quantitative assessment of these products in ground and surface water, though, cannot be
made until additional mobility studies (batch equilibrium) are completed.
. ' j
Amitraz use on pears and cotton may also pose a chronic risk to nontarget avian and
mammalian species. The EECs calculated using maximum and typical Kenaga values and
residues from a foliar field dissipation study exceed the lowest effect level (LEL) which is
defined by the range of the NOEL to the LOEL. Amitraz use on pears may also pose a
chronic risk to nontarget aquatic invertebrates because the EEC for the degradate BTS-27271
exceeds 0.01 EC
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these data and any revised labels and finding them acceptable in accordance with Section
3(c)(5) of FEFRA, the Agency will reregister a product. However, those products which bear
uses of this or any other active ingredients which have not been determined to be eligible for
reregistration will be reregistered only when such uses and active ingredients are determined
to be eligible for reregistration.
IX
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I.
INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was
amended to accelerate the reregistration of products with active ingredients registered prior to
November 1, 1984. The amended Act provides a schedule for the reregistration process to be
completed in nine years. There are five phases to the reregistration process. The first four
phases of the process focus on identification of data requirements to support the reregistration
of an active ingredient and the generation and submission of data to fulfill the requirements.
The fifth phase is a review by the U.S. Environmental Protection Agency (referred to as "the
Agency") of all data submitted to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for registration" before
calling in data on products and either reregistering products or. taking "other appropriate
regulatory action." Thus, reregistration involves a thorough review of the scientific data base
underlying a pesticide's registration. The purpose of the Agency's review is to reassess the
potential hazards arising from the currently registered uses of the pesticide; to determine the
need for additional data on health and environmental effects; and to determine whether the
pesticide meets the "no unreasonable adverse effects" criterion of FIFRA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of amitraz. The document consists of six sections. Section I is the
introduction. Section n describes amitraz, its uses, data requirements and regulatory history.
Section IE discusses the human health and environmental assessment based on the data
available to the Agency. Section IV presents the reregistration decision for amitraz. Section
V discusses the reregistration requirements for amitraz. Finally, Section VI is the Appendices
which support this Reregistration Eligibility Decision. Additional details concerning the
Agency's review of applicable data are available on request from the Office of Pesticide
Programs, Public Response Section in the Public Response and Program Resource Branch,
401 M Street, S.W., Washington, D.C. 20460. Telephone number: (703) 305-5805.
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H. CASE OVERVIEW
A. Chemical Overview
The following active ingredient is covered by this Reregistration Eligibility Document:
Common Name: Amitraz or BAAM
An insecticide/acaricide with registered food/feed uses on crops (cotton and
pears), animals (cattle and hogs), and home use (pets).
Chemical Name: Nl-(2,4-dimethylphenyl)-N-(((2,4-
dimethylphenyl)imino)methyl)-N-methyl-
methanimidamide
Empirical Formula:
Molecular Weight:
CAS Registry No.:
Shaughnessy No.:
Basic Manufacturer:
293
33089-61-1
106201
AgrEvo Chemical Company
Pure amitraz is an off-white crystalline solid, and technical amitraz is a straw-colored
crystalline solid with a melting point of 86-87ฐ C and a density of 1.13 g/ml. At 20-25ฐ C,
amitraz is soluble at <1 ppm in water, 66.6 g/100 ml in xylene, 50 g/100 ml in acetone, and
2.38 g/100 ml in methanol.
B. Use Profile
The following is information on the currently registered uses of amitraz. A detailed
table listing the eligible and ineligible uses as well as methods, application rates, limitations,
and use restrictions is included in Appendix A.
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Type of Pesticide:
formamidine insecticide/acaricide
Mechanism of Action:
contact
Use Groups And Sites:
Terrestrial Food Crop: Pear
Terrestrial Food and Feed Crop: Cotton
Indoor Residential: Dogs/canines
- Indoor Food: .Dairy cattle (lactating or unspecified), beef/range/feeder cattle
. (meat), hog/pig/swine (meat)
Pests:
Pear psylla and livestock ticks, lice and mange mites. Also lepidopteran pests,
whiteflies and mites on cotton.
Formulation Types Registered:
Unspecified solid formulation for manufacturing: 97%
Emulsifiable concentrate: 12.5%, and 19.8%
Wettable powder: 50%
Impregnated collar/tag (dog): 9%
Method and Rates of Applications:
Cotton: Up to 1 Ib a.i./acre during the growing season with a maximum
of 8 applications per year. Label indicates amitraz is often
mixed with other insecticides.
Pear: Up to 3 Ib a.i./acre applied during dormancy and throughout the
growing season excluding prebloom applications.
Livestock
(dairy cattle/beef cattle/swine): Spray or dip at up to 0.2 Ib ai./50 gallons
of water
Dog collar: 3 month collar.
Application of product can be either by aerial or ground equipment, including airblast
sprayers and hand sprayers delivering either dilute or concentrated applications. The dog
collar, impregnated with amitraz, is considered a homeowner product.
Use Practice Limitations: Refer to appendix A.
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C. Estimated Usage of Pesticide
This section summarizes the best estimates available of amitraz use. These estimates
are derived from a variety of published and proprietary sources available to the Agency. The
data reflect annual fluctuations in use patterns as well as the variability in using data from
various information sources. However, data were not available for the use of amitraz in dog
collars.
Site
U.S. Amitraz Use
Estimated Annual 1989 - 1992
Grown Acres
(000)
Treated Acres
(000) (%)
a.i. Ibs.
(000)
PEAR
California
Colorado
Massachusetts
Michigan
New Jersey
New York
Ohio
Oregon
Pennsylvania
Washington
Total for Pears*
25.8
0.6
0.1
1.6
0.1
3.2
0.1
18.3
1.5
26.0
77.3
2-6
0.1-0.2
N/A
0.5 - 0.8
N/A
1.3-1.9
0.002
5-15
0.8 - 1.3
4-6
16-31
10-25
19-31
N/A
32-48
N/A
46-72
2-3
26-88
51-85
15-23
19-37
2.5 - 8.0
0.1-0.2
'N/A
0.5-0.8
N/A
2.3 - 2.9
0.001
8-21
2.3 - 3.8
6-8
21-71
COTTON
California only
1040
0.07
0- <1
0.06
(*) Total for pears also includes other states which are not listed above.
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U.S. Amitraz Use
Estimated Annual 1989 - 1992
Livestock
Commodity
Cattle'
Swine
Total for Livestock
Millions
96
111
207
Millions
: 2-3
11-22
13-25
(% treated)
2-3
10-20
6 - 12
a.i. Ibs.
N/A
N/A
N/A
N/A indicates not available. ,
D.. Data Requirements
Data requested in the October 1987 Registration Standard for amitraz included studies
on product chemistry, ecological effects, environmental fate, and residue chemistry. These
data were required to support the uses listed in the Registration Standard. Additionally, a
Data Call-In issued by the Agency in September 1991 requested product chemistry,
ecological, environmental, and residue chemistry data that the Agency had determined were
needed for reregistration. Appendix B lists all data requirements identified by the Agency, as
needed to support reregistration of currently registered uses.
E. Regulatory History
Amitraz was first registered in 1975 as a 93% technical to be used in the preparation of
experimental miticide/insecticide formulations. The first application for registration of an
end-use formulation was made in 1976 for a product to be used on apples and pears. In April
1977, prior to any registration decision on these uses, the Agency published a notice in the
Federal Register (42 FR 18299) of a rebuttable presumption against registration (RPAR, now..'
referred to as Special Review) of pesticide products containing amitraz on the basis that
amitraz met the risk criteria for carcinogenic effects. An 80-week mouse carcinogenicity
study showed a significant increase in the incidence of lymphoreticular tumors in mice.
The RPAR or Special Review process resulted in the Agency conclusion that there is
"weakly positive evidence" that amitraz is a possible human carcinogen. The Agency also
concluded that the proposed use on apples and pears might pose a very small risk of cancer to
certain exposed groups. A review of the benefits and risks surrounding the proposed uses
resulted in the Agency determination that there would be significant benefits from the use on
pears since amitraz will control pear psylla, a serious pest for which there were no viable
alternatives. It was concluded however, that there were little or no benefits to the use oil
apples since alternative products were available. The Agency's decision was published in the
Federal Register in October, 1979 (44 FR 59939-59946) where it was also announced that the
Agency intended to conditionally register amitraz on pears for four years. The registration
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was issued in January, 1980 with the conditions of the registration requiring the registrant to
a) submit additional benefits data for the pear use, b) submit a new mouse carcinogenicity
study, c) label the product "Restricted Use," and d) add additional precautionary text to the
label.
The conditional registration requirements for the use of amitraz on pears were
satisfied. A new mouse carcinogenicity study was referred to the Agency's Cancer
Assessment Group (CAG) for evaluation in 1986. The study showed an increase in the
incidence of hepatocellular tumors in female mice. Based on the two studies, CAG concluded
that amitraz has carcinogenic activity in the mouse, and should therefore be classified as a
Group C, possible human carcinogen. Amitraz was referred to the FJJFRA Scientific Advisory
Panel (SAP) which recommended that it be classified as a Group D since the panel believed
that the weight of the evidence was inadequate to clearly categorize the cancer potential. The
Agency then reconsi.dered the classification but determined that amitraz would still be
regulated as a Group C carcinogen. In 1986 amitraz was registered for use as an emulsifiable
concentrate to control ticks on cattle and lice on hogs.
The Registration Standard ("Guidance for the Reregistration of Pesticide Products")
was issued in October 1987 (EPA Case No. 234). The Standard reported that the Agency
would continue the registration on pears, cattle and hogs, but stated that the tolerances for the
proposed uses on apples and citrus would not be issued. The Standard also required that
certain environmental fate and avian reproduction studies be conducted, and additional plant
metabolism data be submitted. The Restricted Use classification for amitraz end-use products
was lifted by the Standard, but a 24-hour reentry interval for pears was retained.
Subsequent registrations of amitraz-containing products were issued for use on dogs
(1992), in beehives (1992), and on cotton (1993). End-use formulations include emulsifiable
concentrates, a wettable powder, a dog collar, and an impregnated strip to control parasitic
mites in beehives. There are a total of six active amitraz registrations, including one technical
product. The technical product is not produced domestically. AlsOj an import tolerance for
hops was recently proposed in the Federal Register.
In October 1990, the Agency's Office of Pesticide Programs, Health Effects Division,
Peer Review Committee met to discuss amitraz and evaluate its carcinogenic potential. The
Committee considered the weight-of-the-eyidence and reaffirmed the Group C classification,
and additionally recommended that the risks be quantified by unit risk.
On January 13, 1994, one of the amitraz registrants requested voluntary cancellation of
two of his products: the dairy cattle collar (EPA Registration Number 54382-4) and the
impregnated strip controlling parasitic mites in beehives (bee mite strips), (EPA Registration
Number 543 82-5).
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HI. SCIENCE ASSESSMENT
The Agency has conducted a thorough review of the scientific data base for amitraz
for the purpose of determining the reregistration eligibility of amitraz.
A. Physical Chemistry Assessment
- The physical and chemical properties of amitraz are as follows:
Amitraz Technical
Color:
Physical State:
Odor:
Melting Point:
Specific Gravity:
Solubility:
Vapor Pressure:
pH:
Stability:
either off-white or straw-colored
crystalline solid
slight amihe odor .
86-87ฐC
1.128g/mlat200C
at 20-25ฐ C, soluble at 1 ppm in water, 66.6 g/100 mlin xylerie,
50 g/100 ml in acetone, and 2.38 g/100 ml in methanol
3,4xlO-4Pa@25ฐC .
N/A (product has low solubility and decomposes in water).
stable at ambient temperature
There is a single registered manufacturing-use product (MP): the AgrEvo Chemical
Company 97% technical amitraz (T; EPA Registration Number 45 63 9-51).
The product chemistry data base for amitraz is adequate and will support the
reregistration eligibility of amitraz as a food use pesticide. References (MRIDs) for all studies
submitted in support of the product chemistry data requirements are listed in the data tables,
Appendix B, part of this document.,
B. Human Health Assessment
1. Toxicology Assessment
The lexicological data base of amitraz is adequate and will support reregistration as a
food use pesticide. Although a confirmatory study (a combined developmental/neurological/
reproductive toxicity study in rats) is required for continued registration of amitraz, the
information available is sufficient to evaluate the chemical's toxicity.
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a. Acute Toxicity .
The acute toxicity data for the technical grade of amitraz are summarized below:
Test
(81-1) Oral LD50- rat
(81-2) Dermal LDio - rabbit
(81-3) Inhalation LC50- rat
Results LD,n
531 mg/kg (M); 515 nig/kg (F) (MRID 00041539)
> 200 mg/kg (MRID 00040862)
2.4mg/L (MRID 00029963)
Category
m
n
ni
The table below presents additional amitraz acute toxicity information. Data
pertaining to acute eye irritation, dermal irritation, and dermal sensitization are not required to
support the reregistration of the TGAI. These data are presented for informational purposes.
Test
(81-4) Eye Irritation -rabbit'
(81-5) Dermal Irritation -rabbit
(81-6) Dermal Sensitization - guinea pig
(N/A) in vitro acetvlcholinesterase inhibition study - housefly
Results LD
Non-irritating (MRID 00040861)
Non-irritating (MRID 00040862)
Negative (MRID 00029965)
Negative (MRID 00040324) ,
Category
IV
IV
N/A
N/A
N/A - Not applicable
b. Subchronic Toxicity
In a subchronic oral toxicity study, mice were administered amitraz by gavage, at
levels of 0, 3, 12, 50, or 200 mg/kg/day for 90 days. The systemic NOEL was 3 mg/kg/day..
Higher doses produced reduced body weight gain and liver toxicity (increased serum glutamic.
pyruvate transaminase activity, increased liver weight, hepatocyte enlargement, bile duct
proliferation, and focal necrosis). The systemic LOEL was 12 mg/kg/day (MRID 00028715).
In another subchronic oral toxicity study, Beagle dogs were administered amitraz, by
capsules, at levels of 0, 0.25, 1.0, or 4.0 mg/kg/day for 90 days. The systemic NOEL was
0.25 mg/kg/day. At the LOEL (1.0 mg/kg/day) there were slight enlargement of the central
and midzonal hepatocytes of the liver and slight hyperplasia of the zona glomerulosa of the
adrenals. Both the LOEL and the high dose (4 mg/kg/day) produced transient CNS (central
nervous system) depression, decrease in pulse rate, glucosuria, neutrophilia of the bone.
marrow and recurrent hypothermia of short-lasting duration that appeared within three hours
after dosing and only lasted a few hours. The high dose additionally produced ataxia, emesis,
and catarrhal conjunctivitis. (MRIDs 00040345, 00028716).
In a 21-day dermal toxicity study in rabbits, doses of 50 or 200 mg/kg/day were
applied to the skin of rabbits (6 hours/day for a total of 15 times over the 21-day period).
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Moderate erythematous reactions with desquamation of the skin and subcutaneous r
hemorrhage, along with anorexia, sedation, hyperglycemia, testicular degeneration, lymph
node nodular hyperplasia, and generalized neutrophilia of various organs occurred at both
doses. The NOEL was less than 50 mg/kg/day (MRID 00029972).
c. Chronic Toxicity ,
The required chronic toxicity study in rodents is satisfied by a chronic/carcinogenicity
feeding study in rats (MRID 00044585).'
In a 2-year chronic toxicity study, amitraz was administered to dogs, by oral capsule,
at doses of 0, 0.1, 0.25 or 1.0 mg/kg/day. The systemic NOEL was 0.25 mg/kg/day. The
LOEL was 1.0 mg/kg/day, based upon central nervous system depression, increased blood
glucose levels, and hypothermia (MRID 00044586).
d. Carcinogenicity
Carcinogenic effects were not observed in a combined chronic/carcinogenicity study.
Wistar rats were fed levels of 0, 15,50, or 200 ppm (0, 0.77,2.5 or 10.18 mg/kg/day for
males and 0, 0.97, 3.13 or 12.59 mg/kg/day for females) for two years. The systemic NOEL
was 15 ppm. The systemic. LOEL was 50 ppm, based upon findings of aggressive or
excitable behavior, clinical signs, and reduced weight gain at this level arid at 200 ppm
(MRID 00044585). .
In a carcinogenicity feeding study, CFLP mice were fed diets containing 0, 25, 100, or
400 ppm amitraz (0, 3.75, 15, or 60 mg/kg/day) for 80 weeks. Amitraz produced
lymphoreticular tumors in females at 400 ppm, the highest le.vel studied. Tumors were not
evident at the mid dose level of 100 ppm. The systemic NOEL was 25 ppm, due to a
reduction in body weight gain at higher doses (MRID 00111886).
In another carcinogenicity feeding study, B6C3F1 mice were fed diets containing
0,25,100, or 400 ppm amitraz for 104 weeks. Amitraz produced liver adenomas and
carcinomas as well as lung adenomas at the highest dose level studied, 400 ppm
(50.1 mg/kg/day for females and 44.7 mg/kg/day for males). Tumors were not evident at the
next dose level (100 ppm; 15 mg/kg/day). The systemic NOEL was less than the lowest level
tested. The systemic LOEL was 25 ppm (the lowest level tested; 2.6 mg/kg/day for females
and 2.3 mg/kg/day for males), based upon stomach hyperkeratosis, spleen hematopoiesis, and
liver changes (nodules, and telangietactic and basophilic foci). Hyperactive or aggressive
behavior, reduced weight gain, and a reduced myeloid/erythroid ratio in bone marrow were
observed at the 100 and 400 ppm levels (MRID 00013952).
Amitraz is currently classified by the Agency's Health Effects Division Cancer Peer
Review Committee (October 1990) as a "Group C" (possible human) carcinogen, based on the
'9
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finding of combined hepatocellular adenomas and carcinomas in female B6C3F1 mice. A
quantification of the risks was recommended by the Committee. The upper bound (95%) of
the estimated potency (Qi*) for amitraz was calculated to be 5 x 10'2 (mg/kg/day)"1. This new
classification reflects a change from previous evaluations. In 1986 the Office of Research and
Development's Cancer Assessment Group concluded that amitraz should be classified as a
"Group C" carcinogen, with no risk quantification, based on the same carcinogenic evidence.
In the same year (02/24/86), the FIFRA Scientific Advisory Panel concluded amitraz should
be classified in Group D (not classifiable as to human carcinogenicity).
e. Developmental Toxicity '
In two developmental toxicity studies, Wistar rats were dosed with amitraz at 0, 1, 3,
or 12 mg/kg/day, by gavage (assumed route). No treatment related maternal or
developmental effects were observed in one study. In the other study, the maternal and
developmental NOELs were 3 mg/kg/day. Both maternal and reproductive LOELs were
12 mg/kg/day, based on decreased weight gain. These studies do not satisfy the data
requirements for developmental toxicity, but together they can be used for risk assessment
(MRIDs 00029959; 00029960).
In another developmental toxicity study, New Zealand White rabbits were dosed with
amitraz at 0,1, 5, or 25 mg/kg/day, from gestation days 6 through 18. The NOEL for both
maternal and developmental effects was 5 mg/kg/day. The LOEL for both maternal effects
(reduced body weight and increased abortions on gestation days 17 to 20) and developmental
effects (decreased litter size and weight, and reduced implantation and viability indices) was
25 mg/kg/day. This study does not meet the present Agency standards for a developmental
toxicity study, but the information is adequate for risk assessment purposes
(MRID 00029961). .
f. Reproductive Toxicity
In a multi-generation reproduction study, (MRID 00029962), Boots-Wistar rats were
fed diets containing 0,15, 50, or 200 ppm amitraz. The systemic toxicity NOEL was
50 ppm (4.84 mg/kg/day/ male and 5.22 mg/kg/day/female) and the LOEL was 200 ppm
(16.41 mg/kg/day/male and 20.06 mg/kg/day/female), based on reduced body weight gain
and food consumption in F0 animals. The reproductive toxicity NOEL (15 ppm;
1.47 mg/kg/day/male and 1.69 mg/kg/day/female) was lower man the systemic NOEL. The
reproductive toxicity LOEL (50 ppm; 4.84 mg/kg/day/male and 5.22 mg/kg/day/female) was
also lower than the systemic LOEL and was based on reduced litter size and pup survival in
all 3 generations (F1? F^ and F3), and a slight reduction in pup weights in the Fl and F2
generations. Further reproductive toxicity was observed at the high dose (most of the Ft
generation rats died, and there were not enough animals left for subsequent matings). This
10
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study was unacceptable and does not satisfy the data requirements for Guideline 83-4
(Reproductive Toxicity). A study addressing the developmental neurotoxicity and
reproductive toxicity potential of amitraz in the rat is required as confirmatory of the present
data.
g. Mutagerticity
Results of mutagenic studies (table below) indicate that amitraz is not mutagenic.
Guideline
84-2(a)
84-2(a)
84-2(b)
84-4
84-4
Study Type
Salmonella Reverse Gene Mutation (Ames
Assay)
Forward Gene Mutation Assay mouse
L5178Ylymphoma cells)
In- vitro Structural Chromosome Aberration
(human lymphocytes)
Unscheduled DNA Synthesis (human
embryonic lung fibroblast) .
Morphological Transformation
(C3H/10T1/2 cells derived from mouse
embryo fibroblast
Results
Negative at ฃ 10 rng/plate, with/ without metabolic
activation. (Accession 253131)
Negative at 0.06-20 ug/ml w/wo activation. HOT is
highest non-cytotoxic dose. (Accession 253 13 1).
Negative up to cytotoxic and/or insoluble concentrations.
(MRID 4179501)
Negative up to cytotoxic concentrations, w/wo activation.
(Accession 161011)
Negative up to cytotoxic concentrations, w/wo activation.
(Accession 161010)
Two metabolites of amitraz [N-(2,4-dimethylphenyl)-N-methyl formamidine
(BTS-27271)] and [2,4-dimethylformanilide (BTS-27919)] were also shown to be negative
for reverse gene mutation in the Salmonella assay (MRID 00161008). A third metabolite
[2,4-dimethylaniline (BTS-24868)] was reported to be positive for forward gene mutation in
the mouse lymphoma assay with metabolic activation (MRID 00161012).
h.
'Metabolism
Extensive metabolism studies have been conducted with amitraz in several species,
including humans, baboons, dogs, rats, and mice. In all species, amitraz was rapidly
metabolized in the stomach, following oral administration, to form at least six metabolites,
among which are the three cited above. Metabolites BTS-27271 and BTS-27919 (which are
formed via hydrolysis at the C-N [N-methylmethanimidamide] bond) are the primary
metabolites of amitraz. Excretion of metabolites occurred mainly in the urine over 48 hours
(62%-82% in all species) and to a lesser extent in feces (9%-39%), with no unchanged parent
compound observed in urine. The proportion of various metabolites recovered in the urine of
all species was also similar. The highest levels of 14C tissue residues in animals were found
over 3 to 4 days in the liver, bile, kidney, adrenal glands, and pigmented areas of the eye.
(MRID 00160964)
11
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i. Dermal Adsorption .
Male rats were given a dermal dose of 91 ug/cm2 of amitraz. The material remaining
on the skin or in urine, feces, skin, digestive tract, and remaining carcass was analyzed at
24 hours and 120 hours after dosing. The mean percents of dose absorbed were 6.67% at
24 hours post-dosing and 7.79% at 120 hours post-dosing, indicating continued absorption
with time (MRID 42133501). A dermal adsorption rate of 7.79% was recommended for
oncogenic risks assessment.
A subsequent dermal absorption study (MRID 43396801) has been submitted to the
Agency for review. Although the California Environmental Protection Agency, Department
of Pesticide Regulation (CEP A DPR), reviewed and found the study acceptable, the Agency
has determined the study to be supplementary. However, the Agency has concluded that the
study still supplies valuable information and concurs with California EPA that the dermal
absorption of 13.8% be used to estimate absorbed doses.
j. Special Studies
Animal Study; AJ; ->raz was investigated for its effects on estrous cycles in female rats and
mice, and on hormone levels in female mice. In 8 week old rats, administration of
20 mg/kg/day amitraz in the feed for 18 weeks resulted in a significant prolongation of the
estrous cycle length (length = 4.3 days in control animals and 6.1 days in treated animals)
(MRID 00040323). In mice, administration of 3.75 mg/kg/day (NOEL) for 28 weeks caused
no effects on the estrous cycle or on hormone levels. Higher doses of 15 and 60 mg/kg/day
given for the same time period produced increases in blood dehydroepiandrosterone sulfate
levels, reductions in progesterone and prolactin levels, and an elevated liver weight. At the
60 mg/kg/day dose there was also reduced body weight gain, decreased urea and glucose
levels, and prolonged proestrus with reduction of the duration of diestrus; thus, there was no
overall effect on the total estrous cycle length.
Human Study; In a human double blind randomized crossover study of acute neurotoxicity,
6 male volunteers were given sequential oral doses of amitraz by capsule, at 0.0625 or
0.125 mg/kg with a placebo control. There were at least 14 days between treatments. Vital
signs (pulse, respiration rate, blood pressure, and body temperature) and ECGs were taken.
Pupil responsiveness and psychomotor performance were evaluated. Urine was collected for
testing. Minimal and transient changes in blood pressure, temperature, ECG rate, and
psychomotor performance were observed at 0.125 mg/kg. In another human metabolism
study, 2 male volunteers given 0.250 mg/kg by oral route experienced sedation,
disorientation, and hypothermia. For the purpose of risk assessment, the human acute oral
doses of 0.125 mg/kg and 0.25 mg/kg (for effects in two human subjects, should be used for
the NOEL and LOEL, respectively.
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k. Other Toxicological Considerations
Neurotoxic signs were observed in chronic oral toxicity studies in rodents (aggressive
. or excitable behavior in mice and rats; MRIDs 00013953, 00044585) as well as in subchronic
and chronic oral toxicity studies in non-rodents (CNS depression and hypothermia in dogs;
MRIDs 00040345, 00028716, 00044586). Acute signs (hypothermia, drowsiness,
disorientation) consistent with an effect on the CNS were also observed in human volunteers.
I. Reference Dose (RfD)
A RfD for amitraz was determined to be 0.0025 mg/kg/day, based on a NOEL of
0^25 mg/kg/day from the chronic oral toxicity study in dogs (MRID 00044586). An
uncertainty factor of 100 (a factor of 10 each for interspecies extrapolation and intraspecies
variance) was used. The critical effects were increased blood glucose concentration,
hypothermia and CNS depression. An ADI for amitraz was established by WHO (1990) at
0.003 mg/kg/day, based on the same chronic dog study and using the same uncertainty factor.
The Agency's RfD Committee additionally concluded that developmental
(MRID Q0029959) and reproductive (MRID 00029962) toxicity studies in rats were
supplementary, and, therefore, neither should be considered as a reliable assessment of the
developmental or reproductive toxicity potential for amitraz. Since there was some evidence
that amitraz was associated with reproductive and developmental toxicity at relatively low
dose levels, and neurotoxicity was observed in both rodents and non-rodents, the registrant
should 1) submit a new, confirmatory combined developmental, neurological, and
reproduction toxicity study in rats and 2) consult with the Agency on the protocols for this
study.
2. Exposure Assessment
a. Dietary Exposure
The residue chemistry data base for amitraz is adequate and will support reregistration
as a food use pesticide.
Plant Metabolism: The qualitative nature of the residue in plants is adequately understood.
The metabolism of amitraz in plants occurs via hydrolysis at the C-N [N-methyl-
methanimidamide] bond to yield BTS-27271 and BTS-27919. Both of these metabolites are
further degraded by a break of either the C=N or the C-N bond to form 2,4-dimethylaniline
(2,4-DMA or BTS-24868). Amitraz may also be demethylated to form N,N'-bis
(2,4-dimethylphenyl) methanimidamide (BTS-28037). Oxidation of the 4-methyl group on
2,4-DMA yields 4-amino-m-toluic acid (BTS-28369), and oxidation of the 4-methyl group on
N-(2,4-dimethylphenyl)formamide yields 4-formamido-m-toluic acid (BTS-39098); another
toluic acid metabolite is 4-acetamido-m-toluic acid (FBC-31158). The terminal residues of
13
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concern are amitraz and its metabolites containing the 2,4-DMA moiety (BTS-27919 and
BTS-27271-); these are the residues which are presently included in the tolerance expression
(MRIDs 00028664, 00028666, 00055718, 00161022, 00161023, 40590601,40590801,
40999502,41206701).
Animal Metabolism; The qualitative nature of the residue in poultry and ruminants
following cral dosing is adequately understood. Studies involving laying hens and dairy cows
have indicated that amitraz metabolism is fairly rapid and that *he major route of elimination
is via the excreta. The metabolic pathway in poultry and ruminants is similar to that in plants.
The terminal residues of concern in animals, based on oral feeding studies, are amitraz and its
metabolites containing the 2,4-DMA moiety (BTS-27919 and BTS-27271). The results of a
swine dermal metabolism study (MRIDs 42969301, 43287101) indicated that the nature of
the residue in swine following dermal application is similar to the nature of the residue '
following oral dosing. In both ruminant oral and swine dermal metabolism studies, residues
in tissues consisted primarily of the (unregulated) acidic metabolites, and lower levels of the
regulated metabolites.
Residue Analytical Method: There are two adequate methods listed in FDA's Pesticide
Analytical Manual (PAM Vol. IT) for purposes of data collection and enforcement of
tolerances for residues of amitraz and its metabolites containing the 2,4-DMA moiety.
Methods I (designed for animal tissues and milk) and n (designed for plant commodities) are
both GLC methods with electron capture detection, and convert residues of amitraz to
2,4-DMA'by acid and base hydrolysis, respectively. The detection limits of the methods are
0.01 ppm for milk and 0.05 ppm for plant and other animal commodities. Amitraz and its
metabolites containing the 2,4-DMA moiety have been tested using FDA's Multiresidue
Method Protocol D; the metabolite BTS-27919 was the only compound which could be
analyzed by this protocol (MRIDs 00046030, 00051929, 00051930, GS00234013, 40811310,
40811311,40811312).
Storage Stability: Adequate storage stability studies have been conducted using fortified
samples of citrus fruits, cow tissues and milk, and cottonseed. Residues of BTS-27271 and
BTS-27919 are stable in/on citrus fruits stored at -20ฐC for up to 18 months. Residues of
amitraz, BTS-27271, and BTS-27919 are stable in cow tissues and milk stored at -20ฐC for up
to 12-15 months. Residues of amitraz are stable in cottonseed for over one year of frozen
storage. The storage intervals and conditions from the magnitude of the residue studies in
plants are adequately supported by storage stability data (MRIDs 00046029, GS00234014,
40811308,40811309,40999508).
Magnitude of the Residue in Plants: The magnitude of the residue data in food/feed crops
for which there are presently registered uses (pears and cotton) are adequate. The residue
chemistry data for honey and honeycomb are also adequate (MRJDs 00046029, 00051717).
14
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Processed Food/Feed; There are no processed commodities associated with the use of
amitraz on pears. Adequate cotton processing studies indicate that the amitraz residues of
concern do not concentrate in the hull meal, crude oil, refined oil, and soapstock processed
from cottonseed following application at exaggerated rates (MRIDs 41444201 41444202
. 41444203,41478901).
Magnitude of the Residue in Meat. Milk. Poultry and Eggs: It is highly unlikely that beef
cattle would be exposed to amitraz via consumption of treated commodities; dairy cattle in
milksheds in which cottonseed is readily available may be exposed to amitraz both dermally
and in the diet. Residues of amitraz in meat, fat, and meat byproducts are likely to result from
dermal application only, while amitraz residues in milk may be the result of dermal
application and/or consumption of the treated feed commodity. Acceptable dairy cattle and
poultry feeding studies have been submitted, evaluated, and accepted by the Agency in
connection with several past or pending tolerance petitions. Magnitude of the residue studies
in cattle following dermal application have been reviewed and found acceptable by the
Agency in conjunction with past petitions. (MRIDs 40811306, 40811307, 40999504
40999505,41295501,41295502,41295503).
Confined/Field Rotational Crops; A confined rotational crop study was submitted in
connection with the effort to register the 1.5 Ib/gal SC/L formulation on cotton. The guideline
requirement is satisfied.
Two field rotational crop studies were submitted and reviewed. These two studies
together were adequate to satisfy the requirements of Guideline 165-2 for cotton. The data
support the crop rotation restrictions of 44 days for "root and leafy vegetables" and of 60 days
for "small grains and other crops" for amitraz when used on cotton (MRIDs 40999509
41637302).
The published tolerance for pears (2 ppm) was based on a pre-harvest interval (PHI) of
14 days. ^
b. Occupational and Residential Exposure
An occupational and/or residential assessment is required for an active ingredient if
(1) certain toxicological criteria are triggered and (2) there is potential exposure to handlers
(mixers, loaders, applicators, etc.) during use or to persons entering treated sites after
application is complete.
(1) Use Summary
Amitraz is an insecticide/acaricide used to control whitefly, pear psylla, dog and
livestock ticks, lice, and mange mites. Amitraz is formulated into a wettable powder (WP)
and emulsifiable concentrates (EC) for use on pears, soluble concentrate/liquid (SC/L) for use
15
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on cotton, and impregnated collars for use on dogs. One EC formulation is also registered for
dermal treatment of cattle and swine. Amitraz is applied as an airblast and concentrate spray
to pears, by ground boom or aircraft to cotton, and as a dip or low pressure hand spray to
swine, beef cattle, and dairy cattle. Impregnated collars are used to control ticks on dogs.
Application rates are as follow: ', '
For pear use, application rates range from 0.187 to 1.5 Ib ai per acre, with a
maximum seasonal rate of 3 Ib ai/acre. The typical rate for pear treatment
(1.49 Ib ai/A;) is almost half the maximum seasonal rate.
For cotton use, application rates are 0.125 to 1.0 Ib ai per acre, with a maximum of
8 applications per year.
For livestock use, an application rate of 0.2 Ib ai/50 gallons (2 gal/animal), with a
repeated application in 10 to 14 days recommended.
Some products containing amitraz are intended primarily for occupational use and one
is primarily intended for homeowner use (pet collars).
(2) Summary of Toxicity Concerns Impacting
Occupational and Residential Exposures
Acute Toxicity; The acute lexicological database for amitraz indicates toxicity category n
for acute dermal toxicity, HI for acute oral and acute inhalation toxicity, toxicity category IV
for eye irritation potential and skin irritation potential. Amitraz is not a sensitizer. The vapor
pressure for amitraz is low. ., . '
Other Adverse Effects: In a human study, acute exposure to amitraz was associated with
central nervous system (CNS) toxicity symptoms of sedation, disorientation, and
hypothermia. The NOEL for acute human neurptoxicity (0.125 mg/kg) was selected by the
Agency's HED Toxicological Endpoint Selection Committee to be the acute toxicological
endpoint for short-term occupational risk. Studies also indicate that amitraz causes cancer in
animals. It is currently classified as a "Group C" (possible human) carcinogen, with an upper
bound (95%) of the estimated potency (Qj*> of 5 x 10'2 (mg/kg/day)'1, based on findings of
combined hepatocellular adenomas and carcinomas in female B6C3F1 mice. Amitraz may
also cause neurological, developmental, and/or reproductive adverse effects in animals but the
data are incomplete. Studies indicate that a dermal absorption rate of 13.8% and an inhalation
absorption rate of 100% should be used to estimate occupational/residential exposures.
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(3) Summary of Potential Occupational and Residential
Exposures .
Handlers (Mixers, Loaders. Applicators, etc.) Exposures: The Agency has determined
that there is an exposure potential for handlers (mixers, loaders, applicators, etc.) during the
usual use-patterns associated with amitraz. Exposures to mixer, loaders and applicators are
likely when liquid (emulsifiable concentrate) and wettable powder formulations are used.
Post-Application Exposures; The Agency has determined that there is a potential for an
exposure risk for persons entering treated sites after application is complete, especially for
entry into treated pear orchards and cotton fields.
(4) Mixer/Loader/Applicator Exposure
Mixer/loader/applicator (M/L/A) exposure data were submitted for the end-use product
Mitacฎ WP that is applied by open cab/airblast to pear trees (pear orchards)
(MRID 42496003). In the study, the applicator also performed the mixing and loading
activities. The monitoring period ranged from 13 to 17 mix/load/spray cycles per day over a
period of approximately 6 to 7 hours. Each cycle consisted of applying 1.5 Ib ai in 400
gallons of water per acre.
No exposure data were submitted for the cotton and livestock uses. Consequently
surrogate data from the Pesticides Handlers Exposure Data Base (PHED) are used to assess
handlers'exposure from these two uses.
Based on amitraz pattern of use, several exposure scenarios are plausible as defined by
the types of application equipment and procedures that may be employed by amitraz handlers.
These include the mixing, loading, and application activities associated with the use of
amitraz to treat pear orchards, cotton fields, and livestock. The routes of exposure are both
dermal and inhalation. The exposure scenarios are presented in the attached Table 1 along
with the corresponding exposure assessment. The data have been normalized to simulate
workers wearing a single layer of clothing (coveralls or long pants plus long-sleeve shirts) and
chemical-resistant gloves. Shoes and socks are assumed.
Handlers' exposure may be expressed as the daily dose (DD), according to the
following equation: .
DD = A/day x Ib ai/A x Unit Exposure x absorption rate
handler's kg body weight
17
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where: .
- - the unit of exposure-mg/lb ai handled
absorption rates are 13.8% (dermal) and 100% (inhalation)
handler's body weight = 76 kg
handlers wear a single layer of clothing (coveralls or long pants plus long-
sleeve shirts) and chemical resistant gloves
Shoes and socks are assumed.
The exposure assessment for pear uses used the exposure data from the registrant-
submitted studies (MRIDs 42496003,43396801) and the following assumptions:
17 acres are treated per day,
Application rate = maximal/typical rate for all M/L/A exposure scenarios
(1.5 Ib ai/A; twice/year) + minimal rate (0.187.1b ai/A; once/year) for scenario
I on Table 1, and
M/L/A Dermal (D) and Inhalation (I) Exposure Units in mg/lb ai handled as
follows:
. 4.13/0.03 (M/L/A; open bag; open cab; air blast)
. 0.2/0.0037 (M/L; open bag)
. 0.02/0.003 (M/L; water soluble pack).
. 1.8/0.0037 (A; open cab; air Wast)
. 0.02/0.0037 (A; closed cab; air blast)
The exposure assessment for cotton uses used surrogate data from PHED, the high
application rate (1 Ib ai/acre), and the following assumptions:
A liquid formulation is used,
- A ground boom applicator can treat 100 acres per day and aerial applicators
can treat 350 acres per day. For the aerial applications, the mixer/loader and
application functions are assumed to be conducted by separate individuals.
For the ground boom application, these functions may be performed by the
same or by separate individuals, and
D/I Exposure Units in mg/lb ai handled as follows:
. 0.113/0.0037 (M/L/A; ground boom; open pour)
. 0.0046/0.00007 (M/L; ground boom; closed system)
. 0.014/0.0004 (A; ground boom; open cab)
. 0.0046/0.00006 (M/L;-aerial support; closed system)
. 0.004/0.001 (A; pilot)
18
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The exposure assessment for livestock uses used surrogate data from PHED. A
scenario was selected in which a low pressure sprayer was used to spray manure and poultry
litter indoors. The following assumptions were used:
application rate = 0.5 Ib ai/100 gallons (2 gal/animal),
exposure rate = 10 hrs/day; 3 days/yr; 500 heads treated manure (maximal
exposure),
A handler is exposed to 0:2 mg/Ib ai handled by the dermal route and
0.03 mg/lb ai handled by inhalation route.
Handlers's dermal, inhalation, and total (dermal & inhalation) daily doses are shown in
Table 1 of this section. Pear use is associated with the highest total exposure
(0.022 mg/kg/day), followed by cotton use (0.024 mg/kg/day), and lastly, by livestock use
(0.004 mg/kg/day). Within the pear use handlers' group, exposures are highest when the
mixing/loading is accomplished using an open system and the application, is by open
cab/airblast (exposure scenario I) (0.22 mg/kg/day). Total exposure is low when the ,
mixing/loading is accomplished using water soluble packs (exposure scenario HI)
(0.0011 mg/kg/day), and the application is by closed cab/air blast (exposure scenario V)
(0.0011 mg/kg/day).
These calculations of daily exposure to amitraz by handlers are used to assess the risk
to those handlers.
1 19
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(5) Post-Application Exposure .
Post-application exposure is greatest, during post-application tasks requiring substantial
dermal contact with treated foliage (i.e., limb spreading and fruit thinning or harvesting). The
significant route of exposure is dermal. Inhalation exposure during post-application activities
is expected to be minimal, because amitraz has a low vapor pressure/
Foliar dislodgeable residue (FDR) data ware submitted by the registrant for amitraz
and its two metabolites BTS-27271 and BTS-27919 (MRID 42496002). In the study, two
applications (14 days apart) of the wettable powder formulation, at the highest rate (1.5 Ib./A),
were applied to pear orchards located in the Yakima Valley, WA, a principal pear growing
region. The residues remained constant for 21 days. Because of this lack of dissipation, it is
possible that the residues measured are from both treatments.
The average daily exposure (ADE) is estimated based on only one application at the
maximum rate and assuming a worker1 body weight of 76 kg, an 8-hour work day, a dermal
absorption rate of. 13.8% and a transfer coefficient of 3800 cm2/hr. ADEs are expressed as the
systemic dose, which includes exposure to the foliar dislodgeable residues of amitraz and
BTS-27271 (the residue of concern for neurotoxic effects). Systemic doses are estimated for
various post-application time points up to 35 days. The estimated systemic doses are shown
in Table 2 of this section.
Table 2
PEAR Use: Post-Application Exposures and MOEs
Days after
Treatment
0
1
2
5
7
14
21
28
35
Amitraz Residues
Hg/cm2
0;33
0.345
0.335
0.31
0.40 .
0.30
0.32
0.115
0.135 . . -
BTS 27271
Residues
Hg/cm2
0.06
0.06
0.065
0.055
0.05
0.045
0.045
0.035
0.03
Combined
Residues
jug/cm2
0.39
0.405
0.40 ,
0.365
0.45
0.345
0.365
0.15
0.165
Systemic Dose
mg/kg/day
0.222
0.023
0.022
0.020
0.025
0.019
0.020
0.008
'0.009
-MOE
5.7
' 5.4
5.7
6.2
5.0
6.6
6.2
15.0
14.0
Systemic Dose includes the dislodgeable residues from amitraz plus the metabolite BTS-27271. Residues reflect one application (54 the total
residuefortwotreataents),theuseofatransfercoefficientof3,80pcm1iranda76kgindividual(CAstandard). '
21
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The US EPA performed regression analysis for amitraz and its metabolites and agrees
with the California Environmental Protection Agency, Department of Pesticide Regulation
(CEP ' DPR) regarding the length of time required between applications when based solely
on tfcu atural log of the dissipation rate. In the study submitted by the registrant (both
Federal and State agencies agree was not of high quality), there was no apparent dissipation
until 21 days after the second application. After the 21st day, residue levels drop-off by about
two thirds and remain constant until the. 25th day (the last day of sampling). This "tailing-off V
of data coupled with linear regression analysis can suggest some very slow dissipation rates.
Additionally, the Agency determined that for pears a 28-day interval is required for a Reentry
Interval (REI) because MOEs are greater than 10 only after 28-days, and with amitraz an
MOE greater than 10 is acceptable because the NOEL was determined on a human study.
What is most notable about the data is the sudden drop-off, which coincidentally or
not, is 35 days after the first application. Thus, rather than over-interpreting the marginal
data, US EPA decided to use the most significant aspect of the study, the sudden drop-off.
The Agency has also requested confirmatory data because the current study was conducted in
the absence of concurrent dermal exposure data. In a recent meeting with representatives of
US EPA, CEPA DPR, and Health Welfare Canada, it was agreed that the 3 5 days between
applications (with confirmatory data) is preferred over the use of linear regression.
Potential exposure resulting from the cotton use, use in livestock buildings and on
animal collars is minimal.
Cotton Use: Potential exposure is minimal because of the lower application rate and the
mechanical harvesting of cotton.
Livestock Buildings: Since livestock buildings are often well ventilated or have controlled
environments with adequate ventilation, inhalation exposure is minimal.
Animal Collars; The Agency has assumed that the potential for contact with amitraz to
children exposed to pets wearing animal collars is negligible because of the type of
formulation (impregnated plastic), the low duration and frequency of exposure. In a previous
Agency assessment addressing potential exposure to children resulting from impregnated pet
collars, these exposures were also considered negligible.
(6) Additional Occupational/Residential Exposure
Studies
Mixer/loader/applicator (i.e., handler) exposure study requirements are addressed by
Subdivision U of the Pesticide Assessment Guidelines. Additional confirmatory exposure
studies for handler (mixer, loader, applicator) exposure are required at this time. Due to the
limited data available reflecting applications to livestock, the Agency is requiring
confirmatory dermal exposure (Guideline 231) and inhalation exposure data (Guideline 232)
to support the reregistratioh of the livestock spray and dip treatments.
22
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Post-application exposure study requirements (i.e.; reentry) are addressed by
Subdivision K of the Pesticide Assessment Guidelines. Additional confirmatory exposure
studies for post-application exposures are required at this time. Due to the uncertainties
associated with using a generic transfer coefficient and the minimum quality data submitted
by the registrant, The Agency is requiring concurrent DFR (Guideline 132-la) and dermal
exposure (Guideline 133-4) data to support the reregistration of amitraz on pears.
3. Risk Assessment
a. Dietary Risk
The following data were used to assess amitraz's dietary risk:
(1) Toxicological Endpoints
An estimated unit risk (Qi*) of 0.05 (mg/kg/day)'1, for carcinogenic dietary risks
assessment,
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A RfD of 0.0025 mg/kg bodyweight (bwt) per day, for chronic dietary risk assessment,
and
A NOEL of 0.125 mg/kg bwt, for acute dietary risk assessment, based on a human
acute neurotqxicity study.
(2) Residue Information
Food uses evaluated in the DRES analysis are the published non-zero tolerances listed
in 40 CFR 180.287 and in the Tolerance Index System (TIS) for the combined residues of
amitraz and its metabolites BTS-27271 and BTS-27919, expressed as the parent compound.
All published non-zero tolerances for amitraz are being supported through reregistration.
Although the registration for honey has been voluntarily canceled, it should be noted that the
tolerance still exists .and existing stocks are still being used.
For chronic and carcinogenic risk assessment, the DRES analysis uses anticipated
residues (ARs) and percent crop treated data. AR values for pears reflect a 14-day PHI and
use of the WP formulation. The DRES analysis uses mean ARs for pears. The chronic ARs
for pears reflect the amitraz parent, BTS-27919, BTS-27271, and 2,4-DMA. All other ARs
used in the chronic exposure analysis and cancer risk assessment are based on field trial data,
processing studies^plant and animal metabolism studies, livestock feeding and direct dermal
application studies. Average values, not maxima, were used for the chronic analysis if both
, were available. A default of 100 percent crop treated is assumed for honey, since an estimate
was not available from the data. Chronic risk is also assessed based on tolerance levels and
100% crop treated information.
23
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The DRES acute analysis uses high end residues for pears associated with the
currently required 14-day PHI. The review of a new pear field trial submission (MRID
43370301) reflecting residues at the 14-day PHI, supports the registrant's contention that total
amitraz residues resulting from application of the WP formulation are generally lower that
those resulting from application of the EC formulation. Residues of concern for neurotoxic
effects (i.e. amitraz and BTS-27271) were lower overall than those of the currently regulated
(determined using the common moiety) residues. The acute AR (pears) for amitraz plus
BTS-27271 is 0.42 ppm.
(3) Results ' , .
Chronic Dietary Risks: The DRES chronic exposure analysis assumes tolerance level
residues and 100 percent crop treated information to estimate the Theoretical Maximum
Residue Contribution (TMRC) for the overall U.S. population and 22 population subgroups.
Refinements in residue and percent crop treated information were considered in calculating
the Anticipated Residue Contribution (ARC) for those same population groups. The ARC is
considered the more accurate estimate of dietary exposure. These exposure estimates were
then compared to the RfD for amitraz to get estimates of chronic dietary risk.
Based on tolerance level residues and 100% crop treated data, the TMRC for the
overall U.S. population is 0.000795 mg/kg bwt/day (32% of RfD), with a 14-day PHI for
pears. The TMRC for non-nursing infants less than one year old, the DRES subgroup most
highly exposed, is 0.005556 mg/kg bwt/day (222% of RfD), with a 14-day PHI for pears.
Based on average ARs and percent crop treated data, the ARCs for the overall U.S.
population is 0.000028 mg/kg bwt/day (1.1% of RfD) with a 14-day PHI for pears. The
ARCs for non-nursing infants less than one year old, the DRES subgroup most highly
exposed, is 0.000113 mg/kg bwt/day (4.5% of RfD) with a 14-day PHI for pears. Based on
the low ARCs, it appears that chronic, non-cancer dietary risk from exposure to amitraz is
minimal. . . .
Carcinogenic Dietary Risk; The upper bound carcinogenic risk from amitraz may be
estimated for the overall U.S. population using the following equation:
Upper Bound Cancer Risk = Dietary Exposure (ARC) x Qt*
A Qj* of 5.0 x 10'2 (mg/kg/day)"1 and a 70 year lifetime exposure were assumed in this
calculation. Upper bound cancer risks by commodity are listed in the following table:"
24
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Table 3 - Upper Bound Estimates of Cancer Risk by Commodity
Commodity
pears (PHI = 14 days)
poultry and eggs
honey
milk
beef
hogs
cottonseed
TOTAL
14-day PHI for pears
Upper Bound Cancer Risk
8.4xlO-7
2.7 xW7
1.3 xlO-7
6.8 xlO-8
8.7-x'lO*
2.2 x Id"8
8.0 xlO-10
1.4 x 10"*
The bulk of exposure is attributed to one commodity, pears; (58% of total exposure
based on 14-day PHI). Upper bound cancer risk is 1.4 x 1 (T6 from published uses.
Acute Dietary Risk; The DRES detailed acute exposure analysis evaluates individual food
consumption as reported by respondents in the USD A 1977-78 Nationwide Food
Consumption Survey (MFCS) and estimates the distribution of single day exposures of
consumers through the diet for the U.S. population and certain subgroups^ The analysis
assumes uniform distribution of amitraz in the commodity supply. Because neurotoxicity is
the endpoint of concern, exposure and risk are calculated for all standard DRES subgroups.
The Margin of Exposure (MOE) is a measure of how closely exposure comes to the
NOEL (the highest dose at which no effects were observed in the study), and is calculated as
the ratio of the NOEL to the exposure (NOEL/exposure = MOE). In general, an MOE of 10
or greater is considered acceptable when the NOEL is based on a human study.
For this analysis, MOEs are calculated using both high end exposure and 98th
percentile exposure for all five of the standard DRES subgroups (U.S. population - 48 states,
Infants < 1 yr., Children 1 through 6 years, Females (13+ years) and Males (13+ years).
The acute anticipated residues (pears) for amitraz + BTS-27271 (the residue of
concern for neurotoxic effects) is 0.42 ppm. Based on the 14-day PHI and at 98th percentile
consumption values for pears, MOEs are greater or equal to 10 for'all U.S. population
subgroups.
The registrant submitted pear processing data (MRID 43396902) in support of the
Canadian registration and continued U.S. registration and to determine if the data should be
included in the Agency's risk assessment. The Agency concluded that the processing data
not be included in the dietary risk assessment, since inadequate information was provided
25
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regarding sampling and the analytical method used. The Agency does not typically use
monitoring data to assess the acute risk.
i '
b. Occupational/Residential Risk
(1) Toxicological Endpoints
The toxicological endpoints of concern for occupational exposure are (1) acute
neurotoxicity resulting from short-term (one day to one week) and (2) the classification of
amitraz as a "Group C" (possible human) carcinogen, with an upper bound (95%) of the
estimated potency (Qi*) of 5 x 10"2 (mg/kg/day)"1.
(2) Calculating Risk
Risk of Excess Cancer: Upper bound (95%) carcinogenic risk may be estimated using
the following equation:
Upper Bound Cancer Risk = LADD x Ch*
where Qj* = 5 x 10'2 (mg/kg/day)"1 and
LADD = Total daily dose (from Table 1) x davs/vear x 35 years
65 days 70 years
Risk of Neurotoxicity: Acute neurotoxicity risk may be expressed by the margin of
ex-osure (MOE), according to the following equation:
Margin of Exposure (MOE) =
NOEL ftng/ke/dav>
Exposure (mg/kg/day)
where the NOEL = 0.125 mg/kg/day, and exposures are the total (dermal + inhalation)
exposure values from Table 1. The MOEs take into consideration all currently required PPE.
Because the toxicity endpoint is from a human study, MOEs less than 10 would trigger an
acute neurotoxicity risk concern.
(3) Risk to Handlers (Mixers, Loaders, Applicators, etc.)
Risk of Excess Cancer from Long-Term Exposures; Handlers using amitraz to treat pear
orchards, cotton fields, and livestock on a long-term basis may be at risk from its carcinogenic
effects. Handlers' estimated upper bound cancer risk are shown in Table 4 of this section.
26
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The highest carcinogenic risk is associated with the pear use (1.2 x 10's), followed by cotton
use (1.6 x 10's), and lastly, by livestock use (8.2 x 10'7). It is the Agency's policy to seek risk
reduction for non-dietary cancer risk to the greatest extent possible, preferably to the
negligible level.
Therefore, the Agency expects to reduce these risks as a result of the following
measures required in this document. These measures include increasing the interval between
amitraz applications to pears, increasing the restricted-entry interval (REI) for both pears and
cotton, specifying minimum (baseline) personal protective equipment (PPE) for all
occupational uses, and requiring engineering controls.
Additionally, in order to refine the risk assessment the registrant is required to submit a
developmental/neurological/reproductive study and a dislodgeable foliar residue (DFR) study
as confirmatory data.
-' < . - '" "
Risk of Neurotoxic Effects from Short-Term Exposures: MOEs associated with the pear,
cotton, and livestock uses are shown in Table 4. MQEs are greater than 10 for most exposure
scenarios. MOEs are less than 10 for only three scenarios of handler exposure including 1)
Scenario I (pear-use involving the wettable powder formulation mixed/loaded via open bag
and applied via open cab/air blast) applied at both the maximal (and typical) and minimal
rates, 2) Scenario IV (pear-use involving the wettable powder formulation applied via open
cab/air blast) and 3) Scenario VI (cotton-use involving the liquid formulation mixed/loaded
via open pour and applied at the maximal rate via ground boom).
The risk mitigation measures being imposed for handlers should mitigate these high
risks to acceptable levels. These measures include those outlined in Section IV.B.4.
27
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(4) Risk from Post-Application Exposures
Risk of Excess Cancer from Long-Term Exposures: Reentry workers involved on a long-
term basis with post-application tasks requiring substantial dermal contact with treated foliage
resulting from the pear use (i.e., suckering, limb spreading and fruit thinning or harvesting)
and resulting from the cotton use (i.e., harvesting and crop-advising) may also be at risk from
amitraz carcinogenic effects. - .
Based on the foliar dislodgeable residue data obtained from application of amitraz to
pears, and with an REI of 28 days, the estimated carcinogenic risk for the reeentry worker is
not expected to exceed 1.0 x W4. Again, because the Agency's policy intent is to seek risk
reduction for non-dietary risks to the greatest extent possible, preferably to the negligible
level, the Agency is increasing the restricted-entry interval (REI) for both pears (from 24
hours to 28 days) and cotton (from 24 to 48 hours) and mandating of minimum (baseline)
personal protective equipment (PPE) for all occupational uses as well as engineering controls.
Riskof Neurotoxic.Effects from Short-Term Exposures: MOEs for the pear use were 5.0
at 7 days following foliar applications and 6.6 at 14 days following foliar applications, based
on the human acute neurotoxicity NOEL of 0.125 mg/kg/day and on exposure values
representing the foliar dislodgeable combined residues of amitraz plus its two metabolites
BTS-27271 and BTS-27919 (systemic dose values in Table 2).
The data the registrant has submitted for purposes of estimating reentry exposure
consist of two-sided DFR (dislodgeable foliar residue) data collected from pear leaves on pear
trees growing in eastern Washington state. DFR data were collected following two
applications timed 14 days apart. The residues remained constant for,21 days. Because of
this lack of dissipation, its possible that the residues measured are from both treatments. One
major flaw with the DFR study however, is the fact that the residues were not dislodged from
the leaf samples until up to 103 days after they were collected. Although, they, were
maintained in freezer storage during that time, some residues, that would have otherwise been
dislodged, may have been absorbed into the foliar matrix.
Neurotoxicity risks resulting from the use of amitraz on cotton could only be roughly
estimated, because of lack of data. The Agency roughly estimated risks to cotton harvesters
and crop advisors (i.e., scouts) by using a dermal transfer coefficient similar to that for pears,
prorating the dislodgeable foliar residue used for pears to reflect the lower application rate in
cotton, and estimating 8 hours of daily exposure for harvesters and 6 hours of daily exposure
for crop advisors. The MOE for cotton harvesters was unacceptable (less than 10) at both 24
and 48 hours after application. The roughly estimated MOE for cotton scouts was marginally
acceptable (approximately 11) at 24 hours after application. Due to the low MOEs obtained
from the rough risk assessment, the low MOE values for mixers, loaders, and applicators for
cotton uses, and the lack of cotton-specific post-application exposure data, the Agency is
29
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requiring worker safety measures to mitigate the post-application exposure risks to cotton
workers., Refer to Section V for a listing of these. .
Neurotoxicity risks resulting from the use indoors on livestock are considered
negligible for r?: -try workers, since the expected inhalation and dermal exposures are
assumed to be negligible. Additionally, neurotoxicity risks resulting from the use of amitraz
in pet collars is also considered negligible for homeowners, including children, because the
expected exposure is negligible.,
Due to the uncertainties associated with using a generic transfer coefficient, and the
questionable data submitted by the registrant, the Agency is requiring worker safety measures
to mitigate risk to post-application workers. Refer to Section V for a listing of these
measures.
t
C. Environmental Assessment
' There are sufficient data for a comprehensive qualitative environmental fate
assessment. The October 1987 Amitraz Registration Standard required the following
environmental fate studies: hydrolysis, photodegradation in water and on soil, aerobic and
anaerobic soil metabolism, leaching and adsorption/desorption, lab and field volatility studies,
soil dissipation, and accumulation studies in fish and in aquatic non-target organisms.
At this time, however, only a preliminary quantitative assessment is possible. The
environmental fate data base review indicates the following studies are still required: Droplet
size spectrum (Guideline 201-1), and drift field studies (Guideline 202-1). Additionally,
although the aged portion of the leaching/adsorption-desorption (Guideline 163) is fulfilled,
batch equilibrium data on the amitraz degradates BTS-27271 and BTS-27919 are required to
provide a more complete quantitative environmental fate and transport assessment.
The existing environmental fate studies show that parent amitraz degrades rapidly in
the environment (aquatic and terrestrial) to form the primary transformation products
BTS-27271 and BTS-27919 and a secondary transformation product BTS-24868. Even
though parent amitraz is moderately mobile in sandy soil, it is of limited concern in ground
and surface water because of its rapid degradation. In contrast, amitraz transformation
products have been shown to be moderately persistent in aquatic and terrestrial environments
and appear to be relatively immobile in soil column and field dissipation studies. Additional
mobility studies (batch equilibrium) are needed in order to fully assess the mobility of amitraz
transformation products in ground and surface waters.
30
-------
1.
Environmental Fate
-
a. Environmental Chemistry, Fate and Transport Data
Hydrolysis; The major route of degradation of amitraz in the environment appears to be
hydrolysis. Abiotic hydrolysis studies show that amitraz rapidly hydrolyzes to form the
primary transformation products BTS 27271 and BTS 27919 and a secondary transformation
product BTS 24868. The hydrolysis rate is inversely related to the pH of the medium,
whereby amitraz hydrolyzes faster in slightly acidic environments (tl/2 = 2 hours) than in
alkaline environments (t1/2 = 25.5 hours). Furthermore, one of the transformation products
BTS 27271 hydrolyzes to form BTS 27919. In contrast to the primary degradation process,
this secondary degradation is faster in slightly alkaline environments (t1/2 = 5 hours) than in
slightly acidic environments (tV2 = 2,280 days). Although BTS 27919 is stable to abiotic
hydrolysis, it appears to break down to BTS 24868 in the environment, probably by microbial
transformation (MRIDs 40780512, 42124616, 42124617).
Photodegradation; Photodegradation of amitraz in water occurred at approximately the
same rate as the control, indicating that photodegradation is not the primary route of
degradation. Photodegradation of amitraz in soil is even more rapid with a_DT50 of less than
20 minutes (MRIDs 40780513, 41206703, 00407805, 4144420). ~ . '
Aerobic and Anaerobic Soil Metabolism; In aerobic soil metabolism studies, parent
amitraz had a half life of less than one day. The amitraz transformation products formed
during aerobic soil metabolism were BTS 27271 (13% of applied), BTS 27919 (35% of
applied), BTS 24868 (13% of applied), and CO2 (35% of applied). The half-lives of
BTS 27271 and BTS 27919 ranged from 67-82 days and 61-1 17 days, respectively. The
amitraz transformation products have been found to be more persistent in soil metabolism
studies than parent amitraz. Similar degradation rates and transformation products were
observed in anaerobic soil metabolism studies (MRIDs 40798003, 42124620).
Aquatic Metabolism; In aquatic metabolism studies in microcosms, amitraz degrades
rapidly with a 50% dissipation time (DT50) of less than 6 hours. The primary transformation
products BTS 27271 and BTS 27919 were more persistent than parent amitraz. The DTSO for
BTS 27271 ranged from 6-7 days, while the DTSO for BTS 27919 ranged from 9-21 days
(MRIDs 42124618, 42124622, 41444205).
Soil Adsorption; Parent amitraz had Freundlich adsorption coefficients of 1.69 (l/n=0.53) in
a Shelby loamy sand soil, 3.01 (l/n=0.76) in a Speyer sand, 89.13 (l/n=l. 22) in a Terling clay
loam soil, and 16.31 (l/n=0.75) in a Shelford Field clay soil (MRIDs 41206704, 40780515).
Soil Column Leaching: Batch equilibrium studies indicated that amitraz was moderately
mobile in sandy loam, silt loam, and clay soils and was very mobile in sandy soils. Although
amitraz was considered moderately mobile in the environment, it degraded rapidly in the
environment and is not expected to be a concern in ground and surface waters. The major
31
-------
transformation products of amitraz BTS 27271 and BTS 27919 appeared to be relatively
immobile ;u column leaching and field dissipation studies. He ever, soil TLC studies
indicated that BTS 27271 was moderately mobile in sandy lc; silt loam, and clay textured
soils (Rf 0.36-0.48) and very mobile in sand (Rf 0.91). It she he noted that the
physiochemistry of BTS 27271 and BTS 27919 suggest that tr.e> should be in the cationic
form (pKb>9.0) in most soil environments and could electrostatically bind to soil. Additional
mobility studies (batch equilibrium) are needed in order to fully assess the mobility of amitraz
transformation products in ground and surface, waters (MRIDs 40931501, 42124614,
42124615,42124620,40780516).
Volatility: Although the amitraz transformation products (BTS 27271, BTS 27919 and
BTS 24868) have vapor pressures that exceed the W6 mm Hg trigger, laboratory soil
volatility data indicate that BTS 24868 and CO2 are the only volatile products (MRCD
40780518).
Bioaccumulation in Fish; Amitraz and its primary transformation products do not appear to
accumulate in fish. In bioaccumulation studies, the bioconcentration factors for viscera, flesh,
and carcass of bluegill sunfish were 1821X, 588X, and 1838X, respectively. Residues were
identified as BTS 27919, BTS 27271, and unidentified polar degradates. However, these
residues were eliminated over a 14-day depuration period, indicating that amitraz residues do
not bioaccumulate in fish (MRIDs 41444206,42124623,40780519, 00072503).
Terrestrial Field Dissipation: The existing environmental fate data indicated that amitraz
breaks down rapidly in the.environment (t1/2 = 1 day) to form the transformation products
BTS 27271 and BTS 27919 and a secondary transformation product BTS 24868. Field
dissipation studies conducted in Florida, California, and Texas showed that these products
were more persistent than parent amitraz under typical use conditions. Field dissipation halfr
lives for BTS 27271 ranged from 17-110 days and for BTS 27919 from 70-150 days.
Although these studies indicated that amitraz residues for BTS-27271 and BTS 27919 were
retained in the surface 15 cm of soil, false positive detections of these products were found in
deep soil samples. BTS-27271, BTS 27919 and BTS 24868 were detected at depths of 30 cm
(12 inches) in the Texas study. These data suggest that BTS 27271 and BTS 27919 are
moderately persistent and appear to be relatively immobile under actual field conditions
(MRIDs 40798004,41637301).
Droplet Size Spectrum and Field Drift Studies; Droplet size spectrum (Guideline 201-1)
and field drift studies (Guideline 202-1) are needed to support ground spray, aerial spray, and
air-blast application methods for amitraz. Spray drift studies are required for aerially applied
insecticides (e.g., air blast, etc.) with Tox 1 or Tox 2 classifications; or if the insecticide is
deemed as posing an environmental hazard. The registrant may elect to satisfy both data
requirements through the participation in the Spray Drift Task Force.
32
-------
b. , Environmental Fate Assessment
There are sufficient data for a comprehensive qualitative environmental fate
assessment of amitraz. Based on acceptable and supplemental environmehtal fate data from
the Registration Standard to present, indicates, that parent amitraz degrades rapidly in the
environment (t1/2=l day) to form the primary transformation products N-2,4-dimethyl-phenyl-
N-methylformanidine (BTYS-27271), 2,4-dime|:hylformanilide (BTS 27919) and the
secondary transformation product 2,4-dimethylaniline (BTS-24868). Soil column leaching
studies indicate that BTS 27271 and BTS 27919 are more persistent than parent amitraz under
typical use conditions.
Even though the parent amitraz is moderately mobile in sandy loam, silt loam., and
clay soils and very mobile in sandy soils, it is of limited concern in ground and surface waters
because of its rapid, degradation. The same cannot be said about the dissipation of amitraz
degradates. The major transformation products, though have been shown to be relatively
immobile in column leaching and field dissipation studies. Although there are acceptable
laboratory and field data on the degradation of BTS-27919 (t1/2 = 10 to 150 days) and
BTS-27271 (t1/2 = 7 to 110 days) and data requirements have been fulfilled for the mobility of
these compounds, only qualitative conclusions can be drawn on the mobility of the amitraz
degradates. The mobility of BTS-27271 and BTS-27919 has been addressed in soil column
leaching, soil TLC, and field dissipation studies. These studies provide only a qualitative
assessment of pesticide partitioning between soil and water.
Additional confirmatory data on the mobility of the primary amitraz degradates
BTS-27271 and BTS-27919 is necessary to complete a quantitative environmental fate
assessment. Without clearly defined partition coefficients (Kds) from acceptable batch
equilibrium studies on BTS-27271 and BTS-27919, the relative rates of dissipation through
transport to surface water or groundwater cannot be assessed. Therefore, batch equilibrium
studies (Guideline 163-1) for BTS-27271 and BTS-27919 are required to allow for a complete
quantitative environmental fate assessment. A more quantitative estimate of the fate of
BTS-27271 and BTS-27919 would provide a more precise measurement of the aquatic effects
of these degradates. However, based on acceptable field dissipation data, the amitraz
degradates do not appear to be mobile under typical use conditions.
2. Ecological Effects
a. Ecological Effects Data
The October 1987 Amitraz Registration Standard required the following ecological
effects data: avian subacute dietary, avian reproduction, freshwater and warmwater fish
toxicity, acute toxicity to freshwater, estuarine and marine organisms, fish early life stage, and
aquatic invertebrate life cycle.
33
-------
There are sufficient studies on amitraz (the parent and its two primary degradates -
BTS-27271 and BTS-27919) to permit a comprehensive ecological effects assessment.
(1) Terrestrial Data
Effects to Non-Target Birds: In order to establish the toxicity of amitraz to birds, the
following tests were required for the pear, cotton and cattle/swine uses: two subacute dietary
studies CLCSO) on one species of waterfowl (preferably the mallard duck) and one species of
upland game bird (preferably bobwhite quail or ring-necked pheasant); one avian single-dose
oral (LDso) study on one species (preferably mallard or bobwhite quail). For the dog use,
which is considered indoor, one avian single dose oral and one eight-day dietary LC50 are
required.
The Agency required studies on the two major metabolites (BTS-27271, BTS 27919)
of amitraz because of their potential increased toxicity when compared to the parent
compound.
Avian Acute Oral Toxicitv Studies; The existing data demonstrate that parent amitraz is
slightly toxic to mallard ducks. However, BTS-27271 is moderately toxic to the bobwhite
quail and BTS-27919 is slightly toxic to the bobwhite quail.
Gdln.No.
71-100
71-100
7l-Kซ>
MRIDNo.
000304S1
42124602
42124603
Species
Mallard Duck
Bobwhite Quail
Bobwhite Quail
%A.L
Technical
BTS-27271 (99% a.i.)
BTS-27919 (99.1% a.i.)
LDซ
788 mg/kg
71mg/kg
1827 mg/kg
Fulfills Gdln
Yes
Yes
Yes
Avian Subacute Dietary Toxicitv Studies: Parent and Primary Degradates: The
acceptable subacute dietary toxicity data for amitraz technical and degradates, BTS-27271
and BTS-27919, are listed below:
Gdln. No.
71-260
71-2(b)
71-2(a)
71-200
71-200
71-2(b)
71-2(b)
MRIDNo.
00030452
00030453
40780501
42124604
42124605
42124606
42124607
Species
Mallard
Japanese Quail
Bobwhite
Bobwhite
Mallarr
Mallard
Bobwhite
%A.L
Technical
Technical
98.2%
BTS-27271 (99.91% ai)
BTS-27919 (99. ai)
BTS-27271 (99% ai)
BTS-27919 (99% ai)
LCM
7000 ppm
1800 ppm
3081 ppm
1276 ppm
>5200 ppm
>5200 ppm
>5200p^m
Fulfills Gdln
Yes
Partial
Yes
Yes
Yes
Yes
Yes
34
-------
The existing data demonstrate that parent amitraz is practically nontoxic to the mallard
duck and slightly toxic to the bobwhite quail. BTS-27271 is practically nontoxic to the
mallard and slightly toxic to the bobwhite quail. BTS-27919 is practically nontoxic to both
the mallard and the bobwhite on a subacute dietary basis.
Avian Reproduction Studies: Parent and Primary Degradate; Avian reproduction
studies are required for the cotton and pear uses since amitraz may be applied in multiple
applications. In addition, available laboratory and field date indicate that amitraz degradates
may persist under certain environmental conditions: BTS-27919 tV2 = 10 to 150 days;
BTS-2727111/2 = 7 to 110 days.
The acceptable avian reproduction tests for amitraz technical and degradates
(BTS-27271 and BTS-27919) are listed below:
Gdln. No.
71-4(a)
71-4(b)
71-4(a)
71-4(a)
71-4(b)
71-4(a)
71-4(a)
MRID No.
00072412
00072411
40840301
42336001
42336002
42797801
42797802
Species
Bobwhite Quail
Mallard Duck
Bobwhite Quail
' Bobwhite Quail
Mallard Duck
Bobwhite Quail
Mallard Duck
%A.L
Technical
Technical
97.5
98.9
98.9
BTS-27271 97.7-99.1%
BTS-27271 97.7 - 99.1%
NOEL/LOEL
ND*/40ppm1
ND*/40ppirf
40/160 ppm3
24.6/50.5 ppm4
24.6/50.5 ppm5
25/100 ppm"
5/25 ppm'
Fulfills Gdln
Partial
Partial -
Partial
Yes
t Partial
Partial
Partial
3.
4.
5.
6.
7.
*ND
The specific impairments noted were increases in eggshell cracking and reduced percentages of three-week embryos that survived to
become normal hatchlings at < 40 ppm. The mean body weights of chicks hatched were significantly affected hi the 100 and 250
ppm groups, and egg weights and eggshell thickness were significantly reduced at 250 ppm'.
Numbers of 14-day old survivors produced per week were significantly less than the control at <40 ppm. Reductions in percentage of
viable embryos that survived to 3 weeks and percentage of 3-week embryos that survived to become normal hatchlings were noted at
the 250 ppm level but not at 40 and 100 ppm.
Dietary concentrations of up to 40 ppm had no effect oh adult buds or their reproductive performance. At 160 ppm, the adult birds ate
marginally less food and the overall mean chick hatching weight was slightly low. However, these results must be considered in light ,
of the high percentage, of cracked eggs, particularly in the control group.
.The NOEL was determined to be 24.6 ppm ai based upon reductions in viable embryos/eggs set at 50.5 ppm ai.
The NOEL was determined to be 24.6 ppm ai based upon reduced hatchling weight and increased male body weight (both growth
effects) at 50.5 ppm ai. This study only partially fulfilled guidelines since it failed to detect reproductive effects.
The specific impairments noted were significant reductions at the 100 ppm test level in hatchlings as a percentage of eggs set, two-
week survivors as a percentage of eggs set an'd two-week survivors as a percentage of eggs laid.
The specific impairments noted were significant increases at the 25 ppm test level in the total number of eggs cracked and in the
number of eggs cracked as a percentage of eggs laid.
Not determined. -_..-
The existing data show statistically significant effects by parent amitraz on avian
reproduction at dietary levels of 40 - 50.5 ppm (i.e. reduction in number of viable embryos
per eggs set; increase in eggshell cracking; reduction in number of three-week embryos that
survived to become normal hatchlings; reduction in number of 14-day old survivors produced
per week) (MRID 42336001).
35
-------
The existing data show statistically significant effects by BTS-27271 on avian <
reproduction at dietary levels of 25 ppm for the mallard duck (i.e. increase in the total number
of eggs cracked) and 100 ppm for the bobwhite quail (i.e. reduction in number of hatchlings
as a percentage of eggs set; reduction in number of 14-day survivors as a percentage of eggs
set and eggs laid) (MRIDs 42797801, 42797802).
There were no studies with the amitraz degradate BTS-27919 submitted or required
based upon the test results of the avian acute and subacute studies.
Mammal Studies: Wild mammal testing is required on a case-by-case basis, depending on
the results of the lower tier studies such as acute and subacute testing, intended use pattern,
and pertinent environmental fate characteristics. Li most cases, however, a rat acute oral LDSO
is used as a small mammal surrogate to estimate toxicity to mammals. This LD50 is reported
below.
Mammalian Acute Oral Toiidty Findings
Species
Rat (small mammal surrogate)
%A.L
90
LD,. (mg/kg)
515
MRIDNo.
00041539
Toxicity
Category
slightly toxic
Fulfills Guideline
Requirement
Yes
The available mammalian data indicate that amitraz is slightly toxic to small mammals
on an acute oral basis (MP D 00041539).
(2) Aquatic Data
Effects on Freshwater Fish: For the pear, cotton and cattle/swine uses, the minimum data
required for establishing the acute toxicity of amitraz to freshwater fish are the results from
two 96-hour studies with the technical product. One study.should use a coldwater species
(preferably the rainbow trout) and the other should use a warmwater species (preferably the
bluegill sunfish). The dog use requires only one 96-hour study with a coldwater fish.
Acute Aquatic Toxicitv Studies - Technical. Formulated Product, and Primary
Degradates: The studies with technical amitraz indicate that parent amitraz is highly toxic to
freshwater fish. Formulated product testing on fish is required when the chemical is applied
directly to water. While amitraz does not have such a use pattern, formulated product testing
was rec-iired since several studies suggested that amitraz may be more toxic in a 20% EC
formu; :on than by itself. A possible explanation is that this probably was the result of an
inert ingredient making the active ingredient more available to the fish. Studies reviewed
indicated that a 20% EC formulation of amitraz ranged from moderately to very highly toxic
to freshwater fish.
36
-------
Studies were also required on the two major amitraz metabolites (BTS-27271,
BTS-27919) because of their potential increased toxicity when compared to the parent
compound. BTS-27271 and BTS-27919 can be characterized as slightly toxic to practically
nontoxic, respectively, to freshwater fish.
Gdln. No.
MRID No.
Species
% A.I.
96-hrLQ.
Fulfills Gdln
TECHNICAL
72-l(a)
72-1&)
72-10,)
72-l(b)
72-l(c)
72-1(0
72-l(a)and(b)
72-Kb)
72-Kb)
72-l(d)
72-l(d)
72-l(b)
72-l(d)
72-Kb)
72-l(d)
40798001
00030444
00030447
00030448
00030445
00030446
00030448
00030444
00030447
00039445
40780505
Bluegill Sunfish
Carp ;
Bluegill Sunfish
Harlequin Fish
Rainbow Trout
Rainbow Trout
98.08
Technical
Technical
Technical
Technical
Technical
0.34 ppm
1.17 ppm**
1.34 ppm
3.2 -4.3 ppm
2.7 -4.0 ppm*
0.74 ppm
Yes
Partial
Partial
Partial
Partial .
Yes
FORMULATED PRODUCT
Harlequin Fish
Carp
Bluegill Sunfish
Rainbow Trout
Rainbow Trout
20% EC
20% EC
20% EC
20% EC
20% EC
8.74 ppm ai
0.56 ppm**
3. 14 ppm ai
0.2 -0.4 ppm ai**
2.20 ppm ai
Partial
Partial
Partial
Partial
Yes
' .
DEGRADATES
41827202
41827203
41827206 :
41827205
Bluegill Sunfish
Rainbow Trout
Rainbow Trout
Bluegill Sunfish
Technical
BTS-27271
Technical
BTS-27271
Technical BTS-
27919
Technical
BTS-27919
, 29.3 ppm
28.4 ppm
66.2 ppm
>100'ppm
Yes
Yes
Yes
Yes
* 48-hour test
** 120-hour test
Fish Early Life Stage Studies: A fish early life stage test is required when a product is
applied directly to water or is expected to be transported'to aquatic sites and 1) exposure of
aquatic organisms will be continual or recurrent; or 2) the lowest LCSO is 1 mg/L or less; or 3)
the EEC in water is equal to or greater than 0.01 of any LC50; or 4) if the EEC is less than any
LC50 and the product has reproductive effects on, or cumulative effects in, aquatic organisms
or has a half-life in water greater than 4 days.
37
-------
Fish early life-stage testing was required because amitraz is highly toxic to freshwater
fish and may be applied repeatedly during the season. Furthermore, an estimate of the,initial
environmental concentration suggested that residues could be greater than 0.01 of the fish
LC50. An early life stage test with a freshwater fish species is required for the pear and
cotton uses. No chronic aquatic studies are required for the cattle/swine, and dog uses.
Gldn-No.
72-4(a)
72-4(a)
MRIDNo.
40798002
41288702
%A.L
98.8%
98.8%
Species
Fathead Minnow
(embryo-larvae)
Fathead Minnow
(embryo-larvae)
Results
NOEC & MATC < 3.53 ppb based
on weight (most sensitive
parameter)
MATC > 1.48 < 2.71 ppb based on
length
Fulfill Gdln.
Partial
Yes
An early life-stage study performed with the fathead minnow shows that body length
is impaired at environmental concentrations of >2.71 ppb. The MATC (Maximum Allowable
Toxic Concentration) is > 1.48 < 2.71 ppb.
Effects on Freshwater Invertebrates; The minimum data requirements for establishing the
acute toxicity of amitraz to aquatic invertebrates depend upon the results from one 48-hour
acute toxicity test, preferably using first instar Daphnia magna or early instar amphipods,
stoneflies, mayflies, or midges. This study is required for all amitraz use patterns.
Acute Aquatic Invertebrate Toxicitv Studies - Technical, Formulated Product, and
Primary Pegradates; Parent amitraz can be characterized as very highly toxic to aquatic
invertebrates.
Gldn-No.
MRIDNo.
Spedes
%A.L
TECHNICAL
72-2(a)
RIOAMI01
Daphnia magna
Technical
ECM
,
35 ppb
Fulfills Gdln.
Yes
FORMULATED PRODUCT
72-2(b)
40780506
Daphnia magna
20% EC
3.4 ppm
Yes
DEGRADATES
72-2(b)
72-2(b)
4182720*
41827207
' Daphnia magna
Daphnia magna
BTS-27271 Technical
BTS-27919 Technical
2.59 ppm
>100 ppm
Yes
Yes
Testing with the formulated product was required since several fish studies suggested
that amitraz may be more toxic when in a 20% EC formulation than by itself. The review of
the study characterizes the 20% EC formulation of amitraz as moderately toxic to aquatic
invertebrates.
38
-------
Studies on the two major degradates of amitraz (BTS-27271 and BTS-27919) were
.also required because of their potential increased toxiciry when compared to the parent
compound. BTS-27271 and BTS-27919 can be characterized as moderately toxic and
practically nontoxic, respectively, to Daphnia magna.
Aquatic Invertebrate Life-Cycle Study- Terhnipai? A freshwater invertebrate life-cycle
test is required when a product is applied directly to water or is expected to be transported to
aquatic sites and 1) exposure of aquatic organisms will be continual or recurrent; or 2) the
lowest LC5o is 1 mg/L or less; or 3) the EEC in water is equal to or greater than 0.01 of any
LCSO; or 4) if the EEC is less than any LCSO and the product has reproductive effects on, or
cumulative effects in, aquatic organisms or has a half-life in water greater than 4 days.'
Aquatic invertebrate life cycle testing was required because parent amitraz is highly
toxic and may be applied repeatedly during the season. Furthermore, an estimate of the initial
environmental concentration suggested that residues (i.e., parent plus degradates) could be
greater than 0.01 of the aquatic invertebrate LC50. A freshwater invertebrate life-cycle test is
required for the pear and cotton uses.
The aquatic invertebrate life-cycle test performed with Daphnia magna shows a
significant reduction in growth and fecundity at > 2.21 ppb. The MATC (Maximum
Allowable Toxic Concentration) is > 1.10 < 2.21 ppb. (MRIDs 40780511,41288701)
Effects on Marine and Estuarine Organisms; Acute toxicity testing with estuarine and
marine organisms is required when an end-use product is intended for direct application to the
manne/estuarine environment or is expected to reach this environment in significant
concentrations. The requirements under this category include a 96-hour LCSO for an estuarine
fish, a 96-hour LC5p for shrimp, and either a 48-hour embryo-larvae study or a 96-hour shell
deposition study with oysters. Estuarine/marine testing is required for the pear and cotton
uses only.
Acute Estuarine and Marine Toxicitv Studies - Technical. Formulated Product, and
Primary Degradates: There is sufficient information to characterize parent amitraz as highly
toxic to oysters, moderately toxic to the sheepshead minnow and slightly toxic to grass
shrimp. While the sheepshead minnow study was of supplemental status, this study combined
with other estuarine fish tests can be used to satisfy guideline requirements.
Formulated product testing with estuarine/marine species was required since several
fish studies suggested that technical amitraz may be more toxic when in a 20% EC
formulation than by itself. These studies were originally required for a proposed citrus use
and are also applicable to the cotton use pattern. Based on the reviewed data, the 20% EC
formulation of amitraz is very highly toxic to the eastern oyster, highly toxic to the mysid
shrimp and slightly toxic to the sheepshead minnow.
39
-------
Studies were also required on the two major amitraz metabolites (BTS-27271
BTS-27919) because of their potential increased tpxicity when compared to the parent
compound. BTS-27271 can be characterized as slightly toxic to the sheepshead minnow and
eastern oy and moderately toxic to the mysid shrimp. BTS-27919 can be characterized as
practical!} ./atoxic to the sheepshead minnow and eastern oyster and moderately toxic to the
mysid shrimp. The Agency has determined that the existing database is sufficient to
characterize the toxicity of amitraz degradates to estuarine/marine organisms.
Gdln.No.
MRTONo.
Species
% A.I.
LC,.
Fulfills Gdln.
TECHNICAL
72-3{a)
72-3(b)
72-3(c)
72-3(c)
407X0507
RIOAMI02
00030450
00030450
' Sheepshead Minnow
Atlantic Oyster
Grass Shrimp
Fiddler Crab
98%
95%
Technical
Technical
96-hr LGป = 2.4 ppm
48-hr TLffl = 0.85 ppm
96-hr ECa = 65. 1 ppm
> 1000 ppm
Partial
Yes
Yes
Partial
FORMULATED PRODUCT
72-3(d)
72-3(e)
72-3(f)
40780508
40780509
40780510
Sheepshead Minnow.
Eastern Oyster
Mysid Shrimp
20% EC
20% EC
20% EC
96-hr LCjj > 7.9 ppm
96-hr ฃ0,, = 85 ppb '
96-hr ECป = 0.48 ppm
Yes
Yes
Yes
DEGRADATES
72-3(d)
72-3(d)
72-3(e)
72-3(e)
72-3(ฃ)
72-3{f)
42124608
42134609
42124610
42124611
, 42J24612
42124613
Sheepshead Minnow
Sheepshead Minnow
Eastern Oyster
Eastern Oyster
Mysid Shrimp
Mysid Shrimp
BTS-27271
99.6%
BTS-27919
99.8%
BTS-27271
99.6%
BTS-27919
99.8%
BTS-27271
100%
BTS-27919
99.8%
96-hr LC,o = 1 1.5 ppm
96-hr LCjj =>102 ppm
96-hr EC,, = 13.1 ppm
96-hr ECป =>128 ppm
96-hr EC,,, = 5.81 ppm
96-hr ECป = 8.2 ppm
Yes
Yes
Partial
No
Yes
Partial
(3) Non-Target Insects Data
The minimum data required to establish the acute toxicity of parent amitraz to honey
bees is an acute contact LD50 study with the technical material. This study is required for the
pear and cotton uses only. There is sufficient information to characterize amitraz as
practically nontoxic to bees. .
40
-------
Gdln.No.
141-1
141-1
141-1
141-1
MRID No.
00030455
00074486
00052490
00059461
Species
Apis mellifera
Apis mellifera
Stethorus punctum
Stethorus punctum
%AJ.
20% EC
Tech.
20% EC
20% EC
LDป
no death or repellency in field test
> lOOug/bee
low toxicity at 6 oz ai/ 100 gal.
low toxicity at 0.375 Ib ai/100 gal
Fulfills
Gdln.
Yes
Yes
Yes
Yes
(4) Non-Target Plants Data
No studies were submitted under this topic and none are required.
b. Ecological Effects Risk Assessment
(1) Terrestrial Food/Nonfood Crops: Cotton and Pears
(a) Terrestrial Organisms
Amitraz is applied to pears in two types of formulations, a 50% a.i. WP and a
19.8% EC. Both labels specify a maximum use rate of 1.5 Ibs a.i./A not to exceed 3 Ibs. per
season. Pears are grown in New England and the far west (California, Washington and
Oregon). Pear orchards are normally used as a food source (buds, fruit, seeds and blossoms)
by grouse, finch, orioles and sparrows. A variety of mammals (including squirrels, rabbits,
muskrat, fox and coyote) utilize the fruit and bark of pear trees.
s Amitraz is also applied to cotton in a 19.8% EC formulation with a maximum use rate
of 1.0 Ib. a.i./A/season. Cotton is grown throughout the southern United States. A variety of
avian and mammalian organisms use cotton fields for feeding, cover and brooding. These
organisms include both nongame and game species: bobwhite quail, wild turkey, ring-necked
pheasant, mourning dove, ducks, geese, sandhill crane, songbirds, prairie chicken, deer,
rabbit, raccoon, opossum and antelope.
To characterize the possible effects posed by amitraz use, the following possible
scenarios are presented below: acute and chronic risk analyses to terrestrial and aquatic
organisms.
Acute Risk to Terrestrial Organisms
Parent Amitraz; For both the cotton and the pear use, parent amitraz does not appear to
pose an acute risk to either endangered or non-endangered terrestrial organisms. . .
41
-------
Amitraz Pegradate BTS-27271: BTS-27271 may be a potential acute hazard to avian
species since it is more acutely toxic and is more persistent in the environment (aerobic soil
metabolism tjQ = 75 days) than the parent.
_Jn the following table, the number of single dose oral LDSO per bird per day for several
species of birds exposed to BTS-27271 were calculated for both the cotton and the pear use
patterns using three different scenarios: the maximum and typical residue levels from Kenaga
(1973) and the values derived from a foliar field dissipation study on cotton. While the foliar
dissipation study contains limited information on the dissipation of amitraz and its degradates,
it was included in the risk assessment in order to have amitraz specific data with which to
compare to Kenaga's general values. It should be noted, however, that one can place only
limited confidence in these numbers due to lack of sample replication at each test site and
sampling time. In addition, amitraz residues were measured on cotton foliage only; other
avian food items (i.e. seeds, grass, insects) were not sampled.
As the foliar dissipation study provided residue levels on cotton foliage only (after a
single 1.0 Ib. ai/A application and after four 0.25 Ib. ai/A applications), the residue levels for
other substrates (i.e. short grass, seeds, etc.) were extrapolated using the proportions found in
Kenaga's table. For example, if Kenaga determined that the maximum residues on short grass
exceed those on foliage by a factor of 1.92, then the foliage residue level from the dissipation
study was multiplied by this factor in order to calculate an appropriate value for short grass.
LDj.3 per Bird per Day for Several Avian Species Exposed to BTS-27271:
Cotton and Fear Use Patterns '
Avian Species
Carolina Wren
Mallard Duck
COTTON (1.0 Ib. a.L/A)
Maximum Kenaga
0.15"
0.06
Typical Kenega
0.09"
0.03
Foliar Field Dissipation
0.07
0.03
PEAR (1.5 lb.a.L/A)
Maximum
Kenaga
0.23'
0.10"
Typical
Kenaga
0.13"
O.Oi
* Restricted use classification LOG (0.2 LQ, per day) is exceeded.
ซซ Endangered species LOG (0.1 LQo per day) is equaled or exceeded.,
The use of amitraz on cotton may pose an acute risk to endangered birds feeding on
insects. The endangered species LOG (0:10 LD50/day) is exceeded for the Carolina wren (an
insect eater) in the maximum Kenaga scenarios. The endangered species LOG is not
exceeded for insect eating birds in the field dissipation scenario.
The use of amitraz on pears may also pose an acute risk to endangered birds feeding
on insects and on short grass. The endangered species LOG (0.10 LD50/day) is exceeded for
the Carolina wren in the typical and maximum Kenaga scenarios. Additionally, this use may
pose an acute risk for endangered birds feeding on grass. The endangered species LOG is
equaled for the mallard (a grass eater) in the maximum Kenaga'scenario.
42
-------
While the restricted use classification LOG (0.2 LDso/day) is exceeded for the Carolina
wren in the maximum Kenaga scenario, the high LOG (0,5 LD50/day), however, has not been
surpassed.
Due to the persistent nature of BTS-27271, a second 1.5 Ibs ai/A application of amitraz
to pears at a 10-day interval would essentially double residue values in the above table for
pears thereby increasing risk to nontarget birds.
Chronic Risk to Terrestrial Organisms
Chronic, risk to terrestrial organisms are presented in the following tables for both the
cotton and pear uses for parent amitraz and the degradate BTS-27271. The diet composition
of five avian species was factored into the calculations of total residue (ppm) values. For
example, it was assumed that the mourning dove consumes 100% seeds while the Carolina
wren eats 99% insects and 1% seeds. These species were used because they are
representative of large groups of birds that have similar feeding habits. Maximum and typical
residue levels from Kenaga (1973) and the values derived from the registrant's foliar field
dissipation study on cotton were used for this risk assessment (MRID 42124619).
Amitraz use on Cotton: Parent Amitraz; Estimated environmental concentrations (EEC's)
were calculated for a LO Ib. ai/A (maximum application rate) and four 0.25 Ib. ai/A
applications (typical use pattern indicated by registrant) using both the maximum and typical
residue levels for parent amitraz from Kenaga (1973) and the values derived from the
registrant's foliar field dissipation study on cotton (MRID 42124619). ,_
Parent Amitraz Chronic Risk; 1 Ib. ai/A Application
LOC 1 NOEL (25 DDml: Shaded blocks renresent LOC exceedance.
SPECIES
Bobwhite QuaiF
Mourning Dove?
Field Sparrow7
Carolina Wren*
Mallard Duck?
TOTAL RESIDUE (ppm)
Max.1 Kenaga
" " 24,* '"'" ""'
12.0
?5,r "\
"'^'" '''-...-..' I
??,$ ;
s " '' * S :
-' *&m ," --" i
RQ*
i' l&~ -' ",
0.5
&, '.
IA '"
. '&,
- fc? ' "
?ฃ -" ', "
Typ.1 Kenaga
11.1
3.0
18.3
- -y^f.,. m
" ป5<& *. ซ,,,"'
RO
0.4
0.1
0.7
s
- -is- -
%^ ^ ฅ
^'5,0 %
Field Study1
12.2
6.0
17.7
'"<' ' ../
- 28# - '
&&$--- - 7^
RQ
0.5
0.2
0.7
" 4
-------
Similar LOG exceedances are indicated for the typical use rate of four 0.25 ai parent
amitraz/A applications (risk quotients ranging from 1.0. to 7.0).
Parent Amitraz Chronic Risk
0.25 Ib. ai/A Application (4 applications separated by 7-day intervals)
LOCSNOEL (25 ppm); Shaded blocks represent LOG exceedance
SPECIES
Bobwhite Quaff
Mourning Dove?
Field Sparrow7
Carolina Wren*
Mallard Duck?
TOTAL RESIDUE (ppm)
Max.1 Kenaga
17.7
8.7
" "-"v fff
,\ , ? ' J ' ' ''>'
3$$- '' "
*&r:"-v.
AS <{f % *^ f , ,
\-^lJ4$*' K^
RQ2
0.7
0.3
xo';
'''/," ,:
'," 13 -
\ \
', ซr,o, , -4
Typ.* Kenaga
7.8
2.0
13.1
23.6
' f , }
, -:mp t'}j- A
RQ
0.3
0.1
0.5
0.9
f~''M/i
Field Study*
8.8
4.3
12.8
20.8
f s s< s "
-j 'S&B ; -,';*-
RQ
0.3
0.2
0.5
0.8
u bcl* '-
1. Maximum residue levels were calculated for 4 x 0.25 Ib. ai/A with an application interval of 7 days. The residue value determined
after a single 0.25 Ib. ai/A application (Kenaga) was run through an EFED fate model using a maximum half-life of 36.9 days for total
amhraz residues (derived from Nor-Am's field dissipation study). . ,
2. RQป risk quotient , ,
3. Typical residues were calculated by the same method described in footnote 1. ,
4. Foliar field dissipation study on cotton (Nor-Am, 1991). Residue values for appropriate diet substrates are extrapolated from the
maximum total residue level of 44.6 ppm measured after four 0.25 Ib. ai/A applications separated by 7 day interval (see
Attachment2). .
5. Assumption: bobwhitc quail consumes 27% forage (e.g. alfalfa, small insects) and 73% seeds.
6. Assumption: mourning dove consumes 100% seeds. '
7. Assumption: field sparrow consumes 51% forage (insects)rand 49% seeds. ' ' ' "
8. Assumption: Carolina > ~ซn consumes 99% forage (insects) and 1% seeds.
9. Assumption: mallard consumes 100% short grass.
Avian reproduction studies with parent amitraz indicate that the no observable effect
level (NOEL) is 25 ppm. Use of amitraz on cotton may adversely affect avian reproduction.
The LOG is exceeded in all three scenarios for a 1.0 Ib. ai parent amitraz/A application (foliar
field dissipation study and maximum and typical Kenaga) for insect and grass eating birds
(risk quotients ranging from 1.1 to 9.6). The LOG is also equaled or exceeded for bird species
which eat both seeds and insects (risk quotients ranging from 1.0 to 1.4).
In the core bobwhite quail study, a statistically significant reduction (12%) as
comped to the control, was observed at the 50.5 ppm test level in.the number of viable
embryos per egg set. A 13% reduction in the number of 14-day survivors per egg set and an
11% reduction in the number of hatchlings per egg set were also observed at the 50.5 ppm test
level, although these effects were not found to be significantly different from the controls
(MGRID 42336001).
A supplemental bobwhite reproduction study with parent amitraz demonstrated an
increase in eggshell cracking and a reduction in the percentage of viable embryos that
survived to become normal hatchlings at 40 ppm; a NOEL was not determined in this study as
reproductive effects were seen at the lowest level tested. A supplemental mallard
reproduction study with parent amitraz demonstrated a significant reduction at 40 ppm, in
comparison to the control, in the number of 14-day old survivors produced per week; again, a
44
-------
NOEL was not determined in this study since reproductive effects were seen at the lowest
level tested (MKEDs 00072411, 00072412).
s - '
Amitraz Use on Cotton: Amitraz Deeradate BTS-27271: When birds consume amitraz
their stomachs rapidly metabolize the residues to the major degradates (BTS-27271 and
BTS-27919). Thus, a chronic avian risk assessment was also conducted on the major
degradate, BTS-27271. EEC's were calculated after a 1.0 Ib. ai amitraz/A equals 0.55 Ib. ai
BTS-27271/A application using both the maximum and typical residue levels from Kenaga
(1973) and residues from the foliar field dissipation study.
SPECIES
Bobwhite QiiaiF
Mourning Dove?
Field Sparrow7
Carolina Wren*
Mallard Duck*
BTS-27271
1.0 Ib. ai amitraz/A Application
(yielding 0.55 Ib. ai BTS-27271/A) LOC> NOEL (25 ppm); "
Sshaded blocks represent LOG exceedance
Total Residue (pmnt
Max.1 Kenaga
13.5
6.6
19.5
^liri' /:
. ;, 132,-t}- ' "*' ; ,
,RQ*
0.5
' 0.3
0.8
..- 'S . "
' 13- "- :
*,t- '^ % '"'
Typ.1 Kenaga
6.1
1.7
10.1
18.0
$ y&Scv^acS '','
,1 -mSf'^.;:-" <:''<
RQ
0.2
0.1
0.4 '
0.7
''*'""
''*">" &,1 '"
Field Study*
6.7
3.3
9.7
15.8
- ', ,fi&ป ' ''
RQ
0.3
0.1
0.4
0.6
' ' -A V""
2xซ " ,
2.
3.
4.
5.
6.
7.
8.
9.
Maximum residue levels were calculated for4 x 0.25 Ib. ai/A with an application interval of 7 days. The residue value determined
after a single 0.25 Ib. ai/A application (Kenaga) was run through an EFED fate program using a maximum half-life of 36.9 days for
total amitraz residues (derived from Nor-Am's field dissipation study).
RQ = risk quotient (EEC/NOEL); LOG = 1.0. .
Typical residues were calculated by the same method described in footnote 1. ,
Foliar field dissipation study on cotton (Nor-Am, 1991). Residue values for appropriate diet substrates are extrapolated from the
maximum total residue level of 44.6 ppm measured after four 0.25 Ib. ai/A applications separated by 7 day interval (see
Attachment 2).
Assumption: bobwhite quail consumes 27% forage (e.g. alfalfa, small insects) and 73% seeds.
Assumption: mourning dove consumes 100% seeds.
Assumption: field, sparrow consumes 51% forage (insects) and 49% seeds.
Assumption: Carolina wren consumes 99% forage (insects) and 1% seeds.
Assumption: mallard consumes 100% short grass.
In determining LOG exceedance, the NOEL from the BTS-27271 study with the
bobwhite quail was used. The bobwhite reproduction study indicated a NOEL of 25 ppm and
a LOEL of 100 ppm based on statistically significant reductions, as compared to the control,
in the number of hatchlings as a percentage of eggs set (16% reduction) and the number of '
two-week survivors as a percentage of eggs set (18% reduction).
A lower NOEL of 5 ppm exists for BTS-27271 (found in the mallard study).
However, the confidence that can be placed on these results is questionable since the lab
which conducted the study has historically encountered problems with eggs cracking in their
avian reproduction studies; the statistically significant parameter in the mallard study was a
49% increase, as compared to the control, in the number of eggs cracked.
45
-------
The risk assessment for BTS-27271 strengthens the conclusions that use of amitraz on
cotton may adversely affect avian reproduction as comparable LOG exceedances are indicated
(risk quotients of 1.3 to 5.3).
Amitraz Use on Pears; Parent Amitraz; Maximum residues (EEC's) were calculated for
parent amitraz for a 1.5 Ib. ai/A applications using both the maximum and typical residue
levels from Kenaga (1973).
Use of amitraz on pears may adversely affect avian reproduction. The LOG is
exceeded in both the typical and maximum Kenaga scenarios with a single 1.5 Ib. ai/A parent
amitraz application for insect, grass and seed/insect eating birds (risk quotients ranging from
1.0 to 14.0).
Parent Amitraz
1.5 Ib. ai/A Application LOO NOEL (25 ppm);
shaded blocks represent LOC exceedance
SPECIES
Bobwhhe Quail*
Mourning Dove*
, Field Sparrow*
Carolina Wren7
Mallard Duck?
Total Residue (p
Max. Kenaga1
,; -.% ป!'.si*ซ' #ฃ ?ป'/-. V"
> - A .>>x- - .: w %" ~.f '
'*$' " *
^ftf', f ***:* f
3.4 -,>', '
'l^f^C';
Typ. Kenaga1
16.6
4.5
: ' >. " '''# '" ..''' .. *y
'-'"ZiA '' * '/ ' ~
/> ,ฃ, "/;-'/" - -/ซ
,-/4S*/, - ' '-;
*nwiป^''''r '/I
RQ
0.7
0.2
'i*; - - ' -~
#-**^5 " M '*. "f
- ,& /' '
f ""^ -.s
:%$ ''" v
1 . Maximum residues to expected food hems (Kenaga, 1973).
2. RQ -risk quotient (EEC/NOEL); LOC =1.0.
3. Typical residues to expected food items (Kenaga, 1973).
4. Assumption: bobwhite quail consumes 27% forage (e.g. alfalfa, small insects) and 73% seeds.
5. Assumption: mourning dove consumes 100% seeds.
S. Assumption: field sparrow consumes 51% forage (insects) and 49% seeds.
7. Assumption: Carolina wren consumes 99% forage (insects) and 1% seeds.
J. Assumption: mallard consumes 100% short grass.
Amitraz Use on Pears; Amitraz Degradate BTS-27271; Maximum residues (EEC's) for
BTS-27271 were calculated after a 1.5 Ib. ai/A amitraz (equals 0.83 Ib. ai BTS-27271/A)
application using both the maximum and typical residue levels from Kenaga (1973). As in
the preceding tables, the diet composition of five different avian species was factored into the
calculations of total residue (ppm) values.
A second 1.5 Ib. ai/A application of amitraz at a 10-day interval would essentially
double residue values in the above tables due to the persistent nature of BTS-27271 (aerobic
soil metabolism t^ = 75 days). In any case, it has been concluded that pesticide effects on
avian reproduction can occur within a matter of days (e.g., 8 days or less) after treatment
(Bennett and Ganio, 1991). Thus, reproductive effects are not merely a function of chronic
exposure to a pesticide.
46
-------
"; BTS-27271; 1,5 Ib. ai amitraz/A Application (yielding 0.83 Ib. ai BTS-27271/A); LOC! NOEL (25ppm);
shaded blocks represent LOC exceedance
SPECIES
Bobwhite Quail1
Mourning Dove?
Field Sparrow'
Carolina Wren7 ...
Mallard Duck?
BTS 27271 Residues (ppm)
Max. Kenaga1
20.3
10.0
"" f f
'3?,-*
......v. %% '""^ ,. ,
<*&ซ
&ป$ - ;
RQ1
0.8
0.4
'\A " '"' "-
l# "--.-' ?>'"
8>o . ,
Typ. Kenaga1
9.1
2.5
18.9
"c'ii$~ ^ '::" I
mii:- ' i
RQ
0.4
0.1
0.7
- U ' :
^'%
, *& ,
I. Maximum residues to expected food items (Kenaga, 1973).
2. RQ = risk quotient (EEC/NOEL); LOC = 1.0. . ,
3.' Typical residues to expected food hems (Kenaga, 1973).
4. Assumption: bobwhite quail consumes 27% forage (e.g. alfalfa, small insects) and 73% seeds.
5. Assumption: mourning dove consumes 100% seeds.
6. Assumption: field sparrow consumes 51% forage (insects) and 49% seeds. '
7. Assumption: Carolina wren consumes 99% forage (insects) and 1% seeds.
8. Assumption: mallard consumes 100% short grass.
The risk assessment for a major degradate (BTS 27271) indicates that use of amitraz
on pears may adversely affect avian reproduction as comparable LOC exceedances are
indicated (risk quotients of 1.1 to 8.0).
For the pear use, a second application of amitraz at 1.5 Ib. ai/A would essentially
double the risk quotients listed above.
Risks to Small Mammals; Cotton and Pear Use
Small mammal exposure is addressed using acute oral LD50 values converted to
estimate a LCSO value for dietary exposure. The estimated LC50 is derived using the following
formula: '
LC50 = LDซn x body weight
food cons, per day (g)
Small Mammal Food Consumption in ppm
(Based on an LDM = 515 mg/kg) ' ,
Small Mammal
Meadow vole
Adult field mouse
Least shrew
Body Weight in
Grams
46 .
13
5
% of Weight Eaten Per
Day
61
16
110
Food Consumed Per Day in
Grams
28.1
2.1
5.5
Estimated LQ. Per
Day (ppm)
843
3188
566
The above table is based on information contained inPrinciples of Mammologvbv D. E. Davis and F. Golly, published by Reinhold Corporatioi,
47
-------
Acute Risks to Mammals: The estimated LC50 is then compared to the residues listed above
to calculate a risk quotient (EEC/LC50). The table below indicates the risk quotients for
application of amitraz at the highest application rate of 1.5 Ib. a.i./A on pears.
IWanuna^'an
(based
Mammal Type
Meadow vole consuming range grasses
Adult field mouse consuming seeds
Least shrew consuming insects .
Dietary Risk Quotients on Fears
on Dietary RQ = EEC/LQ.)
Food Item
long grasses
seeds
small insects
Residues
(ppm)
165
18
87
Risk Quotient
0.19
0.005
0.15
The table below indicates the risk quotients for application of amitraz at the
application rate of 1.0 Ib. a.i./A on cotton.
Mammalian Dietary Risk Quotients on Vegetables and Cotton
(based on Dietary RQ = EEC/LQ.)
Mammal Type
Meadow vole consuming range grasses
Adult field mouse consuming seeds
Least shrew consuming insects
Food Item
long grasses
seeds '
small insects
Residues
(ppm)
110
12
"58
Risk Quotient
0.13
0.003
0.1
The LOG for high acute risk (0.5) and restricted use (0.2) to mammals have not been
exceeded. However, endangered small mammals exposed to areas treated with amitraz may
be affected (RQ for endangered species LOG of 0.1).
Chronic Risks to Mammals: The following table indicates the Chronic risk quotients for
application of amitraz at various application rates. For purposes of establishing chronic risk, a
three-generation reproduction study on rats was used, with a NOEL of 15 ppm/day. The
LOEL for this study was 50 ppm/day, resulting in decrease in litter size.
Use Rate
lb.aJJA(Crop)
1.5 (pears)
1.5 (pears)
1.0 (cotton)
0.25 (cotton
Food Item.
long grass
insects
insects
insects
Mammalian
(based on Dietan
Maximum
Residues (ppm)
165
87
58
15
Chronic Risk Quotients
RQ = EEC/15 ppm NOEL)'
Maximum
Risk Quotient
11
5.8
3.8
1
Typical
Residues (ppm)
13.8
49
33
8.
Typical
Risk Quotient
9.2
3.2
2.2
0.5
LOG
1
1
1
1
48
-------
Small mammals are a vital link in the food chain; a reduction in their numbers may
dramatically impact top carnivores (hawks, owls, foxes, etc...).
Using maximum and typical residues on representative food items for mammals, the
risk quotients exceed the chronic LOG. However, the factors, as outlined below, all lend to
the uncertainty in the conclusion of high chronic (sublethal or reproductive) risk.
Other factors should be considered when assessing the extent of risk and the certainty
that chronic effects will occur. Uncertainty stems both from using laboratory toxicity test
results, and from limitations in estimating actual exposure.
* '
1. The study, from which the chronic NOEL was derived was a 3-generation
feeding study. It is not known at what poirit-in-time during the test .(at 50 ppm
exposure) the observed effects were noted. Parent amitraz has a short half-life
(<1 day) jferobic soil metabolism), but the degradates are persistent.
2. It is assumed that other mammals would have different sensitivities than the
representative test organism (laboratory rat). It is not known if wild mammals
would be more or less sensitive. If they are more sensitive, even the lower
. residue levels may result in sublethal or reproductive risk.
3. It is not known how long the exposure residues will last on mammalian food
items. Residues of parent amitraz will not remain the full time the rat
3-generation study lasted, especially at levels exceeding the LOEL. However,
because rather short exposure periods could cause sublethal or reproductive
effects, this does not preclude the presumed risk.
4. In pear orchards, where the predominant vegetation type is long grass, risk
from consumption of maximum or typical residues exceed the LOG for chronic
risk. However, small mammals will graze on the lower portions of the grass
and would not ingest the highest residues that would be at the upper portions of
the long grass..
5. In cotton, the greater chronic risk may come from repeated applications at
0.25 Ib. a.i./A rather than a single application of 1.0 Ib. a.i./A.
6. Mammals could move about and feed on a variety of items, not just the food
items with the maximum residues.
These factors all lend to the uncertainty in the conclusion of chronic (sublethal or
reproductive) risk.
49
-------
Risk to Aquatic Organisms
Acute Toxicitv: For the cotton use, an application rate of 1.0 Ib. a.i./A would produce EEC's
of 3.05,16.8 and 31.1 ppb for parent amitraz, BTS-27271 and BTS-27919, respectively. For
the pear use, an application rate of 1.5 Ib. a.i./A would produce EEC's of 4.5, 17^7 and
32.4 ppb for parent amitraz, BTS-27271 and BTS-27919, respectively.
For the cotton use, amitraz degradates (BTS-27919, BTS-27271) should pose minimal
acute risk to aquatic organisms since the EEC's do not exceed the restricted use classification
LOG (1/10 LCSO = 3.5 ppb for daphnia, parent amitraz; 259 ppb for daphnia, BTS-27271;
820 ppb for mysid shrimp, BTS-27919). The aquatic EEC for parent amitraz (3.05 ppb) falls
short of the restricted use LOG (1/10 LCSO = 3.5 ppb for daphnia) but surpasses the
endangered species LOG (1/20 LCSO = 1.75 ppb for daphnia). However, because parent
amitraz is short-lived in the environment (hydrolysis = 22.1 hours @ pH 7; aerobic
metabolism < 1 day), adverse effects to these organisms is expected to be minimal.
For the pear use, parent amitraz may pose acute risk to aquatic invertebrates as the
EEC exceeds the restricted use classification LOG for the daphnia (1/10 ECSO = 3.5 ppb). As
with the cotton use, these effects are expected to be minimal as parent amitraz rapidly
dissipates in the environment.
For the pear use, amitraz degradates (BTS-27919, BTS-27271) should pose minimal
acute risk to aquatic organisms since the EEC's do not exceed the restricted use classification
LOG (1/10 LC50 = 259 ppb for daphnia, BTS-27271; 820 ppb for mysid shrimp, BTS-27919).
Chronic Toxicitv; For both the cotton and the pear use patterns, the maximum application
rates of 1.0 Ib. ai/A and 1.5 Ib. ai/A, respectively, would produce EEC's for parent amitraz
(3.05 ppb and 4.05, respectively) which exceed the MATC (Maximum Allowable Toxic
Concentration) found in the chronic daphnia (MATC > 1.10 < 2.2 ppb) and the fish early-life
stage (MATC >1.48 < 2.7 ppb) studies.
However, parent amitraz is short-lived in the environment (hydrolysis = 22.1 hours
@ pH 7; aerobic metabolism < 1 day) and the potential, for chronic effects to nontarget
aquatic organisms is expected to be minimal, ' . - -
Although amitraz degradates are less acutely toxic than the parent to aquatic
organisms, their potential chronic toxicity is of concern because they are more persistent in
aquatic environments than the parent (see Environmental Fate section).
The cotton use pattern does not appear to pose a chronic risk to aquatic organisms as
the EEC's for BTS-27271 and BTS-27919 (16.8 ppb and 31.1 ppb, respectively) do not
exceed 1/10') EC50 of the most sensitive species (25.3 ppb for daphnia, BTS-27271; 82 ppb
for mysid shrimp, BTS-27919).
50
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The pear use pattern, however, is of concern since it can be applied at a higher
application rate. The EEC would be 33.8 ppb which surpasses 1/100 ECSO (25.3 ppb) when
calculations were made for BTS-27271 using Daphnia magna, the most sensitive species.
Therefore, chronic adverse effects to aquatic invertebrates may be expected from use of
amitraz on pears. Therefore, in order to complete the amitraz aquatic risk assessment, the
Agency is requiring that a daphnia life-cycle study be conducted on the degradate,
BTS-27271.
Risks from Cattle and Swine Use
There are two amitraz containing products (Taktic EC 12.5% a.i. and Taktic Dairy
Collar 10% a:i.) which are used to control ectoparasites on cattle arid swine. The Agency is
mainly concerned with Taktic EC since this product can be applied directly to cattle/swine as
a dip or spray. While swine raised for meat production are mainly restricted to stalls/
farrowing pens, cattle are commonly allowed to range freely. Thus, there is a potential for
exposure to aquatic ecosystems when newly sprayed cattle roam into a pond or stream.
Considering that amitraz is highly toxic to fish and aquatic invertebrates, the Agency is
concerned with any use pattern in which this chemical may be transported to water.
Data available to the Agency indicates that amitraz is used mainly on swine versus
cattle: approximately 2-3% of cattle are treated with amitraz, while 10-20% of swine are
treated. In addition the use of amitraz on cattle is largely in quarantine situations (i.e. cattle
imported into the U.S. from Mexico). Therefore, use of amitraz on cattle and swine is
expected to result in minimal exposure to aquatic organisms. No further data are needed to
characterize this use pattern.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A., Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active
ingredients are eligible for reregistration. The Agency has previously identified and required
the submission of the generic amitraz data-required to support reregistration of products
containing amitraz active ingredients. The Agency has completed its review of these generic
data and has determined that the data are sufficient to support reregistration of all products
containing amitraz. Appendix B identifies the generic data requirements that the Agency
reviewed as part of its determination of reregistration eligibility of amitraz, and lists the
submitted studies that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess the
registered uses of amitraz and to determine that provided certain label modifications were
implemented, amitraz can be used without resulting in unreasonable adverse effects to
humans and the environment. The Agency, therefore, finds that all products containing
51
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amitraz as the active ingredients are eligible for reregi strati on. The reregistration of particular
products is addressed in Section V of this document.
The Agency made its reregistration eligibility determination based upon the target data
base required for reregistration, the current guidelines for conducting acceptable studies to
generate such data and the data identified in Appendix B. Although the Agency has found
that all uses of amitraz are eligible for reregistration, it should be understood that the Agency
may take appropriate regulatory action, and/or require the submission of additional data to
support the registration of products containing amitraz, if new information comes to the
Agency's attention or if the data requirements for registration (or the guidelines for generating
such data) change.
1. Eligibility Decision
Based on the reviews of the generic data for amitraz, the Agency has sufficient
information on the health effects of amitraz and on its potential for causing adverse effects in
humans, fish and wildlife, and the environment to make a reregistration eligibility decision.
Therefore, the Agency concludes that products containing amitraz for all registered uses are
eligible for reregistration, provided certain risk mitigation measures outlined and required in
this RED document are implemented.
The Agency has determined that amitraz products, labeled and used as specified in this
RED document, will not pose unreasonable risks or adverse effects to humans or the
environment.
2. Eligible and Ineligible Uses
The Agency has determined that all currently registered uses of amitraz which labels
adhere to the mitigation measures outlined in this RED document are eligible for
reregistration.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for amitraz.
Where labeling revisions are imposed, specific language is set forth in Section V of this
document.
1.
Tolerance Reassessment
Tolerances for residues of amitraz in/on plant and animal commodities are expressed
in terms of the combined residues of amitraz and its metabolites BTS-27271 (N-(2,4-dimethyl
phenyl)-N-methylmethanimidamide) and BTS-27919 (N-(2,4-dimethylphenyl)) formamide
both calculated as the parent compound [40 CFR 180.287]. No food/feed additive tolerances
have been established for amitraz residues.
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, There is an error in the tolerance expression for the BTS-27919 metabolite. The
chemical name for the metabolite now reads N-(2J4-dimethyiphenyl)-N-methyl formamide.
The correct name for the metabolite is N-(2,4-dimethylphenyl) formamide. The tolerances
listed in 40 CFR ง180.287 have been evaluated in the table and are presented below.
- The 0-ppm tolerance for apples should be revoked since there are no registered
uses for this raw agricultural commodity.
The 3.0-ppm tolerance for pears is supported by adequate residue chemistry
data. .
The recently established (58 FR 14314, 3/17/93) tolerances for cottonseed
(1.0 ppm), eggs, (0.01 ppm), poultry fat and meat (0.01 ppm), and poultry meat
byproducts (0.05 ppm) in connection with PP#9F3730 are supported by
adequate residue chemistry data.
' v ' . . ' . .
The recently established (57 FR 53566, 11/12/92) tolerances for honey
(1.0 ppm) and honeycomb (6.0 ppm) in connection with PP#OF3825 are
supported by residue chemistry, data.
Tolerance reassessment summary for amitraz [40 CFR
Commodity
Apples
Beeswak
Cattle, fat
Cattle, mbyp
Cattle, meat
Cotton, seed
Eggs
Goats, fat
Goats, mbyp
Goats, meat
Hogs, fat
Hogs, kidney
Hogs, liver
Hogs, mbyp
Hogs, meat
Current Tolerance
foom)
0.00
6.0
0.1
0.3
0.05
1.0
0.01
0.00
0.00
0.00
0.1
0.2
0.2
0.3
0.05
Tolerance
ง180.287]
Reassessment
Revoke
Adequate
Adequate
Adequate
,
Revoke. .
The registrant must propose to raise the tolerance per
PP#9F3772 - goats meat, and meat-by-products 0.3(ppm),
goats fat 0.5 (ppm)
Adequate
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Tolerance reassessment summary for amrtraz [40 CFRฃ180.2871
Commodity
Honey and Comb
Horses, fat
Horses, mbyp
Horses, meat
Milk
Milk, fat
Pears
Poultry, fat
Poultry, mbyp
Poultry, meat
Sheep, fat
sheep, mbyp
sheep, meat
Current Tolerance
(ppm)
1.0 .
0.00
0.00
0.00
0.03
0.3
3.0
0.01
0.05
0.01
0.00
0.00
0.00
Tolerance Reassessment
Adequate
Revoke
Adequate
2.0 ppm
Adequate
Revoke.
The registrant must propose to raise the tolerance as per
PP#9F3772 - sheep meat and meat-by-products 0.3(ppm),
sheep fat 0.5 (ppm)
2.
Codex Harmonization
Several maximum residue limits (MRLs) for amitraz have been established by Codex
in various commodities. The Codex MRLs are currently expressed as the sum of amitraz and
N-(2,4-dimethylphenyl)-N'-methylfonnamidine calculated as N-(2s4-dimethylphenyl)-N'-
methylformamidine.
The Codex tolerance expression is somewhat different from the U.S. tolerance
expression. The Codex expression is the sum of amitraz plus metabolite BTS-27271,
calculated as BTS-27271. The U.S. expression is the sum of amitraz and its metabolites
BTS-27271 and BTS-27919, both calculated as the parent compound. The enforcement
method for amitraz tolerances in the U.S. (Methods I and II of PAM Vol. H) consists of
hydrolysis of all metabolites containing the 2,4-DMA moiety to 2,4-DMA, extraction, and
determination using gas chromatography with electron capture detection. The enforcement
method under the Codex system involves treatment of the RAC with acidic methanol to
convert the parent compound to metabolite BTS-27271, followed by extraction, cleanup, and
determination of BTS-27271 using gas liquid chromatography with flame ionization.
detection. Presently, compatibility between the Codex MRL and U.S, tolerance cannot be
achieved due to the differences between the tolerance definitions and'analytical enforcement
methods.
A summary of the established and proposed Codex MRLs is presented in the table
below. The U.S. tolerances and Codex MRLs are identical in magnitude for cattle and swine
tissues. When comparing tolerances versus MRLs which the U.S. and Codex have in
54
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common, the Codex MRLs are somewhat lower than the U.S. tolerances. There are several
Codex MRLs> either established or proposed, that do not have analogous U.S. tolerances.
Codex MRLs and applicable U.S. tolerances
Commodity
Cattle meat
Cherries
Cottonseed
Cottonseed crude oil
Cucumber
Edible offal of cattle, pigs,
and sheep
Milk
Oranges, sweet, sour
Peach
Pig meat
Pome fruit
Sheep meat
Tomato
Codex MRL
tag/kg)'
0.05 2
0.5
0.5
0.05
0.5
0.2
0.01 3
0.5
0.5
0.05 2
0.5
, O.I2
0.5
U.S. Tolerance
(ppnO
0.05
None established ' .
1.0
None established .
None established
0.1 (hog fat),
0.2 (hog liver and mbyp),
0.3(hogmbyp)
0.03 (for milk)
0.3 (for milk, fat) ,
None established
None established
0.05
2.0 (for pears) .
0.3 ppm (proposed for the meat and mbyp of sheep)
None established
1. t All amitraz MRLs are final (CXL) except for tomato which is at Step 8.
2. The MRL accommodates veterinary uses.
3. At or about the limit of detection.
3.
Reference Dose
The reference Dose (RfD) for amitraz was determined to be 0.0025 mg/kg/day, based
on a NOEL of 0.25 mg/kg/day from the chronic oral toxicity study in dogs
(MRID 00044586). An uncertainty factor of 100 (a factor of 10 each for interspecies
extrapolation and intraspecies variance) was used. The critical effects were increased blood
glucose concentration, hypothermia and CNS depression. An ADI for amitraz was
established by WHO (1990) at 0.003 mg/kg/day, based on the same chronic dog study and
using the same uncertainty factor.
4. Risk Mitigation Measures
The following risk mitigation measures for post-application workers combined with
generic worker protection labeling, should mitigate the unacceptable neurotoxicity and cancer
risks to workers exposed to amitraz residues after application is complete:
55
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for the pear use: 1) Minimum of 35 days between applications, and
2) Restricted-entry interval of 28 days
for the cotton use: 1) Mechanical harvesting, and
2) Restricted-entry interval cf 48 hours .
The following risk mitigation measures for handlers, combined with generic worker
protection labeling, should mitigate the unacceptable neurotoxicity risks to handlers:
for the pear use: 1)
2)
3)
for the cotton use: 1)
2)
3)
Closed system mixing/loading (e.g, water soluble
packaging)
Application from within an enclosed cab, and
Minimal (baseline) personal protective equipment (PPE)
Closed system mixing/loading (e.g., water soluble
packaging)
Mechanical flagging, and
Minimal (baseline) PPE
for the livestock
spray/dip use:
1) Minimal (baseline) PPE
The following risk mitigation measures are being required to reduce exposure to avjan
species and small mammals:
for the pear use:
1) Deletion of pre-bloom use
2) Limit use to two applications
5. Endangered Species
The Agency has concerns about the exposure of threatened and endangered animal
species to amitraz. Based on the conclusions discussed in the preceding sections of this risk
assessment, amitraz and its two primary degradates may pose an acute risk to nontarget avian
and mammalian species. While the United States Fish and Wildlife Service (USFWS) has
developed a biological opinion for pesticide use on cotton (10/12/83), amitraz was not one of
the pesticides considered in this consultation. Therefore, this information is of limited use to
the Agency with respect to amitraz's exceedance of endangered species criteria for "may
affect." To date, consultation with the USFWS concerning pesticide use on pear orchards has
not been pursued.
Currently, the Agency is developing a program ("The Endangered Species Protection
Program") to identify all pesticides whose use may cause adverse impacts on endangered and
threatened species and to implement mitigation measures that will eliminate the adverse
impacts. The program would require modifications or a generic product label statement,
56
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requiring users to consult county-specific bulletins. These bulletins would provide
information about specific use restrictions to protect endangered and threatened species in the
county. Consultations with the Fish and Wildlife Service will be necessary to assess risks to
newly listed species or from proposed new uses.
Because the Agency is taking this approach for protecting endangered and threatened
species, it is not imposing label modifications at this time through the RED. Rather, any
requirements for product use modifications will occur in the future under the Endangered
Species Protection Program.
6. Labeling Rationale and Requirements
Compliance with the Worker Protection Standard
tany
on
In order to remain in compliance with FIFRA, it is the Agency's position that any
product whose labeling reasonably permits use in the production of an agricultural plant w
any agricultural establishment (farm, forest, nursery, or greenhouse) must comply with the
labeling requirements of the Agency's labeling regulations for worker
(40 CFR part 156, subpart K).
protection statements
These labeling revisions are necessary to implement the 1992 Worker Protection
Standard (WPS) for Agricultural Pesticides (40 CFR Part 170) and must be completed in
accordance with the deadlines specified in the WPS, unless official the Agency guidance
specifies otherwise. The Agency has issued PR Notice 93-7, "Labeling Revisions Required
by the Worker Protection Standard, and PR Notice 93-11, "Supplemental Guidance for
PR Notice 93-7," which contain specific instructions to registrants about how to complete the
required WPS labeling changes and offer guidance and deadline-options for making those
changes. Unless otherwise specifically directed in this RED, all statements required by the
WPS (and reflected in PR Notices 93-7 and 93-11) are to be on the product labeling.
In order to remain in compliance with FIFRA, after April 21, 1994,.except as
otherwise provided in PR Notices 93-7 and 93-11, or other Agency, guidance,
all products within the scope of those notices must bear WPS PR-Notice-
complying labeling when they are distributed or sold by the registrant or any
supplementally registered distributor, or any repackager under the Agency's
Bulk Repackaging Policy.
In order to remain in compliance with FIFRA, after October 23,1995, except
as otherwise provided in PR Notices 93-7 and 93-11 orother Agency guidance,
all products within the scope of those notices must bear WPS PR-Notice-
complying labeling when they are distributed or sold by any person,
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Uses Within the Scope of the Worker Protection Standard .
The 1992 Worker Protection Standard for Agricultural Pesticides (WPS) established
certain worker-protection requirements (personal protective equipment, restricted entry
intervals, etc.) to be specified on the label of all products that contain uses within the scope of
the WPS. Uses within the scope of the WPS include all commercial (non-homeowner) and
research uses on farms, forests, nurseries, and greenhouses to produce agricultural plants
(including food, feed, and fiber plants, trees, turf grass, flowers, shrubs, ornamentals, and
seedlings). Uses within scope include not only uses on plants, but also uses on the soil or
planting medium the plants are (or will be) grown in.
Some of the registered uses of amitraz are within the scope of the Worker Protection
Standard for Agricultural Pesticides (WPS) and some uses are outside the scope of the WPS.
Those that are outside the scope of the WPS include use on livestock or other animals.
Personal Protective Equipment (PPE) and Engineering Controls for Handlers
(Mixer/Loader/Applicators)
Occupational-Use Products (WPS and NonWPS Uses)
For each end-use product, PPE requirements for pesticide handlers will be set during
reregistration in one of two ways:
1. If the Agency has no special concerns about the acute or other adverse effects
of an active ingredient, the PPE for pesticide handlers will be based on the
acute toxicity of the end-use product. For occupational-use products, PPE will
be established using the process described in PR Notice 93-7 or more recent
Agency guidelines.
2. If the Agency has special concerns about an active ingredient due to very high
acute toxicity or to certain other adverse effects, such as allergic effects or
* delayed effects (cancer, developmental toxicity, reproductive effects, etc):
In the RED for that active ingredient, the Agency may establish
minimum or "baseline" handler PPE requirements that pertain to all or
most occupational end-use products containing that active ingredient. .
These minimum PPE requirements must be compared with the PPE that
would be designated on the basis of the acute toxieity of each end-use
product .
58
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The more stringent choice for each type of PPE (i.e., body wear, hand
protection, footwear, eyewear, etc.) must be placed on the label of the
end-use product
There are special toxicological concerns about some uses of amitraz,that warrant the
establishment of active,-ingredient-based minimum PPE and engineering control requirements
for handlers. Amitraz is classified as a Group C carcinogen and has low Margins of Exposure
for handlers based on acute neurotoxic effects. Therefore, active-ingredient-based minimum
PPE requirements will be established for the following handlers.
Handlers associated with amitraz applications to pears,
Handlers associated with amitraz applications to cotton who are exposed to amitraz in
concentrated form (such as for spill clean-up if the closed-system fails),
Handlers associated with amitraz applications to cotton who are exposed to amitraz in
diluted form (such as repairing, cleaning, or adjusting application equipments)
Occupational handlers associated with placing amitraz-impregnated collars on
livestock
Handlers associated with amitraz spray or dip applications to livestock.
Handler PPE for Homeowner-Use Products: One product containing amitraz (impregnated
collars for dogs) is intended primarily for homeowner use. No minimum (baseline) PPE is
being established on this product, since the expected exposure to homeowners placing an
amitraz-impregnated collar on a dog is expected to result in negligible exposure.
ป .
Post-Application/Entry Restrictions
Occupational-Use Products (WPS Uses)
Entry Restrictions for Occupational-Use Products (WPS Uses)
Restricted Entry Interval: Under the Worker Protection Standard (WPS), interim restricted
entry intervals (REI) for all uses within the scope of the WPS are based on the acute toxicity
of the active ingredient. The toxicity categories of the active ingredient for acute dermal
toxicity, eye irritation potential, and skin irritation potential are used to determine the interim
WPS REI. If one or more of the three acute toxicity effects are in toxicity category I, the
interim WPS REI is established at 48 hours. If none of the acute toxicity effects are in
category I, but one or more of the three is classified as category n, the interim WPS REI is
established at 24 hours. If none of the three acute toxicity effects are in category I or n, the
interim WPS REI is established at 12 hours. A 48-hour REI is increased to 72 hours when an
59
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organoph; -ปhate pesticide is applied outdoors in arid areas. In addition, the WPS specifically
retains two types of REI's established by the Agency prior to the promulgation of the WPS:
(1) product-specific REI's established on the basis of adequate data, and (2) interim REI's that
are longer than those ;.at would be established under the WPS.
For occupational end-use products containing amitraz as an active ingredient, the
Agency is establishing a 28-day restricted-entry interval for each use of the product on pears
and a 48-hour restricted-entry interval for each use of the product on cotton. The basis for
this recommendation is that amitraz is categorized as a "Group C" possible human carcinogen
ajid the Agency is concerned about acute neurotoxicity.
The WPS places very specific restrictions on entry during restricted-entry intervals
when that entry involves contact with treated surfaces. The Agency believes that these
existing WPS protections are sufficient to mitigate post-application exposures of workers who
contact surfaces treated with amitraz.
The WPS REI in effect until now was 24 hours. The Agency found no reason to retain
the 24-hour interim REI placed on amitraz products by PR Notice 93-7. The 24-hour interim
WPS REI was established because amitraz is in toxicity category n for acute dermal toxicity,
but did not take into account the acute neurotoxicity concerns or amitraz's classification as a'
Category C carcinogen. .
Early-Entry PPE: The WPS establishes very specific restrictions on entry by workers to
areas that remain under a restricted-entry interval if the entry involves contact with treated
surfaces. Among those restrictions are a prohibition of routine entry to perform hand labor
tasks and requirement that personal protective equipment be worn. Personal protective
equipment requirements for persons who must enter areas that remain under a restricted-entry
interval are based on the toxicity concerns about the active ingredient. The requirements are
set in one of two ways.
1. If the Agency has no special concerns about the acute or other adverse effects of an
active ingredient, it establishes the early-entry PPE requirements based on the acute
dermal toxiciiy, skin irritation potential, and eye irritation potential of the active
ingredient. >
2. If the Agency has special concerns about an active ingredient due to very high acute
toxicity or to certain other adverse effects, such as allergic effects, cancer,
developmental toxicity, or reproductive effects, it may establish early-entry PPE
requirements that are more stringent than would be established otherwise.
There are special concerns about amitraz based on the toxicological endpoint for short-
term exposures, the carcinogenic concern for long-term exposures, and the low MOEs for
certain handlers. Therefore, for early entry following applications of amitraz, the Agency is
60
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establishing PPE for dermal protection that is more stringent than the PPE that would
otherwise be established based on the acute toxicity of the active ingredient. Since amitraz is
classified as category IV for eye irritation potential, protective eyewear is not required.
Entry Restrictions for Occupational-Use Products (Non WPS Uses)
The Agency is establishing no entry restrictions at this time for nonWPS occupational
uses of amitraz enct-use products. .
Entry Restrictions for Homeowner-Use Products
The Agency is establishing no entry restrictions at this time for amitraz end-use
products that are intended primarily for homeowner use.
Additional Labeling Requirements
i . -- . ,
The Agency is requiring labeling statements to be located on all end-use products
containing amitraz that are intended primarily for occupational use. For the specific labeling
statements, refer to Section V of this document.
V. ACTIONS REQUIRED BY REGISTRANTS
This section specifies the data requirements and responses necessary for the
reregistration of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of amitraz for the eligible uses has
been reviewed and determined to be substantially complete. However, the following
confirmatory studies listed below are needed:
Life-Cycle Aquatic Invertebrate (Guideline 72-4(b)) is required for the degradate
BTS-27271 for the pear use.
Concurrent Dislodgeable Foliar Residue (Guideline 132-l(a)) and Dermal Exposure
. (Guideline 133-3) data. ,
Batch equilibrium (Guideline 163-1) be conducted for BTS-27271 and BTS-27919.
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Droplet size spectrum (Guideline 201-1) and field drift (Guideline 202-1). The
registrant may elect to satisfy both data requirements through the Spray Drift Task
Force.
Dermal Exposure Data (Guideline 231) and Inhalation Exposure Data (Guideline 232)
to support the reregistration of amitraz spray/dip treatment of livestock.
An additional confirmatory study, not part of the target database for amitraz, is
required to support the continued registration of amitraz. This requirement is:
A combined developmental/neurological/reproduction toxicity study in rats. The
reason for requiring this confirmatory study is that both the developmental and
reproductive toxicity studies in rats were supplementary and neither could be
considered as a reliable assessment of the potential developmental or reproductive
toxicity for amitraz. Furthermore, there exists "...some evidence that amitraz was
associated with maternal/reproductive/ developmental toxicity at relatively low dose
levels," and the fact that neurotoxicity was observed in both rodents and non-rodents.
Prior to initiation, the registrant should consult with the Agency on the protocols for
this study.
2. Labeling Requirements for Manufacturing-Use Products
The Agency has determined that the current label precautions are still applicable and
are required for product reregistration. Refer to the October 1987 Amitraz Registration
Standard). Further, to remain in compliance with FIFRA, manufacturing use product (MP)
labeling must be revised to comply with all current Agency regulations, PR Notices and
applicable policies. The MP labeling must bear the following statement under Directions for
Use:
"Only for formulation into an
[fill blank with Insecticide,
Herbicide or the applicable term which describes the type of pesticide use(s)] for the
following use(s): . . [fill blank only with those uses
that are being supported by MP registrant]."
An MP registrant may, at his/her discretion, add one of the following statements to an
MP label under "Directions for Use" to permit the reformulation of the product for a specific
use or all additional uses supported by a formulator or user group:
(a) "This product may be used to formulate products for specific use(s) not listed
on the MP label if the formulator, user group, or grower has complied with
U.S. EPA submission requirements regarding the support of such use(s)."
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(b) "This product may b used to formulate products for any additional use(s) not
listed on the MP label if the formulator, user group, or grower has complied
with U.S. EPA submission requirements regarding the support of such use(s)."
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-
specific data regarding the pesticide after a determination of eligibility has been made The
product specific data requirements are listed in Attachment 3 of Appendix D in the Combined
Generic and Product Specific Data Call-In Notice. ' ;
Registrants must review previous data submissions to ensure that they meet current
EPA acceptance criteria and if not, commit to conduct new studies. If a registrant believes
that previously submitted data meet current testing standards, then study MRTO numbers
should be cited according to the instructions in the Requirement Status and Registrants
Response Form provided for each product.
2. Labeling Requirements for End-Use Products
The labels and labeling of all products must comply with EPA's current regulations
and requirements as specified in 40 CFR ง156.10.
a. Occupational/Residential Labeling
Personal Protective Equipment Requirements for Pesticide Handlers (Mixers. Loaders.
Applicators. Etc) s
Sole-active-ingredient end-use products that contain amitraz must be revised to adopt
the handler personal protective equipment requirements set forth in this section. Any
conflicting PPE requirements on their current labeling must be removed.
Multiple-active-ingredient end-use products that contain amitraz must compare the
handler personal protective equipment requirements set forth in this section to the PPE
requirements on their current labeling and retain the more protective. For guidance on which
PPE is considered more protective, see PR Notice 93-7.
Handler PPE for Occupational-Use Products (products NOT intended primarily for
home use ~. (see text in PR Notice 93-7 and 93-11):
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Minimum (Baseline) Personal Protective Equipment Requirements: The minimum
(baseline) BPE requirements are:
For Pear Uses:
Applicators and other handlers must wear:
coveralls over long-sleeve shirt and long pants,
chemical-resistant footwear plus socks,
chemical-resistant gloves*, -
chemical-resistant headgear for overhead exposure,
chemical-resistant apron when cleaning equipment, mixing, or loading
For Cotton Uses:
Mixers, loaders, and others exposed to the concentrate must wear:
coveralls over long-sleeve shirt and long pants,
chemical-resistant footwear plus socks,
chemical-resistant gloves*,
chemical-resistant headgear for overhead exposure,
chemical-resistant apron
Applicators and other handlers exposed to the dilute must wear:
long-sleeve shirt and long pants
chemical-resistant gloves*
shoes plus socks .
For Livestock Spray or Dip Uses:
Applicators and other handlers must wear:
coveralls over long-sleeve shirt and long pants,
chemical-resistant footwear plus socks,
chemical-resistant gloves*,
chemical-resistant headgear for overhead exposure,
chemical-resistant apron when cleaning equipment, mixing, or loading**
For Livestock Impregnated Collar Uses:
Applicators and other handlers must wear:
long-sleeve shirt and long pants . .
chemical-resjstant gloves*
shoes plus socks
* The glove statement for amitraz is the statement established through the instructions in Supplement Three of PR Notice 93-7.
** The words, "mixing, or loading" may be removed if the product is formulated as "ready-to-use."
64
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Actual End-Use Product Personal Protective Equipment Requirements; The PPE that
would otherwise be established based on the acute toxiciry of each end-use product must be
compared to the minimum (baseline) personal protective equipment, if any, specified above.
The more protective PPE must be placed on the product labeling. For guidance on which PPE
is considered more protective, see PR Notice 93-7.
Placement in Labeling; The personal protective equipment must be placed on the end-use
product labeling in the location specified in PR Notice 93-7 and the format.and language of
the PPE requirements must be the same as is specified in PR Notice 93-7.
Products Intended Primarily For Homeowner Use
Personal Protective Equipment Requirements for Homeowners; The Agency is not
establishing minimum (baseline) handler PPE for amitraz end-use products that are intended
primarily for homeowner use. Personal protective equipment, if appropriate, will be
established based on the acute toxicity of the end-use product.
Placement in Labeling; The personal protective equipment requirements, if any, must be
placed on the end-use product labeling immediately following the precautionary statements in
, the labeling section "Hazards to Humans (and domestic animals)."
Entry Restrictions; Labeling
Sole-active-ingredient end-use products that contain amitraz must be revised to adopt
the entry restrictions set forth in this section. Any conflicting entry restrictions on their
current labeling must be removed.
Multiple-active-ingredient end-use products that contain amitraz must compare the
entry restrictions set forth in this section to the entry restrictions on their current labeling and
retain the more protective. A specific time-period in hours or days is considered more
protective than "sprays have dried" or "dusts have settled."
'Occupational-Use Products (Products NQT Intended Primarily For Home Use):
Uses Within the Scope of the WPS:
Restricted-Entry Interval; A restricted entry interval (REI) is specified for uses within the
scope of the WPS (see PR Notice 93-7) on all end-use products (see tests in PR Notices 93-7
and 93-11). This REI must be inserted onto the revised labeling as required by Supplement
Three of PR Notice 93-7.
For Pear Uses: The restricted-entry interval is 28 days.
65
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For Cotton Uses: The restricted-entry interval requirement must state:
"Do not enter or allow workers entry into the treated area during the restricted-entry interval
of 48 hours. Note: mechanical harvesting may be performed during the restricted-entry
interval ONLY if the harvesters will have no dermal or inhalation contact with treated
surfaces, including both the treated foliage and the residues in airborne dusts generated by the
mechanical harvesting." Crop advisor may enter if they are wearing full early entry Personal
Protective Equipment (PPE) described below.
Early-Entry Personal Protective Equipment (PPE);
For Pear and Cotton Uses:
The PPE required for early entry is:
coveralls over long-sleeve shirt and long pants,
chemical-resistant gloves,
chemical-resistant footwear plus socks,
chemical-resistant headgear for overhead exposures.
Placement in Labeling; The REI must be inserted into the standardized REI statement
required by Supplement Three of PR Notice 93-7. The PPE required for early entry must be
inserted into the standardized early entry PPE statement required by Supplement Three of
PR Notice 93-7.
Uses Not Within the Scope of the WPS:
No entry restrictions are being established for nonWPS uses.
Products Primarily Intended for Home Use:
No entry restrictions are being established for products intended primarily for home
use.
b. Other Labeling Requirements
The Agency is requiring the following labeling statements to be located on all end-use
products containing amitraz that are intended primarily for occupational use:
66
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Application Restrictions .
"Do not apply this product in a way that will contact workers or other persons, either
directly or through drift. Only protected handlers may be in the area during
application."
"For livestock spray or dip applications in enclosed areas: Apply only in well-
ventilated areas." ......
"For pear applications, allow a minimum of 35 days between applications."
"Do not rotate to root and leafy vegetables for 44 days or to small grains and other
crops for 60 days following application."
Engineering Controls
"When handlers use closed systems, enclosed cabs, or aircraft in a manner that meets
the requirements listed in the Worker Protection Standard (WPS) for agricultural
pesticides (40 CFR 170,240(d)(4-6), the handler PPE requirements may be reduced or
modified as specified in the WPS."
"No human flaggers allowed. Mechanical flaggers are required,"
"Cotton must be harvested mechanically. No hand harvesting is allowed."
"For pear uses, this product must be mixed and loaded using a closed system (water-
soluble bags are considered a closed mixing/loading system) and the applicator must
be inside an enclosed cab during application. The closed mixing/loading system and
enclosed cab must meet the requirements listed in the Worker Protection Standard
(WPS) for agricultural pesticides [40 CFR 170.240(d)(4-5)]. When these engineering
controls are used correctly, the handler PPE requirements may be reduced or modified.
as specified in the WPS."
"For cotton uses, this product must be mixed and loaded using a closed system (water-
soluble bags are considered a closed mixing/loading system). The closed
mixing/loading system must meet the requirements listed in the Worker Protection
Standard (WPS) for agricultural pesticides [40 CFR 170.240(d)(4-5)]. When these
engineering controls are used correctly, the handler PPE requirements may be reduced
or modified as specified in the WPS."
67
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User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such
instructions exist for washables, use detergent and hot water. Keep and wash
PPE separately from other laundry."
User Safety Recommendations
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or
using the toilet."
"Users should remove clothing immediately if pesticide gets inside. Then wash
thoroughly and put on clean clothing."
"Users should remove PPE immediately after handling this product. Wash the outside
of gloves before removing. As soon as possible, wash thoroughly and change into
clean clothing."
Notification Requirement for WPS Uses
"Notify workers of the application by warning them orally and by posting warning
signs at entrances to treated areas." _
Labeling for Fish and Wildlife Hazard
.In order to remain in compliance with FIFRA, labels must bear the following in the
Precautionary Statements section under the subheading Environmental Hazards:
End Use - Emulsiflable Concentrate and Wettable Powder Formulations
"This pesticide is toxic to fish and aquatic invertebrates. Do not apply directly to
water, or to areas where surface water is present or to intertidal areas below the mean
water mark. Drift and runoff from treated areas may be hazardous to aquatic
organisms in adjacent sites. Do not contaminate water when disposing of equipment
washwaters orrinsate."
68
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MTTACWP label
Additionally, for the MIT AC WP label, revise the Directions for use to control pear
psylla statement to include the following restrictions:
% - - , ' .
PEAR PSYLLA: Apply a maximum of 1 1/2 pounds of amitraz per acre.
Do not exceed 3 Ibs of amitraz per acre per season. Do not make more than two
applications of amitraz per season. .
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for
26 months from the date of the issuance of this Reregistration Eligibility Decision (RED).
Persons other than the registrant may generally distribute or sell such products for 50 months
from the date of the issuance of this RED. However, existing stocks time frames will be
established case-by-case, depending on the number of products involved, the number of label
changes, and other factors. Refer to "Existing Stocks of Pesticide Products; Statement of
Policy"; Federal Register. Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell amitraz products
bearing old labels/labeling, i.e., labels absent the modifications specified in this RED
document, except as noted below, for 26 months from the date of issuance of this RED.
Persons other than the registrant may distribute or sell such products for 50 months from the
date of the issuance of this RED document. Registrants and persons other than registrants
remain obligated to meet pre-existing Agency imposed label changes and existing stocks
requirements applicable to products they sell or distribute. .
69
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VI. APPENDICES
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for
active ingredients within the Case 0234 covered by this Reregistration Eligibility Decision
Document. It contains generic data requirements that apply to 0234 in all products, including
data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column IV The data reqmrp>tnp.ntg are nc+ปd ;ป fr0 orjer in
which they appear in 40 CFR Part 158. the reference numbers accompanying each test refer
to the test protocols set in the Pesticide Assessment Guidelines, which are available from the
National Technical Information Service, 5285 Port Royal Road, Springfield VA 22161 (703)
487-4650.
2. Use Pattern (Column 2): This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food .
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3.. Bibliographic citation (Column 3) If the Agency has acceptable data in its files,
this column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
77
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GUIDE TO APPENDIX G
CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies in
this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources
including the published literature, in those instances where they have been considered,
are included.
UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the
case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a
distinct title (or at least a single subject), can stand alone for purposes of review and
can be described with a conventional bibliographic citation. The Agency has also
attempted to unite basic documents and commentaries upon them, treating them as a
single study.
IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID number". This number is unique
to the citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify volumes
of submitted studies (see paragraph 4(d)(4) below for further explanation). In a few
cases, entries added to the bibliography late in the review may be preceded by a nine
character temporary identifier. These entries are listed after all MRID entries. This
temporary identifying number is also to be used whenever specific reference is needed.
FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown an identifiable laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the
first submitter as the author. ,
b. Document date. The date of the study is taken directiy from the document.
When the date is followed by a question mark, the bibliographer has deduced
the date from the evidence contained in the document. When the date appears
.as (19??), the Agency was unable to determine or estimate the date of the
document.
87
-------
Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
Trailing parentheses. For studies submitted to the Agency in the past, the
trailing parentheses include (in addition to any self-explanatory text) the
following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the
word "under" is the registration number, experimental use permit
number, petition number, or other administrative number associated
with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is
defaulted to the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the
trailing parentheses identifies the EPA accession number of the volume
in which the original submission of the study appears. The six-digit
accession number.follows the symbol "CDL," which stands for
"Company Data Library." This accession number is in turn followed by
an alphabetic suffix which shows the relative position of the study
within the volume.
-------
BIBLIOGRAPHY
MRID
CITATION
00028664 Lewis, D.K. (1970) RD 27 419, Plant Biochemistry Report No. 1:FM70 158.
(Unpublished study received Apr 9, 1980 under 43142-EX1; submitted by
Boots Hercules Agrochemicals Co., Wilmington, Del.; CDL:099371-A)
00028666 Somerville, L.; Spiers, MJ. (19??) BTS 27 419: Metabolism in Apple Leaves:
, AX 72 002. (Unpublished study received Apr 9, 1980 under 43142-EX-l;
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099371-C)
00028712 Sutton, M.M.; Williams, GA.H. (1973) BTS 27 419: 90-Day Toxicity Study in
Rats: P. 71548; C44. (Unpublished study received Apr 9,1980 under
43142-EX-l; submitted by Boots Hercules Agrochemicals Co., Wilmington,
Del.; CDL:099365-A) '..,
00028715 Shaw, J.W.; Williams, GA.H. (1972?) BTS 27 419: 90-Day Chronic Toxicity
Study in Mice: TX 74 016; C47. (Unpublished study received Apr 9, 1980 .
under 43142-EX-l; submitted by Boots Hercules Agrochemicals Co.,
Wilmington, Del.; CDL:099365-D)
00028716 Patton, D.S.G.; Williams, G.AH. (19??) BTS 27 419: 90-Day Toxicity Study
in Dogs: P71547; C48. (Unpublished study received Apr 9, 1980 under
43142-EX-l; submitted by Boots Hercules Agrochemicals Co., Wilmington,
Del.; CDL:099365-E),
00029959 Sutton, M.M. (19??) BTS 27 419: Teratogenicity in the Rat: Report No, TX
73028. (Unpublished study received Apr 9, 1980 under 43142-EX-l;
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099368-I)
00029960 Sutton, M.M. (19??) BTS 27 419: Effect on Pregnancy, Parturition and Care of
the Young in Rats: Report No. TX 73031. (Unpublished study received Apr 9,
1980 under 43142-EX-l; submitted by Boots Hercules Agrochemicals Co.,
Wilmington, Del.; CDL: 099368-J)
00029961 Sutton; M.M. (19??) BTS 27 419: Teratogenicity in the Rabbit: Report No. TX
73029. (Unpublished study received Apr 9, 1980 under 43142-EX-l;
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099368-K)
00029962 Sutton, M.M. (19??) BTS 27 419: Multigeneration Feeding Test in Rats:
Report No. TX 73036. (Unpublished study received Apr 9, 1980 under
43142-EX-l; submitted by Boots Hercules Agrochemicals Co., Wilmington,
Del.; CDL:099368-L)
89
-------
MRID
BIBLIOGRAPHY
CITATION
00029963 Berczy, Z.S.; Binns, R.; Newman, AJ. (1972) Acute Inhalation Toxieity to the
Rat of BTS 27419: Report No. 4971/72/406. (Unpublished study received Apr
9, 1980 under 43142-EX-l; prepared by Huntingdon Research Centre,
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099368-M) .
00029965 Sutton, M.M. (1971) BTS 27 419: Contact Sensitisation sic in the Guinea Pig
(Unpublished study received Apr 9, 1980 under 43142-EX-l; submitted by
Boots Hercules Agrochemieals Co., Wilmington, Del.; CDL:099368-O)
00029972 Sutton, M.M. (1977) BTS 27 419: Three Week Dermal Toxieity to Rabbits:
Report No. TX 73026. (Unpublished study received Apr 9,1980 under
43142-EX-l; submitted by Boots Hercules Agrochemicals Co., Wilmington,
Del.; CDL:099368-V)
00030051 Boots Hercules Agrochemicals Company (19??) Chemical Information on
'Amitraz. (Unpublished study received Apr 9, 1980 under 43142-EX-l;
CDL:099362-A)
^ , .
00030444 Nissan Chemical Industries, Limited (1972) JA-119 (BTS-27419): Test on Fish
Toxieity. (Unpublished study received Apr 9, 1980 under 43142-EX-l;
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099369-B)
00030445 Fraser, W.D.; Jenkins, G. (1972) The Acute Toxicities of BTS 27419 (Tech)
and BTS 27419 (20% E/C) to Rainbow Trout under Continuous Flow
Conditions: 4880/72/315. (Unpublished study received Apr 9, 1980 under
43142-EX-l; prepared by Huntingdon Research Centre, submitted by Boots
Hercules Agrochemicals Co., Wilmington, Del.; CDL:099369-D)
00030446 Bentley, R.E. (1975) Acute Toxieity of Technical Amitraz to Rainbow Trout'
(Salmo gairdneri). (Unpublished study received Apr 9,1980 under
43142-EX-l; prepared by Bionomics, EG&G, submitted by Boots Hercules
Agrochemicals Co., Wilmington, Del.; CDL: 099369-E)
00030447 Fraser, W.D.; Jenkins, G. (1973) The Acute Toxicities of Technical and
Formulated BTS 27419 to Blue Gill (Lepomis macrochirus): BTS/73116.
(Appendix 4; unpublished study received Apr 9, 1980 under 43141 EX-1;
prepared by Huntingdon Research Centre, submitted by Boots He; ,,ules
Agrochemicals Co., Wilmington, Del.; CDL:099369-F)
90
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BIBLIOGRAPHY
MRID
CITATION
00030448 Fraser, W.D.; Jenkins, G. (1973) The Acute Toxicities of Technical and
Formulated BTS 27419 to Harlequin Fish (Rasbora heteromorpha) under
Continuous Flow Conditions: BTS/73117. (Appendix 5; unpublished study
received Apr 9, 1980 under 43142EX-1; prepared by Huntingdon Research
Centre, submitted by Boots Hercules Agrochemicals Co., Wilmington, Del.;
CDL:099369-G) .
00030450 Bentley, R.E..(1973) Acute Toxicity of BTS-27419 Technical to Grass Shrimp
(Palaeomonetes vulgaris) and Fiddler Crab (Uca pugilator). (Appendix 7;
unpublished study received Apr 9, 1980 under 43142-EX-l; prepared by
Bionomics, Inc., submitted by Boots Hercules Agrochemicals Co., Wilmington,
' Del.; CDL: 099369-1) '
00030451 Fink, R. (1976) Final Report: Acute Oral LD50~Bobwhite Quail: Project No.
137-105. (Unpublished study including unofficial analytical report, received
Apr 9, 1980 under 43142-EX-1; prepared by Truslow Farms, Inc., submitted by
Boots Hercules Agrochemicals Co., Wilmington, Del.; CDL:099369-J)
00030452 Ross, D.B.; Roberts, N.L. (1973) The Acute Toxicity (LC50) of BTS 27 419 to
Mallard Duck: BTS/73497: (Appendix 9; unpublished study received Apr 9,
1980 under 43142-EX-l; prepared by Huntingdon Research Centre, submitted
by Boots Hercules Agrochemicals Co., Wilmington, Del.; CDL:099369-K)
00030453 Ross, D.B.; Roberts, N.L. (1973) The Acute Toxicity (LC50) of BTS 27 419 to
Japanese Quail: BTS/73498. (Appendix 8; unpublished study received Apr 9,
1980 under 43142-EX-l; prepared by Huntingdon Research Centre, submitted
.by Boots Hercules Agrochemicals Co., Wilmington, Del.; CDL:099369-L)
00030455 Palmer-Jones, T.; Clinch, P.O. (1973) Effect on honey bees of BTS 27419
applied as a spray to apple trees. New Zealand Journal of Experimental
Agriculture 1(? ):195-196. (Also~In~unpublished submission received Apr 9,
' 1980 under 43142-EX-l; submitted by Boots Hercules Agrochemicals Co.,
Wilmington, Del.; CDL: 099369-N)
00040323 Merryman, D.C.; Sutton, M.M. (1972) BTS 27 419 Effects on the Oestrus
Cycle of the Rat: PM72003. (Unpublished study received Oct 7, 1974 under
5G1558; submitted by Upjohn Co., Kalamazoo, Mich.; CDL:094252-R)
00040324 Lewis, O.K. (1970) Anticholinesterase Activity of RD 27,419, a Promising
Acaricide, and Some Derivatives. (Unpublished study received Oct 7, 1974
under 5G1558; prepared by Boots Pure Drug Co., Ltd., submitted by Upjohn
Co., Kalamazoo, Mich.; CDL: 094252-S)
91
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BIBLIOGRAPHY
MRID
CITATION
00040345
00040861
00040862
00041513
00041539
00044585
00044586
00044591
00046029
Patton, D.S.G.; Williams, G.A.H, (1973) BTS 27 419: 90-Day Toxicity Study
in Dogs: P 71547. (Unpublished study received Oct 7, 1974 under 5G1558;
submitted by Upjohn Co., Kalamazoo, Mich.; CDL: 094252-AN)
Sutton, M.M.; Metcalf, W. (1972) BTS 27 419. Eye Irritancy in the Rabbit:
TXM72037. (Unpublished study received Oct 7,1974 under 5G1558;
submitted by Upjohn Co., Kalamazoo, Mich.; CDL:094254-H)
Sutton, M.M.; Williams, P.A. (1972) BTS 27 419: Acute Dermal Toxicity to
Rabbits: YM72011. (Unpublished study received Oct 7,1974 under 5G1558;
submitted by Upjohn Co., Kalamazoo, Mich.; CDL.-094254-I)
*
Clegg, D.E. (1973) Residues of BTS27,419 in Animal Tissues. (Unpublished
study received Jun 24, 1976 under 6F1817; submitted by Upjohn Co.,
Kalamazoo, Mich.; CDL:096423-AH)
Shaw, J.W. (1973) BTS 27 419: Acute Oral Toxicity to Male and Female Rats:
TXM 73041. (Unpublished study received Jun 24, 1976 under 6F1817;
submitted by Upjohn Co., Kalamazoo, Mich.; CDL: 096419-AE)
Sutton, M.M.; Offer, J. (1973) BTS 27 419: Carcinpgenicity and Long-Term
Toxicity Study in Rats: Report TX 73043. (Unpublished study received Jun
24,1976 under 6F1817; submitted by Upj ohn Co., Kalamazoo, Mich "
CDL:096417-A)
Morgan, H.E.; Patton, D.S.G.; Turnbull, GJ. (19??) BTS 27 419: Two-Year
Oral Toxicity Study in Dogs: TX 73035. (Unpublished study received Jun 24,
1976 under 6F1817; submitted by Upjohn Co., Kalamazoo, Mich.;
CDL:096415-A)
Kakuk, T.J.; Weddon, T.E,. (1976) U-36059: Safety Evaluation of Baam 1.5 EC
in Dogs following a Single Topical Exposure: 527-9610-TJK-76-1.
(Unpublished study received Jun 24, 1976 under 6F1817; submitted by Upjohn
Co., Kalamazoo, Mich.; CDL: 096415-K)
Joos, J.L.; Sigetko, J.; Lee, B.L.; et al. (1980) Baam WP Insecticide for Pears.
(Compilation; unpublished study received Jul 25,1980 under 1023-61;
submitted by Upjohn Co., Kalamazoo, Mich.; CDL:242996-C)
92
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BIBLIOGRAPHY
MRID
CITATION
00051930
00046030 Nappier, J.L.; Honiish, R.E.; Lane, R.E. (1976) Total Residue Method for
U-36,0591,5-Di-(2,4-dimethylphehyl)-3-methyl-l53,5triazapenta-l,4-dienein
Oranges: Report No. 315-9760-70. Metihod dated Mar 24, 1976. (Unpublished
study received Jul 25,1980 under 1023-61; submitted by Upjohn Co.,
Kalamazoo, Mich.; CDL:242996-D) .
00051717 Holifield, EX.; Bowers, R.C.; Lee, B.L.; et al. (1975) Residue Data for Baam
on Pears. (Unpublished study received Jun 24, 1976 under 6F1817; submitted
by Upjohn Co., Kalamazoo, Mich.; CDL:096422-E)
00051929 Nappier, J.L.; Hornish, R.E. (1975) Total Residue Method for U3 6,059...in
Apples, Pears and Soils: Report No. 315-9760-32. Method dated Sep 26,1975.
(Unpublished study received Dec 18, 1975 under 1023-EX-34; submitted by
Upjohn Co., Kalamazoo, Mich.; CDL:094993-D)
Upjohn Company (1975) Comparison of the Analytical Residue Procedures for
U-36,059 and U-40,481 (Used in 1973 and 1974) with the Degradative
Procedure (Used in 1975). (Unpublished study received Dec 18, 1975 under ,
1023-EX-34; submitted by Upjohn Co., Kalamazoo, Mich.; CDL:094993-E) .
Bender, E.; Asquith, D. (1972) Toxicity Studies on Beetles. (Unpublished
study received Jun 24, 1976 under 6F1817; prepared by American Cyanamid
Co. in cooperation with Pennsylvania State Univ., Fruit Research Laboratory,
submitted by Upjohn Co., Kalamazoo, Mich.; CDL:096412-G)
00055718 Somerville, L.; Nicholson, J.E. (1977) BTS 27 419-Metabolism in Apples,
Variety Cox's Orange Pippin. (Unpublished study received Oct 7,1974 under
5G1558; submitted by Upjohn Co., Kalamazoo, Mich.; CDL:094250-C)
00072411 Fink, R.; Beavers, J.B. (1980) Final Report: One-generation Reproduction
Study-Mallard Duck: Project No. 137-113. (Unpublished study received Apr
9, 1981 under 43142-EX-l; prepared by Wildlife International, Ltd., submitted
by Boots Hercules Agrochemicals Co., Wilmington, Del.; CDL:244830-A)
00072412 Fink, R.; Beavers, J.B. (1980) Final Report: One-generation Reproduction
' StudyBobwhite Quail: Project No. 137-112. (Unpublished study received
Apr 9,,1981 under 43142-EX-l; prepared by Wildlife International, Ltd.,
submitted by Boots Hercules Agrochemicals Co., Wilmington, Del
CDL:244831-A)
00052490
93
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BIBLIOGRAPHY
MRID
CITATION
00072503
00074486
00114299
00111886
00139552
40590601
40590801
40650701
Barrows, M.E.; Mastone, J.D. (1980) Accumulation and Elimination of
14C-Residues by Bluegill Sunfish (Lepomis macrochirus) Exposed to
14C-Labelled Amitraz (Ref. No. EG2001): Report #BW-80-10-760.
(Unpublished study received May 1, 1981 under 43142-45; prepared by EG &
G, Bionomics, submitted by Boots Hercules Agro- Chemicals Col, Wilmington
Del.; CDL:244967-A)
Atkins, E.L.; Kellum, D. (1980) Effects of Pesticides on Appiculture:
Maximizing the Effectiveness of Honey Bees as Pollinators: Project No. 1499.
1980 annual rept. (Unpublisheed study received June 8, 1981 under 241-259;
prepared by University of CaliforniaRiverside, Citrus Research Center and
Agricultural Experiment Station, Dept. of Entomology, submitted by American
Cyanamid Co., Princeton, N.J.; CDL:07014'?-G).
Leake, C.; Sommerville, L.; Lines, D.; et. al. (1982) The Leaching of Amitraz
in Four Soil types Using Soil T.L.C.: METAB/(Unpublished study received
September 8,1982 under 45639- , prepared by FBC, Ltd., England, submitted
by BFC Chemical Inc.,. Wilmington, DE; CDL: 248318-B).
Barnett, R.; Crowley, J.; Lessel, B.; et al. (1976) BTS 27 419: 80-week
Carcinogenicity Study in Mice: Report No. 76059. Final rept. (Unpublished
study received Jun 24, 1976 under 6F1817; prepared by Boots Co., Ltd.,
submitted by Upjohn Co., Kalamazoo, MI; CDL.-096416-A)
Colley, J.; Dawe, S.; Heywood, R.; el d. (1983) Amitraz: 104 Week
Tumorigenicity Study in Mice: HRC import No. BTS 153/8262/A; T233. Final
rept. (Unpublished study received Jan 5, 1984 under 1023-59; prepared by
FBC, Ltd., Eng., submitted by Upjohn Co., Kalamazoo, MI; CDL:252098-A;
252099; 252100; 252101; 252102)
Smith, S.; Campbell, J. (1988) M73 Metabolism of Carbon 14 Amitraz in
Lemons: Laboratory Project ID ENVTR/87/44. Unpublished study prepared by
Sobering Agrochemicals Limited. 64 p.
Fortsch, A. (1988) M77 Amitraz: The Fate of Amitraz in Cotton: Late Season
Application: Laboratory Project ID UPSR 5/88. Unpublished study prepared by
Sobering AG. 76 p.
Johnson, M. (1987) Amitraz Manufacturing Process and Discussion,of . '
Formation of Impurities; Description of Beginning Materials: Project ID: AD
49/87; AD 51/87. Unpublished study prepared by Sobering Agrochemicals
Ltd. 49 p.
94
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BIBLIOGRAPHY
MRID
CITATION
40650702 . Lai, S.;Brehm,M. (1987) Preliminary Analysis of Technical Amitraz
Determination of N-Nitrosoamihes in Technical Amitraz: Project ED: AD
62/87; APC 57/86. Unpublished study prepared by Schering Agrochemicals
Ltd and Sobering AG. 41 p.
40650703 Johnson, M. (1987) Amitraz Chemical Product Composition: Project ID: AD
56/87. Unpublished study prepared by Sobering Agrochemicals Ltd. 6 p.
40650704 Leete, A: (1987) The Determination of Amitraz in Technical Material and
Formulations by Gas Chromatography (GC): The Validation of the Analytical
Method AM 1800/1/6 for the Determination of Amitraz in its Technical
Material and Wettable Powder Formulation: Project ID; AM 1800/6/1 and
AD/65/87. Unpublished study prepared by Schering Agrochemicals Ltd. 19 p.
40650705 Lai, S. (1987) The Determination of BTS 27919, BTS 27271, BTS 28037 and
BTS 24868 Impurities in Amitraz Technical by Gas Chromatography: An
Assessment of the Accuracy ...in Technical Amitraz by Gas Chromatography:
Project ID: AM No. 1800/5/1; AD 68/87. Unpublished study-prepared by
Schering Agrochemicals Ltd. 33 p.
40650706 Lai, S. (1987) The Determination of C..) in Technical Amitraz by Gas
Chromtography (GC): An Assessment of the Accuracy and Precision of the
Analytical Method (AM 1800/6/1) for the Determination of (...) in Technical
Amitraz by Gas Chromatography: Project ID: AM 1800/6/1; AD 69/87.
Unpublished study prepared by by Schering Agrochemicals Ltd. 13 p.
40650707 Johnson, M.; Leete, A.; Bright, A.; et al. (1987) Amitraz: Physical and
Chemical Characteristics: Project No. AD 52/87 CHEM/87/78. Unpublished
study prepared by Schering Agrochemicals Ltd. 88 p.
40780501 Roberts, N.; Hakin, B..0988) W81 Technical Amitraz: Subacute Dietary
Toxicity (LC50) to Bobwhite Quail: Laboratory Project JD: TOX 87261.
Unpublished study prepared by Huntingdon Research Centre. 23 p.
40780502 Bright, J. (1988) (W81 A) Determination of Amitraz Dietary Concentrations for
an LC50 Dietary Study in the Bobwhite Quail: Laboratory Project ID:
RESTJD/87/94. Unpublished'study prepared by Schering Agrochemicals Ltd.
14 p.
40780505 Caunter, J. (1988) W94 Amitraz ,20 EC Formulation: Determination of Acute
Toxicity to Rainbow Trout (Salmo gairdneri): Laboratory Project ID: .
ENVJJR/88/9. Unpublished study prepared by ICIPLC. 23 p.
95
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BIBLIOGRAPHY
MRID
CITATION
40780506 Hill, R.; Williams, T.; Harland, 1-. (1988) W95 Amitraz 20 EC Formulation:
Determination of Acute Toxicity to Daphnia magna: Laboratory Project ID:
ENVIR/88/10: ENVIR/84L. Unpublished study prepared by ICIPLG. 28 p.
40780507 Hill, R.; Comber, M.; Gaunter, J. (1988) W96 Amitraz Technical:
Determination of Acute Toxicity to Sheepshead Minnow (Cyprinodon
variegatus): Laboratory Project ID: ENVIR/88/11. Unpublished study prepared
bylCIPLC. 24p.
40780508 Hill, R; Caunter, J. (1988) W98 Amitraz 20 EC Formulation: Determination of
Acute Toxicity to Sheepshead minnow (Cyprinodon variegatus): Laboratory
Project ID: ENVER/88/13: ENVIR/98L. Unpublished study prepared by ICI
PLC. 22 p.
40780509 Surprenant, D. (1988) W100 Amitraz: Acute Toxicity of Amitraz 20 EC to
Eastern Oysters (Crassostrea virginica) under Flow-through Conditions:
Laboratory Project ID: ENVIR/88/5: 88-1-2621. Unpublished study prepared .
by Springbora Life Sciences, Inc. 43 p.
40780510 Smyth, D.; Comber, M.; Hill, R. (1988) W93 Amitraz 20 EC Formulation:
Determination of Acute Toxicity to Mysid Shrimp (Mysidopsis bahia):
Laboratory Project ID: ENVIR/88/8: ENVIR/83L* Unpublished study prepared
bylCIPLC. 24p.
40780511 Thompson, R. (1988) W97 Amitraz Technical: Determination of Chronic
Toxicity to Daphnia magna: Laboratory Project ID: ENVIR/88/12:
ENVIR/79L. Unpublished study prepared by ICI PLC. 40 p.
40780512 Campbell, J. (1988) W89 Amitraz: The Hydrolysis of Amitraz in Aqueous
Solution at 25 degrees under Acid Neutral and Alkaline Conditions: Laboratory
Project ID: ENVIR/88/4. Unpublished study prepared by Sobering
Agrochemicals Ltd. 26 p.
40780513 Brehm, M. (1988) W101 Amitraz: The Photolysis of Amitraz (Schering Code
No. ZK 49 974) in Aqueous Solution: Laboratory Project ID: APC 06/88 :
87/114. Unpublished study prepared by Schering Ag. 48 -p.
40780514 Brehm, M. (1987) (W85) The Photodegradation of Amitraz (Schering code
No. ZK 49974) on Soil Surfaces: Laboratory Project ID: APC 54/87:87/115.
Unpublished study prepared by sheering Ag. 46 p.
96
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BIBLIOGRAPHY
MRID
CITATION
40780515
40780516
40780518
40798001
40798002
40798003
40798004
40811305
Arnold, D.; Barrett, K. (1988) (W83) The Adsorption Equilibria of Amitraz in
Sand, Sandy Loam, Clay Loam and Clay Soils: Laboratory Project ID:
ENVIR/87/45. Unpublished study prepared by Sobering Agrochemicals Ltd
25 p. ..-'.,.'
Fortsch, A. (1988) (W91) Mobility ofN-(2>4-dimemylphenyl)-Nformyl-amine
(BTS-27 919) in the German Standard Soils 2.1, 2.2 and 2.3: Laboratory
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/ '
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GS00234022 Sleight, B.H. (1973) Acute Toxicity to BTS-27419 to Atlantic Oysters
(Crassostrea Virginica). (Unpublished study received April 9, 1980 under
45639-EUP-l; submitted by Boots Hercules Agrochemicals Co., Wilmington,
DE; CDL: 099369)
MEMOS AND OTHER DOCUMENTS
ADI reference: Pesticide Residues in Food - 1990. In FAO PLANT .
PRODUCTION AND PROTECTION PAPER 102, pps. 14-15.
Bennett, R.S. and L.M. Ganio. 1991 (July). Overview of methods for
evaluating effects of pesticides on reproduction in birds. EPA 600/3-91/048.
U.S. Environmental Research Laboratory, Corvallis, Oregon, pp. 106.
Campbell, J.K. (1984) Urinary excretion of 14C-amitraz by five human males
following a single oral dose of 0.25 mg/kg bwt. Unpublished Report submitted
by FBC limited to WHO.
Memo J.Evans: Pear reentry worker exposure to the acute central nervous
system (CNS) effects of amitraz and the metabolites BTS 27271 and BTS
27919; 7/20/94. . .
MemoG. Ghali: Amitraz: RfD/Peer Review Report; 11/24/93.
. Gusey,W.F. and Z.D. Maturgo. 1973. Wildlife Utilization of Croplands.
Environmental Affairs, Shell Oil Comapny. Houston, Texas. 278 pp.
Hill, E.F. etal. 19785. Lethal Dietary Toxicities of Environmental Pollutants to
b; -ds. U.S. Fish and Wildlife Service. Special Scientific Report - Wildlife No.
191, February. 57 pp.
Kenaga, E.E. 1973. Factors to be considered in the Evaluation of Toxicity of
Pesticides to Birds in Their Environment. Environmental Quality and Safety.
Academic Press, N.Y. H: 66-18i.
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BIBLIOGRAPHY
MRID
CITATION
Memo R. Landolt: Quantitative Risk Assessment Based on Hepatocellular
Adenomas and Carcinomas in Female Mice; 01/17/91.
Memo R. Landolt: Review of Amitraz (BAAM); 01/31/91.
Memo R. Landolt dated 07/15/94 and DER of human study entitled "Amitraz:
Report of a double blind tolerance study of amitraz in 6 adults healthy
volunteers" (Simbec Res. Ltd., UK; conducted 06/08/92).
Martin, A.C., H.S. Zim and A.L. Nelson. 1951. American Wildlife and Plants:
AXJuide to Wildlife Food Habits. Dover Publication Inc., N.Y. 500pp.
Memo A. Mehta: Exposure Assessment for amitraz, an insecticide/ acaricide in
dog collars (HED Project 1-0562).
Memo M. van Geniert; Toxicological Endpoint Selection Document on
Amitraz; 06/08/94.
Urban, D.J. and N.J. Cook 1986 (June). Ecological Risk Assessment. EPA
540/9-86-001. U.S. EPA, Washington, DC, pp96.
Memo R. Zendzian: Amitraz, Dermal Absorption; 09/22/93.
Popendorf, W.J; Leffmgwell, J.T.- Residue Review, 1982, Volume 82, page
125 (Reported as .1,900 cm2/hr single sided resides).
State of California EPA review of a dermal absorption study of (14C)-amitraz in
male rats, October 28, 1994.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DrC. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
NOV 22 1396
CERTIFIED MAIL
Dear Registrant: . -
This Notice requires you and other registrants of pesticide products containing the
active ingredient identified in Attachment A of this Notice, the Data Call-in Chemical Status
Sheet to submit certain data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient: Within 90 days after you receive this Notice you
must respond as set forth in Section m below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 7; or
!
2. Why you believe you are exempt from the requirements listed in this Notice
and in Attachment 3 (for both generic and product specific data), the
: Requirements Status and Registrant's Response Form, (see section ffl-B); or
3. Why you believe EPA should not require your submission of data in the
manner specified by this Notice (see section m-D).
,' ^
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list of
all of your products subject to this Notice in Attachment 2.~ All products are listed on both the
generic and product specific Data Call-in Response Forms. Also included is a list of all
registrants who were sent this Notice (Attachment 5).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
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information is authorized underthe Paperwork Reduction Act by OMB Approval No.
2070-0107,and 2070-0057 (expiration date 3-31-96).
This Notice is divided into six sections and seven Attachments. The Notice itself
contains information and instructions applicable to all Data Call-In Notices. The Attachments
contain specific chemical information and instructions. The six sections of the Notice are:
Section I
Section It
Section m
Section IV
Section V
Section VI
Why You are Receiving this Notice
Data Required by this Notice
Compliance with Requirements of this Notice
Consequences of Failure to Comply with this Notice
Registrants' Obligation to Report Possible Unreasonable Adverse
Effects . .
Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2- Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions (Form A)
3- . Generic Data Call-In and Product Specific Data Call-In Requirements Status
and Registrant's Response Forms with Instructions (Form B)
4- EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
6- . Cost Share and Data Compensation, and Confidential Statement of Formula
Forms
SECTION I.
WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the.
data needed to support continued registration of the subject active ingredient(s). This
reevaluation identified additional data necessary to assess the health and safety of the
continued use of products containing this active ingredient(s). You have been sent this Notice
because you have produces) containing the subject active ingredients.
SECTION EL
DATA REQUIRED BY THIS NOTICE
H-A. DATA REQUIRED .
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Forms: Attachment 3 (for both generic and product specific data
requirements). Depending on the results of the studies required in this Notice, additional
studies/testing may be required.
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n-B. SCHEDULE FOR SUBMISSION OF DATA ;
You are required to submit the data or otherwise satisfy the data requirements
specified in the Requirements Status and Registrant's Response Forms (Attachment 3) within
the timeframes provided.
H-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (Telephone number:
703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR ง 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR ง 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
.accordance with acceptable standards. The OECD protocols are available from OECD, 2001
L Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-03 50). ,
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160].
H-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B} NOTICES ISSUED
BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or
change the requirements of any previous Data Call-InfsX or any other agreements entered into
with the Agency pertaining to such prior Notice/Registrants must comply with the
requirements of all Notices to avoid issuance of a Notice of Intent to Suspend their affected
products.
SECTIONm.
COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
You must use the correct forms and instructions when completing your response to
this Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is
specified in item number 3 on the four Data Call-In forms (Attachments 2 and 3).
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EI-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for generic and product
specific data must be submitted to the Agency within 90 days after your receipt of this Notice.
Failure to adequately respond to this Notice within 90 days of your receipt will be a basis for
issuing a Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for
issuance of NOIS due to failure to comply with this Notice are presented in Section IV-A and
IV-B. .
IH-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a)
voluntary cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to satisfy
the generic data requirements imposed by this Notice or (e) request a data waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option, the
Delete Use(s) option or the Generic Data Exemption option is presented below. A discussion
of the various options available for satisfying the generic data requirements of this Notice is
contained in Section IQ-C. A discussion of options relating to requests for data waivers is
contained in Section ffl-D.
Two forms apply to generic data requirements, one or both of which must be used in
responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
(contained in Attachments 2 and 3, respectively).
The Data Call-in Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms also must be submitted if
you do not qualify for a Generic Data Exemption or are not requesting voluntary cancellation
of your registration(s). Please note that the company's authorized representative is required to
sign the first page of both Data Call-in Response Forms and the Requirements Status and
Registrant's Response Forms (if this form is required) and initial any subsequent pages. The
forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write the
contact person(s) identified in Attachment 1.
a.
Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your produces) containing the active ingredient that is the subject of this Notice. If you wish
to vc' itarily cancel your product, you must submit completed Generic and Product Specific
Data Call-in Response Forms (Attachment 2), indicating your election of this option.
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Voluntary cancellation is item number 5 on both Data Call-In Response Form(sV If you
choose this option, these are the only forms that you are required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice, which are contained in Section IV-C, '
b.
Use Deletion
You may avoid the requirements of this Notice by eliminating the uses of your product
to which the requirements apply. If you wish to amend your registration to delete uses, you
must submit the Requirements Status and Registrant's Response Form (Attachment 3), a
completed application for amendment, a copy of your proposed amended labeling, and all
other information required for processing the application. Use deletion is option number 7
under item 9 in the instructions for the Requirements Status and Registrant's Response Forms.
You must also complete a Data Call-in Response Form by signing the certification, item
numbers. Application forms for amending registrations may be obtained from the
Registration Support Branch, Registration Division, Office of Pesticide Programs, EPA, by
calling (703) 308-8358. .
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one year from the due date
of your 90 day response, is allowed only if the product bears an amended label.
c.
Generic Data Exemption
Under section 3 (c)(2)(D) of FIFRA, an applicant for registration of a product is
exempt from the requirement to submit or cite generic data concerning an active ingredient if
the active ingredient in the product is derived exclusively from purchased, registered pesticide
products containing the active ingredient. EPA has concluded, as an exercise of its discretion,
that it normally will not suspend the registration of a product which would qualify and
continue to qualify for the generic data exemption in section 3(c)(2)(D) of FIFRA. To qualify,
all of the following requirements must be met:
(i). The active ingredient in your registered product must be present solely because of
incorporation of another registered product which contains the subject active
ingredient and is purchased from a source not connected with you;
(ii). Every registrant who is the ultimate source of the active ingredient in your
product subject to this DCI must be in compliance with the requirements of this Notice
and must remain in compliance; and
(iii). You must have provided to EPA an accurate and current "Confidential Statement
of Formula" for each of your products to which this Notice applies.
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To apply for the Generic Data Exemption you must submit a completed Data Call-In
Response Form. Attachment 2 and all supporting documentation. The Generic Data
Exemption is item number 6a on the Data Call-in Response Form. If you claim a generic data
exemption you are not required to complete the Requirements Status and Registrant's
Response Form. Generic Data Exemption cannot be selected as an option for responding to
product specific data requirements.
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 registrant(s) who have committed to
generate and submit the required data fail to take appropriate steps to meet requirements or
are no longer in compliance with this Data Call-In Notice, the Agency will consider that both
they and you are not compliance and will normally initiate proceedings to suspend the
registrations of both your and their produces), unless you commit to submit and do submit the
required data within the specified time. In such cases the Agency generally will not grant a
time extension for submitting the data.
d.
Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this
Notice. These options are discussed in Section ffl-C.l. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the Requirements Status and Reeistrant'sResponse
Form and item 6b on the Data Call-in Response Form. If you choose item 6b (agree to satisfy
the generic data requirements), you must submit the Data Call-in Response Form and the
Requirements Status and Registrant's Response Form as well as any other information/data
pertaining to the option chosen to address the data requirement. Your response must be on
the forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers. '
Waivers for generic data are discussed in Section ffl-D. 1. of this Notice and are
covered by options 8 and 9 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose one of these options, you must submit both forms
as well as any other information/data pertaining to the option chosen to address the data
requirement
2.
Product Specific Data Requirements
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this
Notice or (c) request a data waiver(s). .
A discussion of how to respond if you choose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section ffl-C.2. A discussion of
options relating to requests for data waivers is contained in Section m-D.2.
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Two forms apply to the product specific data requirements one or both of which must
be used iri responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
for product specific data (contained in Attachments 2 and 3, respectively). The Data Call-in
Response Form must be submitted as part of every response to this Notice. In addition, one
copy of the Requirements Status and Registrant's Response Form also must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation
option is selected.' Please note that the company's authorized representative is required to sign
the first page of the Data Gall-In Response Form and Requirements Status and Registrant's
Response Form (if this form is required) and initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If you
have questions or need assistance in preparing your response, call or write the contact
person(s) identified in Attachment 1.
a.
Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your produces) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit a completed Data Call-In Response
Form, indicating your election of this option. Voluntary cancellation is item number 5 on both
the Generic and Product Specific Data Call-in Response Forms If you choose this
option, you must complete both Data Call-in response forms. These are the only forms that
you are required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
t>. Satisfying the Product Specific Data Requirements of this Notice
t , -
There are various options available to satisfy the product specific data requirements of
this Notice. These options are discussed in Section ffl-C.2. of this Notice and comprise
options 1 through 6 of item 9 in the instructions for the product specific Requirements Status
and Registrant's Response Form and item numbers 7a and 7b (agree to satisfy the product
specific data requirements for an MUP or EUP as applicable) on the product specific Data
Call-in Response Form. Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements.
Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements. It is important to ensure that you are using the correct
forms and instructions when completing your response to the Reregistration Eligibility
Decision document.
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c.
Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section III-D.2. of this Notice and
are covered by option 7 of item 9 in the instructions for the Requirements Status and
Registrant's Response Form. If you choose this option, you must submit the Data Call-In
Response Form and the Requirements Status and Registrant's Response Form as well as any
other information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" in item number 3. .
M-C. SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-in Response Form that you agree to
satisfy the generic data requirements (i.e. you select item number 6b), then you must select
one of the six options on the Generic Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are
the first six options discussed under item 9 in the instructions for completing the
Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide you to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified timeframe (Developing
Data) ,
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an
existing study that has been submitted but not reviewed by the Agency (Citing
an Existing Study)
Option 1. Developing Data .
If you choose to develop the required data it must be in conformance with Agency
deadlines and with other Agency requirements as referenced herein and in the attachments.
All data generated and submitted must comply with the Good Laboratory Practice (GLP) rule
(40 CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG)
and be in conformance with the requirements of PR Notice 86-5. Li addition, certain studies
require Agency approval of test protocols in advance of study initiation. Those studies for
which a protocol must be submitted have been identified in the Requirements Status and
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Registrant's Response Form and/or footnotes to the form. If you wish to use a protocol which
differs from the options discussed in Section II-G of this Notice, you must submit a detailed
description of the proposed protocol .and your reason for wishing to use.it. The Agency may
choose to reject a protocol not specified in Section n-C. If the Agency rejects your protocol
you will be notified in writing, however, you should be aware that rejection of a proposed
protocol will not be a basis for extending the deadline for submission of data.
A progress report must be submitted for each study within 90 days from the date you '-
are required to commit to generate or undertake some other means to address that study
requirement, such as making an offer to cost share or agreeing to share in the cost of
developing that study. This 90-day progress report must include the date the study was or
will be initiated and, for studies to be started within 12 months of commitment, the name and
address of the laboratory(ies) or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1 year,
interim reports must be submitted at 12 month intervals from the date you are required to
commit to generate or otherwise address the requirement for the study! In addition to the other
information specified in the preceding paragraph, at a minimum, a brief description of current
activity on and the status of the study must be included as well as a full
description of any problems encountered since the last progress jeport.1
The time frames in the Requirements Status and Registrant's Response Form are the
time frames that the Agency is allowing for the submission of completed study reports or
protocols. The noted deadlines run from the date of the receipt of this Notice by the registrant.
If the data are not submitted by the deadline,,each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to
the Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-step
basis. You must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your request, the
original deadline remains. The Agency will respond to your request in writing. If EPA does
not grant your request, the original deadline remains. Normally, extensions can be requested
only in cases of extraordinary testing problems beyond the expectation or control of the
registrant. Extensions will not be given in submitting the 90-day responses. Extensions will
not be considered if the request for extension is not made in a timely fashion; in no event shall
an extension request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2. Agreement to Share in Cost to Develop Data
If you choose to enter into an agreement to share in the cost of producing the required
data but will not be submitting the data yourself, you must provide the name of the registrant
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who will be submitting the data. You must also provide EPA with documentary evidence that
an agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
\
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an agreement or amend an
existing agreement to meet the requirements of this Notice and have been unsuccessful, you
may request EPA (by selecting this option) to exercise its discretion not to suspend, your
registration^), although you do not comply with the data submission requirements of this
Notice. EPA has determined that as a general policy, absent other relevant considerations, it
will not suspend the registration of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost sharing program, but the other
registrants) developing the data has refused to accept the offer. To qualify for this option,
you must submit documentation to the Agency proving that you have made an offer to
another registrant (who has an obligation to submit data) to share in the burden of developing
that data. You must also submit to the Agency a completed EPA Form 8570-32, Certification
of Offer to Cost Share in the Development of Data, Attachment 7. In addition, you must
demonstrate that the other registrant to whom the offer was made has not accepted your offer
to enter into a cost-sharing agreement by including a copy of your offer and proof of the other
registrant's receipt of that offer (such as a certified mail receipt). Your offer must, in addition
to anything else, offer to share in the burden of producing the data upon terms to be agreed to
or, failing agreement, to be bound by binding arbitration as provided by FIFRA section
3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also inform EPA of its
election of an option to develop and submit the data required by this Notice by submitting a
Data Call-in Response Form and a Requirements Status and Registrant's Response Form
committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the 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. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant normally will be subject to initiation of
suspension proceedings, unless you commit to submit, and dp submit, the required data in the
specified time frame. In such cases, the Agency generally will not grant a time extension for
submitting the data. .
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this Notice. You may only
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submit a study that has not been previously submitted to the Agency or previously cited by
anyone. Existing studies are studies, which predate issuance of this Notice. Do not use this
option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met: ",--
a. You must certify at the time that the existing study is submitted that the raw
data and specimens from the study are available for audit and review and you
must identify where they are available. This must be done in accordance with
the requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR
Part 160. As stated in 40 CFR 160.3 'Raw data1 means any laboratory
worksheets, records, memoranda, notes, or exact copies thereof, that are the
result of original observations and activities of a study and are necessary for the
reconstruction and evaluation of the report of that study. In the event that exact
transcripts of raw data have been prepared (e.g., tapes which have been
, transcribed verbatim, dated, and verified accurate by signature), the exact copy
or exact transcript may be substituted for the original source as raw data. "Raw
data1 may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data
from automated instruments." The term "specimens", according to 40 CFR
160.3, means "any material derived from a test system for examination or
analysis." -
b. Health and safety studies completed after May 1984 also must also contain all
GLP-required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants also must certify at the time of
submitting the existing study that such GLP information is available for post
May 1984 studies by including an appropriate statement on or attached to the
study signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the
Guideline relevant to the study provided in the FIFRA Accelerated
Reregistration Phase 3 Technical Guidance and that the study has been
conducted according to the Pesticide Assessment Guidelines (PAG) or meets
the purpose of the PAG (both available from NTIS). A study not conducted
according to the PAG may be submitted to the Agency for consideration if the
registrant believes that the study clearly meets the purpose ,of the PAG. The
registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in
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addition to certifying that the purposes of the PAG are met by the study, clearly
articulate the rationale why you believe the study meetsthe purpose of the
PAG, including copies of any supporting information or data. It has been the
Agency's experience that studies completed prior to January 1970 rarely
satisfied the purpose of the PAG and that necessary raw data usually are not
available for such studies.
If you submit an existing study, you must certify that the study meets all requirements
of the criteria outlined above..
If EPA has previously reviewed a protocol for a study you are submitting, you must
identify any action taken by the Agency on the protocol and must indicate, as part of your
certification, the manner in which all Agency comments, concerns, or issues were addressed
in the final protocol and study.
If you know of a study pertaining to any requirement in this Notice which does not
meet the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable, you may submit
data to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still
be required to submit new data normally without any time extension. Deficient, but
upgradeable studies will normally be classified as supplemental. However, it is important to
note that not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call or write the
contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct all deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied
or corrected and why the study should be rated as acceptable to EPA- Your submission must
also specify the MRJD number(s) of the study which you are attempting to upgrade and must
be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option also should be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRlD number of the study being upgraded.
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The criteria for submitting an existing study, as specified in Option 4 above, apply to
all data submissions intended to upgrade studies. Additionally, your submission of data
intended to upgrade studies must be accompanied by a certification that you comply with
each of those criteria, as well as a certification regarding protocol compliance with Agency
requirements. , ;
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA, that study
must have been previously classified by EPA as acceptable, or it must be a study which has
not yet been reviewed by the Agency. Acceptable toxicology studies generally will have been
classified as "core-guideline" or "core-minimum." For ecological effects studies, the
classification generally would be a rating of "core." For all other disciplines the classification
would be "acceptable." With respect to any studies for which you wish to select this option,
you must provide the MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study.
If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-31, Certification with Respect to Data
Compensation Requirements.
2.
Product Specific Data
If you acknowledge on the product specific Data Call-in Response Form that you
agree to satisfy the product specific data requirements (i.e. you select option 7a or 7b), then
you must select one of the six options on the Requirements Status and Registrant's Response
Form related to data production for each data requirement. Your option selection should be
entered under item number 9, "Registrant Response." The six options related to data
production are the first six options discussed under item 9 in the instructions for completing
the Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing
Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study) .
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an
existing study that has been
submitted but not reviewed by the Agency'(Citing an Existing Study)
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Option 1. Developing Data ~ The requirements for developing product specific data are
the same as those described for generic data (see Section IHC.1, Option 1)
except that normally no protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data If you enter into an agreement to
cost share, the same requirements apply to product specific data as to generic
data (see Section IHC.1, Option 2). However, registrants may only choose this
option for acute toxicity data and certain efficacy data and only if EPA has
indicated in the attached data tables that your product and at least one other
product are similar for purposes of depending on the same data. If this is the
case, data may be generated for just one of the products in the group. The
registration number of the product for which data will be submitted must be
noted in the agreement to cost share by the registrant selecting this option.
Option 3. Offer to Share in the Cost of Data Development The same requirements for
generic data (Section IHCl., Option 3) apply to this option. This option only
applies to acute toxicity and certain efficacy data as described in option 2
above.
Option 4. Submitting an Existing Study The same requirements described for generic
data (see Section ffl.C.1., Option 4) apply to this option for product specific
data.
Option 5. Upgrading a Study The same requirements described for generic data (see
Section m.C.l., Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies The same requirements described for generic data
(see Section IQ.C. 1., Option 6) apply to this option for product specific data.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-in Response Form and the
Requirements Status and Registrant's Response Form, and in the generic data requirements
section (m.C.l.), as appropriate.
m-D. REQUESTS FOR DATA WAIVERS
1. Generic Data
There are two types of data waiver responses to this Notice. The first is a request for a
low volume/minor use waiver and the second is a waiver request based on your belief that the
data requirement(s) are not appropriate for your product.
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a.
Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response
Form. Section 3(c)(2)(A) of FIFRA requires EPA to consider the appropriateness of
requiring data for low volume, minor use pesticides. In implementing this provision,
EPA considers low volume pesticides to be only those active ingredients whose total
production volume for all pesticide registrants is small. In determining whether to
grant a low volume, minor use waiver, the Agency will consider the extent, pattern and
volume of use, the economic incentive to conduct the testing, the importance of the
pesticide, and the exposure and risk from use of the pesticide. If an active ingredient is
used for both high volume and low volume uses, a low volume exemption will not be
approved. If all uses of an active ingredient are low volume and the combined volumes
for all uses are also low, then an exemption may be granted, depending on review of
other information outlined below. An exemption will not be granted if any registrant of
the active ingredient elects to conduct the testing. Any registrant receiving a low
volume minor use waiver must remain within the sales figures in their forecast
supporting the waiver request in order to remain qualified for such waiver. If granted a
waiver, a registrant will be required, as a condition of the waiver, to submit annual
sales reports. The Agency will respond to requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this
Notice: -
(i). Total company sales (pounds and dollars) of all registered prbduct(s)
containing the active ingredient. If applicable to the active ingredient,
include foreign sales for those products that are not registered in this
country but are applied to sugar (cane or beet), coffee, bananas, cocoa,
and other such crops. Present the above information by year for each of
the past five years.
(ii) Provide an estimate of the sales (pounds and dollars) of the active
ingredient for each major use site. Present the above information by
year for each of the past five years.
(iii) Total direct production cost of produces) containing the active
ingredient by year for the past five years. Include information on raw
. material cost, direct labor cost, advertising, sales and marketing, and
'any other significant costs listed separately.
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and
equipment) charged to product(s) containing the active ingredient by
year for the past five years. Exclude all non-recurring costs that were
directly related to the active ingredient, such as costs of initial
registration and any data development.
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(v) A list of each data requirement for which you Seek a waiver. Indicate
the type of waiver sought and the estimated cost to you (listed
separately for each data requirement and associated test) of conducting
the testing needed to fulfill each of these data requirements.
*
(vi) A list of each data requirement for which you are not seeking any
waiver and the estimated cost to you (listed separately for each data
requirement and associated test) of conducting the testing needed to
fulfill each of these data requirements.
(vii) For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient, direct production costs of
product(s) containing the active ingredient (following the parameters in
item 2 above), indirect production costs of product(s) containing the
active ingredient (following the parameters in item 3 above), and costs.
of data development pertaining to the active ingredient.
(viii) A description of the importance and unique benefits of the active
ingredient to users. Discuss the use patterns and the effectiveness of the
active ingredient relative to registered alternative chemicals and
non-chemical control strategies. Focus on benefits unique to the active
ingredient, providing information that is as quantitative as possible. If
you do not have quantitative data upon which to base your estimates,
then present the reasoning used to derive your estimates. To assist the
Agency in determining the degree of importance of the active ingredient
in terms of its benefits, you should provide information on any of the
following factors, as applicable to your produces): (a) documentation of
the usefulness of the active ingredient in Integrated Pest Management;
(b) description of the beneficial impacts on the environment of use of
the active ingredient, as opposed to its registered alternatives, (c)
information on the breakdown of the active ingredient after use and on
its persistence in the environment, and (d) description of its usefulness
against a pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a
determination regarding a request for a low volume/minor use waiver will result in
denial of the request for a waiver.
b.
Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response
Form. This option may be used if you believe that a particular data requirement should
not apply because the requirement is inappropriate. You must submit a rationale
explaining why you believe the data requirements should not apply. You also must
submit the current label(s) of your product(s) and, if a current copy of your
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Confidential Statement of Formula is not already on file you must submit a current
copy: ';.,-. *"-'
You will be informed of the Agency's decision in writing. If the Agency
determines that the data requirements of this Notice are not appropriate to your
product(s), you will not be required to supply the data pursuant to section 3(c)(2)(B). If
EPA determines that the data are required for your productCs). you must choose a
method of meeting the requirements of this Notice within the time frame provided by
this Notice. Within 30 days of your receipt of the Agency's written decision, you must
submit a revised Requirements Status and Registrant's Response Form indicating the
option chosen.
2.
Product Specific Data
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request including
technical reasons, data and references to relevant EPA regulations, guidelines or
policies. (Note: any supplemental data must be submitted in the format required by PR
Notice 86-5). This will be the only, opportunity to state the reasons or provide
information in support of your request. If the Agency approves your waiver request,
you will not be required to supply the data pursuant to section 3(c)(2)(B) of FIFRA. If
the Agency denies your waiver request, you must choose an option for meeting the
data requirements of. this Notice within 30 days of the receipt of the Agency's decision
You must indicate and submit the option chosen on the product specific Requirements
Status and Registrant's Response Form. Product specific data requirements for product
chemistry, acute toxicity and efficacy (where appropriate) are required for all products
and the Agency would grant a waiver only under extraordinary circumstances. You
should also be aware that submitting a waiver request will not automatically extend the
due date for the study in question. Waiver requests submitted without adequate
supporting rationale will be denied and the original due date, will remain in force.
UENCES OF FAILURE TO COMPLY WITH THIS
SECTION IV.
IV-A NOTICE OF INTENT TO SUSPEND
,. " The Agency may issue a Notice of Intent to Suspend products subject to this Notice
due to failure by a registrant to comply with the requirements of this Data Call-in Notice,
pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice
of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of
this Notice.
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7.
8.
Failure to submit on the required schedule an acceptable proposed or final
protocol when such is required to be submitted to the Agency for review.
Failure to submit on the required schedule an adequate progress report on a
study as required by this Notice:
Failure to submit on the required schedule acceptable data as required by this
Notice.
Failure to take a required action or submit adequate information pertaining to
any option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration
concerning joint data development or failure to comply with any terms of a data
waiver). .
Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section ffl-C of this Notice.
Withdrawal of an offer to share in the cost of developing required data.
Failure of the registrant to whom you have tendered an offer to share in the cost
of developing data and provided proof of the-registrant's receipt of such offer or
failure of a registrant on whom you rely for a generic data exemption either to:
i.
11.
Inform EPA of intent to develop and submit the data required by this
Notice on a Data Call-In Response Form and a Requirements Status and
Registrant's Response-Form.
Fulfill the commitment to develop and submit the data as required by
this Notice; or
9.
iii. Otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in
the specified time frame.
Failure to take any required or appropriate steps, not mentioned above, at any
time following the issuance of this Notice.
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IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The, Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The
grounds for suspension include, but are not limited to, failure to meet any of the following:
1) EPA requirements specified in the Data Call-In Notice or other, documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test
Guidelines) regarding the design, conduct, and reporting of required studies.
Such requirements include, but are not limited to, those relating to test material,
test procedures, selection of species, number of animals, sex and distribution of
animals, dose and effect levels to be tested or attained, duration of test, and, as
applicable, Good Laboratory Practices.
2) EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3) EPA requirements regarding the reporting of data, including the manner of
reporting, the completeness of results, and the adequacy of any required
supporting (or raw) data, including, but not limited to, requirements referenced
or included in this Notice or contained in PR 86-5. All studies must be
submitted in the form of a final report; a preliminary report will not be
considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act. ,
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding generally would
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended produces) only in
exceptional circumstances. If you believe such disposition of existing stocks of your
produces) which may be suspended for failure to comply with this Notice should be
permitted, you have the burden of clearly demonstrating to EPA that granting such permission
would be consistent with the Act. You also must explain why an "existing stocks" provision is
necessary, including a statement of the quantity of existing stocks and your estimate of the
time required for their sale, distribution, and use. Unless you meet this burden, the Agency
will not consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
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If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on a case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due, unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3-year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V.
REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the
information to the Agency. Registrants must notify the Agency of any factual information
they have, from whatever source, including but not limited to interim or preliminary results of
studies, regarding unreasonable adverse effects on man or the environment. This requirement
continues as long as the products are registered by the Agency.
SECTION VI.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person(s) listed in Attachment 1, the Data Call-in Chemical Status
Sheet.
All responses to this Notice must include completed Data Gall-In Response Forms
(Attachment 2)and completed Requirements Status and Registrant's Response Forms
(Attachment 3), for both (generic and product specific data) and any other documents
required by this Notice, and should be submitted to the contact person(s) identified in
Attachment 1. If the voluntary cancellation or generic data exemption option is chosen, only
the Generic and Product Specific Data Call-in Response Forms need be submitted.
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The Office of Compliance (OC) of the Office of Enforcement and Compliance
Assurance (OECA), EPA, will be monitoring the data being generated in response to this
Notice. .
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
The Attachments to this Notice are:
la- Product Specific Data Call-In Chemical Status Sheet
Ib -. Generic Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions
3 - Generic Data Call-In and Product Specific Data Call'-In Requirements Status
and Registrant's Response Forms with Instructions
4- EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
6- Confidential Statement of Formula (with Instructions), and Cost Share and
Data Compensation Forms
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la- PRODUCT SPECIFIC DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have
product(s) containing Amitraz.
This Product Specific Data Call-in Chemical Status Sheet contains an overview of
data required by this notice, and point of contact for inquiries pertaining to the reregistration
of 0234. This attachment is to be used in conjunction with (1) the Product Specific Data Call-
In Notice, (2) the Product Specific Data Call-in Response Form (Attachment 2), (3) the
Requirements Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirement (Attachment 4), (5) a list of
registrants receiving this DCI (Attachment 5) and (7) the Cost Share and Data Compensation
Forms in replying to this 0234 Product Specific Data Call-In (Attachment 6). Instructions and
guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for amitraz are
contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency
has concluded that additional data on amitraz are needed for specific products.
o
These data are required to be submitted to the Agency within the time frame listed.
These data are needed to fully complete the reregistration of all eligible amitraz products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic database of amitraz, please contact
Mario F. Fiol at (703) 308-8049.
If you have any questions regarding the product specific data requirements and
procedures established by this Notice, please contact CP Moran at (703) 308-8590.
All responses to this Notice for the Product Specific data requirements should be
submitted to:
CP Moran, Chemical Review Manager
Product Reregistration Branch
Special Review and Reregistration Division (7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D..C. 20460
RE: 0234
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Ib. GENERIC DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s)
containing 0234.
This Generic Data Call-In Chemical Status Sheet contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of
0234. This attachment is to be used in conjunction with (1) the Generic Data Call-In Notice,
(2) the Generic Data Call-In Response Form (Attachment 2), (3) the Requirements Status and
Registrant's Form (Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4),
(5) and (6) the Cost Share and Data Compensation Forms in replying to this 0234 Generic
Data Callln (Attachment 6). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for 0234 are
contained in the Requirements Status and Registrant's Response. Attachment C.
The Agency has concluded that additional product chemistry data on 0234 are needed.
These data are needed to fully complete the reregistration of all eligible 0234 products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures
established by this Notice, please contact Mario F. Fiol at (703) 308-8049.
All responses to this Notice for the generic data requirements should be submitted to:
Mario F. Fiol, Chemical Review Manager
Reregistration Branch
Special Review and Registration Division (75 08W)
Office of Pesticide Programs
U.S. En vironmentalProtection Agency
Washington, D.C. 20460
RE: 0234
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2.
INSTRUCTIONS FOR COMPLETING THE "DATA CALL-IN RESPONSE
FORMS" FOR THE GENERIC AND PRODUCT SPECIFIC DATA CALL-IN
INTRODUCTION
These instructions apply to the Generic and Product Specific "Data Call-in Response
Forms" and are to be used by registrants to respond to generic and product specific Data
Call-ins as part of EPA's Reregistration Program under the Federal Insecticide, Fungicide, and
Rodenticide Act. If you are an end-use product registrant only and have been sent this DCI
letter as part of a RED document you have been sent just the product specific "Data Call-In
Response Forms." Only registrants responsible for generic data have been sent the generic
data response form. The type of Data Call-In (generic or product specific) is indicated in
item number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both generic and product specific data, instructions
for completing these forms are different. Please read these instructions carefully before filling
outthe forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms with a number of items. DONOT use these forms for any other active ingredient
Items 1 through 4 have been preprinted on the form. Items 5 through 7 must be
completed by the registrant as appropriate. Items 8 through 11 must be completed by the
registrant before submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average
15 minutes per response, including time for reviewing instructions, searching existing data
sources,.gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing this burden to Chief
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget Paperwork
Reduction Project 2070-0107, Washington, D.C. 20503.
INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 1.
Item 2.
ON BOTH FORMS: This item identifies your company name, number and
address.
ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
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ItemS. ON BOTH FORMS: This item identifies the type'of Data Call-In. The date
of issuance is date stamped.
Item 4. ON BOTH FORMS: Thisite: dentifies the EPA product registrations
relevant to the data call-in. Please note that you are also responsible for
informing the Agency of your response regarding any product that you believe
may be covered by this Data Cali-In but that is not listed by the Agency in Item
4. You must bring any such apparent omission to the Agency's attention within
the period required for submission of this response form.
Item 5. ON BOTH FORMS: Check this item for each product registration you wish
to cancel voluntarily. If a registration number is listed for a product for which
you previously requested voluntary cancellation, indicate in Item 5 the date of
that request. Since this Data Call-in requires bom generic and product specific
data, you must complete item 5 on both Data Call-In response forms. You do
not need to complete any item on the Requirements Status and Registrant's
Response Forms.
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is for
generic data as indicated in Item 3 and you are eligible for a Generic Data
Exemption for the chemical listed in Item 2 and used in the subject product.
By electing this exemption, you agree to the terms arid conditions of a Generic
Data Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA
registration Number of each registered source of that active ingredient that you
use in your product.
Typically, if you purchase an EPA-registered product from one or more other
producers (who, with respect to the incorporated product, are in compliance
with this and any other outstanding Data Call-In Notice), and incorporate that
product into all your products, you. may complete this item for all products
listed on this form. If, however, you produce the active ingredient yourself, or
use any unregistered product (regardless of the fact that some of your sources
are registered), you may not claim a Generic Data Exemption and you may not
select this item.
Item 6b. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is
for generic data as indicated in Item 3 and if you are agreeing to satisfy the
generic data requirements of this Data Call-in. Attach the Requirements Status
and Registrant's Response Form that indicates how you will satisfy those
requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
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Item 7a.
Item 7b,
ItemS.
Item 9.
Item 10.
ON THE PRODUCT SPECIFIC DATA FORM: For each manufacturing
use product (MUP) for which you wish to maintain registration, you must agree
to satisfy the data requirements by responding "yes."
For each end use product (EUP) for which you wish to maintain registration,
you must agree to satisfy tile data requirements by responding "yes."
FOR BOTH MUP and EUP products
You should also respond "yes" to this item (7a for MUP's and 7b for EUP's) if
your product is identical to another product and you qualify for a data
exemption. You must provide the EPA registration numbers of your source(s);
dp not complete the Requirements Status and Registrant's Response form.
Examples of such products include repackaged products and Special Local
Needs'(Section 24c) products which are identical to federally registered
products.
If you are requesting a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form under Item 9, you must
respond with option 7 (Waiver Request) for each study for which you are
requesting a waiver.
\ - '
NOTE: Item 7a and 7b are not applicable for Generic Data.
ON BOTH FORMS: This certification statement must be signed by an
authorized representative of your company and the person signing must include
his/her title. Additional pages used in your response must be initialled and
dated in the space provided for the certification. .
ON BOTH FORMS: Enter the date of signature.
ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS: Enter the phone number of your company contact.
Note:
You may provide additional information that does not fit on this form in a signed letter mat accompanies your response. For example, you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this
product. For these cases, please supply all relevant details so that EPA can ensure that its records are correct. '
137
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3. INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS
AND REGISTRANT'S RESPONSE FORMS" FOR THE GENERIC AND
PRODUCT SPECIFIC DATA CALL-IN
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status and
Registrant's Response Forms" and are to be used by registrants to respond to generic and
product specific Data Call-in's as part of EPA's reregistration program under the Federal
Insecticide, Fungicide, and Rodenticide Act. , If you are an end-use product registrant only
and have been sent this DCI letter as part of a RED document you have been sent just the
product specific "Requirements Status and Registrant's Response Forms." Only registrants
responsible for generic data have been sent the generic data response forms. The type of
Data Call-In (generic or product specific) is indicated in item number 3 ("Date and
Type of DCI") on each form.
Although the form is the same for both product specific and generic data, instructions
for completing the forms differ slightly. Specifically, options for satisfying product specific
data requirements do not include (1) deletion of uses or (2) request for a low volume/minor .
use waiver. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms to include certain information unique to this chemical. DO NOT use these forms
for any other active ingredient. ^
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by the
registrant as appropriate. Items 10 through 13 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average
30 minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget, Paperwork
Reduction Project 2070-0107, Washington, D.C. 20503.
139
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address. . , ' ..
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number,
case name, EPA chemical number and chemical name.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
case number, case name, and the EPA Registration Number of the product for
which the Agency is requesting product specific data.
ItemS. ON THE GENERIC DATA FORM: This item identifies the type of Data
Call-In. The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
type of Data Call-In. The date of issuance is also date stamped. Note the
unique identifier, number (TD#) assigned by the Agency. This ID number must
be used in the transmittal document for any data submissions in response to this
Data Call-in Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of
studies required. These guidelines, in addition to the requirements specified in
the Data Call-In Notice, govern the conduct of the required studies. Note that
series 61 and 62 in product chemistry are now listed under 40 CFR 158.155
through 158.180, Subpartc.
Item 5. ON BOTH FORMS: This item identifies the study title associated with the
guideline reference number and whether protocols and 1,2, or 3-year progress
reports are required tp be submitted in connection with the study. As noted in
Section HI of the Data Call-in Notice, 90-day progress reports are required for
all studies.
If an asterisk appears in Item 5, EPA has attached information relevant to this
guideline reference number to the Requirements Status and Registrant's
Response Form.
Item 6. ON BOTH FORMS: This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
requirement), the required study only pertains to products which have the use
sites and/or pests indicated. A brief description of each code follows:
140
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A Terrestrial food
B Terrestrial feed
. C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor <
F Aquatic non-food industrial
G' Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
Item 7. ON BOTH FORMS: This item identifies the code assigned to the substance
that must be used for testing. A brief description of each code follows:
EUP
MP
MP/TGAI
PAI
PAI/M
PAI/PAIRA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP %
TEP/MET
TEP/PAI/M
TGAI
TGAI/PAI
TGAI/PAIRA
TGAFTEP
End-Use Product
Manufacturing-Use Product ,
Manufacturing-Use Product and Technical Grade Active
Ingredient
Pure Active Ingredient
Pure Active Ingredient and Metabolites
Pure Active Indredient or Pute Active
Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled and Metabolites
Pure Active Ingredient Radiolabelled and Plant
Metabolites
Typical End-Use Product
Typical End-Use Product, Percent Active Ingredient
Specified
Typical End-Use Product and Metabolites
Typical End-Use Product or Pure Active Ingredient and
Metabolites
Technical Grade Active Ingredient
Technical Grade Active Ingredient or Pure Active
Ingredient
Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabelled
Technical Grade Active Ingredient or Typical End-Use
Product
141
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MET
IMP
DEGR
Metabolites
Impurities
Degradates
See: guideline comment
Item 8. This item completed by the Agency identifies the time frame allowed for
submission of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of
your receipt of the Data Cal1 In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for
submission of procbct specific studies begins from the date stamped on the
letter transmitting t,: Reregistration Eligibility Decision document, and not
from the date of receipt. However, your response to the Data Call-in itself is
due 90 days from the date of receipt.
Item 9. ON BOTH FORMS: Enter the appropriate Response Code or Codes to show
how you intend to comply with each data requirement. Brief descriptions of
each code follow. The Data Call-In Notice contains a fuller description of each
of these options.
Option 1. ON BOTH FORMS: (Developing DataVI will conduct a new study
and submit it within the time frames specified in item 8 above. By
indicating that I have chosen this option, I certify that I will comply with
all the requirements pertaining to the conditions for submittal of this
study as outlined in the Data Call-in Notice and that I will provide the
protocols and progress reports required in item 5 above.
Option 2. ON BOTH FORMS: (Agreement to Cost Shared I have entered into an
agreement with one or more registrants to develop data jointly. By
indicating that I have chosen this option, I certify that I will comply with
all the requirements pertaining to snaring in the cost of developing data
as outlined in the Data Call-In Notice.
However, for Product Specific Data, I understand that this
option is available for acute toxicity or certain efficacy data ONLY if
the Agency indicates in an attachment to this notice that my product is
similar enough to another product to qualify for this option. I certify that
another party in the agreement is committing to submit or provide the
required data; if the required study is not submitted on time, my product
may be subject to suspension.
142
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Options: ON BOTH FORMS: (Offer to Cost Share* T have ma I am citing an existing study
that has been previously classified by EPA as acceptable, core, core
minimum, or a study that has not yet been reviewed by the Agency. If
reviewed, I am providing the Agency's classification of the study.
However, for Product Specific Data, I am citing another
registrant's study. I understand that this option is available ONLY for
acute toxicity or certain efficacy data and ONLY if the cited study was
conducted on my product, an identical product or a product which the
Agency has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am citing
143
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. ' my own data. In either case, I wil} provide the MRJOD or Accession
number (s). If I cite another registrant's data, I will submit a completed
"Certification With Respect To Data Compensation Requirements"
form.
FOR THE GENERIC DATA FORM ONLY: The following three options
(Numbers 7, 8, and 9) are responses that apply only to the "Requirements Status
and Registrant's Response Form" for generic data.
f
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
Option 8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-in
Notice and I request a low-volume minor use waiver of the data
requirement. I am attaching a detailed justification to support this
waiver request including, among other things, all information required
to support the request. I understand that, unless modified by the Agency
in writing, the data requirement as stated in the Notice governs.
Option 9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than lowvolume minor-use data waivers in the Data
Call-In Notice and I request a waiver of the data requirement. I am
attaching a rationale explaining why I believe the data requirements do
not apply. I am also submitting a copy of my current labels. (You must
also submit a copy of your Confidential Statement of Formula if not
already on file with EPA). I understand that, unless modified by the
Agency in writing, the data requirement as stated in the Notice governs.
FOR PRODUCT SPECIFIC DATA; The following option (number 7) is a
response that applies to the "Requirements Status and Registrant's Response
Form" for product specific data.
Option 7. (Waiver Request) I request a waiver for this study because it is
inappropriate for my product. I am attaching a complete justification for
this request, including technical reasons, data and references to relevant
EPA regulations, guidelines or policies. [Note: any supplemental data
must be submitted in the format required by P.R. Notice 86-5]. I
understand that this is my only opportunity to state the reasons or
provide information in support of my request. If the Agency approves
my waiver request, I will not be required to supply the data pursuant to
Section 3(c) (2) (B) of FIFRA. If the Agency denies my waiver request,
I must choose a method of meeting the data requirements of this Notice
by the due date stated by this tice. In this case, I must, within 30
days-of my receipt of the Age;, -y's written decision, submit a revised
"Requirements Status" form specifying the option chosen. I also
144 .
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Item 10.
Item 11.
Item 12.
understand that the deadline for submission of data as specified by the
original Data Call-In, notice will not change.
ON BOTH FORMS: This item must be signed by an authorized representative
of your company. The person signing must include his/her title, and must initial
and date all. other pages of this form.
ON BOTH FORMS: Enter the date of signature.
ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. ON BOTH FORMS: Enter the phone number of your company contact.
NOTE: You mj>y Provide additional information that does not fit on this form in a signed letter flat accompanies this your response. For example, you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this
145
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4. EPA'S BATCHING OF PRODUCTS CONTAINING AMITRAZ AS THE
ACTIVE INGREDIENT FOR MEETING ACUTE TOXICITY DATA
REQUIREMENTS FOR REREGISTRATION
; . ' >
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregistratibn of products containing the active ingredient
Amitraz, the Agency has batched products which can be considered similar in terms of acute
toxicity. Factors considered in the sorting process include each product's active and inert
ingredients (identity, percent composition and biological activity), type of formulation (e.g.,
emulsifiable concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal
word, use classification, precautionary labeling, etc.). Note that the Agency is not describing
batched products as "substantially similar" since some products within a batch may not be
considered chemically similar or have identical use patterns.
Using available information, batching has been accomplished by the process described
in the preceding paragraph. Notwithstanding the batching process, the Agency reserves the
right to require, at any time, acute toxicity data for an individual product should the need
arise.
Registrants of products within a batch may choose to cooperatively generate, submit or
cite a single battery of six acute toxicological studies to represent all the products within that
batch. .It is the registrants' option to participate in the process with all other registrants, only
some of the other registrants, or only their own products within a batch, or to generate all the
required acute toxicological studies for each of their own products. If a registrant chooses to
generate the data for a batch, he/she must use one of the products within the batch as the test
material. If a registrant chooses to rely upon previously submitted acute toxicity data, he/she
may do so provided that the data base is complete and valid by today's standards (see
acceptance criteria attached), the formulation tested is considered by EPA to be similar for
acute toxicity, and the formulation has not been significantly altered since submission and
acceptance of the acute toxicity data. Regardless of whether new data is generated or
existing data is referenced, registrants must clearly identify the test material by EPA
Registration Number. If moire than one confidential statment of formula (CSF) exists for a
product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF. .
In deciding how to meet the product specific data requirements, registrants must
follow the directions given in the Data Call-In Notice and its attachments appended to the
RED. The DCI Notice contains two response forms which are to be completed and submitted
to the Agency within 90 days of receipt. The first form, "Data Call-In Response," asks
whether the registrant will meet the data requirements for each product. The second form,
"Requirements Status and Registrant's Response," lists the product specific data required for
each product, including the standard six acute toxicity tests. A registrant who wishes to
participate in a batch must decide whether he/she will provide the data or depend on someone
else to do so. If a registrant supplies the data to support a batch of products, he/she must
147
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select one of the following options: Developing Data (Option 1), Submitting an Existing
Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study
(Option 6). If a registrant depends on another's data, he/she must choose among: Cost
Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an Existing Study (Option 6).
If a registrant does not want to participate in a batch, the choices are Options 1, 4, 5 or 6.
However, a registrant should know that choosing not to participate in a batch does not
preclude other registrants in the batch from citing his/her studies and offering to cost share
(Optijon 3) those studies. .
Table 1 displays the batch for the active ingredient amitraz.
Table 1.
EPA Reg. No.
54382-4
54382-5
Active Ingredient
Amitraz ... 10.0%
, Amitraz ... 10.0%
Formulation Type
collar
collar
Table 2 lists those products the Agency was unable to batch. These products were
either considered not to be similar to other products for purposes of acute toxicity or the
Agency lacked sufficient information for decision making. Registrants of these products are
responsible for meeting the acute toxicity data requirements for each product.
Table 2. ' '
EPA Reg. No.
2382-104
45639-49
45639-51
45639-61
45639-146
54382-3
Active Ingredient
Amitraz... 9.0%
Amitraz ... 19.8%
Amitraz... ^97%
Amitraz ... 50.0%
" Amitraz ;.. 19.8%
Amitraz ... 12.5%
Formulation Type
collar
liquid
solid
solid
liquid
liquid
148
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible,
signed copies of the form are required. Following are basic instructions:
a.
b.
c.
d.
f.
g-
h.
i.
j-
k.
1.
m.
n.
All the blocks on the form must be filled in and answered completely.
Ifany block is not applicable, mark it N/A. ,.
The CSF must be signed, dated and the telephone number of the responsible
party must be provided.
All applicable information which is on the product specific data submission
must also be reported on the CSF.
All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
Flashpoint must be in degrees Fahrenheit and flame extension in inches.
For all active ingredients, the EPA Registration Numbers for the currently
registered source products mustjbe reported under column 12.
The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and
all common names for the trade names must be reported.
For the active ingredients, the percent purity of the source products must be
reported under column 10 and must be exactly the same as on the source
product's label.
All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or
grams. In no case will volumes be accepted. Do not mix English and metric
system units (i.e., pounds and kilograms).
All the items under column 13.b. must total 100 percent.
All items under columns 14.a. and 14.b. for the active ingredients must
represent pure active form.
The upper and lower certified limits for ail active and inert ingredients must
follow the 40 CFR 158.175 instructions. An explanation must be provided if
the proposed limits are different than standard certified limits.
* ' .
When new CSFs are submitted and approved, all previously submitted CSFs
become obsolete for that specific formulation.
151
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r/EPA
United
Agency
States Environmental Protection
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
Z070-0057
Approval Expire* 3-31-%
Public reporting burden for this collection of information is estimated to average 15 minutes per response including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief. Information Policy
Branch. PM-223. U.S. Environmental Protection Agency, 401 M St., S.W.. Washington. DC 20460; and to the Office
of Management and Budget. Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill in blanks below.
Company Number
EPA Rce-No.
! Certify that: .
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide. Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of develooino
data. - - . _ ,; .. , .
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Name of Flrm(ป)
Certification;
Date of Offer
certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and afl attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative .
Date ,
Name and Title (Please Type or Print) '
EPA Foiro 8570-32 (5/91) Replaces KPฃ Form 8580, which is obsolete
-------
-------
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-96
3ublic reporting burden for this collection of information is estimated to average. 15 minutes per response, including time for
eviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the
Election of information. Send comments regarding the burden estimate or any other aspect of this collection of information,
ncluding suggestions for reducing this burden to, Chief Information Policy Branch, PM-233, U.S. Environmental Protection
\gency, 401 M St., S.W., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project
2070-0106), Washington, DC 20503.
'lease fill in blanks below.
Jompany Name - -
'roductName
Company Number
EPA Reg. No.
Certify that:
For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rbdenticide Act
FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
lata submitter to cite that study.
That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
iriginal data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
iompany(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
'(cXI )(F) and 3(c)(2)(D) of FIFRA; and (b) Commence negotiation to determine which data are subject to the compensation
equirement of FIFRA and the amount of compensation due, if any. The companies I have notified are. (check one)
[ ] The companies who have submitted the studies listed on the back of this form or attached sheets, or indicated on the attached
Requirements Status and Registrants' Response Form,"
That I have previously complied with section 3(c)(1)(F) of FIFRA for the studies I have cited in support of registration or
sregistration under FIFRA.
ignature ...
Date
lame and Title (Please Type or Print)
iENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or
eregistration of my products, to the extent required by FIFRA section 3(c)(1)(F) and 3(c)(2)(D).
ignature
Date '
ame and Title (Please Type or Print)
rorm 00/0-31 (4-ao)
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LIST OF AVAILABLE RELATED DOCUMENTS
The following is a list of available documents related to 0234. It's purpose is to provide a
path to more detailed information if it is needed. These accompanying documents are part of
the Administrative Record for 0234 and are included in the EPA's Office of Pesticide
Programs Public Docket.
1. Health and Environmental Effects Science Chapters
2. Detailed Label Usage Information System (LUIS) Report
3. 0234 RED Fact Sheet
. 4. PR Notice 86-5 (included in this appendix)
5. PR Notice 91-2 (included in this appendix) pertains to the Label Ingredient
Statement
161
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