United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-96-031
November 1996
R.E.D. FACTS
Amitraz
Pesticide
Reregistration
Use Profile
Regulatory
History
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 reregi strati on, 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 reregi strati on, 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
reregi strati on 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.
Amitraz was registered as a technical grade pesticide in 1975. EPA
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.
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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.
Human Health
Assessment 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 III for these effects.
Amitraz is non-irritating to the eyes and skin and has been placed in
Toxicity Category IV 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 developmental 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 toxicity 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 in 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 amitraz' 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 1,000,000.
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, which is
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 dermal
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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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 neurotoxicity 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 Environmental Fate
AsSGSSITIGnt The Agency has performed a comprehensive qualititative
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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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.
Use of amitraz on cattle and swine is expected to result in minimal
exposure to aquatic organisms.
Risk Mitigation 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,
amitraz' risk potential is reduced.
The following risk mitigation measures, combined with generic
worker protection labeling, should mitigate the unacceptable neurotoxicity
risks to amitraz handlers:
• 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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Additional Data
Required
Product Labeling
Changes
Required
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.
EPA is requiring the following additional generic data for amitraz to
confirm its regulatory assessments and conclusions:
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 reregi strati on.
All amitraz end-use products must comply with EPA's current
pesticide product labeling requirements and those summarized below. For
a complete 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 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 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."
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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 PSYLLA: 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 reregi strati on.
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 Reregi strati on 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 Reregi strati on Information System
at 703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER.EPA.GOV, or using ftp on FTP.EPA.GOV, or using
WWW (World Wide Web) on WWW.EPA.GOV.
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 reregi strati on program,
the [name] RED, or reregi strati on of individual products containing [name],
please contact the Special Review and Reregi strati on 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.
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