United States Prevention, Pesticides EPA 738-R-98-020
Environmental Protection And Toxic Substances December 1998
Agency (7508C)
£EPA Reregistration
Eligibility Decision (RED)
Alachlor
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United States prevention, resucraes Er/v
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\
Use Profile Alachlor is a herbicide used for weed control on corn, soybeans,
sorghum, peanuts, and beans. There are liquid, dry flowable,
microencapsulated, and granular formulations. The timing of applications is
preplant, pre-emergent, at plant for com and soybeans, post-transplant, post-
emergent, and at ground crack for peanuts only. Alachlor is applied by ground,
aerial, and chemigation equipment It can also be mixed with dry bulk
fertilizer.
Regulatory Alachlor was first registered in 1969 as a selective herbicide for control
History of broadleaf weeds and grasses. Alachlor is produced by the Monsanto
Company in the US.
A Registration Standard was issued for alachlor on November 20, 1984.
The Registration Standard involved a thorough review of the scientific data
base underlying pesticide registrations and an identification of essential, but
missing, studies. The Registration Standard (1) stated that alachlor was
classified as an oncogen, (2) required additional data on the leaching and
mobility of alachlor to examine the potential of alachlor to contaminate ground
; and surface water, (3) required a monitoring study of ground and surface water
were required, and required additional data in the areas of toxicology, product
chemistry, and residue chemistry.
On January 9,1985, the Agency published a Notice of Initiation of
Special Review of Registrations of Pesticide Products Containing Alachlor
(Federal Register. Volume 50, No. 1115) and the Alachlor Position Document
(PD-1) that detailed the basis for the Special Review. The Special Review was
initiated under the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) because pesticide products containing alacMor met or exceeded the
Agency's oncogenicity criteria.
Following the review of public comments and additional information
received in response to the Notice of Initiation of Special Review and the
Alachlor PD-1, EPA issued a Notice of Preliminary Determination on October
8, 1986 (Federal Register, Volume 51, No. 36106). In this notice the Agency
proposed to allow the continued use of alachlor products subject to
modifications of the terms and conditions of registration .
Following review of comments and additional information received in
response to the Preliminary Notice, EPA issued a notice entitled "Alachlor;
Notice of Intent to Cancel Registrations, Conclusion of Special Review on
December 31, 1987 (Federal Register. Volume 52, No. 49480). This notice is
2
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also known as Alachlor Position Document 4 (PD-4). The PD-4 concluded the
Special Review and stated that EPA would cancel the registrations and deny
applications for registration of products containing alachlor that did not
comply with the modified terms and conditions of registration set forth in this
notice. The PD-4 stated that tolerances would be rewritten once all residue
data required by the Registration Standard were received and evaluated. The
PD-4 required the following label amendments: Restricted Use due to
Oncogenicity, a tumor hazard warning, use of a mechanical transfer system to
be used by mixer/loaders and/or applicators who treat 300 or more acres
amlually, and human flaggers were prohibited for aerial application. Additional
ground water monitoring data were required. Labeling bearing required
changes was submitted and accepted in early 1988.
Human Health Toxicity
Assessment Data from acute toxicity studies serve as the basis for labeling and
packaging requirements. In studies using laboratory animals, alachlor generally
has been shown to be of low acute toxicity. All acute studies have been
classified as either Category III or IV, the two lowest classifications.
Alachlor has been evaluated for carcinogenic activity in rats and mice. In
accordance with the 1996 EPA proposed Guidelines for Carcinogen Risk
Assessment, alachlor was classified as "likely" to be a human carcinogen at
high doses, but" not likely" at low doses. Based on numerous studies
submitted by the registrant that were reviewed by Agency scientists/as well as
an external peer review panel, it was agreed that a margin of exposure (MOE)
approach (indicative of a non-linear dose response) should be used for the risk
assessment.
The scientific validity of the MOE approach has been documented by
various review panels, such as the FIFRA Scientific Advisory Panel, and the
Cancer Review Committee. However, the policy implications, methodology,
and appropriateness of using an MOE approach in regulatory decision making
have not yet been fully developed by the Agency. Perhaps, the most critical of
the decision criteria to develop are those for determining the appropriate
regulatory level. While informed by the science, this determination is
ultimately a risk management decision. Once this methodology has been
developed, then the available chemical-specific data would be used to
determine whether or not the MOEs identified in the risk assessment constitute
acceptable risks.
For now, the regulatory decision for alachlor will be based on both the
Q,' approach and the MOE approach for the evaluation of carcinogenic
potential. These arc not directly comparable approaches. The Q," approach
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is indicative of a linear approach and reflects the assumption that any exposure
to alachlor could cause cancer. The MOE approach is indicative of a non-
linear approach and reflects the assumption that there is an exposure dose
below which tumor formation is not likely to occur. Thus, the risk numbers do
not translate from one approach to the other. Each approach must be
considered separately.
The alachlor database for pre-and post-natal effects is complete based on
current requirements. The Agency has reviewed two developmental toxicity
studies: one in rats, and one in rabbits. Developmental studies are designed to
identify possible adverse effects on the developing organism during pre-natal
development, which may result from the mother's exposure to the pesticide.
For alachlor, there is also a multi-generation rat reproduction study. A
reproduction study is designed to provide general information concerning the
effects of a test substance on mating begavior, conception, parturition,
lactation, weaning, and growth and development of the offspring.
Review by Agency scientists indicates no evidence of increased
susceptibility of rats or rabbits to jn utero and/or early postnatal exposure to
alachlor. Based on this conclusion, as well as additional information on
exposure to alachlor in food and water, the Agency has concluded that the
additional safety factor, as required by FQPA for the protection of infants and
children, can be removed. Therefore, this safety factor need not be applied to
the alachlor risk assessment
The toxicological effects of a pesticide can vary with different exposure
durations and routes. For example, an individual may be exposed throughout
their lifetime to pesticide residues in the food and water consumed, but a farm
worker could also be exposed for several days or a month to pesticide
formulations that can enter the body through the skin, or be inhaled. The
Agency considers the entire toxicity database and, based on the effects seen for
different durations and routes of exposure, determines which risk assessments
are necessary to insure that the public is adequately protected from any
pesticide exposure.
The alachlor reregistration eligibility review considered the following
assessments to be appropriate:
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Assessment
Exposure Route
NOEL1 for Use in |
Estimating Risk 1
Acute
Dietary
(food and water)
Not required - no evidence
of significant toxicity from
a one day or single event
exposure by the oral route 1
1 Chronic
| (non-carcinogenic)
Dietary
(food and water)
RfD2*3 = 0.01 mg/kg/day j
a Short-Term
I Occupational
Dermal + Inhalation
NOEL = 150 mg/kg/day 1
Use of dermal absorption 1
factor (0.24) required.4 |
| Intermediate-Term
Dermal + Inhalation
NOEL = 50 mg/kg/day j
Use of dermal absorption 1
factor not required since j
NOEL is from a dermal 1
study.4 |
| MOE Approach5
I Carcinogenic
Dietary
(food and water)
NOEL = 0.5 mg/kg/day j
(nasal) I
NOEL = 14 mg/kg/day j
(stomach) |
1 MOE Approach
B Carcinogenic
I Occupational
Dermal + Inhalation
Not appropriate - Exposure j
assessment does not 1
indicate that use is long- 1
term and continuous. J
1Q,* Approach6
Carcinogenic
Dietary
(food and water)
Q,* = 0.08 (mg/kg/day)"1 j
Residential
Dermal + Inhalation
Not appropriate - The 1
Agency has not identified |
any alachlor products that |
are intended for home use, £
or uses in/around schools,
parks or other public areas.
A NOEL (no observed effect level) is the dose at which no effects were
observed in the test animals.
The chronic Reference Dose (RID) is the traditionally selected endpoint
for chronic dietary risk. The RID represents the quantity of a substance
which if absorbed on a daily basis over a lifetime, is not expected to pose
significant risk of adverse health effects.
Acceptable risk is less than 100% of the RfD.
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4 Acceptable risk results in a MOE that is greater than 100,
5 Acceptable risk has not been determined.
6 Acceptable risk is 1 x 10"*, or lower.
Dietary Risk (Food Only)
People may be exposed to small amounts of alaehlor through the
consumption of food containing residues of alaehlor. Tolerances are pesticide
residue levels that should not be exceeded in or on a raw agricultural
commodity in the channels of interstate commerce when the pesticide is
applied according to label directions. Tolerances have been established (see 40
CFR 180.249) for residues of alaehlor in/on a variety of food and feed
commodities:
• beans, which includes dry beans, lima beans, forage and fodder;
• corn, fresh sweet, and forage, fodder, and grain;
eggs;
• milk;
• peanuts, forage, hay, and hulls;
• sorghum, fodder, forage, and grain;
• soybeans, forage, and hay;
• meat and meat byproducts of cattle, goats, hogs, poultry and horses.
Sufficient data are available to determine the adequacy of most
established tolerances. Based on this data, some tolerances need to be
revoked, and some need to be increased. The reassessed tolerances for
alaehlor will range from 0.02 to 10 ppm.
EPA has also assessed the chronic (non-carcinogenic) dietary risk posed
by alaehlor. Using refinements to the dietary assessment process and
considering all food uses recommended through reregistration, the Anticipated
Residue Concentration (ARC) for the overall U.S. population represents less
than 1 % of the chronic Reference Dose (RfD), the amount believed not to
cause adverse effects if consumed daily over a 70-year lifetime. The most
highly exposed subgroup, non-nursing infants less than one year old, has an
ARC which also represents less than 1% of the chronic RfD. This low fraction
of the allowable RfD is considered to be an acceptable dietary risk,
EPA has assessed the total carcinogenic dietary risk posed by alaehlor by
both the Q,* approach and the MOE approach. Both approaches are discussed
below in the Aggregate Dietary Discussion.
Dietary Risk (Drinking Water Only)
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People may be exposed to small amounts of alachlor through the
consumption of water containing residues of alachlor. Alachlor residues in
drinking water are regulated under the SDWA (Safe Drinking Water Act).
The MCL (Maximum Contaminant Level), set by the Agency, for alachlor is 2
ppb. An MCL is the maximum permissible level of a contaminant in drinking
water that is delivered to any user of a public water supply system. For
alachlor, there is extensive monitoring data for both ground and surface water
sources.
EPA has assessed the chronic (non-carcinogenic) drinking water risk
posed by alachlor. Using the monitoring data for alachlor only and Agency
assumptions on the amount of water consumed, the estimated exposure
represents less than 1% of the chronic Reference Dose (RfD), for adult males,
adult females, and children (1-6 years) sub-population groups. This is
considered to be an acceptable drinking water risk.
EPA has assessed the carcinogenic drinking water risk posed by alachlor,
using water monitoring data and Agency assumptions on the amount of water
consumed, for both the Q,* approach and the MOE approach. Both approaches
are discussed below in the Aggregate Dietary Discussion.
Aggregate Dietary Risk (Food and Drinking Water)
FQPA requires that the Agency consider aggregate risk, that is, exposure
from all food, water, and residential (non-occupational, non-dietary) exposures
when making a safety determination. Since there are no residential uses of
alachlor, the aggregate exposure is for food and water only. The highest
chronic risk is 4% of the chronic RfD which represents the sub-population
children (1-6 years). This was calculated considering both food and water
containing residues of alachlor as well as consumption of water containing
residues of the alachlor ESA degradate. The Agency considers this to be an
acceptable risk.
The aggregate carcinogenic risk using the Q," approach considers
exposures from both food and water. For adult males and adult females
carcinogenic risks range from 7.8 x 10"7 to 1.4 x 10"4. These risks are
consistent with the carcinogenic level (1 x 10"6) that the Agency considers to
be negligible.
The aggregate carcinogenic MOEs (food and drinking water) for adult
males and adult females vary from 29,000 to 1,400,000. At this time, the
Agency is not making any conclusions regarding the adequacy of these
calculated MOEs for carcinogenic dietary risk. This is due to the fact that the
Agency has not yet made a final decision as to the appropriate uncertainty
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factors which would be adequately protective of a carcinogenic endpoint
regulated using a non-linear approach. However, given that the cancer risk
using the Q,* approach is acceptable and that the magnitude of the calculated
MOEs is quite large, the Agency believes that the dietary cancer risk from the
use of alachlor is not of concern.
Occupational Exposure
Based on current use patterns, handlers (mixers, loaders, and applicators)
may be exposed to alachlor during normal use of gran ular, liquid, and dry
flowable formulations. No protective equipment is required for the granular
formulations. For worker protection, the Agency will require the use of
additional protective equipment (chemical resistant gloves, apron, and chemical
resistant shoes) when handling liquid and dry flowable formulations for
workers supporting groundboom applications. For workers supporting aerial
applications, closed (mechanical transfer) systems will be required for liquid
formulations. Monsanto will be required to develop water soluble packaging
for dry flowable formulations for aerial applications. Closed (mechanical
transfer)systems will be required for the dry bulk fertilizer impregnation
process.
The levels of protection required were based on the intermediate-term
exposure (one week to several months) scenario. As previously stated, the
exposure assessment indicated that use of alachlor is an intermittent exposure
(not long-term and continuous.) The carcinogenic MOE approach is not
appropriate for an occupational risk assessment for alachlor, because the
exposure is not of sufficient duration (i.e., chronic) to produce tumors.
Unlike the MOE approach to carcinogenic risk assessment, the Q,*
approach assumes that any exposure could result in tumor formation. Thus,
this type of assessment could be performed for an intermittent exposure.
However, the scientific validity of the MOE approach for carcinogenic risk
assessment of alachlor has been documented. Alachlor was classified as
"likely" to be a carcinogen at high doses, but "not likely" at low doses. It is
only the policy on determining an appropriate regulatory level that has not been
fully developed by the Agency. Since, performing a carcinogenic MOE risk
assessment for the occupational scenario is not appropriate, a Q," carcinogenic
occupational assessment for comparison purposes is not necessary.
The potential for post-application worker exposure is negligible,
provided the Restricted Entry Interval of 12 hours is observed. This is due to
the timing of applications. Alachlor is applied to the soil and/or soil
incorporated preplant, and pre-emergent. Thus the application of alachlor to
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
§158.175) or (2) provide certified limits that are supported by the analysis of five batches. If you
choose the second option, you must submit or cite the data for the five batches along with a
certification statement as described in 40 CFR §158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e. Certification With Respect to Citation of Data and Data Matrix. Complete and
sign EPA forms 8570-34 and 8570-35 for each product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
Bv U.S. Mail:
Document Processing Desk (REI)-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
Bv express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregistration determination within 14 months after the RED has been
issued.
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RFJD1
T
1. DATA CALL-IN fDCI) OR "90-DAY RESPONSE"—If generic data are required for
reregistration, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and product
specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2. TIME EXTENSIONS AND DATA WAIVER REQUESTS—No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies off draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
"regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further labeling
guidance, refer to the labeling section of the EPA publication "General Information on Applying
for Registration in the U.S., Second Edition, August 1992" (available from the National Technical
Information Service, publication #PB92-221811; telephone number 703-605-6000).
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).
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
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For More EPA is requesting public comments on the Reregistration Eligibility
Information Decision (RED) document for alachlor 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 Information and Records Integrity
Branch, Information Resources and Services Division (7502C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Electronic copies of the RED and this fact sheet are available on the
Internet. See http://www.epa.gov/REDs.
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 45242-2419, telephone 1-800-
490-9198; fax 513-489-8695.
Following the comment period, the Alachlor RED document also will be
available from the National Technical Information Service (NTIS), 5285 Port
Royal Road, Springfield, VA 22161, telephone 703-605-6000.
For more information about EPA's pesticide reregistration program, the
Alachlor RED, or reregistration of individual products containing alachlor
please contact the Special Review and Reregistration Division (7508C), 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 Pesticide Telecommunications Network (NPTN). Call toll-free 1-
800-858-7378, from 6:30 am to 4:30 pm Pacific Time, or 9:30 am to 7:30 pm
Eastern Standard Time, seven days a week. Their website address is
ace.orst.edu/info/nptn/.
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Changes Required
a comprehensive list of labeling requirements, please see the Alachlor RED
Document, Table 78.)
Classify alachlor as a Restricted Use Pesticide (RUP) for ground water
concerns,
• Label language regarding mixing/loading setback must appear in
Precautionary Statements in the Environmental Hazards Section.
• Groundwater advisory language.
• Surface water advisory language.
« Advisory statement in the Environmental Hazards Section of toxicity to
terrestrial and aquatic plants, fish, and aquatic invertebrates.
• Advisory statement for granular products.
• Spray Drift Labeling Language.
• For liquid (emulsiftable concentrate) formulations or dry flowable
formulations require that mixers, loaders, and persons cleaning
equipment must wear long-sleeved shirt, long pants, chemical-resistant
gloves, chemical-resistant footwear, and chemical-resistant apron for
those workers supporting groundboom application.
• For workers supporting aerial applications and chemigation, for liquid
(emulsifiable concentrate) formulations require that mixers, and loaders,
must wear long-sleeved shirt, long pants, and chemical-resistant gloves,
and the use of closed (mechanical transfer) systems.
For workers supporting aerial applications and chemigation, for dry
flowable formulations require that Monsanto develop water soluble
packaging.
• For impregnating dry bulk fertilizer with alachlor require the use of
closed mixing systems.
A 12 hour restricted entry interval (REI) is required for uses within the
scope of the WPS. The PPE required for early entry is coveralls,
chemical-resistant gloves, and shoes plus socks.
Regulatory EPA has determined that the reassessed tolerances for alachlor meet the
Conclusion safety standard under the FQPA, and that there is a reasonable certainty that no
harm will result to infants and children or to the general population from
aggregate exposure to alachlor residues. The use of currently registered
products containing alachlor 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. Alachlor
products will be reregistered once the required product-specific data, revised
Confidential Statements of Formula, and revised labeling are received and
accepted by EPA.
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Osb)\
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C, 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL "
DEC 2 9
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 alachlor. The '
enclosed Reregistration Eligibility Decision (RED), which was approved on September 30, 1998,
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 generic data on alachlor to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED," This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the date of your
receipt of this letter. The second set of required responses is 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 the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it will be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it proceeds with further policy
development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, tliat any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or w ish to meet with the
Agency, please contact the Special Review and Reregistration Division representative Kathryn
Boyle at (703) 305-6304.
Sincerely yours,
Ja tor
Special Review and Reregistration Division
Enclosures
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregi strati on eligibility review and decisions on the pesticide chemical case alachlor. The
enclosed Reregi strati on Eligibility Decision (RED), which was approved on September 30, 1998,
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 generic data on alachlor to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the date of your
receipt of this letter. The second set of required responses is 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 the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it will be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it proceeds with further policy
development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or wish to meet with the
Agency, please contact the Special Review and Reregi strati on Division representative Kathryn
Boyle at (703) 305-6304.
Sincerely yours,
Jack E. Housenger, Acting Director
Special Review and Reregi strati on Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCD OR "90-DAY RESPONSE" -If generic data are required for
reregi strati on, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and product
specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2 TIME EXTENSIONS AND DATA WAIVER REQUESTS-No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect.
3 APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE" -You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-11 Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration. For further labeling
guidance, refer to the labeling section of the EPA publication "General Information on Applying
for Registration in the U.S., Second Edition, August 1992" (available from the National Technical
Information Service, publication #PB92-221811; telephone number 703-605-6000).
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).
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
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
§158.175) or (2) provide certified limits that are supported by the analysis of five batches. If you
choose the second option, you must submit or cite the data for the five batches along with a
certification statement as described in 40 CFR §158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e. Certification With Respect to Citation of Data and Data Matrix. Complete and
sign EPA forms 8570-34 and 8570-35 for each product.
4 COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5 WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
Bv U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
Bv express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregi strati on determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
Alachlor
LIST A
CASE 0063
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
ALACHLOR REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY v
I. INTRODUCTION 1
II. 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
III. SCIENCE ASSESSMENT 7
A. Physical Chemistry Assessment 7
B. Human Health Assessment 8
1. Toxicology Assessment 8
a. Acute Toxicity 10
b. Subchronic Toxicity 11
c. Chronic Toxicity and Carcinogenicity 12
d. Developmental Toxicity 16
e. Reproductive Toxicity 16
f. Mutagenicity 17
g. Metabolism 20
h. Special Studies 23
i. ESA Metabolite of Alachlor 35
2. Dose Response Assessment 39
a. Reference Dose 39
b. Dermal Absorption 40
c. Cancer Classification 41
d. Other Toxicological Endpoints 44
e. Determination of the FQPA 10X Safety Factor 48
3. Exposure Assessment 50
a. Dietary Exposure 50
b. Dietary Exposure from Drinking Water 58
c. Occupational 63
4. Risk Characterization 79
a. Dietary 79
b. Drinking Water 86
c. Aggregate (Food and Water) 89
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d. Occupational 94
e. FQPA Considerations 108
C. Environmental Assessment 112
1. Use Characterization 112
2. Ecological Toxicity Data 115
a. Terrestrial Animals 116
b. Aquatic Animals 118
c. Plants 121
d. Conclusions 123
3. Environmental Fate Data 123
a. Degradation 123
b. Metabolism 124
c. Mobility/Leachability of Alachlor 126
d. Mobility of Alachlor Degradates 128
e. Volatility 131
f. Field Dissipation 131
g. Bioaccumulation 134
h. Spray Drift 134
4. Environmental Fate Assessment 134
a. Degradation and Metabolism 135
b. Mobility 135
c. Bioaccumulation 136
d. Field Dissipation 136
e. Volatility 137
f. Spray Drift 137
5. Terrestrial Exposure Assessment 137
6. Ground Water Monitoring Data 138
a. Introduction 138
b. Recent Groundwater Monitoring Data 139
c. Possible Concerns 147
7. Surface Water Monitoring Data 147
a. Introduction 147
b. Surface Water Data 148
c. Possible Concerns over Alachlor and Alachlor ESA in Surface
Water 152
8. Water Resource Assessment 153
a. Ground Water Assessment 153
b. Surface Water Assessment 156
c. Alachlor Degradates in Water 158
9. Aquatic Exposure Assessment 158
10. Comparative Assessment with Other Acetanilides 162
a. Environmental Fate Characteristics 162
b. Ecotoxicity 162
c. Comparative Assessment Tables for the Acetanilides Alachlor,
Acetochlor, Metolachlor, and Propachlor 164
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11. Environmental Risk Assessment 172
a. Introduction 172
b. Risk to Nontarget Terrestrial Animals 173
c. Risk to Nontarget Aquatic Animals 174
d. Risk to Nontarget Plants 175
e. Aquatic LOC Exceedances 176
f. Environmental Risk Summary 179
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 179
A. Determination of Eligibility 179
B. Determination of Eligibility Decision 180
1. Eligibility Decision 180
2. Eligible and Ineligible Uses 180
C. Regulatory Position 180
1. Food Quality Protection Act Findings 181
a. Determination of Safety for U.S. Population 181
b. Determination of Safety for Infants and Children 183
c. Endocrine Disrupter Effects 184
2. Tolerance Reassessment 184
3. Ecological Risk Mitigation 187
4. Surface Water Protection Measures 188
5. Ground Water Protection Measures 189
6. Restricted Use Classification 190
7. Pesticides Management Plan (PMP) Candidate 190
8. Endangered Species Statement 191
9. Labeling Rationale 191
10. Spray Drift Advisory 196
V. ACTIONS REQUIRED OF REGISTRANTS 196
A. Manufacturing-Use Products 196
1. Additional Generic Data Requirements 196
2. Labeling Requirements for Manufacturing-Use Products 197
B. End-Use Products 197
1. Additional Product-Specific Data Requirements 197
2. Labeling Requirements for End-Use Products 197
C. Existing Stocks 210
VI. APPENDICES 211
A. Table of Use Patterns Subject to Reregistration 213
B. Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision 215
C. Citations Considered to be Part of the Data Base Supporting the Reregistration
Decision 227
D. Combined Generic and Product Specific Data Call-In 258
1. Chemical Status Sheets 279
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2. Combined Generic and Product Specific Data Call-In Response Forms
(Insert A) Plus Instructions 281
3. Generic and Product Specific Requirement Status and Registrant's
Response Forms (Insert B) and Instructions 290
4. EPA Batching of End-Use Products for Meeting Data Requirements for
Reregistration 304
5. List of All Registrants Sent This Data Call-In (insert) Notice .... 307
E. List of Available Related Documents and Electronically Available Forms 313
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ALACHLOR REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Neil Anderson
Arthur Grube
Cynthia Doucoure
Herbicide and Insecticide Branch
Economic Analysis Branch
Science Information and Analysis Branch
Environmental Fate and Effects Risk Assessment
Nelson Thurman
Richard Felthousen
Jose Melendez
Sid Abel
Laurence Libelo
Health Effects Risk Assessment
Kathryn Boyle
Susan Hummel
Stephen Dapson
Carol Lang
Registration Division
Vickie Walters
Risk Management
Judith Loranger
Kathryn Boyle
Environmental Risk Branch IV
Environmental Risk Branch IV
Environmental Risk Branch IV
Environmental Risk Branch IV
Environmental Risk Branch IV
Reregi strati on Branch 1
Chemistry and Exposure Branch 2
Toxicology Branch 2
Chemistry and Exposure Branch 1
Herbicide Branch
Reregi strati on Branch 3
Reregi strati on Branch 3
l
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Intentionally Blank Page
11
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
DRES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (D WEL) The DWEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HDT Highest Dose Tested
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/L, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50%
of the test animals when administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOC Level of Concern
LOD Limit of Detection
LOEC Lowest Observed Effect Concentration
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
|ig/g Micrograms Per Gram
fj-g/L Micrograms per liter
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
MPI
Maximum Permissible Intake
MRID
Master Record Identification (number). EPA's system of recording and tracking studies submitted.
N/A
Not Applicable
NOEC
No Observable Effect Concentration
NPDES
National Pollutant Discharge Elimination System
NOEL
No Observed Effect Level
NOAEL
No Observed Adverse Effect Level
OP
Organophosphate
OPP
Office of Pesticide Programs
Pa
pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
PADI
Provisional Acceptable Daily Intake
PAG
Pesticide Assessment Guideline
PAM
Pesticide Analytical Method
PHED
Pesticide Handler's Exposure Data
PHI
Preharvest Interval
PPb
Parts Per Billion
PPE
Personal Protective Equipment
ppm
Parts Per Million
PRN
Pesticide Registration Notice
Q*i
The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC
Red Blood Cell
RED
Reregistration Eligibility Decision
REI
Restricted Entry Interval
RfD
Reference Dose
RS
Registration Standard
RUP
Restricted Use Pesticide
SLN
Special Local Need (Registrations Under Section 24 (c) of FIFRA)
TC
Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD
Toxic Dose. The dose at which a substance produces a toxic effect.
TEP
Typical End-Use Product
TGAI
Technical Grade Active Ingredient
TLC
Thin Layer Chromatography
TMRC
Theoretical Maximum Residue Contribution
torr
A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
TWMC
Time Weighted Mean Concentration
WP
Wettable Powder
WPS
Worker Protection Standard
iv
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EXECUTIVE SUMMARY
This Reregi strati on Eligibility Decision Document (RED) addresses the reregi strati on
eligibility of the pesticide alachlor, 2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide.
Alachlor is a herbicide used for weed control on corn, soybeans, sorghum, peanuts, and beans. There
are liquid, dry flowable, microencapsulated, and granular formulations. The timing of applications
is preplant, pre-emergent, at-plant for corn and soybeans, post-transplant, post-emergent, and at
ground crack for peanuts only. Alachlor is applied by ground, aerial, and chemigation equipment.
It can also be mixed with dry bulk fertilizer.
Alachlor was first registered in 1969 as a selective herbicide for control of broadleaf weeds
and grasses. Alachlor is produced by the Monsanto Company in the US.
EPA has completed its reregi strati on eligibility decision for the pesticide alachlor and
determined that all uses, when labeled and used as specified in this document, are eligible for
reregi strati on. This decision includes a comprehensive reassessment of the required target data base
supporting the use patterns of currently registered products. This decision considered the
requirements of the "Food Quality Protection Act of 1996" (FQPA) which amended the Federal Food
Drug and Cosmetic Act and the Federal Insecticide Fungicide and Rodenticide Act, the two Federal
statutes that provide the framework for pesticide regulation in the United States. FQPA became
effective immediately upon signature and all Reregistration Eligibility Decisions (REDs) signed
subsequent to August 3, 1996, are accordingly being evaluated under the new standards imposed by
FQPA.
Reregistration Eligibility
The Agency has concluded under the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) that all uses, as prescribed in this document, will not cause unreasonable risks to humans
or the environment and therefore all products are eligible for reregistration. The Agency has accepted
a risk mitigation measure, proposed by the technical registrant Monsanto, requiring application rate
reductions. To assure protection of ground water as a resource, Monsanto has offered to classify
alachlor as a Restricted Use Pesticide for ground water concerns. Certain ecological data, residue
chemistry data, and exposure data are required to confirm the Agency's risk assessment and
conclusions.
In establishing or reassessing tolerances, FQPA requires the Agency to consider aggregate
exposures to pesticide residues, including all anticipated dietary exposures and other exposures for
which there is reliable information, as well as the potential for cumulative effects from pesticides and
other compounds with a common mechanism of toxicity. FQPA further directs EPA to consider the
potential for increased susceptibility of infants and children to the toxic effects of pesticide residues,
and to develop a screening program to determine whether pesticides produce endocrine disrupting
effects.
v
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FQPA requires that the Agency consider the cumulative effects of alachlor and other
chemicals that have a common mechanism of toxicity. The Agency first must determine if a common
mechanism of toxicity exists for a group of chemicals. If so, the Agency must decide on the
appropriate methodology for combining exposures, and then, after reviewing use
information/patterns, determine which of the exposures/scenarios for which chemicals are to be
combined, (i.e., cumulative exposure does occur.)
Alachloris structurally similarto four other pesticides: acetochlor, butachlor, propachlor, and
metolachlor. The Agency has not yet completed its assessment of whether or not these chemicals
actually have a common mechanism of toxicity. However, a presentation was made to the FIFRA
Scientific Advisory Panel (SAP) in March 1997 in which six chloroacetanilide chemicals were
presented as a case study. In this case study, several groupings of the chemicals were possible:
I.acetochlor, alachlor and butachlor - based on structure activity relationships (SAR) consideration
of common reactive intermediates
II.acetochlor, alachlor, and butachlor - based on statistically significant increases in nasal tumors
(metolachlor nasal tumors were not statistically significant)
• acetochlor, alachlor, and butachlor - based on thyroid follicular cell tumors
• acetochlor, alachlor, propachlor, and butachlor - based on stomach tumors or lesions
• acetochlor, alachlor, and butachlor - based on kidney effects
• acetochlor, alachlor, propachlor, butachlor, and dimethamide - based on liver effects
• dimethamide, metolachlor, and propachlor - based on liver tumors
At this time, no determination on the appropriate grouping to use in the assessment has been
made. The Agency is in the process of responding to comments resulting from the SAP. For
alachlor, neither the appropriate methodology for combining exposures nor the exposures to combine
has been determined. However, the Agency has just released a guidance document describing the
approach that EPA will use for identifying mechanisms of toxicity and categorizing pesticide
chemicals that have a common mechanism of toxicity. Additionally, the single chemical/multi-
pathway assessments of each of the chemicals must be completed before the Agency could perform
the multi-chemical/multi-pathway assessment. Metolachlor was a 1995 RED. Acetochlor was
registered in the early 1990s. Both chemicals would need updated risk assessments. Propachlor is
also a 1998 RED. As a result, the Alachlor RED can only go forward at this time as a single
chemical/multi-pathway assessment.
The Agency has reassessed all alachlor food and feed related tolerances under the standards
of FQPA and determined that, based on available information, there is a reasonable certainty that no
harm will result to infants and children or to the general population from aggregate exposure to
alachlor residues. The only type of exposures evaluated were dietary (food and drinking water)
exposures, since non-occupational exposures (primarily residential) are unlikely to occur with alachlor
use.
vi
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Human Health Effects
Alachlor has been evaluated for carcinogenic activity in rats and mice. In accordance with
the 1996 EPA proposed Guidelines for Carcinogen Risk Assessment, alachlor was classified as
"likely" to be a human carcinogen at high doses, but" not likely" at low doses. Based on numerous
studies submitted by the registrant that were reviewed by Agency scientists, as well as an external
peer review panel, it was agreed that a margin of exposure (MOE) approach (indicative of a non-
linear dose response) would be appropriate for evaluating carcinogenic risk in a human health risk
assessment.
The scientific validity of the MOE approach has been documented by various review panels,
such as the FIFRA Scientific Advisory Panel, and the Cancer Review Committee. However, the
policy implications, methodology, and appropriateness of using an MOE approach in regulatory
decision making have not yet been fully developed by the Agency. Perhaps, the most critical of the
decision criteria to develop are those for determining the appropriate regulatory level. While
informed by the science, this determination is ultimately a risk management decision. Once this
methodology has been developed, then the available chemical-specific data would be used to
determine whether or not the MOEs identified in the risk assessment constitute acceptable risks.
For now, the regulatory decision for alachlor will be based on both the Qx* approach and the
MOE approach for the evaluation of carcinogenic potential. These are not directly comparable
approaches. The Qx* approach is indicative of a linear approach and reflects the assumption that any
exposure to alachlor could cause cancer. The MOE approach is indicative of a non-linear approach
and reflects the assumption that there is an exposure dose below which tumor formation is not likely
to occur. Thus, the risk numbers do not translate from one approach to the other. Each approach
must be considered separately.
The alachlor database for pre-and post-natal effects is complete based on current
requirements. The Agency has reviewed two developmental toxicity studies: one in rats, and one
in rabbits. Developmental studies are designed to identify possible adverse effects on the developing
organism during pre-natal development which may result from the mother's exposure to the
pesticide. For alachlor, there is also a multi-generation rat reproduction study. A reproduction study
is designed to provide general information concerning the effects of a test substance on mating
behavior, conception, parturition, lactation, weaning, and growth and development of the offspring.
In both of the developmental toxicity studies, the NOELs for developmental effects are the
same as the NOELs for maternal effects. Generally, the Agency would be particularly concerned
when developmental effects are seen at doses lower than those which cause maternal effects, i.e. a
situation in which the mother is not impacted, but the developing organism would be impacted. For
alachlor, there is no evidence of a unique sensitivity to the developing organism from pre-natal
exposure. In the reproductive toxicity study, the reproductive NOEL is higher than the systemic
NOEL, indicating that the parents would be impacted before the offspring. No special sensitivity for
infants or children is indicated. Thus, review by Agency scientists indicates no evidence of increased
vii
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susceptibility of rats or rabbits to in utero and /or early postnatal exposure to alachlor.
Based on this conclusion, as well as the available information on exposure to residues of
alachlor in food and water, the Agency has concluded that the additional safety factor, as required
by FQPA for the protection of infants and children, can be removed. Therefore, this safety factor
need not be applied to the alachlor risk assessment.
The toxicological effects of a pesticide can vary with different exposure durations and routes.
For example, an individual may be exposed throughout their lifetime to pesticide residues in the food
and water consumed, but a farm worker could also be exposed for several days or a month to a
pesticide by the dermal and/or inhalation routes of exposure. The Agency considers the entire
toxicity database and, based on the effects seen for different durations and routes of exposure,
determines which risk assessments are necessary to insure that the public is adequately protected from
any pesticide exposure.
The alachlor reregistration eligibility review considered the following assessments to be
appropriate:
Assessment
Exposure Route
NOEL1 for Use in Estimating Risk
Acute
Dietary
(food and water)
Not required - no evidence of significant
toxicity from a one day or single event
exposure by the oral route
Chronic
(non-carcinogenic)
Dietary
(food and water)
RfD2'3 = 0.01 mg/kg/day
Short-Term
Occupational
Dermal + Inhalation
NOEL =150 mg/kg/day
Use of dermal absorption factor (0.24)
required.4
Intermediate-Term
Dermal + Inhalation
NOEL = 50 mg/kg/day
Use of dermal absorption factor not required
since NOEL is from a dermal study.4
MOE Approach5
Carcinogenic
Dietary
(food and water)
NOEL = 0.5 mg/kg/day (nasal)
NOEL =14 mg/kg/day (stomach)
MOE Approach
Carcinogenic
Occupational
Dermal + Inhalation
Not appropriate - Exposure assessment does
not indicate that use is long-term and
continuous.
Qj* Approach6
Carcinogenic
Dietary
(food and water)
Qj* = 0.08 (mg/kg/day)"1
viii
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Assessment
Exposure Route
NOEL1 for Use in Estimating Risk
Residential
Dermal + Inhalation
Not appropriate - The Agency has not
identified any alachlor products that are
intended for home use, or uses in/around
schools, parks or other public areas.
A NOEL (no o
^served effect level) is the dose at which no effects were observed in the test
animals.
2 The chronic Reference Dose (RfD) is the traditionally selected endpoint for chronic dietary
risk. The RfD represents the quantity of a substance which if absorbed on a daily basis over
a lifetime, is not expected to pose significant risk of adverse health effects.
3 Acceptable risk is less than 100% of the RfD.
4 Acceptable risk results in a MOE that is greater than 100.
5 Acceptable risk has not been determined.
6 Acceptable risk is 1 x 10"6, or lower.
Dietary Risk (Food Only')
People may be exposed to small amounts of alachlor through the consumption of food
containing residues of alachlor. Tolerances are pesticide residue levels that should not be exceeded
in or on a raw agricultural commodity in the channels of interstate commerce when the pesticide is
applied according to label directions. Tolerances have been established (see 40 CFR 180.249) for
residues of alachlor in/on a variety of food and feed commodities:
• beans, which includes dry beans, lima beans, forage and fodder;
• corn, fresh sweet, and forage, fodder, and grain;
eggs;
• milk;
• peanuts, forage, hay, and hulls;
• sorghum, fodder, forage, and grain;
• soybeans, forage, and hay;
• meat and meat byproducts of cattle, goats, hogs, poultry and horses.
Sufficient data are available to determine the adequacy of most established alachlor tolerances.
However, some tolerances need to be revoked, and some need to be increased. The reassessed
tolerances for alachlor will range from 0.02 to 10 ppm.
EPA has assessed the chronic (non-carcinogenic) dietary risk posed by alachlor. Using
refinements to the dietary assessment process and considering all food uses recommended through
reregi strati on, the Anticipated Residue Concentration (ARC) for the overall U.S. population
represents less than 1% of the chronic Reference Dose (RfD), the amount believed not to cause
adverse effects if consumed daily over a 70-year lifetime. The most highly exposed subgroup, non-
nursing infants less than one year old, has an ARC which also represents less than 1% of the chronic
RfD. This low fraction of the allowable RfD is considered to be an acceptable dietary risk.
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EPA has assessed the carcinogenic dietary risk posed by alachlor by both the Qx* approach
and the MOE approach. Both approaches are discussed below in the Aggregate Dietary Exposure
Discussion.
Dietary Risk (Drinking Water Only")
People may be exposed to small amounts of alachlor through the consumption of water
containing residues of alachlor. Alachlor is regulated under the SDWA (Safe Drinking Water Act).
The MCL (Maximum Contaminant Level) for alachlor is 2 ppb. An MCL is the maximum permissible
level of a contaminant in drinking water that is delivered to any user of a public water supply system.
For alachlor, there is extensive monitoring data for both ground and surface water.
EPA has assessed the chronic (non-carcinogenic) drinking water risk posed by alachlor.
Using the monitoring data for alachlor only and Agency assumptions on the amount of water
consumed, the estimated exposure represents less than 1% of the chronic Reference Dose (RfD), for
adult males, adult females, and children (1-6 years) sub-population groups. The Agency considers
this to be an acceptable risk due to consumption of drinking water containing small amounts of
alachlor.
EPA has assessed the carcinogenic drinking water risk posed by alachlor, using monitoring
data and Agency assumptions on the amount of water consumed, for both the Qx* approach and the
MOE approach. Both approaches are discussed below in the Aggregate Dietary Exposure Discussion.
Aggregate Dietary Risk (Food and Drinking Water)
FQPA requires that the Agency consider aggregate risk, that is, exposure from all food, water,
and non-occupational, non-dietary exposures. For alachlor, the aggregate exposure is for food and
water only. The highest chronic risk was 4% of the chronic RfD which represents the sub-population
child (1-6 years). This was calculated considering both food and water containing residues of
alachlor as well as consumption of water containing residues of the alachlor ESA degradate. The
Agency considers this to be an acceptable risk.
The aggregate carcinogenic risk using the Q, approach considers exposures from both food
and water. For adult males and adult females carcinogenic risks range from 7.8 x 10"7 to 1.4 x 10"6.
These risks are consistent with the carcinogenic level (1 x 10"6) that the Agency considers to be
negligible.
The aggregate carcinogenic MOEs (food and drinking water) for adult males and adult
females vary from 29,000 to 1,400,000. At this time, the Agency is not making any conclusions
regarding the adequacy of these calculated MOEs for carcinogenic dietary risk. This is due to the fact
that the Agency has not yet made a final decision as to the appropriate uncertainty factors which
would be adequately protective of a carcinogenic endpoint regulated using a non-linear approach.
However, given that the cancer risk using the Q, approach is acceptable and that the magnitude of
x
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the calculated MOEs is quite large, the Agency believes that the dietary cancer risk from the use of
alachlor is not of concern.
A comparison of the two approaches is given in the following Table:
Comparison of Carcinogenic Dietary Assessments
Source of Water
used in
Assessment
Exposure
(food and water)
MOE
(nasal tumors)
(MOE)
(stomach
tumors)
q;
Adult Male
NAWWS1
(ground water)
0.0000127
39,000
1,100,000
1.0 X 10"6
USGS2
(reservoir data)
0.0000132
38,000
1,100,000
1.1 x 10"6
ARP3
(surface water)
0.0000098
51,000
1,400,000
7.8 x 10"7
Adult Female
NAWWS
(ground water)
0.0000166
30,000
840,000
1.3 x 10"6
USGS
(reservoir)
0.0000173
29,000
810,000
1.4 x 10"6
ARP
(surface water)
0.0000133
38,000
1,100,000
1.1 x 10"6
Data is from the National Alach
or Well Water Survey
2 Data is from the United States Geological Survey
3 Data is from the Acetochlor Registration Partnership
Occupational Risk
Based on current use patterns, handlers (mixers, loaders, and applicators) may be exposed to
alachlor during normal use of granular, liquid, and dry flowable formulations. No protective
equipment is required for the granular formulations. For worker protection, the Agency will require
the use of additional protective equipment (chemical resistant gloves, apron, and chemical resistant
shoes) when handling liquid and dry flowable formulations for workers supporting groundboom
applications. For workers supporting aerial applications, closed (mechanical transfer) systems will
be required for liquid formulations. Monsanto will be required to develop water soluble packaging
for dry flowable formulations for aerial applications. Closed (mechanical transfer) systems will be
XI
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required for the dry bulk fertilizer impregnation process.
The levels of protection required were based on the intermediate-term (one week to several
months) exposure scenario. The exposure assessment indicated that use of alachlor is an intermittent
exposure. The MOE methodology is consistent with a non-linear mechanism which requires
continuous exposure. Due to the existence of an exposure pattern that is intermittent (not long-term
and continuous), it is not appropriate to perform a carcinogenic MOE risk assessment for the
occupational scenario.
Unlike the MOE approach to carcinogenic risk assessment, the Qx* approach assumes that
any exposure could result in tumor formation. Thus, this type of assessment could be performed for
an intermittent exposure. However, the scientific validity of the MOE approach for carcinogenic risk
assessment of alachlor has been documented. Alachlor was classified as "likely" to be a carcinogen
at high doses, but "not likely" at low doses. It is only the policy on determining an appropriate
regulatory level that has not been fully developed by the Agency. Since, performing a carcinogenic
MOE risk assessment for the occupational scenario is not appropriate, a Qx* carcinogenic
occupational assessment for comparison purposes is not necessary.
The potential for post-application worker exposure is negligible, provided the Restricted Entry
Interval (REI) of 12 hours is observed. This is due to the timing of applications. Alachlor is applied
to the soil and/or soil incorporated pre-plant, and pre-emergent. Thus the application of alachlor to
emerging plants, well before the plants are mature, mitigates the potential for post-application
exposure.
Environmental Assessment
The Environmental Fate Assessment for alachlor shows that:
• Alachlor has a low affinity to adsorb to soils and is expected to be highly mobile.
• Alachlor is moderately persistent and dissipates primarily by aerobic soil metabolism
processes with a half-life of 2-3 weeks.
• The major acid degradates of alachlor are very mobile and appear to be persistent.
• Field dissipation studies confirm this fate profile (half-life of 6-11 days; leaching through 42-
48 inches in one of the studies).
The Water Resources Assessment concludes that:
• Alachlor is highly mobile and moderately persistent. These two characteristics are generally
observed in chemicals that reach ground water and surface water.
• Alachlor presents a clear hazard to groundwater quality. Reliable monitoring studies have
demonstrated that alachlor, even when used according to the label instructions, results in
significant groundwater contamination. Alachlor use also results in groundwater in the use
areas being contaminated with degradation products, which are also very mobile and
persistent,
• Monitoring studies show that alachlor levels in surface water result in effects on aquatic plants
Xll
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and indirectly on aquatic animals.
• Available information indicates that (surface) drinking water supply systems will usually
comply with the SDWA.
The available toxicity data for alachlor indicate that alachlor is:
• Slightly to practically non-toxic to birds on an acute oral basis (LD50 of 1500 mg/kg).
• Slightly toxic to mammals, based on a rat study (LD50 of 930 mg/kg).
• Slightly toxic to honey bees (LD50 >36 (jg/bee).
• Slightly to moderately toxic on an acute basis to freshwater fish (LC50 1-33 ppm).
• Highly to moderately toxic to freshwater fish on a chronic basis (NOEC> 0.1 ppm, LOEC> 0.2
ppm).
• Moderately toxic to saltwater fish (3.9 ppm), moderately toxic to saltwater mysid (2.4 ppm)
and moderately toxic to shellfish (1.6 ppm).
• Highly toxic to aquatic plants (based on a single species tested: NOEL=0.3 5 ppb, LOEL=0.69
ppb, EC50=1.64ppb).
Therefore, a potential risk to nontarget terrestrial and aquatic plants, and endangered plant
species exists. Additionally, the available information on the major alachlor degradates indicates that
the degradates appear to be less toxic to aquatic organisms than the parent.
An evaluation of the risk to nontarget organisms from the use of alachlor products, combining
toxicity data with potential exposure, indicates that:
• Alachlor poses a potential risk to terrestrial animals on a chronic basis. Additional
information are required to confirm this assessment.
• The granular formulations and high use rate pose the greatest risk to nontarget organisms.
• Alachlor levels observed in surface water monitoring studies could result in extensive adverse
effects on aquatic plants.
• Aquatic animals are not at acute risk due to exposure to alachlor, but chronic effects may be
observed under certain circumstances.
The Agency has significant concerns about the impact alachlor and its degradates may have
on groundwater quality. Consideration of environmental chemistry and fate properties indicates that
alachlor and a number of alachlor degradates will leach to ground water. An extensive body of
groundwater monitoring information has been reviewed which confirms that alachlor and alachlor
degradates do in fact contaminate groundwater.
To mitigate these concerns, the Agency will:
• Classify alachlor as a Restricted Use Pesticide (RUP) for ground water concerns
• Add labeling language requiring a 50 ft setback of mixing and loading activities from wells,
rivers, or lakes unless such activity is protected by an impervious pad.
• After promulgation of the Ground Water and Pesticides Management Plan Rule, require use
in accordance with an approved State or Tribal Management Plan
Xlll
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Product Reregistration
Before reregistering the products containing alachlor, the Agency is requiring that product
specific data, revised Confidential Statements of Formula (CSF) and revised labeling be submitted
within eight months of the issuance of this decision document. These data include product chemistry
for each registration and acute toxicity testing. After reviewing these data and any revised labels and
finding them acceptable in accordance with Section 3(c)(5) of FIFRA, the Agency will reregister a
product. Those products which contain other active ingredients will be eligible for reregistration only
when the other active ingredients are determined to be eligible for reregistration.
xiv
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to
accelerate the reregi strati on of products with active ingredients registered prior to November 1,1984.
The amended Act provides a schedule for the reregi strati on process to be completed in nine years.
There are five phases to the reregi strati on process. The first four phases of the process focus on
identification of data requirements to support the reregi strati on of an active ingredient and the
generation and submission of data to fulfill the requirements. The fifth phase is a review by the U.S.
Environmental Protection Agency (referred to as "the Agency") of all data submitted to support
reregi strati on.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine whether
pesticides containing such active ingredient are eligible for reregi strati on" before calling in data on
products and either reregistering products or taking "other appropriate regulatory action." Thus,
reregi strati on involves a thorough review of the scientific data base underlying a pesticide's
registration. The purpose of the Agency's review is to reassess the potential hazards arising from the
currently registered uses of the pesticide; to determine the need for additional data on health and
environmental effects; and to determine whether the pesticide meets the "no unreasonable adverse
effects" criterion of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170)
was signed into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 301 etseq., and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C.
136 et seq. The FQPA amendments went into effect immediately. As a result, EPA has embarked
on an intensive process, including consultation with registrants, States, and other interested
stakeholders, to make decisions on the new policies and procedures that will be appropriate as a result
of enactment of FQPA. This process includes a more in depth analysis of the new safety standard and
how it should be applied to both food and non-food use pesticides. The FQPA does not, however,
amend any of the existing reregi strati on deadlines set forth in §4 of FIFRA. In addition, in light of
the unaffected statutory deadlines with respect to reregistration, the Agency will continue its ongoing
reregi strati on program while it continues to determine how best to implement FQPA.
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of alachlor including the risk to infants and children for any potential dietary, drinking
water, dermal or oral exposures, and cumulative effects as stipulated under the FQPA. The document
consists of six sections. Section I is the introduction. Section II describes alachlor, its uses, data
requirements and regulatory history. Section III discusses the human health and environmental
assessment based on the data available to the Agency. Section IV presents the reregistration decision
for alachlor. Section V discusses the reregistration requirements for alachlor. 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.
1
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II. CASE OVERVIEW
a. Chemical Overview
The following active ingredient is covered by this Reregi strati on Eligibility Decision:
! Common Name: Alachlor
! Chemical Name: 2-chloro-N-(2,6-diethylphenyl)-
N-(methoxy methyl)acetami de
! Chemical Family: Acetanilide
! CAS Registry Number: 15972-60-8
! OPP Chemical Code: 090501
! Empirical Formula: C14H20NO2Cl
! Trade and Other Names: Lasso, Alanex
! Basic Manufacturer: Monsanto Chemical Company
b. Use Profile
The following is information on the currently registered uses with an overview of use sites and
application methods. A detailed table of these uses of alachlor is in Appendix A.
Type of Pesticide: Herbicide
Mode of Action: Chloroacetamides are known to inhibit biosynthesis of fatty acids,
lipids, protein, isoprenoids, flavonoids, and gibberellins.
Use Sites:
TERRESTRIAL FOOD+FEED CROP
Crops Grown for Oil: Soybeans
Grain Crops: Corn (Field), Sorghum
Groups of Agricultural Crops Which Cross Established Crop Groupings: Corn (unspecified),
Peanuts (unspecified), Soybeans (unspecified)
-------
Seed and Pod Vegetables: Beans (Dried-Type), Beans (Mung), Beans (Succulent, Lima),
Soybeans (Edible)
Specialized Field Crops: Corn (Pop)
TERRESTRIAL FEED CROP
Forage Grasses: Corn
Forage Legumes and Other Nongrass Forage Crops: Soybeans
TERRESTRIAL NON-FOOD+OUTDOOR RESIDENTIAL
Ornamental Woody Shrubs and Vines
Target Pests for Single Active Ingredient Products:
Barnyardgrass, Crabgrass, Cupgrass (woolly), Foxtail (giant, green, robust, purple, yellow,
robust white), Goosegrass, Johnsongrass, Millet, Panicum (browntop, fall, Texas), Rice (red),
Sandbur, Grassbur, Shattercane (wildcane), Signalgrass (broadleaf), Red Sprangletop,
Witchgrass, Florida Beggarweed, Carpetweed, Cocklebur, Coffeeweed, Copperleaf,
Galinsoga, Groundcherry (annual), Groundcherry (cutleaf), Jimsonweed, Kochia,
Lambsquarters, Morningglory (tall, pitted, ivyleaf, entireleaf, smallflower), Mustard,
Nightshade (black, hairy), Pigweed, Carelessweed, Purslane, Florida Pusley, Common
Ragweed, Giant Ragweed, Sicklepod, Smartweed, Bristly Starbur, Common Sunflower,
Velvetleaf, Buttonweed, Waterhemp, Yellow Nutsedge, Amaranths, Milkweed, Russian
Thistle, Canada Thistle, Horseweed, Fleabane, Prickly Lettuce, Hophornbeam copperleaf,
Burcucumber, Yellow Nutgrass, Texasweed, Mexicanweed, Spotted Spurge, Quackgrass,
WildPoinsettia, Brachiaria, Smooth Brome, Downy Brome, Orchardgrass, Fescue, Perennial
Ryegrass, Wirestem Muhly, Wheat, Corn, Annual Bluegrass, Kentucky Bluegrass, Sorghum,
Alfalfa, Hemp Sesbania, Red Clover, White Clover, Venice Mallow, Sida (prickly, spiny),
Teaweed, Ladysthumb, Curly Dock, Witchweed, Redweed, Common Mullein, Marestail,
Eastern Black Nightshade, Puncturevine.
Formulation Types Registered:
Technical Grade Active Ingredient
End Use Products
• Emulsifiable Concentrate
• Flowable Concentrate
• Granular
• Microencapsulated
• Soluble Concentrate/Liquid
3
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Multiple Active Ingredient Products Contain:
• 036101 (Trifluralin)
• 080803 (Atrazine)
• 103601 (Glyphosate-salt)
• 128848 (Imazaquin)
• 080803 + 129043 (Atrazine + Dicamba)
Method and Rates of Application:
Method and Rate - see Appendix A
Equipment - Aircraft; Boom sprayer; Center pivot irrigation; Granule applicator; Ground;
Pneumatic (compressed air) applicator; Sprayer; Spreader
Type of Treatment - Band treatment; Chemigation; Conservation tillage; Directed spray;
Soil broadcast treatment; Soil incorporated treatment; Soil treatment;
Spray
Timing - At planting; Early preplant; Ground-crack; Postemergence; Postplant;
Posttransplant; Preemergence; Preplant
c. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of alachlor. These
estimates are derived from a variety of published and proprietary sources, as well as USDA and State
statistics that are available to the Agency. The data, reported on an aggregate and site (crop) basis,
reflect annual fluctuations in use patterns as well as the variability in using data from various
information sources.
Table 1 below summarizes the pesticide's use by site.
Table 1: Percent of Various U.S. Crops Treated Annually with Alachlor,
1993 - 1995
Site/1
Acres
Grown
/2 (X 000)
Acres Treated
(X 000 )/3
Percent
Crop
Treated
Pounds AI
Applied (X 000)
Major Region
or State
Beans, Dry
1,826
150-170
<10
270 - 330
Nationwide
Beans, Succulent
44
5 - 15
10-35
15-25
CA and ID
Corn, Sweet
763
235 -250
30-35
400 - 500
Nationwide
4
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Table 1: Percent of Various U.S. Crops Treated Annually with Alachlor,
1993 - 1995
Site/1
Acres
Grown
/2 (X 000)
Acres Treated
(X 000 )/3
Percent
Crop
Treated
Pounds AI
Applied (X 000)
Major Region
or State
Corn, Field
77,235
15,000 -20,000
20-25
20,000 - 30,000
Nationwide
Ornamentals
597
15-20
<5
20-25
Southeast
Peanuts
1,688
20-30
<5
100-150
Southeast
Sorghum
10,944
1,050 - 1,450
10-15
1,500 -2,500
Nationwide
Soybeans
60,418
4,000 - 6,000
5 - 10
7,000 - 11,000
Nationwide
Sunflowers
2,837
20-30
<1 - 1
20-40
SDandNE
Totals
20,495 - 27,965
29,325 - 44,570
/1 - Site identification based on REFS.
/2 - Acres grown based on USDA, Agricultural Census, and state statistics.
/3 - Acres treated represents the number of acres treated times the number of applications.
d. Data Requirements
Data requested in the 1984 Registration Standard for alachlor include studies on product
chemistry, environmental fate, toxicology and residue chemistry. Pursuant to FIFRA, Data Call-In
Notices (DCIs) were issued on June 9, 1986, (required the submission of residue chemistry data),
June 18, 1986, (required the submission of use and exposure data pertaining to the ground and
surface water studies), August 28, 1991, (required the submission of ecological effects, residue
chemistry and environmental fate studies), and October 13, 1995, (required the submission of
exposure data). These data were required to support the uses listed in the Registration Standard.
Appendix B includes all data requirements identified by the Agency for currently registered uses
needed to support reregi strati on.
e. Regulatory History
Alachlor was registered in 1969 as a selective herbicide for control of broadleaf weeds and
grasses. In the US, technical alachlor alachlor is produced by Monsanto Company. There are 12
active products and one 24(c) registration. Monsanto has ten active products and American Cyanamid
has two active products.
A Registration Standard was issued for alachlor on November 20, 1984. The Registration
Standard stated that (1) alachlor was classified as an oncogen and therefore subject to the Agency's
requirement that it be considered for Special Review, (2) that the Agency would not approve any
new uses for alachlor during the period of the Special Review, and (3) that alachlor appeared to leach
through the soil and had been found in groundwater. Monsanto voluntarily removed the use of
5
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alachlor on potatoes. Several label restrictions were required to mitigate risk from alachlor. These
restrictions included: the use of protective clothing, a tumor hazard warning statement, a water
contamination warning statement, prohibition of aerial application, and handling instructions to reduce
applicator exposure. A special information and training program available to all users of alachlor was
required.
The Registration Standard required additional data on the leaching and mobility of alachlor
to examine the potential of alachlor to contaminate ground and surface water. A monitoring study
of ground and surface water was required. Additional studies were also required in the areas of
toxicology, product chemistry, and residue chemistry.
Alachlor has been the subject of previous Agency regulatory action. On January 9, 1985, the
Agency published a Notice of Initiation of Special Review of Registrations of Pesticide Products
Containing Alachlor (Federal Register. Volume 50, No. 1115) and issued the Alachlor Position
Document (PD-1) the document detailing the basis for the Special Review. The Special Review was
initiated under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) because pesticide
products containing alachlor met or exceeded the Agency's then applicable oncogenicity criteria at
40 CFR 162.11 (a)(3). Specifically EPA determined that exposure to pesticide products containing
alachlor resulted in the increased incidence of tumors at multiple sites in two species of laboratory
animals (mice and rats). Subsequently, the risk criteria in 40 CFR 162.11 were superceded by revised
criteria set forth in 40 CFR 154.7 (a) (2). The Agency determined that alachlor exceeded the revised
criteria for oncogenicity, which is now referred to as carcinogenicity, as well.
Following the review of public comments and additional information received in response to
the Notice of Initiation of Special Review and the Alachlor PD-1, EPA issued a Notice of Preliminary
Determination on October 8, 1986 (Federal Register. Volume 51, No. 36106). In this notice the
Agency announced its proposed decision to allow the continued use of alachlor products subject to
modifications of the terms and conditions of registration. This notice also announced the availability
of the Alachlor Technical Support Document (TSD) which detailed the basis for the Agency's
Preliminary Determination. The TSD was a detailed discussion of the risk and benefit data considered
by EPA. These documents were distributed in accordance with Sections 8 and 25 of FIFRA and sent
to all registrants and applicants for registrations of alachlor products.
In the Preliminary Notice the Agency proposed to reclassify alachlor as a restricted use
pesticide, to require the use of a closed mixing/loading system whenever alachlor was applied to 300
acres or more, to allow aerial applications of alachlor but prohibit the use of human flaggers, and to
retain the tumor warning on labels. In addition, pursuant to 40 CFR 162.17, EPA notified producers
of all alachlor products registered solely for intrastate sale and distribution, that they were required
to submit complete applications for registration. In response to the Preliminary Notice, the registrant
provided additional residue data that indicated that residues in lima beans and dry beans were lower
than previously estimated. The registrant also agreed to remove green peas from the labeling.
Following review of comments and additional information received in response to the
6
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Preliminary Notice, EPA issued a notice entitled "Alachlor; Notice of Intent to Cancel Registrations,
Conclusion of Special Review on December 31, 1987 (Federal Register. Volume 52, No. 49480).
This notice, known as the Alachlor Position Document 4 (PD-4) concluded the Special Review, and
stated that EPA would cancel the registrations and deny applications for registration of products
containing alachlor that did not comply with the terms and conditions of registration set forth in the
PD-4. The PD-4 stated that tolerances would be rewritten once all residue data required by the
Registration Standard were received and evaluated. The PD-4 required the following label
amendments; Restricted Use due to Oncogenicity, a tumor hazard warning, and use of mechanical
transfer systems by mixer/loaders and/or applicators who treat 300 acres or more annually. Human
flaggers were prohibited during aerial application. Labeling bearing required changes was submitted
and accepted in early 1988.
The Notice of Final Determination stated that the available data were adequate for
demonstrating alachlor's potential to contaminate ground water. However, the available data were
considered to be inadequate for a risk assessment considering the inadequate representation of
alachlor's use in terms of geographic area and associated hydrogeologic conditions. Thus, this issue
was deferred pending completion of the National Alachlor Well Water Survey (NAWWS). As
discussed in this RED, the Agency has received and reviewed the NAWWS data. It was one of the
studies relied on in determining quantitative drinking water risks. The other commitment made in the
PD-4 was "to revisit the risk and benefits of alachlor on a crop-by-crop basis." Since the dietary
risks, considering both food and water, for chronic and carcinogenic risks are not of concern, the
Agency will not perform a risk/benefit analysis.
In 1996 the Food Quality Protection Act of 1996 (FQPA) was signed into law. Since FQPA
requires the Agency to consider the potential for cumulative effects from alachlor and other
compounds with a common mechanism of toxicity, Monsanto has submitted its assessment of the
common mechanism of alachlor with other pesticides. Additionally, based on the results of the
Agency's Cancer Peer Review, Monsanto petitioned for removal of the Restricted Use classification
of alachlor.
III. SCIENCE ASSESSMENT
a. Physical Chemistry Assessment
Technical alachlor is a colorless to white crystalline solid with a melting point of 39.5-41.5
°C and a specific gravity of 1.133 g/mL at 25 °C. At 25 °C alachlor is soluble in water at 242 ppm.
Alachlor is soluble in ether, acetone, benzene, alcohol, and ethyl acetate, and is slightly soluble in
hexane. The following figure shows the chemical structure of alachlor.
7
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Empirical Formula:
Molecular Weight:
CAS Registry No.:
Shaughnessy No.:
C14H20NO2Cl
269.77
15972-60-8
090501
b. Human Health Assessment
1. Toxicology Assessment
Toxicology data are used to assess the hazards to humans and domestic animals. The data are
derived from a variety of acute, subchronic, and chronic toxicity tests; developmental/reproductive
tests; and tests to assess mutagenicity and pesticide metabolism. Reregi strati on eligibility decisions
require that the Agency have sufficient information to select the appropriate end-points for
performing a human health risk assessment. This requires a toxicological database that is not only
complete, but of acceptable quality.
The toxicological data base on alachlor is adequate and will support reregi strati on eligibility.
(See Table 2)
Table 2: Alachlor Toxicological Database
Guideline
Study Type
MRID No.
Required?
Satisfied?
OPPTS GLN
870.1100
(formerly 81-1)
Acute oral toxicity
- rat
00139383
yes
yes
OPPTS GLN
870.1200
(formerly 81-2)
Acute dermal
toxicity - rabbit
00139384
yes
yes
8
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Table 2: Alachlor Toxicological Database
Guideline
Study Type
MRID No.
Required?
Satisfied?
OPPTS GLN
870.1300
(formerly 81-3)
Acute inhalation
toxicity - rat
00109561
yes
yes
OPPTS GLN
870.2400
(formerly 81-4)
Primary eye
irritation - rabbit
00139385
yes
yes
OPPTS GLN
870.2500
(formerly 81-5)
Primary dermal
irritation - rabbit
00139386
yes
yes
OPPTS GLN
870.2600
(formerly 81-6)
Dermal
sensitization-
guinea pig
00161728
yes
yes
OPPTS GLN
870.3100
(formerly 82-la)
Sub chronic oral
toxicity - rat
00023658
yes
no
(satisfied by
83-la)
OPPTS GLN
870.3150
(formerly 82-lb)
Sub chronic oral
toxicity - dog
00087479
yes
yes
OPPTS GLN
870.3200
(formerly 82-2)
21-day dermal
toxicity - rabbit
00147328
yes
yes
OPPTS GLN
870.4100
870.4200
870.4300
(formerly 83-la,
83-2a, 83-5)
Chronic oral
toxicity/
carcinogenicity -
rat or Combined
chronic toxicity/
carcinogenicity
00091050,
00139021,
00141060
yes
yes
OPPTS GLN
870.4100
(formerly 83-lb)
Chronic oral
toxicity - dog
00148923
yes
yes
OPPTS GLN
870.4200
(formerly 83-2b)
Carcinogenicity -
mouse
00075709,
43507601
yes
yes
9
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Table 2: Alachlor Toxicological Database
Guideline
Study Type
MRID No.
Required?
Satisfied?
OPPTS GLN
870.3700
(formerly 83-3 a)
Teratology - rat
Prenatal
developmental
toxicity
00043645
yes
yes
OPPTS GLN
870.3700
(formerly 83-3b)
Teratology - rabbit
Prenatal
developmental
toxicity
40579402
yes
yes
OPPTS GLN
870.3800
(formerly 83-4)
Multi-generation
reproduction - rat
Reproduction and
fertility effects
00075062
yes
yes
OPPTS GLN
870.5300
870.5385
870.5500
870.5550
870.5575
(formerly 84-2,
84-4)
Mutagenicity -
various assays
00109563,
00141061,
00141062,
00149821
yes
yes
OPPTS GLN
870.7485
(formerly 85-1)
General
metabolism - rat
Metabolism and
Pharmacokinetics
00132045
yes
yes
OPPTS GLN
870.7600
(formerly 85-3)
dermal penetration
(absorption)
00149403,
00149404,
00149405
yes
yes
a. Acute Toxicity
Data from acute toxicity studies serve as the basis for labeling and packaging requirements.
Acute toxicity studies with alachlor indicate low toxicity. Table 3 below summarizes the available
information on the acute toxicity of alachlor.
10
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Table 3: Acute Toxicity of Alachlor
GLN
No.
Study Type
(%a.i.)
MRID No.
Results
Toxicity Category
870.1100
Acute Oral
(92.8%)
00139383
LD50 = 930 mg/kg
III
870.1200
Acute Dermal
(90.0%)
00139384
LD50 = 13.3 g/kg
IV
870.1300
Acute Inhalation
(95.3%)
00109561
LC50 > 1.04 mg/L
(4 hours)
III
870.2400
Primary Eye
Irritation
(92.8%)
00139385
No significant irritation
IV
870.2500
Primary Skin
Irritation
(92.8%)
00139386
No significant irritation
IV
870.2600
Dermal Sensitization
(94.5%)
00161728
Sensitizer
N/A
The oral LD50 for alachlor in a rat study was 930 (810-1050) mg/kg (MRID No. 00139383).
Clinical signs observed after oral dosing included ataxia, muscle tremors, hyperactivity, lethargy,
dyspnea, and convulsions. The LC50 for rat inhalation was 1.04 mg/L for 4 hours. Clinical signs
were related to eye and nasal irritation (MRID No. 00109561).
Alachlor has been shown to be a skin sensitizer in guinea pigs (MRID No. 00161728). Alachlor
was also a skin sensitizer in a repeated insult patch test in humans (MRID No. 00023611, 00023612).
b. Subchronic Toxicity
In an IBT (Industrial Biotest) subchronic toxicity study (MRID No. 00023658), male and
female Charles River albino rats from Charles River Breeding Laboratories, Inc., North Wilmington,
MA received 0, 20, 200, or 2000 ppm CP50144 technical alachlor which is 0, 1.5, 15, or 146
mg/kg/day for the control, low, mid and high dose groups, respectively by standard conversion
factors for 90 days. Systemic toxicity was noted in the high dose animals as decreased body weights
and body weight gains, decreased food consumption and efficiency, increased absolute and relative
spleen weights, increased relative liver weights, increased relative to body weight kidney weights, and
decreased relative gonad weights (testis and ovaries). The systemic toxicity NOEL (No Observed
Effect Level) is 15 mg/kg/day. The systemic toxicity LOEL (Lowest Observed Effect Level) is 146
mg/kg/day based on decreased body weights, body weight gains, reduced food consumption,
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increased spleen, liver and kidney weights, and decreased gonad weights. This study is classified as
unacceptable since it is an invalidated IBT study. Guideline requirements are not satisfied.
However, this study was not repeated since an adequate chronic toxicity study was performed by the
registrant.
In a subchronic feeding study, Beagle dogs were administered doses of 0, 5, 25, 50, or 75
mg/kg/day of alachlor (93.3% a.i.; Lot No. MTLT 1128X) in capsules for six months. Systemic
toxicity was noted as an increase in liver weights at the lowest dose tested (LDT; 5 mg/kg/day) and
above in males, and at 25 mg/kg/day and above in females. An increase in the incidence of gross
pathological observations (discoloration of the liver and biliary hyperplasia) in the liver were noted
at 25 mg/kg/day and above in both sexes. Dose related body weight gain decrement, reduction in
total serum protein levels, globulin levels, increase in Serum AP (alkaline phosphatase), LDH (lactate
dehydrogenase) and occasionally SGPT (serum glutamic-pyruvic transaminase) activities in both
sexes were noted at 25 mg/kg/day and above. Increased incidence of emaciation and mortality were
noted at 50 mg/kg/day and above. The systemic toxicity NOEL could not be determined, but would
be less than 5 mg/kg/day (LDT). The systemic toxicity LOEL is equal to or less than 5 mg/kg/day
based on increased liver weight (MRID No. 00087479).
In a 21-day dermal toxicity study, alachlor (EC MCB/C9; Lot# MDLL0407B, 45.3% a.i. and
Lot# MDLL0429B, 45.2% a.i.) was administered to New Zealand white rabbits at dose levels of 0,
50, 300, or 1000 mg/kg. Repeated exposure resulted in skin damage ranging from dermal irritation
to corrosion. The observations occurred in a dose-related manner. Systemic toxicity was noted as
an increase in polymorphonuclear leukocytes which may have resulted from the presence of the
chronic inflammatory reaction in the dermis. There was also a significant (p < 0.01) decrease in body
weight in both sexes at the high dose. There was also regenerative anemia, with an elevated white
blood cell count, and platelet counts, and a decreased albumin/globulin ratio. Also, there was
evidence of liver glycogen depletion at the high dose. Three animals in the mid dose and 6 animals
in the high dose died or were sacrificed in extremis. The cause of death may be related to bacterial
pneumonia due to bacteria entering through damaged skin.
The systemic toxicity NOEL is 50 mg/kg/day. The systemic toxicity LOEL is 300 mg/kg/day
based on hematological and clinical chemistry changes. The dermal toxicity NOEL could not be
determined, but would be less than 50 mg/kg/day. The dermal toxicity LOEL is equal to or less than
50 mg/kg/day due to skin damage (MRID No. 00147328).
c. Chronic Toxicity and Carcinogenicity
In a one-year study in beagle dogs, alachlor technical (94.1% a.i.; Lot# MULT 0417B) was
given by capsule at doses of 0 (control), 1.0, 3.0, or 10 mg/kg/day. Systemic toxicity was noted at
the 3 mg/kg/day dose as hemosiderosis in the kidney of one male dog and in the spleen of another
male dog; and at the high dose as hemosiderosis and hemolytic anemia in the liver of males (3/6). The
systemic toxicity NOEL is 1 mg/kg/day. The systemic toxicity LOEL is 3 mg/kg/day based upon
signs of hemosiderosis and hemolytic anemia (MRID No. 00148923).
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In a two-year feeding study, Long-Evans rats received doses of 0, 100, 300, or 1000 ppm
(approximately 0 (control), 14,42, or 126 mg/kg/day) technical alachlor in the diet for approximately
117 weeks in males (812 to 813 days) and 106 weeks in females (741 to 744 days). It should be
noted that the test substance used for the first 11 months of the study was stabilized with 0.5%
epichlorohydrin (Lot # XHI-167, 92.6% a.i.), while the test substance used for the remaining 16
months of the study was stabilized with epoxidized soybean oil (Lot # MHK-6, 92.19% a.i.).
Epichlorohydrin is carcinogenic for male Wistar rats and Sprague-Dawley rats: when given in
drinking water epichlorohydrin has been found to cause forestomach tumors (squamous cell
papillomas and carcinomas) in male Wistar rats (Konishi et al. Gann 71:922-923, 1980). By the
inhalation route epichlorohydrin has been found to cause squamous carcinomas of the nasal cavity
(Laskin, et al. J. Natl. Cancer Inst. 65:751-755, 1980). The effect of epichlorohydrin on tumor
formation in this study is not known.
Systemic toxicity was noted at 14 mg/kg/day and above as ocular lesions in the form of uveal
degeneration syndrome, and as increased thyroid weights in both sexes; and as increased liver weight
in the high dose groups. These observations were correlated with degenerative liver changes at all
dose levels. There were decreased body weights in the mid and high dose males and the high dose
females during the second year of the study. Statistical evaluation of mortality indicated an increasing
trend for male and female rats with increasing doses. Male rats had an increased incidence of nasal
respiratory epithelium adenomas, and adenomas and/or adenocarcinomas combined at 42 and 126
mg/kg/day (p < 0.01 and significant trends). Also, there was increased incidence in malignant mixed
gastric tumors and gastric adenocarcinomas and/or malignant mixed gastric tumors combined at 126
mg/kg (p < 0.01 and significant trends). There were increased incidences in thyroid follicular cell
adenomas and adenomas and/or carcinomas combined at 126 mg/kg (p < 0.01 and significant trends).
There were increased incidences in the 126 mg/kg/day dose group for stomach osteosarcomas, and
thyroid follicular cell carcinomas (both at p < 0.05). There were increased incidences of brain
oligodendrogliomas of the hypothalamus, stomach osteosarcomas, and thyroid follicular cell
carcinomas (all at p < 0.01) and significant trends. For female rats there was increased incidence of
nasal turbinate adenomas, and adenomas and/or adenocarcinomas combined at 42 (p < 0.05) and 126
(p < 0.01) mg/kg/day and significant trends for these tumor types. There was also an increased
incidence of malignant mixed gastric tumors, and gastric adenocarcinomas and/or malignant mixed
gastric tumors combined (p < 0.01) at 126 mg/kg/day, as well as significant trends for these tumor
types. Also, increased incidence at 14 and 126 mg/kg/day of mammary gland adenofibromas,
adenofibromas and/or fibroadenomas combined, and adenofibromas, fibroadenomas, and papillary
adenocarcinomas combined (p < 0.05). There were significant increasing trends in liver adenomas,
stomach osteosarcomas, and thyroid follicular cell adenomas and/or adenocarcinomas combined (all
at p < 0.01). Of all the tumors listed above, the increasing trend observed in brain
oligodendrogliomas of the hypothalamus, and the significant trend in brain ependymomas and
ependymomas and/or malignant ependymomas combined in male rats and the significant pair-wise
comparisons for mammary gland adenofibromas, adenofibromas and/or fibroadenomas combined, and
adenofibromas, fibroadenomas, and papillary adenocarcinomas combined and liver adenomas in
female rats were considered to have occurred at excessively toxic doses, and only the tumors of the
nasal epithelium, stomach, and thyroid were treatment related and are the basis for considering
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alachlor to be carcinogenic in the rat. The systemic toxicity NOEL could not be determined but
would be less than 14 mg/kg/day. The systemic toxicity LOEL is equal to or less than 14 mg/kg/day
based on ocular lesions (uveal degeneration syndrome) and hepatic toxicity (MRID No. 00091050).
In a second long-term study, Long-Evans rats were fed doses of 0, 0.5, 2.5 or 15 mg/kg/day
technical alachlor (94.13%; Lot# MULT 0417B; stabilized with 1.28% epoxidized soybean oil) for
110 weeks (25 to 26 months). Systemic toxicity was noted at 15 mg/kg/day, highest dose tested
(HDT), as molting of the retinal pigmentation (uveal degeneration syndrome), increased mortality rate
(significant increasing trend) in females (no effect in males) and abnormal disseminated foci in male
livers. Male rats had increased incidence of nasal respiratory epithelium adenomas at 15 mg/kg/day
(p < 0.01 with significant trend). Female rats had an increased incidence of adrenal benign
pheochromocytomas and nasal respiratory epithelium adenomas at the 15 mg/kg/day dose level (p
< 0.05 and p < 0.01, respectively and significant trend). There was also increased incidence of
thymus malignant lymphosarcomas at the 15 mg/kg/day dose level (p < 0.05); however, only the
tumors of the nasal epithelium were treatment related and are the basis for considering alachlor to be
carcinogenic in the rat. The systemic toxicity NOEL is 2.5 mg/kg/day and the systemic toxicity
LOEL is 15 mg/kg/day, based on molting of retinal pigmentation and increased mortality in females,
with abnormal disseminated foci of the liver in males (MRID No. 00139021).
In a special two-year study, technical alachlor (94.13% a.i.; Lot# MULT-0417B; stabilized with
1.28% epoxidized soybean oil) was administered in the diet at 126 mg/kg/day to Long-Evans rats for
two years to assess ocular effects of the compound (uveal degeneration syndrome). It was observed
that females were more sensitive than males, and that once the uveal degeneration syndrome was
observed, it was irreversible (a group exposed to alachlor for the first 5 to 6 months). The nasal,
thyroid and gastric tumors observed in earlier investigations were observed. The nasal tumors were
noted at the end of the study (2 years) in the group that was exposed to alachlor for the first 5 to 6
months (MRID No. 00141060).
In a carcinogenicity study, technical (alachlor; Lot# XHI-167, 92.6% a.i.; Lot# MHK-6,
92.19%) a.i.) stabilized with epichlorohydrin at the start of the study (for 11 months) and then with
a lot stabilized with epoxidozed soybean oil was given to CD-I albino mice in the diet for 18 months
at doses of 0 (control), 26, 78 or 260 mg/kg/day. Systemic toxicity was noted in the mid and high
dose groups as increased liver weights, increased kidney weight in the mid and high dose males, and
in the high dose females as reduced survival (statistical evaluation of mortality showed no significant
incremental changes with increasing doses of alachlor in male mice while female mice showed a
significant increasing trend in mortality with increasing doses of alachlor) and body weight gains
(10%>), males were not similarly affected. Thyroid follicular atrophy was noted in the mid and high
dose males and the high dose females. There was an increase in water consumption in the high dose
groups. Males had a significant increasing trend in bronchioalveolar adenomas at p < 0.05. There
were no significant differences in the pair-wise comparisons of the male dosed groups with the
controls. Female mice had significant increasing trends, in addition to significant differences in the
pair-wise comparisons of the 260 mg/kg/day dose group with the controls, for bronchioalveolar
adenomas and adenomas and/or carcinomas combined, all at p < 0.01 (MRID No. 00075709).
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In a second carcinogenicity study, CD-I albino mice (60 animals/sex/dose) from Charles River
Laboratory (Portage MI) received 0 (control), 100, 400 or 1600 ppm (male: 0, 16.64, 65.42, or
262.40 mg/kg/day; and female: 0,23.73, 90.34, or 399.22 mg/kg/day respectively, calculated directly
from food consumption data) of alachlor (94.64% a.i.; Lot# MUS-9107-3181-T) in the diet for 18
months. Ten animals/ sex/ dose were sacrificed at 12 months. Systemic toxicity was noted in high
dose males as lower body weight gains for the period ending on day 91; high dose males and females
with lower body weight gains for the period ending on day 372 and high dose females with lower
body weight gains to the end of the study. There were no decreases in food consumption, rather
there were increases in high dose females. No treatment related effects on food efficiency were noted
in the treated males; however, the high dose females had a dose related decrease in food efficiency
at 12 and 18 months.
Gross pathological observations included (at 18 months) a mass/nodule of the liver as noted
in 6/41, 7/40, 10/41, and 10/41 in males and 1/40, 0/42, 1/36, and 3/40 in females for the control,
low, mid and high dose groups, respectively; a mass/nodule of the lung in 3/41, 9/40, 10/41, and
12/41 in males and 1/40, 2/42, 9/36, and 6/40 in females for the control, low, mid and high dose
groups, respectively. There was a statistically significant increase in absolute liver weights of the low
and high dose females and liver weights relative to brain weights in high dose females at 12 months.
Also, there was an increase in relative liver weights in high dose females at 18 months. The high dose
males showed a statistically significant increase in absolute and relative liver weights at 18 months.
There was a statistically significant decrease in kidney weights relative to body weights in high dose
females at 12 months and a decrease in absolute kidney weight in high dose females at 18 months.
The males at 18 months had a significant increase in absolute kidney weights in all dose groups,
increased kidney weights relative to body weights in the low and high dose groups and increased
kidney weights relative to brain weight in the mid and high dose groups.
Non-neoplastic observations included slight increases in tubular epithelium
hyperplasia/regeneration in the kidney(s) of high dose males, an increase in centrilobular
hepatocellular hypertrophy in mid and high dose males along with an increase in high dose females
of fibrous osteodystrophy of the sternum. Neoplastic observations included an increase in
bronchoalveolar adenomas in all treated groups in males (7, 18, 27, and 22%, for the control, low,
mid and high dose groups, respectively) and females (5, 14, 10, and 17% for the control, low, mid
and high dose groups, respectively), statistical significance was achieved in mid dose males. The
combined incidence of bronchoalveolar adenomas/carcinomas was increased in all treated groups in
males (7, 18, 32, and 22% for the control, low, mid and high dose groups, respectively). Only the
mid dose males were statistically significantly different from the controls.
These data indicate that CD-I mice showed evidence of bronchoalveolar adenomas (mostly)
and/or carcinomas in the lung, but the data were considered to be inconclusive in terms of the
relationship to alachlor treatment especially when both mouse carcinogenicity studies are considered
together. The systemic toxicity NOEL for males is 16.64 mg/kg/day and the systemic toxicity LOEL
for males is 65.42 mg/kg/day based on an increase in centrilobular hepatocellular hypertrophy in mid
and high dose males. The systemic toxicity NOEL for females is 90.34 mg/kg/day and the systemic
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toxicity LOEL for females is 399.22 mg/kg/day based on body weight gain decrements and an
increase in fibrous osteodystrophy of the sternum. (MRID No. 43507601).
d. Developmental Toxicity
Developmental studies are designed to identify possible adverse effects on the developing
organism which may result from the mother's exposure to the pesticide during pre-natal development.
In a developmental toxicity (teratology) study, Charles River rats were given 0 (control), 50,
150 or 400 mg/kg/day of alachlor (92.19% a.i.; Lot# MHK-6) by gavage on gestation days 6 through
19, inclusive. Maternal systemic toxicity was noted at the high dose as maternal deaths, and
increased incidence of soft stools, red matter around the nose and mouth and anogenital staining and
reduced body weight gains. Developmental toxicity was noted at the high dose as a slight increase
in the mean number of early and late resorptions with related increased post-implantation loss and a
slight reduction in the mean number of viable fetuses. The maternal toxicity NOEL is 150 mg/kg/day.
The maternal toxicity LOEL is 400 mg/kg/day based on increased mortality, increased incidence of
clinical signs and reduced body weight gains. The developmental toxicity NOEL is 150 mg/kg/day.
The developmental toxicity LOEL is 400 mg/kg/day based on increased resorptions and decreased
litter size (MRID No. 00043645).
In a developmental toxicity study, New Zealand white rabbits received doses of 0 (control), 50,
100 or 150 mg/kg/day alachlor (94.7% a.i., Lot# 51486-C) by gavage on days 7 through 19,
inclusive. Maternal systemic toxicity was noted at the high dose as decreased body weight gain
during the dosing period followed by a rebound in body weight gain during the period following
dosing. No developmental toxicity was noted in the parameters measured. The maternal toxicity
NOEL is 100 mg/kg/day. The maternal toxicity LOEL is 150 mg/kg/day based upon a reduction in
body weight gains. The developmental toxicity NOEL is equal to or greater than 150 mg/kg/day
(highest dose tested) and the developmental toxicity LOEL is greater than 150 mg/kg/day (MRID
No. 40579402).
e. Reproductive Toxicity
A reproduction study is designed to provide general information concerning the effects of a test
substance on mating behavior, conception, parturition, lactation, weaning, and growth and
development of the offspring.
In a three-generation reproduction study, Sprague Dawley CD rats received either 0 (control),
3, 10, or 30 mg/kg/day technical alachlor (92.6% a.i.; Lot# XHI-167) in the diet. Parental/ Offspring
systemic toxicity was noted at the high dose in the form of discoloration of the kidney and reduced
kidney weights (especially in F2 parents and F3b pups). Histopathology revealed chronic nephritis in
the high dose males. The high dose females of each parental generation and the F3b females had lower
ovary weights (this decrease was maximal (17%) and significant in the F0 generation, and was also
associated with 17% decrease in the ovaries to body weight ratio). No microscopic changes were
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reported in the ovaries and no effect was noted on reproductive parameters. The parental/offspring
systemic toxicity NOEL is 10 mg/kg/day. The parental/offspring systemic toxicity LOEL is 30
mg/kg/day based on kidney effects. Since there were no effects on reproductive parameters, the
reproductive toxicity NOEL is equal to or greater than 30 mg/kg/day (HDT). The reproductive
toxicity LOEL is greater than 30 mg/kg/day. (MRID No. 00075062).
f. Mutagenicity
Alachlor
A reverse mutation assay in five strains of Salmonella tvphimurium (TA1535,TA100, TA1537,
TA1538, and TA98) using 10 to 5000 //g/plate with and without S9 metabolic activation was
negative (MRID No. 00109563).
An R coli WP2 her reverse mutation assay using 10 to 5000 //g/plate with and without S9
metabolic activation was negative (MRID No. 00109563).
A rec assay with Bacillus subtilis (H17 and M45) using 20 to 2000 //g/disk was negative
(MRID No. 00109563).
Alachlor was positive in an in vivo/in vitro unscheduled DNA synthesis (UDS) assay at 1000
mg/kg, a dose approximating the LD50 in rats. Doses tested were 50, 200, and 1000 mg/kg with
evaluations at 2 and 12 hours (MRID No. 00141061).
An assay of structural chromosomal aberrations (e.g., in vivo cytogenetics in rat bone marrow)
was negative. Single doses of 0, 100, 300, or 1000 mg/kg with sacrifice times of 6, 12, 24, and 48
hours (MRID No. 00141062).
A CHO (Chinese hamster ovaries) HGPRT mammalian cell forward mutation test was negative.
Dose levels tested were 15 to 150 //g/ml without S9 metabolic activation and 15 to 330 /ig/ml with
S9 metabolic activation (MRID No. 00148921).
Alachlor was negative in an Ames Salmonella tvphimurium mammalian microsome plate
incorporation assay, conducted in the absence of S9 and with S9 prepared from uninduced rat,
mouse, or monkey nasal turbinates, at concentrations ranging from 50 to 5000 //g/plate. Tester
strains TA98, TA100, TA1535, and TA1537 were used (MRID No. 42651301).
Alachlor was positive for inducing UDS in hepatocytes recovered from male Fischer-344 rats
at 12 hours after oral gavage administration of 1000 mg/kg. (It is noted that the dose at which a
positive response was observed approximates the LD50 of alachlor in rats.) The average number
of net nuclear grains counts were increased by >5 compared with the controls, with > 10% of the cells
in repair (increased net nuclear grains counts over control were obtained with 2/5 animals, and
increases of >5 net grains were observed with 3/5 animals. Similarly, a comparison of the individual
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data from treated animals and the vehicle control group showed that hepatocytes recovered from 3
of 5 animals were positive for UDS, cells from one animal showed a borderline positive response, and
liver cells from the remaining animal was negative. These data are suggestive of a genotoxic
response. There was no indication of UDS activity at 12 hours after oral gavage administration of
lower doses (50, 200, or 500 mg/kg) or at 2 hours following gavage with 1000 mg/kg (MRID No.
42651302).
Alachlor was negative in a micronucleus assay in Long-Evans rats conducted with a single
intraperitoneal injection of 150, 300, or 600 mg/kg and 24-, 48-, and 72-hour sacrifice times. Two
males and one female receiving the high dose died, and clinical signs of toxicity were observed in
males at all doses and in mid- and high-dose females. A separate experiment in the same study with
radiolabeled alachlor provided evidence that the test material reached the target organ, bone marrow,
when administered intraperitoneally. (MRID No. 42651303).
In a mouse micronucleus assay (MRID No. 44032103), groups of 10-15 male CD-I mice
received single oral gavage administrations of 250, 500 or 1000 mg/kg alachlor (>99%). The test
material was delivered to the animals in corn oil. Animals were sacrificed at 24 and 48 hours post-
administration; bone marrow cells were harvested and 2000 polychromatic erythrocytes per male
were examined for the incidence of micronucleated polychromatic erythrocytes (MPEs). Death and
other clinical signs (i.e., piloerection and/or decreased defecation) were observed at the highest dose
tested. Cytotoxicity for the target organ was not observed at any dose. The positive control induced
the expected high yield of MPEs in the treated males. There was, however, no evidence that alachlor
induced a clastogenic or aneugenic effect at any dose or sacrifice time. The study contained major
guideline deficiencies (i.e, use of a single sex, only 5 males/dose/sampling time and no 72-hour post-
treatment sacrifice). However, the study is classified as acceptable for the following reasons:
Previous studies have shown that alachlor is not active in the mouse bone marrow
micronucleus assay.
Adequate justification for the use of males only was provided.
Variations within and among treatment groups were minimal; hence, the findings with
the smaller than recommended sample size are considered valid.
The uniformly negative response in conjunction with the absence of an effect on cell
cycling suggest that sampling cells 72 hours after compound administration would not
have altered the outcome of the study.
Based on these considerations, the Agency concluded that the study satisfied the requirements
for 84-2 for in vivo cytogenetic mutagenicity data.
Metabolites of Alachlor
Urine from alachlor treated rats was tested in an Ames Salmonella assay using strains TA98,
TA100, TA1535, and TA1537 in the presence and absence of arochlor 1254-induced mammalian
activation system and/or B-glucuronidase/sulfatase and dose levels of 0.005 to 0.5 ml/plate. There
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was a weak mutagenic response in strain TA98 in the presence of B-glucuronidase. A weak mutagenic
response was also observed in strain TA1537 in the presence of both B-glucuronidase and metabolic
activation (MRIDNo. 00155389, 00155392).
Bile from alachlor treated Long-Evans rats tested in an Ames Salmonella assay using strains
TA98, TA100, TA1535, and TA1537 in the presence and absence of arochlor 1254-induced liver
homogenate (S-9) or B-glucuronidase at dose levels of 0.01 to 0.20 ml/plate was negative under all
conditions (MRID No. 00155389, 00155393).
Ames Salmonella assays with synthesized metabolites of alachlor using strains TA98, TA100,
TA1535, and TA1537 at dose levels of 0.004 to 10.00 mg/plate both with and without S9 metabolic
activation showed that of five metabolites tested (t-hydroxy sulfone [CP 1013 94; rat, mouse, goat, hen,
rotation crops metabolite], sec- amide p-hydroxy methylsulfone [CP51214; rat metabolite],
t-sulfinyllacetic acid [CP108267; corn metabolite], t-oxanilic acid [CP108064; soil, water, soybean
metabolite], and t-sulfonic acid [CP 108065; corn, soil, soybeans, water metabolite]), only the
t-hydroxysulfone metabolite was observed to be mutagenic (strain TA100 at 3 and 10 mg/plate in the
presence and absence of metabolic activation). (MRID No. 00151394, 00151395, 00151396,
00151397, 00151398, 001513999)
In Ames Salmonella assays with synthesized metabolites of alachlor (CP97230 and CP 1013 84
[s-hydroxysulfone]) using strains TA98, and TA100 at dose levels of 0.01 to 10.00 mg/plate both
with and without S9 metabolic activation only the s-hydroxysulfone metabolite was observed to be
weakly mutagenic (strain TA100 at 1, 3 and 10 mg/plate in the presence and absence of metabolic
activation). The responses that were less than a 2-fold increase indicating a positive response.
(MRIDNo. 00155389, 00155391).
Two alachlor metabolites, 2'6'-diethyl-2-methyl thioacetanilide (DMTA) and
2'6'-Diethylaniline (DEA), were tested (MRID No. 42651301) in an Ames Salmonella tvphimurium
mammalian microsome plate incorporation assay in the absence of S9 and with S9 prepared from
uninduced rat, mouse, or monkey nasal turbinates. Tester strains TA98, TA100, TA1535, and
TA1537 were used. DMTA was positive in strain TA1535 in three independent Salmonella
tvphimurium mammalian microsome plate incorporation assays, conducted with S9 prepared from
mouse nasal turbinates. In addition, there was a tendency for increased numbers of revertants of
TA1535 to occur following exposure to higher dose levels (1500 and/or 5000 //g/plate) of DMTA.
This was also observed in one of two assays conducted with rat nasal turbinate S9. Although only
marginal increases were observed, the increases were reproducible and statistically significant. There
was no response in tester strains TA98, TA100 or TA1537 with the nonactivated test material or in
the presence of S9 prepared from mouse, rat, or monkey nasal turbinates. However, it should be
noted that DMTA is not a stable product of alachlor metabolism.
DEA was positive in strains TA1535 and TA100 in at least two independent Salmonella
tvphimurium/mammalian microsome plate incorporation assays, conducted with S9 prepared from
mouse nasal turbinates. The nonactivated test material and the test material activated with rat nasal
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turbinate S9 were also positive in strain TA100. Although only marginal increases were observed,
they were reproducible and statistically significant. There was no consistent response in tester strains
TA98 and TA1537.
g. Metabolism
Metabolism studies in Sprague Dawley rats found that an oral dose of 7 or 700 mg/kg of
alachlor was mainly eliminated in urine and feces, and that 89% of the dose was eliminated in 10 days
(minimal alachlor was found in the expired C02). The elimination was considered to be biphasic; the
initial rapid phase had a half life of 0.2 to 10.6 hours, which then slowed to a half life of 5 to 16 days.
Fourteen metabolites were identified in urine and 13 in feces. Three of the metabolites were common
to both urine and feces. The eliminated metabolites were conjugates of mercapturic acid, glucuronic
acid, and sulfate (MRID No. 00132045).
From a metabolism study in Rhesus monkeys, five urinary metabolites were identified after
intravenous injection. One of these metabolites, (also found in rat and mouse urine,
N-[2-ethyl-6-(l-hydroxyethyl)-phenyl]-N-(methoxymethyl)-2(methylsulfonyl)acetamide), tested
positive in the Ames test with Salmonella tvphimurium. with and without activation. This metabolite
was an HEEA metabolite not previously identified in the monkey.
Of the metabolites found in the above two metabolism studies, only two urinary metabolites
were common to both the rat and monkey (secondary and tertiary mercapturic acid conjugates). Side
chain hydroxylation and sulfate conjugation metabolites were not found in monkey urine as they were
in rats (MRID No. 40000901).
Another metabolism study was conducted on male and female Long Evans rats (MRID
42651306, 42852107,42651308,42852108). This study consisted of seven groups of rats. Both oral
dosing studies using corn oil as the vehicle and intravenous administration studies using propylene
glycol as the vehicle were performed. Together these seven studies satisfy GLN 85-1. The study is
considered to be the definitive study for understanding how the rat metabolizes alachlor.
Oral administration of alachlor was studied using female Long-Evans Crl:CD(LE)BR rats six
to nine weeks of age in five dose groups. Groups 1, 2, and 3 each consisted of 33 rats. Each group
received single oral doses of radiolabeled alachlor (uniformly labeled in the phenyl ring with 14-C,
and enriched with 13-C at the C-2 carbon) at target doses of 7 (Group 1), 70 (Group 2), or 700
(Group 3) mg/kg. Group 4 consisted of 21 rats which received 15 consecutive daily doses of
radiolabeled alachlor at 700 mg/kg/day. Group 5 consisted of 6 rats which received a single oral dose
of radiolabeled alachlor at 700 mg/kg for the purpose of obtaining plasma samples at 2, 4, and 6
hours post-dosing. Long Evans rats (5/sex/dose) were used to study the disposition and metabolism
of alachlor following intravenous administration at 7 (Group 6) or 70 (Group 7) mg/kg.
In the oral studies, absorption at the 7 or 70 mg/kg dose levels was essentially complete, with
a slight decrease in absorption at the 700 mg/kg dose level. Repeated oral dosing at 700 mg/kg had
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no significant effect on absorption. Residual radioactivity did not exceed 5% of the administered dose
at any of the dose levels in this study. On a ug/g basis, the residual radioactivity in the non-glandular
stomach was higher than in the glandular stomach except at 4 hours post-dose at the 700 mg/kg dose
level. Decreasing the dose decreased the percentage of the dose in the non-glandular stomach but not
in the glandular stomach. Nasal turbinates showed a secondary peak of radioactivity at 8 hours
post-dose at the 700 or 70 mg/kg dose levels in contrast to other tissues. Excretion of alachlor
derived radioactivity was approximately equivalent between urine and feces, with between 30-47%
excreted in urine and 41-45% excreted in feces at single oral doses of 7, 70, or 700 mg/kg.
Intravenous dosing at 7 or 70 mg/kg resulted in a similar excretion profile. Repeated oral dosing at
700 mg/kg resulted in a slight increase in fecal excretion of radioactivity. In urine, the sec- amide
hydroxymethyl sulfone metabolite (metabolite F5) of alachlor was the predominant urinary metabolite
after oral and intravenous administration, ranging from 2.1-7.4%) of the dose. Repeated oral dosing
resulted in the appearance of several additional metabolites, but it is not known whether these
additional metabolites are unique to repeated oral administration of alachlor. In feces, the tert-amide
mercapturic acid and the disulfide appeared to be the major metabolites after single oral doses of
alachlor. Increasing the dose appeared to increase the percentage of these 2 metabolites in feces.
In this study, male and female CD-I mice (10/sex) received a single oral dose of radiolabeled
alachlor in corn oil (890 mg/kg for male mice, 819 mg/kg for female mice). Urine and feces were
collected daily for up to 7 days post-dose for analysis of excreted radioactivity and for identification
of metabolites. In urine, 18.4 ±3.9% and 23.6±4.1%> of the dose was excreted in male and female
mice, respectively. In feces, 66.5±6.9% and 53.6±3.6% of the dose was excreted in male and female
mice, respectively. Total recovery of radioactivity was 85.5±3.7% for male mice, and 79.4±2.7% for
female mice. (The low recoveries may be due to the fact that the mice were housed in pairs in units
larger than those normally used for a mouse.) Analysis of blood at seven days post-dose showed
0.095±0.016% of the dose in males, and 0.075±0.017% of the dose in females. Half life for urinary
elimination was reported as 0.88±0.11 days in males, and 1.18±0.16 days in females. Half-life for
fecal elimination was reported as 0.90±0.06 days in males, and 1.11±0.05 days in females. The data
in this study show that in contrast to the rat, feces is the major route of excretion for alachlor derived
radioactivity in CD-I mice. The high percentage of fecal excretion could be the result of poor
absorption of test chemical or extensive biliary excretion in the mouse.
Pooled urine and fecal samples representing the 0-48 hour collection time for urine and the 0-96
hour collection time for feces, were analyzed for metabolites of alachlor in male and female CD-I
mice. In feces, at least 10 metabolites were isolated (See Table 4). Urinary metabolites are in Table
5.
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Ta
)le 4: Metabolites in Mouse Feces
Metabolite
% of Dose - Male Feces
% of Dose - Female Feces
alachlor
1.8
2.2
tert-amide mercapturic acid
4.1
3.3
disulfide conjugate
0.6
1.0
sec-amide mercapturic acid
0.7
0.6
tert-amide thioacetic acid
1.2
0.9
tert-amide hydroxy sulfone
0.6
0.5
tert-amide dihydroxysulfone
0.0
0.0
benzyl glucuronide
2.1
1.0
tert-amide cysteine conjugate
+NCH20-glucuronide
5.0
3.7
Table 5: Urinary Metabolites Characterized in the Mouse
Metabolite
% of Dose - Male Urine
% of Dose - Female Urine
tert-amide cysteine conjugate
0.1
0.3
NCH20 glucuronic acid
1.9
3.2
cysteine sulfoxide (proposed)
0.2
0.3
sec-amide dihydroxysulfone
0.1
0.2
sec-amide hydroxy sulfoxide
0.1
0.2
sec-amide hydroxy sulfone
0.1
0.2
para-amino sulfate
0.1
0.2
While metabolism of alachlor utilizes the same metabolic pathways in mice as in rats, there are
quantitative differences between mice and rats in the metabolite profile present. Mouse feces were
found to contain greater amounts of mercapturic acid conjugate and lesser amount of disulfide
conjugate than in rat feces. The number of urinary metabolites observed in mouse urine was greater
than in rat urine. Mouse urine was found to contain greater amounts of glucuronic acid conjugates
and cysteine conjugates than the rat, but a lesser amount of phenolic (hydroxylated) metabolites
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(MRID No. 42651305, 42852106).
h. Special Studies
Monsanto has voluntarily submitted a number of special studies on alachlor which were
performed to better understand the mechanisms involved in the toxic responses induced by alachlor,
including tumor formation. The following special studies can be categorized in the following groups:
in vivo metabolism studies, in vitro metabolism studies, whole body autoradiography (WBA) studies,
mutagenicity studies, and cell proliferation/cytotoxicity studies. Some of the submitted data used for
cancer peer review consisted of studies conducted with butachlor, a structural analog of alachlor.
These special studies do not satisfy any guideline requirements. Further discussion of the conclusions
of these studies is in the Dose Response Assessment Section under the Cancer Classification
discussion.
In Vivo Metabolism Studies
• Effect of Multiple Oral Dosing on the Metabolism, Distribution, and Elimination of Alachlor
in the Long-Evans Rat. (MRID Nos. 42651310, 42852109)
• A Study of the Metabolism and Excretion of Alachlor in Rats Chronically Exposed to Alachlor;
Routes and Rates of Elimination. (MRID No. 42651307) Characterization of Metabolites in
the Urine and Feces. (MRID No. 42931101)
• Metabolism of Alachlor Methyl Sulfide in Long-Evans Rats. (MRID No. 42651309)
In Vitro Metabolism Studies with Alachlor and Alachlor Metabolites
• A Study of the In Vitro Liver Slice Metabolism of Alachlor in the Male Rat, Mouse, and
Monkey. (MRID No. 42651311)
• A Study of the In Vitro Metabolism of Alachlor Using Enzyme Preparations From Selected Rat
Tissues. Part I. Preparation of Tissue Homogenates. (MRID No. 42651312)
• In Vitro Metabolism of Alachlor by Rat Liver, Kidney, Lung, Nasal, and Stomach
Homogenates. (MRID No. 42852110)
• In Vitro Metabolism of Alachlor by Rat and Mouse Liver and Nasal Enzymes. (MRID No.
42852111)
• Metabolism of Alachlor Methyl Sulfide in Long-Evans Rats. (MRID No. 42651309)
• In Vitro Metabolism Study of Alachlor, Alachlor Secondary Methyl Sulfide, and
2,6-Diethylaniline by Rat and Monkey Nasal Turbinate Part II. (MRID No. 42651314)
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• In Vitro Metabolism of Alachlor, Alachlor Secondary Sulfide, Alachlor Sec-Amide, and
2,6-Diethylaniline by Rat and Human Nasal Turbinates and Liver. (MRID No. 43482301)
• Effects of Alachlor on Tissue Levels of Glutathione in the Rat. (MRID No. 42651318)
• Effect of Alachlor on Glutathione Levels of Cultured Adult Rat Hepatocytes. (MRID No.
43641603) (Note: This study was not conducted according to 40 CFR Part 160, but is a report
based on university thesis research conducted at Searle, a Monsanto subsidiary.)
Studies on Alachlor Using Whole Body Autoradiography fWBA)
• Whole Body Autoradiography Studies on 14-C Alachlor in Rats, Mice, and Monkeys. (MRID
No. 42852103)
• A Comparative Study of the Distribution and Localization of Alachlor, Metolachlor, and MON
4601 in Rats Using WBA. (MRID No. 42852104)
• A Study of the Distribution and Localization of Alachlor-Methylsulfide in Rats Using WBA.
(MRID No. 42651304)
• A Study of the Distribution and Localization of Diethylaniline (DEA) in Rats and Mice Using
WBA. (MRID No. 43507401)
• A Study of the Distribution and Localization of Dimethylaniline (DMA) in Rats and Mice Using
WBA. (MRID No. 43706001)
• Comparison of the Distribution and Excretion of Radiolabeled Alachlor in the Sprague-Dawley,
Fisher 344 and Long-Evans Rat and Golden Syrian Hamster. (MRID No. 42852105)
Mutagenicity Studies with Alachlor
• Determination of CP-50144-Derived Radioactivity in Rat. (MRID No. 43369201)
• Study of the Effects of Alachlor on Cellular Stress Response Genes in Rat Nasal Turbinate
Tissue. (MRID No. 43590002)
Cell Proliferation / Cytotoxicity Studies
• Characterization of Covalent Adducts Formed with Nasal Tissue Protein Following Dietary
Administration of 14-C Alachlor to Female Long-Evans Rats. (MRID No. 43641604)
• A Study of the Effect of Alachlor and Selected Metabolites on Cytotoxicity Markers in Nasal
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Tissue of the Long-Evans Rat. (MRID No. 43641602)
• Gastric Tumor Initiation/Promotion Study of Butachlor in Sprague-Dawley Rats (Monsanto
Company, The Agricultural Group, Environmental Health Laboratory for Monsanto
Company, Monsanto Study#: ML-92-365, Monsanto EHL Study#: EHL 92142, August 18,
1994, MRID No. 43729502).
• A Study of the Mechanism of Butachlor Induced Carcinogenicity in F emale Sprague-Dawley
Rats (Monsanto Company, The Agricultural Group, Environmental Health Laboratory for
Monsanto Company, Monsanto Study#: EHL-92049, Monsanto Study#: ML-92-146,
February 9, 1995, MRID No. 43750801).
• A Study on the Effect of Butachlor on Cell Proliferation in Selected Tissues of the Mouse
(Monsanto Company, The Agricultural Group, Environmental Health Laboratory for
Monsanto Company, Monsanto Study#: EHL-93064, Monsanto Study#: ML-93-153, August
11, 1994, MRID No. 43729503).
• Effects of Butachlor on Cell Proliferation and Mucosal Thickness in the Gastric Tissue of
Female Rhesus Monkeys (American Health Foundation and White Sands Research Center and
Environmental Health Laboratory for Monsanto Company, Monsanto Study#: EHL-93064,
Monsanto Study#: WS-93-164 and WS-93-165, MRID No. 43729501).
• Gastric Tumor Promotion Study of Alachlor in Long-Evans Rats. Monsanto Company, The
Agricultural Group, Environmental Health Laboratory for Monsanto Company, Monsanto
Study No. ML-93-137, Monsanto EHL Study# EHL 93049, February 3, 1995. MRID No.
43590001.
The data from these studies were used to draw the following conclusions:
Nasal Tumors
Based upon the available data for alachlor, the following hypothesis has been proposed for
the production of tumors in the nasal mucosa: alachlor is metabolized in the rat to the glutathione
(mercapturic acid) conjugate, which is excreted through the bile into the gut. In the gut, enteric
bacteria metabolize the conjugate to the thiol conjugate, with subsequent S-methylation of the thiol.
This product, the methyl sulfide, is re-absorbed into the systemic circulation where conversion to the
secondary sulfide occurs. Hydrolysis of the secondary sulfide by arylamidase produces the
diethylaniline metabolite of alachlor. Oxidation of the diethylaniline metabolite produces the putative
toxic metabolite, diethylbenzoquinone imine (DEBQI). This metabolite binds to cellular protein,
resulting in eventual cell death. Ensuing regenerative cell proliferation can then lead to neoplasia
through "fixation" of spontaneous mutations.
The registrant presented data in support of their conclusion that the nasal tumors observed
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following alachlor administration are unique to the rat based on differences in disposition of alachlor
in the rat versus other species. In vivo studies in Long-Evans rats (MRID No. 42651306, 42651308,
42852107, 42852108) and CD-I mice (MRID No. 42651305, 42852106) showed that a greater
percentage of a given dose of alachlor was eliminated in feces of mice vs rats. In addition, it was
shown that mouse urine contained a greater percentage of glucuronide conjugates and cysteine
conjugates of alachlor, while rat urine contains a greater amount of phenolic (hydroxylated)
metabolites. In addition, rat feces were found to contain greater percentages of mercapturic acid
conjugates and sulfone metabolites than mouse feces. These data are supportive of the proposed
metabolic pathway for production of the putative toxic intermediate of alachlor in the rat. In addition
to the comparative metabolism of alachlor in rats versus mice, the in vivo metabolism of the methyl
sulfide metabolite of alachlor in female Long-Evans rats demonstrated the production of
4-amino-3,5-diethylphenylsulfate, a stable end-product indicative of the formation of the quinone
imine precursor (MRID No. 42651309).
In vitro studies conducted by the registrant demonstrated the presence of the reactions
necessary for production of the DEBQI intermediate. These include glutathione conjugation of
alachlor, hydrolysis of the secondary sulfide by arylamidase, and hydroxylation of 2,6-diethylaniline.
Further, in vitro studies demonstrated significant species differences in the rates of these reactions.
Comparative in vitro metabolism of alachlor by several tissues in the Long-Evans rat (MRID No.
42852110) showed the presence of arylamidase activity in liver and nasal tissue resulting in formation
of the 2,6-diethylaniline metabolite. Oxidation of the 2,6-diethylaniline metabolite to
4-amino-3,5-diethylphenol was shown to be approximately 50 times greater in nasal microsomes than
in liver microsomes. Rat and mouse liver and nasal tissues were compared for their ability to
metabolize alachlor to the proposed DEBQI intermediate (MRID No. 42852111). The velocity of
the nasal aryl amidase reaction in rat nasal tissue towards the sec-amide metabolite of alachlor was
observed to be 14-20 times higher in rat than in mouse. The velocity of the nasal arylhydroxylase
towards diethylaniline in rat nasal tissue was found to be approximately 2-fold higher than in mouse.
This study demonstrated that certain key enzymes responsible for production of the proposed toxic
intermediate of alachlor are more active in rat nasal mucosa vs mouse nasal mucosa. Liver and nasal
cytosolic or microsomal fractions were used from rat and monkey to study metabolism of alachlor
to the GSH conjugate, the hydrolysis of alachlor secondary sulfide by arylamidase, and the
hydroxylation of 2,6-diethylaniline (MRID No. 42651314). Velocity of rat liver GST was 3.9 times
greater than monkey GST towards alachlor. Velocity of rat nasal GST was 114.3 times greater than
monkey GST towards alachlor. Velocity of secondary sulfide hydrolysis was equivalent in rat and
monkey liver preparations, but was 4 times greater in rat nasal tissue vs monkey nasal tissue.
Velocity of DEA hydroxylation in rat liver was 3 times greater than in monkey liver, and 7.6 times
greater in rat nasal tissue than in monkey nasal tissue. Thus, the enzymes thought to be responsible
for production of the toxic intermediate of alachlor are more active in rat nasal tissue vs monkey nasal
tissue.
In MRID No. 43482301, cytosolic and microsomal fractions from rat and human liver and
nasal tissue were studied to determine the differential species capability to conjugate alachlor with
glutathione, to hydrolyze the secondary methyl sulfide (secondary sulfide), and to hyroxylate the
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2,6-diethylaniline metabolite of alachlor. Velocity of glutathione conjugation in rat liver and nasal
tissue was 4.0 and 32.5 times greater than in human liver and nasal tissue, respectively. Velocity of
hydrolysis of the secondary sulfide was 5.8 times greater in rat nasal tissue vs human. Velocity of
DEA hydroxylation was 7.5 times greater in rat liver vs human, and 129.8 times greater in rat nasal
tissue vs human.
Whole body autoradiographic (WBA) studies conducted in rats, mice, and monkeys provided
further support for the species specificity of the mechanism of alachlor-induced nasal tumors. In
MRID No. 42852103, WBA studies in rats, mice, and monkeys following single oral doses of 7, 70,
and 700 mg/kg were conducted. A similar picture of tissue distribution was observed in all species
with the exception of blood, in which significant amounts were observed only in the rat at 5 days
post-dose, and the nasal turbinates, in which significant accumulation was observed in the rat, less
in the mouse, and none in the monkey. Comparative WBA studies on the localization of alachlor,
metolachlor, and MON 4601 were conducted in male and female rats after target doses of 7 and 700
mg/kg (MRID No. 42852104). Nasal turbinate localization appeared less for alachlor than for
metolachlor and MON 4601 at one day post-dose at the 7 and 700 mg/kg dose. The data in this
study indicated a faster clearance of alachlor from the intestinal tract vs metolachlor and MON 4601,
and also indicate that metolachlor and MON 4601 undergo biliary excretion and enterohepatic
circulation. Whole body autoradiography studies of the localization of the methylsulfide metabolite
in rats after oral administration at 0.7 and 7.0 mg/kg (MRID No. 42651304) and localization of the
diethylaniline metabolite of alachlor in rats after oral administration of 7 and 70 mg/kg (MRID No.
43507401) showed that for the methyl sulfide metabolite, localization in the nasal turbinate was
evident up to 5 days post-dose, while for the diethylaniline metabolite, nasal turbinate localization was
evident in the rat but not the mouse. Comparative distribution of alachlor using WBA after oral doses
of 7 and 70 mg/kg was examined in Sprague-Dawley, Long-Evans, and Fisher 344 rats as well as in
Syrian hamsters (MRID No. 42852105). Nasal localization was evident in all three strains, but was
most apparent in the Long-Evans rat. Nasal localization was not evident in the hamster.
Collectively, these WBA studies support the conclusion that the distribution of alachlor
derived radioactivity to the nasal turbinates, as well as that of alachlor metabolites thought to be
involved in nasal tumor formation, is greater in the rat than in the mouse or monkey. When
considered in conjunction with in vitro studies on the activities of enzymes responsible for formation
of the DEBQI intermediate, it is evident that not only does alachlor derived radioactivity localize to
the rat nasal turbinate tissue to a greater degree than in mice or monkeys, but that the activities of the
enzymes involved in the conversion of the secondary sulfide to the DEBQI intermediate are
significantly higher in the rat than in the mouse, monkey, or human.
The mechanism of alachlor-induced nasal tumors is considered by the registrant as a
non-genotoxic mechanism. This argument is largely based upon the mutagenicity database, in which
it is argued that alachlor has no significant genotoxic activity in mammalian systems. Studies
examining the effect of alachlor administration on tissue glutathione levels following in vivo
administration of oral and intraperitoneal doses of alachlor to Long-Evans rats as well as the effect
of alachlor on glutathione levels in cultured hepatocytes have been conducted (MRID Nos. 42651318
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and 43641603). These studies showed depletion of hepatic glutathione followed by recovery after
a single i.p. dose of 350 mg/kg or single oral doses of 126 or 350 mg/kg. Alachlor was hepatotoxic
at concentrations above 400 fjM, and significant glutathione depletion was also observed at
concentrations above 300 fjM alachlor. While no significant depletion of nasal glutathione levels
were observed, the DNA damaging effect of alachlor might be related to depletion of glutathione and
subsequent tissue toxicity, and not to a direct mode of action. It is noted that significant hepatoxicity
in the form of elevated serum ALT (alanine amino transferase), AST (aspartate amino transferase),
and LDH (lactate dehydrogenase) as well as centrilobular cytoplasmic eosinophilia, centrilobular
inflammation, and centrilobular hepatocellular degeneration/necrosis was observed at a dose of
alachlor (1000 mg/kg) which also caused a weak UDS response. These data are consistent with a
non-genotoxic mode of action for alachlor.
With regard to the nasal tissue, two studies addressed the mechanism of nasal turbinate
induced tumors. In the first study (MRID No. 43641604), female Long-Evans rats were fed 14-C
alachlor in the diet at a targeted dose level of 126 mg/kg/day for a total of 13 days. On days 1, 3, 7,
and 13, 3 rats were sacrificed and the covalent binding of alachlor derived radioactivity to nasal
protein was determined. The results of this study showed a direct correlation between the total level
of alachlor binding to rat nasal proteins and length of treatment. The major adduct was identified as
the 3,5-diethylbenzo-quinone-4-imime (DEBQI)-cysteine adduct. Formation of DEBQI in the rat
nasal tissue is believed to be required for induction of nasal tumors. In the second study (MRID No.
43641602), the in vitro cytotoxicity of alachlor, DEA, secondary sulfide, and secondary amide were
assessed in preparations of rat nasal turbinate as evidenced by leakage of the enzyme acid phosphatase
into the culture medium. Concentrations of alachlor and metabolites used were either 1 or 5 mM.
Alachlor at both 1 and 5 mM was shown to increase acid phosphatase levels in the culture medium.
Neither the secondary sulfide or secondary amide caused an increase in acid phosphatase levels at 1
mM (5 mM concentration not possible due to solubility limitations). DEA was observed to increase
acid phosphatase levels at 5 mM in nasal tissue. The cytotoxicity observed with alachlor in nasal
tissue is consistent with the cell proliferation response observed in nasal tissue after administration
of alachlor. but the entity responsible for the cytotoxic response is not known with certainty.
Gastric Tumors
In response to scientific and regulatory questions raised in Japan, an extensive research
program was undertaken to understand the mechanism by which chloroacetanilides induce stomach
tumors in rats. The majority of this work was conducted with butachlor in Sprague-Dawley rats.
Since butachlor is a close structural analog of alachlor, and the two compounds produce the same
glandular stomach tumors, extrapolation of the mechanistic information to alachlor is scientifically
justified. To further support this, some bridging data have been developed with alachlor and were
previously reported to the Agency. The purposes of these provided data are to: (a) report the results
and conclusions of the mechanistic studies conducted with butachlor; and (b) integrate these results
with those from the alachlor work to show that the same mechanisms are operative for both
herbicides.
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In a gastric tumor initiation/promotion study (MRID No. 43729502) the results showed that
butachlor had no initiating potential of its own when used at dose levels which produced gastric
tumors in the chronic toxicity study in rats. Butachlor was found to enhance the formation of gastric
neoplasms when combined with an initiating agent. This occurs primarily in females and at the dose
which induced neoplasms in the chronic rat study. In a study of the mechanism of butachlor induced
carcinogenicity in female Sprague-Dawley rats (MRID No. 43750801) the investigators concluded
that these data delineated the mechanistic processes involved in the production of the gastric, nasal
and thyroid tumors for butachlor. It was suggested that the data provided support for the
involvement of non-genotoxic mechanisms that would be threshold sensitive to humans. They also
stated that these studies further support the view that the rat tumors induced by butachlor are not
relevant to man and that butachlor does not pose a human health risk (not formally reviewed by the
Agency). In a study on the effect of butachlor on cell proliferation in selected tissues of the mouse
(MRID No. 43729503) the investigators found no consistent increase in cell proliferation in either
the fundic or pyloric regions. There was a slight increase in the fundic neck region but not in the base
region and there was no evidence of toxicity in the mucosa. In another study on the effects of
butachlor on cell proliferation and mucosal thickness in the gastric tissue of female Rhesus monkeys
(MRID No. 43729501), according to the investigators there were no relevant changes in cell
proliferation in any area of the stomach and no changes in the mucosal thickness in any of the
monkeys up to and including 400 mg/kg. The results of this study differ from those studies in the rat,
where increases in proliferative activity and reductions in mucosal thickness were observed. The
doses used in the monkey are reported to exceed the MTD in the rat by 2 to 4 times.
The registrant conducted an initiation-promotion study with alachlor (MRID No. 43590001)
as a follow-up to a stomach tumor initiation/promotion study with butachlor. In this study, 100 male
and 100 female Long-Evans rats obtained from Charles River Breeding Laboratory, Portage, MI, 6
weeks of age and weighing 168-219 g for males and 139-176 g for females were administered by oral
gavage a single dose of 150 mg/kg of the known gastric tumor initiator N-methyl-N'-ni tro-N-nitroso-
guanidine (MNNG) to 4 groups of 20 animals per sex. One of these groups was not further treated.
Another group received dietary administration of 8000 ppm catechol, and two groups received either
15 or 126 mg/kg/day of alachlor in the diet for 1 year while another group (not MNNG treated)
received a single oral dose of DMSO (5 mL/kg) followed by dietary administration of alachlor at a
level of 126 mg/kg/day (there was another group of 15 animals per sex obtained near the end of the
study to serve as "control" animals for serum gastrin levels, gastric fluid amount, pH, and HC1
concentration). The investigators determined, at the end of the study, stomach pH, gastric acid
secretion over a 4 hour period in 5-6 of the control and DMSO/Alachlor treated animals. They also
obtained blood from 9-10 control and DMSO/Alachlor treated animals for serum gastrin
determinations. The stomachs of all animals were examined grossly and microscopically.
Alachlor was found to promote the development of glandular stomach tumors in females and
to a lesser extent in males. No effect of treatment was noted in the animals treated with MNNG alone
(1 tumor). Alachlor alone produced no tumors in males and 4 tumors in females. MNNG/alachlor
treated animals produced tumors in 75% of treated females and 30% of treated males at 126
mg/kg/day. These tumors were neoplasms of the glandular stomach, mostly in the fundus region.
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In the 15 mg/kg/day alachlor + MNNG no tumors were observed in the females. However several
tumors were found in males at both doses and in females at the 126 mg/kg/day dose following
MNNG. The investigators interpreted this as due to MNNG rather than alachlor, since they occurred
at equivalent frequency in the males at both doses, the lower of which had no promotional activity.
In a previous butachlor initiation/promotion study, the group treated with MNNG only induced
adenomas and adenocarcinomas in the pyloric region. Alachlor administration was noted to produce
atrophy of the fundic mucosa in almost every animal at 126 mg/kg/day both with and without the
initiator, MNNG. No atrophy was noted in any animal at 15 mg/kg/day alachlor for one year. The
high dose alachlor animals of both sexes had reduced amounts of fluid in the stomachs. Stomach pH
was numerically increased, and gastric hydrochloric acid secretion was decreased and serum gastrin
levels were elevated in high dose animals.
The Agency believes that the data provide evidence that alachlor produces glandular stomach
tumors in rats through the same non-genotoxic, non-linear sensitive mechanism as butachlor and that
this mechanism may be operative in humans under certain specific pathological states.
Alachlor has been shown to produce glandular stomach tumors in Long-Evans rats at doses
considered in excess of an adequate dose for carcinogenicity testing. Butachlor also induced these
gastric neoplasms in Sprague-Dawley rats following chronic high dose exposure. In this butachlor
bioassay, the occurrence of gastric tumors was restricted solely to the highest dose tested (150
mg/kg/day), a level of exposure which was considered greatly in excess of an adequate dose for
carcinogenicity testing. In a butachlor chronic bioassay with F-344 rats, the highest dose was
considered adequate for carcinogenicity testing, and no gastric tumors were found. This and other
information indicate that chloroacetanilides produce stomach tumors in rats via a non-linear type
mechanism.
The Agency evaluated the data submitted by the registrant in support of the threshold (non-
linear) type mechanism for induction of gastric tumors by alachlor and concurred with the explanation
put forth by the registrant.
Thyroid Tumors
Mechanistic data in support of the thyroid tumors consisted of two studies. In the first, dose
levels of 0 or 126 mg/kg/day were used to measure indices of thyroid function (T3, T4, and TSH
levels). While the results of this study showed no significant effect of alachlor on T3, T4, or TSH
levels, the results pertaining to TSH levels were considered invalid based on the use of human
antibodies in the TSH assay.
In the second study (MRID No. 42957201), Long-Evans rats were dosed with alachlor for
up to 120 days at dose levels of 0 and 126 mg/kg/day. Separate groups were exposed to control diet
or alachlor in the diet for 7, 14, 28, 60, or 120 days, with a separate group exposed to alachlor for
60 days in the diet and then control diet for 60 days. The results of this study showed increased liver
weights at all time points, increased activity of uridine 5'-di-phosphoglucuronyl transferase
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(UDPGT), and increased thyroid weights from day 14 throughout the remainder of the study. TSH
levels were statistically significantly increased from day 14 on, although the increase at day 120 was
not significant. T3 levels were increased over control at 7, 14, 60, and 120 days; T4 levels were
decreased at 7 and 28 days and increased at 14 days, returning towards normal at following time
points. The dose group which received alachlor for 60 days followed by 60 days of control diet
showed relatively unaffected T3, T4 and TSH levels. Thyroid follicular hypertrophy/hyperplasia was
also noted in the treated animals mainly in the 28 and 60 day groups, with 1 animal in the 120 day
group progressing to nodular hyperplasia.
The results of the above studies suggest that thyroid tumors (which only occur in the male
rat), result from induction of hepatic UDPGT, with a consequent decrease in circulating T3 and T4
and a subsequent increase in TSH (the compensatory response resulted in increased T3 levels). This
action is known to result in a hyperplastic response of the thyroid. The mechanism of thyroid
tumorigenesis observed with alachlor is consistent with the mechanism of thyroid tumorigenesis
observed with other chemicals causing a disruption of thyroid hormone balance.
Human Studies
Human Biomonitoring
A biomonitoring study of a pesticide involves following a group of workers during a defined
field use of the pesticide. Urine is collected before and after exposure and analyzed for metabolites
of the pesticide. From this data one determines the quantity of pesticide absorbed during the defined
field exposure. Thus, a biomonitoring study consists of two parts (1) a qualitative and quantitative
identification of the metabolites of the pesticide, usually by following radiolabel in a mammalian
species, and (2) the field study in human subjects.
In the three submitted biomonitoring studies the internal dosage of alachlor was estimated by
analysis of the urinary excretion of alachlor metabolites which contained the DEA and HEEA
moieties.
The first biomonitoring study (MRID No. 00150089) was conducted using two formulations
of alachlor, the EC (emulsifiable concentrate) and the Mcap (microencapsulated). The study was
designed to determine the dosages of alachlor in workers, and to compare the dosages of the two
formulations. The study was conducted in Indiana during May 1984. Both the EC and Mcap were
applied by shallow incorporation to corn fields at an application rate of 4 lbs a.i./acre. Each
formulation was applied by four different individuals. Applicators 1, 3, 5, and 7 applied EC and
applicators 2,4, 6, and 8 applied Mcap. Additionally a control subj ect was present at the field during
the application.
The subjects were Monsanto employees who wore goggles and elbow length rubber gloves
during mixing/loading and leather boots, trouser, long sleeve shirts and caps throughout the entire
operation. The clothing was in agreement with the protective clothing requirements stated on the
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labels. Each applicator emptied eight 2.5 gallon containers of EC or Mcap into 200 gallon tanks.
Water was added from nurse tanks with constant agitation. Immediately following mixing, the
worker entered a closed cab and applied the alachlor to 20 acres.
The urine from each worker was collected in a borosilicate glass bottle with teflon cap for 120
hours (5 days) after the alachlor application was completed. The samples were analyzed for
metabolites of alachlor containing the DEA and HEEA moieties using GC/MS. Urine samples with
non-detectable levels of alachlor metabolites were computed as containing 1.25 ppb (one-half the
LOD, limit of detection, of 2.5 ppb). The practice of using one-half of the LOD is a standard
analytical procedure for dealing with the analytical LODs for chemical residues.
The highest internal dosage for mixing, loading and applying (of the four replicates) for EC
formulation was estimated to be 0.0066 /zg/kg/lb ai. The internal dosage for the Mcap was estimated
to be 0.027 //g/kg/lb ai.
Another biomonitoring study (MRID No. 00159365) was conducted in May and July 1985
in Missouri. In this study the Mcap and WDG (a water dispersable granular formulation), were
evaluated. This study was conducted in a manner similar to that of the May 1984 bio-monitoring
study: Monsanto employees wearing clothing in accordance with the label, 4 lbs ai/acre, and 20
acres. Open loading was used, with each subject handling 80 lbs ai. Control urine samples were
collected prior to study initiation. Urine was collected for 5 days. The urine samples were also
analyzed for alachlor metabolites containing the DEA and HEEA moities, but by HPLC (high
performance liquid chromatography).
No measurable levels of the alachlor metabolites containing the HEEA moiety were detected
in any urine samples for all study subjects. Measurable levels of DEA metabolites were detected for
most of the subjects, primarily within the first 48 hours. The internal dosage of the Mcap was
estimated to be 0.0038 //g/kg/ai. The internal dosage of the WDG was estimated to be 0.0059
/ig/kg/lb ai.
A third biomonitoring study (MRID No. 00159364) was also performed in May and July
1985. This study was also conducted in the same manner as that of the Mcap and WDG 1985 bio-
monitoring study. However, a closed loading system was used to transfer the EC. The internal
dosage of the EC was estimated to be 0.0034 //g/kg/lb ai.
For all three studies the Agency has concerns due to the small number of replicates as well
as the use of protective clothing and the use of the closed cab. Only 20 acres were treated instead
of the 100 to 120 acres that could be expected to be treated and incorporated. Additionally, the
scenario is only representative of 4 lb ai/acre. The small number of replicates cannot indicate the
range of dosage that would be expected. Due to the protected nature of the applicators (clothing and
cab) it was assumed that the dosage estimate is from the lower end of the range. A literature search
of ground boom application studies indicated that exposure to the applicators ranged over three
orders of magnitude. In the alachlor PD4 two orders of magnitude was chosen by the Agency to
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define the exposure range since mixing and loading is included in the dosage estimates with the
estimate from the Monsanto bio-monitoring studies considered to be the low end of the range.
As part of the reregi strati on process, the first biomonitoring study (May 1984, Indiana) was
rereviewed. The review indicated that there is probably a formulation related difference for
application of the EC versus the Mcap. For the 4 lb ai/acre scenario, the internal estimated dosages
were: EC = 0.0032 //g/kg/lb ai, and Mcap = 0.0126 //g/kg/lb ai. The same internal exposure
estimates would be appropriate for mixer/loaders, mixer/loader/applicators, or applicators.
Epidemiology Study of Ocular Health Among Alachlor Manufacturing Workers
During a chronic feeding study (MRID No. 00139021) with alachlor, Long-Evans rats were
noted to develop severe ocular lesions at the highest test doses. Therefore, another study in Long-
Evans rats was conducted to characterize the progression of the previously observed eye lesions
(MRID No. 00141060). It was observed that females were more sensitive than males, and that once
the uveal degereration syndrome was observed, it was irreversible.
To determine if human workers might be at risk of developing similar lesions, it was decided
to conduct an ophthalmologic study which would focus on a human eye lesion that could be
considered equivalent to the initiating eye lesion found in Long-Evans rats. Differences between
Long-Evans rat and human eyes were considered to be minor; thus, an equivalence for the purpose
of evaluating a potential effect of alachlor exposure among workers could be assumed. The uveal
tract consists of the iris, ciliary body, and choroid. Long-Evans rats, like humans, have pigmented
eyes and each uveal component has melanin-containing cells. The human equivalent of the initiating
lesions, uveal pigment disruption and dispersion, is the clinically described Pigment Dispersion
Syndrome (PDS). PDS consists of the loss of pigment from the mid-posterior iris with deposition
of the pigment on the cornea, trabecular meshwork, lens, and iris.
The study site was the Muscatine, Iowa plant, which began operation in 1961. At Muscatine,
herbicide production began in 1964, with the production of alachlor beginning in 1969. To determine
whether there were ocular effects among exposed workers, a group of 135 highly exposed alachlor
production workers were examined for the presence of PDS. There was a control group of 84
unexposed co-workers and relatives. All participants were examined by the same ophthalmologist
at the University of Iowa. The ophthalmologist was unaware of the exposure status of the individual
participants.
Components of the eye exam included slit-lamp biomicroscopy of the anterior chamber and
a dilated exam of the lens and fundus with scleral depression as well as the routine functional exam.
Intraocular pressure was measured prior to dilation. Only one study participant had eye defects
meeting the study criteria of PDS. This person was in the control group. For eye abnormalities other
than PDS, prevalence rates were similar for exposed and unexposed study participants.
Thus, no evidence of increased risk of ocular disease was found when workers were compared
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to controls. Only one subject, who was from the control group, had the same defect as reported in
the study of Long-Evans rats. (MRID No. 43267501)
Epidemiologic Study of Workers
Monsanto performed an epidemiologic study of workers at an alachlor manufacturing plant
in Muscatine, Iowa. The product has been manufactured in this plant since 1969. (MRID No.
43878501). The population studied included 1199 workers employed for 1 year or more between
1961 and December 1993. Both mortality and cancer incidence were assessed in this cohort.
Mortality follow-up was by company records, social security number, national death index, credit
agency, and state motor vehicle records. Follow-up for vital status was very successful, covering
over 99% of the cohort. Death certificates were obtained for all 17 decedents.
Assessment of cancer incidence was conducted using the statewide cancer registry in Iowa
which was initiated in 1969. Linking with the registry was by social security number, full name, and
birth date. Inexact matches were verified by consulting with employee records and the State Health
Registry. Workers who left Iowa (< 1/3 the cohort) did not have cancer incidence assessed but were
assumed to be similar to those who remained in state.
Quantitative data were insufficient to estimate actual exposure at the plant. Qualitative
estimates (high, medium, and low) were made by industrial hygienists based primarily on work history
and the potential for dermal exposure. Alachlor's low vapor pressure and airborne measurements
taken at the plant (averaging less than 10 ppb) suggest this route of exposure is not significant. The
potential for contaminated water occurred between 1968 and 1975. In 1975 low levels of alachlor
were detected in the plant's drinking water. However, when the alachlor first appeared in the drinking
water is not known. Exposure characterization took into account the contaminated drinking water.
Analysis both included and excluded this possibility due to the uncertainty associated with it.
Twenty-six non-whites were excluded from the analysis due to inadequate sample size for statistical
analysis. However, it was noted that no cancers occurred in this group where 0.1 cases would have
been expected.
No deaths or incidence of cancer were reported for the stomach, thyroid, or nasal cavities,
as reported in laboratory rats. The study did not find any evidence of statistically increased incidence
or mortality from cancer either overall or by individual cancer site with one exception. The one
statistically significant finding was based on two cases of chronic myeloid leukemia where only 0.1
cases would have been expected. The 95 percent confidence interval for the standardized incidence
ratio was quite wide, 1.9 to 58.1. Given that this ratio is based on only two cases (one of whom had
worked at the plant less than 5 years) and the number of statistical tests performed, this result should
probably be considered a chance finding without other supporting evidence.
By completion of this study only 24 cancers and 8 cancer deaths had been reported in the
entire cohort. The overall cancer mortality ratio (number of observed/expected cases) was 0.9 with
a 95% confidence interval of 0.4 to 1.7. The overall cancer incidence ratio was 1.4 based on 24
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observed and 17.1 expected cases (95% confidence interval 0.9 to 2.1). For those workers
categorized as having high exposure to alachlor (68% of the cohort), the cancer incidence ratio was
1.2 (95%) confidence interval 0.7 to 2.0). The Agency concludes that while no appreciable hazard
has been identified to date, one cannot rule out adverse effects in this cohort until these individuals
have been followed-up over the course of a lifetime.
i. ESA Metabolite of Alachlor
The ethane sulfonic acid (ESA) metabolite of alachlor is variously referred to as MON 5775,
2',6'-diethyl-N-methoxymethyl-2-sulfoacetanilide, sodium salt or 2-[2,6-diethylphenyl
(methoxymethyl) amino]-2-oxoethane sulfonic acid, sodium salt. The formation of alachlor ESA
involves the displacement of a chlorine atom by a sulfonic acid moiety. The metabolic route leading
to alachlor ESA is postulated to involve initial glutathione displacement of the chlorine atom,
followed by successive degradation of the sulfur conjugated moiety through organic acid and
methylsulfone intermediates, to ultimately form the sulfonic acid group as a terminal oxidative
degradate. Alachlor ESA has always been isolated from natural matrices and synthetic preparations
as a salt. The sodium salt has always been utilized for toxicology studies.
Alachlor ESA was originally identified as a metabolite of alachlor in soil (MRID No.
00134327). The alachlor ESA metabolite was determined to be 15 - 25% of the total applied
radioactivity, making it the first or second most prevalent degradate in soil. Alachlor ESA has also
been quantified in field soil dissipation studies following alachlor applications (MRID Nos. 42528002,
43774701). Low concentrations were detected, but alachlor ESA was not found to persist or leach
below 18 inches.
Alachlor ESA has also been identified as a minor alachlor degradate in a laboratory aqueous
sediment metabolism study (MRID No. 43774702). It has also been detected in water samples from
Indiana (MRID No. 42479901) and Wisconsin (no MRID, submitted under FIFRA 6(a)(2)). In the
Indiana well water samples, alachlor ESA concentrations ranged from <1.0 - 23.0 /i-g/L, and in
Wisconsin they ranged from <1.0 - 26.7 //g/L.
Acute Toxicity
In an acute oral toxicity study in rats, the acute oral LD50of alachlor ESA is greater than 6000
mg/kg. This is toxicity category IV (MRID No. 42701501).
Subchronic Toxicity
In a special 91-day drinking water study, male and female Fischer CDF® F-344 Crl BR
VAF/Plus® rats from Charles River Laboratories, Inc. (Raleigh, NC) received either 0, 200, 2000,
or 10000 ppm (male: 0 (control), 16, 157, or 896 mg/kg/day; female: 0 (control), 23, 207, or 1108
mg/kg/day) alachlor ESA. Systemic toxicity was observed in high dose male and female rats, with
increased incidences of decreased activity with rapid/shallow breathing, few feces and feces small in
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size, dehydration, urine staining, emaciation, hunched posture, rough coat, unkempt appearance, and
dark material/stain on pads of forelimb, around eyes, mouth and nose, clear and red ocular discharge,
and hair loss around eyes. Slight decreased body weight gains (10%) were also noted in high dose
male rats (decreased body weight gains were noted in all treated females; however, no dose response
was noted). Several statistically significant hematological effects (decreased hemoglobin, hematocrit,
red cells, increased MCH and MCHC) and clinical chemistry alterations (decreased AST, ALT, urea
nitrogen, albumin, glucose, increased bilirubin and phosphorous) were observed at the mid and high
dose in males and/or females, but were minor, mostly not dose related and were not considered
biologically relevant, especially in the absence of any organ or tissue pathology at this dose. Eye
lesions noted in this study were determined not to be related to treatment or to those lesions seen with
the parent compound, alachlor. The clinical observations reported related to the eye are due to ocular
abnormalities specific to the F-344 rat. The systemic toxicity NOEL was 2000 ppm (157 mg/kg/day
in males and 207 mg/kg/day in females). The systemic toxicity LOEL was 10,000 ppm (896
mg/kg/day in males and 1108 mg/kg/day in females) based on increased incidence of clinical signs of
toxicity in males and females, and decreased body weight gains in males (MRID No. 42863701).
Developmental Toxicity
In a prenatal developmental toxicity (teratology) study, female Sprague-Dawley Crl:CD®BR
rats from Charles River Breeding Laboratories, Inc., (Portage, Michigan) received 0 (control), 150,
400, or 1000 (limit dose) mg/kg/day alachlor ESA (90.0% a.i.; LotNo.: NPD-9203-3974-T) in corn
oil by oral gavage from days 6 through 15 of gestation, inclusive. Actual doses were 0, 135, 360, or
900 mg/kg/day based on 90.0% a.i. No maternal toxicity was noted in any measured parameter at
the dose levels tested. The maternal toxicity NOEL is equal to or greater than 900 mg/kg/day and
the maternal toxicity LOEL is greater than 900 mg/kg/day. No developmental toxicity was noted in
any measured parameter at the dose levels tested. Therefore, the developmental toxicity NOEL is
equal to or greater than 900 mg/kg/day, and the developmental toxicity LOEL is greater than 900
mg/kg/day (MRID No. 43908101).
Mutagenicity
In an Ames Salmonella mutagenicity assay, alachlor's ethanesulfonic acid, or ESA metabolite,
did not cause increases in the reversion of four S. tvphimurium strains (TA98, TA100, TA1535, and
TA1537) in either the presence or absence of S9 activation at dose levels of 0.01 to 10.00 mg/plate
under the conditions of two independent assays (MRID No. 00151398).
In a mouse micronucleus assay, groups of five male CD-I mice received single oral gavage
administrations of 500, 1000 or 2000 mg/kg alachlor ESA (90.7%). The test material was delivered
to the animals in deionized water. Animals were sacrificed at 24 and 48 hours postadministration;
bone marrow cells were harvested and 2000 erythrocytes per male were examined for the incidence
of micronucleated polychromatic erythrocytes (MPEs). No overt toxicity for the treated animals or
cytotoxicity for the target organ was observed up to the currently recommended limit dose (2000
mg/kg). The positive control induced the expected high yield of MPEs in the treated males. There
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was, however, no evidence that the test material induced a clastogenic or aneugenic effect at any dose
or sacrifice time (MRID No. 43889403).
Metabolism
In a special metabolism study, two groups of male and female Long-Evans rats
(two/sex/group) were administered alachlor ESA at a dose of 70 mg/kg by gavage. Group 1 rats were
sacrificed 24 hours after treatment and Group 2 rats at 5 days after treatment. Disposition of alachlor
ethane sulfonate was determined by collection of excreta and by whole-body autoradiography.
Metabolism was assessed by HPLC analysis of processed urine and feces samples. The major route
of excretion for alachlor ESA at 70 mg/kg was the feces, with 71-82% of the administered dose
excreted by this route. Excretion was rapid with the majority of radioactivity excreted by 24 hours
post-dose. HPLC analysis of urine and feces showed alachlor ESA to be the major component in
both urine and feces, with three other components isolated but not identified, each comprising less
than 2% of the dose. Autoradiographic data on alachlor ESA derived radioactivity at 14 hours
postdose showed the major areas of localization were stomach contents, cecum, intestinal contents
and urinary bladder. The data indicate that alachlor's ESA metabolite is poorly absorbed, rapidly
excreted, and undergoes minor metabolism. (MRID No. 43889404).
Special Studies
In a special study, the proliferating cell nuclear antigen (PCNA) technique was utilized to
determine the effect of treatment with 2000 ppm alachlor ESA (157 mg/kg/day for 91 days) on cell
proliferation in the olfactory region at the second palatial ridge (Level III), where alachlor-induced
tumors are found. Mean nasal cell proliferation values (number of labeled cells per mm of mucosal
length) showed no statistically significant increases in cell proliferation in either the olfactory septum
or turbinates of male Fischer 344 rats administered alachlor ESA in drinking water for 91 days.
(MRID No. 43889401).
In a special study, glandular stomach tissue from female Fischer 344 rats treated with alachlor
ESA in drinking water at a dose of 10,000 ppm for 91 days was evaluated using PCNA for evidence
of a proliferative response or changes in mucosal thickness. A significant increase in the percentage
of labeled cells in the fundic neck region was observed in treated rats, but there were no significant
changes in labelling of the fundic base nor in mucosal thickness (MRID No. 43889402).
Conclusions
Table 6: Comparison of Alachlor and Alachlor ESA
Test
Alachlor
Alachlor ESA
Acute oral LD50
930 mg/kg
Toxicity category III
> 6000 mg/kg
Toxicity category IV
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Table 6: Comparison of Alachlor and Alachlor ESA
Test
Alachlor
Alachlor ESA
Subchronic
Toxicity (1)
90 day invalidated feeding
study
91-day drinking water study
males
NOEL =157 mg/kg/day
LOEL = 896 mg/kg/day
females
NOEL = 207 mg/kg/day
LOEL =1108 mg/kg/day
Developmental
Toxicity
maternal
NOEL =150 mg/kg/day
LOEL = 400 mg/kg/day
developmental
NOEL =150 mg/kg/day
LOEL = 400 mg/kg/day
maternal
NOEL => 900 mg/kg/day
LOEL > 900 mg/kg/day
developmental
NOEL => 900 mg/kg/day
LOEL > 900 mg/kg/day
Mutagenicity
weakly mutagenic -
tested positive in 2 UDS
studies. Other alachlor
metabolites also found to be
weakly mutagenic
no mutagenic activity in two studies
Metabolism (2)
Absorption was essentially
complete with alachlor
being present in the blood at
24 hours and 5 days post
dose. Alachlor excreted
approximately equally
between urine and feces.
Alachlor ESA is the major
component in both urine and feces.
Alachlor ESA is poorly absorbed,
rapidly excreted (71-82% in the feces
within 24 hours), and undergoes
minor metabolism.
(1) The subchronic data available for comparison of alachlor with the ESA metabolite of
alachlor are not by the same route of administration (in the diet for alachlor per se and in the drinking
water for the ESA metabolite of alachlor). Also, the study with alachlor per se is an IBT study which
was not validated nor repeated; therefore the data may be suspect. It is important to note that the
subchronic and chronic toxicity studies with alachlor were conducted with different strains of rats
("Charles River Albino rats" vs Long-Evans rats) than the 91 day drinking water study (Fisher 344
rats); however, the available metabolism data do not show any major differences in the handling of
the compounds in the Long-Evans versus the Fisher rats.
(2) The available in vivo metabolism data indicate that in comparison to alachlor, the alachlor
ESA metabolite is poorly absorbed and metabolized to only a minor degree. The products of alachlor
ESA metabolism were not identified. The available autoradiography data indicate that in comparison
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to alachlor, its ESA metabolite does not show any significant localization to the nasal cavity, thyroid
and glandular stomach (gastric mucosa). The available cell proliferation data indicate that in
comparison to alachlor, alachlor ESA does not induce cell proliferation.
Overall, the data provided indicate that alachlor's ESA metabolite has less toxic potential than
the parent alachlor.
Metabolism Committee Meeting for Alachlor ESA Metabolite
A Metabolism Committee meeting held 1/18/95 discussed the available toxicity data for the
alachlor ethane sulfonic acid (ESA) metabolite.
The Metabolism Committee concluded the following:
• Since alachlor ESA is sulfonated, and highly polar, there is likely to be little absorption via
the oral or dermal routes, and even if absorbed, it is expected to be readily excreted.
• Information has been provided by the Registrant which indicates toxicity of the parent is
based in part on formation of the quinone imine.
• Formation of the potentially carcinogenic quinone-imine from alachlor ESA is unlikely if the
metabolite occurs solely in the sulfonated form in the body, or if minimal cleavage to the
unsulfonated form occurs.
• Because of the reasons cited above, alachlor ESA is unlikely to be carcinogenic in a 2-year
bioassay.
• Alachlor ESA should, however, continue to be included in non-cancer dietary exposure
estimates (for comparison to the RfD).
• Alachlor ESA was non-mutagenic in two studies.
2. Dose Response Assessment
a. Reference Dose
A Reference Dose (RfD) represents the quantity of a substance which if absorbed on a daily
basis over a lifetime, is not expected to pose significant risk of adverse health effects.
The RfD for alachlor was first assessed on February 21, 1986. This RfD was subsequently verified
by the Agency RfD Work Group on March 11, 1986, and again on March 27, 1991.
At that time the RfD was based on a NOEL of 1 mg/kg/day in a one year chronic dog study
(MRIDNo. 00148923). TheLOELwas3 mg/kg/day based on hemosiderosis and hemolytic anemia.
An uncertainty factor (UF) of 100 was used to account for interspecies extrapolation and intraspecies
variability. The RfD was calculated to be 0.01 mg/kg/day.
The RfD Committee met on 8/19/93 (actual memo was signed 1/31/94) to discuss and
reevaluate the RfD for alachlor. At this meeting, it was recommended that the RfD of 0.01
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mg/kg/day remain unchanged.
b. Dermal Absorption
The requirement for a dermal absorption study in the rat was waived, since data from three
Rhesus monkey studies (MRID Nos. 00149403, 00149404, 00149405) were combined to determine
the dermal absorption factor.
Three pharmacokinetic studies on Rhesus monkeys were performed: an intravenous route
of administration study, dermal application of alachlor emulsifiable concentrate (EC), and a dermal
application of alachlor micro-encapsulate formulation (Mcap). In all three studies, the levels of
radioactivity were monitored in the blood for 7 days, and urine and feces for 9 to 14 days.
The purpose of the intravenous study was to determine the pharmacokinetics of alachlor
distribution and elimination. Two monkeys/sex/dose were given single doses of 0.24 or 2.4
mg/kg/day. Alachlor was rapidly distributed in the blood (whole, plasma, and red blood cells) within
the first 15 minutes, and rapidly eliminated in urine primarily within the first 24 hours. Approximately
93.3 percent of the low dose and 99.6 percent of the high dose were eliminated in excreta during the
10-day study period. The majority of this elimination was via the urine (82.1% low dose, and 91.4%,
high dose).
In both the EC and the Mcap dermal studies, the formulations were tested undiluted and
diluted (1:29 for EC and 1:17 for Mcap) with water, 2 monkeys/sex/formulation or dilution/EC or
Mcap. The dosages (EC: 32 //g/cm2 and 300 //g/cm2; and Mcap 10.8 //g/cm2 and 217 //g/cm2) were
applied to a 40 cm2 skin area and were left on the skin for 12 hours before removal.
For the EC the rate of alachlor absorption was slow and reached a peak in the blood after 24
hours. The total dermal absorption in the low dose animals (32 //g/cm2), estimated from excretion
of radiolabel and retention of label in tissues, was 6-7% in males and 12-13% in females, uncorrected.
However, calculation of the actual amount of test material absorbed through the skin was complicated
by the fact that recovery of radiolabeled test material in this test group was poor, ranging from 21
to 77%) of the nominal amount applied. Data were submitted demonstrating that up to 40% of the
applied dose could apparently evaporate from skin (under conditions simulated in vitro') and that
application error could result in application of up to 20% less than the nominal value. In the face of
these uncertainties, values for excretion and absorption were calculated based upon the amount of
radiolabel that was recovered. Using these correction factors, absorption was 10-24 % (low dose)
in males and 16-20% (low dose) in females.
For the EC, recovery of radiolabel was better in the high dose animals (300 jug/cm2), and
application of a correction factor had little effect. Absorption was 4-9% in males and 10-11% in
females.
It is also possible to estimate a percent dermal absorption by using a ratio of the corrected
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percent radiolabel excreted in urine after dermal application to the average percent radiolabel excreted
in urine after intravenous administration, which is 87%. Using this ratio, the dermal absorption
estimates for the low dose EC group were 9.2-24.8% for males and 16-21.8%) for females. For the
high dose EC group, the dermal absorption estimates were 4.7-8.9%) for the males and 10.7-11.4%
for the females. Thus, similar estimates of dermal absorption were obtained by either method of
calculation.
For the Mcap, the total dermal absorption for the low dose (10.8 //g/cm2) ranged from 3-23%
in males and 6-7% in females. For the high dose (217 /ig/cm2) the total dermal absorption ranged
from 2-4%o in males and 3-4% in females. Percent dermal absorptions were also estimated using the
ratio specified in the discussion of the EC group. Using this ratio, the dermal absorption estimates
for the low dose Mcap group were 3.2-23.4% for males and 6.7-7.1%) for females. For the high dose
Mcap group, the dermal absorption estimates were 2-3.8% in males, and 2.2-3.9%) in females. Again,
similar estimates of dermal absorption were obtained by either method of calculation.
c. Cancer Classification
The carcinogenicity of alachlor was first evaluated by the Agency's Cancer Peer Review
Committee on March 25, 1986. The information available at the time included two chronic rat
studies, a special 2-year rat study for ocular lesions, and an 18 month mouse study, as well as
historical control data on the mouse, several in vitro and in vivo mutagenic assays, and metabolism
data.
The Committee concluded that the data available for alachlor was sufficient for a classification
of B2, probable human carcinogen.
Alachlor met all but one of the criteria specified for the B2 classification, any of which
alone can be sufficient for such a classification. That is, alachlor produced an
increased incidence in malignant, or combined malignant and benign, nasal turbinate
tumors and (other tumor types) in Long-Evans rats in three different experiments at
more than one dose level via dietary administration. Alachlor also produced a
statistically significant increase in lung tumors in female CD1 mice at 2 dose levels.
In a special experiment with Long-Evans rats, nasal turbinate tumors were observed
at the end of the study (2 years), in rats that received alachlor for 5 - 6 months. The
tumor incidence was as high as 50% and tumor site was unusual; i.e., not an increase
of a normal high background tumor type. Additionally, a metabolite of alachlor was
mutagenic in the Ames test at 6 dose levels.
On November 19, 1986, the Scientific Advisory Panel (SAP) upheld the B2 classification
concluding that alachlor was a B2 carcinogen since it produced "an unusual type of neoplasm (nasal
turbinate tumors) in the rat, coupled with the finding that two metabolites of alachlor are mutagenic."
The Committee reconsidered the classification on April 15, 1987, in light of the conclusions
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of the SAP and the registrant's rebuttal that alachlor should be classified as a C, possible human
carcinogen. Upon reconsideration of the available data and review of the registrant's arguments and
the SAP's decision, the Committee determined that alachlor's classification as a B2, probable human
carcinogen, was appropriate; thus, corroborating the March 25, 1986, decision.
A low dose extrapolation model was applied to the animal data to calculate the cancer
potency factor. The Qx* was calculated to be 0.08 (mg/kg/day)"1. This information was verified and
then entered into the Agency's Integrated Risk Information System (IRIS).
As part of the Agency's peer review process, alachlor was reconsidered by the Agency's
Carcinogenicity Peer Review Committee on September 27, and October 3, 1995, and January 3,
1996. The registrant, Monsanto, voluntarily provided new data to the Agency consisting of a new
mouse carcinogenicity study, additional mutagenicity studies, mechanistic data, special metabolism,
pharmacokinetic, and cell proliferation studies in support of a request for re-classification of the
carcinogenic potential of alachlor. These new data were reviewed by the Agency with respect to the
proposed mechanism(s) for induction of nasal, gastric, and thyroid tumors in the rat. The rat tumors
were considered to be the most relevant to alachlor risk assessment. The type of lung tumor in the
mouse is a common tumor. Since, in one of the mouse studies, the lung tumors were higher in the
males, and in the other mouse study the lung tumors were higher in females, it is possible that this is
a random event.
Upon evaluation of all of the submitted data regarding the carcinogenicity potential of alachlor
and consideration of the full weight-of-the-evidence, the Committee could not reach a consensus as
to the classification of alachlor as a carcinogen. Therefore the Committee recommended to defer the
carcinogenicity classification of alachlor and reconsider the classification at a later date, using the new
Cancer Assessment Guidelines when such guidelines are in effect. In addition, the Committee
recommended not to utilize the linear low dose approach, but to utilize the Margin of Exposure
(MOE) methodology for the estimation of human risk. The Committee concluded that the data in
support of the mechanism for the nasal turbinates is indicative of a rat specific response. Although
the rat and human were recognized to possess the same enzyme(s) involved in production of the
putative toxic species from alachlor, it was also recognized that the activity of these enzymes was
substantially greater in the rat compared to the human. Thus, the model of rat nasal tumorigenesis
may not be relevant for human cancer assessment. Thyroid tumors have been proposed to be the
result of induction of hepatic glucuronyl transferase with subsequent decrease in circulating T3 and
T4, a subsequent increase in TSH, and eventual hyperplastic response of the thyroid. The mechanistic
data for thyroid tumor formation meet the criteria established by the Agency and the use of the MOE
approach for human cancer assessment is consistent with Agency policy. The Committee stated that
the stomach tumor formation was a direct contact effect, non-genotoxic mechanism which parallels
human pathological conditions. These tumors result from an indirect response to change in pH. The
use of the MOE approach for human cancer assessment was consistent with Agency policy.
On October 30,1996, the SAP met to consider the weight-of-evidence for alachlor. The SAP
was asked to comment on mode of action data, provided by the registrant, for the tumor types in the
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rat associated with administration of alachlor. The Committee met on February 5, 1997, to discuss
and evaluate the weight-of-the-evidence on alachlor with particular reference to its carcinogenic
potential and to consider the comments from the SAP. The SAP and the Committee conclusions on
the tumors induced by alachlor in the rat are summarized as follows:
Thyroid tumors: Both the SAP and the Committee agreed that the Agency requirements for
demonstrating a hormonal mode of action were met by the registrant and that the tumors
were observed only at an excessive dose.
Stomach: Evidence was presented that the carcinomas resulting from alachlor were examined
to prove that they were carcinoids, not adenocarcinomas or gastric sarcomas, and that these
carcinoids are probably related to the proposed gastrin-induced effect. Based on additional
information, the evidence alluded to was based on the butachlor study and that the tumors in
the alachlor study are considered to be carcinoids. According to the investigators: The
alachlor-induced stomach tumors were evaluated microscopically and histochemically by the
same scientists involved in the pathological/mechanistic investigations with butachlor (MRID
No. 44032101). They concluded that the tumors were gastric carcinoid, stating that the
alachlor-associated gastric tumors are poorly differentiated gastric carcinoids, histologically
and histochemically resembling the gastric tumors reported with butachlor exposure. Results
of these studies indicate that the pathogenesis and progression of the gastric tumors, and the
response of the fundic mucosa, are identical with both alachlor and butachlor. Although the
tumor increases were significant only at the highest dose (excessive), it was noted that there
was also 1 tumor (vs 0 in controls) at the mid-dose (which was considered to be adequate,
not excessive) and this is a rare tumor type.
Nasal tumors: The SAP considered these possibly relevant to humans but only at exposures
in excess of anticipated human exposures for pesticide use. The Committee considered these
tumors relevant to humans (with a quantitative difference). There also was 1 tumor at the
mid-dose (not excessive) and this too is a rare tumor type.
In accordance with the EPA proposed Guidelines for Carcinogen Risk Assessment (April 23,
1996), alachlor was characterized as "likely" to be a human carcinogen at high doses, but "not likely"
at low doses, by all routes of exposure. This conclusion was based on increased incidences of
malignant and combined benign/malignant multiple tumor types in both sexes of the Long Evans rat,
which occurred mainly at higher doses. Based on a consideration of modes of action for these
tumors, the Committee agreed that a non-linear margin of exposure (MOE) approach should be used
for the purpose of risk assessment. The consensus of the Committee was that MOEs for both the
malignant mixed gastric tumors and the nasal adenomas be presented for a risk management decision.
The Committee recognizes that while the response occurs only at higher doses and
quantitative differences exist in sensitivity between rats and humans, a similar mechanism for nasal
tumor production is present in humans, and therefore its relevance to humans cannot be dismissed.
The SAP agrees with this position. The rarity of the nasal tumor type and analysis of the structure
43
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activity relationships also adds to the Committee's concern. The presence of stomach tumors, which
are also considered a rare tumor type, and the lack of a consistent histopathologic response, leads to
the conclusion that some hazard potential may exist in humans after intense exposures. Clarification
of the similarity or dissimilarity of the relevance of the rat stomach tumors could shed light on this
uncertainty. The Committee agrees that the rat stomach tumors are relevant to humans at this time.
The Committee agrees with the SAP in that thyroid tumor induction may be relevant to humans, but
that the tumors in rats were seen at an excessive dose.
Since these are considered rare tumor types, for purposes of risk assessment, the MOE for
the nasal tumors should be determined with 0.5 mg/kg/day as the "point of departure" as no tumor
response was seen at this dose level. (Tumors were present at the next highest tested dose level,
females at 2.5 mg/kg/day, in the 1983 rat study for nasal tumors). The MOE for the stomach tumors
should be determined with 14 mg/kg/day as the "point of departure" as no tumor response was seen
at this dose level. (Tumors were present at the next highest tested dose level, females at 42
mg/kg/day, in the 1981 rat study for stomach tumors). While not statistically significant at these next
higher dose levels, the Committee considered tumor presence biologically significant due to their
rarity in rats. Thyroid tumors were observed only at an excessive dose; therefore, no "point of
departure" was determined.
d. Other Toxicological Endpoints
The toxicological effects of a pesticide can vary with different exposure durations. The
Agency considers the entire toxicity data base, and based on the effects seen for different durations
and routes of exposure, determines which risk assessments are necessary to assure that the public is
adequately protected from any pesticide exposure scenario. Both short and long durations of
exposure are always considered. Typically, risk assessments include "acute", "short-term",
"intermediate term", and "chronic" risks. These assessments are defined as follows:
Acute risk results from a one day or single event consumption of food and water, and reflects
toxicity which could be expressed following oral exposure to the pesticide residues. High-end
exposure to food and water residues are assumed.
Short-term risk results from exposure to the pesticide for a period of 1-7 days, and therefore
overlaps with the acute risk assessment. Historically, this risk assessment was intended to
address primarily dermal and inhalation exposure which could result, for example, from
occupational pesticide applications. Since enaction of FQPA, this assessment has been
expanded. The assessment will be performed when there are primary dermal and inhalation
exposures that result from residential or occupational exposures lasting from 1-7 days.
However, the analysis for residential exposures will now address both dietary and non-dietary
sources of exposure, and will typically consider exposure from food, water, and residential
uses when reliable data are available. In a short term assessment, risks from average food
and water exposure, and high-end residential exposure, are aggregated. High-end exposures
from all three sources are not typically added because of the very low probability of this
44
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occurring in most cases, and because the other assumptions built into the assessment assure
adequate protection of public health.
Intermediate-term risk results from exposure for 7 days to several months. This assessment
is handled in a manner similar to the short-term risk assessment.
Chronic risk assessment describes risk which could result from several months to a lifetime
of exposure. For this assessment, risks are aggregated considering average exposure from
all sources for representative population subgroups including infants and children.
An Agency Committee of toxicologists and scientists met three times to select the appropriate
endpoints for use in the alachlor risk assessment. The results of the latest meeting of that Committee
on May 14, 1996, are presented below.
Acute Dietary Assessment:
As part of the dose-response assessment, the Agency's toxicologists review the available
database to determine the endpoints of concern. For alachlor, there is no concern for an acute dietary
assessment since the available data do not indicate any evidence of significant toxicity from a one day
or single event exposure by the oral route. Therefore, this assessment for a one day high-end dietary
exposure is not required.
Short-Term (1 to 7 days) Occupational Exposure Assessment:
This assessment is required. The NOEL to be used for calculating the MOE (Margin of
Exposure) is 150 mg/kg/day from a rat developmental toxicity study (MRID No. 00043645). (The
LOEL was 400 mg/kg/day based on maternal hair loss, soft stools, anogenital staining, increased
mortality, increased post-implantation loss and a reduced number of live fetuses.) The rat
developmental toxicity study was chosen instead of the rabbit development toxicity study since the
effects in the rat developmental toxicity study were more indicative of toxicity (clinical signs and body
weights) versus those in the rabbit developmental toxicity study (body weights). Since the selected
NOEL is from a gavage study, the dermal exposure will need to be adjusted by the dermal absorption
factor to convert to oral-equivalents. Since the selected NOEL is from a developmental study, the
appropriate population subgroup is females 13+ years old.
For all occupational scenarios, the Agency has no concerns for an MOE in excess of 100 for
non-cancer effects when the NOEL used in calculating the MOE is from an animal study.
Intermediate-Term (1 week to several months') Occupational Exposure Assessment:
This assessment is required. The NOEL to be used for calculating the MOE is 50 mg/kg/day
from a 21-day dermal toxicity study (MRID No. 00147328). (The LOEL was 300 mg/kg/day based
on hematological and clinical chemistry changes.) Since the selected NOEL is from a dermal study,
45
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the dermal exposure will not need to be adjusted by the dermal absorption factor. The selected
NOEL is from a dermal study; therefore, it could be considered inappropriate to use the total dose
(combined dermal and inhalation exposure) in the MOE calculation. However, in the case of alachlor,
the inhalation component is insignificant when compared to the dermal, so the combined total is
essentially a dermal exposure.
For all occupational scenarios, the Agency has no concerns for an MOE in excess of 100 for
non-cancer effects when the NOEL used in calculating the MOE is from an animal study.
Long-Term (several months to lifetime^) Occupational Exposure Assessment:
As part of the hazard assessment process an endpoint of concern was determined for the
chronic occupational assessment. However, during the exposure assessment process, the exposures
which would result from the use of alachlor were determined to be of an intermittent nature. The
frequency and duration of these exposures do not exhibit a chronic exposure pattern. The exposures
do not occur often enough to be considered a chronic exposure, i.e. a continuous exposure that
occurs for at least several months. Therefore, performing a long-term occupational assessment is not
appropriate.
If a chronic scenario can be identified, then this assessment is required. The NOEL to be used
for calculating the MOE is 1 mg/kg/day from a 1-year dog study (MRID No. 00148923). ( The
LOEL is 3 mg/kg/day based upon signs of hemosiderosis and hemolytic anemia.) Since the selected
NOEL is from an oral (capsules) study, the exposure will need to be adjusted by the dermal exposure
factor.
For all occupational scenarios, the Agency has no concerns for an MOE in excess of 100 for
non-cancer effects when the NOEL used in calculating the MOE is from an animal study.
Residential
Alachlor is a restricted use pesticide; therefore, alachlor can be used only by certified
applicators and cannot be purchased or used by the general public. The Agency has not identified any
alachlor products that are intended for home use, or uses in/around schools, parks, or other public
areas. Therefore, residential assessments are not appropriate.
Inhalation
A separate risk assessment for inhalation exposure will not be performed. The inhalation
exposure will be added to the dermal exposure, thus implicitly assuming 100% inhalation exposure.
Percent Dermal Absorption:
A dermal absorption factor of 24% as determined from the three rhesus monkey studies
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(MRID Nos. 00149404, 00149403) will be used to adjust dermal exposures when compared to a
NOEL from an oral study.
Chronic Dietary:
The RfD is the traditionally selected endpoint for chronic dietary risk. As previously
discussed, the RfD for alachlor was determined to be 0.01 mg/kg/day. The aggregate dietary
assessment will consider both food and water. As previously stated, there is no chronic residential
assessment to aggregate with the chronic dietary assessment.
Carcinogenic Dietary MOE Approach:
A carcinogenic assessment is required for the dietary and/or drinking water scenario. It is
likely that individuals will consume alachlor residues throughout their lifetime in the food and water
consumed.
Given that these are rare tumor types, the MOE for the nasal tumor should be determined
using 0.5 mg/kg/day as the dose "point of departure". No tumor response was seen at this dose level.
Nasal tumors were present at the next highest dose level (2.5 mg/kg/day) in the 1983 rat study for
nasal tumors. The MOE for the stomach tumors should be determined using 14 mg/kg/day as the
dose "point of departure" as no tumor response was seen at this dose level. Stomach tumors were
present at the next highest dose level (42 mg/kg/day) in the 1981 rat study for stomach tumors.
Thyroid tumors were observed only at an excessive dose; therefore, no "point of departure" was
determined.
Carcinogenic Dietary Qt* Approach:
A carcinogenic assessment is required for the dietary and/or drinking water scenario. It is
likely that individuals will consume alachlor residues throughout their lifetime in the food and water
consumed. The Qx* of 0.08 (mg/kg/day)"1 will be used for assessing dietary cancer risk, assuming a
linear approach.
Carcinogenic Occupational MOE Approach:
The Agency's Cancer Peer Review Committee recommended not to use the linear low dose
approach, but to utilize the MOE methodology for estimation of human risk. The MOE methodology
is consistent with a non-linear mechanism which requires continuous exposure. Thus, the likelihood
of a positive carcinogenic response depends on the duration of the exposure as well as the magnitude
of the exposure.
It is not appropriate to calculate a carcinogenic MOE for the occupational scenario, as there
are no chronic/1 ong-term exposure scenarios for the application of alachlor. Calculation of a
carcinogenic MOE for agricultural workers based on intermittent exposure is not appropriate.
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Carcinogenic Occupational Ot* Approach:
Unlike the MOE approach to carcinogenic risk assessment, the Qx* approach assumes that
any exposure could result in tumor formation. Thus, this type of assessment could be performed for
an intermittent exposure. However, the scientific validity of the MOE approach for carcinogenic risk
assessment of alachlor has been documented. Alachlor was classified as "likely" to be a carcinogen
at high doses, but "not likely" at low doses. It is only the policy on determining an appropriate
regulatory level that has not been fully developed by the Agency. Since, performing a carcinogenic
MOE risk assessment for the occupational scenario is not appropriate, a Qx* carcinogenic
occupational assessment for comparison purposes is not necessary.
e. Determination of the FQPA 10X Safety Factor
FQPA directs the Agency to "ensure that there is a reasonable certainty that no harm will
result to infants and children" from aggregate exposure to a pesticide chemical residue in setting and
reassessing tolerances. The law further states that in the case of threshold effects, for purposes of
providing this reasonable certainty of no harm, "an additional tenfold margin of safety for the
pesticide chemical residue and other sources of exposure shall be applied for infants and children to
take into account potential pre- and post-natal toxicity and completeness of the data with respect to
exposure and toxicity to infants and children. Notwithstanding such requirement for an additional
margin of safety, the Administrator may use a different margin of safety for the pesticide residue only
if, on the basis of reliable data, such margin will be safe for infants and children."
In determining what safety factor is appropriate for assessing risks to infants and children,
EPA considers all available reliable data and makes a decision using a weight-of-evidence approach.
This approach takes into account the completeness and adequacy of both the toxicity (hazard) and
exposure databases.
The Agency's FQPA Safety Factor Committee met on March 30, 1998, to evaluate both the
hazard and exposure databases for alachlor and determine the removal, retention, or reduction of the
FQPA Safety Factor (as required by FQPA), to ensure the protection of infants and children from
exposure to alachlor. Based on a weight of the evidence approach, the Committee determined that
the lOx Safety Factor for enhanced sensitivity to infants and children (as required by FQPA) should
be removed. This decision was based on the following information:
Hazard Consideration - Determination of Susceptibility
There is no evidence of increased susceptibility of rats or rabbits to in utero and/or postnatal
exposure to alachlor. In the prenatal developmental toxicity studies in rats and rabbits and the multi-
generation reproduction study, effects in the offspring were not observed at levels which resulted in
evidence of parental toxicity.
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Hazard Consideration - Adequacy of the Toxicological Database
There are no data gaps for the assessment of the effects of alachlor following in utero and/or
postnatal exposure. Based on the toxicity profile for alachlor, a developmental neurotoxicity study
in rats is not required.
Exposure Consideration - Dietary (Tood)
The established alachlor tolerances are expressed as "alachlor and its metabolites." The
current enforcement method measures alachlor and its metabolites containing the DEA and HEEA
moieties. There are several other classes of alachlor metabolites that are not included in the tolerance
expression.
Alachlor is a herbicide, generally used pre-emergence or early postemergence. Residues are
systemic. Rotational crop tolerances are needed indicating that residues remain in the soil for at least
a year after use.
Anticipated residues were used in the alachlor chronic and carcinogenic dietary exposure
assessment. Anticipated residues for alachlor were based on the average residues found in field trials
where alachlor was used at the maximum typical application rate and weighted for the percent of use
at each application timing (i.e., preemergence vs. postemergence). Adequate information on percent
of crop treated is available for all crops. Up to 35% of corn and lima beans are treated, and up to 15
% of soybeans. Lesser amounts of other crops are treated (e.g., <5% of peanuts). These percentages
are down from 10 years ago (when 62% of peanuts were treated).
Since the dietary exposure assessment is based on field trial data, the anticipated residues are
likely to overestimate the dietary exposure because application rates and timing assumed in the dietary
exposure analysis are conservative, and residues are likely to degrade after the farm gate where field
trial samples are obtained. Crops contributing most highly to the dietary exposure for both adults and
children were legumes (beans and soybeans) and milk, followed by corn.
Exposure Consideration - Dietary (Drinking Water)
Estimates of alachlor concentrations in ground water are based on the National Alachlor Well
Water Survey (NAWWS). These samples represent approximately 6 million wells from which
approximately 20 million people draw their drinking water. Reported values are for alachlor per se.
No degradates of alachlor were analyzed in the NAWWS. NAWWS data are considered to be of
high quality, and because of the statistical design of the survey, are also considered to be the best
available data concerning alachlor per se residues in ground water.
Estimates of alachlor concentrations in surface water are also based on available monitoring
data. Additionally, in surface water, there is some monitoring data available for the alachlor ESA
degradate. Concentrations are reported as time weighted mean concentrations (TWMC) which
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reflect "amortization" of periods of high and low concentrations. Therefore, annual TWMCs
(calculated using at least one year of sampling data) are the most appropriate values to use for
estimation of chronic exposure to alachlor in drinking water.
The information available to the Agency, a partial toxicological database, indicates that the
alachlor ESA degradate is of lower toxicity than the parent. But, the Agency does not have
toxicological databases on all degradates of alachlor. However, based on metabolism studies and
knowledge of the chemical structures of the degradates, the Agency does not believe that the toxicity
of the degradates would exceed that of alachlor. Therefore, the Agency will assume that structurally
similar alachlor degradates are no more or no less toxic than alachlor. The Agency has used the
available exposure data on alachlor and alachlor ESA to determine that 4% of the RfD is occupied
by food and water (children 1-6 years). Even if many of the alachlor degradates were present, it
is not likely that the RfD would be exceeded.
Exposure Consideration - Residential (Non-occupational. Non-dietary') Uses
Alachlor is a restricted use pesticide; and therefore, can only be used by certified applicators
and cannot be purchased or used by the general public. The Agency has not identified any alachlor
products that are intended for residential use.
Decision of the FOPA IPX Safety Factor Committee
Based on their consideration of the above hazard and exposure databases, the Agency's FQPA
10X Safety Factor Committee recommended that the lOx factor for enhanced sensitivity to infants
and children (as required by FQPA) should be removed. The rationale for this decision is
summarized below:
# There was no indication of increased susceptibility of rats or rabbits to in utero and/or
postnatal exposure to alachlor. In the prenatal developmental toxicity studies in rats
and rabbits and the multi-generation reproduction study, effects in the offspring were
not observed at levels which resulted in evidence of parental toxicity.
# The toxicology data base for alachlor is complete. The toxicity profile does not
indicate the need for a developmental neurotoxicity study.
# The use of generally high quality data together with conservative models in the
exposure assessment provided adequate protection for infants and children.
# Alachlor is not currently registered for any residential uses.
3. Exposure Assessment
a. Dietary Exposure
The residue chemistry database includes information on the pesticide residues found in plants
and animals, the levels of the detected pesticide residues, and a description of the analytical methods
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used. Residue chemistry data are used by the Agency to determine the residues of concern and to
establish tolerances in food and feed. Tolerances are pesticide residue levels that should not be
exceeded in or on a raw agricultural commodity in the channels of interstate commerce when the
pesticide is applied according to label directions. Tolerances for residues of alachlor in/on raw plant
commodities, and in animal commodities are currently expressed in terms of the combined residues
of alachlor and its metabolites (calculated as alachlor) (40 CFR §180.249). These tolerances are set
at 0.02-3.0 ppm. No food/feed additive tolerances have been established for alachlor residues of
concern.
The residue chemistry database for alachlor is adequate and will support reregi strati on
eligibility.
Nature of the Residue - Plants: OPPTS GLN 860.1300 (formerly 171 -4a)
The qualitative nature of the residue in plants is adequately understood. Studies with corn
and soybeans indicate that alachlor is readily absorbed from soils and translocated throughout the
plant. Very little alachlor is translocated from the foliage. Metabolism involves the displacement of
chlorine by oxygen or sulfur nucleophiles, hydroxylation at the 1- position of the ethyl group, and
conjugation of the metabolites with sugar. The terminal residues to be regulated are those
metabolites which can be hydrolyzed under basic conditions to 2,6-diethylaniline (DEA) and 2-ethyl-
6-(l-hydroxyethyl)aniline (1-HEEA). (MRID Nos. 00026221, 00081314, 00131424).
The alachlor ESA metabolite was identified as one of many alachlor metabolites present in
these crops. Since alachlor ESA is converted to diethylaniline (DEA) by the alachlor crop residue
methodology, it has been quantified in the crop residue analyses conducted for alachlor and is
therefore included in the existing crop tolerances listed at 40 CFR § 180.249.
The chemical structures of representative metabolites are presented in Figure A.
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7igure A. The Chemical Structures of Representative Metabolites of Concern of Alachlor.
Common Name
Chemical Name
Chemical Structure
alachlor
2-chloro-2',6'-diethyl-N-(methoxy-
methyl)acetanilide
alachlor alcohol metabolite (A-23)
N- [(2,6-diethy l)phenyl ] -N-methoxy methyl -
2-hydroxyacetamide
alachlor ESA metabolite
MON 5775,
2',6'-diethyl-N-methoxymethyl-2-sulfoacet
anilide, sodium salt or 2-[2,6-diethylphenyl
(methoxymethyl) amino] -2-oxoethane
sulfonic acid, sodium salt.
\
0
0"
HgC 0 Na.+
Alachlor ESA
A-ll
N-{ [2-ethyl-6-( 1 -hydroxy ethyl)]phenyl} -2-
hydroxyacetamide
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A-18
N- [(2,6-di ethyl)pheny 1] oxanilic aci d
A-20/AP-7
N-[(2,6-diethyl)phenyl]-2-
hydroxyacetamide
alachlor sulfone metabolite (S-24)
N-{[2-ethyl-6-(l-hydroxyethyl)phenyl}-N-
methoxymethyl-2-(methyl-
sulfone)acetami de
S-16
N-{ [2-ethyl-6-( 1 -hydroxy ethyl)]phenyl} -2-
(methyl-sulfone)acetamide
Nature of the Residue - Livestock: OPPTS GLN 860.1300 (formerly 171 -4b)
The qualitative nature of the residue in animals is adequately understood. Studies involving
lactating goats and laying hens fed an alachlor alcohol or sulfone metabolite indicate that metabolism
of alachlor in hens and ruminants is similar. After displacement of chlorine, metabolites undergo loss
of the methoxymethyl group, hydroxylation of the ethyl side-chain(s) usually at the 1- position, and
formation of glucuronide conjugates. (MRID Nos. 00137777, 00137778, 00147472, 00147473,
40393901, 40394001, 42594901, 42594902, 42594903, 42594904)
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In animals dosed with technical alachlor, alachlor's ESA metabolite was identified as a
metabolite of alachlor in rat, mice, or monkey metabolism studies. (MRID Nos. 00132045,
42852107, 42931101, 42852106, 00154238, 40000901). The initial chlorine displacement step
involving glutathione catalyzed by glutathione transferase has been firmly established in these
mammals. Methylsulfone and sulfur-conjugated organic acids have been shown to arise from further
metabolic conversion of the glutathione adduct in rats and monkeys. Although the initial metabolism
of alachlor in mammals is oxidative conversion of the sulfur atom, the metabolic product is not
alachlor ESA.
Livestock metabolism studies which included alachlor ESA as one of the dosed components
were performed (MRID Nos. 00147472, 00147473). Results from these experiments demonstrated
that alachlor ESA was excreted by the animals unchanged, largely via the feces (goats). It did not
accumulate in edible tissues.
The residues to be regulated are those metabolites which can be hydrolyzed under basic
conditions to 2,6-diethylaniline (DEA) and 2-ethyl-6-(l-hydroxyethyl)aniline (1-HEEA). See Figure
A.
Residue Analytical Methods: OPPTS GLN 860.1340 (formerly 171-4^")
Three GLC methods, Methods 1(a), 1(b), and II, are currently available in the Pesticide
Analytical Manual (PAM) Vol. II for the enforcement of tolerances for alachlor residues of concern;
however, these methods do not recover 1-HEEA-yielding metabolites. An HPLC method, which
determines DEA- and 1-HEEA-yielding metabolites has been validated by the Agency and is
considered acceptable for enforcement purposes for plant commodities. The method uses HPLC with
oxidative coulometric electrochemical detection of both DEA- and 1-HEEA-producing residues, and
was recommended for inclusion in PAM Vol. II as Method III; the limit of detection is 0.01 ppm for
each metabolite class. (MRID Nos 00023663, 00093160, 00148285, 00149999, 00152197,
00154237,00154332,00155732,00159793,00159796,00162939,40039901,40040301,40040401,
40271801,40271802,40529201,40558001,40820601,41916001,42086001,42192501,42286701,
42286702, 42308701, 42349101, 43140001, and PP#9F0740)
Multiresidue Methods: OPPTS GLN 860.1360 (formerly 171-4m)
The FDA Pestrak database (PAM Vol. I, Appendix II, dated 11/90) indicates that alachlor,
per se. is completely recovered through Multiresidue Protocols D and E. In addition, multiresidue
protocol testing of five alachlor metabolites has been submitted and forwarded to FDA (MRID No.
41949601).
Storage Stability Data: OPPTS GLN 860.1380 (formerly 171 -4e)
Adequate storage stability data are available for corn, peanuts, soybeans and their processed
commodities, for sorghum, and for animal commodities. Residues of alachlor metabolites are stable
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during frozen storage (<-18 °C) in/on corn forage and fodder, sorghum grain, forage, and fodder, and
soybeans for up to 1394 days. Residues of alachlor metabolites are stable during frozen storage in/on
sunflower seeds for up to 280 days and in the processed commodities of sunflowers for up to 91 days.
These storage stability data can be translated to all crops for which alachlor is currently registered.
(MRID Nos. 00149406, 00150090, 00152198, 00152868, 00154237, 40491101, 40628301,
40946901, and 42239501)
Crop Field Trials: OPPTS GLN 860.1500 (formerly 171 -41<)
The conclusions regarding the reregi strati on eligibility of alachlor are based on the use
patterns registered by the basic producer, Monsanto Corporation.
Some of the data used in support of existing or proposed tolerances were generated at Craven
Laboratories. The Agency determined that it would not rely on Craven data for regulatory decisions,
and identified the data that would need to be replaced. However, replacement of the Craven
generated magnitude of the residue data were not required for soybeans, provided postemergence and
sequential uses on soybeans were removed from all alachlor labels. At this time these use patterns
have been deleted from the label.
Data for magnitude of the residue in sorghum grain, forage, and fodder have been evaluated
and deemed adequate. Data are available to support the G formulation of alachlor on sweet corn
applied preplant incorporated and preemergence at up to 4 lb ai/A. Data are available to support the
use of the Mcap/G formulation on sweet corn: preemergence and preplant incorporated and
postemergence at 4 lb ai/A. Data have been submitted to support use of the Mcap formulation on
corn at 4 lb ai/A preemergence followed by 2 lb/A when used as a sequential application for early
postemergence (before the corn is 5" high). The maximum single application rate is 4 lb ai/A.
Additional field residue data are no longer required for beans (dry and succulent), to support
pre-emergence uses; for field corn grain, forage, and stover, to support sequential uses of the EC
formulation; for sweet corn (K+CWHR) and sweet corn forage and stover to support postemergence
and sequential uses of the EC formulation and uses in excess of 4 lb ai/A/season; and for peanuts to
support postemergence and sequential uses. Monsanto has elected to delete these uses rather than
generate additional residue data at this time. The labels have been changed to reflect these changes.
The proposed tolerances for soybeans and soybean aspirated grain fractions must be revised;
higher tolerances are required. Tolerance petitions for bean vines and hay, corn forage and fodder,
peanuts, peanut hulls, and sorghum forage are pending. (MRID Nos. 00022988, 00023664,
00023665,00024526,00025262,00026995,00028556,00028557,00028558,00035389,00035390,
00035391,00035395,00035399,00068044,00068045,00081311,00147475,00148285,00152197,
00152199,00155732,00159793,00159796,00159936,41083801,40039901,40040301,40189701,
40271801,40341201,40502101,40511201,40511301,40511901,40662601,40820601,41083801,
41862901,41916301,42309001,42313301,42348901,42348902,42349101,42741601,42741601,
42929901, 42971701)
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Feeding restrictions have been established for peanut vines and hay, and soybean forage and
hay; therefore, the established tolerances for these commodities should be revoked. Note that
Monsanto will be submitting data to support sunflower and cotton. Tolerances will need to be
established for these commodities.
Processed Food/Feed: OPPTS GLN 1520 (formerly 171-40
No food or feed additive tolerances for alachlor are needed on any processed product of any
commodity for which alachlor is currently registered. However, all data submitted for magnitude of
the residue in processed food/feed have been evaluated and deemed adequate. (MRID Nos.
00148285,00152197,00154239,00154240,00162937,00162939,40040401,40271802,40788201,
40947101, 41856301, 41862901, 41916301, 42302001, and PP#0F2313/FAP#1H5612)
Reduction of residue data were submitted for dry beans and peanuts as required by a June 9,
1986, DCI. Residues were determined in canned beans, peanut butter, dry and oil roasted peanuts
following commercial processing. A processing factor of 0.2x was determined for canning beans.
Processing factors of0.70x, 0.75x, and 0.83xwere determined for peanut butter, dry roasted peanuts,
and oil roasted peanuts, respectively. These factors will be used for the determination of anticipated
residues for alachlor.
Limited monitoring studies were submitted for peanut butter and infant soy formula. Three
major brands of peanut butter were collected in major cities across the US in 1989 in 2 studies. Of
the 192 samples collected, 89% had detectable residues of alachlor metabolites. The average residue
found was 0.029 ppm alachlor equivalents (with no correction for percent crop treated). In another
study, several samples of 2 major brands of soy formula were collected in 9 major cities across the
US. No detectable residues of alachlor DEA or HEEA metabolites were found (LOD=0.01 ppm) in
any of the 1,398 samples. (MRID Nos. 40330301, 40820601, 40820701, 42158601, 42276701,
42300701, 42309001).
Meat. Milk. Poultry and Eggs: OPPTS GLN 860.1480 (formerly 171-40
Data for magnitude of the residue in meat, milk, poultry, and eggs have been evaluated
previously; however, the adequacy of the data could not be assessed because at that time the
qualitative nature of the residue in animals was not adequately understood. These data were
generated from feeding studies in which dairy cattle and poultry were dosed with of a mixture of
DEA- and 1 -HEEA-yielding metabolites (60% DEA-yielding and 40% 1 -HEEA-yielding metabolites)
at approximately 4,12, and 40 ppm. Tissues, milk, and eggs were analyzed for residues of DEA- and
1-HEEA-yielding metabolites and residues were expressed as alachlor equivalents. The maximum
residues of DEA-yielding metabolites were 0.9 ppb in milk, 1.0 ppb in fat, 6.2 ppb in kidney, 3.6 ppb
in liver, and 0.8 ppb in muscle, and the maximum residues of 1-HEEA-yielding metabolites were 1.6
ppb in milk, 1.5 ppb in fat, 5.4 ppb in kidney, 6.8 ppb in liver, and 1.1 ppb in muscle of dairy cattle
fed at approximately 12 ppm (1,7x the maximum expected dietary burden). The maximum residues
of DEA-yielding metabolites were 1.0 ppb in eggs, <0.5 ppb (nondetectable) in fat, 1.0 ppb in kidney,
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1.1 ppb in liver, and <0.5 ppb in muscle, and the maximum residues of 1-HEEA-yielding metabolites
were 7.8 ppb in eggs, <0.5 ppb in fat, <1.0 ppb (nondetectable) in kidney, <1.0 ppb in liver, and 0.5
ppb in muscle of poultry fed at 4 ppm (approximately 2x the maximum expected dietary burden)
(MRIDNos. 00149406, 00150090, 00152198, and 00152868).
These results support the established tolerances of 0.02 ppm for eggs; milk; and the fat, meat,
and meat byproducts of cattle, goats, hogs, horses, poultry and sheep. The maximum expected
dietary burdens of alachlor residues for cattle and poultry are calculated below; soybean forage and
hay, and peanut vines and hay were not included in this calculation since feeding restrictions have
been established for these commodities and tolerance revocations have been recommended.
Table 7:
Calculated Dietary Burdens
Commodity
Percent in Diet
Percent Dry Matter
Tolerance1
ppm
(in diet")
Cattle:
Field corn grain
30
0.88
0.2
0.07
Bean vines
25
0.35
5
3.6
Soybean hulls
25
0.90
5
1.4
Soybean grain dust
20
0.85
10
2.4
Dietarv RnrHen
Total =75
Poultry:
Soybeans
50
—
1
0.5
Soybean meal
20
—
1
0.2
Soybean grain dust
20
—
10
1.0
Corn Grain
10
—
0.2
0.02
Dietarv Burden
Total = 1.8
In cases where tolerance proposals are required or pending, appropriate tolerance levels from
the Tolerance Reassessment Summary were used.
Water. Fish, and Irrigated Crops: OPPTS GLN 860.1400
Alachlor is not registered for direct use of water and aquatic food and feed crops; therefore,
no residue chemistry data are required under this guideline topic.
Food Handling: OPPTS GLN 860.1460
Alachlor is not registered for use in food-handling establishments; therefore, no residue
chemistry data are required under this guideline topic.
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Confined Accumulation in Rotational Crops: OPPTS GLN 860.1850 (formerly 165-1")
All data for confined rotational crops have been evaluated and deemed adequate (MRID Nos.
42395301 and 42395302). Alachlor residues were found to accumulate in all three rotational crops
tested. Radishes, lettuce, and wheat were planted 31,91, 120, or 365 days following the second of
two applications of uniformly ring-labeled [14C]-alachlor to sandy loam soil at 4 and 2 lb ai/acre (total
6 lb ai/A). Alachlor per se was not detected in the plants. The maj or classes of alachlor metabolites
found were those containing the DEA and 1-HEEA moities.
Field Accumulation in Rotational Crops: OPPTS GLN 860.1900 (formerly 165-2")
Limited field rotational crop studies have been submitted (MRID No. 43442001). Soybeans
and wheat were planted at various plant-back intervals following preemergence application at 4 lb
ai/A (lx) and postemergence application at 2 lb ai/A (lx) of a representative 4 lb/gal Mcap
formulation to corn. The data indicate that residues of alachlor and its metabolites containing the
DEA and HEEA moieties exceed 0.01 ppm (the LOQ) in/on many raw agricultural commodities of
soybeans and wheat. Because quantifiable alachlor residues are present in/on rotational crops,
rotational crop tolerances need to be established, or the labels may be changed to prohibit rotation
to any crop not specified on the label.
Soybeans and wheat can represent legume vegetables and cereal grains. Therefore, data
pertaining to field rotational crop studies are still required for a root crop and a leafy crop. Monsanto
plans to support cereal grains (except rice), and non-grass animal feeds as rotational crops.
b. Dietary Exposure from Drinking Water
Alachlor is regulated under the SDWA (Safe Drinking Water Act). The MCL (Maximum
Contaminant Level) for alachlor is 2 ppb. An MCL is the maximum permissible level of a
contaminant in drinking water which is delivered to any user of a public water supply system. Water
systems are required to test for regulated chemicals on a quarterly basis. A public water supply is
considered in violation of the SDWA when the average of four consecutive monitoring events exceed
the MCL or a single event exceeds 4 times the MCL. Cost and the availability of treatment
technologies are also considered in promulgating an MCL, as well as the capability of available
laboratory facilities of measuring to a common analytical level.
F or the purposes of estimating human exposure through drinking water, the Agency has relied
on one groundwater study (NAWWS) and two surface water studies (ARP and USGS). (These
studies as well as other ground water and surface water studies are discussed in the Environmental
Assessment Section of this RED.) The NAWWS study was chosen because it is representative of
Midwestern use of alachlor. NAWWS data are considered to be of high quality, and because of the
statistical design of the survey are also considered to be the best available data concerning alachlor
per se residues in ground water and the population exposed to those residues. The USGS Survey was
used because of the detections of alachlor ESA. The ARP is the most recent as well as the most
extensive data on alachlor concentrations. The Acetochlor Registration Partnership (ARP) data was
collected at drinking water treatment facilities and is therefore finished water. The use of finished
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water in this assessment is appropriate since (1) this is the water that is actually consumed, and (2)
generally surface water is treated before consumption. However, it is noted that the primary
treatment processes employed by most surface water drinking water supply systems are not expected
to be effective in removing alachlor. ARP data was collected for both ground and surface water sites.
However, the ARP ground water data has not yet been fully analyzed, and thus cannot be used in this
assessment. Additionally, it is believed that alachlor use is decreasing, so the most recent data would
reflect this decrease.
Ground Water
Estimates of alachlor concentrations in well or ground water were prepared by the Agency
and are based on the National Alachlor Well Water Survey (NAWWS). Monsanto conducted
NAWWS to estimate the proportions of private, rural domestic wells with detectable concentrations
of alachlor. NAWWS was a complex, statistically designed survey of alachlor occurrences which
targeted counties where alachlor was used in 1986. These samples represent approximately 6
million wells from which approximately 20 million people draw their drinking water.
Water samples were collected from 1,430 wells beginning in July 1988, and continuing
through May 1989. The samples were analyzed by GC/MS (gas chromatography using a mass
selective detector) in SIM (selected ion monitoring) mode. The limit of detection (LOD) for alachlor
was 0.03 ppb.
Reported values are for alachlor per se. No degradates of alachlor were analyzed for in the
NAWWS. All "Non-detects" (values reported as ND) were averaged in (with the detected residues)
using '/2 of the LOD, or 0.015 ppb. This is an acceptable procedure for dealing with the analytical
limits of detection for chemical residues.
Table 8: NAWWS Data - Residue Levels for Use in Risk Assessment
Alachlor Residue Level
Detected in Ground Water
(ppb)
Estimate of the Population
Exposed
Percentage of the Population
Exposed
0.015
(These are non-detects - use
'/2 the LOD)
19,603,040
99.5
<0.2
63,249
0.32
>=0.2
35,647
0.18
>2
3,000
0.015
The approximate proportion of the population in the alachlor use area exposed to the various
levels of alachlor in ground water is estimated above, using the data from the NAWWS. It was
estimated that 19,704,936 people received ground water from wells included in the survey area.
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Surface Water
Approximately 29 million people rely on surface water for their drinking water in the 11 maj or
corn-producing states.
Alachlor can contaminate surface water at the time of application via spray drift or for several
weeks postapplication due to run-off Alachlor surface water concentrations tend to peak in May to
early June during the first runoff events following application with rapid decline to approximately pre-
application levels by July or August. Concentration of alachlor in surface water depends on numerous
factors including the quantity of alachlor used on the drainage area upstream, the infiltration
characteristics of the drainage area soils, and the timing, frequency, and intensities of post-application
runoff events.
Degradates of alachlor were analyzed in one study, the USGS Reservoir Study. Alachlor per
se concentrations are reported as time weighted mean concentrations (TWMCs) which reflect
"amortization" of periods of high concentration and of low concentration. A TWMC is calculated
as follows: (1) Take the length of time from one measurement to the next and divide by two (For
the first and last measurements, the length of time between the first and second was assumed for the
first measurement and the time between the last and second to last measurement was assumed for the
last measurement); (2) Multiply the measurement by the number of days between each sample event;
and (3) Sum those results, then divide by the total number of days during which the measurements
occurred. Annual TWMCs (calculated using at least a year's worth of sampling data) are the most
appropriate values to use for estimation of chronic exposure to alachlor in drinking water because
TWMCs compensate for times of high and low contamination which occur during the year.
USGS Midwestern Reservoir Study
In 1992 and 1993, USGS sampled 76 Midwestern reservoirs. Each reservoir was sampled
4 times each year. The samples were analyzed for both alachlor and alachlor ESA. The LOD for
alachlor was 0.05 ppb. The LOD for alachlor ESA was 0.03 ppb. The TWMC for the 2 year period
(90th percentile) for alachlor was 0.22 ppb, and for alachlor ESA was 3.00 ppb.
Acetochlor Registration Partnership f ARP) Data (1995-1996")
This is the most recent as well as the most extensive data on alachlor concentrations in surface
waters currently available. All of the data were collected at drinking water treatment facilities and
is therefore finished (treated) water. Samples were collected at 179 sites in 12 states (Delaware,
Illinois, Indiana, Iowa, Kansas, Maryland, Minnesota, Missouri, Nebraska, Ohio, Pennsylvania, and
Wisconsin) once every two weeks from April through September for both 1995 and 1996. Two to
three additional samples were collected at each site, one or two in the fall and the other in the winter.
Unfiltered samples were analyzed for alachlor using GC/MS. The LOD for the study was 0.02 ppb.
A TWMC was estimated by the Agency for each monitoring site in the ARP. These sites
were then ranked from highest to lowest. The 90th percentile TWMC for the 2 year period was 0.1
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ppb. Thus, 10% of the monitoring sites have TWMCs greater than 0.1 ppb, and 90% of the
monitoring sites have TWMCs less than 0.1 ppb.
Exposure Estimates
Adult Female
The exposure estimate for an adult female (13+ years) is calculated by the following
equation:
Exposure = (chemical concentration in |ig/L in consumed water) X (10"3 mg/|ig) -h
(60 kg body weight) X (2L water consumed/day)
The 2 Liters of water is a default assumption used by the Agency. The 60 kilograms is the
Agency's default female body weight.
Adult Male
The exposure estimate for an adult male is calculated by the following equation:
Exposure = (chemical concentration in |ig/L in consumed water) X (10"3 mg/|ig) -h
(70 kg body weight) X (2L water consumed/day)
The 2 Liters of water is a default assumption used by the Agency. The 70 kilograms is the
Agency's default male body weight.
Child (1-6 years)
The exposure estimate for a child (1-6 years) is calculated by the following equation:
Exposure = (chemical concentration in |ig/L in consumed water) X (10"3 mg/|ig) -h
(10 kg body weight) X (1L water consumed/day)
The 1 Liter of water is a default assumption used by the Agency. The 10 kilograms
is a default value for a child's body weight.
The other assumption used is assuming that water from the same source containing the same
contaminant level is consumed throughout a 70 year lifetime. Most of the US population moves at
some time during their life and does not live in the same area, drinking from the same water source
for a 70 year lifetime. It could be considered as either an over-estimation or an under-estimation of
risk depending on the contaminant levels in the other sources of drinking water.
Information on detections of the ESA degradate of alachlor was available for only one study -
the USGS Reservoir Study. Thus, for all other studies the exposure estimates should be considered
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as under-estimated. The alachlor ESA degradate has been detected in Midwestern reservoirs and
streams at concentrations and frequencies that greatly exceed that of alachlor detections.
Table 9: Drinking Water Exposure Estimates - Adult Male
STUDY
Concentration
(ppb)
Exposure
(mg/kg/day)
MCL
2
0.0000571
Surface Water
USGS - Alachlor (reservoir)
0.22
0.0000062
USGS - Alachlor ESA (reservoir)
3.00
0.0000857
ARP Data (1995-1996) (finished water)
0.1
0.0000028
Ground Water
NAWWS
0.2
0.0000057
NAWWS
0.015
0.0000004
Table 10: Drinking Water Exposure Estimates - Adult Female
STUDY
Concentration
(ppb)
Exposure
(mg/kg/day)
MCL
2
0.0000666
Surface Water
USGS - Alachlor (reservoir)
0.22
0.0000073
USGS - Alachlor ESA (reservoir)
3.00
0.0001
ARP Data (1995-1996) (finished water)
0.1
0.0000033
Ground Water
NAWWS
0.2
0.0000066
NAWWS
0.015
0.0000005
Table 11: Drinking Water Exposure Estimates - Child (1-6 years)
STUDY
Concentration
(ppb)
Exposure
(mg/kg/day)
MCL
2
0.0002
Surface Water
USGS - Alachlor (reservoir)
0.22
0.000022
USGS - Alachlor ESA (reservoir)
3.00
0.0003
ARP Data (1995-1996) (finished water)
0.1
0.00001
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Ground Water
NAWWS
0.2
0.00002
NAWWS
0.015
0.0000015
c. Occupational
The Agency has not identified any alachlor products that are intended for home use.
Therefore, only an occupational assessment is required.
An occupational exposure assessment is required for an active ingredient if (1) certain
toxicological criteria are triggered and (2) there is potential exposure to handlers (mixers, loaders,
applicators; M/L/As) during use or to persons entering treated sites after application is complete.
In the case of alachlor the identification of short-term and intermediate-term endpoints triggers the
toxicological criteria and exposure to M/L/As has been identified.
As previously stated, there are no chronic (long-term) occupational exposure scenarios for
the application of alachlor. Therefore, a long-term exposure/risk assessment has not been performed.
Calculation of a carcinogenic MOE for agricultural workers based on intermittent exposure is not
appropriate. Therefore, in this occupational assessment for alachlor, the following scenarios are
considered: short-term and intermediate-term.
Use Patterns
Alachlor is a broad spectrum herbicide used on terrestrial food and feed crops and on
terrestrial non-food targets. The timing for applications is just prior to, at, or shortly after planting
(i.e., preplant, pre-emergent, at planting for corn and soybeans, post-transplant for ornamentals,
post-emergent, and at ground-crack for peanuts only).
Agricultural use sites include corn, soybeans, peanuts, grain sorghum (milo), and beans (i.e.
dry, lima, red kidney, and mung). Non-food and ornamental uses include applications to ornamental
woody shrubs and vines (i.e., junipers and yew). Alachlor is formulated as a liquid (active ingredient
25.2 to 45.1 percent), as a dry flowable (active ingredient 65 percent), as a microencapsulate (active
ingredient 41.5 percent) and as a granular (15 percent active ingredient). The maximum application
rates range from 4.0 lb ai/acre for corn to 3.0 lb ai/acre for soybean. Several of the application
methods involve soil incorporation techniques. Dry bulk fertilizers are impregnated with alachlor at
commercial fertilizer or farm chemical dealerships using specially designed, closed systems. In these
systems, alachlor and the fertilizers are mixed and blended in a system such as a closed rotary drum
container, or similar system. Nozzles situated inside the rotary drum are used to apply the alachlor
onto the fertilizer. The fertilizer impregnated with alachlor is then applied using spin-type spreaders,
or positive displacement equipment.
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Incident Data
Alachlor is considered a mild irritant according to EPA's "Recognition and Management of
Pesticide Poisoning" (Fourth Edition, 1989). No serious cases (deaths or hospitalized cases) have
been reported in national surveys of deaths (in the 1960s or 1970s, the last surveys completed) or
hospitalization (1971 through 1982). California reported just 3 physician-treated cases in the 12 year
period, 1982 through 1993. Two of these three cases involved skin or eye effects and one case was
considered a possible systemic poisoning. Thirteen unconfirmed cases have been screened by the
Office of Pesticide Program's Incident Data system, most of which reportedly experienced minor
dermal effects. No changes in labeling are warranted based on this incident data.
Previous Agency Regulatory Action/ Special Review
At the time of the Special Review of alachlor the Agency used the best available data to
estimate worker exposure. Risk estimates for the PD-1 were based on patch data supplied by the
registrant which measured exposure to the EC, Mcap, and G formulations. However, in response
to the PD-1, the registrant submitted additional data; namely, the previously discussed 1984 and
1985 human biomonitoring data. The Agency reviewed these data. Numerous limitations were
identified related to the biomonitoring data, such as: (1) the small number of replicates (4 persons per
study) which cannot indicate the range (the expected variability) of exposure to alachlor; (2) study
subjects were Monsanto employees; (3) mixer/loaders wore protective goggles, rubber gloves, and
rubber overshoes; (4) applicators used enclosed cab tractors exclusively; (5) only 20 acres were
treated with alachlor-containing formulations instead of the 80 to 120 acres that could be expected
to be treated; (6) some products were soil incorporated; and (7) biological monitoring and passive
dosimetry were conducted concurrently on the same individual which may reduce the amount of
pesticide reflected in biomonitoring results.
At the time of the PD-4, the biomonitoring data were the best data available, so the Agency
used the biomonitoring data to estimate exposure. In fact, the PD-4 stated that the Agency believed
that biomonitoring data from well-designed and executed studies, if supported by adequate
pharmacokinetic studies, provide a better measure of exposure than patch data. At the time of the
PD-4, the Agency used monkey data showing the rate and ratio of excreted alachlor metabolites to
interpret the results of the biomonitoring data.
Using the previously submitted patch data from the registrant, and data available in the
literature documenting exposure variability, the Agency estimated a range of exposures of two orders
of magnitude, with the biomonitoring data representing the low end of the range for exposure to
alachlor during mixing/loading and groundboom application. In 1987 the Agency believed the range
of exposures defined by the biomonitoring data, the patch data, and the open literature values more
accurately reflected applicator exposure estimates than the estimates that were used in the PD-1.
In this risk assessment for the purpose of the re-registration of alachlor, the Agency has used
data from PHED as well as the registrant-generated biomonitoring data. As noted previously
limitations were identified. Of particular significance were (1) the small number of replicates (4
persons per study), and (7) biological monitoring and passive dosimetry were conducted concurrently
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on the same individual. The small number of replicates lowers the confidence level in the results;
however, the higher of the two values (0.0000126 mg/kg/lb ai.) was used in the assessment. The
concurrent monitoring is in all probability a small percent of the total amount of alachlor that could
be absorbed given the small surface areas of the patches. These data do not meet the Agency's
guideline requirements (875.2600), for biological monitoring.
During the 10 year interval since the PD-4, the Pesticide Handlers Exposure Database
(PHED; currently Version 1.1) was developed. PHED was developed by Health Canada, the
American Crop Protection Association, and EPA, and initially released for public use in 1992. PHED
is a comprehensive generic/surrogate exposure database containing a large number of measured
values of dermal and inhalation exposure for pesticide workers (e.g., mixers, loaders, and applicators)
involved in the handling or application of pesticides in the field. Use of surrogate or generic data is
appropriate since it is generally believed that the formulations and the method of application, not the
chemical properties of the pesticide control the amount of dermal and inhalation exposure. Thus,
PHED allows exposure and risk assessments to be conducted with a much larger number of
observations than available from a single exposure study. The current version of PHED (Version 1.1)
contains larger numbers of exposure replicates and a broader spectrum of mixer/loader and applicator
scenarios reflecting use of a variety of personal protective equipment. Note that Table 12 rates the
data (for number of replicates and quality control parameters) used to estimate exposure for mixing
liquids and groundboom application (baseline) as high confidence with the number of replicates
varying up to 122.
Generally, biomonitoring data are preferable to passive-dosimetry data. The use of a dermal
absorption factor is not necessary for biomonitoring data. Biomonitoring data can give a more
accurate estimate of absorbed dose. But, biomonitoring does not determine the source of the
exposure (inhalation/dermal; hands/head), and thus, cannot be used to identify what measures, to
mitigate exposures, are likely to be the most effective.
Therefore, for the Alachlor Reregistration Eligibility Decision Document, the Agency is using
PHED Version 1.1 to assess pesticide handlers exposure to alachlor. However, the results of the
biomonitoring study will be used for comparison purposes.
PHED is a comprehensive generic/surrogate exposure database containing a large number of
measured values of dermal and inhalation exposure for pesticide workers (e.g., mixers, loaders, and
applicators) involved in the handling or application of pesticides in the field. The database currently
contains data for over 2000 monitored exposure events. Use of surrogate or generic data is
appropriate since it is generally believed that the physical parameters of the handling and application
process (e.g. the type of formulations, the method of application, and the type of clothing), not the
chemical properties of the pesticide, control the amount of dermal and inhalation exposure. Thus,
PHED typically allows exposure and risk assessments to be conducted with a much larger number
of observations than available from a single exposure study.
PHED also contains algorithms that allow the user to complete surrogate task-based exposure
assessments beginning with one of the four main data files contained in the system (i.e., mixer/loader,
applicator, flagger, and mixer/loader/applicator). Users select data from each file and construct
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exposure scenarios that are representative of the use of the chemical. EPA, in conjunction with the
PHED task force, has evaluated all of the data currently in PHED, and developed a surrogate
exposure table that contains a series of standard exposure estimates for various scenarios. These
standard unit exposure values are the basis for this assessment. The standard exposure values (i.e.,
the unit exposure values included in the exposure and risk assessment tables) are based on the "best
fit" values calculated by PHED. PHED calculates "best fit" exposure values by assessing the
distributions of exposures for each body part included in datasets selected for the assessment (e.g.,
chest or forearm) and then calculating a composite exposure value representing the entire body.
PHED categorizes distributions as normal, lognormal, or in an "other" category. Generally, most data
contained in PHED are lognormally distributed or fall into the PHED "other" distribution category.
If the distribution is lognormal, the geometric mean for the distribution is used in the calculation of
the "best fit" exposure value. If the data are an "other" distribution, the median value of the dataset
is used in the calculation of the "best fit" exposure value. As a result, the surrogate unit exposure
values that serve as the basis for this assessment generally range from the geometric mean to the
median of the selected dataset.
The first step in performing a handler exposure assessment is to complete a baseline exposure
assessment. The baseline scenario generally represents a handler wearing long pants, a long-sleeved
shirt, and no chemical-resistant gloves. If, there is a level of concern, then increasing levels of risk
mitigation, such as PPE (personal protective equipment) and engineering controls, are used to achieve
an appropriate margin of exposure (MOE).
Occupational Exposure Scenarios
The Agency has determined that there are potential exposures to mixers, loaders, applicators,
or other handlers during usual use-patterns associated with alachlor. Based on the use patterns, nine
major exposure scenarios were identified for alachlor:
(la) mixing/loading liquids for aerial and chemigation application;
(lb) mixing/loading liquids for groundboom application;
(2) mixing/loading granulars for drop type tractor drawn application;
(3a) mixing/loading dry flowables for aerial application;
(3b) mixing/loading dry flowables for groundboom application;
(4) aerial application of liquids (fixed-wing);
(5) aerial application of liquids (helicopter);
(6) groundboom application of liquids;
(7) granular drop type tractor drawn application;
(8) mixing/loading and application to dry bulk fertilizer; and,
(9) fl aggers.
A summary and description of the caveats and parameters specific to each exposure scenario
is shown in Table 12.
Occupational Exposure Tables
66
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Two types of assessments (short-term and intermediate-term) are required for evaluating
occupational risk assessment. The NOEL for estimating short-term risk is from a developmental
(oral) toxicity study, which requires the use of a dermal absorption factor (24%), and the average
body weight of a female (60 kg) is used in the assessment. The NOEL for estimating intermediate-
term risk is from a dermal toxicity study; therefore, no dermal absorption factor is applied. The
demonstrated effects from that study are not sex-specific; therefore, the average body weight of
humans (70 kg) is used in the assessment.
Table 13 shows the calculations of daily total exposure to alachlor:
! with baseline attire (long-sleeve shirt, long pants, shoes, and socks).
Table 14 shows the calculations of daily total exposure to alachlor:
! with the addition of personal protective equipment (chemical-resistant gloves and
double-layer clothing)
Table 15 shows the calculations of daily total exposure to alachlor:
! with the use of engineering controls (closed systems for mixing and loading, closed
cabs/cockpits for applications and flagging).
Tables 13, 14, and 15 show the calculations of occupational handler exposure for both the
short- and intermediate-term scenario. For the short-term assessment, each table includes a 24%
dermal absorption adjustment to the "daily dermal exposure" (column 6). This daily absorbed dermal
exposure (column 9) is added to the daily inhalation exposure (column 7) to calculate the daily
absorbed total exposure (column 10). This exposure calculation (column 10 in Tables 13, 14, and
15) is used to assess the short-term risk in Table 28. For the intermediate-term assessment, "daily
dermal exposure" (column 6) is added to "daily inhalation exposure" (column 7) to calculate the
"daily total exposure" (column 8). This exposure calculation (column 8 in Tables 10, 11, and 12 is
used to assess the intermediate-term risk in Table 29.
Table 16 is data from the registrant-submitted biomonitoring study.
In Table 14, the level of personal protective equipment (PPE) added (i.e., only chemical-
resistant gloves or double-layer body protection plus chemical-resistant gloves) varies among the
exposure scenarios based on whether the eventual margins of exposures (MOEs) would be 100 or
greater solely with the addition of gloves.
In Table 28, "baseline absorbed total dose" (column 3) is calculated by dividing the value in
Table 13 "daily absorbed total exposure" (column 10) by the average female body weight (60 kg).
Similarly, in Table 28 "PPE daily total dose" (column (5) is calculated by dividing the value in Table
14 "PPE daily absorbed total exposure" (column 10) by 60 kg. Finally, in Table 28 "Eng. C daily
total dose" (column 7) is calculated by dividing the value in Table 15 "Eng. C daily absorbed total
exposure" (column 10) by 60 kg.
In Table 29, "baseline total dose" (column 3) is calculated by dividing the value in Table 13
"baseline daily total exposure" (column 8) by the average human body weight (70 kg). Similarly, in
Table 29 "PPE daily total dose" (column 5) is calculated by dividing the value in Table 14 "PPE daily
67
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total exposure" (column 8) by 70 kg. Finally, in Table 29 "Eng. C daily total dose" (column 7) is
calculated by dividing the value in Table 15 "Eng. C daily total exposure" (column 8) by 70 kg.
Further explanation of the calculations are in the footnotes.
68
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Table 12: Exposure Scenario Descriptions for Uses of Alachlor
Exposure Scenario (Number)
Data Source
Daily Acres
Treateda
Commentsb
Mixer/Loader Exposure
Mixing/Loading Liquid (la and b)
PHED VI. 1
80 acres groundboom;
350 acres aerial and
chemigation
Baseline: "Best Available" grades: Hands, dermal, and inhalation acceptable grades.
Hands = 53 replicates; Dermal = 25 to 122 replicates; Inhalation = 85 replicates. High
confidence in dermal data; high confidence in inhalation data.
PPE: "Best Available" grades: Hands and dermal acceptable grades. Hands = 59
replicates; Dermal = 25 to 122 replicates. High confidence in dermal and inhalation data.
Engineering Controls: "Best Available" grades: Dermal and inhalation acceptable
grades. Hands = 31 replicates, Dermal = 16 to 22 replicates; Inhalation = 27 replicates.
High confidence in dermal and inhalation data.
PHED data used for baseline and engineering controls, no Protection Factor (PF) were
necessary. Fifty percent PF was used for coveralls (PPE).
Mixing/Loading Granulars (2)
PHED VI. 1
80 acres
Baseline: "Best Available" grades: Hands all grades, dermal and inhalation acceptable
grades. Dermal = 29 to 36 replicates; inhalation = 58 replicates; and hands = 10 replicates.
Low confidence in dermal data, high confidence in inhalation data.
PHED data used for baseline, no PFs were necessary.
Mixing/Loading Dry Flowables (3a and 3b)
PHED VI. 1
80 acres
Baseline: "Best Available" grades: Hands grades A,B, C; dermal and inhalation acceptable
grades. Dermal = 16 to 26 replicates; inhalation = 23 replicates; and, hands = 7 replicates.
Low confidence in dermal data, high confidence in inhalation data.
PPE: "Best Available" grades: Hands, dermal and inhalation acceptable grades. Hands =
21 replicates; Dermal = 16 to 26 replicates, inhalation = 23 replicates. High confidence in
dermal and inhalation data.
PHED data used for baseline, no PFs were necessary. Fifty percent PF was used for
coveralls (PPE).
Applicator Exposure
Aerial equipment—fixed wing enclosed cab (liquids) (4)
PHED VI. 1
350 acres
Engineering Controls: "Best Available" grades: Hands acceptable grades, dermal and
inhalation grades A,B,C. Hands = 34 replicates; Dermal = 24 to 48 replicates; Inhalation =
23 replicates. Medium confidence in dermal and inhalation data.
PHED data used for engineering controls, no PFs were necessarv.
69
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Table 12: Exposure Scenario Descriptions for Uses of Alachlor
Exposure Scenario (Number)
Data Source
Daily Acres
Treateda
Commentsb
Aerial equipment—helicopter enclosed cab (liquids) (5)
PHED VI. 1
350 acres
Engineering Controls: "Best Available" grades: dermal grades A,B,C; inhalation grades
"acceptable". Hands = 2 replicates, Dermal = 3 replicates; Inhalation = 3 replicates. Low
confidence in dermal and inhalation data.
PHED data used for engineering controls, no PFs were necessary.
Groundboom Application (liquids) (6)
PHED VI. 1
80 acres
Baseline: "Best Available" grades: Hands, dermal, and inhalation acceptable grades.
Hands = 29 replicates; Dermal = 32 to 42 replicates; Inhalation = 22 replicates. High
confidence in dermal and inhalation data.
PPE: "Best Available" grades: Hands grades ABC and dermal acceptable grades. Hands =
21 replicates Dermal = 32 to 42 replicates Medium confidence in dermal data; high
confidence in inhalation data.
Engineering Controls: "Best Available" grades: Hands, and dermal = ABC grades;
Inhalation = acceptable grades. Hands = 16 replicates Dermal = 20 to 31 replicates;
Inhalation = 16 replicates. Medium confidence in dermal data; high confidence in
inhalation.
PHED data used for baseline and engineering controls, no PFs were necessary. Fifty percent
PF was added for coveralls for PPE.
Granular Drop Type Tractor Drawn Spreader
Application (7)
PHED VI. 1
80 acres
Baseline: "Best Available" grades: Hand, dermal and inhalation acceptable grades.
Dermal = 4 to 5 replicates; hands = 5 replicates; inhalation = 5 replicates. Low confidence
in dermal and inhalation data.
PHED data was used for baseline, no PFs were necessary.
Mixer/Loader/Applicator
Mixing/Loading and Application for Dry Bulk Fertilizer
(8)
No data
No data
No data
Flaggers
Flaggers for Aerial Applications (9)
PHED VI. 1
350 acres
Baseline: "Best Available" grades: Hand, dermal and inhalation acceptable grades.
Dermal = 16 to 18; hands = 16; inhalation = 18. High confidence in dermal, hand and
inhalation data.
PHED data was used for baseline, no PFs were necessary.
a Daily acres treated are from EPA estimates of acreage that could be treated in a single day for each exposure scenario of concern.
b These grades are based on Quality Assurance/Quality Control data provided as part of the exposure studies. A replicate refers to data acquired during one complete work cycle. "Best Available" grades are defined by EPA SOP for meeting
Subdivision U Guidelines. Best available grades are assigned as follows: matrices with grades A andB data and a minimum of 15 replicates; if not available, then grades A, B, and C data and a minimum of 15 replicates; if not available,
then all data regardless of the quality and number of replicates. Data confidence are assigned as follows:
High confidence = grades A and B and 15 or more replicates per body part
Medium confidence = grades A, B, and C and 15 or more replicates per body part
Low confidence = grades A, B, C, D, and E or any combination of grades with less than 15 replicates
70
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Table 13: Alachlor Exposure Estimates to be Used in Short-Term and Intermediate-Term Risk Assessments - Baseline PHED Values
Exposure Scenario
(Scenario #)
Baseline Dermal
Unit Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and
Application Rate
(lb ai/acre)c
Daily Acres
Treated"1
Daily
Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
Baseline
Daily Total
Exposure
(mg/day)f
Daily
Absorbed
Dermal
Exposure
(mg/day)8
Baseline
Daily
Absorbed
Total
Exposure
(mg/day)h
Mixer/Loader Exposure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
2.9
0.0012
Corn 4.0
350
4,060
1.68
4,061.7
974
976
Soybeans 3.0
3,045
1.26
3,046.3
731
732
Mixing/Loading Liquids for Groundboom
Application (lb)
Corn 4.0
80
928
0.384
928.4
223
223
Soybeans 3.0
696
0.288
696.3
167
167
Mixing/Loading Granulars for Drop Type
Tractor Drawn Spreaders (2)
0.0076
0.0017
Corn 4.0
80
2.4
0.544
2.9
0.58
1.1
Soybeans 3.0
1.8
0.408
2.2
0.43
0.83
Mixing/Loading Dry Flowables for Aerial
Application (3a)
0.07
0.00077
Corn 4.0
350
98
1.08
99.08
24
25
Soybeans 3.0
73.5
0.81
74.31
18
18
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
Corn 4.0
80
22.4
0.25
22.65
5.4
5.6
Soybeans 3.0
16.8
0.19
16.99
4.0
4.2
Applicator Ex|
)osure
Aerial Application of Liquids - Fixed-Wing
Aircraft - Enclosed Cockpit (4)
See Engineering
Controls
See Engineering
Controls
Corn 4.0
350
See
Engineering
Controls
See Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
Soybeans 3.0
Aerial Application of Liquids - Helicopter
Aircraft - Enclosed Cockpit (5)
See Engineering
Controls
See Engineering
Controls
Corn 4.0
350
See
Engineering
Controls
See Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
Soybeans 3.0
Groundboom Application of Liquids - (6)
0.015
0.0007
Corn 4.0
80
4.8
0.224
5.02
1.2
1.4
Soybeans 3.0
3.6
0.168
3.77
0.86
1.0
Granular Drop Type Tractor Drawn
Spreader Application (7)
0.01
0.00022
Corn 4.0
80
3.2
0.07
3.3
0.77
0.84
Soybeans 3.0
2.4
0.053
2.5
0.58
0.63
Mixer/Loader/Applicator Exposure
Mixing/Loading and Application of
Impregnated Dry Bulk Fertilizer (8)
See text
Flaaaers
71
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Table 13: Alachlor Exposure Estimates to be Used in Short-Term and Intermediate-Term Risk Assessments - Baseline PHED Values
Exposure Scenario
(Scenario #)
Baseline Dermal
Unit Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and
Application Rate
(lb ai/acre)c
Daily Acres
Treated"1
Daily
Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
Baseline
Daily Total
Exposure
(mg/day )f
Daily
Absorbed
Dermal
Exposure
(mg/day)8
Baseline
Daily
Absorbed
Total
Exposure
(mg/day)h
Flaggers for Aerial Applications (9)
0.01
0.00028
Corn 4.0
350
14.0
0.39
14.39
3.4
3.8
Soybeans 3.0
10.5
0.29
10.79
2.5
2.8
a Baseline dermal unit exposure represents long pants, long sleeve shirts, no gloves, open mixing/loading, open cabs or cockpits. Note that data on open cockpit aerial applications are not available,
b Baseline inhalation exposure represents no respirator.
c Application rate comes from maximum values found in the alachlor labels EPA Reg Nos. 524-344, 524-403, 524-418, 524-422 and 524-314.
d Daily acres treated are from EPA estimates of acreage that could be treated in a single day for each exposure scenario of concern,
e Daily exposure (mg/day) = Exposure (mg/lb ai) * Appl. rate (lb ai/A) * Acres Treated.
f Total daily exposure (mg/day) = daily dermal exposure (mg/day) + daily inhalation exposure (mg/day). Note that this exposure number is used for the intermediate-term scenario only since the NOEL for calculating the MOE is from
a dermal study and the use of the dermal absorption factor is not necessary.
g Daily absorbed dermal exposure (mg/day) = daily dermal exposure (mg/day) * dermal absorption factor (0.24)
h Total absorbed daily exposure (mg/day) = daily absorbed dermal exposure (mg/day) + daily inhalation exposure (mg/day) Note that this exposure is used for the short-term scenario only since the NOEL
for calculating the MOE is from an oral study and it was necessary to use the dermal absorption factor.
72
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Table 14: Alachlor Exposure Estimates to be used in Short-Term and Intermediate-Term Risk Assessments -
PHED Personal Protective Equipment (PPE) Values
Exposure Scenario
(Scenario #)
PPE Dermal
Unit
Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and Application
Rate (lb ai/acre)c
Daily
Acres
Treated"1
Daily Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
PPE Daily
Total
Exposure
(mg/day)f
Daily
Absorbed
Dermal
Exposure
(mg/day)8
PPE Daily
Absorbed
Total
Exposure
(mg/day)h
Mixer/Loader Exposure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
0.043
0.0012
Corn 4.0
350
60.2
1.7
61.9
14.4
16.1
Soybeans 3.0
45.2
1.3
46.5
10.8
12.1
Mixing/Loading Liquids for Groundboom
Application (lb)
0.043
0.0012
Corn 4.0
80
13.8
0.38
14.2
3.3
3.7
Soybeans 3.0
9.6
0.29
9.9
2.3
2.6
Mixing/Loading Granulars for Drop Type
Tractor Drawn Spreaders (2)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Mixing/Loading Dry Flowables for Aerial
Application (3a)
0.04
0.00077
Corn 4.0
350
56
1.1
57.1
13.4
14.5
Soybeans 3.0
42
0.81
42.8
10.1
10.9
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Applicator Exposure
Aerial Application of Liquids - Fixed-Wing
Aircraft - Enclosed Cockpit (4)
See
Engineering
Controls
See Engineering
Controls
Corn 4.0
350
See Engineering
Controls
See Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
Soybeans 3.0
Aerial Application of Liquids - Helicopter
Aircraft - Enclosed Cockpit (5)
See
Engineering
Controls
See Engineering
Controls
Corn 4.0
350
See Engineering
Controls
See Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
See
Engineering
Controls
Soybeans 3.0
Groundboom Application of Liquids - (6)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Granular Drop Type Tractor Drawn
Spreader Application (7)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Mixer/Loader/Applicator Exposure
Mixing/Loading and Application of
Imoresnated Drv Bulk Fertilizer (8s)
See text
73
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Table 14:
Alachlor Exposure Estimates to be used in Short-Term and Intermediate-Term Risk Assessments -
PHED Personal Protective Equipment (PPE) Values
Exposure Scenario
(Scenario #)
PPE Dermal
Unit
Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and Application
Rate (lb ai/acre)c
Daily
Acres
Treatedd
Daily Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
PPE Daily
Total
Exposure
(mg/day)f
Daily
Absorbed
Dermal
Exposure
(mg/day)8
PPE Daily
Absorbed
Total
Exposure
(mg/day)h
Flaggers
Flaggers for Aerial Applications (9)
n/a
n/a
Corn 4.0
350 acres
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
n/a No longer necessary to carry scenario through analysis as exposure in baseline scenario is sufficiently low to calculate an MOE that will exceed 100
a Scenario la and lb single layer clothing and chemical resistant gloves, open mixing/loading
Scenario 3a: open mixing/loading, double layer of clothing and chemical resistant gloves,
b Baseline inhalation exposure represents no respirator.
c Application rate comes from maximum values found in the alachlor labels EPA Reg Nos. 524-344, 524-403, 524-418, 524-422 and 524-314.
d Daily acres treated are from EPA estimates of acreage that could be treated in a single day for each exposure scenario of concern,
e Daily exposure (mg/day) = Exposure (mg/lb ai) * Appl. rate (lb ai/A) * Acres Treated.
f Total daily exposure (mg/day) = daily dermal exposure (mg/day) + daily inhalation exposure (mg/day). Note that this exposure number is used for the intermediate-term scenario only since the NOEL for calculating the MOE is from
a dermal study and the use of the dermal absorption factor is not necessary.
g Daily absorbed dermal exposure (mg/day) = daily dermal exposure (mg/day) * dermal absorption factor (0.24)
h Total absorbed daily exposure (mg/day) = daily absorbed dermal exposure (mg/day) + daily inhalation exposure (mg/day) Note that this exposure is used for the short-term scenario only since the NOEL
for calculating the MOE is from an oral study and it was necessary to use the dermal absorption factor.
74
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Table 15: Alachlor Exposure Estimates to be Used in Short-Term and Intermediate-Term Risk Assessments - Engineering Control
(Eng C) PHED Values
Exposure Scenario
(Scenario #)
Eng C
Dermal Unit
Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and Application
Rate (lb ai/acre)c
Daily
Acres
Treated"1
Eng C Daily
Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
Eng C
Daily Total
Exposure
(mg/day)f
Eng C Daily
Absorbed
Exposure
(mg/day)8
Eng C
Daily
Absorbed
Total
Exposure
(mg/day)h
Mixer/Loader Ex
posure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
0.009
0.00008
Corn 4.0
350
9.8
0.11
9.9
2.4
2.5
Soybeans 3.0
7.4
0.08
7.5
1.8
1.9
Mixing/Loading Liquids for Groundboom
Application (lb)
Corn 4.0
80
2.2
0.026
2.2
0.54
0.57
Soybeans 3.0
1.7
0.02
1.7
0.4
0.42
Mixing/Loading Granulars for Drop Type
Tractor Drawn Spreaders (2)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Mixing/Loading Dry Flowables for Aerial
Application (3a)
No data
No data
Corn 4.0
350
No data
No data
No data
No data
No data
Soybeans 3.0
No data
No data
No data
No data
No data
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
Applicator Exposure
Aerial Application of Liquids - Fixed-Wing
Aircraft - Enclosed Cockpit (4)
0.005
0.000068
Corn 4.0
350
7
0.095
7.1
1.7
1.8
Soybeans 3.0
5.3
0.07
5.3
1.3
1.4
Aerial Application of Liquids - Helicopter
Aircraft - Enclosed Cockpit (5)
0.0021
0.0000018
Corn 4.0
350
3.0
0.003
3.0
0.7
0.7
Soybeans 3.0
2.2
0.002
2.2
0.53
0.53
Groundboom Application of Liquids - (6)
n/a
n/a
Corn 4.0
80
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
75
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Table 15: Alachlor Exposure Estimates to be Used in Short-Term and Intermediate-Term Risk Assessments - Engineering Control
(Eng C) PHED Values
Exposure Scenario
(Scenario #)
Eng C
Dermal Unit
Exposure
(mg/lb ai)a
Baseline
Inhalation Unit
Exposure
(mg/lb ai)b
Crop and Application
Rate (lb ai/acre)c
Daily
Acres
Treatedd
Eng C Daily
Dermal
Exposure
(mg/day)e
Daily Inhalation
Exposure
(mg/day)e
Eng C
Daily Total
Exposure
(mg/day )f
Eng C Daily
Absorbed
Exposure
(mg/day)g
Eng C
Daily
Absorbed
Total
Exposure
(mg/day)h
Granular Drop Type Tractor Drawn
Spreader Application (7)
n/a
n/a
Corn 4.0
Soybeans 3.0
80
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
Mixer/Loader/Applicator Exposure
Mixing/Loading and Application of
Impregnated Dry Bulk Fertilizer (8)
See text
Flaggers
Flaggers for Aerial Applications (9)
n/a
n/a
Corn 4.0
350 acres
n/a
n/a
n/a
n/a
n/a
Soybeans 3.0
n/a
n/a
n/a
n/a
n/a
n/a No longer necessary to carry scenario through analysis as exposure in baseline scenario or with addition of PPE is sufficiently low to calculate an MOE that will exceed 100
a Engineering controls dermal unit exposure represents long pants, long sleeve shirts, closed mixing/loading, closed cab tractor.
Scenarios la: chemical resistant gloves.
Scenarios 4 and 5: closed cockpit single layer clothing, and no gloves,
b Baseline inhalation exposure represents no respirator.
c Application rate comes from maximum values found in the alachlor labels EPA Reg Nos. 524-344, 524-403, 524-418, 524-422 and 524-314.
d Daily acres treated are from EPA estimates of acreage that could be treated in a single day for each exposure scenario of concern,
e Daily exposure (mg/day) = Exposure (mg/lb ai) * Appl. rate (lb ai/A) * Acres Treated.
f Total daily exposure (mg/day) = daily dermal exposure (mg/day) + daily inhalation exposure (mg/day). Note that this exposure number is used for the intermediate-term scenario only since the NOEL for calculating the MOE is from
a dermal study and the use of the dermal absorption factor is not necessary.
g Daily absorbed dermal exposure (mg/day) = daily dermal exposure (mg/day) * dermal absorption factor (0.24)
h Total absorbed daily exposure (mg/day) = daily absorbed dermal exposure (mg/day) + daily inhalation exposure (mg/day) Note that this exposure is used for the short-term scenario only since the NOEL
for calculating the MOE is from an oral study and it was necessary to use the dermal absorption factor.
76
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Table 16: Alachlor Exposure Estimates
Risk Assessments - Values from
to be Used in Short-Term and Intermed
legi strant-Submitted Biomonitoring Stuc
iate-Term
ies
Exposure Scenario
(Scenario #)
Biomonitoring
Internal Estimated
Exposure
(mg/kg/lb ai)a
Adjusted
Biomonitoring
Internal
Estimated
Exposure
(mg/kg/lb ai)b
Crop and Application
Rate (lb ai/acre)°
Daily
Acres
Treated11
Biomonitoring
Internal Dose
(mg/kg/day)e
Mixer/Loader Exposure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
0.0000126
n/a
Corn 4.0
350
0.01764
Mixing/Loading Liquids for
Groundboom Application (lb)
Corn 4.0
80
0.004032
Mixing/Loading Granulars for Drop
Type Tractor Drawn Spreaders (2)
n/a
0.0000000647
Corn 4.0
80
0.0000207
Mixing/Loading Dry Flowables for
Aerial Application (3a)
n/a
0.000000316
Corn 4.0
350
0.0004424
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
n/a
0.00000032
Corn 4.0
80
0.0001024
Applicator Exposure
Aerial Application of Liquids - Fixed-
Wing Aircraft - Enclosed Cockpit (4)
This scenario not performed for biomonitoring data
Aerial Application of Liquids -
Helicopter Aircraft - Enclosed Cockpit
(5)
This scenario not performed for biomonitoring data
Groundboom Application of Liquids -
(6)
0.0000126
n/a
Corn 4.0
80
0.004032
Granular Drop Type Tractor Drawn
Spreader Application (7)
n/a
0.00000767
Corn 4.0
80
0.002454
Mixer/Loader/Applicator Exposure
Mixing/Loading and Application of
Impregnated Dry Bulk Fertilizer (8)
This scenario not performed for biomonitoring data
Flaggers
Flaggers for Aerial Applications (9)
This scenario not performed for biomonitoring data
n/a = not applicable
77
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a Biomonitoring internal estimated exposure represents Monsanto employees who wore long pants, long sleeve shirts, elbow length rubber gloves, caps, goggles, open mixing/loading, no respirator, closed cab tractor,
b The biomonitoring studies were conducted with liquid formulations. Therefore, these internal estimated exposures are not appropriate for use with granular or dry flowable formulations. In an attemptto estimate the internal estimated
exposure a ratio of PHED exposure values that have been converted to baseline absorbed total doses were used in a ratio of other formulation/liquid formulation. The alachlor baseline absorbed total doses are from Table 25.
Scenario 2: (0.0000126 mg/kg/lb ai)( 0.019/3.7) = 0.0000000647 mg/kg/lb ai
Scenario 3a: (0.0000126 mg/kg/lb ai )(0.41/16.3) = 0.000000316 mg/kg/lb ai
Scenario 3b: (0.0000126 mg/kg/lb ai )(0.094/3.7) = 0.00000032 mg/kg/lb ai
Scenario 7: (0.0000126 mg/kg/lb ai )(0.014/0.023) = 0.00000767 mg/kg/lb ai
c Application rate comes from the application rate of 4 lbs ai used in the Monsanto study.
d Daily acres treated are from EPA estimates of acreage that could be treated in a single day for each exposure scenario of concern,
e Biomonitoring internal dose (mg/kg/day) = Biomonitoring internal estimated exposure (mg/kg/lb ai) * Appl. rate (4 lb ai/A) * Acres Treated/day.
78
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Post Application Exposure
The potential for post-application worker exposure is low, provided the Restricted Entry
Interval (12 hours) is observed. This is due to the timing of applications. Alachlor is applied to the
soil and/or soil incorporated preplant, pre-emergent, at planting for corn and soybeans, post-
transplant for ornamentals, early post-emergent on corn, and at ground-crack for peanuts. This is
well before the plants are mature, which mitigates the potential for post-application exposure.
Exposure to alachlor during harvesting, even with sweet corn harvesting or seed corn detasseling, is
not likely to occur as alachlor is applied primarily preplant and pre-emergent. Therefore, the Agency
does not require that any post-application exposure or residue dissipation monitoring data be
generated to support the reregi strati on of alachlor.
4. Risk Characterization
a. Dietary
As previously stated, an acute dietary risk assessment is not required. The RfD of 0.01
mg/kg/day was used for calculating chronic dietary risk. For calculating carcinogenic dietary risk two
NOELs (14 mg/kg/day for stomach tumors and 0.5 mg/kg/day for nasal tumors) was used.
The tolerances used in this analysis are listed in Table 78: Tolerance Reassessment. At the
time that the dietary assessment was performed, the registrant had expressed interest in supporting
rotational crop tolerances for cotton and sunflowers. For this reason these uses were included in the
assessment at the tolerance levels that were recently revoked. However, in alachlor petition 8F5000
dated June 25, 1998, Monsanto is requesting to establish tolerances for the direct application of
alachlor to cotton and sunflower. This petition is now in review.
The consumption information used in this analysis is derived from USDA's 1977-78
Nationwide Food Consumption Survey (NFCS). Over 30,000 respondents were surveyed over three
days as to what foods they ate, with each individual's consumption information being associated with
their body weight, sex, age, ethnicity and other sociodemographic information. Individual
consumption estimates were weighted to be nationally representative. From these data single day and
3 day average consumption estimates were derived for the U.S. population and select population
subgroups. Three day average information is used in the DRES chronic exposure analyses.
The Agency acknowledges that the data from this survey are more than 20 years old.
However, at the time that the dietary assessment for alachlor was conducted, the data were the best
information available to the Agency.
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High End Chronic Dietary (Food Source) Risk
The DRES chronic exposure analysis assumes tolerance level residues and one hundred
percent crop treated to calculate the Theoretical Maximum Residue Contribution (TMRC) for the
overall U.S. population and 22 population subgroups. Selected subgroups are reported in Table 17.
Table 17: Chronic Dietary Analysis (Food Only)
Subgroup
Exposure
(mg/kg/day)
%Reference Dose
U.S. population
0.000756
8
Non-nursing Infants
(<1 year)
0.003258
33
Children (1-6)
0.001744
17
Children (7-12)
0.001221
12
All other population subgroups were less than 10% of the RfD.
Refined Chronic Dietary (Food Source') Risk
The Dietary Exposure Assessment was refined using anticipated residues (ARs) and percent
crop treated (%CT) to give a refined, i.e. more realistic, dietary assessment.
Calculation of Anticipated Residues
Existing FDA monitoring data were not used in calculating alachlor ARs because the data
were considered to be of limited usefulness for dietary risk assessment. FDA found no detectable
residues of alachlor, per se, in 53,600 samples, but the analyses did not include any of the alachlor
metabolites of concern.
The anticipated residues, which are presented below in Table 18, were based on the average
residue found in field trials where alachlor was used at the maximum application rate. Additionally
a weighting factor was used for the percent of use at each application timing (i.e., preemergence vs.
postemergence). For example, 90% of corn is typically treated preemergence at 4 lb ai/A or less with
less than 10% treated postemergence (including sequential applications). Results of processing
studies were also used to adjust the residue levels found in the raw commodity to account for changes
in residue levels due to processing (both commercial and other types of processing). The typical
application rates and timing used for the anticipated residue analysis is provided in Table 18 for each
crop.
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Table 18: Anticipated Residues, Plant Commodities: Calculations and Summary
Average
lesidues from Alac
llor Uses
Avg. Residue
Proc. Factor
Avg. Residue
Corn- 90% of use was preemergence at 4 lb ai/A, 10% of use was postemergence at 4 lb
ai/A or sequential applications (4+2 lb ai/A)
Corn grain
0.011
0.011
Corn meal
0.911
0.010
Corn oil (refined)
0.121
0.0014
Corn starch
0.192
0.0022
Corn forage7
0.21
0.21
Corn silage7
0.22
0.22
Corn stover7
0.12
0.12
Sweet Corn K+CWHR
preemergence 4 lb ai/A
0.007
0.007
Peanuts-35% of use was preemergence, 75% of use was cracking
Peanut hulls7
0.38
0.38
Peanut nutmeat
0.15
0.15
Peanut meal7
1.371
0.21
Peanut oil (refined)
"vb
o
o
0.009
Peanut butter
0.703
0.11
Peanuts, dry roasted
0.753
0.11
Peanuts, oil roasted
0.833
0.12
Sorghum preemergence 4 lb ai/A
Sorghum grain
0.02
0.02
Sorghum forage7
0.29
0.29
Sorghum fodder7
0.29
0.29
Sorghum stover7
0.2
0.20
Soybeans preemergence 4 lb ai/A
Soybean grain and
soybean full fat and low fat flour
0.105
0.11
Soybean grain dust7
6.004
0.63
Soybean hulls7
1.224
0.13
Soybean toasted meal (feed)7
0.884
0.092
Soybean defatted meal (food)
1.304
0.137
Soybean oil (refined)
0.174
0.018
Soybean protein concentrate
0.324
0.034
81
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Table 18: Anticipated Residues, Plant Commodities: Calculations and Summary
Average
lesidues from Alac
llor Uses
Avg. Residue
Proc. Factor
Avg. Residue
Soybean protein isolate
0.214
0.022
Soybean defatted flour
0.090s
Soybean forage7
1.36
1.36
Soybean hay7
2.61
2.61
Dry Beans preplant incorporated 3
b ai/A
Dry beans
0.048
0.206
0.010
Dry lima beans
0.040
0.206
0.008
Bean forage7
0.340
0.34
Bean vines7
0.396
0.40
Bean hay7
0.866
0.87
1 MRID 00162939
2 MRID 40788201
3 MRID 40820601
4 MRID 00154239, 00154240, 40947101, 41862901 41916301
5 4/7 defatted meal + 3/7 protein concentrates and isolates
6 MRID 40820701
7 Livestock feed only
In estimating anticipated residues for milk, poultry and eggs, anticipated residues as calculated
in Table 18 were used in estimating the dietary burden. (See Table 7 for example of calculation.)
Estimated dietary burdens based on these anticipated residues in livestock feeds for cattle, poultry,
and swine were determined to be 0.49, 0.20, and 0.27 ppm, respectively. The anticipated residues
in livestock commodities were then corrected for the expected recovery in each livestock tissue.
Anticipated residue estimates for livestock commodities are listed in Table 19.
Table 19' Anticinated Residues in Livestock Commodities
Alachlor Feeding Study Results
Estimated Residues
Feeding
Level
(ppm)
Residue
(ppb)
Dietary
Burden
(ppm)
Residue
Measured
by Method
(ppb)
% Residue
of Concern
Measured
by Method
Total Residue
of Concern
(ppb)
BEEF
muscle
4.20
1.20
0.53
0.15
38%
0.40
fat
4.20
1.90
0.53
0.24
70%
0.34
82
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Table 19' Anticinated Residues in Livestock Commodities
Alachlor Feeding Study Results
Estimated Residues
Feeding
Level
(ppm)
Residue
(ppb)
Dietary
Burden
(ppm)
Residue
Measured
by Method
(ppb)
% Residue
of Concern
Measured
by Method
Total Residue
of Concern
(ppb)
liver
4.20
7.80
0.53
0.98
58%
1.70
kidney
4.20
8.70
0.53
1.10
68%
1.61
milk
4.20
1.50
0.69
0.25
40%
0.62
POULTRY
muscle
12.00
1.00
0.09
0.01
34%
0.02
fat
12.00
1.30
0.09
0.01
75%
0.01
liver
4.00
2.10
0.09
0.05
51%
0.09
eggs
4.00
6.90
0.09
0.16
60%
0.26
SWINE
muscle
4.00
1.30
0.19
0.06
38%
0.16
fat
4.00
2.60
0.19
0.12
70%
0.18
liver
4.00
4.10
0.19
0.19
58%
0.34
kidney
12.00
7.40
0.19
0.12
68%
0.17
Since the dietary exposure assessment is based on field trial data, the anticipated residues are
likely to overestimate the dietary exposure because the application rates and timing assumed in the
dietary exposure analysis were at the highest rate on the label, which is not necessarily the typical rate
used by the applicator. Additionally, residues are likely to degrade from the time that samples are
obtained at the farm gate during transportation, processing and storage, prior to consumption. For
the livestock commodities, the following assumptions were used: (1) all alachlor metabolite residues
found in the livestock animal metabolism studies are residues of concern and (2) the percentage
recovery of the analytical method in livestock commodities is based on the percentage of metabolites
recovered in metabolism studies. Alachlor metabolites not identified specifically in the metabolism
studies may also respond to the analytical method, so the analytical recovery may be higher than
estimated.
Percent Crop Treated Data
Percent crop treated (CT) information are from a three year period 1993 - 1995. The FQPA
amendments to Section 408(b)(2)(F) of the FFDCA require that if a tolerance relies on percent crop-
treated data, that the Agency make a determination as to the reliability of the data. The percent crop
treated estimates used by EPA are derived from Federal and private market survey data. Typically,
the Agency considers the range of percent crop treated data from a period of several years, and uses
83
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the upper end of this range for estimating dietary exposure. In so doing, the Agency is reasonably
certain that exposure is not understated for any maj or population sub-group. Additionally, the DRES
(Dietary Risk Evaluation System) used in estimating chronic dietary risk uses regional consumption
information to estimate exposure for four population sub-groups that are based on geographical
regions of the United States. The Agency will provide for the periodic evaluation of these estimates
of percent crop treated, as long as the tolerances for alachlor remain in force.
When a range of percent of crop treated estimates was supplied, the upper end (in bold) was
used. One hundred percent CT (default assumption) was used if no information was provided for a
crop. This data is now several years old. However, information available to the Agency indicates
that alachlor usage has fallen. Thus, these percent crop treated estimates can be considered as slight
over-estimates.
Table 20: Percent of Various U.S. Crops Treated Annually
with Alachlor
Commodities
Percent Crop
Treated
Major Region or
State
Beans, Dry
<10
Nationwide
Beans, Succulent
10-35
CA and ID
Corn, Sweet
30-35
Nationwide
Corn, Field
20-25
Nationwide
Peanuts
<5
Southeast
Sorghum
10 - 15
Nationwide
Soybeans
5 - 10
Nationwide
Sunflowers
<1 - 1
SD and NE
Refined dietary exposures and percent RfDs for selected subgroups are reported in Table 21.
84
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Table 21: C
ironic Refined Dietary Analysis
Food Only)
Subgroup
Exposure
(mg/kg/day)
%Reference Dose
U.S. population
0.000011
0.1
Non-nursing Infants
(<1 year)
0.000050
0.5
Children (1-6 years)
0.000029
0.3
Children (7-12 years)
0.000019
0.2
Male (20+ years)
0.000007
0.07
Female (13+ years), nursing
0.000010
0.1
All other population subgroups were less than 0.2% of the RfD. Thus, when using anticipated
residues and percent crop treated data, all population subgroups are well below the RfD for alachlor.
Chronic dietary risk from alachlor from all food uses for which tolerance reassessments have been
performed is not of concern.
Dietary Carcinogenic (Food Sources') Risk (MOE Approach')
As stated previously, the Committee recommended using a Margin of Exposure (MOE)
approach for estimation of human risk, rather than the linear low dose approach. The NOELs, 0.5
mg/kg/day for nasal tumors and 14 mg/kg/day for stomach tumors, were used for estimating MOEs
for adult females and adult males using the chronic exposures in Table 21. It should be noted that
alachlor ESA is included in these estimates of exposure, since it is converted in the alachlor crop
residue methodology to DEA. Since alachlor ESA is unlikely to be carcinogenic in a 2-year bioassay
these residues should not be included in the carcinogenic assessment, but cannot be separated out.
Therefore, these exposure estimates are very slight over-estimates.
Carcinogenic MOE = NOEL / exposure
At this time the Agency is not making any recommendations on the level of MOEs to be
considered acceptable for dietary risk. However, given the magnitude of the calculated MOEs,
dietary cancer risk from all food uses for which tolerance reassessments have been performed is not
expected to be of concern. All MOEs in Table 22 have been rounded to two significant figures.
85
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Table 22: Carcinogenic MOEs
Population Group
Exposure
MOE
Nasal Tumors (0.5 mg/kg/day)
Adult Male
0.000007
71,000
Adult Female
0.000010
50,000
Stomach Tumors (14 mg/kg/day)
Adult Male
0.000007
2,000,000
Adult Female
0.000010
1,400,000
b. Drinking Water
Chronic Drinking Water Risk
Percent RfDs for consumption of drinking water containing residues of alachlor per se were
estimated using the RfD for alachlor of 0.01 mg/kg/day for adult males, adult females and child (1 -
6 years). There are no default assumptions for estimating risk for non-nursing infants (< 1 year),
although the same assumptions as used for a child (1 -6 years) could be used. Since, the chronic food
source risk for both of these sub-population groups was < 1%, the total dietary risk would be similar.
All RfDs were rounded to one significant figure.
Table 23: Drinking Water Percent RfDs for Alachlor per se- Adult Male
STUDY
Concentration
(ddM
Exposure
(mg/kg/dav)
% RfD
MCL
2
0.0000571
0.6
Surface Water
USGS - Alachlor (reservoir)
0.22
0.0000062
0.06
ARP Data (1995-1996) (drinking water)
0.1
0.0000028
0.03
Ground Water
NAWWS
0.2
0.0000057
0.06
NAWWS
0.015
0.0000004
0.004
86
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Table 24: Drinking Water Percent RfDs for Alachlor per se- Adult Female
STUDY
Concentration
(mb)
Exposure
(ms/kg/dav)
% RfD
MCL
2
0.0000666
0.7
Surface Water
USGS - Alachlor (reservoir)
0.22
0.0000073
0.07
ARP Data (1995-1996) (drinking water)
0.1
0.0000033
0.03
Ground Water
NAWWS
0.2
0.0000066
0.07
NAWWS
0.015
0.0000005
0.005
Table 25: Drinking Water Percent RfDs for Alachlor per se
- Child (1-6 years)
STUDY
Concentration
(mb)
Exposure
(ms/kg/dav)
% RfD
MCL
2
0.0002
2
Surface Water
USGS - Alachlor (reservoir)
0.22
0.000022
0.2
ARP Data (1995-1996) (drinking water)
0.1
0.00001
0.1
Ground Water
NAWWS
0.2
0.00002
0.2
NAWWS
0.015
0.0000015
0.02
All % RfD values are well below 100%. Chronic dietary risk from alachlor from consumption
of water containing residues of alachlor per se is not of concern.
No RfD for alachlor ESA has been determined; the toxicological data base is incomplete.
Therefore, a default assumption would be to use the parent alachlor RfD for the metabolite. Using
the exposures estimated in Tables 6, 7, and 8 and the alachlor RfD of 0.01 mg/kg/day, percent RfDs
were estimated to be of 0.9%, 1%, and 3% for adult male, adult female and children (1-6 years),
respectively. Another assumption would be to calculate a value for use in a chronic dietary risk
assessment using the NOEL from the 91-day alachlor ESA drinking water study. Using the NOEL
of 157 mg/kg/day and an uncertainty factor of 1000 (to account for interspecies extrapolation,
intraspecies variability and lack of a complete database) a value of 0.16 mg/kg/day was calculated.
This gives percent RfDs of 0.05%, 0.06%, and 0.2% for adult male, adult female and children (1-6
years), respectively. Note that both of these approaches indicate little concern for consumption of
alachlor ESA in the drinking water.
87
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Carcinogenic Drinking Water Risk
Carcinogenic MOEs were calculated for adult males and females only. Alachlor ESA is not
included in the MOEs since it was determined that alachlor ESA is unlikely to be carcinogenic in a
2-year bioassay. All MOEs were rounded to two significant figures.
Table 26:
Drinking Water C
arcinogenic MOEs
- (Adult Male
)
STUDY
Concentration
(ppb)
Exposure
(mg/kg/day)
MOE1
MOE2
MCL
2
0.0000571
8,800
250,000
Surface Water
USGS - Alachlor
0.22
0.0000062
45,000
2,300,000
ARP Data
(1995-1996)
0.1
0.0000028
180,000
6,400,000
Ground Water
NAWWS
0.2
0.0000057
88,000
2,500,000
NAWWS
(99.5% population)
0.015
0.0000004
1,200,000
35,000,000
MOE for nasal tumors (0.5 mg/kg/day)
2 MOE for stomach tumors (14 mg/kg/day)
Table 27:
Drinking Water Ca
rcinogenic MOEs
- (Adult Fema
le)
STUDY
Concentration
(ppb)
Exposure
(mg/kg/day)
MOE1
MOE2
MCL
2
0.0000666
7,500
210,000
Surface Water
USGS - Alachlor
0.22
0.0000073
68,000
1,900,000
ARP Data
0.1
0.0000033
150,000
5,400,000
Ground Water
NAWWS
0.2
0.0000066
76,000
21,000,000
NAWWS
(99.5% population)
0.015
0.0000005
1,000,000
28,000,000
MOE for nasal tumors
2 MOE for stomach tumors
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At this time the Agency is not making any recommendations on the level of MOEs to be
considered acceptable for dietary (drinking water) risk. However, given the magnitude of the
calculated MOEs, dietary (drinking water) cancer risk is not expected to be of concern.
c. Aggregate (Food and Water)
Aggregate Chronic Dietary (Food Source and Drinking Water) Risk
This assessment combines the food residue exposure estimates with drinking water exposure
estimates to calculate an aggregate chronic exposure. Percent RfDs for aggregate chronic dietary risk
were calculated for adult males, adult females, and children (1-6 years). All RfDs were rounded to
one significant figure.
Adult Male - Alachlor
Using the refined adult male food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 23:
Exposure = 0.000007 mg/kg/day +0.0000057 mg/kg/day = 0.0000127 mg/kg/day
% RfD = 0.0000127 / 0.01 (100)= 0.1 %
Using the refined adult male food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 23:
Exposure = 0.000007 mg/kg/day + 0.0000062 mg/kg/day = 0.0000132 mg/kg/day
%RfD =0.0000132 / 0.01 (100) = 0.1 %
Using the refined adult male food source exposure from Table 21 and ARP (12 state area surface
water) from Table 23:
Exposure = 0.000007 mg/kg/day +0.0000028 mg/kg/day = 0.0000098 mg/kg/day
% RfD = 0.0000098 / 0.01 (100) = 0.1 %
Adult Male - Alachlor and Alachlor ESA
Using the refined adult male food source exposure from Table 21 and USGS reservoir (Midwest
surface water) exposure from Table 23:
Exposure = 0.000007 mg/kg/day + 0.0000062 mg/kg/day + 0.0000857 mg/kg/day =
0.0000989 mg/kg/day
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% RfD = 0.0000989 / 0.01 (100) = 1 %
Adult Female Alachlor
Using the refined adult female food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000066 mg/kg/day = 0.0000166 mg/kg/day
% RfD = 0.0000166 / 0.01 (100) = 0.2 %
Using the refined adult female food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000073 mg/kg/day = 0.0000173 mg/kg/day
% RfD = 0.0000173 / 0.01 (100) = 0.1%
Using the refined adult female food source exposure from Table 21 and ARP (12 state area surface
water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000033 mg/kg/day = 0.0000133 mg/kg/day
% RfD = 0.0000133 /0.01 = 0.1%
Adult Female - Alachlor and Alachlor ESA
Using the refined adult female food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000073 mg/kg/day +0.0001 mg/kg/day =
0.0001173 mg/kg/day
% RfD = 0.0001173 / 0.01 (100) = 1 %
Child (1-6 years) - Alachlor
Using the refined child (1-6 years) food source exposure from Table 21 and NAWWS (Midwest
ground water) exposure from Table 24:
Exposure = 0.000029 mg/kg/day + 0.00002 mg/kg/day = 0.000049 mg/kg/day
% RfD = 0.000049 / 0.01 (100) = 0.5%
90
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Using the refined child (1-6 years) food source exposure from Table 21 and USGS reservoir
(Midwest surface water) from Table 25:
Exposure = 0.000029 mg/kg/day + 0.000022 mg/kg/day = 0.000051 mg/kg/day
% RfD = 0.000051 / 0.01 (100) = 0.5 %
Using the refined child (1-6 years) food source exposure from Table 21 and ARP (12 state area
surface water) from Table 25:
Exposure = 0.000029 mg/kg/day + 0.00001 mg/kg/day = 0.000039 mg/kg/day
% RfD = 0.000039 / 0.01 (100) = 0.4 %
Child (1-6 years) - Alachlor and Alachlor ESA
Using the refined child (1-6 years) food source exposure from Table 21 and USGS reservoir
(Midwest surface water) from Table 25:
Exposure = 0.000029 mg/kg/day + 0.000022 mg/kg/day + 0.0003 mg/kg/day =
0.000351 mg/kg/day
% RfD = 0.000351 / 0.01 (100) = 4 %
All % RfDs for aggregate chronic dietary risk are well below 100%. Chronic dietary risk from
alachlor from food containing residues of alachlor and from consumption of water containing residues
of alachlor per se and/or residues of alachlor ESA is not of concern.
Aggregate Carcinogenic Dietary (Food and Water) Risk (MOE Approach')
MOEs for aggregate carcinogenic dietary risk were calculated for adult males and females.
All MOEs were rounded to two significant figures. Per the recommendations of the Metabolism
Committee, alachlor ESA is not included in the carcinogenic assessment.
Adult Male
Using the refined adult male food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 23:
Exposure = 0.000007 mg/kg/day +0.0000057 mg/kg/day = 0.0000127 mg/kg/day
MOE (nasal) = 0.5 / 0.0000127 = 39,000
91
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MOE (stomach) = 14 / 0.0000127 = 1,100,000
Using the refined adult male food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 23:
Exposure = 0.000007 mg/kg/day + 0.0000062 mg/kg/day = 0.0000132 mg/kg/day
MOE (nasal) = 0.5 / 0.0000132 = 38,000
MOE (stomach) = 14 / 0.0000132 = 1,100,000
Using the refined adult male food source exposure from Table 21 and ARP (12 state area surface
water) from Table 23:
Exposure = 0.000007 mg/kg/day +0.0000028 mg/kg/day = 0.0000098 mg/kg/day
MOE (nasal) = 0.5 / 0.0000098 = 51,000
MOE (stomach) = 14 / 0.0000098 = 1,400,000
Adult Female
Using the refined adult female food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000066 mg/kg/day = 0.0000166 mg/kg/day
MOE (nasal) = 0.5 / 0.0000166 = 30,000
MOE (stomach) = 14 / 0.0000166 = 840,000
Using the refined adult female food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000073 mg/kg/day = 0.0000173 mg/kg/day
MOE (nasal) = 0.5 / 0.0000173 = 29,000
MOE (stomach) = 14 / 0.0000173 = 810,000
Using the refined adult female food source exposure from Table 21 and ARP (12 state area surface
water) from Table 24:
92
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Exposure = 0.000010 mg/kg/day + 0.0000033 mg/kg/day = 0.0000133 mg/kg/day
MOE (nasal) = 0.5 /0.0000133 = 38,000
MOE (stomach) = 14 / 0.0000133 = 1,100,000
At this time the Agency is not making any recommendations on the level of MOEs to be
considered acceptable for aggregate (food and water) dietary risk. However, given the magnitude
of the calculated MOEs (ranging from 29,000 to 1,400,000), aggregate carcinogenic dietary risk from
all food uses for which tolerance reassessments have been performed is not expected to be of concern.
Aggregate Carcinogenic Dietary (Food and Water) Risk (O, Approach')
Aggregate carcinogenic dietary risk using the Qx* approach were calculated for adult males
and females. All risks were rounded to two significant figures. Per the recommendations of the
Metabolism Committee, alachlor ESA is not included in the carcinogenic assessment.
Risk = ( Qj* )(exposure)
Adult Male
Using the refined adult male food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 23:
Exposure = 0.000007 mg/kg/day + 0.0000057 mg/kg/day = 0.0000127 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000127 mg/kg/day] = 1.0 x 10"6
Using the refined adult male food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 23:
Exposure = 0.000007 mg/kg/day + 0.0000062 mg/kg/day = 0.0000132 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000132 mg/kg/day] = 1.1 x 10"6
Using the refined adult male food source exposure from Table 21 and ARP (12 state area surface
water) from Table 23:
Exposure = 0.000007 mg/kg/day +0.0000028 mg/kg/day = 0.0000098 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000098 mg/kg/day] = 7.8 x 10"7
Adult Female
93
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Using the refined adult female food source exposure from Table 21 and NAWWS (Midwest ground
water) exposure from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000066 mg/kg/day = 0.0000166 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000166 mg/kg/day] = 1.3 x 10"6
Using the refined adult female food source exposure from Table 21 and USGS reservoir (Midwest
surface water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000073 mg/kg/day = 0.0000173 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000173 mg/kg/day] = 1.4 x 10"6
Using the refined adult female food source exposure from Table 21 and ARP (12 state area surface
water) from Table 24:
Exposure = 0.000010 mg/kg/day + 0.0000033 mg/kg/day = 0.0000133 mg/kg/day
Risk = [0.08 (mg/kg/day)"1 ][ 0.0000133 mg/kg/day] = 1.1 x 10"6
All carcinogenic risks estimated using the Qx* are within the risk range considered by the
Agency to represent negligible risk.
d. Occupational
Short Term Risk
For the short-term risk assessment, a NOEL of 150 mg/kg/day was used to calculate the
MOE. The Agency used a 60 kg body weight, the Agency's default female body weight since the
selected endpoint is from a developmental study. Since the NOEL is from an oral study, the dermal
absorption factor of 24% was used to estimate oral-equivalents for the dermal exposure.
Intermediate Term Risk
For the intermediate-term risk assessment, a NOEL of 50 mg/kg/day was used to calculate
the MOE. The Agency used a 70 kg body weight, the Agency's default adult body weight. Since the
NOEL is from a dermal study, use of the dermal absorption factor is not appropriate.
Estimates of short-term and intermediate-term occupational risk to alachlor are summarized
in Tables 28 and 29. All MOEs have been rounded to 1 or 2 significant figures.
94
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i
able 28: Sh
ort-Term Risk
from Alac
hi or
Exposure Scenario
(Scenario #)
Crop/
Ratea
Baseline
Absorbed Total
Dose
(mg/kg/day)b,e
Baseline
MOE°
PPE
Absorbed Dosebf
(mg/kg/day)
PPE
MOE°
Eng. C
Absorbed
Doseb'8
(mg/kg/day)
Eng. C
MOE°
Biomonitoring
Internal Dose
(mg/kg/day)d
Biomonitoring
MOE°
Mixer/Loader Exposure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
Corn 4.0
16.3
9
0.27
560
N/A
N/A
0.01764
8500
Soybean 3.0
12.2
12
0.20
750
N/A
N/A
N/A
N/A
Mixing/Loading Liquids for
Groundboom Application (lb)
Corn 4.0
3.7
41
0.061
2,500
N/A
N/A
0.004032
37,000
Soybean 3.0
2.8
54
0.046
3,300
N/A
N/A
N/A
N/A
Mixing/Loading Granulars for Drop
Type Tractor Drawn Spreader
Application (2)
Corn 4.0
0.019
7,900
N/A
N/A
N/A
N/A
0.00002070
720,000
Soybean 3.0
0.014
11,000
N/A
N/A
N/A
N/A
N/A
N/A
Mixing/Loading Dry Flowables for
Aerial Application (3a)
Corn 4.0
0.41
370
N/A
N/A
N/A
N/A
0.0004424
34,000
Soybean 3.0
0.31
480
N/A
N/A
N/A
N/A
N/A
N/A
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
Corn 4.0
0.094
1,600
N/A
N/A
N/A
N/A
0.0001024
150,000
Soybean 3.0
0.07
2,100
N/A
N/A
N/A
N/A
N/A
Applicator Exposure
Aerial Application of Liquids -
Fixed-Wing Aircraft - Enclosed
Cockpit (4)
Corn 4.0
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
0.030
5000
N/A
N/A
Soybean 3.0
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
0.022
6800
N/A
N/A
Aerial Application of Liquids -
Helicopter - Enclosed Cockpit (5)
Corn 4.0
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
0.012
13000
N/A
N/A
Soybean 3.0
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
See Eng.
Controls
0.009
17000
N/A
N/A
Groundboom Application of Liquids
(6)
Corn 4.0
0.023
6,500
N/A
N/A
N/A
N/A
0.004032
35,000
Soybean 3.0
0.017
8,800
N/A
N/A
N/A
N/A
N/A
N/A
Granular Drop Type Tractor Drawn
Spreader Application (7)
Corn 4.0
0.014
11,000
N/A
N/A
N/A
N/A
0.002454
61,000
Soybean 3.0
0.01
15.000
N/A
N/A
N/A
N/A
N/A
N/A
95
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Table 28: Short-Term Risk from Alachlor
Exposure Scenario
(Scenario #)
Crop/
Rate"
Baseline
Absorbed Total
Dose
(mg/kg/day)b'e
Baseline
MOE°
PPE
Absorbed Dosebf
(mg/kg/day)
PPE
MOE°
Eng. C
Absorbed
Doseb'8
(mg/kg/day)
Eng. C
MOE°
Biomonitoring
Internal Dose
(mg/kg/day)d
Biomonitoring
MOE°
Mixer/Loader/Applicator
Mixing/Loading and Application for
Dry Bulk Fertilizer (8)
See text
Flaggers
Flaggers for Aerial Applications (9)
Corn 4.0
0.063
2,400
N/A
N/A
N/A
N/A
N/A
N/A
Soybean 3.0
0.047
3200
PPE personal protective equipment
Eng. C engineering controls
a Rates are from Alachlor labels EPA Reg Nos. 524-344, 524-403, 524-418, 524-422 and 524-314.
b Absorbed Total Dose ((daily dermal exposure * dermal absorption rate 0.24) + (daily inhalation exposure)) / 60 kg.
c MOE = NOEL (150 mg/kg/day) / absorbed total dose,
d Biomonitoring (See Table 16) Estimated only for 4 lb ai.
e See Table 13 footnotes for explanation of calculations
f See Table 14 footnotes for explanation of calculations and description of PPE
g See Table 15 footnotes for explanation of calculations and description of engineering controls
96
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Tab
e 29: Inte
rmediate-Ter
m Risk fror
n Alachlor
Exposure Scenario
(Scenario #)
Crop/
Ratea
Baseline Total
Dosebe
(mg/kg/day)
Baseline
Total
Dermal
MOE°
PPE Daily
Total Doseb,f
(mg/kg/day)
PPE Total
MOE°
Eng. C Daily
Total Doseb,s
(mg/kg/day)
Eng. C Total
MOE°
Biomonitoring
Internal Dose
(mg/kg/day)''
Biomonitoring
MOE°
Mixer/Loader Exposure
Mixing/Loading Liquids for Aerial
Application and Chemigation (la)
Corn 4.0
58.0
0.9
0.54
93
0.18
280
0.01764
2800
Soybean 3.0
43.5
1
0.39
130
N/A
N/A
N/A
N/A
Mixing/Loading Liquids for
Groundboom Application (lb)
Corn 4.0
13.3
4
0.2
250
N/A
N/A
0.004032
12,000
Soybean 3.0
9.9
5
0.17
300
N/A
N/A
N/A
N/A
Mixing/Loading Granulars for Drop
Type Tractor Drawn Application (2)
Corn 4.0
0.04
1,300
N/A
N/A
N/A
N/A
0.0000207
2,400,000
Soybean 3.0
0.03
1,700
N/A
N/A
Mixing/Loading Dry Flowables for
Aerial Application (3a)
Corn 4.0
1.42
35
0.82
61
No data
No data
0.0004424
110,000
Soybean 3.0
1.05
47
0.61
82
N/A
N/A
Mixing/Loading Dry Flowables for
Groundboom Application (3b)
Corn 4.0
0.32
160
N/A
N/A
N/A
N/A
0.0001024
490,000
Soybean 3.0
0.24
210
N/A
N/A
Applicator Exposure
Aerial Application of Liquids -
Fixed-Wing Aircraft - Enclosed
Cockpit (4)
Corn 4.0
See Engineering Controls
See
Engineering
Controls
See
Engineering
Controls
0.10
500
N/A
N/A
Soybean 3.0
0.08
630
N/A
N/A
Aerial Application of Liquids -
Helicopter - Enclosed Cockpit (5)
Corn 4.0
See Engineering Controls
See
Engineering
Controls
See
Engineering
Controls
0.042
1,200
N/A
N/A
Soybean 3.0
0.031
1,600
N/A
N/A
Groundboom Application of Liquids
(6)
Corn 4.0
0.072
690
N/A
N/A
N/A
N/A
0.004032
12,000
Soybean 3.0
0.054
930
N/A
N/A
N/A
N/A
N/A
N/A
Granular Drop Type Tractor Drawn
Spreader Application (7)
Corn 4.0
0.047
1,100
N/A
N/A
N/A
N/A
0.002454
20,000
Soybean 3.0
0.036
1.400
N/A
N/A
97
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Tab
e 29: Intermediate-Term Risk from Alachlor
Exposure Scenario
(Scenario #)
Crop/
Ratea
Baseline Total
Doseb'e
(mg/kg/day)
Baseline
Total
Dermal
MOE°
PPE Daily
Total Doseb,f
(mg/kg/day)
PPE Total
MOE°
Eng. C Daily
Total Doseb,s
(mg/kg/day)
Eng. C Total
MOE°
Biomonitoring
Internal Dose
(mg/kg/day)''
Biomonitoring
MOE°
Mixer/Loader/Applicator
Mixing/Loading and Application for
Dry Bulk Fertilizer (8)
See text
Flaggers
Flaggers for Aerial Applications (9)
Corn 4.0
0.206
240
N/A
N/A
N/A
N/A
N/A
N/A
Soybean 3.0
0.154
330
N/A - not applicable
a From Alachlor labels EPA Reg Nos. 524-344, 524-403, 524-418, 524-422 and 524-314.
b Total dose = (daily dermal exposure) + (daily inhalation exposure) / 70 kg.
c MOE = NOEL (50 mg/kg/day) / total dose (mg/kg/day).
d Biomonitoring (See Table 16) Estimated only for 4 lb ai.
e See Table 13 footnotes for explanation of calculations
f See Table 14 footnotes for explanation of calculations and description of PPE
g See Table 15 footnotes for explanation of calculations and description of engineering controls
98
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Occupational Risk Characterization
Short-Term Exposure
Usingthe registrant-submittedbiomonitoring data, all short-term MOEs are much greater than
100.
Using PHED data for estimating short-term risk the MOEs are more than 100 at baseline for
scenarios:
(2) mixing/loading granulars for drop type tractor drawn spreader application,
(3a) mixing/loading dry flowables for aerial application,
(3b) mixing/loading dry flowables for groundboom application,
(6) liquid groundboom application,
(7) granular drop type tractor drawn spreader application, and
(9) fl aggers
Using PHED data with additional PPE and the corresponding decreases in exposure, the
MOEs are more than 100 for short-term risk for scenarios:
(la) mixing/loading liquids for aerial application and chemigation, and
(lb) mixing/loading liquids for groundboom application.
Using PHED data with engineering controls (no other data were available) the calculated
MOEs are more than 100 for short-term risk for scenarios:
(4) liquid aerial application (fixed-wing), and
(5) liquid aerial application (helicopter).
Thus, it was possible to achieve MOEs greater than 100 for all scenarios for which data
existed in PHED.
Intermediate-Term Exposure
Using the registrant-submitted biomonitoring data, all intermediate MOEs are much greater
than 100.
Using PHED for intermediate term risk the MOEs are more than 100 at baseline for risk for
scenarios:
(2) mixing/loading granulars groundboom application,
(3b) mixing/loading dry flowables for groundboom application,
(6) liquid groundboom application, and
(9) fl aggers.
Using PHED with additional PPE and the corresponding decreases in exposure the MOEs
are more than 100 for intermediate-term risk for scenarios:
99
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(la) mixing/loading liquids for aerial application (for rate of 3.0 lb ai/acre for soybeans), and
(lb) mixing/loading liquids for groundboom application.
Using PHED with engineering controls and the corresponding decreases in exposure the
MOEs are more than 100 for intermediate-term risk for scenarios:
(la) mixing/loading liquids for aerial application (for the rates of 4.0 lb ai/acre for corn),
(4) aerial application of liquids (fixed-wing aircraft), and
(5) aerial application of liquids (helicopter).
However, despite available PPE mitigation measures, it was not possible to achieve an MOE
of greater than 100 for scenario (3a) mixing/loading dry flowables for aerial application. There are
no engineering controls currently available for dry flowable formulations. Therefore, estimation of
exposure and resultant risk was not performed.
Dry Bulk Fertilizer Scenario
Using information provided by Monsanto, the Agency estimated MOEs for mixer/loaders
using a liquid alachlor product to impregnate dry bulk fertilizer, and for applicators applying the
treated fertilizer. This assessment was based on information provided by Monsanto in which the
processes involved in treating fertilizer with alachlor and applying the treated fertilizer were
described. (MRID No. 44492302)
Dry bulk fertilizer impregnated with alachlor is typically prepared by local agricultural dealers,
and is then transported to the fields and applied. According to the information provided by Monsanto
there is a division of labor, in that most dealers, even small dealer operations, usually have different
individuals running the mixing equipment and applying the mix to fields. This is because of the
different skill requirements and to achieve better productivity. Thus, the Agency performed separate
assessments for mixer/loaders, and applicators. If an individual were to mix/load/apply, then the risk
would increase correspondingly.
There is also a Granu-Blend system, which is a system for applying granular alachlor at the
same time as application of the fertilizer, and is thus similar to the mixer/loader and applicator
scenarios for granular materials discussed in other sections of this alachlor RED chapter.
Mixer/Loaders
The Agency's preliminary review of exposure to workers impregnating dry bulk fertilizer with
liquid formulations of alachlor expressed concern over an absence of data and the potential for
significant exposure.
According to the labels the blending must be performed by commercial fertilizer or chemical
dealerships properly equipped for the procedure. The amount of fertilizer and alachlor handled
depends on the number of acres to be treated. According to alachlor labels, from 200 to 450 lbs. of
100
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impregnated fertilizer may be applied per acre, preplant to corn, grain sorghum, and soybeans. The
maximum single application rate for alachlor is 4 lbs ai/acre per new labels approved by the Agency
on June 30, 1998.
According to the University of Illinois Extension Service: The herbicide is metered from a
mini-bulk tank (several hundred gallons) to a mixing drum via a closed system. The herbicide is
sprayed onto the fertilizer, which is stirred by an auger that lifts it to the top of the drum. After
impregnation, the treated fertilizer is gravity-fed through a hopper onto a conveyor belt leading to
an auger truck, which carries it to the field. At the field, the auger truck feeds the treated fertilizer
onto the applicator vehicle, which dispenses it from either a rotary spinner or a boom with numerous
outlets. The transfer of the treated fertilizer in each instance is nearly dust-free, as it has been
moistened by the herbicide. Because all processes are mechanized, there is minimal contact of either
the mixer at the treatment site or the loader at the transfer sites. Applicator exposure is minimized
by the use of a closed cab.
The information supplied by Monsanto indicates that impregnation of fertilizer in a mixing
tower is typically a closed system operation. Monsanto provided a diagram of a mixing/loading tower
which specifies that up to 120 tons of fertilizer can be processed per hour. If the tower were assumed
to process for 8 hours per day, then this would be 960 tons of fertilizer processed per 8 hour day.
At 3 to 4 lbs active ingredient per 200 lbs fertilizer, each ton of fertilizer would require 30 to 40 lbs
of alachlor active ingredient. Thus, the total amount of active ingredient for 960 tons at the 4 lb ai
rate is (960)(40) = 38400 lbs, and at the 3 lb ai rate is (960)(30) = 28800 lbs. The new information
submitted by Monsanto, and confirmed by the Agency, specified that the typical or average fertilizer
use rate is approximately 400 lbs/acre. At 4 lbs active ingredient per 400 lbs fertilizer, each ton of
fertilizer would require 20 lbs of alachlor active ingredient. Thus, the total amount (based on 400 lbs
fertilizer per acre) for 4 lbs ai handled is (960)(20) = 19,200 lbs.
Using the above information, the Agency has estimated risk for mixers/loaders impregnating
the dry bulk fertilizer assuming use of engineering controls (metered delivery from a mini-bulk tank).
Only the dermal values will be used in this assessment, since technical alachlor is classified as toxicity
category III, and for liquids, the unit inhalation exposure value is insignificant (differing by several
orders of magnitude) when compared to the unit dermal exposure value.
Daily exposure (mg/day) is estimated using the following equation:
unit exposure (mg/lb ai) x lbs ai handled per day
Daily dose (mg/kg/day) is calculated by dividing the daily exposure (mg/day) by the body
weight (bw) of the worker. For the short-term scenario, the Agency used a 60 kg body weight, the
Agency's default adult female body weight since the selected endpoint is from a developmental study.
Since the selected endpoint is from an oral study, the exposure must be adjusted to account for
dermal exposure. The dermal absorption factor is 24 percent (0.24).
101
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Thus, for the short-term scenario, absorbed daily dose = daily exposure (mg/day) / 60 kg x
0.24.
For the intermediate-term scenario, the Agency used a 70 kg body weight, the Agency's
default adult body weight. Since the NOEL is from a dermal toxicity study, the dermal exposure will
not need to be adjusted by the dermal absorption factor.
Thus, for the intermediate-term scenario, daily dose = daily exposure (mg/day) / 70 kg.
Risk, in terms of margins of exposure (MOE), is calculated by using the following equation:
NOEL (mg/kg/day) / daily dose (mg/kg/day) = MOE.
All MOEs are rounded to one or two significant digits. For the short-term scenario, the
NOEL is 150 mg/kg/day. Forthe intermediate-term scenario, the NOEL is 50 mg/kg/day. Generally,
the Agency has no concerns for an MOE greater than or equal to 100 for non-cancer effects when
the NOEL used in estimating the MOE is from an animal study.
The PHED VI. 1 unit dermal exposure for a closed mixing/loading mechanical transfer system
(single layer clothing - with gloves) is 0.009 mg/lbs ai - high confidence.
Table 30: Short-Term with Engineering Controls (Closed Transfer System)
Unit Exposure
(mg/lbs ai)
Application Rate
(lbs ai/day)
Daily Exposure
(mg/day)
Daily Dose
(mg/kg/day)
MOE
0.009
38400
346
1.38
110
0.009
28800
259
1.04
140
0.009
19200
173
0.69
220
Table 31: Intermediate-Term with Engineering Controls (Closed Transfer System)
Unit Exposure
(mg/lbs ai)
Application Rate
(lbs ai/day)
Daily Exposure
(mg/day)
Daily Dose
(mg/kg/day)
MOE
0.009
38400
346
4.9
10
0.009
28800
259
3.7
14
0.009
19200
173
2.5
20
The Agency made assumptions in performing this assessment and acknowledges that many
of the assumptions were deliberately intended toward performing an upper-end assessment. One of
the most conservative of these assumptions was that the mixing tower would run at full capacity for
102
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8 hours a day, thus generating 960 tons of alachlor impregnated fertilizer. It could require 32 to 96
truckloads per day (assuming 10 to 30 tons of fertilizer per truck) to spread the towers output. The
impregnated fertilizer market is likely to be a custom operation, in that (1) the blending occurs on an
as needed/as ordered basis, and (2) only the amount ordered is prepared.
All intermediate-term MOEs are less than 100; however, the Agency acknowledges that the
estimation of these MOEs did contain the conservative estimate of the mixing tower working 8 hours
per day. The short-term MOEs are greater than 100 considering mitigation with a closed transfer
system. Only the dermal component of the exposure - no inhalation exposure component - was
considered.
The Agency also has concerns that the data in PHED may not adequately represent this
scenario. This is not a typical usage under agricultural field conditions. The amount of alachlor
necessary to impregnate the tons of fertilizer that can be processed in a day is far too large to be
handled by opening individual bottles or containers (as data collected for PHED), and probably
involves transfer from large containers such as tanker trucks or railroad tank cars.
Extrapolating a unit exposure in the range of 19200 to 38400 lb ai/day from the available data
in PHED is likely to result in an over-estimate. The Agency does not have any bulk transfer/loading
data. This type of exposure data may be necessary for refining this assessment, and a possible option
for Monsanto would be to supply data per GLN 875.2400 (dermal exposure) and GLN 875.2500
(inhalation exposure) for mixer/loaders.
Applicators - Baseline - Open Cab
The Agency has no data for spreader trucks applying treated fertilizer, and therefore selected
from PHED "solid broadcast spreader application - open cab" as a suitable surrogate. The dermal unit
exposure value (baseline - single layer clothing, no gloves, open cab) for a granular drop-type
spreader applicator is 0.01 mg/lb ai, and the inhalation unit exposure value (baseline - open cab) is
0.0012 mg/lbs ai (PHED V 1.1, low confidence dermal and inhalation). Inhalation and dermal unit
exposures will be combined for the applicator scenario since the values are within two orders of
magnitude.
MOEs for both the short-term and intermediate-term scenarios have been estimated.
However, the Agency believes that the intermediate-term scenario is the most appropriate scenario
for estimating risk, since available information indicates that for pre-plant herbicide and fertilizer
applications that a "window" of approximately 28 days is available once the weather and field
conditions are right and the equipment can enter the fields.
For the short-term scenario, the total daily absorbed exposure (mg/day) is estimated using the
following equation:
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[dermal unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated x
dermal absorption factor] + [inhalation unit exposure (mg/lb ai) x application rate (lbs
ai/acre) x number of acres treated]
Given:
dermal unit exposure = 0.01 mg/lbs ai,
inhalation unit exposure = 0.0012 mg/lbs ai,
maximum application rate = 4 lbs ai per acre,
max number of acres treated = 800
typical number of acres treated = 500
dermal absorption factor = 0.24
Therefore:
Max total daily absorbed exposure = (0.01)(4)(800)(0.24) + (0.0012)(4)(800)
= 11.52 mg/day.
Typical total daily absorbed exposure = (0.01)(4)(500)(.24) + (0.0012)(4)(500)
= 7.2 mg/day
Total daily absorbed dose (mg/kg/day) is calculated by dividing the total daily absorbed
exposure (mg/day) by 60 kg, the Agency's default adult female body weight since the NOEL used
in estimating short-term risk is from a developmental study.
Max total daily dose = 11.52 mg/day / 60 kg = 0.192 mg/kg/day
Typical total daily dose = 7.2 mg/day / 60 kg = 0.12 mg/kg/day
Risk is estimated by using the following equation:
MOE = NOEL (mg/kg/day) / max total daily dose (mg/kg/day) = 150 / 0.192 = 780
MOE = NOEL (mg/kg/day) / typical total daily dose (mg/kg/day) = 150 / 0.12 = 1300
For the short-term scenario, the MOE for applicators applying fertilizer impregnated with
alachlor at the maximum application rate of 4 lbs ai to 800 acres per day is 780, and to 500 acres per
day is 1300. If lower application rates such as 3 lb ai/acre were to be used in the calculation, the
MOEs would be even higher.
For the intermediate-term scenario, the total daily exposure (mg/day) is calculated using the
following equation:
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[dermal unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated] +
[inhalation unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated]
Given:
dermal unit exposure = 0.01 mg/lbs ai,
inhalation unit exposure = 0.0012 mg/lbs ai,
maximum application rate = 4 lbs ai per acre,
max number of acres treated = 800
typical number of acres treated = 500
Therefore:
Max total daily exposure = (0.01)(4)(800) + (0.0012)(4)(800) = 35.84 mg/day.
Typical total daily exposure = (0.01)(4)(500) + (0.0012)(4)(500) = 22.4 mg/day
Total daily dose (mg/kg/day) is calculated by dividing the daily exposure (mg/day) by 70 kg, the
Agency's default male body weight.
Max total daily dose = 35.84 (mg/day) / 70 kg = 0.512 mg/kg/day
Typical total daily dose = 22.4 (mg/day) / 70 kg = 0.32 mg/kg/day
Risk is estimated by using the following equation:
MOE = NOEL (mg/kg/day) / max total daily dose (mg/kg/day) = 50 / 0.512 = 98
MOE = NOEL (mg/kg/day) / typical total daily dose (mg/kg/day) = 50 / 0.32 = 160
For the intermediate-term scenario, the MOE for applicators applying fertilizer impregnated
with alachlor equals 98 at the 4 lbs ai rate for 800 acres and 160 at the 4 lbs ai rate for 500 acres.
The Agency made assumptions in performing this risk assessment and acknowledges that
many of the assumptions were deliberately used with the intent of performing an upper-end risk
assessment. Additionally, the Agency had only low confidence data due to the number of replicates
(5) in PHED.
Applicators - Use of Engineering Controls
The Agency has no data for spreader trucks applying treated fertilizer, and therefore selected
from PHED "solid broadcast spreader application - closed cab" as a suitable surrogate. The dermal
unit exposure (closed cab) is 0.002 mg/lb ai, and the inhalation unit exposure (closed cab) is 0.00022
105
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mg/lbs ai (PHED VI . 1, low confidence dermal; high confidence hands and inhalation; no PFs
were used). Inhalation and dermal unit exposures will be combined for the applicator scenario since
the exposures are within two orders of magnitude.
MOEs for both the short-term and intermediate-term scenarios have been estimated. For the
short-term scenario, the total daily absorbed exposure (mg/day) is estimated using the following
equation:
[dermal unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated x
dermal absorption factor] + [inhalation unit exposure (mg/lb ai) x application rate (lbs
ai/acre) x number of acres treated]
Given:
dermal unit exposure = 0.002 mg/lbs ai,
inhalation unit exposure = 0.00022 mg/lbs ai,
maximum application rate = 4 lbs ai per acre,
max number of acres treated = 800
typical number of acres treated = 500
dermal absorption factor = 0.24
Therefore:
Max total daily absorbed exposure = (0.002)(4)(800)(.24) + (0.00022)(4)(800)
= 2.24 mg/day.
Typical total daily absorbed exposure = (0.002)(4)(500)(.24) + (0.00022)(4)(500)
= 1.4 mg/day
Total daily absorbed dose (mg/kg/day) is calculated by dividing the total daily absorbed exposure
(mg/day) by 60 kg, the Agency's default adult female body weight since the NOEL is from a
developmental study.
Max total daily dose = 2.24 (mg/day) / 60 kg = 0.037 mg/kg/day
Typical total daily dose =1.4 (mg/day) / 60 kg = 0.0233 mg/kg/day
Risk is estimated by using the following equation:
MOE = NOEL (mg/kg/day) / max total daily dose (mg/kg/day) = 150 / 0.037 = 4000
MOE = NOEL (mg/kg/day) / typical total daily dose (mg/kg/day)
= 150/0.0233 = 6400
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For the short-term scenario, the MOE for applicators applying fertilizer impregnated with
alachlor at the maximum application rate of 4 lbs ai to 800 acres per day is 4000, and to 500 acres
is 6400. If lower application rates such as 3 lbs ai were to be used in the calculation, the MOEs
would be even higher.
For the intermediate-term scenario, the total daily exposure (mg/day) is calculated using the
following equation:
[dermal unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated] +
[inhalation unit exposure (mg/lb ai) x application rate (lbs ai/acre) x number of acres treated]
Given:
dermal unit exposure = 0.002 mg/lbs ai,
inhalation unit exposure = 0.00022 mg/lbs ai,
maximum application rate = 4 lbs ai per acre,
max number of acres treated = 800
typical number of acres treated = 500
Therefore:
Max total daily exposure = (0.002)(4)(800) + (0.00022)(4)(800) = 7.1 mg/day.
Typical total daily exposure = (0.002)(4)(500) + (0.00022)(4)(500) = 4.44 mg/day
Total daily dose (mg/kg/day) is calculated by dividing the daily exposure (mg/day) by 70 kg, the
Agency's default male body weight.
Max total daily dose = 7.1 (mg/day) / 70 kg = 0.101 mg/kg/day
Typical total daily dose = 4.44 (mg/day) / 70 kg = 0.063 mg/kg/day
Risk is estimated by using the following equation:
MOE = NOEL (mg/kg/day) / max total daily dose (mg/kg/day) = 50 / 0.101 = 490
MOE = NOEL (mg/kg/day) / typical total daily dose (mg/kg/day) = 50 / 0.063 = 790
For the intermediate-term scenario, the MOE for applicators applying fertilizer impregnated
with alachlor using a closed cab, at the 4 lbs ai rate to 800 acres is 490, and to 500 acres is 790.
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With one exception (a MOE of 98), all MOEs, both short-term and intermediate-term, are
greater than 100. Generally, the Agency has no concerns for an MOE greater than or equal to 100,
for non-cancer effects when the NOEL used in estimating the MOE is from an animal study.
Additional Occupational Exposure Studies
Handler Studies
Optimally, worker exposure assessments are based on adequate data of acceptable quality.
Handler exposure studies are sometimes required for reregi strati on in situations in which no data or
no acceptable data exist. In this case exposure data are necessary to assess exposure to alachlor
resulting from the process of impregnating dry bulk fertilizer. While the Agency has used PHED data
in its assessment, the PHED data used are not directly related to this type of process. It appears that
this is a closed system; however, exposure may be significant based on the large volumes of alachlor
involved. PHED does not contain any data for transferring from mini-bulk containers. Therefore,
additional confirmatory data are required. The confirmatory data should address the dry bulk
fertilizer impregnation process, with alachlor in mini-bulk containers. This data should address both
dermal and inhalation exposure at both outdoor and indoor (at least partially enclosed) sites.
Post-Application Studies
The Agency believes that, based on the current uses of alachlor, post-application exposure
will be low and therefore is not requiring post-application exposure studies at this time.
e. FQPA Considerations
Aggregate Risk
In examining aggregate risk, FQPA directs EPA to take into account the available information
concerning exposures from the pesticide residue in food and all other exposures for which there is
reliable information. These other sources of exposure can include pesticides residues in drinking
water, pesticide uses in and around the home, and pesticide uses in non-residential settings, such as
schools or parks.
Alachlor is used on food crops. Alachlor as well as its metabolites have been detected in both
ground and surface water. Therefore, specific consideration of potential risks to infants and children,
as well as aggregate exposures, is warranted.
Alachlor is a restricted use chemical. The Agency has not identified any alachlor products that
are intended for home use, or uses in/around schools, parks, or other public areas. Therefore, a
residential exposure and risk assessment was not required. For alachlor there is no residential
component to be added to the dietary (food and water) assessment.
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Acute Aggregate Risk
Based on the available toxicity database, an acute dietary risk assessment was not required.
Chronic Aggregate Risk
Since alachlor has no residential uses to aggregate with the dietary assessment, the chronic
aggregate risk assessment is the same as the dietary (food and water)assessment. As previously
discussed in this document, the percent RfDs were calculated for adult males, adult females, and
children (1-6 years) using the food exposure estimated by DRES, and one source of drinking water.
All percent RfDs were rounded to one significant figure.
Table 32: Summary of Alachlor Aggregate Risk
Source of Drinking Water
% RfD
Adult Male
NAWWS (Midwest groundwater)
0.1
USGS reservoir (Midwest surface water)
0.1
ARP 12 state area surface water
0.08
Adult Female
NAWWS (Midwest groundwater)
0.1
USGS reservoir (Midwest surface water)
0.1
ARP 12 state area surface water
0.1
Child (1-6 years)
NAWWS (Midwest groundwater)
0.5
USGS reservoir (Midwest surface water)
0.5
ARP 12 state area surface water
0.4
There are some data (USGS reservoir Midwest surface water) available on detections of the
alachlor ES A degradate. Using these data, aggregate risk can be estimated for consumption of water
containing both parent alachlor and alachlor ESA.
109
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Table 33: Summary of Alachlor and Alachlor ESA Aggregate Risk
Population Group
% RfD
Adult Male
1%
Adult Female
1%
Child (1-6 years)
4%
All % RfD values are well below 100%. Aggregate chronic dietary risk from all food uses
for which tolerance reassessments have been performed is not expected to be of concern.
Carcinogenic (MOE Approach') Aggregate Risk
Since alachlor has no residential uses to aggregate with the dietary assessment, the
carcinogenic aggregate risk assessment is the same as the carcinogenic (food and water) dietary
assessment. As previously discussed in this document, the carcinogenic MOEs were calculated for
adult males and adult females, using the food exposure estimated by DRES, and one source of
drinking water. All cancer MOEs were rounded to two significant figures.
Table 34: Summary of Alachlor Aggregate Carcinogenic (MOE Approach) Risk
Source of Drinking Water
MOE
Nasal Tumors
MOE
Stomach Tumors
Adult Male
NAWWS (Midwest
groundwater)
39,000
1,100,000
USGS reservoir (Midwest
surface water)
38,000
1,100,000
ARP 12 state area surface
water
51,000
1,400,000
Adult Female
NAWWS (Midwest
groundwater)
30,000
840,000
USGS reservoir (Midwest
surface water)
29,000
810,000
ARP 12 state area surface
water
38,000
1,100,000
110
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At this time the Agency is not making any recommendations on the level of MOEs to be
considered acceptable for the carcinogenic MOE approach aggregate risk. However, given the
magnitude of the calculated MOEs, aggregate carcinogenic risk from all food uses for which
tolerance reassessments have been performed is not expected to be of concern.
Carcinogenic (Ot* Approach') Aggregate Risk
Since alachlor has no residential uses to aggregate with the dietary assessment, the
carcinogenic aggregate risk assessment is the same as the carcinogenic (food and water) dietary
assessment. As previously discussed in this document, the carcinogenic risks were calculated for
adult males and adult females, using the food exposure estimated by DRES, and one source of
drinking water. All risk estimates were rounded to two significant figures.
Table 35: Summary of Alachlor Aggregate Carcinogenic (Qx* Approach) Risk
Source of Drinking Water
Risk
Adult Male
NAWWS (Midwest groundwater)
1.0 x 10"6
USGS reservoir (Midwest surface water)
1.1 x 10"6
ARP 12 state area surface water
7.8 x 10"7
Adult Female
NAWWS (Midwest groundwater)
1.3 x 10"6
USGS reservoir (Midwest surface water)
1.4 x 10"6
ARP 12 state area surface water
1.1 x 10"6
All carcinogenic risks estimated using the Qx* are within the risk range considered by the
Agency to represent negligible risk.
Cumulative Effects
The Food Quality Protection Act of 1996 (FQPA) amended the Federal Food, Drug, and
Cosmetic Act (FFDCA) by setting a new safety standard for the establishment of tolerances. Section
408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish, modify, or
revoke a tolerance, the Agency consider "available information" concerning the cumulative effects
of a particular pesticide's residues and "other substances that have a common mechanism of toxicity."
The Agency believes that "available information" in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and methodologies for understanding
common mechanisms of toxicity and conducting cumulative risk assessments. For most pesticides,
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although the Agency has some information in its files that may turn out to be helpful in eventually
determining whether a pesticide shares a common mechanism of toxicity with any other substances,
EPA does not at this time have the methodologies to resolve the complex scientific issues concerning
common mechanism of toxicity in a meaningful way. EPA has begun a pilot process to study this
issue further through the examination of particular classes of pesticides. The Agency hopes that the
results of this pilot process will increase the Agency's scientific understanding of this question such
that EPA will be able to develop and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative effects of such chemicals. The
Agency anticipates, however, that even as its understanding of the science of common mechanisms
increases, decisions on specific classes of chemicals will be heavily dependent on chemical specific
data, much of which may not be presently available.
At present there is no methodology for applying the information in the Agency's files
concerning common mechanism issues for most risk assessments. But, there are pesticides for which
the common mechanism issues can be resolved. For example, pesticides that are toxicologically
dissimilar to existing chemical substances (in which case the Agency can conclude that it is unlikely
that a pesticide shares a common mechanism of activity with other substances) and pesticides that
produce a common toxic metabolite (in which case common mechanism of activity will be assumed).
Due to the structural similarities with acetochlor, metolachlor, butachlor, and propachlor,
alachlor may fall into the second category. However, at this time the Agency has not yet made a final
decision concerning a possible common mechanism of toxicity for these five chemicals to
scientifically apply that information to the tolerance decision. The process has begun, but is not yet
completed. Therefore, for the purposes of this decision document, the tolerance decision will be
reached based upon the best available and useful information for alachlor only. The risk assessment
has been performed for alachlor only assuming that no common mechanism of toxicity exists.
However, these decisions will be reexamined after methodologies and procedures for integrating
information concerning common mechanism of toxicity into risk assessments are developed by the
Agency.
Monsanto must submit, upon EPA's request and according to a schedule determined by the
Agency, such information as the Agency directs to be submitted in order to evaluate issues related
to whether alachlor shares a common mechanism of toxicity with any other substance and, if so,
whether any tolerances for alachlor need to be modified or revoked.
c. Environmental Assessment
1. Use Characterization
Alachlor is a herbicide registered for use on the following crops: succulent and dry beans;
field, pop, and sweet corn; peanuts; grain sorghum; and soybeans.
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Use in Corn and Soybean Areas
Corn is grown in almost every state in the continental U. S. Maj or corn-growing areas include
the Midwest and Great Plains states (from Ohio west to Nebraska and from southern
Minnesota/Wisconsin south to Illinois/Missouri), the Mississippi River Valley, and the East Coast
(from southeastern Pennsylvania to North Carolina) (USDANational Agricultural Statistics Service,
1996 Harvested Acres by County). These regions include such wildlife-rich areas as the Prairie
Pothole region, Sandhills Lake region of Nebraska, and coastal/estuarine regions of the Delmarva
peninsula and North Carolina. Many of these areas are used by waterfowl and shorebirds as breeding,
feeding, and migratory resting grounds. In addition, corn may be grown in the vicinity of freshwater
and estuarine/marine aquatic habitats. This can lead to exposure of aquatic resources from the off-
site movement of chemicals applied to cornfields near such habitats.
The corn-growing region includes localized areas which have a high potential vulnerability
for contamination of shallow ground water with pesticides (Kellog et al., 1992). Such vulnerable
areas include the eastern coastal plain from southern Georgia to New Jersey, eastern Nebraska, and
southern portions of the Great Lakes region. While the maj ority of corn-growing areas are dominated
by soils which have a moderate runoff potential and moderate infiltration and permeability (also
referred to as Hydrologic Group B soils), localized regions are more susceptible to runoff (Kellog et
al., 1992). Areas with significant percentages of soils with moderately high to high runoff potential
(Group C and D soils) include the Gulf Coast region of Texas, the lower Mississippi River Valley,
the Missouri River Valley in South Dakota, the extreme eastern coastal plain of Georgia, South
Carolina, and North Carolina, and portions of the Ohio River Valley. These soils are more prone to
runoff because of slow permeability (low saturated hydraulic conductivities) and/or a relatively
shallow water table.
Use in Sorghum Areas
Major sorghum-growing areas in the U.S. are the central and southern Great Plains (from
Nebraska south to Texas and from eastern Colorado to Missouri) and the Mississippi River Valley
from southern Illinois to Louisiana (USDANational Agricultural Statistics Service, 1996 Harvested
Acres by County). The number of acres planted to sorghum appears to be increasing in the coastal
plains of the Carolinas and Georgia. While the geographic extent of the sorghum area is less than that
of corn, it does include significant areas of wildlife habitat. It may also be found in the vicinity of
estuarine/marine habitats, especially along the Gulf Coast region of Texas. Potential exposure of
aquatic resources may occur from the off-site movement of chemicals applied to sorghum fields near
such habitats.
Sorghum is more tolerant of dry conditions than corn and is typically grown in warmer
climates which have a lower rainfall than the corn region. Overall, the major sorghum areas also have
a lower potential vulnerability for contamination of shallow ground water, except in the southeastern
U.S., where the acreage of sorghum is increasing (Kellog et al. 1992). Large areas of Texas and the
Mississippi River Valley are dominated by the high runoff potential Hydrologic Group C and D soils.
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In such areas, the adjacent aquatic habitats may be vulnerable to off-site movement of chemicals from
runoff.
Use on peanuts areas
Peanuts are grown primarily in the southern Coastal Plain, from Virginia to Alabama and in
the plains of central Texas and Oklahoma (USDA National Agricultural Statistics Service, 1996
Harvested Acres by County). The Coastal Plain region includes significant areas used by waterfowl
and shorebirds as breeding, feeding, and migratory resting grounds. Peanut-growing areas may occur
in the vicinity of freshwater and estuarine/marine aquatic habitats. The Coastal Plain includes a large
percentage of areas with a high potential vulnerability for contamination of shallow ground water with
pesticides (Kellog et al., 1992).
Figure B: Alachlor and Its Degradates
The structures of alachlor and four of its degradates are illustrated in Figure B:
Nomenclature
Chemical Structure
Alachlor
2-Chloro-2',6'-diethyl-N-
methoxymethylacetanilide
0
H ^CH ^C1
0 N CH
2
^^CH2
H C ^CH
3 I 3
Alachlor - DM-Oxanilic Acid
2',6'-Diethyloxanilic acid
(Compound III)
0
HN C
1
HO
^/CH2 ^^CH2
3 3
114
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Alachlor Sulfinylacetic Acid
(N-Methoxymethyl-N-(2,6-diethylphenyl)-
2-amino-2-oxoethyl)-sulfinylacetic acid
(Compound VIII)
0 0 0
H3C\ /"CH2
>0 CH CH2 OH
/-CH2 /W /CH2
Hs C ^ "^ch3
Alachlor Oxanilic Acid
2',6'-Diethyl-N-methoxymethyloxanilic acid
(Compound X)
C
H >.CH
\ / v. /
0 N
y-CH
h c t;
3
\ /-0H
c
II
0
_y.CU
2
"CH
3
Alachlor Sulfonic Acid
2',6'-Diethyl-N-methoxymethyl-2-
sulfoacetanilide
(Compound XI)
H C. ^CH .
0 N
^ CH
H C t; \
3
0 0 OH
II 11/
c\ / %
CH 0
2
CH
/ 2
ch
3
2. Ecological Toxicity Data
Ecological effects data are used by the Agency to determine the toxicological hazards of
pesticides to various terrestrial and aquatic nontarget organisms. These tests can include acute and
chronic scenarios. These data are then integrated with the environmental fate and exposure data
when the Agency performs a risk characterization.
The following studies provide the basis for the Ecological Effects Hazard Assessment.
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a. Terrestrial Animals
To evaluate the toxicity of a pesticide to birds, the following tests are required using technical
grade material:
• An avian single-dose oral (LD50) study on one species, preferably mallard or bobwhite
quail;
• A subacute dietary (LC50) study using one waterfowl species, preferably the mallard
duck;
• A subacute dietary (LC50) study using one upland game species, preferably bobwhite
quail or ring-necked pheasant.
Tests on wild mammals may be required, depending on intended use pattern, environmental
fate characteristics, and results of lower tier studies such as acute and subacute toxicity tests.
An acute contact LD50 for honey bees is required if the proposed use will result in exposure
of honey bees.
Birds. Acute
The requirement for a measurement of acute oral toxicity to birds is fulfilled based on one
acceptable study, which indicates slight toxicity. Results follow in Table 36. (MRID No. 00079523)
Table 36: Avian Acute Oral Toxicity
Species
% Test Material (TGAI)
LD50 (mg/kg)
Fulfills Guidelines
Bobwhite quail
92.3
1499
Yes
Birds. Subacute
The requirement for a measurement of subacute dietary toxicity is fulfilled based on two
acceptable studies, which indicate that the chemical is practically nontoxic to birds. Results follow
in Table 37. (MRID Nos. 43087101, 43087001)
Table 37: Avian Subacute Dietary Toxicity
Species
% Test Material (TGAI)
LC50 (mg/L)
Fulfills Guidelines
Bobwhite Quail
95.4
>5620
Yes
Mallard Duck
92.3
>5620
Yes
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Birds. Chronic
When birds are expected to be exposed to pesticides for long periods of time or exposed
during the breeding and nesting season avian reproduction studies are sometimes required. Avian
reproduction studies for alachlor are required based on the following criteria:
• Birds are expected to be subjected to repeated or continued exposure to alachlor and or its
degradates preceding or during breeding season. Alachlor is generally applied in the early
spring months when birds are most actively breeding.
• Alachlor and its metabolites or degradates are stable in the environment to the extent that
potentially chronically toxic amounts may be present in avian feed.
• In a rat teratological study both maternal and developmental effects were observed at 400
mg/kg/day (MRID No. 00043645)
• Reproduction studies with acetochlor, a pesticide whose chemical structure is very similar to
alachlor, have shown reproductive effects to mallard duck at 150 ppm and bobwhite quail at
750 ppm (MRID Nos. 43383101, 43383102). In a partially acceptable reproduction study
conducted with metolachlor on mallard duck, eggs in 10, 100, and 1000 ppm test
concentrations showed eggshell thinning (MRID No. 0162292).
Mammals
Ecological effects data on toxicity data to mammals will not be required for alachlor at this
time. Available toxicity data on rats (health effects data requirement) indicate an acute LD50 of 930
mg/L. Mammalian LD50s are not used directly to determine whether LOCs are exceeded, but do
provide some indication of level of toxicity. The available data indicates that alachlor is slightly toxic
to small mammals.
Insects
Honey bee acute contact studies conducted with technical ingredient and 42% formulation
products have been reviewed. These studies indicated low toxicity toward honey bees, with LD50
levels greater than 36.2 jjg ai/bee for the technical and greater than 100 pg ai/bee for the formulated
product. (MRID Nos. 00074486 and 00028772)
Table 38: Toxicity to Honey Bees
%Test Material fTGAD
TT)™ (up ai/hee^
Fulfills Guidelines
Technical
>36.2
Yes
42.2% Formulation
>100
Yes
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b. Aquatic Animals
Freshwater Fish
To evaluate toxicity of a pesticide to freshwater fish, LC50 measurements are required for two
species, using technical grade active ingredient. One study should use a cold water species, preferably
rainbow trout. The other should use a warm water species, preferably bluegill sunfish. Chronic
toxicity testing is required for evaluation of possible effects to growth or reproduction of fish exposed
to persistent pesticides. This requirement is fulfilled by Early Life-stage Testing of one species of
freshwater fish.
The data requirement is fulfilled for alachlor based on studies submitted. Studies submitted
indicate moderate toxicity to warm- and cold- water fish. LCS0 values are displayed in Table 39.
Precautionary toxicity statements are required on labels based on MRID No. 43862601 which shows
alachlor to be highly toxic on a chronic basis to freshwater fish growth, reproduction and
development. Acute toxicity of alachlor and tested formulations is moderate. (MRID Nos.
00023615,00023616,00028549,00028550,00028551,00028553,00028554,00028555,00031524,
00031525, 40098001)
Table 39: Acute Toxicity to Freshwater Fish
Species
% Test Material (TGAI)
LC50 (mg/L)
Fulfills Guidelines
Toxicity Based on Exposure to Technical Active Ingret
ient
Bluegill Sunfish
90
2.8
Yes
100
4.3
Yes
Rainbow Trout
90
1.8
Partially
100
2.4
Yes
Toxicity Levels Based on Ex
posure to End-Use Product
Bluegill Sunfish
43EC
3.2
Partially
45
6.2
Partially
42.4
7.9
Partially
Rainbow Trout
42.5
3.6
Partially
45
3.7
Partially
44
4.2
Partially
43
1.4
Yes
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Table 39: Acute Toxicity to Freshwater Fish
Species
% Test Material (TGAI)
LC5o (mg/L)
Fulfills Guidelines
43
3.2
Yes
Table 40: Chronic Toxicity r
o Freshwater Fish in mg ai/L
Species
% Test Material
NOEL
LOEC
Fulfills Requirement
Rainbow trout
Technical
0.187
0.388
Yes
Toxicity to Freshwater Invertebrates
To evaluate acute toxicity to freshwater aquatic invertebrates, an EC50 measurement is
required based on technical grade active ingredient, preferably using first instar Daphnia magna, or
early-instar amphipods, stoneflies, mayflies, or midges. The requirement is fulfilled based on studies
submitted. Results are displayed in Table 41. The studies submitted indicate moderate to slight acute
toxicity for this category, based on studies reviewed to date. (MRID Nos. 00028549, 00028555,
00031526, 40098001).
Table 41: Toxicity to Freshwater Invertebrates
Species
% Test Material
(TGAI)
ec50
(mg/L)
Fulfills Guidelines
Toxicity Based on Exposure to Technical Active Ingrec
ient
Water Flea
Daohnia magna
90
10
Yes
93
21
Yes
Midge
93
3.2
Yes
Toxicity Levels Based on Exposure to End-Use Product
Water Flea
Daohnia maana
49
33
Partially
45
22
Partially
42.4
27
Partially
43
7.7
Yes
Midge
45
2.5
Yes
119
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Chronic toxicity to freshwater invertebrates is determined by exposing one species of
freshwater invertebrate, preferably Daphnia magna, to the pesticide for a full generation and
observing effects on growth and reproduction. In 21-day full lifecycle testing alachlor was shown to
be highly chronically toxic to growth and reproduction of freshwater invertebrates. Chronic LOEC
and NOEC values are displayed in Table 42. Based on the high chronic toxicity of this pesticide
appropriate environmental warning labels are required. (MRID No. 43774707)
Table 42: Chronic Toxicity Based on Exposure to Technical Active Ingredient
Species
% Test Material
(TGAI)
LOEC
mg ai/L
NOEC
mg ai/L
Fulfills
Requirement
Water Flea,
DaDhnia maana
94.6
0.23
0.11
Yes
Acute Toxicity of Pesticide Metabolites to Freshwater Animals
Aquatic testing with metabolites of pesticide compounds is requested when metabolites are
likely to be persistent in the aquatic habitats in amounts greater than or equal to the parent compound.
Four studies have been submitted to aid in characterization of the acute toxicity of alachlor sulfonic
and oxanilic acids to freshwater invertebrate and fish species. The studies indicate that these
degradate compounds display low acute toxicity to the tested species. The submitted studies are
summarized in Table 43. (MRID Nos. 43774703, 43774704, 43774705, and 43774706)
Table 43: Acute Testing with Alachlor Metabolites
Species Tested
Degradate and % ai
lc50/ec50
frntJ ai/T ^
Fulfills Guidelines
DaDhnia maana
Sulfonic acid, 91.5%
EC,0>104 mg/L
Yes
Oxanilic acid, 92.4%
EC,n>95 mg/L
Yes
Rainbow trout
Sulfonic acid, 91.5%
LC,o>104 mg/L
Yes
Oxanilic acid, 92.4%
LC50>95 mg/L
Yes
Estuarine and Marine Animals
The use pattern of alachlor includes applications to major crops that are sometimes grown in
close proximity to estuarine and marine environments.
The toxicity measurements required are a 96-hour LC50 for an estuarine fish, a 96-hour LC50
for shrimp or mysid, and either a 48-hour embryo-larvae study or a 96-hour shell deposition study
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with an estuarine mollusk species. The data requirement is fulfilled for alachlor based on the studies
submitted (MRID Nos. 44524301, 44524302, 44524303). LC50/EC50 values are shown in Table
44.
"able 44: Acute Toxicity to Estuarine/Marine Species
Species
% Test Material (TGAI)
lc50/ec50
(mg/L)
Fulfills Guideline
Sheepshead minnow
93.8
LC50=3.9
Yes
Mysid
93.8
LC50=2.4
Yes
Eastern Oyster
93.8
EC50=1.6
Yes
A study submitted to the Agency (Kirby-Smith, et. al., 1993), indicates that, in general, there
were no significant differences in diversity, numbers and/or biomass between those creeks and
estuaries that received pesticidal run-off (farm creeks) and those that didn't (forested creeks). The
data derived from this study is confounding because results did not compare with laboratory toxicity
data and EEC estimates. During the course of this study there did not appear to be any significant
chronic adverse effects in terms of species diversity, biomass, energy transfer or nutrient cycling,
occurring in the system.
c. Plants
Data from studies submitted to the Agency, though incomplete, indicate high toxicity to
aquatic and terrestrial plants.
Terrestrial Plants
Studies were required to establish toxicity to nontarget terrestrial plants. Two studies were
received. Of the ten species of terrestrial plants tested, seven had EC25 levels for vegetative vigor less
than maximum permitted rates on present labels. Seedling emergence was also effected in most of
the species tested. Based on the data provided, alachlor is highly toxic to nontarget terrestrial
plants. (MRID Nos. 42468601, 42468701)
Table 45: Toxicity to Terrestrial Plants
Measurement Endpoint
1 1
| Most Sensitive j NOEL (lbs a.i./A)
| Species Tested j
1
| EC25(lbs a.i./A)
1
1
i
Vegetative Vigor3
Phvtotoxicitv
_! Ryegrass _[ 0.019
undetermined
121
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Table 45: Toxicity to Terrestrial Plants
Measurement Endpoint
Most Sensitive
Species Tested
NOEL (lbs a.i./A)
EC25(lbs a.i./A)
21-Day Survival
_l
Onion
- _L_
0.22
0.31
21-Day Height
_l
Ryegrass
_ _L
0.037
0.12
21-Day Weight
1
Ryegrass
L
0.037
0.044
Germination and Growth
6-Day Seed Germination
_l
Cabbage
_ _L_
0.67
undetermined
6-Day Seedling Emergence
_l
Ryegrass
_ _L_
0.019
0.04
21-Day Survival
_l
Onion
_ _L_
0.037
0.011
Phytotoxicity
_l
Lettuce
_ _L_
0.0093
undetermined
Height
4
Ryegrass
- 4-
0.0023 _j_ 0.011
Weight
Ryegrass
s
0.0023 ! 0.0067
I
3 Based on a supplemental study with 94.6% active ingredient that fulfills guideline requirements.
b Based on a supplemental study with 94.2% active ingredient that fulfills guideline requirements.
Aquatic Plants
Studies were required to establish toxicity to nontarget aquatic plants. The requirement is
partially fulfilled by the single study submitted. However, to completely fulfill data requirements for
aquatic plant testing additional studies must be submitted for acute toxicity to an aquatic macrophyte,
a marine diatom, a blue-green algae and a freshwater diatom. Based upon the one study available,
alachlor is highly toxic to aquatic plants. (MRID No. 42763801) Also, effects on aquatic plants
are expected to result in indirect effects on aquatic animals, e.g., by habitat modification or restricted
food supply.
Table 46: Toxicity to Ac
uatic Plants
Species Tested
%Test
Material
Toxicity (|_ig/L)
Fulfills
Guidelines
Freshwater Green alga
Selenastrum capricornutum
98.6
NOEL=0.35
LOEL=0.69
EC50=1.64
(growth effects)
Yes,
partially
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d. Conclusions
The available toxicity data for alachlor, indicate that it is:
• Slightly to practically non-toxic to birds on an acute oral basis (LD50 of 1500 mg/kg), but
chronic data are not available.
• Slightly toxic to mammals, based on a rat study (LD50 of 930 mg/kg).
• Slightly toxic to honey bees (LD50 >36 (jg/bee).
• Slightly to moderately toxic on an acute basis to freshwater aquatic animals (LCS0 /EC501-33
ppm).
• Highly to moderately toxic to freshwater aquatic animals on a chronic basis (NOEC>0.1 ppm,
LOEC>0.2 ppm).
• Moderately toxic to saltwater fish (LC50 3.9 ppm), moderately toxic to saltwater mysid (LCS0
2.4 ppm) and moderately toxic to shellfish (EC50 1.6 ppm).
• Highly toxic to aquatic plants (based on a single species tested: NOEL=0.3 5 ppb, LOEL=0.69
ppb, EC50=1.64 ppb).
Therefore, a potential risk to nontarget terrestrial and aquatic plants, and endangered plant
species exists. Additionally, the available information on the major alachlor degradates indicate that
the degradates appear to be less toxic to aquatic organisms than the parent.
3. Environmental Fate Data
The following studies provide the basis for the Environmental Fate Assessment.
a. Degradation
GLN 161-1 Hydrolysis:
In an acceptable study, [14C] Alachlor (carbonyl labeled) applied at 50 ppm was relatively
stable in sterile commercial pH 3, 6, and 9 buffer solutions, natural lake water, and deionized water
that were incubated in the dark at 25 °C for 30 days. [14C] Alachlor comprised 97.5-98.7% of the
applied radioactivity in all test solutions, with no discernible pattern of decline. The degradate 2',6'-
Diethyl-N-methoxymethyl acetanilide was <1.57% of the applied.
As part of the same study, [14C] alachlor, at 2 ppm, degraded very slowly in nonsterile lake
water, when incubated at an unspecified temperature for 30 days. After 30 days of treatment,
alachlor was 88.8% of the applied concentration in the test solution. Five nonvolatile compounds
were identified, at <2.7% of the applied. (MRID No. 00134327)
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GLN 161-2 Photolysis in Water:
This data requirement will be waived based on the UV absorption spectrum of alachlor in
water. The current policy is to concur with waivers for this requirement when the electronic
spectrum of the chemical does not show significant absorption between 290 and 800 nm, because
photodegradation can only take place when there is an overlap between absorption regions of the
spectrum of the chemical and the irradiation spectrum of the light source. A submitted study
indicated that the UV absorption spectrum of alachlor in water shows no absorption at wavelengths
above 290 nm. (MRID No. 00023012)
GLN 161-3 Photodegradation on Soil:
The Agency will require no additional data to support the Photodegradation on Soil data
requirement at this time. Although the Agency does not have any information about the photolytic
behavior of any of the major degradates of alachlor at this time, an acceptable study will not be
required because the absorption spectrum of the chemical in water does not show significant
absorption at wavelengths above 290 nm.
b. Metabolism
GLN 162-1 Aerobic Soil Metabolism:
Three different studies conducted on various soil types have shown similar half-lives, ranging
from 6 to 21 days. The degradation products were identified only in two of the studies, one of which
is acceptable and the other is supplemental. Three of the four major degradates were observed in
both studies. The compound (N-methoxymethyl-N-(2,6-diethylphenyl)-2-amino-2-oxoethyl)
sulfinylacetic acid, which was up to 15.9% of the applied in one supplemental study (MRID No.#
00101531), was not observed in the acceptable study (MRID No. 00134327). All major metabolites
were monitored in the available Terrestrial Field Dissipation study.
In an acceptable study [14C] alachlor applied at 2 ppm degraded with estimated half-lives of
2-3 weeks in silt, loamy sand, and silt loam soils incubated in the dark at 25 °C and 75% of field
moisture capacity for 175 days. In the silt loam soil, alachlor was 87.7% or the applied at the
initiation of the study, 47.4% at 21 days, and 1.6% at 175 days. In the loamy sand, alachlor was
98.5%) of the applied at 0 days, 52.4% at 14 days, and 2.5% at 175 days. In the silt soil, alachlor was
99.0% of the applied at day 0, 40.4% at day 14, and 0.7% at 175 days.
Four degradates were detected, with significant concentrations (> 10% of the applied):
• Alachlor DM-oxanilic acid was a "water soluble" metabolite that increased gradually to a
maximum of 5.3% of the applied at 50 days post-treatment in the silt loam, it decreased to
3.9%) at 175 days. It increased to a maximum of 15.8-17.0%) of the applied at 175 days post-
treatment (last test interval) in the loamy sand and silt soils;
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• Alachlor oxanilic acid was a "water soluble" metabolite, and was a maximum of 12.7-22.4%
of the applied at 28-50 days post-treatment in all soil types and decreased to 2.9-13.4% of
the applied at 175 days post-treatment;
• Alachlor ESA was a "water soluble" metabolite, which increased to a maximum of 24.9% of
the applied at 50 days post-treatment in the silt loam, 16.9% of the applied at 175 days post-
treatment in the loamy sand, and 16.0% of the applied at 21 days post-treatment in the silt
soil. It decreased to 11.2-18.6%) of the applied at 175 days post-treatment in the silt loam and
silt soils.
• 2',6'-diethyl-2-hydroxy-N-methoxymethylacetanilide was the only maj or "methylene chloride
soluble" degradate and increased to a maximum of 6.7-10.2%) of the applied at 7-21 days
post-treatment and decreased thereafter to < 1.1% of the applied at 175 days in all soil types.
Nine other degradates were also identified, at <10%> of the applied. After 175 days
incubation, 14C02 was 16.17-30.00%) of the applied. [14C] volatiles were <1.15%> of the applied, and
unextracted [14C] residues totaled 19.25-20.76%) of the applied. (MRID No. 00134327)
In a second study (found to be supplemental), [14C] alachlor (phenyl ring-labeled) applied at
2 ppm degraded with half-lives of 6-12 days in silt, loamy sand, and silt loam soils incubated in the
dark at 25 °C for 62 days. The soils were also treated with [14C] alachlor encapsulated in a polyurea
polymer. The rate of degradation is similar for the encapsulated [14C] alachlor, with half-lives of 8-11
days.
Four major degradates were identified in the soil. These degradates were observed in all three
soil types at 62 days; however, testing at various test intervals (monitoring through time) was
performed only for the silt soil:
• Alachlor DM-oxanilic acid comprised a maximum of 14.4% of the applied radioactivity in the
silt soil at 62 days post-treatment. It comprised 2.9-7.3%) of the applied at 62 days in the
loamy sand and the silt loam;
• Alachlor oxanilic acid comprised a maximum of 9.7-10.0%) of the applied radioactivity in the
silt soil at 20 days post-treatment. It decreased to <3.7% of the applied at 62 days in the
loamy sand and the silt loam;
• Alachlor sufinylacetic acid comprised 15.9-16.2%) of the applied radioactivity in the silt loam
soil at 62 days post-treatment. It was a maximum of 12.6-13.3%) of the applied in the silt soil
at 20 days post-treatment, decreasing to <9.7% at 62 days; and
125
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• Alachlor ESA comprised a maximum of 6.5% of the applied radioactivity in the silt soil at 30
days post-treatment and <5.1% at 62 days. It was 2.7-4.1%) of the applied in the loamy sand
and silt loam at 62 days.
This study provides supplemental information about the rate of degradation of alachlor and
the identity of alachlor degradates under aerobic conditions. This study is deficient because up to
22.3%o of the applied radioactivity was not characterized. (MRID No. 00101531)
In a third study (also supplemental) [14C] alachlor applied at 4 ppm degraded appreciably, with
a half-life of <18 days in sandy loam, silt loam, and silty clay loam nonsterile soils incubated at <32°C
in a greenhouse. [14C] Alachlor was <0.5 ppm in all three soil types 72 days after treatment. The
degradate 2-chloro-2',6'-diethylacetanilide was detected at all sampling intervals at <0.8 ppm, with
no definite pattern of formation or decline.
This study was conducted in a greenhouse. It provides supplemental information about the
aerobic soil metabolism of alachlor by identifying one alachlor degradate. The study is deficient when
evaluated according to current guidelines because it was conducted in the greenhouse, and material
balances could not be confirmed. (MRID No. 00023014)
c. Mobility/Leachability of Alachlor
GLN 163-1 Mobility. Leaching and Adsorption/Desorption:
Based upon the studies available and the structural features of the chemicals, it appears that
alachlor degradates, as well as parent alachlor, have a high potential to leach.
An acceptable study partially satisfies the requirement by providing information about the
mobility of unaged alachlor. To satisfy the data requirement a supplemental Batch Equilibrium study
was submitted for alachlor ESA, which is the maj or degradate observed in the aerobic soil metabolism
studies.
[14C] Alachlor (carbonyl labeled), at 3.5 lb a.i./A, was very mobile in 30 cm columns of silt,
sand, and loamy sand soils that were leached with 20 inches of water. The leachate from the silt,
sand, and loamy sand soil columns contained 40.9-96.9%) of the applied radioactivity. This
radioactivity was "mainly" alachlor. The following degradate was identified in these leachates, but
not quantified: 2',6'-diethyl-N-methoxymethylacetanilide.
[14C] Alachlor was mobile in columns of silt loam soil treated under similar conditions. The
leachate from the silt loam soil contained 0.5-0.6% of the applied radioactivity. The radioactivity
remaining throughout the soil columns increased from 1.9-5.4%) of the applied in the 0- to 2-cm
segment, to 10.9-12.9%) in the 10- to 14-cm segments, and declined to 0.1%> in the 28- to 30-cm
segment. The following compounds were detected in the leachates at 5-23% of the recovered
126
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radioactivity: 2',6'-diethyl-N-methoxymethylacetanilide, 2-chloro-2',6'-diethylacetanilide, and 2',6'-
diethyl-N-methoxymethyl-2-methylthioacetanilide.
The analysis of selected soil extracts of all four soils indicated that the radioactivity was
"mainly" alachlor. There was no clear correlation between the mobility of alachlor and the soil
composition; however, it appears that higher organic matter contents favor adsorption of the chemical
to the soil.
Although this study had been found acceptable and provides information about the mobility
of parent alachlor, the following details are noted because they could have had an effect on the
observed results: The columns were packed using a wooden dowel; it is not reported if the columns
were saturated prior to leaching. In addition, it is reported that the water "was added at a rate slower
than the infiltration capacity of the soil." These conditions could have affected the observed leaching
behavior. The parent alachlor could have leached even more under saturated flow conditions which
would be the maximum flow rates. (MRID No. 00134327)
In a leaching study, [14C] alachlor residues leached through the columns, with ~ 96%, ~ 5 1 %,
and 0% of the recovered having leached through a gravelly sand, sandy loam, and a silty clay loam
soil columns, respectively. The soil columns measured 20 cm (8 inches, recommended 30 cm), and
were leached with 10 inches of water (recommended 20 inches). This study was considered
scientifically valid in the original reviews. However, the Agency now believes that these studies only
provide supplemental information, since leaching and soil retention were reported based on 14C rather
than concentrations of alachlor and its degradates. The study indicates a high level of leaching in
sand, sandy loam, and silty clay loam. (MRID Nos. 00027139, and 00027140)
Based on a supplemental Adsorption/Desorption experiment [14C] alachlor, at 1-10 ppm,
appears to have a high mobility in three soil types. The Kd values, calculated based on [14C] instead
of actual alachlor concentrations, decreased with a decrease in soil organic matter. The mean Kd
values were 3.74 for a silty clay loam, 2.88 for sandy loam, and 0.80 for a gravelly sand.
In a supplemental column leaching study alachlor applied at 5 kg ai/A appeared to be very
mobile in a Lakeland sand, with 59% of the applied alachlor recovered from the leachates of a 30 cm
soil column, eluted with 8 inches (20 cm) of water. Alachlor was less mobile in other soils tested,
with maximum leaching depths of 18 cm, 10 cm, and 4 cm in Collenbey sand, silt loam, and sandy
clay loam columns, respectively. The level of leaching appeared to be related to the percent organic
matter, with lower leaching of the soils having higher organic matter.
However, the study does not meet the Subdivision N Guidelines because the columns were
eluted with only 8 inches of water. (Subdivision N Guidelines recommends elution with 20 inches
of water.) In addition, no attempts were made to measure possible degradates or total residues.
Therefore, the Agency is concerned about the validity of the study since insufficient elution water was
applied to demonstrate the mobility of alachlor in the soils. This study is now deemed supplemental
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and gives an indication of the level of leaching in sandy clay loam, silt loam, and sand. (MRID No.
00078301)
Based on supplemental column leaching studies, aged (30 days) uncharacterized [14C]
residues of alachlor were mobile in 30 cm columns with sandy loam soil, treated at 3.5 lb a.i./A, and
leached with 20 inches of water. The radioactivity recovered in the leachate totaled 29.1-31.5% of
the applied. Approximately 10 compounds were isolated from the leachates each at <0.7% of the
applied radioactivity. The major component found in the soil samples was [14C] alachlor.
This portion of the study (aged) is not acceptable, because the soil was aged for 30 days,
which may be a period of time considerably longer than one half-life. The aerobic soil metabolism
studies show estimated half-lives between 2 and 3 weeks. After the aging period, and prior to
leaching, the soil was not characterized; therefore, it is not possible to determine if either sufficient
parent compound remained at the time of leaching, or what was the ratio of the degradates formed.
(MRID No. 00134327)
d. Mobility of Alachlor Degradates
Mobility and Adsorption/Desorption of Alachlor ESA:
Based on batch equilibrium studies, uniformly phenyl ring-labeled [14C]-alachlor ES A (sodium
salt), at approximately 6.0, 1.0, 0.2, and 0.04 //g/mL, was determined to be very mobile in Sable silty
clay loamxalcium chloride solution slurries (1:5) that were equilibrated in the dark for 24 hours at
approximately 25°C. Freundlich Kads value was 0.45 and Koc value was 15. Following one
desorpti on step, Freundlich Kdes value was 1.43. Material balance ranged from 95.8 to 110.9% of the
applied for the definitive study.
Based on batch equilibrium studies, uniformly phenyl ring-labeled [14C]-alachlor ESA, at
approximately 6.0, 1.0, 0.2, and 0.04 //g/mL, was determined to be very mobile in Sarpy sandy loam,
Spinks sandy loam, and Katy loamxalcium chloride solution slurries (1:5) that were equilibrated in
the dark for 24 hours, at approximately 25 °C. Accurate Freundlich Kads values could not be
calculated because levels of adsorbed [14C]-alachlor ESA metabolite were very low. Adsorption
values in these three soils were approximately 0% (MRID No. 44405301).
The study on alachlor ESA does not fully fulfill the data requirement, because Freundlich
adsorption values could not be calculated in three of the soils. However, the study provides
supplemental information about the mobility of alachlor ESA, which has been detected in greater
concentrations than parent alachlor. The Agency believes that a new study would not provide new
information about the mobility of alachlor ESA other than confirming that this degradate is very
mobile; therefore, no additional data on the mobility of alachlor ESA are required at this time.
The registrant has submitted Adsorption/Desorption studies for two propachlor soil
metabolites. Propachlor is structurally similar to alachlor. The mobility characteristics of alachlor
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and propachlor, as well as other physico-chemical characteristics are similar as well. The registrant
proposed to use the mobility data on propachlor degradates as surrogate data for alachlor degradates.
This was accepted by the Agency since (1) the propachlor degradates are structurally similar to
alachlor degradates, and (2) the propachlor degradates are very mobile, which is comparable to the
available information on the mobility of alachlor ES A. Results obtained for the propachlor degradates
are as follows:
Based on batch equilibrium studies, propachlor oxanilic acid was determined to be very mobile
in loamy sand, sandy loam, loam, and silty clay loam soil: solution slurries. Freundlich Kads values
ranged from 0.03 to 0.08. Table 47 summarizes the results obtained in the study. (MRID No.
42485703)
Table 47: Mobility and Adsorption/Desorption
br Propachlor Oxanilic Acid
K ,
loamy sand
0.03
8
4.48
1120
sandy loam
0.04
2
15.86
886
loam
0.08
7
4.34
391
silty clay loam
0.06
10
20.91
3428
An acceptable propachlor sulfonic acid study is available, which can be used to partially satisfy
the data requirement for alachlor. Based on batch equilibrium studies, propachlor sulfonic acid was
determined to be very mobile in sand, sandy loam, loam, and silty clay loam soil solution slurries.
Freundlich Kads values ranged from 0.03 to 0.07. Table 48 summarizes the results obtained in the
study. (MRID No. 42485704)
Table 48: Mobility and Adsorption/Desorption
or Propachlor Sulfonic Acid
K ,
sand
0.03
7
1.33
317
sandy loam
0.06
6
6.24
624
loam
0.05
5
1.73
156
silty clay loam
0.07
3
1.23
47
Mobility characteristics compared for alachlor and propachlor:
An examination of the mobility characteristics of alachlor and propachlor show that both are
very mobile. Generally, propachlor is more mobile than alachlor (except in the Ray silt). It is
129
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observed that %CEC (% cation exchange capacity) and %OM (% organic matter) are good
predictors of alachlor mobility (higher mobility when %CEC is lower, and higher mobility when
%OM is lower). This trend is only general for propachlor. The Agency believes that for both
alachlor and propachlor degradates, that the negative charges play an important role in predicting the
mobility.
Table 49: Mobility Characteristics for Alachlor
Soil type
% sand
% silt
% clay
% OM
% CEC
%
radioactivity
found in
leachates
sand
86.0
11.0
1.8
0.7
5.1
86.7-96.9
silt
4.6
84.2
10.0
1.2
10.4
78.2-82.2
loamy sand
75.1
17.8
4.8
2.4
11.3
40.9-43.4
silt loam
2.4
68.0
25.3
3.4
24.6
0.5-0.6
Table 50: Mobility Characteristics for Propachlor
Soil type
% sand
% silt
% clay
% OM
% CEC
Ave. %
radioactivity
found in
leachates
Lintonia
sand
86.0
11.0
1.8
0.7
5.1
83.1-95.9
Ray silt
4.6
84.2
10.0
1.2
10.4
40.6-71.4
Spinks
loamy sand
75.1
17.8
4.8
2.4
11.3
71.0-84.0
Drummer
silt loam
2.4
68.8
25.3
3.4
24.6
2.9-7.9
The Agency believes that the mobility requirements for alachlor metabolites have been
partially satisfied with the submission of mobility data of the propachlor degradates: propachlor
oxanilic acid and propachlor sulfonic acid. The Agency believes that these degradates show
substantial structural similarity to alachlor degradates, therefore they can be used for a preliminary
assessment of the mobility of alachlor degradates. The Agency believes that the available data
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confirms that all the four major degradates of alachlor are very mobile under normal environmental
conditions.
e. Volatility
GLN 163-2 and 163-3 Laboratory and Field Volatility:
This data requirement was waived, based on the relatively low vapor pressure and levels of
volatiles in the aerobic soil metabolism study.
Alachlor has a vapor pressure of 2.2 x 10"5 mm Hg at 24°C (MRID No. 00152209). Since
this value is relatively low, volatility may not be an important route of dissipation for alachlor. In
addition, the acceptable Aerobic Soil Metabolism study (MRID No. 00134327) showed the presence
of small amounts of [14C] volatiles (<1.15% of the applied after 175 days of incubation). In a
supplemental aerobic soil metabolism study (MRID No. 00101531) [14C] volatiles were <4.84% of
the applied after 40-62 days. This suggests that volatilization is not a significant route of dissipation
for alachlor.
f. Field Dissipation
GLN 164-1 Terrestrial Field Dissipation:
Field dissipation has been evaluated at sites in Chico and Hickman, California. (MRID Nos.
42528001, 42528002, 42528003, 42528004, 43774701) Both terrestrial field dissipation studies
were conducted in California, despite the fact that alachlor is widely used throughout the United
States. These two studies are not adequate to fully characterize the range of field conditions to which
alachlor may be exposed. Despite this fact, a new additional terrestrial field dissipation study will not
be required. The Agency believes that a new study would not provide substantial new information.
The study conducted in Chico, California is acceptable and can be used to partially satisfy the
Terrestrial Field Dissipation (164-1) data requirement. Alachlor (Lasso ®4-EC), applied once at 4
lb a.i./A, dissipated with an observed half-life of approximately 11 days from a plot of loam/sandy clay
loam soil in Chico, California, that was planted to corn immediately after treatment. Alachlor was
detected at a depth of 18-to24-inches (at test intervals 7 and 14 days). In the 0-to 6-inch soil depth,
alachlor averaged 0.781-0.798 ppm at 0-1 days post-treatment, 0.641 ppm at 7 days, and 0.350 ppm
at 11 days. Two samples showed >0.124 ppm at 14 days, both in the 12- to 18- and 18- to 24-inch
soil depths. In addition, five minor detections occurred at 36- to 48-inch soil depth at <0.016 ppm
at 11-18 days. The rainfall plus irrigation totaled 6 inches through 18 days post-treatment.
The following degradates were detected in the soil:
• Alachlor oxanilic acid was detected through 44 days post-treatment in the 0- to 6- and
6- to 12-inch soil depths, at averages <0.047 ppm. There were 15 individual
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detections through 44 days in the 0- to 6-inch soil depth and 10 individual detections
through 21 days in the 6- to 12-inch soil depth. There were also sporadic detections
in the soil depths up to 36- to 48-inch at <0.023 ppm. These included 5 detections
in the 12- to 18-inch soil depth (14-120 days), 2 detections in the 18- to 24-inch soil
depth (18 and 180 days), and 2 detections in the 36- to 48-inch soil depth (44 days);
• Alachlor sulfinylacetic acid was detected from 7 through 44 days post-treatment in
the 0- to 6- and 6- to 12-inch soil depths, at averages <0.039 ppm. There were 13
individual detections through 44 days in the 0- to 6-inch soil depth and 11 individual
detections through 44 days in the 6- to 12-inch soil depth. There were 5 sporadic
detections in the soil depths up to 18- to 24-inch at <0.020 ppm at 14 and 18 days;
• Alachlor ESA was detected from 1 through 44 days post-treatment in the 0- to 6- and
6- to 12-inch soil depths, at averages <0.027 ppm. There were 14 individual
detections through 44 days in the 0- to 6-inch soil depth, 10 individual detections
through 90 days in the 6- to 12-inch soil depth; and 4 detections each in the 12- to 18-
and the 18- to 24- soil depths (at <0.022 ppm) at 14-78 days. Two sporadic
detections at <0.011 ppm were observed in the 24- to 36-inch soil depth, at 18, and
44 days.
• Alachlor DM-oxanilic acid was detected sporadically at <0.061 ppm through 90 days
after treatment, in the 0- to 6- and 6- to 12-inches depths. In addition, there was 1
detection each in the 12- to 18- and the 18- to 24-inch soil depths (90 and 44 days),
and 2 detections in the 24- to 36-inch soil depth (14 and 78 days).
Three samples were tested per test intervals. The lowest limit at which the method was
validated for each metabolite is 0.01 ppm. Detections below this level were reported as <0.01 ppm.
Examination of the soil composition data of the Chico plot shows an increasing percent of clay
with soil depth (to a maximum of 65% clay in the 24- to 36-inch soil depth). This "clay pan" reduces
the flow of water into deeper soil layers, decreasing the possibility of leaching of both parent alachlor
and its degradates. It is possible that under conditions that would favor the flow of water into deeper
soil layers, further leaching would have been detected.
The study conducted in Hickman, California is acceptable and can be used to partially satisfy
the Terrestrial Field Dissipation data requirement.
Alachlor (Lasso® E.C.), applied once at 4 lb a.i./A, dissipated with a registrant-calculated
half-life of 6.2 days from the 0-6 inch soil depth of a bareground plot of sandy loam soil in Hickman,
California. The field was bareground to simulate preemergent application to a crop. In the 0-6 inch
soil depth, alachlor averaged 1.363-1.458 ppm at 0-1 days post-treatment, 0.932 ppm on day 7 after
application, and 0.220 ppm on day 21 after application. Alachlor remained mostly in the 0-6 inch soil
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depth. Detections averaging 0.018-0.046 ppm were reported in the 6-12 inch soil depth on days 0
and 1 after application.
The following degradates were detected in the soil:
• Alachlor DM-oxanilic acid was detected in the 0-6 inch soil depth from day 1 through
day 366 after treatment at average levels from 0.006-0.048 ppm (no clear pattern of
formation or decline). The chemical was detected in the 6-12 inch soil depth only on
day 182 after application, with an average value of 0.004 ppm.
• Alachlor oxanilic acid was detected in the 0-6 inch soil depth from day 0 through day
366 after application at average levels from 0.005 to 0.058 ppm, with no clear pattern
of formation and decline. At three test intervals, detections were reported in the 6-12
inch soil layer. On days 0, 125, and 182, the oxanilate levels were 0.004, 0.004, and
0.013 ppm, respectively. The chemical was also detected in the 12-18 and 18-24 inch
soil layers on day 182 after application, with average values of 0.007, and 0.008,
respectively.
• Alachlor sulfinylacetic acid was observed at low levels in the 0-6 inch soil layer from
day 1 to 182 after application, at average levels ranging from 0.002 to 0.017 ppm.
In addition, the chemical was detected in the 6-12 and 18-24 inch soil layers on day
182 after application, with average values of 0.004 ppm in both cases,
• Alachlor ESA was observed at low levels from day 0 through day 366 after
application at average levels ranging from 0.003-0.010 ppm. Detections were also
reported in the 6-12 inch soil depth on days 182 and 366 after application, with
average values of 0.004 and 0.008 ppm, respectively. Furthermore, the chemical was
detected in the 12-18 inch soil depth on day 182 after application, with an average
value of 0.003 ppm
Another study conducted at Madera, California was considered invalid since the alachlor
concentrations found at all levels in the soils was <0.1 ppm. The application rate was 4 lb a.i./A.
When conducting a Terrestrial Field Dissipation study, the soils are sampled immediately after
treatment. Generally, it is expected that the highest concentration of active ingredient would be
observed at that test interval. Thereafter, a pattern of decline should be observed and a half-life is
calculated. Since the alachlor concentrations found at all levels in the soils was <0.1 ppm, there was
no pattern of decline. Thus, this study is not representative of typical behavior for the test conditions.
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g. Bioaccumulation
GLN 165-4 Bioaccumulation in Fish:
This data requirement was waived. Alachlor has a relatively high water solubility (240 ppm),
and a low octanol/water partition coefficient of434 (one study reports as low as 35). Chemicals with
these physico/chemical properties are not expected to bioaccumulate substantially in fish. Therefore,
the Agency will require no additional information on the Bioaccumulation in Fish (165-4) data
requirement for alachlor at this time.
h. Spray Drift
GLN 201-1 and 201-2 Spray Drift/Droplet Spectrum and Field Evaluation:
Alachlor is highly toxic to nontarget plants. Since alachlor can be applied aerially, data to
satisfy 201-1 and 201-2 was required in a 1991 DCI. The Spray Drift Task Force (SDTF), a
consortium of pesticide registrants, has submitted to EPA a series of studies intended to characterize
spray drift potential due to various factors, including application methods, equipment, meteorological
conditions, crop geometry, and droplet characteristics. EPA is currently evaluating these studies,
which include ground spray as well as aerial application methods. After its review of the studies, the
Agency will determine whether a reassessment of the potential risks from the application of alachlor
to nontarget organisms is warranted. The results would be used to assess the extent of exposure to
nontarget plants. This data requirement is not satisfied, and is being held in Reserve, pending the
evaluation of the work of the industry's SDTF. The registrant is a member of the SDTF.
4. Environmental Fate Assessment
Based on acceptable and supplemental studies, the following conclusions can be drawn:
Alachlor is stable to abiotic processes (hydrolysis, photolysis in aqueous media, or
photodegradation on soil). The major dissipation routes for the chemical appear to be microbially
mediated degradation and leaching. Alachlor is degraded at moderate rates (t,/2« 2-3 weeks) in
aerobic soils, with several degradates observed, including alachlor DM-oxanilic acid, alachlor ethane
sulfonic acid (alachlor ESA), alachlor oxanilic acid, and alachlor sulfinylacetic acid. Currently the
Agency does not have valid Kd's for alachlor. The registrant indicated that a Koc of 124 has been
reported by USDA/ARS in their Internet Web site. However, the Agency has not reviewed the study
used to determine the Koc. The column leaching study for the parent alachlor indicates that it is very
mobile and is not appreciably adsorbed to soils with low organic matter. A batch equilibrium study
on alachlor ESA shows that this degradate is very mobile. The findings in the field confirm the
predicted fate from laboratory studies.
Alachlor dissipated at moderate rates in the field; the observed half-lives of 6 and 11 days are
of the same order of magnitude of the half-lives observed in various aerobic soil metabolism studies
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(2-3 weeks). It appears that the persistence and mobility of the chemical may increase as it reaches
deeper soil horizons which have lower organic matter content and decreased biological activity, thus
increasing its potential to leach into groundwater.
a. Degradation and Metabolism
Alachlor is a soluble molecule (240 ppm in water at 20 °C), with an octanol/water partition
coefficient of 434, and a vapor pressure of 2.2xl0"5 mm Hg at 24°C.
Alachlor was stable to hydrolysis in buffered solutions at pH's 3, 6, and 9. It was also
relatively stable in natural lake water. Alachlor does not show any absorption bands above 240 nm
in the absorption spectrum; therefore, it is not expected to undergo photolysis in water or on soil.
In soils, under aerobic soil metabolism conditions, alachlor appears to degrade at a moderate
rate. Results of three different studies (one acceptable and two supplemental) show that alachlor
degrades with half-lives in the range of 6-21 days. The studies include use of different sites, different
formulations, and different soil types. Several degradates were observed in the studies. The major
degradates in the aerobic soil metabolism studies were alachlor DM-oxanilic acid (with a maximum
of 17.0% of the applied), alachlor ESA (24.9% of the applied), alachlor oxanilic acid (22.4% of the
applied), and alachlor sulfinylacetic acid (16.2% of the applied). Of these major "water-soluble"
degradates, alachlor sulfinylacetic acid was not observed in the valid aerobic soil metabolism study.
However, it was observed in a supplemental study. All four degradates appear to be more persistent
than alachlor, since significant concentrations remained in the soils at the end of the aerobic soil
metabolism studies.
C02 is the ultimate degradate; it comprised 16.17-30.00%) of the applied after 175 days in a
valid study. Unextracted residues comprised <20.76% of the applied at the same test interval.
b. Mobility
Based upon both supplemental and acceptable studies, parent alachlor appears to be highly
mobile in soils. In a column leaching study, in three of the soils with lower organic matter, alachlor
was very mobile: silt, sand, and loamy sand soil (0.7-2.4%) OM) columns, the leachates contained
40.9-96.9%) of the applied radioactivity. In another soil with a higher organic matter content, the
mobility was lower: silt loam soil (3.4% OM), the leachates had only <0.6%> of the applied
radioactivity; however, even though the water was added at a rate slower than the infiltration
capacity, substantial downward movement was observed through the column, with a total of 53.5-
57.7%o of the applied radioactivity found in the soil segments from 9- to 18-cm.
Since all the major water soluble degradates of alachlor have carboxylic or sulfonic acid
functional groups, which render a negative (anionic) character to the molecule under normal
environmental conditions, it is expected that the degradates will be highly mobile in soils. This is
supported by the available mobility data for the degradates of propachlor (propachlor sulfonic acid
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and propachlor oxanilic acid), which are structurally similar to the degradates of alachlor; the data
for these degradates of propachlor has been used as surrogate data in lieu of the original alachlor
metabolites. In addition, a batch equilibrium study on alachlor ESA shows that this degradate is very
weakly absorbed. Quantitative results could be obtained in only one of the soils (very mobile in
Sable silty clay loam, Freundlich Kads value was 0.45 and Koc value was 15).
c. Bioaccumulation
Alachlor is not expected to bioaccumulate significantly in fish, based on high solubility (240
ppm), and relatively low octanol/water partition coefficient (434).
d. Field Dissipation
In a Terrestrial Field Dissipation study conducted in Chico, California, alachlor, at 4 lb. a.i./A,
dissipated with a half-life of 11 days from loam/sandy clay loam soil planted to corn. This half-life
is consistent with those reported in various aerobic soil metabolism studies. Most of the alachlor was
found in the 0- to 18-inch soil layers, with occasional detections in the 18- to 24-, 24- to 36-, and 36-
to 48-inch layers (the deepest layer sampled), indicating a large potential for leaching. The four
major water-soluble metabolites of alachlor were also monitored in this study. The soil composition
data in this study shows increasing percent of clay with soil depth (to a maximum of 65% clay in the
24- to 36-inch soil depth). This "clay pan" reduces the flow of water into deeper soils layers,
decreasing the possibility of leaching of both parent alachlor and degradates.
Degradates of alachlor in the Chico Terrestrial Field Dissipation study (alachlor oxanilic acid,
alachlor sulfinylacetic acid, and alachlor ESA derivatives) were detected in the 0- to 6- and 6- to 12-
inch soil depths at average concentrations of 0.010-0.045 ppm. Detections were observed through
36- to 48- soil depth for the oxanilic acid, 18- to 24-inch soil depth for alachlor sulfinylacetic acid and
alachlor ESA, and 6- to 12-inch soil depth for the alachlor DM-oxanilic acid. Generally, detections
of these alachlor degradates occurred through 44-90 days post-treatment in the subsoils. Once
moved to the subsoils, these degradates appear to persist.
Alachlor, applied once at 4 lb a.i./A, dissipated with a registrant-calculated half-life of 6 days
from the 0-6 inch soil depth of a bareground plot of sandy loam soil in Hickman, California. The field
was bareground to simulate preemergent application to a crop. Alachlor remained mostly in the 0-6
inch soil depth. Detections averaging 0.018-0.046 ppm were reported in the 6-12 inch soil depth on
days 0 and 1 after application.
In the Hickman, California Terrestrial Field Dissipation study the following degradates were
detected: alachlor DM-oxanilic acid, which was detected in the 0-6 inch soil depth from day 1
through day 366 after treatment, and in the 6-12 inch soil depth only on day 182 after application
(with an average value of 0.004 ppm). Alachlor oxanilic acid was detected in the 0-6 inch soil depth
from day 0 through day 366 after application, in addition, at three test intervals, detections were
reported in the 6-12 inch soil layer. Alachlor oxanilic acid was also detected in the 12-18 and 18-24
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inch soil layers on day 182 after application. Alachlor sulfinylacetic acid was observed at low levels
in the 0-6 inch soil layer from day 1 to 182 after application, and in the 6-12 and 18-24 inch soil layers
on day 182 after application. Alachlor ESA was observed at low levels from day 0 through day 366
after application at average levels ranging from 0.003-0.010 ppm. Detections were also reported in
the 6-12 inch soil depth on two test intervals. Furthermore, alachlor ESA was detected in the 12-18
inch soil depth on day 182 after application, with an average value of 0.003 ppm.
e. Volatility
Volatilization is not expected to be an important route of dissipation for alachlor. The
chemical has relatively low vapor pressure (2.2x 10"5 mm Hg). Furthermore, the amount of volatiles
in the aerobic soil metabolism studies were negligible.
f. Spray Drift
The labels indicate that alachlor may be applied aerially. No alachlor-specific spray drift
studies were reviewed. The Spray Drift Task Force (SDTF), a consortium of pesticide registrants,
has submitted to EPA a series of studies intended to characterize spray drift potential due to various
factors, including application methods, equipment, meteorological conditions, crop geometry, and
droplet characteristics. EPA is currently evaluating these studies, which include ground spray as well
as aerial application methods. After its review of the studies, the Agency will determine whether a
reassessment of the potential risks from the application of alachlor to nontarget organisms is
warranted.
5. Terrestrial Exposure Assessment
Nongranular applications:
The terrestrial exposure assessment is based on the methods of Hoerger and Kenaga (1972)
as modified by Fletcher et al. (1994). Terrestrial estimated environmental concentrations (EECs) for
nongranular formulations were derived from maximum application rates up to 4.0 lb ai/acre.
Table 51: Estimated Environmental Concentrations on Avian and Mammalian Food Items
fnnml
Food Items
EEC (ppm) Max.
Residue
EEC (ppm)
Mean Residue
1 lb
ai/acre
41b
ai/acre
1 lb
ai/acre
41b
ai/acre
Short grass
240
960
85
340
Tall grass
110
440
36
144
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Table 51: Estimated Environmental Concentrations on Avian and Mammalian Food Items
fnnml
Food Items
EEC (ppm) Max.
Residue
EEC (ppm)
Mean Residue
1 lb
ai/acre
41b
ai/acre
1 lb
ai/acre
41b
ai/acre
Broadleaf plants and small insects
135
540
45
180
Fruits, cods, seeds, and larse insects
15
60
7
28
Granular applications:
EECs for broadcast granular applications are calculated on the basis of mass (in mg) per area
(square foot), corrected for the fraction of the pesticide left on the surface. For unincorporated
broadcast applications, the entire fraction of the pesticide is assumed to remain on the surface. The
label for granular formulation prescribes adjusting the desired application rate by the fraction: band
width (inches) / row spacing (inches).
6. Ground Water Monitoring Data
The following studies provided ground water monitoring data that were used to develop the
water resource and aquatic exposure assessments for alachlor.
a. Introduction
Ground-water monitoring data collected, since 1991, by the USGS and the Acetochlor
Registration Partnership (ARP) have found alachlor parent in two to eight percent of ground-water
wells sampled. Up to 1.5 percent of these wells were found to have alachlor residues above the MCL
of 2.0 |ig/L. These recent monitoring data are in agreement with earlier studies, such as those
reported in Pesticides in Ground Water Data. The maximum and minimum alachlor concentrations
were 15.89 |ig/L and 0.05 |ig/L, respectively.
Monitoring data collected by the USGS (Kolpin and Goolsby, 1995; Kolpin et al., 1995;
Kolpin et al., 1996) also indicates that in addition to alachlor, more than 40 percent of the wells
sampled in Midcontinental US were contaminated with alachlor ESA degradate and/or 16 percent
were contaminated with the alachlor 2,6-diethylaniline degradate. There are no ground water
monitoring data on the other two major degradates (alachlor oxanilic acid and sulfinylacetic acid).
These results correspond with the fate data, which indicate that these alachlor degradates are more
mobile and persistent than the parent compound.
These recent studies reflect that current alachlor use may still result in ground water
concentrations which exceed the LOCs for alachlor parent as detections have occurred which exceed
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the current MCL of 2.0 |ig/L. Since a much greater proportion of ground water wells are impacted
by alachlor degradates, if an MCL or cancer risk level is established for alachlor ESA at the same
level as alachlor parent, concern would be much greater than for the parent compound only.
Similar chemicals, acetochlor, metolachlor, and propachlor, have also been found in ground
water. Approximately, the same percentage of wells have been found to be contaminated by
propachlor (1.2%) as alachlor (1.8%), although many fewer wells have been analyzed for propachlor.
Although the number of wells sampled for metolachlor and alachlor are similar, there are
approximately twice as many wells with detections of alachlor (1.8%) residues then metolachlor
(0.96%). Acetochlor, with a maximum of 2.17 |ig/L, was detected in eight wells (4.6%) of 173 in
the registrant's ground-water monitoring study.
Detections of alachlor degradates in ground water are important because ground water may
represent an important means of exposure. Four major degradates have been identified for alachlor:
alachlor DM oxanilic acid, alachlor sulfinylacetic, alachlor sulfonic acid (ESA), and alachlor oxanilic
acid. As noted above, the four degradates are more persistent than the parent compound. Batch
equilibrium studies were previously requested on the degradates to assess their mobility. The
registrant has proposed using adsorption data from two propachlor degradates as surrogate data for
the alachlor degradates. This is acceptable for two degradates, but will still require the determination
of the mobility for the alachlor ESA degradate.
b. Recent Groundwater Monitoring Data
USGS Midcontinent Ground Water Monitoring Studies:
In 1991, the USGS sampled 303 wells from a reconnaissance well monitoring network in
near-surface aquifers distributed across 12 Midwestern states. (Kolpin et. al., 1995) These wells
were distributed geographically and hydrogeologically by state, aquifer class (unconsolidated vs
bedrock), and relative depth. At least 25% of the land within a 3.2 km radius of the well was in corn
or soybean production during the 1990 growing season. One hundred wells were resampled during
1992 by selecting wells using a stratified random design based upon State and aquifer class.
The USGS found that five of the six most frequently detected pesticide compounds detected
in ground water of 12 Midwestern states were pesticide metabolites. Kolpin et. al. (1996) also
demonstrated that as the analytical reporting limits are decreased, there is an increase in the
differences in frequencies of detections. Alachlor ESA is reported almost 10 times more frequently
than parent alachlor at the 0.05 |ig/L level.
Alachlor was detected in 6 wells (2%) out of 303 wells in 1991 and 5 wells (5%) out of 100
wells in 1992 in near-surface aquifers in 12 Midwestern states (Kolpin et. al., 1995). The alachlor
reporting limits were 0.05 and 0.002 |ig/L for 1991 and 1992, respectively. Alachlor ESA was the
most frequently detected compound in 1992. It was found in 33 wells (45%) of 73 wells for which
the degradates were analyzed, with a reporting limit of 0.10 |ig/L. In the same study, metolachlor
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was detected in 12 wells (4%) out of 303 in 1991; and, 11 wells (11%) out of 100 in 1992, with the
same reporting limits as stated for alachlor.
Additional samples were collected in 1993 (110 wells) and 1994 (38 wells) from
unconsolidated aquifers (Kolpin et al., 1996). Alachlor was detected in 10 wells (3.3%) out of 303
wells. Alachlor parent was found in 5.9% of the 153 wells for which metabolites were analyzed. The
maximum alachlor concentration detected was 4.27 |ig/L, with a reporting limit of 0.05 |ig/L.
Alachlor ESA was found in 70 wells (45.3%) of 153 wells analyzed for degradates. The maximum
concentration of alachlor ESA was 8.63 |ig/L, with a 0.10 |ig/L reporting limit. A second alachlor
degradate, 2,6-diethylaniline, was also detected in 15 wells (16%) of 94 wells analyzed. The
maximum concentration was 0.02 |ig/L with a reporting limit of 0.003 |ig/L.
Atrazine degradates deisopropylatrazine (10% of 303 well; maximum concentration of 1.17
|ig/L) and deethylatrazine (22.8% of 303 wells; maximum concentration 2.20 |ig/L) were also
detected. Metolachlor was also detected at levels above 0.05 |ig/L in 8 wells {2.1%) out of 300
(Goolsby et. al., 1995).
Table 52: Summary of Wells with Detections of Alachlor ESA
Study
Number of Wells
Concentrations (|ig/L)
Sampled
Detected
Percent
Detected
Maximum
Concentration
Reporting
Limit
USGS 1992
73
33
45%
_
0.1
USGS 1993
153
70
45.3%
8.63
0.1
USGS 1994
38
25
65.8%
8.6
0.1
USGS-IOWA
1995
106
69
65.1%
14.78
0.1
Wisconsin 1993
vulnerable wells
293
206
70%
26.7
(ave. = 4.89)
1.01
1 Analyzed by immunoassay
Acetochlor Registration Partnership Ground Water Monitoring Program f ARP-GWMP):
As a requirement for the registration of acetochlor, the two acetochlor registrants are
conducting a ground-water monitoring program in seven major use states. Analytes are parent (no
degradates) alachlor, acetochlor, atrazine, dimethenamid, and metolachlor (only the first three were
reported). Ground-water samples are collected monthly from 175 wells located in corn producing
areas. The annual report from the first year of monitoring (only for acetochlor, alachlor, and atrazine)
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covers the 13-month period, from December 1994 to December 1995. The limits of detection and
quantification for all analytes are 0.03 |ig/L and 0.05 |ig/L, respectively.
The text of the annual report indicates that alachlor was detected in 45 samples (2.6%) out
of 1720 (27 of which were greater than 0.1 |ig/L). Acetochlor residues were detected in 25 of 1720
samples (15 of which were greater than 0.1 |ig/L) and atrazine was detected in 651 samples (427
were greater than 0.1 |ig/L) out of 1720.
Results for the three pesticides are summarized in Table 53 below. Fourteen of the wells had
alachlor detects greater than limit of quantification (LOQ - 0.05 |ig/L), six wells had detections of
acetochlor above the LOQ, and 75 wells had atrazine detections above the LOQ. Twenty-seven wells
had alachlor detections above the limit of detection (LOD) of 0.03 |ig/L, 93 wells had detections of
atrazine above the LOD, and eight wells had acetochlor levels above the LOD.
Two of the fourteen wells with alachlor detections had detections on more than one sampling
date. One of these wells was located in Illinois. The first detection of alachlor for this well (May
1995) was also the greatest (13.05 |ig/L) concentration. Alachlor concentrations in this well declined
with time, reaching 0.42 |ig/L by December 1995. The second well with multiple detections was
located in Kansas. The first detection (0.3 |ig/L) was reported in March 1995. The highest
detections for this well occurred in May 1995 (14.17 |ig/L) and June (15.89 |ig/L) and then generally
declined, reaching 3.64 |ig/L by December 1995. Seven other wells also had alachlor detections in
March 1995. According to the registrant, these detections in Kansas and Illinois are linked to surface
runoff and ponding near the wellhead rather than leaching. New wells were installed, and follow up
sampling indicates that the underlying aquifers are not contaminated with alachlor.
Table 53: Detections and Concentrations (in |ig/L) of Acetochlor, Alachlor, and Atrazine in
Study Conducted by the Registrants of Acetochlor.
Statistic
Acetochlor
Alachlor
Atrazine
Number of Samples with
Detects >0.05 |ig/L (% of
samples)
18 (1.0)
30 (1.7)
539 (31.3)
Number of Wells
(%of 173)
8 (4.6%)
14(8.1%)
75 (43.4%)
Number of Samples1
1720
1720
1720
Mean
0.39
3.38
0.75
Standard Deviation
0.52
4.89
5.88
Minimum
0.06
0.05
0.05
1st Quartile
0.11
0.12
0.11
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Table 53: Detections and Concentrations (in |ig/L) of Acetochlor, Alachlor, and Atrazine in
Study Conducted by the Registrants of Acetochlor.
Statistic
Acetochlor
Alachlor
Atrazine
Median
0.25
0.73
0.24
3rd Quartile
0.38
5.06
0.56
Maximum
2.17
15.89
131.532
1 It was not possible to c
etermine whether data identified as missing were no data or below
detection limit.
2 The next highest value for atrazine was 30.03 |ig/L.
Alachlor. Metolachlor and Propachlor in the Pesticides in Ground Water Data Base:
The Pesticides in Ground Water Data Base (PGWDB) (USEPA, 1992) reports that alachlor
was detected in 25 states, in 467 wells of 25933 sampled (1.8%). Of the wells with detections 99
wells (0.4%) had concentrations above the MCL. The PGWDB reported propachlor detections in
33(1.2%) wells [in five states] out of 2718 wells sampled in eleven states. The concentrations ranged
from 0.02 to 3.5 |ig/L, thus the maximum concentration exceeded the MCL of alachlor (2 |ig/L), but
not the Lifetime Health Advisory (HAL) for propachlor (90 |ig/L).
The PGWDB also summarizes a number of studies which included metolachlor. Metolachlor
has been analyzed for in 29 states and detected in 20 states. Detections occurred in 213 (1%) wells
out of 22,255 wells sampled, with concentrations ranging from 0.02 to 157 |ig/L. Three exceeded
the lifetime Health Advisory (LHA) of 70 |ig/L for metolachlor, but typically appear to less than 10
Hg/L.
Table 54: Summary of Alachlor, Metolachlor, and Pi
from the Pesticides in Grounc
ropachlor Ground Water Monitoring Data
Water Data Base
Detection
Information
Alachlor
Metolachlor
Propachlor
Number of Wells (Percent of Wells)
MCL or HAL (|ig/L)
2
70
90
> MCL
99 (0.38)
3 (0.01)
0 (0.00)
< MCL
368(1.42)
210(0.94)
33(1.21)
Total Detections
467(1.80)
213(0.96)
33(1.21)
Total Sampled
25993
22255
2718
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Table 54: Summary of Alachlor, Metolachlor, and Pi
from the Pesticides in Grounc
ropachlor Ground Water Monitoring Data
Water Data Base
Detection
Information
Alachlor
Metolachlor
Propachlor
Number of Wells (Percent of Wells)
Number States with
detections
25
20
5
Number of States with
monitoring
35
29
11
Range of concentrations
(mb/L)
trace to 3000
0.001 to 157
0.02 to 3.5
National Pesticide Survey fNPS):
The EPA National Pesticide Survey (USEPA, 1990) was conducted to provide a statistical
estimate of the frequency and concentration of pesticide contamination of drinking water wells in the
United States. From April 1988 to February 1990, EPA collected water samples and well information
from over 1300 community water systems and rural domestic drinking water wells. Based on these
data, EPA estimated that alachlor contamination occurred at or above the detection limit in about
3,140 (0.03 percent) of rural domestic wells nationwide. The detection limit for alachlor was 0.5
|ig/L which likely resulted in the lower frequency of detection reported for alachlor compared with
other studies. Alachlor was not found in samples collected from community water supply wells.
Also, degradates of alachlor were not analyzed in the NPS.
National Alachlor Well Water Survey (NAWWS):
From 1987 - 1990, at the request of the EPA, Monsanto conducted the National Alachlor
Well Water Survey (NAWWS), a large-scale retrospective monitoring study patterned after EPA's
National Pesticide Survey of drinking water wells. (MRID Nos. 41400001, 41400002, 41400003,
41400004) This study was statistically designed to estimate the proportion of rural domestic wells
in alachlor use areas with detectable concentrations of alachlor (Holden et al., 1990, 1992).
Monsanto also chose to include atrazine, cyanazine, metolachlor, and simazine as analytes in the
NAWWS. The limit of detection for most chemicals (including alachlor) was approximately 0.03
|ig/L. No degradates were analyzed in this study.
Wells selected for the NAWWS study were located in the rural portion of 89 counties, in 26
states where alachlor was used in 1986. Wells were selected based on county-level sales information
and vulnerability estimates in counties where corn, soybeans or peanuts were grown. A total of 1430
private rural wells were sampled. Alachlor was estimated to have been used within a half-mile of 58.8
percent of the wells during the last five years. Hydrogeologic characteristics of the aquifers sampled
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were not directly measured; however, the probability that a well was installed in a confined (less
vulnerable) or unconfined (more vulnerable) aquifer was estimated by Monsanto. Nearly one-third
of the wells sampled were estimated to tap surficial, "vulnerable" aquifers. Over one-half of the wells
were located within 300 feet of surface-water sources (e.g. streams or ponds).
Alachlor detections were reported in nearly one percent of the wells sampled in the NAWWS
(Holden and Graham, 1992). Based on the monitoring results (summarized in Table 55), alachlor
was estimated to occur in 0.78 percent (46,800 wells) of the six million private, rural domestic wells
in the alachlor use area. Wells in the study area are estimated to supply drinking water to
approximately 20 million people. Alachlor was estimated to occur at levels exceeding the MCL of
2 |ig/L in about 0.02 percent of private rural drinking water wells in the alachlor use area, or about
1,200 wells.
Table 55: Estimated Percentage of Wells with Detections of Alachlor from the National
Alachlor Well Water Survey (NAWWS).
Concentration (|ig/L)
Percentage of wells
with alachlor
estimated number
of wells1
standard error
(percent of wells)
>0.03
0.78
46,800
0.29
0.1
0.36
22,000
0.22
0.2
0.32
19,000
0.20
0.5
0.06
3,600
0.03
1.0
0.03
1,800
0.02
>2.0
0.02
1,200
-
1 estimated by EPA, based on total rural domestic water wells in the alachlor use area (6,000,000
wells).
USGS Ground Water Study in IOWA (\995):
The USGS, University of Iowa Hygienic Laboratory, and the Iowa Department of Natural
Resources have been involved in a joint program to monitor municipal wells in Iowa since 1982,
known as the Iowa Ground Water Monitoring Program (IGWM). In the summer of 1995, the USGS
sampled 106 municipal wells, representing the maj or aquifer systems in the state in order to determine
the occurrence of selected herbicide compounds (Kolpin and Kalkhoff, 1996). All samples were
analyzed for alachlor and alachlor ESA, with a reporting limit of 0.05 |ig/L for all analytes.
Alachlor was detected in 7.5 percent of wells in the network, with a maximum of 0.63 |ig/L.
Alachlor ESA was the most frequently detected compound, found in 65.1 percent of wells, at a
maximum concentration of 14.78 |ig/L. Consistent with other studies, alachlor ESA was detected
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almost 9-times as frequently as parent alachlor. Factors found to influence the frequency of detection
of both parent and degradates were: well depth, water age, dissolved oxygen content, and aquifer
type. Both parent and degradates are found much more frequently in shallow wells (defined as <50
meters deep), in post-1953 age water, and under reducing conditions. Alluvial and bedrock/karst
aquifers had the most frequent incidence of pesticide detections in this study.
Wisconsin DATCP Alachlor Study:
Following the reports of alachlor ESA in ground water in Ohio in 1993, Wisconsin's
Department of Agriculture Trade and Consumer Protection (DATCP), with the assistance of
Monsanto, began testing monitoring wells and private water supply wells for alachlor ESA in the
summer of 1993. Results indicated that alachlor ESA was present in a large number of samples, and
it was decided to include alachlor ESA in a Wisconsin survey of private wells most at risk. Wells
were selected in an area of high alachlor use from wells that had previous detections of triazine
herbicides or high concentrations of nitrate. The program was designed to indicate whether or not
a problem existed with alachlor or alachlor ESA in wells most at risk. Alachlor was detected in 12
of the 293 samples (4 percent) at concentrations ranging from 0.21 - 6.91 |ig/L. Alachlor ESA was
detected in 206 of 293 samples (70 percent) at concentrations ranging from 1.09 - 26.7 |ig/L. In part
because of these results, the State of Wisconsin established an interim health advisory (20 ppb) and
is considering proceeding to establish an enforcement standard for alachlor ESA.
State of Florida Monitoring Program:
Prior to the ban on the use of alachlor in the State of Florida, Monsanto conducted a ground-
water monitoring study for alachlor in conjunction with the Florida Department of Agriculture and
Consumer Services (FDACS). The main focus of this study was the monitoring of alachlor in open
hole bedrock wells in Jackson County, in northern Florida. After confirmed detections of alachlor
were reported in 13 of 100 wells, the sampling was expanded to include 310 wells in 10 counties.
Alachlor was detected in 189 samples, from 46 (15 percent) of 310 wells during sampling
from July 1989 to May 1990. Reported concentrations ranged from trace levels to 135 |ig/L in a well
in Levy county. This high concentration is above the child one-day health advisory for the chemical,
which is 100 ppb. Concentrations in that particular well above the 100 ppb level were still detected
after 18 months. This pattern (persistent high concentrations of alachlor) was observed in many wells
with lesser concentrations although still above the MCL. FDACS stated that although Jackson
County is underlain by karst limestone, these conditions were not found throughout the 10 county
area where alachlor was detected. The State of Florida does not consider the detections in this study
to be the result of point-source contamination.
State of New York- Suffolk County:
From 1990 to 1992, the Suffolk County Department of Health Services (SCDHS) analyzed
private wells near a plant nursery for alachlor residues. Alachlor was detected in 14 of the 63 wells,
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11 of which had at least one detection equal to or greater than the 2.0 ppb MCL. The highest
concentration detected was 49 |ig/L. Subsequent sampling of 92 wells near plant nurseries resulted
in a single detection of alachlor at 0.6 |ig/L.
The SCDHS did not find any evidence to suspect point source contamination. In their
response to the 1996 draft, the registrant indicated that they suspect that point source contamination
may have occurred. It is indicated that subsequent monitoring has shown that levels in most wells
are dropping below the MCL.
State of North Carolina:
The University of North Carolina-Asheville Environmental Quality Institute (EQI) conducted
a study from 1989 to 1992 to gather information on the spatial distribution of pesticides in rural water
supply wells in eastern North Carolina (Maas et. al., 1995). Alachlor was one of eight chemicals
investigated, with a method detection limit of 0.13 |ig/L. Samples were collected from 171 sites,
which corresponded to individual wells. Alachlor was detected at 8.8 percent of the 171 sites, with
concentration that ranged from 0.23 to 68 |ig/L. Five of the detections were above the 2.0 ppb MCL.
Multiple samples were collected over approximately a year and a half. Results indicated that alachlor
contamination was not a seasonal phenomenon, but persists over longer periods of time in eastern
North Carolina. Two of three wells that were re-sampled maintained levels of alachlor above the
MCL for over a year. The third had an initial detection at 0.3 |ig/L, declined to below the detection
limit a half year later, increasing again to above the MCL one year after the original sampling.
The EQI study concluded that the majority of detections of alachlor encountered in the study
appeared to be the result of normal agricultural use. Only one of the wells was located near a
pesticide mixing area (within 100 feet).
The study authors reported that alachlor detection was not significantly related to distance
from pesticide mixing, storage and loading areas suggesting that the observed groundwater
contamination was not a result of point sources. The authors also found that alachlor was detected
in wells more frequently further from cropped fields, and that the compound was detected in areas
that had received no application for at least several years. These data were interpreted as showing
that the detected alachlor came from a great distance from the well or from applications in the distant
past. The authors concluded that well water contamination was not a seasonal phenomenon but
persists over time.
The Interagency Study of the Impact of Pesticide Use on Groundwater in North Carolina was
conducted in 1991-1996 (Wade et. al., 1997). In phase I of this study 55 wells representing the
state's major drinking water aquifers were sampled at least twice and analyzed for pesticides. No
attempt was made to select these wells where pesticides were known to have been used. In phase
II, 97 shallow monitoring wells were installed and sampled at least twice. Phase II wells were located
in areas believed to represent the highest risk, and were adjacent to or down gradient from areas of
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pesticide application. When pesticides were detected in phase II wells additional sampling was done
from nearby domestic supply wells. Forty-six domestic supply wells were sampled in this phase.
Alachlor was not detected in phase I or phase II wells. Alachlor was detected in two domestic
supply wells near phase II wells that had other pesticides detected. One of the wells with alachlor
was a "shallow bored well" located within an agricultural field and had been used to fill spray
equipment. Two other domestic wells within 0.5 miles did not have detectable pesticides. The other
well with alachlor detected was a "bored well of unknown depth" located 100 feet from corn field
on an adjacent farm. Alachlor was detected in this well at two separate sampling events at 9.2 ppb
and 5 ppb. Three other monitoring and domestic wells near this well did not have detectable alachlor.
Continued sampling following completion of the study by the North Carolina Department of
Agriculture has not detected additional alachlor groundwater contamination. However, the alachlor
degradation products, including alachlor ESA, have been detected in groundwater at concentrations
ranging up to 22 ppb. (H. Wade, Personal communication, 1998)
c. Possible Concerns
Since the degradation of alachlor appears to be much slower in aquifers than in the soil root
zone and since alachlor ESA is reported more frequently than alachlor in ground water, (Kolpin et
al., 1996) concluded that the degradation of alachlor occurs prior to being transported to the aquifer.
They theorize that if alachlor degradation occurred after reaching the aquifer, the frequency of
detections of alachlor and alachlor ESA would be more similar. They also report that alachlor ESA
appears to be persistent in shallow aquifers, because 90 percent of the wells having alachlor ESA
concentrations exceeding 0.10 |ig/L remained at that level during all subsequent samples (1-year time
interval). If an MCL or cancer risk level is established for alachlor ESA at the same level as alachlor
parent and because of the much higher percentages of wells having degradate detections, the concern
for the population being exposed to levels of alachlor exceeding levels of concern is much greater
than for the parent compound only.
Irrigation appears to increase the probability of contaminating ground water. The frequency
of herbicide detection (35%) with irrigation within a radius of 3.2 km was greater than the frequency
of herbicide detections (19%) without irrigation (Kolpin and Goolsby, 1995).
7. Surface Water Monitoring Data
The following studies provided surface water monitoring data that were used to develop the
water resources and aquatic exposure assessments for alachlor.
a. Introduction
Alachlor can contaminate surface water at application via spray drift. Substantial fractions of
applied alachlor could also be available for runoff for several weeks post-application. The relatively
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low soil/water partitioning of alachlor indicates that most of alachlor runoff will occur via dissolution
in runoff water (as opposed to adsorption to eroding soil).
b. Surface Water Data
Acetochlor Registration Partnership Data for 1995-1996:
This study is the most extensive data on alachlor concentrations in finished surface drinking
water available to the Agency. (MRID No. 44592401) Samples were collected at 179 different sites
(drinking water utilities) in the following 12 states: Delaware, Illinois, Indiana, Iowa, Kansas,
Maryland, Minnesota, Missouri, Nebraska, Ohio, Pennsylvania, and Wisconsin. Samples were
collected approximately once every two weeks from April through early September. Two to three
additional samples were collected at most sites, one to two in the Fall and one in the Winter.
Unfiltered samples were analyzed for total alachlor.
A TWMC was estimated by the Agency for each monitoring site in the ARP. These sites
were then ranked from highest to lowest. Based on the reanalysis of data covering 1995 and 1996,
Table 56 provides maximum and 90th percentile (upper 10th percentile) concentrations (peak and
annual TWMC).
Table 56: Summary of 1995 and 1996 Alachlor Monitoring by the ARP
Statistic
Calculation for a given
site
Summary Across Sites
Maximum Value
for any Site (|ig/L)
Value Equaled/Exceeded
on 10% of Sites (|ig/L)
Peak
Concentrations
Highest Value Observed
1995-1996, for any Site
4
0.63
Annual Time
Weighted Mean
Weighted Mean for
1995-1996, for any Site
(weight by time)
0.36
0.1
USGS 1989. 1994. and 1995 Midwestern Stream Reconnaissance Studies :
Since the data submitted by the Acetochlor Registration Partnership was for samples collected
at set intervals once every two weeks, it is probable that the data are generally substantially lower
than peak alachlor concentrations associated with post-application runoff events. Such peak alachlor
concentrations are probably more closely represented by post-application data collected by the USGS
in reconnaissance studies conducted on numerous Midwestern streams. The USGS (Goolsby and
Thurman, 1991; Goolsby, 1995; Goolsby, 1996) conducted reconnaissance surveys of numerous
Midwestern streams in 1989, 1994, and 1995 to determine post-application, and in some cases pre-
application and Fall concentrations of various herbicides including alachlor. Pre-application samples
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collected in 1989 and 1994 and Fall samples collected in 1989 had alachlor concentrations much less
than 1 |ig/L, and generally below the detection limit of 0.05 |ig/L.
Since post-application samples were generally collected during the first major runoff event
after application, the concentrations in those samples should more closely represent peak alachlor
concentrations. The maximum post-application alachlor concentrations for 1989, 1994, and 1995
were 51.3, 10.1, and 19.9 |ig/L, respectively. The 90th percentile (upper 10th percentile) post-
application alachlor concentrations for 1989, 1994, and 1995 were 12, 6.5, and 2.0 |ig/L,
respectively. The substantially lower concentrations in 1994/1995 than in 1989 may reflect reported
decreases in alachlor use.
In 1989, a pre-application sample, a post-application sample, and a Fall sample were collected
from 48 of the sites. The maximum and 90th percentile (upper 10th percentile) annual TWMCs were
11.6 and 3.4 |ig/L, respectively. Annual TWMCs based on 4 quarterly samples (as specified to
determine compliance with the Safe Drinking Water Act) probably would have been somewhat lower
(but not more than 25% lower).
In 1994 and 1995, samples were analyzed for alachlor ESA as well as alachlor. Alachlor ESA
concentrations are much higher than alachlor. This also appears to be true in early spring even before
alachlor application.
USGS 1991-1992 Study of 8 River Locations Mississippi River Basin:
The USGS (Coupe et. al., 1995) sampled 8 locations on rivers within the Mississippi Basin
from April 1991 through March-September 1992 (depending on location) and analyzed the samples
for numerous insecticides and herbicides including alachlor. Samples were collected twice per week
from May 6 to July 15 1991, once per every two weeks from November 1991 to February 1992, and
once per week at other times. The samples were filtered (0.7 |i) and analyzed for dissolved alachlor.
The maximum peak and 1991 annual time weighted mean concentrations over the 8 sites were 3.6
|ig/L and 0.43 |ig/L, respectively (both in the Platte River at Louisville, NE).
For three sites (with the highest 1991 alachlor concentrations) pre-application concentrations
of less than 0.1 ppb in early spring rapidly increased to several ppb during post-application runoff
events in May and June, then rapidly declined to background levels by mid-late summer. The White
River at the Hazelton, IN site was the only one of those three sites at which sampling was performed
far enough into 1992 to give a second set of alachlor peaks (1992) in addition to the 1991 set.
Alachlor concentrations in 1992 were lower than in 1991 at that site.
USGS 1992 Midwestern Reservoir Reconnaissance Study:
The USGS (Goolsby et. al., 1993) sampled each of 76 Midwestern reservoirs four times
during 1992 and analyzed them for various herbicide degradates and herbicides including alachlor and
alachlor ESA. Alachlor was detected above a detection limit of 0.05 |ig/L in 36%, 48%, 26% and
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16% of the samples collected in late April to mid-May, late June to early July, late August to early
September and late October to early November, respectively. Alachlor ESA was detected more
frequently (72, 79, 77, and 64%) and at higher concentrations than alachlor. The highest alachlor and
alachlor ESA concentrations were for samples collected in June or July of 1992. The maximum and
95th percentile alachlor concentrations for June-July over the 76 reservoirs appear to be between 5
and 10 |ig/L. The maximum and 95th percentile alachlor ESA concentrations for June-July appear
to be between 10 and 20 |ig/L. After June-July, alachlor concentrations appear to decrease more
substantially than alachlor ESA concentrations.
Missouri River Public Water Supplies Association 1990 Study:
The Missouri River Public Water Supplies Association (MRPWSA) sampled the raw water
of 8 surface water supplies within the Missouri River Basin. (Keck 1991) Samples were collected
daily May-July 1990. The maximum peak and May-July mean concentrations were 14.9 and 0.47
ug/L, respectively (both at Kansas City, MO). However, the second highest peak and May-July mean
concentrations were 2.9 and 0.29 |ig/L, respectively.
State of Illinois 1986-1988 Study:
The State of Illinois (Moyer and Cross, 1990) collected 4-7 samples per year from each of
30 flowing surface water sites during 1986-1988 and analyzed the unfiltered samples for numerous
pesticides including alachlor. The maximum alachlor peaks over the 30 sites were 5.6, 8.5, and 18
ug/L for 1986,1987, and 1988, respectively. The maximum alachlor annual TWMCs over the 30 sites
were 0.65, 0.76, and 2.0 |ig/L for 1986, 1987, and 1988, respectively. The maximum three year
TWMC over the 30 sites was 0.81 |ig/L.
The State of Illinois (Taylor, 1994) recently summarized pesticide data for surface water
samples collected from 34 stations from October 1, 1985, through February 15, 1994. Thirty of the
stations were the same ones discussed in the Moyer and Cross 1990 document, but the Taylor
summary represents a update to February 1992. A total of 1278 samples were analyzed for alachlor
at a detection limit of 0.05 |ig/L. Apparently assuming non-detects were equal to the detection limit,
Illinois reported maximum, 95th percentile, 90th percentile, and mean total (unfiltered sample)
alachlor concentrations over the 34 sites and 9 years of 18 |ig/L, 0.90 |ig/L, 0.32 |ig/L, and 0.065
|ig/L respectively.
Monsanto 1986 Finished Surface Water Supply Study:
In 1986, Monsanto sampled 30 finished surface water supply systems approximately weekly
from April through August or September and analyzed the samples for 5 herbicides including
principally alachlor. (MRID No. 40265901) The community water systems sampled represented 4
combinations of Lasso ©(alachlor) use and average soil susceptibility to runoff (high use/high runoff,
low use/high runoff, high use/low runoff, low use/low runoff). The susceptibility to runoff was
estimated from the weighted average of hydrological classifications (A, B, C, D) of soils within the
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drainage area. Of the 30 community water systems sampled, 13, 2, and 15 were classified as using
sources which drain areas with high, intermediate, and low susceptibility to runoff, respectively. The
maximum and 90th percentile (upper 10th percentile) peak alachlor concentrations over the 30
systems were 9.5 and approximately 6.0 |ig/L, respectively. The maximum and 90th percentile (upper
10th percentile) alachlor annual TWMCs over the 30 systems were 1.1 and approximately 0.73 |ig/L
respectively.
Monsanto 1985 Finished Surface Water Supply Study:
In 1985, Monsanto had sampled 24 finished surface water supply systems different from the
ones sampled in 1986. (MRID No. 00158911) They also sampled raw water. Samples were
collected approximately weekly from April 1995 through August or September 1995 and analyzed
alachlor parent only. The community water systems sampled represented areas of high, medium and
low alachlor use.
The maximum and 90th percentile (upper 10th percentile) peak alachlor concentrations in
finished water over the 30 systems were 12 and approximately 4.2 ug/L, respectively. The maximum
and 90th percentile (upper 10th percentile) alachlor annual TWMCs over the 30 systems were 1.5
and approximately 0.62 |ig/L, respectively.
Alachlor has a low soil/water partitioning coefficient. Therefore, the primary treatment
processes employed by most surface water drinking water supply systems are not expected to be
effective in removing it.
USGS 1984-1985 Study on the Cedar River Basin. IA:
The USGS (Squillace and Engberg, 1988) collected samples at 6 locations within the Cedar
River Basin (5 along the Cedar River, and one along the Shell Rock River). Samples were collected
approximately monthly from May 1984 through September 1985 at the Floyd and Cedar Falls
sampling locations, and from May 1984 through November 1985 at the other 4 locations.
Two sets of samples were collected. One set was centrifuged for the determination of the
dissolved concentrations of herbicides. "Total recoverable" herbicide concentrations consisting of
both extractable adsorbed and dissolved herbicides were determined in the sample set not centrifuged.
The maximum peak and annual TWMC concentrations over the 12 site-years were 23 and 3.3
|ig/L respectively. The next highest peak and annual TWMCs were 21 and 1.9 |ig/L, respectively.
The maximum two year TWMC over the 6 sites was 1.7 |ig/L.
Baker 1982-1985 Study on Ohio Tributaries to Lake Erie:
Baker collected samples at various times including several times per week from mid-April to
mid-August from 8 Ohio tributaries to Lake Erie during 1982-1985 and analyzed them for many
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pesticides including alachlor. (MRID No. 41065205) Alachlor Peak and 4/15-8/15 TWMCs
concentrations were reported.
The maximum and 90th percentile (upper 10th percentile) peak alachlor concentrations over
the 30 site-years are 76 and 32 |ig/L, respectively. The maximum and 90th percentile (upper 10th
percentile) 4/15-8/15 TWMCs over the 24 site-years are 3.3 and 2.7 |ig/L, respectively.
Baker 1983-1987 Lake Erie Basin Case Study
The Water Quality Laboratory at Heidelberg College, Ohio (Baker et. al., 1991) sampled
seven Ohio streams and rivers of the Lake Erie Basin for a number commonly used herbicides and
insecticides, including alachlor. Samples were collected and analyzed at frequent intervals (daily)
during the pesticide use period mid-April to mid-August, especially during runoff producing storm
events, and twice per month during the remainder of each year's cycle. Samples were collected at
existing USGS Gaging Stations. Alachlor was detected above the level of detection (0.1 ug) at all
sampling stations in all years during the study. Alachlor peak and time weighed mean concentrations
(TWMC) were reported.
The maximum peak concentration over the five-year study of 91.47 ug/L (n=410) occurred
in the smallest basin, Lost Creek. The maximum TWMC over the study period of 1.74 ug/L (n=534)
occurred in Honey Creek basin, the third smallest basin, but the second highest in agriculture
intensity.
Kirbv-Smith 1987-1991 Study on the South River Estuary North Carolina:
In a study of effects of pesticides on marine and estuarine aquatic biota from farmland runoff,
alachlor was monitored in several headwater streams of the South River in the Pamlico Sound, North
Carolina. (MRID No. 441095503) Data collected during the conduct of this study provided
valuable information on the concentrations of alachlor in estuarine waters from known pesticide
applications.
Dissolved alachlor concentrations increased from background (residual) levels of
approximately 0.019 |ig/L to a maximum of 48 |ig/L following pesticide applications and significant
rainfall. Alachlor concentrations rapidly decreased to less than 1 |ig/L following the termination of
pesticide applications and after several runoff producing rain events had occurred. Eventually,
concentrations returned to background level, although specific timing could not be determined from
the submitted study.
c. Possible Concerns over Alachlor and Alachlor ESA in Surface
Water
According to available data, the potential risks to fish and aquatic invertebrates posed by
alachlor in surface water are low. Potential risks to aquatic plants posed by alachlor are currently
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being assessed by the Agency. The potential risks of alachlor ESA to fish, aquatic invertebrates and
aquatic plants has not been well characterized.
In analyzing surface water concentration data, the Agency considers the frequency that annual
averages exceed the drinking water MCL (for alachlor, 2 |ig/L), and the frequency that peak
concentrations exceed the MCL by a factor of 4 or more: Compliance with the Safe Drinking Water
Act is based on comparison of the MCL to an arithmetic average of four quarterly measurements.
Consideration of 4 times the MCL (4MCL) is of interest because if one or more of four measurements
exceeds 4MCL, then the average of the measurements exceeds the MCL.
Originally, most of the Agency's concern over alachlor in drinking water was due to individual
alachlor measurements frequently exceeding 4 times the MCL. The frequency of exceedances of
4MCL was greatest in the 1989 USGS reconnaissance study in which samples were collected during
major runoff events following application, and in the study by Baker (1988), in which samples were
apparently collected at least 3 times a week and not time composited. They were less frequent in the
1994 and 1995 USGS reconnaissance studies (which were also designed to capture peak
concentrations) possibly due to decreases in alachlor use.
With the exception of 2 site-years in the 1984-1985 USGS study of the Cedar River Basin and
one site-year in the 1986-1988 Illinois EPA study, none of the annual TWMCs for alachlor exceeded
the MCL of 2 |ig/L. This includes the 1985-1986 Monsanto studies of drinking water supplies and
the recent 1995 Acetochlor Registration Partnership study of 175 sites over 12 states. In that study,
the maximum annual TWMC was 0.4 |ig/L. Although the study used set sampling intervals that may
often miss peak concentrations associated with runoff events, the once every two weeks sampling
from April through September and the Fall and Winter samples (a total of 14/site) is much more than
the 4 quarterly samples required under the SDWA. Again, the relatively low alachlor concentrations
compared to some earlier studies may reflect substantial decreases in alachlor use.
8. Water Resource Assessment
a. Ground Water Assessment
Alachlor exhibits the properties associated with chemicals that are found in ground water.
The chemical has a high solubility and mobility in soils. Once the chemical reaches deeper soil layers
with lower organic matter content and lower microbial populations, it will persist. An independent
study conducted for EPA indicates that alachlor half-lives at different depths in a sandy loam and a
silt loam soil increased to about 250 to 600 days at a depth of 5 feet (Lavy et al., 1993). Alachlor
has been found to leach in the field at soil depths of up to 36- to 48-inches (the deepest layer
sampled). Considering the nature of the chemical (i.e., moderately persistent and very mobile in many
soils), there is a strong possibility of movement to ground water, especially in vulnerable areas. This
has been confirmed by a substantial number of detections reported in the "Pesticides in Ground Water
Database," and in the National Alachlor Well Water Survey conducted by the registrant, from which
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EPA determined that alachlor residues have had a significant impact on ground-water quality
throughout the use area.
Several sources of information on monitoring/detections of alachlor and alachlor metabolites
in ground water are reviewed in this document. That information confirms that alachlor and alachlor
degradates will move into ground water. These monitoring data are summarized in Table 57.
Tab
e 57: Summary of Wells with Detections of Alachlor (Parent).
Study
Well type
Number of Wells (%)
Sampled
Alachlor
Detected
Concentration
MCT
USGS
(1991-1994)
drinking
303
10(3.3%)
9(3.0%)
1 (0.3%)
ARP-GWMP
monitoring
173
27
(15.6%)
25 (14.5%)
2(1.2%)
PGWDB
mixed, most
drinking
25933
467
(1.8%)
368 (1.4%)
99 (0.4%)
NPS
drinking
1300
1 (<0.1 %)
0 (0%)
1 (<0.1 %)
NAWWS
drinking
1430
28 (2.0%)
26(1.8%)
2(0.1%)
Florida
drinking
310
46(15%)
North Carolina
drinking
171
15 (8.8%)
10 (5.9%)
5 (2.9%)
PGWDB = Pesticides in Ground Water Database,
NPS = National Pesticide Survey;
NAWWS = National Alachlor Water Well Survey,
USGS = U.S. Geological Survey Midcontinent Study,
ARP-GWMP = Acetochlor Registration Partnership Ground-Water Monitoring Program.
Persistence of Alachlor in Ground Water:
Ground-water monitoring studies have shown that alachlor contamination is common in use
areas. Recent data suggests that alachlor can persist in the subsurface for years and that ground water
contamination can be expected long after use has stopped. Maas et. al. (1995) found evidence that
low concentrations of alachlor in drinking water wells persisted over long periods, and contamination
can move off-site via transport in ground water. In Florida, significant alachlor contamination still
occurs years after all alachlor use was canceled in February 1991. Sixteen wells found to have
alachlor at concentrations greater than 2.0 ppb prior to the ban have been sampled yearly since 1991.
The mean alachlor concentrations in these wells have not changed over time (Simons and Fisher,
1997; R.E. Fisher, personal communication, 1998).
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Alachlor Exposure from Drinking Ground Water:
Results of several studies designed to assess the occurrence of alachlor in drinking water wells
makes it possible to roughly estimate the number of people exposed to the compound by drinking
contaminated ground water. Based on U.S. Census data the National Ground Water Association
(NGWA) estimates that 53% of the American public relies on ground water for their drinking water.
This includes about 282,000 public supply wells and approximately 15.1 million households using
private wells. While there is little evidence of contamination in public supply wells a significant
number of private house hold wells will be contaminated. It is possible that a large number of people
in the U.S. can expect to be exposed to alachlor in their drinking water. Hundreds of thousands of
people living in households supplied by private wells will have alachlor and/or alachlor degradates
in their drinking water as a result of labeled use of the compound. Large numbers of Americans can
expect to have alachlor concentrations above the current Maximum Contamination Level (MCL) of
2.0 ppb in their drinking water as a result of labeled use of the compound. MCLs are established for
public drinking water supplies and are not enforceable for private water supplies. A one-time
detection above the MCL does not necessarily constitute a violation in public water systems or trigger
requirements for mitigation. Such actions are based on average annual concentrations, which is a
time-weighted average of all detections, including the exceedance value, for the entire year. Since
drinking water violations reported by EPA's Office of Water are for public water supplies and are
based on average annual concentrations, the frequency of such exceedances is likely to be less than
the frequency of individual detections above the MCL reported here.
The National Alachlor Well Water Survey (MRLD No. 41400001) was designed primarily to
assess the occurrence of alachlor in rural wells in high alachlor use areas. The study estimated 6
million wells, serving 20 million households, occurred in the alachlor use areas, based on Monsanto's
1986 alachlor sales data. The maj ority of the wells were near agricultural areas, and 40% were within
300 feet of fields where alachlor target crops were grown. Alachlor was detected in 2.0 % (standard
error of 0.25) of sampled wells at measurable concentrations. The survey found 0.18 % (standard
error of 0.12) of the sampled wells had alachlor concentrations above 2.0 ppb. No significant
differences were seen in wells on farm and non-farm properties. Exposure estimates by Monsanto
(assuming a nonlinear distribution for detections, which is reasonable for pollutant data with
asymmetric distributions and a relatively low occurrence of events) suggest that more than 100,000
people in the study area had detectable levels of alachlor in their water supply, 35,000 would be
exposed to concentrations of > 0.2 ppb, and more then 3,000 people would have alachlor
concentrations above 2.0 ppb. Weaknesses in the survey include: (a) the NAWWS use area
underestimated the alachlor use area defined by Resources For the Future, (b) the study was
conducted in a relatively dry year (1988) which would have minimized the potential for leaching, and
(c) the estimates do not include small community wells that serve more than 15 households or more
than 25 people, which may underestimate the total number of people exposed to alachlor in drinking
water (Rappaport, ICF, 1991).
Two studies in North Carolina examined levels of alachlor in drinking water wells (Maas et.
al., 1995; Wade et. al., 1997). NGWA estimates that North Carolina has 912,000 household wells
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and 20,000 public and community supply wells. In eastern North Carolina, 8.8% of drinking water
wells sampled between 1989 and 1992 contained measurable alachlor concentrations and 2.9 % were
above the current MCL of 2.0 ppb (Maas et. al. 1995). This study also found that contamination is
not always confined to wells in or close to fields to which alachlor was applied. Results of the eastern
North Carolina study show a higher percentage of wells with alachlor contamination than that found
in the NAWWS study. This study, conducted primarily within the coastal plain, may reflect potential
exposure in an area in which the ground water is highly vulnerable to contamination from pesticides
(as delineated by Kellog et. al., 1992).
Sampling in Florida found that 9.4 % of drinking water wells were contaminated with alachlor
and 5.5 % had alachlor concentrations above 2.0 ppb (Simons and Fisher, 1997). Most of the well
contamination at high levels may be a result of mixing and transfer operations or other point sources
(R.E. Fisher, personal communication, 1998), and the owners have been provided with water
treatment systems or an alternate supply. In Florida, about 794,500 households are served by private
wells; 16,000 are on public and community supply wells. Concerns about such exposure resulted
in a ban of the use of alachlor in Florida. Since the 1991 ban, average alachlor concentrations in wells
initially found to have levels above 2.0 ppb have not changed, and individual treatment systems are
still required to provide safe drinking water to these households. More than five years after alachlor
use was banned, these wells still show contamination.
Despite the large amount of uncertainty associated with exposure estimates, they provide an
indication of the magnitude of people who can expect to have alachlor in their drinking water. Tens
of millions of Americans rely on domestic wells for their drinking water and the majority of these are
in rural areas. Even if a few wells in any study show significant levels of alachlor contamination, or
only a few percent of wells are contaminated, this is suggestive of a large number of people being
exposed.
There are additional concerns related to contamination of ground water used for drinking
water supply. Alachlor appears to be persistent under aquifer biological and geochemical conditions.
This means that alachlor can appear in ground water years after use and can migrate with ground
water away from use areas. Alachlor contamination has resulted in loss of untreated ground water
as a source of drinking water in Florida and other states. Years after alachlor was banned, the
resource is still degraded.
b. Surface Water Assessment
Alachlor can contaminate surface water at application via spray drift. Substantial fractions
of applied alachlor could be available for runoff for several weeks post-application. The relatively
low soil/water partitioning of alachlor indicates that most runoff will occur via dissolution in runoff
water (as opposed to adsorption to eroding soil). The persistence of alachlor in surface waters with
high microbiological activities should be somewhat limited by its susceptibility to biodegradation.
Persistence will also be limited in waters with short hydrological residence times by flow out of the
system. However, its resistance to abiotic hydrolysis and direct aqueous photolysis, coupled with its
156
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low volatilization potential should make alachlor more persistent in waters with low microbiological
activities and long hydrological residence times.
Alachlor may also enter freshwater, estuaries, and coastal marine water in areas of interaction
with ground water. Presence in fresh surface water of alachlor ES A before application suggests that
there has been input to rivers and streams from ground water.
There is an extensive body of information on levels of alachlor and alachlor degradates in
surface water. Table 58 summarizes the major surface water studies:
Table 58: Summary of IV
ajor Surface Water Sources with Alachlor Detections by Study.
Study
Number of
Sites
Maximum Peak
(ug/L)
Maximum TWMC1
(ug/L)
ARP - 1995-1996
175-179
4.0
0.36
USGS - Midwestern
Stream Recon. 1989
48
51.3
11.6
USGS Mississippi River
Basin Study 1991-1992
8
3.6
0.43
State of Illinois 1986-
1988
30
18
0.81
Monsanto Finished
Surface Water Study
1986
30
9.5
1.1
Monsanto Finished
Surface Water Study
1985
30
12
1.5
USGS Cedar River Basin
Study 1984
6
23
1.7
Ohio Tributaries to Lake
Erie 1982-1985
8
76
3.32
Lake Erie Basin Case
Study 1983-1987
7
91.47
1.74
'TWMC: Time weighted mean concentrations, annual unless otherwise noted.
2 Time weighted mean concentration calculated over a 4 month period of the study; April 15 to
August 15
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The monitoring results primarily reflect residue detections in lotic waters, such as rivers and
streams, or large lentic bodies of water, such as man-made reservoirs and lakes. Therefore the levels
observed may have been affected by dilution, degradation, or adsorption to soil or sediment, relative
to edge-of-field levels (values occurring close to sites of application immediately following runoff
events). Edge-of-field levels may be better represented by modeling. (However, at this time only
screening level modeling has been undertaken.) Also, the model scenarios represent small, static
bodies of water. Reported peak concentrations are affected systematically by the intensity of
sampling: with less frequent sampling there is higher probability of levels in the environment that
substantially exceed the highest values detected.
Of the surface water monitoring data available, the U SGS Midwestern Stream Reconnaissance
Studies (1989, 1994, 1995) give what are probably the values closest to the most extreme edge-of-
field levels. In that study peak exposures were 51.3 |ig/L for 1989, 10.1 |ig/L for 1994, and 19.9
|ig/L for 1995. The 90th percentile values (upper 10th percentile values) were 12, 6.5, and 2.0 |ig/L
for the same years.
c. Alachlor Degradates in Water
The major degradates of alachlor are alachlor DM-oxanilic acid, alachlor oxanilic acid,
alachlor sulfinylacetic acid, and alachlor ethane sulfonic acid (alachlor ES A). While uncertainty exists
concerning the environmental or health effects of these breakdown products, available data suggest
that the degradates are more persistent and mobile than parent alachlor. Limited monitoring data
suggest that alachlor ESA is often found in ground water wells 5-10 times more frequently then the
parent compound. Alachlor ESA has been detected frequently in Midwestern reservoirs and streams
at concentrations much greater than alachlor. High concentrations of alachlor ESA in flowing water
even in early spring, before alachlor application, may reflect discharges from ground water. The
major degradates may be available for runoff longer than alachlor, and will probably be transported
primarily by dissolution in runoff water. The degradates will probably readily partition into the water
column and in addition to alachlor ESA, other degradates may also be more persistent in surface
water than alachlor.
9. Aquatic Exposure Assessment
Preliminary aquatic EECs are estimated using GENEEC (GENeric Expected Environmental
Concentration), a screening model that provides an upper-bound estimate of EECs on a high
exposure site. The GENEEC program uses basic environmental fate values (adsorption to soil,
degradation in soil before runoff and in water) and pesticide label information (rates, intervals,
incorporation, method of application) to estimate the EECs in a one-hectare, two-meter deep pond
following the treatment of a 10 hectare field. The runoff event occurs two days after the last
application. The model accounts for direct deposition of spray drift onto the water body (assuming
5% of the application rate for aerial spray applications and 1% for ground spray applications). Some
of the input parameters used for the alachlor GENEEC runs are listed in Table 59.
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Table 59: Environmental Fate Parameters used to Predict Alachlor EECs
Parameter
Value
water solubility (ppm)
242 ppm
Koc
190
aerobic soil metabolism, tl/2
21 days1
hydrolysis tl/2, pH 7
Stable
aerobic aquatic metabolism, tl/2
175 days
aqueous photolysis tl/2
80 days
'The aerobic soil metabolism half-lives in three studies was 6-21 days.
GENEEC modeling was performed for a range of use scenarios based on combinations of
application rate (1-6 lb ai/acre) that were on the label at the time the modeling was performed.
Ground spray and granular applications were evaluated along with the effects of incorporation. In
addition to scenarios involving a single application, a scenario was evaluated with two 2 applications
of 2 lb ai/acre by ground spray without incorporation, separated by 30 days. On June 30, 1998, new
labels were accepted by the Agency in which the maximum single application rate is 4 lb ai/acre.
Thus, the 6 lb ai/acre rates were eliminated from this discussion.
Peak EECs (representing concentration immediately following runoff) ranged from 33 ppb
for 1 lb ai/A to 133 ppb for 4 lb ai/A. The 56-day average EECs ranged from ranged from 27.4 ppb
to 110 ppb for the same range of application rates.
Table 60: Alachlor Screening Level Aquatic EECs Generated by GENEEC
Application
Rate/Method/Incorporation
Peak
EEC Estimates
4 Days
Over Time (p
21 Days
3b)
56 Days
1.01b Granular/Ground/none
33
32.7
30.7
27.4
2.01b Granular/Ground/none
66.3
65.5
61.5
58.9
4.01b Granular/Ground/none
133
131
123
110
1,251b ai/groundspray/none
39
38
36
32
2.51b ai/groundspray/none
78
77
72
65
3.0 lb ai/groundspray/none
94
93
87
78
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Table 60: Alachlor Screening Level Aquatic EECs Generated by GENEEC
Application
Rate/Method/Incorporation
Peak
EEC Estimates
4 Days
Over Time (p
21 Days
3b)
56 Days
4.01b ai/groundspray/none
125
124
116
104
4.0 lb ai/groundspray/2.0 inch
incorporation
64
63
59
53
2.0 lb ai/A twice
groundspray/no incorp./30 day interval
92
91
85
76
For comparison, of the surface water monitoring data available, the USGS Midwestern
Stream Reconnaissance Studies (1989,1994,1995) give what are probably the closest values to peak
exposures occurring close to application sites soon after application. Peak exposures were 51.3 |ig/L
for 1989, 10.1 |ig/L for 1994, and 19.9 |ig/L for 1995. The 90 th percentiles (upper 10th percentiles)
were 12, 6.5, and 2.0 |ig/L for the same years.
The Agency has reviewed an extensive body of information on levels of alachlor and alachlor
degradates in surface water. This database for alachlor is substantially greater than that available for
most pesticides. These monitoring results primarily reflect residue detections in lotic waters such as
rivers and streams or large lentic bodies of water such as man-made reservoirs and lakes. As such
the data are good indications of what residue levels might be expected after residues have traveled
farther down the watershed. These residue detections are influenced by a number of factors including
dilution by the respective waterbody, time of monitoring, position of monitoring stations, and the
number of measurement samples recorded over time (when averaging sample detection levels). Thus,
this information should be used as an indication of levels which might be expected after dilution,
organic degradation, and soil or sediment adsorption factors have acted on the chemical for the period
of time between application and actual sampling at respective monitoring stations. In many cases,
peak concentrations of alachlor occur during early to late spring months when rainfall events lead to
higher than average runoff. Simple averages of measured concentrations are biased towards
representing those time periods with more samples, a bias that can be eliminated by using TWMCs.
An additional limitation of the monitoring information is the likelihood that some actual
environmental concentrations will exceed the highest levels detected. The chance that a peak
concentration will not be detected is expected to differ among monitoring studies, depending on the
frequency of sampling and on the variability of environmental concentrations.
Tables61 and 62 summarize two studies, one conducted by the US Geological Survey in 1991
and one conducted by the State of Illinois in 1990.
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Table 61: USGS Mississippi
River Basin Survey, 1991-19921
Location Sampled
(24 Samples per location)
Alachlor Concentration (
ig/L)
Peak
Arithmetic
average
Annual
TWMC
White River, Hazel ton, In.
3.2
0.3
0.22
Ohio River, Grain Chain, 11.
0.40
0.08
0.07
Miss. River, near Clinton, IA.
0.85
0.16
0.10
Illinois River, Valley City, 11
3.00
0.40
0.22
Platte River, Louisville, NE
3.60
0.43
0.22
Missouri River, Hermann, Mo.
0.92
0.19
0.12
Miss. River, near Thebes, 11.
0.86
0.27
0.23
Miss. River, Baton Rouge, LA.
0.46
0.12
0.09
'Based on bi-weekly samples May to August and weekly samples Sept. to Dec. 1 (Coupe et. al.,
1995).
Table 62: Illinois Surface Water Survey, 1986-19881
Site Type
Alachlor Concentration as a Range (over sites
and years) (ug/L)
Range of Peak values
Range of annual
TWMC
Illinois Rivers (21 Sites-18 Rivers)
0.02- 8.5
0.02-0.65
Illinois Creeks (9 Creeks)
0.02-18.0
0.02-2.0
1 Based on samples from 30 sites representing dif
?erent streams and rivers, 4-7 samples per yr at each
site (Moyer and Cross, 1990).
In addition to surface water data reviewed by the Agency, the following data (see Table 63)
is reported by the Chesapeake Bay Fall Line Toxics Monitoring Program, representing the period
fromMarch 1992 to February 1993. Monitoring data is based on one station per river. This data has
not been reviewed by the Agency. At this time it is viewed as supplementary information that tends
to confirm concerns for adverse effects on aquatic organisms. Also, the study represents an East
Coast tributary and thus provides a wider geographical scope for the monitoring data.
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Table 63: Summary of Chesapeake Bay Fall Line Toxics Monitoring
Program for Alachlor Detections in Major Streams.
Location
Range detected
Hg/L
Mean
^g/L
Susquehanna River
<2.05-23.1
4.4
Potomac River
2.5-20.9
4.1
James River
7.5-20.2
2.9
10. Comparative Assessment with Other Acetanilides
a. Environmental Fate Characteristics
Alachlor, acetochlor and metolachlor are moderately persistent while propachlor appears to
be the least persistent of all the acetanilides. However, the available aerobic soil metabolism values
(t,/2 and DT50) for the four chemicals are within the same order of magnitude. All of the compounds
are highly mobile.
An inspection of the physico-chemical characteristics of these chemicals reveals that alachlor
has the second lowest molecular weight. Alachlor has a high solubility in water, although it is lower
than the solubility of acetochlor and metolachlor. All the compounds have relatively low
octanol/water partition coefficients, low vapor pressures, low calculated Henry' s Law constants, and
relatively low bioaccumulation factors.
Further investigation of the environmental fate characteristics reveals that all four chemicals
are relatively stable to hydrolysis and photolysis in water. Three of the compounds are stable to
photolysis on soil while metolachlor has a half-life of 8 days. In general, it appears that the important
routes of dissipation for these compounds are aerobic soil metabolism and leaching. The aerobic soil
metabolism 50% dissipation rates range from 2.7 days for propachlor, to 2-3 weeks for alachlor, and
67 days for metolachlor. The available studies indicate that anaerobic soil metabolism is not an
important route of degradation for the acetanilides.
The half-lives observed in the field are of the same order of magnitude of the half-lives of
aerobic soil metabolism studies in all cases. Results of the field studies confirm aerobic soil
metabolism as an important route of dissipation for the four compounds.
b. Ecotoxicity
The comparative analysis of the ecotoxicity data for propachlor, alachlor, acetochlor, and
metolachlor is based on data taken from the OPP/EFED Pesticide Ecotoxicity Data Base-1997. Only
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those studies classified as Core data were used in the analysis. Category terminology was taken
directly from Brooks, et al. (1973).
Table 64 summarizes the environmental fate characteristics of the four acetanilides. Tables
65 through 71 show the ecological toxicity data available for birds, mammals, freshwater fish,
estuarine fish, freshwater aquatic invertebrates, and estuarine invertebrates. The analysis suggests
that this group of acetanilides are similar in toxicity. Propachlor appears to be more toxic to fish and
aquatic invertebrates while acetochlor is more toxic to birds. However, no clear differences are
evident.
Avian Species
On an acute oral basis, the toxicity data suggest that acetochlor is the most toxic of the four
herbicides (49 mg/kg), followed in order by propachlor, alachlor and metolachlor. The avian
subacute dietary data suggest that acetochlor is slightly more toxic (4171 ppm) than the other three
herbicides. In general, both the acute and subacute avian toxicity data indicate that all four herbicides
are practically non-toxic to slightly toxic to avian species on both an acute and subacute basis. These
data suggest a low risk to most avian species from either acute or subacute exposure from the use
of these four herbicides.
Mammalian Species
No mammalian toxicity data are available for alachlor. Available toxicity data suggest that
propachlor is practically nontoxic while acetochlor and metolachlor are moderately toxic to
mammalian species.
Fish Species
The 96-hour LC50 values generally indicate that propachlor is highly toxic while alachlor,
acetochlor and metolachlor are moderately toxic to freshwater fish species. Available toxicity data
for alachlor, acetochlor and metolachlor suggest that these herbicides are only moderately toxic to
estuarine fish species.
Aquatic Invertebrates
The freshwater aquatic invertebrate 48-hour LC50/EC50 data suggest that propachlor is the
most toxic (0.79 ppm) of the four herbicides, ranging from moderately to highly toxic to freshwater
invertebrates. The 48-hour LC50 values generally indicate that alachlor, acetochlor and metolachlor
are moderately to slightly toxic to freshwater invertebrate species. Available toxicity data for
alachlor, acetochlor and metolachlor indicate that these herbicides are only moderately toxic to
estuarine invertebrate species.
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c. Comparative Assessment Tables for the Acetanilides Alachlor,
Acetochlor, Metolachlor, and Propachlor
The following Tables provide a comparison of environmental fate and ecological toxicity data
for the acetanilides alachlor, acetochlor, metolachlor, and propachlor.
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Table 64: Comparison of the Environmental Fate Characteristics of Alachlor, Acetochlor, Metolachlor, and Propachlor:
Characteristic
Alachlor
Acetochlor
Metolachlor
Prooachlor
Chemical Structure
H.C
, •'
h3c7 V]
S-j ^=.
\
XC1
Empirical Formula
C14H20NO2Cl
C14H20NO2Cl
C15H22N02C1
c„h14noci
Molecular Weight
269.80
269.80
283.80
211.69
Vapor Pressure (mm Hg)
2.2xl0"5
4.40xl0"5
1.30xl0"5
7.90xl0"5
Log Kow
2.64
3.0
2.30
Henry's Constant (atm
m3/mol)
3.2xl0"8
7.0xl0"8
9.16xl0"9
3.59xl0"8
Solubilit\_in waterjppm)
240
223
530
613
Hydrolysis
Stable at pH 3.0, 6.0, and
9.0
Stable at pH 5.0, 7.0, 9.0
Stable at pH 5.0, 7.0, 9.0
Stable at pH 5.0, 7.0, 9.0
Photolysis in Water
Not expected to be an
important route of
degradation, based on
UV absorption spectrum
Stable
70 days
Stable
Photolysis on soil
Not expected to be an
important route of
degradation, based on
UV absorption spectrum
Stable
8 days
Not an important route of
degradation
Aerobic Soil Metabolism
2-3 weeks in three soil
types
8-14 days
one study reports 110 days
67 days
2.7 days
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Table 64: Comparison of the Environmental Fate Characteristics of Alachlor, Acetochlor, Metolachlor, and Propachlor:
Characteristic
Alachlor
Acetochlor
Metolachlor
Propachlor
Anaerobic Soil Metabolism Not available
230 days in sandy loam 81 days
soil
146 days in a clay4oam
sediment/lake water
system
Mobility
Very mobile in loamy
sand, silt and sand,
mobile in silt loam in
column leaching studies
Estimated Koc=190
Kd variable between 0.81-
7.5
K„ between 0.08 and 4.81
Terrestrial Field Dissipation
11 days in Chico,
California
8-36 days at 5 sites in the
United States
Supplemental studies
show variability between 7
and 292 days
Propachlor Kads=0.45-
1.39; Koc=73-138, in
loamy sand, sandy loam,
loam, silty clay loam.
Propachlor oxanilic acid
Kad =0.03-0.08, Koc=391-
3428.
Propachlor sulfonic acid
Kad=0.03-0.07,
.KQcz47i62Jl
1.0-1.7 days in Janesville,
Iowa; 5.0-5.8 in York,
Nebraska; 2.3-2.8 in
Uvalde. Texas
Bioaccumulation in Fish
Not expected to be
important, based on Kow.
In a supple-mental study
BCF=5.8X in fillet,
BCF=1 IX in whole, and
BCF=15X in viscera
BCF=40X edible
BCF=780X non-edible
BCF=150X whole fish
BCF=15X edible
BCF=69X whole fish
BCF=13X edible
BCF=71X nonedible
BCF=37X whole fish
The above table shows that alachlor, acetochlor, metolachlor, and propachlor are not only structurally related, but they also exhibit similar fate properties.
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Table 65: Comparison of Avian Acute Oral LP,,, data (mg/kg) for Propachlor, Acetochlor, Alachlor and Metolachlor
Chemical Avian Category MRID No. Classification
LPs" (mg/kg)
_Progachlpr 88 Moderatejy toxic 00132907 Core
Alachlor 1499 Slightly toxic 00079523 Core
>2000 Slightly toxic 00160000 Core
>2610 Slightly, toxic 00107908 Core
Acetochlor 49 Highly toxic 41963303 Core
1567 Slightly toxic 00079598 Core
1788 Slightly, toxic 41565129 Core
Metolachlor 4640 Slightly toxic 00015547 Core
* Technical Grade Material
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Table 66: Comparison of Avian Subacute Dietary LC50 data (ppm) for Propachlor, Acetochlor,
Alachlor and Metolachlor
Chemical Avian LCgl Category MRID No. Classification
Propachlor >5000 Practically Non-toxic 00108087 Core
00104335
>5423 Practically Non-toxic 00134006 Core
>5620 Practically, Nontoxic 00132908 Core.
Alachlor >5000 Practically Non-toxic 00093660 Core
>5620 Practically Non-toxic 00106553 Core
>5620 Practically, Nontoxic 00106554 Core.
Acetochlor >4171 Slightly toxic 41565130 Core
>4610 Slightly toxic 41565131 Core
>5620 Practically Non-toxic 00064711 Core
>5620 Practically, Nontoxic 00064710 Core,
Metolachlor >10000 Practically Non-toxic 0016425 Core
>10000 Practically Non-toxic 0016426 Core
*Technical Grade Material
168
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Table 67: Comparison of Freshwater Fish 96-hr LC50 data (ppm) for Propachlor, Acetochlor,
Alachlor and Metolachlor.
Chemical
96-hr LC™*
Category
MRID No.
Classification
Propachlor
0.23
Highly toxic
40098001
Core
0.17
Highly_toxic
00041335
Core
Alachlor
1.0
Highly toxic
00234628
Core
5.6
Moderately toxic
00234628
Core
2.8
Moderately toxic
00023615
Core
4.3
Moderately toxic
40094602
Core
2.4
Moderately toxic
40094602
Core
Acetochlor
1.2
Moderately toxic
41963306
Core
1.5
Moderately toxic
41565133
Core
0.38
Highly toxic
41565132
Core
1.6
Moderately toxic
41565133
Core
Metolachlor
3.9
Moderately toxic
0018722
Core
4.9
Moderately toxic
0015534
Core
8.0
Moderately toxic
40098001
Core
10.0
Moderately toxic
00018723
Core
169
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Table 68: Comparison of Aquatic Invertebrate 48-hour LCS0 data (ppm) for Propachlor,
Acetochlor, Alachlor and Metolachlor.
Chemical
48-hr LC™*
Category
MRID No.
Classification
Propachlor
0.79
Highly toxic
40098001
Core
7.8
Moderately toxic
00041336
Core
6.9
Moderately toxic
40098001
Core
Alachlor
21.0
Slightly toxic
40098001
Core
3.2
Moderately toxic
40098001
Core
Acetochlor
8.2
Moderately toxic
41565134
Core
14.0
Slightly toxic
00064714
Core
Metolachlor
25.1
Slightly toxic
226955
Core
23.5
Slightly toxic
40098001
Core
3.8
Moderately toxic
40098001
Core
* Technical grade material
Table 69: Comparison of Estuarine Fish 48-hour LCS0 data (ppm) for Propachlor, Acetochlor,
Alachlor and Metolachlor
Chemical
48-hr LC™*
Category
MRID No.
Classification
Propachlor
No Data
Alachlor
3.9
Moderately toxic
44524301
Core
Acetochlor
2.1
Moderately toxic
42713102
Core
3.9
Moderately toxic
41565137
Core
Metolachlor
9.8
Moderately toxic
43487101
Core
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Table 70: Comparison of Estuarine Invertebrate 96-hour LC50/EC50 data (ppm) for Propachlor,
Acetochlor, Alachlor and Metolachlor.
Chemical
48-hr LC™*
Category
ID#
Classification
Propachlor
No Data
Alachlor
2.4
1.6
Moderately toxic
Moderately toxic
44524302
44524303
Core
Core
Acetochlor
2.2
Moderately toxic
42713101
Core
8.0
Moderately toxic
41565136
Core
5.3
Moderately toxic
41565135
Core
3.82
Moderately toxic
42713103
Core
Metolachlor
4.9
Moderately toxic
43487103
Core
1.6
Moderately toxic
43487102
Core
Table 71: Comparison of Mammalian Acute Oral LD50 data (mg/kg) for Propachlor,
Acetochlor, Alachlor and Metolachlor
Chemical
96-hr LD™*
Category
ID#
Classification
Propachlor
1800
NA
Alachlor
Not Required
Acetochlor
2.2
Moderately toxic
42713101
Core
8.0
Moderately toxic
41565136
Core
5.3
Moderately toxic
41565135
Core
3.82
Moderately toxic
42713103
Core
Metolachlor
4.9
Moderately toxic
43487103
Core
1.6
Moderately toxic
43487102
Core
* Technical grade material
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11. Environmental Risk Assessment
a. Introduction
Risk Quotients (RQs) are used to evaluate the potential risk to nontarget organisms from the
use of alachlor products. RQs are calculated by dividing an appropriate exposure estimate, (such as
the estimated environmental concentration; EEC) by an appropriate toxicity test effect level. Typical
acute effect levels are: EC25 for terrestrial plants, EC50 for aquatic plants and invertebrates, LC50 for
fish and birds, and LD50 for birds and mammals. Typical chronic effect levels are: No Observed Effect
Level (NOEL) for avian and mammal reproduction studies, and either the NOEL, or the Maximum
Allowable Toxicant Concentration (MATC), (which is the geometric mean of the NOEL and the Low
Observed Effect Level (LOEL), for chronic aquatic studies. The NOEL and LOEL are sometimes
referred to as No Observed Effect Concentration (NOEC) or the Lowest Observed Effect
Concentration (LOEC).
RQs are then compared to established levels of concern (LOC) for determination of potential
ecorisk and the consideration of regulatory action. There are two general categories of LOCs: acute
and chronic. The levels of concern are criteria used to indicate potential risk to nontarget organisms.
The criteria indicate that a chemical, when used as directed, has the potential to cause undesirable
effects on nontarget organisms.
When the risk quotient exceeds the LOC for a particular category of organism, there is
presumed to be risk to that particular category. Risk presumptions for particular categories of
organisms are presented in Table 72 along with the corresponding LOC's.
Table 72: Levels of Concern and Associated Risk Presumptions:
Criterion
Presumption when Criterion Met
Mamr
rials and Rirds
Acute RQ>0.5
High acute risk.
Acute RQ>0.2
Risk that may be mitigated through restricted use.
Acute RQ>0.1
Endangered species may be affected acutely.
Chronic RQ> 1
Chronic risk, endangered species may be affected
chronically.
Fish and An
uatic Invertebrates
Acute RQ>0.5
High acute risk
Acute RQ>0.1
Risk that may be mitigated through restricted use.
Acute RQ>0.05
Endangered species may be affected acutely.
Chronic RQ> 1
Chronic risk, endangered species may be affected
chronically.
Plants
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Table 72: Levels of Concern and Associated Risk Presumptions:
Criterion
Presumption when Criterion Met
RQ> 1
High risk.
RO>1
Endangered nlants mav be affected
b. Risk to Nontarget Terrestrial Animals
Although available information does not indicate acute risk concerns for birds or mammals,
an LC50 measurement for a small mammal would be required for a conclusive finding.
Birds
Alachlor emulsifiable concentrate at a maximum rate of 6 lbs a.i./A, would produce a
maximum expected concentration of approximately 1440 ppm on range grasses. (Note that the
maximum single application rate is now 4 lb a.i./A.) Alachlor is practically nontoxic to birds on a
dietary basis: in the acute tests with two avian species, little or no mortality was observed at the
highest measured concentration (5620 ppm). Therefore, no exceedances of Agency levels of concern
for acute dietary risk are expected.
The avian acute oral data (LD50 = 1499 mg/kg) can be used to evaluate avian exposure to
granules. The potential hazard to birds from exposure to granules should be slight. Granules are
deposited typically in bands 6 inches wide, with 32 inches between band centers. This implies that
the pesticide is applied to an area of 8,163 square feet in every acre. At the maximum label rate (for
granular uses) of 4.0 lb ai per acre, there will be 222 mg ai/sq.ft. for the area within bands. If 85%
of the granules are incorporated (Erbach and Tollefson, 1983) the potential surface residue is
33 mg/sq.ft. This value does not indicate an acute toxicity concern for non-endangered species
(LOC=0.5). Exposures exceeding 150 mg/sq ft would exceed the endangered species LOC of a tenth
of the LD50. Without incorporation, exposure could approach this level of concern. However, the
registrant has indicated that Lasso ®II is applied in 10 and 14-inch bands, reducing the level of
exposure and attenuating the concern.
Assessment of chronic effects to terrestrial vertebrates is based on results of reproduction
studies. Properties and use conditions of alachlor indicate a need for such studies. To date the
Agency has not received or reviewed data on possible reproductive or growth effects to birds from
exposure to alachlor. There is some certainty that the nesting and breeding seasons of many bird
species will coincide with the usual preemergent application periods for alachlor. The persistence of
the compound indicates that it will be available for a relatively long period of time on the application
site, with an aerobic soil half life of 2-3 weeks and longer half lives for abiotic processes (photolysis,
hydrolysis).
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Mammals
Available information for mammals is inconclusive regarding concerns for acute risk. LD50
values for laboratory rats indicate slight acute toxicity. An LC50 measurement would be required to
calculate a risk quotient for non-target mammals. It is common for mammals to be somewhat less
sensitive than birds, and risk quotients calculated above for birds do not indicate a concern for acute
effects.
Regarding the possibility of chronic effects on mammals, three-generation rat studies
produced a parental/offspring systemic toxicity NOEL of 10 mg/kg/day and an LOEC of 30
mg/kg/day. (MRID No. 00075062) Renal toxicity was observed in F2 males. There were no effects
on reproductive parameters. The rat developmental toxicity study showed maternal and
developmental effects at dose levels of 400 mg/kg/day and a NOEC of 150 mg/kg/day. (MRID No.
00043645) Based on the computations for mg ai/sq ft for a granular application, the LOEC for a 1
kg mammal could be contained within a square foot of surface area. Higher exposure is expected for
surface application with no incorporation. Ingestion of this amount of active ingredient for the
extended periods represented in these studies would, however, seem unlikely as the herbicide would
dissipate downward or laterally once irrigation or rainfall events occurred. In the absence of rainfall,
irrigation is recommended within five days of planting to move the chemical to the root zone.
c. Risk to Nontarget Aquatic Animals
Freshwater Animals
The following features of alachlor use are relevant to the determination of aquatic exposures:
(1) alachlor is a pre-emergent herbicide and is usually applied only once a year, (2) there are some
postemergence uses that allow two applications, and (3) in the absence of rainfall, irrigation is
recommended within five days of planting to move the chemical to the root zone.
Sufficient information is available to characterize the toxicity of alachlor to freshwater
animals. Alachlor shows moderate acute toxicity to both coldwater fish and warmwater fish, based
on measurement with TGAI or formulated EC 45. Alachlor TGAI and formulated products (42-
45%EC) are slightly to moderately toxic to freshwater aquatic invertebrates on an acute basis.
Alachlor is highly toxic to freshwater fish and invertebrates chronically. The LOEC values
for growth and reproductive effects are below 400 ppb. NOEC's are below 190 ppb.
Alachlor is not expected to cause freshwater fish or invertebrates to be at acute risk. Results
of screening level modeling do not exclude the possibility of chronic effect threshold exceedance for
fish and invertebrates through spray drift or runoff in areas close to application sites, particularly for
smaller bodies of water with little inflow or outflow. Based on monitoring results, chronic thresholds
in areas farther down the watershed from these smaller tributaries or ponds are not expected to
exceed acute or chronic levels of concern for fish or invertebrates.
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Estuarine and Marine Animals
Sufficient data are available to characterize alachlor as being only moderately toxic to
saltwater fish (sheepshead minnow), saltwater mysid and shellfish (Eastern oyster).
Bioaccumulation
Alachlor is not expected to bioaccumulate significantly in fish, based on high solubility (240
ppm), and relatively low octanol/water partition coefficient (434).
d. Risk to Nontarget Plants
Toxicity data for plants, though incomplete, are sufficient to characterize alachlor as highly
toxic for both terrestrial and aquatic plants. Alachlor poses substantial risks to aquatic and terrestrial
plants near use sites. Terrestrial plants may be exposed to alachlor via drift and runoff from areas of
application, or via irrigation with contaminated ground water. Aquatic plants may be exposed via
runoff or drift, or by discharge of contaminated ground water into surface water.
Aquatic Plants
Alachlor has an aquatic plant EC50 of 1.64 //g/L and NOEC of 0.35 |ig/L, based on a green
alga study. The risk quotients (based on screening models) using this EC50 range from 21 to 124,
values that substantially exceed the level of concern (LOC=l). Based on monitoring results average
detection levels often exceed levels of concern for aquatic plants.
Measurements of alachlor in surface and ground water were previously described in this
document. The ECS0 of 1.64 |ig/L for aquatic plants approximately equals the alachlor MCL (2
|ig/L); therefore the frequency of acute exposures exceeding the LOC for plants (LOC=l)
approximately equals the frequency of exceeding the MCL.
Aquatic plants may be adversely affected by alachlor in ground water, in places where ground
water discharges into surface water. Regarding ground water, the measured concentration of alachlor
was higher than the MCL in 21% of wells (99 of 467 wells) that had detectable alachlor, as recorded
in the Pesticides in Ground Water Database.
Terrestrial Plants
For terrestrial plants, the RQ is the ratio of the EEC to the EC25, and RQ values 1 or larger
indicate high risk. Based on calculations that follow, RQ values are equal to 5 or larger, which is
indicative of high risk.
Typically alachlor is applied by ground equipment at rates of 4 lbs a.i./A. With 5% runoff the
EEC is 0.2 lbs a.i./A. The EC25 for seedling emergence was 0.04 lbs a.i./A, based on a study that was
175
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found to be supplemental. The corresponding RQ is 5 (0.2/0.04). Alachlor is persistent, so additional
applications would be additive, to some extent.
Semi-Aquatic Plants
Semi-aquatic plant species live for some part of a year in wet soil near freshwater wetlands
or estuarine marshes. For these plants, the most appropriate toxicity measurements are those for
terrestrial plants. Exposure scenarios are similar to those described previously for aquatic organisms.
Risk to semi-aquatic plants exceeds levels of concern. Risk is assessed using two different
risk quotients, representing exposure by drift and runoff. Both are compared to an LOC of 1.
A risk quotient based on exposure to aerial drift of alachlor is as follows: Alachlor
is applied aerially at 4 lbs a.i./A, and drifts to a plot with area equal to that of the
application plot. A loading of 0.2 lbs a.i./A (=5% drift) is calculated as for aquatic
organisms. The most applicable toxicity data is that for vegetative vigor of terrestrial
plants, with EC25 measurements as low as 0.044 lbs a.i./A. The value of the risk
quotient is 0.2 / 0.044 = 5.
A risk quotient based on exposure to runoff of water contaminated with alachlor is
calculated as follows: If the pesticide is applied aerially at 4 lbs a.i./A to a 10-acre
application plot and is transported to a 1-acre plot, a loading of 1.2 lbs a.i./A is
calculated. The most applicable toxicity data is that for germination and growth of
terrestrial plants, with EC25 measurements as low as 0.0067 lbs a.i./A. The value of
the risk quotient is 1.2 / 0.0067 = 179.
e. Aquatic LOC Exceedances
For freshwater animals (fish or invertebrates) exposure estimates based on Tier I modeling
(GENEEC) exceed LOCs (levels of concern) only for chronic effects, and only at application rates
of 4 lb ai/A (invertebrates) without incorporation. For estuarine/marine organisms (fish, shrimp and
shellfish), exposure estimates based on Tier 1 modeling (GENEEC) do not exceed concern levels for
acute effects. (See Table 73)
Table 73: Alachlor Screening Level Aquatic EECs Generated by GENEEC, with LOC
Exceedances.
Application
Rate/Method/Incorporation
EE
Peak
C Estimates
4 Days
Over Time
21 Days
(ppb)
56 Days
Species with LOC exceedance,
(risk quotient)
1.01b Granular/Ground/none
33
32.7
30.7
27.4
Aquatic Plant (21)
2.01b Granular/Ground/none
66.3
65.5
61.5
58.9
Aquatic plant (41)
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Table 73: Alachlor Screening Level Aquatic EECs Generated by GENEEC, with LOC
Exceedances.
Application
Rate/Method/Incorporation
EE
Peak
C Estimates
4 Days
Over Time
21 Days
(ppb)
56 Days
Species with LOC exceedance,
(risk quotient)
4.01b Granular/Ground/none
133
131
123
110
Daphnid Chronic NOEC (1)
Aquatic Plant (83)
1.251b ai/groundspray/none
39
38
36
32
Aquatic Plant (24)
2.51b ai/groundspray/none
78
77
72
65
Aquatic Plant (49)
3.0 lb ai/groundspray/none
94
93
87
78
Daphnid Chronic (1)
Aquatic Plant (57)
4.01b ai/groundspray/none
125
124
116
104
Daphnid Chronic NOEC (1)
Aquatic plant EC50 (76)
4.0 lb ai/groundspray/2.0
inch incorporation
64
63
59
53
Aquatic plant (40)
2.0 lb ai/A twice
groundspray/no incorp./30
day interval
92
91
85
76
Daphnid Chronic NOEC (1)
Aquatic Plant (57)
Alachlor concentration levels observed in monitoring studies do not indicate a risk for acute
or chronic effects on aquatic animals. Thus, while a chronic risk cannot be dismissed for small,
shallow, relatively static bodies of water (such as farm ponds or small freshwater marshes) from
unincorporated applications of alachlor at 4 lbs ai/A (invertebrates), the information available suggests
that impacts are not expected in larger water bodies such as rivers or large lakes. (See Tables 74, 75,
and 76)
Table 74: USGS Mississippi River Basin Survey, 1991-19921
Location Sampled
(24 Samples per location)
Alachlor Concentration (ng/L)
LOC Exceedance-Organisms
Affected
Peak
Arithmeti
c average
Annual
TWMC
White River, Hazelton, In.
3.2
0.3
0.22
Aquatic Plants-(Peak only;
based on EC50 (=1.64 ug/L)
Ohio River, Grain Chain, 11.
0.40
0.08
0.07
No
177
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Table 74: USGS Mississippi River Basin Survey, 1991-19921
Location Sampled
(24 Samples per location)
Alachlor Concentration (pg/L)
LOC Exceedance-Organisms
Affected
Peak
Arithmeti
c average
Annual
TWMC
Miss. River, near Clinton, IA.
0.85
0.16
0.10
No
Illinois River, Valley City, 11
3.00
0.40
0.22
Aquatic Plants-(Peak only,
based on EC50)
Platte River, Louisville, NE
3.60
0.43
0.22
Aquatic Plants-(Peak only,
based on EC50)
Missouri River, Hermann,
Mo.
0.92
0.19
0.12
No
Miss. River, near Thebes, 11.
0.86
0.27
0.23
No
Miss. River, Baton Rouge,
LA.
0.46
0.12
0.09
No
'Based on bi-weekly samples May to August and weekly samples Sept. to Dec. 1 (Coupe et. al. 1995).
Table 75: Illinois Surface Water Survey, 1986-19881
Site Type
Alachlor Concentration as a Range
(over sites and years) (ug/L)
LOC Exceedance
Organism Effected
Range of Peak
values
Range of
annual TWMC
Illinois Rivers (21 Sites-18 Rivers)
0.02- 8.5
0.02-0.65
Aquatic Plants based on
ec50
Illinois Creeks (9 Creeks)
0.02-18.0
0.02-2.0
1 Based on samples from 30 sites representing different streams and rivers, 4-7 samples per yr at each site
(Moyer and Cross, 1990).
Table 76: Summary of Chesapeake Bay Fall Line Toxics Monitoring Program for Alachlor
Detections in Major Streams.
Location
Range detected
^g/L
Mean
^g/L
LOC Exceedances
by Mean
Susquehanna River
<2.05-23.1
4.4
Aquatic Plants,
based on EC50
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Table 76: Summary of Chesapeake Bay Fall Line Toxics Monitoring Program for Alachlor
Detections in Major Streams.
Potomac River
2.5-20.9
4.1
James River
7.5-20.2
2.9
f. Environmental Risk Summary
An evaluation of the risk to nontarget organisms from the use of alachlor products, combining
toxicity data with potential exposure, indicates that:
• Alachlor poses a potential risk to terrestrial animals on a chronic basis. Additional
information must be submitted by the registrant to rule out risk.
• The granular formulations and high use rate pose the greatest risk to nontarget organisms.
• Alachlor levels observed in surface water monitoring studies could result in extensive adverse
effects on aquatic plants.
• Aquatic animals are not at acute risk as a result of exposure to alachlor, but chronic effects
may be observed under certain circumstances.
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
(i.e. active ingredient specific) data required to support reregistration of products containing alachlor
as an active ingredient. 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 alachlor.
Appendix B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregistration eligibility of alachlor, 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 alachlor and to determine that alachlor can be used without resulting in unreasonable adverse
effects to humans and the environment. The Agency therefore finds that all products containing
alachlor as an active ingredient are eligible for reregistration. The reregistration of particular products
is addressed in Section V of this document.
The Agency made its reregistration eligibility determination based upon the target database
required for reregistration, the current guidelines for conducting acceptable studies to generate such
data, published scientific literature, etc. and the data identified in Appendix B. Although the Agency
has found that all uses of alachlor are eligible for reregistration, it should be understood that the
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Agency may take appropriate regulatory action, and/or require the submission of additional data to
support the registration of products containing alachlor, if new information comes to the Agency's
attention or if the data requirements for registration (or the guidelines for generating such data)
change.
b. Determination of Eligibility Decision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient alachlor, the Agency has
sufficient information on the health effects of alachlor and on its potential for causing adverse effects
in fish and wildlife and the environment. The Agency has determined that alachlor products, labeled
and used as specified in this Reregi strati on Eligibility Decision Document (RED), will not pose
unreasonable risks or adverse effects to humans or the environment. If the terms and conditions of
registration for products containing the active ingredient alachlor are amended as specified in this
RED, then the Agency concludes that products containing alachlor are eligible for reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of alachlor are eligible for reregistration.
c. Regulatory Position
To lessen the risks posed by alachlor, EPA is requiring the following mitigation measures for
alachlor-containing products.
To protect non-target species:
- Require labeling as specified in Section V.
To control surface water contamination:
- Require labeling as specified in Section V.
- Require labeling to implement spray drift best management practices
To control ground water contamination:
- Require labeling as specified in Section V.
- Classify alachlor as a Restricted Use Pesticide (RUP) for ground water concerns
- Add labeling language requiring a 50 ft setback of mixing and loading activities from wells,
rivers, or lakes unless such activity is protected by an impervious pad.
- After promulgation of the Ground Water and Pesticides Management Plan Rule, require use
in accordance with an approved State or Tribal Management Plan
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To protect workers:
- For liquid (emulsifiable concentrate) formulations for workers supporting groundboom
application require that mixers, loaders, and persons cleaning equipment must wear long-
sleeved shirt, long pants, chemical-resistant gloves, chemical-resistant footwear, and
chemical-resistant apron.
- For dry flowable formulations for workers supporting groundboom application require that
mixers, loaders, and persons cleaning equipment must wear long-sleeved shirt, long pants,
chemical-resistant gloves, chemical-resistant footwear, and chemical-resistant apron.
- For liquid (emulsifiable concentrate) formulations for workers supporting aerial application
require that mixers and loaders must wear long-sleeved shirt, long pants, and chemical
resistant gloves, and the use of a closed transfer system.
- For dry flowable formulations for workers supporting aerial application require that mixers
and loaders must wear long-sleeved shirt, long pants, and chemical resistant gloves, and the
use of a closed transfer system.
-For mixers and loaders who impregnate dry bulk fertilizer require long-sleeved shirt, long
pants, and chemical-resistant gloves, and the use of a closed transfer system.
To control the amount of alachlor present in rotated crops:
- Until the rotational crop data are received and reviewed, rotation to crops not specified on
this label is prohibited.
1. Food Quality Protection Act Findings
The following is a summary of the Agency's regulatory position and rationale for managing
the risks associated with uses of alachlor.
a. Determination of Safety for U.S. Population
EPA has determined that the established tolerances for alachlor, with amendments and
changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(D) of the FFDCA, and that there is a reasonable certainty of no harm for the
general population. In reaching this determination, EPA has considered the available information on
the aggregate exposures (both chronic and carcinogenic) from food and drinking water.
The Agency has concluded that there are no alachlor products registered for home use, or use
in or around schools, parks or other public areas. For this reason a residential assessment was not
conducted and there is no residential assessment to aggregate with the total dietary assessment.
As previously discussed, available data do not indicate any evidence of significant toxicity
from a one day or single event exposure by the oral route; therefore, an acute dietary assessment was
not conducted.
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The Agency assessed the chronic (non-cancer) dietary risk using the chronic RfD of 0.01
mg/kg/day based a NOEL of 1 mg/kg/day from a one year chronic dog study (with an uncertainty
factor of 100 to account for interspecies extrapolation and intraspecies variability). The Agency's
aggregate chronic risk assessment was performed considering exposures from food and water.
Values ranged from less than 1% to 4% of the RfD. The Agency concluded that the chronic dietary
risk from food containing residues of alachlor and from consumption of water containing residues of
alachlor and alachlor ESA is not of concern.
Using the MOE approach, the Agency calculated carcinogenic dietary risk using two
endpoints of concern: the NOEL of 14 mg/kg/day for stomach tumors and 0.5 mg/kg/day for nasal
tumors. The Agency's estimated MOEs for aggregate dietary carcinogenic risk considering exposures
from food and water. The MOEs ranged from 29,000 to 1,400,000 indicating that the dietary cancer
risk from the recommended uses of alachlor is not expected to be of concern.
Using the Qx* approach, the Agency calculated carcinogenic dietary risk using the Q, of 0.08
(mg/kg/day)"1. The Agency's estimated risks for aggregate dietary carcinogenic risk considering
exposures from food and water. The risks ranged from 7.8 x 10"7 to 1.4 x 10"6 which is generally
within the risk range considered to be negligible.
With regard to water monitoring data, sufficient analytical information on detections of all
alachlor degradates were not available. The available information indicates that alachlor ESA is
detected more often and in larger concentrations than alachlor, and that degradates of alachlor are
probably more mobile and more persistent than alachlor per se. Toxicity information is available only
for alachlor ESA. Due to the lack of available information on detections in ground and surface water
of all degradates of alachlor (of which alachlor ESA is only one degradate) and on the toxicity of
these degradates, the Agency is concerned about the exposure to drinking water containing alachlor
and all alachlor degradates.
Alachlor, acetochlor, metolachlor, butachlor, and propachlor are structurally similar and
therefore may share a common mechanism of toxicity. For the purpose of implementation of FQPA,
common mechanism of toxicity is defined as pertaining to two or more pesticides that produce an
adverse effect(s) to human health by the same, or essentially the same, sequence of maj or biochemical
events. On August 6, 1998, the Notice of Availability for the "Guidance for Identifying Pesticide
Chemicals that have a Common Mechanism of Toxicity for Use in Assessing the Cumulative Toxic
Effects of Pesticides" was published in the Federal Register. (Federal Register. Volume63,No. 151).
The Agency is proposing to use the following process for identifying those pesticides that share a
common mechanism of toxicity: (1) identify pesticides that are likely to have a common mechanism
of toxicity using available information on structural similarity, mechanism of pesticidal action, and
common toxic effect, (2) identify the mechanism of toxicity of each pesticide, and (3) categorize
pesticides according to mechanism of toxicity.
At this time the Agency has not yet made a final decision concerning a possible common
mechanism of toxicity for alachlor, acetochlor, metolachlor, butachlor, and propachlor to
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scientifically apply that information to the tolerance decision. Therefore, for the purposes of this
decision document, the tolerance decision will be reached based upon the best available and useful
information for alachlor only. Thus, the alachlor risk assessment has been performed assuming that
no common mechanism of toxicity exists.
However, the process for determining whether a common mechanism of toxicity exists has
begun, but is not yet completed. Thus, the decisions made in this RED will be reexamined after the
Agency (1) finalizes the process for determining whether a common mechanism of toxicity exists for
these chemicals, (2) determines those chemicals with which alachlor does share a common mechanism
of toxicity (cluster), (3) determines the potency equivalencies for each chemical of the cluster, (4)
adds the potency equivalencies to determine the cumulative magnitude of the effect, and (5) after
reviewing the use information/patterns, determines for which of the exposures/scenarios for which
of the chemicals that cumulative exposure exists. Once the methodologies and procedures for
integrating information concerning common mechanism of toxicity into risk assessments are
developed, the Agency can determine the appropriateness of a cumulative assessment.
b. Determination of Safety for Infants and Children
EPA has determined that the established tolerances for alachlor, with amendments and
changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) of the FFDCA, and that there is a reasonable certainty of no harm for infants
and children. The safety determination for infants and children considers the factors noted above for
the general population, but also takes into account the possibility of increased dietary exposure due
to the specific consumption patterns of infants and children, as well as the possibility of increased
susceptibility to the toxic effects of alachlor residues in this population subgroup.
In determining whether or not infants and children are particularly susceptible to toxic effects
from alachlor residues, EPA considered the completeness of the database for developmental and
reproductive effects, as well as other available information such as the nature of the effects observed.
There is no evidence of increased susceptibility of rats or rabbits to in utero and/or postnatal
exposure. There are no data gaps for the assessment of the effects of alachlor following in utero
and/or postnatal exposure.
Based on the current data requirements, alachlor has a complete database for developmental
and reproductive toxicity. Reliable studies cited earlier in this document indicate no special sensitivity
of young organisms to alachlor. Therefore, the Agency has concluded that the 10X FQPA safety
factor for the protection of infants and children can be removed.
EPA estimates that the residues of alachlor in the diets of children (1-6 years) represent less
than 1% of the chronic RfD and residues in drinking water, including residues of alachlor ESA,
represent approximately 3% of the chronic RfD. The aggregate chronic dietary exposure for infants
and children utilizes approximately 4% of the chronic RfD. Thus, the Agency concludes that
aggregate risks for infants and children resulting from alachlor uses are not of concern.
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In deciding to continue to make reregi strati on determinations during the early stages of FQPA
implementations, EPA recognizes that it will be necessary to make decisions relating to FQPA before
the implementation process is complete. In making these early, case-by-case decisions, EPA does
not intend to set broad precedents for the application of FQPA to its regulatory determinations.
Rather, these early decisions will be made on a case-by-case basis and will not bind EPA as it
proceeds with further policy development and rulemaking that may be required.
If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will consider itself free
to pursue whatever action may be appropriate, including but not limited to, reconsideration of any
portion of this RED.
c. Endocrine Disrupter Effects
EPA is required to develop a screening program to determine whether certain substances
(including all pesticides and inerts) "may have an effect in humans that is similar to an effect produced
by a naturally occurring estrogen, or such other endocrine effect..." The Agency is currently working
with interested stakeholders, including other government agencies, public interest groups, industry
and research scientists in developing a screening and testing program and a priority setting scheme
to implement this program. Congress has allowed 3 years from the passage of FQPA (August 3,
1999) to implement this program. At that time, EPA may require further testing of this active
ingredient and end use products for endocrine disrupter effects.
2. Tolerance Reassessment
The tolerances listed in 40 CFR §180.249 are for the combined residues of alachlor and its
metabolites (calculated as alachlor).
The Agency has determined that all alachlor metabolites which can be converted to 2,6-
diethylaniline (DEA) and 2-ethyl-6-(l-hydroxyethyl)aniline (1-HEEA) upon basic hydrolysis are to
be regulated and will be included in the tolerance expression. Therefore, the tolerance expression in
40 CFR §180.249 should be modified as follows: "Tolerances are established for the combined
residues of the herbicide alachlor (2-chloro-2',6'-diethyl-N-(methoxymethyl) acetanilide) and its
metabolites which can be converted to 2,6-diethylaniline or 2-ethyl-6-(l-hydroxyethyl)aniline upon
basic hydrolysis, (calculated as alachlor), in or on the following raw agricultural commodities: ...".
Thus, for some commodities tolerance increases will be necessary. The more recent residue
chemistry data reflect analysis for two classes of alachlor metabolites (DEA and HEEA); whereas
some of the older data used to establish the existing tolerances reflect analysis for DEA metabolites
only.
Sufficient data are available to ascertain the adequacy of the established tolerances listed in
40 CFR § 180.249 for beans, dry; beans, lima(green); corn, sweet (K + CWHR); corn, grain; sorghum
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grain and fodder; eggs; milk; and fat, meat, and meat byproducts of cattle, goats, hogs, horses,
poultry, and sheep. See Table 77 for modifications in commodity definitions.
Tolerances for the following commodities have been reassessed based on the available data:
corn, field, forage, and stover; corn, pop, grain, and stover (translated from field corn grain); sweet
corn, forage and stover; peanuts; and soybeans.
Field rotational crop studies are still required for a root crop and a leafy vegetable; rotational
crop tolerances are needed. Monsanto plans to support cereal grains (except rice), and non-grass
animal feeds as rotational crops.
Table 77: Tolerance Reassessment Summary.
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Correct Commodity
Definition/Comment
Beans, dry
0.1
0.1
Beans, forage
0.2
5.0
Cowpeas, forage
Beans, hay
0.2
5.0
Cowpeas, hay
Beans, lima (green)
0.1
0.1
Beans, succulent lima
Cattle, fat
0.02
0.02
Cattle, mbyp
0.02
0.02
Cattle, meat
0.02
0.02
Corn, fodder
0.2
2.0
Corn, field, stover
2.0
Corn, pop, stover
2.0
Corn, sweet, stover
Corn, forage
0.2
2.0
Corn, field, forage
2.0
Corn, sweet, forage
Corn, fresh (inc. sweet
K+CWHR)
0.05
0.05
Corn, sweet (K+CWHR)
Corn, grain
0.2
0.2
Corn, field, grain
0.2
Corn, field, pop
Eggs
0.02
0.02
Goats, fat
0.02
0.02
Goats, mbyp
0.02
0.02
Goats, meat
0.02
0.02
Hogs, fat
0.02
0.02
Hogs, mbyp
0.02
0.02
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Table 77: Tolerance Reassessment Summary.
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Correct Commodity
Definition/Comment
Hogs, meat
0.02
0.02
Horses, fat
0.02
0.02
Horses, mbyp
0.02
0.02
Horses, meat
0.02
0.02
Milk
0.02
0.02
Peanuts
0.05
0.5
Peanuts, forage
3.0
Revoke
Feeding restrictions
exist; not considered a
major livestock feed.
Peanuts, hay
3.0
Revoke
Feeding restrictions
exist.
Peanuts, hulls
1.5
Revoke
Based on Table II,
peanut hulls are not
considered to be a major
livestock feed.
Poultry, fat
0.02
0.02
Poultry, mbyp
0.02
0.02
Poultry, meat
0.02
0.02
Sheep, fat
0.02
0.02
Sheep, mbyp
0.02
0.02
Sheep, meat
0.02
0.02
Sorghum, fodder
1.0
1.0
Sorghum, grain, stover
Sorghum, forage
2.0
2.0
Sorghum, grain, forage
Sorghum, grain (milo)
0.1
0.1
Sorghum, grain, grain
Soybeans
0.2
1
Soybeans, forage
0.75
Revoke
All alachlor products
with uses on soybeans
have feeding restrictions
or are in the process of
being canceled.
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Table 77: Tolerance Reassessment Summary.
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Correct Commodity
Definition/Comment
Soybeans, hay
0.2
Revoke
All alachlor products
with uses on soybeans
have feeding restrictions
or are in the process of
beinp canceled
Codex Harmonization
No maximum residue limits (MRLs) for alachlor have been established by CODEX for any
agricultural commodity. Therefore, no questions of compatibility exist with respect to U.S.
tolerances.
3. Ecological Risk Mitigation
For terrestrial animals there are concerns for acute effects. There is not an avian reproduction
study for alachlor, but avian reproduction studies for other acetanilides (metolachlor, acetochlor)
suggest high toxicity on a chronic basis. Based on this, and on consideration of the scope and
seasonal pattern of use (including application at times when birds will be breeding) there is a concern
that alachlor may adversely affect avian reproduction. The information available on persistence of
alachlor is consistent with a chronic concern since alachlor is moderately persistent in soil. The major
dissipation route in soil is microbially mediated, with half lives of 2-3 weeks under aerobic conditions.
Avian reproduction studies are required.
Large scale use of a herbicide ordinarily poses concern for terrestrial plants at least in the
vicinity of application sites. There are no special concerns for effects of alachlor on terrestrial plants,
relative to other herbicides with extensive use. The evaluation of risk to terrestrial plants indicates
high risk from exposure to alachlor drift and runoff. There is no information on toxicity of alachlor
degradates to terrestrial plants.
Alachlor levels observed in surface water monitoring studies could result in extensive effects
on aquatic plants. Such effects could in turn cause population level effects on aquatic animals
(including fish and amphibians) via habitat modification or decreased food supply. Information is not
available on the effects of degradates on aquatic plants.
For aquatic animals, risk quotients based on screening-level exposure estimates do exceed
levels of concern for chronic effects. However, the monitoring information available does not
suggest widespread effects by direct acute or chronic toxicity. The available information does not
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suggest high toxicity of alachlor degradates to aquatic animals. For estuarine/marine species, risk
quotients, based on screening-level exposure estimates, do not exceed level of concerns for acute
effects for saltwater fish, saltwater mysid or shellfish.
Based on the aquatic plant data, the Agency is confident that adverse effects on aquatic
ecosystems, including potential for population level effects on aquatic animals, will occur.
Alachlor is expected to have some adverse effects on terrestrial plants, at least close to
application sites. The greatest concern at present is for impacts on aquatic ecosystems, resulting from
effects on aquatic plants, and perhaps occasionally from direct effects on aquatic animals.
Substantial reduction in the risk to aquatic species and ecosystems can only be obtained by
a widespread reduction in use. The registrant has voluntarily reduced the maximum single application
rate of alachlor from 6 to 4 lb ai/acre. New labels with the 4 lb ai/acre rate were approved by the
Agency on June 30, 1998.
4. Surface Water Protection Measures
Alachlor levels observed in monitoring studies are sufficient to result in effects on aquatic
plants and indirectly on aquatic animals. The available monitoring information indicate that drinking
water supply systems usually comply with the Safe Drinking Water Act. Alachlor in the water
sources (i.e., annual averages) will rarely exceed the current MCL of 2 |ig/L. Particularly relevant
sources of monitoring information are recent (1992-1996), extensive data collected by the Acetochlor
Registration Partnership monitoring 175 surface water sites, and by the US Geological Survey in
reconnaissance surveys of Midwestern streams and reservoirs. Such data may reflect reported
substantial decreases in alachlor use. However, the concentration of alachlor ESA in surface water
poses a potential human health risk. The concentration of alachlor ESA often greatly exceeds the
concentration of parent alachlor and often occurs at concentrations of several ppb even in early spring
before alachlor application.
At this time the toxicity of alachlor ESA to certain aquatic species cannot be fully assessed.
Additional studies to characterize the potential ecological effects of alachlor ESA are required. There
are concerns about the possible risk posed by exposure to other major degradates of alachlor such
as alachlor DM-oxanilic acid, alachlor oxanilic acid, and alachlor sulfinylacetic acid.
Since available monitoring data show that alachlor degradates are more frequently found than
the parent, validated analytical methods for these degradates (including alachlor ESA) are needed.
These methods must have minimum detection limits of equal to or less than 0.1 |ig/L in water. In
addition to the parent alachlor, it is required that the registrant supply standards of alachlor
degradates (alachlor ESA, alachlor DM-oxanilic acid, alachlor oxanilic acid, and alachlor
sulfinylacetic acid) to the EPA Pesticide Repository.
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Labeling as specified in Section V will reduce the potential for incidents of contamination of
surface water. Surface water monitoring, which will include some of the alachlor degradates,
is being performed by the Acetochlor Registration Partnership (ARP), USGS National Water Quality
Assessment Program (NAWQA), and various State Programs.
5. Ground Water Protection Measures
Several recent studies have found alachlor degradates in groundwater samples, including
alachlor ESA and alachlor oxanilic acid. These degradates are more persistent than parent alachlor
and appear to be widespread in groundwater. Alachlor ESA has been detected almost 10 times more
frequently than alachlor, and is the most frequently reported pesticide related compound in ground
water monitoring studies for pesticides in the midcontinent area. Alachlor ESA has been found up
to a maximum concentration of 8.6 |ig/L in 45 to 70 percent of Midwestern groundwater wells
sampled in a study focused on near-surface aquifers in corn and soybean growing areas. Another
study (Potter and Carpenter, 1995) sampled groundwater from a cornfield in Massachusetts. The last
application of alachlor was three years prior to the sampling. Twenty alachlor degradation products
as well as atrazine, metolachlor, carbofuran and their various degradation products were detected.
The Agency has significant concerns about the impact alachlor and its degradates may have
on ground water quality. Consideration of environmental chemistry and fate properties indicates that
alachlor and a number of alachlor degradates will leach to ground water. An extensive body of
groundwater monitoring information has been reviewed which confirms that alachlor and alachlor
degradates do in fact contaminate groundwater.
EPA will take additional measures for the protection of groundwater resources as follows:
• EPA will require labeling as specified in Section V to reduce the potential for incidents of
contamination of groundwater.
• EPA will classify alachlor as a restricted use pesticide for groundwater concerns.
• EPA has included alachlor in its proposed Ground Water and Pesticides Management Plan
Rule as one of the chemicals that would require an approved State or Tribal Management
Plan to allow its use within the State or Tribe's jurisdiction.
• EPA will continue to consider results of monitoring by others such as the USGS National
Water Quality Assessment program (NAWQA), and the Acetochlor Registration
Partnership(ARP).
Additionally, once the Agency's Ground Water and Pesticides Management Plan Rule is final,
the Agency will utilize as appropriate, sampling information that may be available as a result of State
and Tribal Plans. If new information on the toxicity of the degradates or their cumulative or
aggregate effects come to the Agency's attention, or if monitoring and sampling data demonstrate
increased risk , then EPA may reassess its position relative to ground water concerns.
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6. Restricted Use Classification
Currently all alachlor labels contain the following statement "RESTRICTED USE
PESTICIDE due to oncogenicity. For retail sale to and use only by Certified Applicators or persons
under their direct supervision and only for those uses covered by the Certified Applicator's
certification."
This restriction is no longer required. However, the registrant, Monsanto, has voluntarily
offered to classify alachlor as a Restricted Use Pesticide due to groundwater concerns. Thus, alachlor
remains a Restricted Use Pesticide. See Section V Table 78 for labeling language.
7. Pesticides Management Plan (PMP) Candidate
In addition to classifying a pesticide for restricted use for or by a certfied applicator as
discussed above, FIFRA section 3(d)( 1 )(C)(ii) gives EPA authority to classify a pesticide subject to
such other restrictions, if EPA finds its use may cause unreasonable adverse effects on the
environment. EPA is proposing to restrict the legal sale and use of several pesticides, one of which
is alachlor, by requiring Pesticide Management Plans (PMPs) as an "other restriction" through the
proposed Ground Water and Pesticides Management Plan Rule (formerly, State Management Plan
Rule) fFederal Register. Volume 61, No. 124, June 26, 1996).
Once the Rule is finalized, the labels of these pesticides would be changed to require use in
accordance with an EPA-approved PMP. All products subject to a PMP would bear the following
statement "For use only in accordance with an EPA-approved Pesticide Management Plan (PMP) for
groundwater protection. Sale and use are prohibited in States and Indian Nations that do not have
an EPA-approved PMP." Once the Rule becomes effective, use of the chemicals subject to the rule
will not be allowed unless an approved Plan is in place.
PMPs will provide States and Tribes with the flexibility to protect the groundwater in the
most appropriate way for local conditions. To help States and Tribes achieve the ability to protect
their groundwater, EPA strongly encourages the alachlor registrants to cooperate with States and
Tribes, particularly with monitoring and vulnerability assessments. Registrants are also encouraged
to help with other requirements as outlined in the EPA "Guidance for Pesticides and Ground Water
State Management Plans" EPA 735-B-93-005a, December 1993. Without this cooperation, State
and Tribal lead agencies must assume the major burden for Plan development to address potential
ground water concerns related to the continued use of alachlor.
The eligibility determination made at this time is based upon a presumption that registrations
will conform to all applicable requirements of the final regulation addressing this issue.
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8. Endangered Species Statement
Currently, the Agency is developing "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
use restrictions to protect endangered and threatened species at the county level. Consultations with
the Fish and Wildlife Service may be necessary to assess risks to newly listed species or from
proposed new uses. In the future, the Agency plans to publish a description of the Endangered
Species Program in the Federal Register and have available voluntary county-specific bulletins.
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.
9. Labeling Rationale
Occupational Labeling Rationale/Risk Mitigation
Alachlor is a restricted use pesticide; therefore, alachlor can be used only by certified
applicators and cannot be purchased or used by the general public. The Agency has not identified any
alachlor products that are intended for home use, or uses in/around schools, parks, or other public
areas. No registered use is likely to involve applications at residential sites.
Restricted Use Classification
Alachlor will be classified as a RUP due to groundwater concerns.
The Worker Protection Standard fWPS)
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. At this time
all registered uses of alachlor are within the scope of the WPS.
In general, WPS products had to bear WPS-complying labeling when sold or distributed after
April 21, 1994. The WPS labeling requirements pertaining to personal protective equipment (PPE),
restricted-entry intervals (REI), and notification are interim. These requirements are to be reviewed
and revised, as appropriate, during reregi strati on and other Agency review processes.
Personal Protective Equipment for Handlers (Mixers. Loaders. Applicators, etc.')
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For each end-use product, PPE requirements for pesticide handlers are set during
reregi strati on in one of two ways:
1. If EPA determines that no regulatory action must be taken as the result of the acute effects
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 must be
established using the process described in PR Notice 93-7 or more recent EPA guidelines.
2. If EPA determines that regulatory action on an active ingredient must be taken as the result
of very high acute toxicity or certain other adverse effects, such as allergic effects or systemic
effects (cancer, developmental toxicity, reproductive effects, etc.):
# In the RED for that active ingredient, EPA may establish minimum or "baseline"
handler PPE requirements that pertain to all or most 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 toxicity of the end-use product.
# The more stringent choice for each type of PPE (i.e., bodywear, hand protection,
footwear, eyewear, etc.) must be placed on the label of the end-use product.
Personal protective equipment requirements usually are set by specifying one or more pre-
established PPE units — sets of items that are almost always required together. For example, if
chemical-resistant gloves are required, then long-sleeve shirts, long pants, socks, and shoes are
assumed and are also included in the required minimum attire. If the requirement is for two layers
of body protection (coveralls over a long- or short-sleeve shirt and long or short pants), the minimum
must also include (for all handlers) chemical-resistant footwear and chemical-resistant headgear for
overhead exposures and (for mixers, loaders, and persons cleaning equipment) chemical-resistant
aprons.
Occupational-Use Products
EPA is establishing ai specific requirements for some occupational handlers for certain
formulations of alachlor. The MOE's for short- and intermediate-term exposure were a concern for
some occupational mixers, loaders, applicators, and flaggers. Since the NOELs for estimating short-
and intermediate-term occupational risks are different, the resultant MOEs are also different. EPA
is regulating on the intermediate-term endpoint, since (1) the risks resulting from intermediate-term
exposures are greater, and (2) the available information for pre-plant herbicide and fertilizer
applications indicate that a window of approximately 28 days is available once weather and field
conditions are right and equipment can enter the fields.
For the granular formulations, (for mixer/1 oader/applicators) the estimated risks were greater
than 100 at baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks). Therefore, no ai
specific requirements are being established for the granular formulations of alachlor.
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For the liquid (emulsifiable concentrate) formulations, the risks were greater than 100 at
baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks) for applicators using groundboom
equipment, and for flaggers.
However, for mixers and loaders supporting groundboom application, the MOEs estimated
for intermediate term risk are acceptable (i.e., 250 at 4.0 pounds active ingredient per acre and 300
at 3.0 pounds active ingredient per acre) only with the addition of personal protective equipment.
Instead of requiring mixers and loaders to wear a coverall, over their long-sleeve shirts and long
pants, EPA will require the addition of a chemical-resistant apron and chemical-resistant footwear
(plus chemical-resistant gloves). Although EPA has no data to specifically assess the exposure
reduction to mixers and loaders afforded by a chemical-resistant apron, the Agency is persuaded that
the exposure reduction would be significant. Available data indicate that the preponderance of non-
hand exposure to mixers and loaders is to the front torso. Therefore, for mixers and loaders the use
of a chemical-resistant apron is probably approximately equivalent to double-layer body protection.
The chemical-resistant footwear will provide an additional, although not quantifiable, reduction in
exposure.
For mixers and loaders supporting aerial application, the MOEs estimated for intermediate-
term risk are 93 at 4.0 pounds active ingredient per acre and 130 at 3.0 pounds active ingredient per
acre) only with the addition of personal protective equipment (i.e., double-layers of body protection
and chemical-resistant gloves). Current labels require the use of a closed (mechanical transfer) system
for all mixer/loaders and/or applicators who treat 300 acres or more annually with pesticides
containing alachlor. Thus, due to the existence of these systems, the Agency does not believe that
requiring closed (mechanical transfer) systems for mixer/loaders supporting aerial application and
chemigation will create an undue hardship. Therefore, for liquid (EC) formulations for workers
supporting aerial applications, EPA will require the use of a closed (mechanical transfer) system.
Workers will be required to wear long pants, long-sleeved shirts, and chemical resistant gloves.
For the dry flowable formulations, the estimated risks from both the short- and intermediate-
term endpoint were greater than 100 at baseline attire (i.e., long-sleeve shirt, long pants, shoes, and
socks) for mixers and loaders supporting groundboom application, applicators using groundboom
equipment, and for flaggers. EPA will require the addition of a chemical-resistant apron and
chemical-resistant footwear (plus chemical-resistant gloves).
However, for mixers and loaders supporting aerial application, the MOEs estimated for
intermediate-term risk endpoint are marginal (i.e., 61 at 4.0 pounds active ingredient per acre and 82
at 3.0 pounds active ingredient per acre) even with the addition of personal protective equipment (i.e.,
double-layers of body protection and chemical-resistant gloves). To mitigate the risks Monsanto may
develop water soluble packaging (WSP) for the dry flowable formulations. However, if the WSP
is not practicable, then this use will be voluntarily canceled by Monsanto.
For applicators using fixed- and rotary-wing aircraft to apply the liquid or dry flowable
formulations, the risks are acceptable (i.e., ranging from 500 to 1,600) when enclosed cockpits are
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assumed. Since the Pesticide Handlers Exposure Database does not contain sufficient data to estimate
exposure to applicators using aircraft with open cockpits, only exposure for aerial applicators using
engineering controls, (i.e., enclosed cockpits) was estimated. Since the MOEs are acceptable at
baseline attire for applicators using groundboom equipment and for flaggers, and the MOEs are high
for applicators using enclosed cockpits, the Agency does not have concerns for handlers who may
apply alachlor using aircraft with open cockpits. Additionally, the Agency does not believe that open
cockpits are being used extensively.
For mixers and loaders who impregnate dry bulk fertilizer with alachlor, the estimated risks
are acceptable (ranging from 110-220) for short-term exposures with the use of baseline attire plus
chemical-resistant gloves and a closed transfer system; however the risks are unacceptable (ranging
from 10-20) for intermediate-term exposures even with the use of baseline attire, chemical-resistant
gloves, and a closed transfer system. EPA notes that many assumptions were made in performing this
assessment and acknowledges that many of the assumptions were deliberately intended toward
performing an upper-end assessment. For example, one high-end assumption is that the mixing tower
would run at full capacity for 8 hours a day and thus generate 960 tons of alachlor impregnated
fertilizer. EPA also notes that these estimates are based on using dermal unit exposure data from
PHED VI. 1. for a closed mixing/loading system (i.e., mechanical transfer) from individual containers
into mix tanks typically used in agricultural field conditions. The amount of alachlor necessary to
impregnate the tons of fertilizer processed in a day probably involves transfer from huge containers
such as tanker trucks or railroad tank cars, rather than from individual containers. Therefore, using
unit exposure from the available PHED data is likely to result in an over-estimate. EPA currently does
not have data for bulk transfer/loading. Given these and other uncertainties, EPA has determined that
additional data are necessary to appropriately assess this use pattern. Therefore, the Agency is calling
in data on dermal and inhalation exposure to handlers who are engaged in impregnating fertilizer with
alachlor. In the interim, EPA is requiring such handlers to wear long pants, long sleeved shirts, and
chemical-resistant gloves, and to use closed (e.g., mechanical transfer) systems. This exposure
scenario will be reevaluated upon receipt of the requested data.
For handlers who apply dry bulk fertilizer impregnated with alachlor, the estimated risks were
acceptable (ranging from 98 to 1300) at baseline attire using open cabs. Therefore, no ai specific
requirements are being established for the application of dry bulk fertilizer impregnated with alachlor.
Post-Application/Entry Restrictions
Occupational-Use Products (WPS Uses)
Restricted-Entry Interval: Under the Worker Protection Standard (WPS), interim
restricted-entry intervals (REI's) 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
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the three is classified as category II, the interim WPS REI is established at 24 hours. If none of the
three acute toxicity effects are in category I or II, the interim WPS REI is established at 12 hours. A
48-hour REI is increased to 72 hours when an organophosphate 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 that would be established under the WPS.
During the reregi strati on process, EPA considers all relevant product-specific information to
decide whether there is reason to shorten or lengthen the previously established REI.
During the reregi strati on process, EPA determined that the restricted-entry interval for all
occupational-use products that contain alachlor and are within the scope of the Worker Protection
Standard for Agricultural Pesticides (WPS) should be 12 hours.
Alachlor is not a candidate for the 4-hour REI, since both the acute oral and acute inhalation
toxicity studies are category III.
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 a
requirement that personal protective equipment be worn. Under the WPS, these personal protective
equipment requirements for persons who must enter areas that remain under a restricted-entry interval
are based on the acute toxicity category of the active ingredient.
During the reregi strati on process, EPA considers all relevant product-specific information to
decide whether there is reason to set personal protective equipment requirements that differ from
those set through the WPS. The RED requirements for early-entry personal protective equipment
are set in one of two ways:
1. If EPA determines that no regulatory action must be taken as the result of the acute effects
or other adverse effects of an active ingredient, it establishes the early-entry PPE requirements
on the basis of the acute dermal toxicity category, skin irritation potential category, and eye
irritation potential category of the active ingredient.
2. If EPA determines that regulatory action on an active ingredient must be taken as the result
of very high acute toxicity or to certain other adverse effects, such as allergic effects or
delayed effects (cancer, developmental toxicity, reproductive effects), it may establish early-
entry PPE requirements that are more stringent than would be established otherwise.
During the reregi strati on process, EPA determined that the early-entry personal protective
equipment for all occupational-use products that contain alachlor and are within the scope of the
Worker Protection Standard for Agricultural Pesticides (WPS) are: coverall, chemical-resistant
gloves, and shoes plus socks.
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WPS Double Notification Statement:
"Double" notification is the statement on the labels of some pesticide products requiring
employers to notify workers about pesticide-treated areas orally as well as by posting of the treated
areas. The interim WPS "double" notification requirement is imposed if the active ingredient is
classified as toxicity category I for acute dermal toxicity or skin irritation potential. During the
reregi strati on process, EPA determined that for alachlor double notification is not required.
Other Labeling Requirements
The Agency is also requiring other use and safety information to be placed on the labeling of
all end-use products containing alachlor. For the specific labeling statements, refer to Section V of
this document.
10. Spray Drift Advisory
The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and
State Lead Agencies for pesticide regulation to develop the best spray drift management practices.
The Agency is now requiring interim measures that must be placed on product labels/labeling as
specified in Section V. Once the Agency completes its evaluation of the new data base submitted by
the Spray Drift Task Force, a membership of U.S. pesticide registrants, the Agency may impose
further refinements in spray drift management practices to further reduce off-target drift and risks
associated with this drift.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregi strati on of
both manufacturing-use and end-use products containing alachlor as an active ingredient..
a. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of alachlor for the above eligible uses has
been reviewed and determined to be substantially complete. The following studies are required and
considered confirmatory to our conclusion of Eligibility for reregistration:
• 71-4 Avian reproduction (two species)
• 122-2 Aquatic plant studies with the parent alachlor with an aquatic macrophyte, a marine
diatom, a blue-green algae and a freshwater diatom (These studies were recently submitted
to the Agency and are now under review.)
• 122-2 Aquatic plant studies with alachlor ESA with 5 aquatic plant species
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• 171-4 Validated analytical method for degradates, methods must have minimum detection
limits equal to or less than 0.1 ug/L in water
• 231, 232, 233, and 234 (now 875.2400 and 875.2500) Handler exposure studies are required
for impregnating dry bulk fertilizer with alachlor (including use of mini-bulk containers) and
distribution-to-field application exposure scenarios. Samples for dermal and inhalation
exposure should be taken concurrently. Both outdoor and indoor (at least partially enclosed)
sites are required.
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP) labeling must be
revised to comply with all current EPA regulations, PR Notices and applicable policies. The MP
labeling must bear the labeling contained in Table 78 at the end of this section.
b. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific data
regarding the pesticide after a determination of eligibility has been made. The product specific data
requirements are listed in Appendix G, the Product Specific Data Call-In Notice.
Registrants must review previous data submissions to ensure that they meet current EPA
acceptance criteria (Appendix F; Attachment E) and if not, commit to conduct new studies. If a
registrant believes that previously submitted data meet current testing standards, then study MRID
numbers should be cited according to the instructions in the Requirement Status and Registrants
Response Form provided for each product.
2. Labeling Requirements for End-Use Products
All end-use products should have clear, concise and complete labeling instructions. Proper
labels can improve reader understanding, thereby reducing misuse and the potential for incidents.
Towards this end, the Agency is requiring the following:
Directions for Use:
Directions for Use must be stated in terms that can be easily read and understood by the
average person likely to use or to supervise the use of the pesticide. It must be presented in a format
that is easy to understand and follow. The Directions for Use section of a pesticide label must provide
the necessary information to answer four major categories regarding the use of the pesticide. These
four questions are:
1) Why is the pesticide being used? For what pest(s) or problem?
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2) Where is the pesticide applied? (Where should it not be applied?)
3) How is the pesticide applied? (What special precautions must the user take? How
much should they use?)
4) When should the pesticide be applied?
In addition, the Agency encourages the use of clearly understood, widely recognized graphic
symbols whenever possible, to clarify the written label.
National Pesticide Telecommunications (NPTN) Hotline Number
All alachlor labels must refer consumers to the NPTN number for additional information. This
reference must bear the labeling contained in Table 78 at the end of this section.
First Aid (Statement of Practical Treatments
The Agency is requiring that all labels with Statement of Practical Treatment sections be
amended so that these sections are entitled, "First Aid." First aid statements must be brief, clear,
simple and in straightforward language (conforming to the labeling required by the Agency) so that
the average person can easily and quickly understand the instructions. These statements should be
appropriate for all ages or, when necessary, should include distinctions between the treatments for
different ages.
Labeling Requirements
Table 78 summarizes the labeling requirements being imposed by this RED for all alachlor
products. Any use instructions on current labels that conflict with those listed in Table 78 should be
removed.
For sole-active-ingredient end-use products that contain alachlor:
Revise the product labeling to adopt the handler personal protective
equipment/engineering control requirements set forth in Table 78, and .
Revise the product labeling to adopt the entry restrictions set forth in Table 78.
For multiple-active-ingredient end-use products that contain alachlor:
Compare the handler personal protective equipment/engineering control requirements
set forth in Table 78 to the requirements on the current labeling, then
Retain the more protective requirements. (For guidance on which requirements are
considered more protective, see PR Notice 93-7).
Compare the entry restrictions set forth in Table 78 to the entry restrictions on the
current labeling, then
Retain the more protective restrictions. (A specific time period in hours or days is
considered more protective than "sprays have dried" or "dusts have settled.")
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The PPE that would be established on the basis of the acute toxicity category of the end-use
product must be compared to the active-ingredient specific personal protective equipment specified
above. The more protective PPE must be placed on the product labeling. For guidance on which PPE
is considered more protective, see PR Notice 93-7.
EPA is not establishing active-ingredient-specific PPE for WPS occupational uses of alachlor
end-use products formulated as a granular, or for the application of dry bulk fertilizer impregnated
with alachlor.
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
Manufacturing Use
One of these statements
may be added to a label to
allow reformulation of the
product for a specific use
or all additional uses
supported by a formulator
or user group
"Only for formulation into a herbicide for the following use(s) [fill blank only with those uses that
are being supported by MP registrant]."
"This product may be used to formulate products for specific use(s) not listed on the MP label if
the formulator, user group, or grower has complied with U.S. EPA submission requirements
regarding support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the MP
label if the formulator, user group, or grower has complied with U.S. EPA submission
requirements regarding support of such use(s)."
Directions for Use
Environmental Hazards
Statements
"This chemical is toxic to terrestrial and aquatic plants, fish and aquatic invertebrates. Do not
discharge effluent containing this product into lakes, streams, ponds estuaries, oceans or other
waters unless in accordance with the requirements of a National Pollutant Discharge Elimination
System (NPDES) permit and the permitting authority has been notified in writing prior to
discharge. Do not discharge effluent containing this product to sewer systems without previously
notifying the local sewage treatment plant authority. For guidance contact your state Water
Board or Regional Office of the EPA."
End-Use Products Intended for Occupational Use (WPS )
Restricted Use Pesticide
"RESTRICTED USE PESTICIDE due to groundwater concerns. For retail sale to and use only
by Certified Applicators or persons under their direct supervision and only for those uses covered
by the Certified Applicator's Certification."
Top of Front Panel and
Beginning of Directions
for Use
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
Notice to Users
While alachlor has produced tumors in laboratory animals, extensive studies have established that
alachlor is unlikely to be a human carcinogen at low levels of exposure. However, even when
used according to label directions, some exposure will result. Therefore, users must read and
follow all Precautionary Statements, Environmental Hazards, and Directions for Use to minimize
exposure to this product.
Beginning of Directions
for Use
Precautionary Labeling
"For information on this pesticide product (including health concerns, medical emergencies, or
pesticide incidents), call the National Pesticide Telecommunications Network at 1-800-858-
7378."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Precautionary Labeling
"This product may cause skin sensitization reactions in some people."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
PPE Requirements:
Liquid (emulsifiable
concentrate) and dry
flowable formulations
"Mixers, loaders, and persons cleaning equipment in support of groundboom application must
wear:
-long-sleeved shirt and long pants,
-chemical-resistant gloves,*
-chemical-resistant footwear, and
-chemical-resistant apron."
*For the glove statement, use the statement established for alachlor through the instructions in
Supplement Three of PR Notice 93-7.
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for
washables exist, use detergent and hot water. Keep and wash PPE separately from other
laundry."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
(Immediately following
the PPE Requirements)
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
Engineering Controls
"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 (40CFR
170.240(d)(4.6), the handler PPE requirements may be reduced or modified as specified in the
WPS."
"Mixers and loaders supporting aerial applications, chemigation, or impregnation of dry bulk
fertilizer are required to use closed systems. The closed system must be used in a manner that
meets the requirements listed in the Worker Protection Standard (WPS for agricultural pesticides
(40CFR 170.240(d)(4))."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals (Immediately
following PPE and user
Safety Statements
Engineering Controls for
all Dry Flowable
Formulations
In addition to the above Engineering Controls statement, dry flowable formulations must also
have the following statement:
"Water soluble packaging when used correctly qualify as a closed loading system under the WPS.
Handlers handling this product while it is enclosed in intact water-soluble packaging are
permitted to wear long-sleeved shirt, long pants, shoes and socks, and chemical resistant gloves."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
(Immediately following
User Safety
Requirements)
Engineering Controls for
all Liquid (emusifiable
concentrate) Formulations
In addition to the above Engineering Controls statement, liquid formulations must also have the
following statement:
"Mixers and loaders are required to use closed (mechanical transfer) systems. Handlers using
closed systems are permitted to wear long-sleeved shirt, long pants, shoes and socks, and
chemical resistant gloves."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals (Immediately
following User Safety
Requirements)
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
User Safety
Recommendations
"User Safety Recommendations"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the
toilet."
"Users should remove clothing/PPE 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."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
(Must be placed in a
box.)
(Immediately following
Engineering Controls)
Environmental Hazards
for liquid (emulsifiable
concentrate) or dry
flowable formulations
"This chemical is toxic to terrestrial and aquatic plants, 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 high-water mark. Runoff may be hazardous to aquatic organisms in neighboring areas."
Precautionary
Statements under
Environmental Hazards
Section
Environmental Hazards
for granular product
formulations
"This chemical 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 high-water mark.
Runoff may be hazardous to aquatic organisms in neighboring areas. Cover or incorporate
granules that are spilled during loading or are visible on soil surface in turn areas. "
Precautionary
Statements under
Environmental Hazards
Section
Ground and Surface Water
Statements
"Alachlor can contaminate surface water through spray drift. Under some conditions, alachlor
may also have a high potential for runoff into surface water (primarily via dissolution in runoff
water), for several weeks post-application. These include poorly draining or wet soils with
readily visible slopes toward adjacent surface waters, frequently flooded areas, areas over-laying
extremely shallow ground water, areas with in-field canals or ditches that drain to surface water,
areas not separated from adjacent surface waters with vegetated filter strips, and areas over-laying
tile drainage systems that drain to surface water. Do not apply to water or to areas where surface
water is present, or to intertidal areas below the mean high water mark."
Environmental Hazards
Section
Ground and Surface Water
Statements
"Do not contaminate water when disposing of equipment wash water or rinsate."
Environmental Hazards
Section
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
Ground and Surface Water
Statements
"This chemical and/or its metabolites are known to leach through soil into ground water under
certain conditions as a result of registered uses. Use of this chemical in areas where soils are
permeable, particularly where the water table is shallow, may result in ground-water
contamination."
Environmental Hazards
Section
Ground and Surface Water
Statements
"Do not apply to highly permeable soils (as classified by the USD A Natural Resources
Conservation Service) where the depth to ground water is 30 feet or less."
Environmental Hazards
Section
Restricted-Entry Interval
(required by Supplement
Three of PR Notice 93-7)
"A 12-hour restricted-entry interval (REI) is required for uses within the scope of the WPS on all
alachlor end-use products. Exception: if the product is soil-injected or soil-incorporated, the
Worker Protection Standard, under certain circumstances, allows workers to enter the treated area
if there will be no contact with anything that has been treated."
Directions for Use,
Agricultural Use
Requirements Box
Personal protective
equipment required for
early entry
"The PPE required for early entry is:
-coveralls,
-chemical-resistant gloves, and
-shoes plus socks."
Directions for Use,
Agricultural Use
Requirements Box
Application Restrictions
"Do not apply this product by any method not specified on this label."
"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."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"Aerial Spray Drift Management"
"Avoiding spray drift at the application site is the responsibility of the applicator. The interaction
of many equipment-and-weather-related factors determine the potential for spray drift. The
applicator and the grower are responsible for considering all these factors when making
decisions."
Directions for Use
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
The following language
must be placed on each
product that can be
applied aerially:
"The following drift management requirements must be followed to avoid off-target drift
movement from aerial applications to agricultural field crops. These requirements do not apply to
forestry applications, public health uses or to applications using dry formulations.
1.The distance of the outer most nozzles on the boom must not exceed 3/4 the length of the
wingspan or rotor.
2.Nozzles must always point backward parallel with the air stream and never be pointed
downwards more than 45 degrees.
Where states have more stringent regulations, they should be observed.
The applicator should be familiar with and take into account the information covered in the
Aerial Drift Reduction Advisory Information."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"Aerial Drift Reduction Advisory"
"This section is advisory in nature and does not supersede the mandatory label requirements."
"INFORMATION ON DROPLET SIZE"
"The most effective way to reduce drift potential is to apply large droplets. The best drift
management strategy is to apply the largest droplets that provide sufficient coverage and control.
Applying larger droplets reduces drift potential, but will not prevent drift if applications are made
improperly, or under unfavorable environmental conditions (see Wind, Temperature and
Humidity, and Temperature Inversions)."
Directions for Use
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
"CONTROLLING DROPLET SIZE"
" ! Volume - Use high flow rate nozzles to apply the highest practical spray volume. Nozzles with
higher rated flows produce larger droplets.
The following language
must be placed on each
product that can be
applied aerially:
! Pressure - Do not exceed the nozzle manufacturer's recommended pressures. For many nozzle
types lower pressure produces larger droplets. When higher flow rates are needed, use higher
flow rate nozzles instead of increasing pressure.
! Number of nozzles - Use the minimum number of nozzles that provide uniform coverage.
! Nozzle Orientation - Orienting nozzles so that the spray is released parallel to the airstream
produces larger droplets than other orientations and is the recommended practice. Significant
deflection from horizontal will reduce droplet size and increase drift potential.
! Nozzle Type - Use a nozzle type that is designed for the intended application. With most nozzle
types, narrower spray angles produce larger droplets. Consider using low-drift nozzles. Solid
stream nozzles oriented straight back produce the largest droplets and the lowest drift."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"BOOM LENGTH"
"For some use patterns, reducing the effective boom length to less than 3/4 of the wingspan or
rotor length may further reduce drift without reducing swath width."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"APPLICATION HEIGHT"
"Applications should not be made at a height greater than 10 feet above the top of the largest
plants unless a greater height is required for aircraft safety. Making applications at the lowest
height that is safe reduces exposure of droplets to evaporation and wind."
Directions for Use
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
The following language
must be placed on each
product that can be
applied aerially:
"SWATH ADJUSTMENT"
"When applications are made with a crosswind, the swath will be displaced downward.
Therefore, on the up and downwind edges of the field, the applicator must compensate for this
displacement by adjusting the path of the aircraft upwind. Swath adjustment distance should
increase, with increasing drift potential (higher wind, smaller drops, etc.)"
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"WIND"
"Drift potential is lowest between wind speeds of 2-10 mph. However, many factors, including
droplet size and equipment type determine drift potential at any given speed. Application should
be avoided below 2 mph due to variable wind direction and high inversion potential. NOTE:
Local terrain can influence wind patterns. Every applicator should be familiar with local wind
patterns and how they affect spray drift."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"TEMPERATURE AND HUMIDITY"
"When making applications in low relative humidity, set up equipment to produce larger droplets
to compensate for evaporation. Droplet evaporation is most severe when conditions are both hot
and dry."
Directions for Use
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
The following language
must be placed on each
product that can be
applied aerially:
"TEMPERATURE INVERSIONS"
"Applications should not occur during a temperature inversion because drift potential is high.
Temperature inversions restrict vertical air mixing, which causes small suspended droplets to
remain in a concentrated cloud. This cloud can move in unpredictable directions due to the light
variable winds common during inversions. Temperature inversions are characterized by
increasing temperatures with altitude and are common on nights with limited cloud cover and
light to no wind. They begin to form as the sun sets and often continue into the morning. Their
presence can be indicated by ground fog; however, if fog is not present, inversions can also be
identified by the movement of smoke from a ground source or an aircraft smoke generator.
Smoke that layers and moves laterally in a concentrated cloud (under low wind conditions)
indicates an inversion, while smoke that moves upward and rapidly dissipates indicates good
vertical air mixing."
Directions for Use
The following language
must be placed on each
product that can be
applied aerially:
"SENSITIVE AREAS"
"The pesticide should only be applied when the potential for drift to adjacent sensitive areas (e.g.
residential areas, bodies of water, known habitat for threatened or endangered species, non-target
crops) is minimal (e.g. when wind is blowing away from the sensitive areas)."
Directions for Use
Application Rate Limit for
All End-Use Products
If any alachlor end-use products have application rates that are greater than 41b ai/acre/year, then
the label must be amended to be no more than 4 lb ai/acre/year.
Directions for Use
Directions for
Application
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Table 78: Summary of Required Labeling Changes for Alachlor Products
Description
Required Labeling
Placement
Application Restrictions:
Mixing/Loading Setbacks
"This product may not be mixed or loaded within 50 feet of perennial or intermittent streams and
rivers, natural or impounded lakes and reservoirs. This product may not be mixed/loaded or used
within 50 feet of all wells, including abandoned wells (unless the well has been properly capped
or plugged), drainage wells, and sink holes. Operations that involve mixing, loading, rinsing, or
washing of this product into or from pesticide handling or application equipment or containers
within 50 feet of any well are prohibited unless conducted on an impervious pad constructed to
withstand the weight of the heaviest load that may be positioned on or moved across the pad.
Such a pad shall be designed and maintained to contain any product spills or equipment leaks,
container or equipment rinse or wash-water, and rain water that my fall on the pad. Surface
water shall not be allowed to either flow over or from the pad, which means the pad must be self-
contained. The pad shall be sloped to facilitate material removal. An unroofed pad shall be of
sufficient capacity to contain at a minimum 110% of the capacity of the largest pesticide
container or application equipment on the pad. A pad that is covered by a roof of sufficient size
to completely exclude precipitation from contact with the pad shall have a minimum containment
capacity of 100% of the capacity of the largest pesticide container or application equipment on the
pad. Containment capacities as described above shall be maintained at all times. The above-
specified minimum containment capacities do not apply to vehicles when delivering pesticide
shipments to the mixing/loading site."
Directions for Use
Application Restriction
"Do not apply to highly permeable soils (as classified by the USD A Natural Resources
Conservation Service) where the depth to ground water is 30 feet or less."
Directions for Use
(Under Use Precautions
and Restrictions)
Rotational Crop
Restriction
"Rotation to crops not specified on this label is prohibited"
Directions for Use
(Under Use Precautions
and Restrictions)
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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 Reregi strati on 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 alachlor products bearing
old labels/labeling for 26 months from the date of issuance of this RED. Persons other than the
registrant may distribute or sell such products for 50 months from the date of the issuance of this
RED. Registrants and persons other than registrants remain obligated to meet pre-existing Agency
imposed label changes and existing stocks requirements applicable to products they sell or distribute.
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APPENDICES
211
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Intentionally Blank Page
212
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Appendix A - Table of Use Patterns Subject to this RED
Appendix A is 52 pages long and is not being included in this RED. Copies of Appendix A are
available upon request per the instructions in Appendix E.
213
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Intentionally Blank Page
214
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregi strati on for active
ingredients within the case alachlor covered by this Reregi strati on Eligibility Decision
Document. It contains generic data requirements that apply to alachlor in all products, including
data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which they
appear in 40 CFR Part 158. the reference numbers accompanying each test refer to the test
protocols set in the Pesticide Assessment Guidelines, which are available from the National
Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703)605-6000.
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 31 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.
215
-------
Intentionally Blank Page
216
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT USE PATTERN CITATION(S)
PRODUCT CHFMTSTRY
830.1550
Product Identity
All
00146114
830.1600
830.1620
830.1650
Starting Material & Mnfg. Process
All
00146114, 40396301
830.1670
Formation of Impurities
All
00146114, 00152206
830.1700
Preliminary Analysis
All
00146114, 00152206
830.1750
Certification of limits
All
00146114
830.1800
Analytical Method
All
00146114, 00147476, 00152206, 40396301
830.6302
Color
All
00146114
830.6303
Physical State
All
00146114
830.6304
Odor
All
00146114
830.6313
Stability
All
00146114
830.7000
pH
All
00146114
830.7050
UV
44492301
830.7200
Melting Point
All
00146114
830.7220
Boiling Point
N/A
830.7300
Density
All
00146114
830.7550
Dissociation Constant
N/A
217
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
830.7550
830.7560
830.7570
830.7840
830.7860
Octanol/Water Partition
Solubility
830.7950 Vapor Pressure
ECOLOGICAL EFFECTS
71-1A Acute Avian Oral - Quail/Duck
71-2A Avian Dietary - Quail
71-2B Avian Dietary - Duck
71-4A Avian Reproduction - Quail
71-4B Avian Reproduction - Duck
72-1 Fish Toxicity Bluegill
72-1 Fish Toxicity Rainbow Trout
72-2 Invertebrate Toxicity
72-3 Estuarine/Marine Toxicity - Fish
72-3 Estuarine/Marine Toxicity -
Mollusk
72-3 Estuarine/Marine Toxicity -
Shrimp
72-4A Early Life Stage Fish
All
All
All
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
AB
00146114, 00152209, 00152210, 40396301
00146114, 00152209, 40396301
00146114, 00152209
00079523
43087101
43087001
Data Gap
Data Gap
00023615, 00028551, 00028554, 00031525,
40098001, 43774706
00023616, 00028550, 00028553, 00031524,
40098001, 43774704
00028549, 00028555, 00031526, 40098001,
43774703(2), 43774705(2)
44524301
44524303
44524302
43862601
218
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
72-4B Life Cycle Invertebrate
122-2 Aquatic Plant Phytotoxicity
123-1A Seed Germination/Seedling
Emergence
123-1B Vegetative Vigor
123-2 Aquatic Plant Growth
141-1 Honey Bee Acute Contact
TOXICOLOGY
870.1100 Acute Oral Toxicity - Rat
870.1200 Acute Dermal Toxicity -
Rabbit/Rat
870.1300 Acute Inhalation Toxicity - Rat
870.2400 Primary Eye Irritation - Rabbit
870.2500 Primary Dermal Irritation -
Rabbit
870.2600 Dermal Sensitization - Guinea Pig
870.3100 90-Day Feeding - Rodent
870.3150 90-Day Feeding - Non-rodent
870.3200 21-Day Dermal - Rabbit/Rat
870.4100 Chronic Toxicity and
870.4200 Carcinogenicity - Rodent
870.4300
AB
AB
AB
AB
AB
AB
all
all
all
all
all
all
AB
AB
AB
AB
43774707
Data Gap
for alachlor (data in review)
for alachlor ESA
42468701
42468601
42763801
00074486,00028772
00139383, 42701501(1)
00139384
00109561
00139385
00139386
00161728
00023658, 42863701(1)
00087479
00147328
00139021, 00075709, 00091050, 00141060,
43507601
219
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
870.4100
870.3700
870.3700
870.3800
870.5300
870.5385
870.5500
870.5550
870.5575
870.7485
Chronic Toxicity and
Carcinogenicity - Non-Rodent
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
2-Generation Reproduction - Rat
Mutagenicity
General Metabolism
AB
AB
AB
AB
AB
AB
00148923
00043645, 43908101(1)
40579402
00075062
00109563, 00141061, 00141062, 00148921,
00155389(2), 00155391(2), 00155392(2),
00155393(2), 00151394(2), 0015395(2),
00151396(2), 00151397(2),
00151398(1),00151399(2), 42651301, 42651301(2),
42651302, 42651303, 43889403(1), 44032103
000132045, 43889404(1), 40000901, 42651306,
42852107, 42651308, 42852108, 42651305,
42852106
870.7600
Dermal Penetration
AB
00149403, 00149404, 00149405
Special Studies AB
00023611, 00023612, 00149402, 00149403,
00149404, 00149405, 00150089, 00154238,
00159365, 00159364, 42852102, 43590002,
43889401(1), 43889402(1), 42651307, 42651310,
42852109, 42931101, 42651304, 42651309,
42651311, 42651312, 42651314, 42651318,
42852103, 42852104, 42852105, 42852110,
42852111, 42957201, 43267501, 43369201,
43482301, 43504101, 43507401, 43641603,
43706001, 43590001, 43641604, 43641602,
43729502, 43750801, 43729503, 43729501,
43878501
220
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION(S)
OCCUPATIONAL/RESIDENTIAL EXPOSURE
132-1A
Foliar Residue Dissipation
132-1B
Soil Residue Dissipation
133-3
Dermal Passive Dosimetry
Exposure
133-4
Inhalation Passive Dosimetry
Exposure
231
Estimation of Dermal Exposure at
Outdoor Sites
AB
Data Gap - Impregnation of Dry Bulk
Fertilizer
232
Estimation of Inhalation Exposure
at Outdoor Sites
AB
Data Gap - Impregnation of Dry Bulk
Fertilizer
233
Estimation of Dermal Exposure at
Indoor Sites
AB
Data Gap - Impregnation of Dry Bulk
Fertilizer
234
Estimation of Inhalation Exposure
at Indoor Sites
AB
Data Gap - Impregnation of Dry Bulk
Fertilizer
ENVIRONMENTAL FATE
161-1
Hydrolysis
AB
00134327
161-2
Photodegradation - Water
AB
00023012
162-1
Aerobic Soil Metabolism
AB
00023014, 00101531, 00134327
163-1
Leaching/Adsorption and
Desorption
AB
00027139, 00027140, 00078301, 00134327,
42485703®, 42485704(3), 44405301(1)
164-1
Terrestrial Field Dissipation
AB
42528001, 42528002, 42528003, 42528004,
43774701
221
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
201-1 Droplet Size Spectrum
202-1 Drift Field Evaluation
Special Studies Monitoring Data
RESIDUE CHEMISTRY
165-1 Rotational Crop (Confined)
165-2 Rotational Crop (Field)
171-4A Nature of Residue - Plants
171-4B Nature of Residue - Livestock
AB
AB
AB
AB
AB
AB
AB
Reserved - Spray Drift Task Force (data in
review)
Reserved - Spray Drift Task Force (data in
review)
41400001, 41400002, 41400003, 41400004,
44592401, 40265901, 00158911, 41065205,
441095503
42395301, 42395302
43442001
Data Gap (Data in Review)
00026221, 00081314, 00131424
00137777, 00137778, 00147472,
00147473, 40393901, 40394001, 42594901,
42594902, 42594903, 42594904
171-4C/D Residue Analytical Method -
Plants and Animals
AB
171-4C/D Residue Analytical Method -
Water
AB
00023663,
00149999,
00155732,
40039901,
40271802,
41916001,
42286701,
43140001
Data Gap
PP#9F0740, 00093160, 00148285,
00152197, 00154237, 00154332,
00159793, 00159796, 00162939,
40040301, 40040401, 40271801,
40529201, 40558001, 40820601,
41949601, 42086001, 42192501,
42286702, 42308701, 42349101,
222
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
171-4E Storage Stability
171-4J Magnitude of Residues -
Meat/Milk/Poultry/Egg
171-4K Crop Field Trials
Root and Tuber Vegetable Group
Potatoes
Legume Vegetables (Dry
Succulent) Group
-Beans, succulent and dry
-Peas, succulent and dried
-soybeans
Foliage of Legume Vegetables
Group
-beans, vines and hay
-peas, vines and hay
-soybeans, forage and hay
AB
AB
AB
AB
AB
AB
00149406, 00150090, 00152198, 00152868,
00154237, 40491101, 40628301, 40946901,
42239501
00149406, 00150090, 00152198, 00152868
tolerance revoked
00022988, 00026995, 00035389, 00035390,
00035391, PP#3F1406, 00147475, 40039901,
40040301, 40189701, 40341201, 41083801
tolerance revoked
00023664, 00025262, 00148285, 00152197,
40511901, 41862901, 41916301, 42309001,
42313301, 42348901, 42349101, PP#3F2313
00022988, 00026995, 00035389, 00035390,
00035391, PP#3F1406, 00147475, 40039901,
40040301, 40189701, 40341201, 41083801,
PP#3F4179
tolerance revoked
00023664, 00025262, 00152197, 41140801,
42348901, 42349101, PP#9F3776
223
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT
USE PATTERN
CITATION!S)
Cereal Grains Group
-corn, field, grain
-corn, sweet
-sorghum, grain
Forage. Fodder and Straw of
Cereal Grains Group
-corn, field, forage and fodder
-corn, sweet, forage
-sorghum, forage and fodder
Miscelllaneous Commodities
-Cotton
AB
AB
AB
AB
AB
AB
AB
00023665, 00035395, 00035399, PP#9F0740,
00152197, 00155732, 00159793, 40502101,
42348902, 42349101, 42741601
00023665, 00035395, 00035399, PP#9F0470,
00152197, 00155732, 00159793, 40502101,
40662601, 42929901, 42934401
00028556, 00028557, 00028558,00068044,
00068045, PP#0F2338, 00159796, 40271801,
PP#8F3671
00023665, 00035395, 00035399, PP#9F0740,
00152197, 00159793, 40502101, 42348902,
42349101, PP#0F2348
00023665, 00035395, 00035399, PP#9F0740,
00152197, 00159793, 40502101, 40662601,
42741601, 42929901, PP#0F2348
00068044, 00068045, 00159796, 40271801,
40511201, PP#8F3671
tolerance revoked
-peanuts AB
-sunflower AB
00024526, 00081311, PP#7G2002, 00152199,
00159936, 40511301, 40820601, 42971701,
PP#0F2313, FAP#1H5612
tolerance revoked
224
-------
Data Supporting Guideline Requirements for the Reregistration of Alachlor
REQUIREMENT USE PATTERN CITATION(S)
171-4L
171-5
Processed Food
-corn, field
-peanuts
-sorghum
-soybeans
-sunflower
Reduction of Residues
AB
AB
AB
AB
AB
AB
00162939, 40788201
PP#0F2313/FAP#1H5612, 00162937,
40040401, 41856301, 42302001
40271802
00148285, 00152197, 00154239, 00154240,
40947101, 41862901, 41916301
00147471, 40040101, 40314601, 40529201
40330301, 40820601, 40820701, 42158601,
42276701, 42300701,
42309001
Footnotes:
(1). test material alachlor ESA
(2). test material other metabolites
of alachlor
(3). Test material metabolites of
propachlor
225
-------
Intentionally Blank Page
226
-------
GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies considered
relevant by EPA in arriving at the positions and conclusions stated elsewhere in the Reregi strati on
Eligibility Document. Primary sources for studies in this bibliography have been the body of data
submitted to EPA and its predecessor agencies in support of past regulatory decisions. Selections
from other sources including the published literature, in those instances where they have been
considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case of published
materials, this corresponds closely to an article. In the case of unpublished materials submitted to the
Agency, the Agency has sought to identify documents at a level parallel to the published article from
within the typically larger volumes in which they were submitted. The resulting "studies" generally
have a distinct title (or at least a single subject), can stand alone for purposes of review and can be
described with a conventional bibliographic citation. The Agency has also attempted to unite basic
documents and commentaries upon them, treating them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by Master
Record Identifier, or "MRID number". This number is unique to the citation, and should be used
whenever a specific reference is required. It is not related to the six-digit "Accession Number" which
has been used to identify volumes of submitted studies (see paragraph 4(d)(4) below for further
explanation). In a few cases, entries added to the bibliography late in the review may be preceded by a
nine character temporary identifier. These entries are listed after all MRID entries. This temporary
identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists of a
citation containing standard elements followed, in the case of material submitted to EPA, by a
description of the earliest known submission. Bibliographic conventions used reflect the standard of
the American National Standards Institute (ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to show a
personal author. When no individual was identified, the Agency has shown an identifiable laboratory
or testing facility as the author. When no author or laboratory could be identified, the Agency has
shown the first submitter as the author.
b. Document date. The date of the study is taken directly from the document. When the date is followed
by a question mark, the bibliographer has deduced the date from the evidence contained in the
document. When the date appears as (19??), the Agency was unable to determine or estimate the date
of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or enhance a
document title. Any such editorial insertions are contained between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing parentheses include
(in addition to any self-explanatory text) the following elements describing the earliest known
submission:
(1) Submission date. The date of the earliest known submission appears immediately following the
word "received."
227
-------
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.
Submitter. The third element is the submitter. When authorship is defaulted to the submitter,
this element is omitted.
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.
228
-------
BIBLIOGRAPHY
MRID
CITATION
00022998 Monsanto Company (1968) Full Reports of Investigations Made with Respect to the Safety of
the Pesticide Chemical: [Lasso], Summary of studies 004026-C through 004026-E.
(Unpublished study received Dec 20, 1968 under 524-287; CDL:004026-B)
00023012 Sutherland, M.L.; Curtis, T.G.; Darlington, W.A.; et al. (1972) Final Report on Lasso and the
Environment: Part 4: Photolysis of Lasso on Soil and in Water: Agricultural Research Report
No. 262. (Unpublished study received Jun 29, 1973 under 3F1372; submitted by Monsanto
Co., Washington, D.C.; CDL:093660-L)
00023014 Sutherland, M.L.; Curtis, T.G.; Darlington, W.A.; et al. (1972) Final Report on Lasso and the
Environment: Part 6: Soil Dissipation of Lasso: Agricultural Research Report No. 264.
(Unpublished study received Jun 29, 1973 under 3F1372; submitted by Monsanto Co.,
Washington, D.C.; CDL:093660-N)
00023611 Shelanski, M.V. (1968) To Determine Whether or Not Repeated Contact with the Test
Material under Controlled Conditions Presents a Hazard to the Skin of Human Volunteers:
Project No. SH-67-9. (Unpublished study received Aug 16, 1978 under 524-285; prepared by
Industrial Biology Research and Testing Laboratories, Inc., submitted by Monsanto Co.,
Washington, D.C.; CDL:234629-B)
00023612 Shelanski, M.V. (1968) To Determine If the Test Material Is Capable of Irritating the Skin of
Humans under Controlled Test Conditions: IBT: 1978 under 524-285; prepared by Industrial
Biology Research and Testing Laboratories, Inc., submitted by Monsanto Co., Washington,
D C.; CDL:234629-C)
00023615 Thompson, C.M.; Forbis, A.D.; McAllister, W.A. (1978) Acute Toxicity of Technical Alachlor
(AB-78-166) to Bluegill Sunfish (Lepomis macrochirus). (Unpublished study received Aug 16,
1978 under 524-285; prepared by Analytical Biochemistry Laboratories, Inc., submitted by
Monsanto Co., Washington, D.C.; CDL: 234628-C)
00023616 Forbis, A.D.; McAllister, W.A. (1978) Acute Toxicity of Technical Alachlor to Rainbow Trout
(Salmo gairdneri). (Unpublished study received Aug 16, 1978 under 524-285; prepared by
Analytical Biochemistry Laboratories, Inc., submitted by Monsanto Co., Washington, D.C.;
CDL:234628-D)
00023658 Wolf, C. (1966) Report to Monsanto Company: 90-Day Subacute Oral Toxicity of
CP50144—Albino Rats: IBT No. B4477. (Unpublished study received Dec 1, 1966; prepared
by Industrial Bio-Test Laboratories, Inc., submitted by Monsanto Co., Washington, D.C.;
CDL: 090813-C)
00023663 Monsanto Company (19??) Chemical Analytical Residue Methods. Three undated methods.
(Unpublished study received Dec 1, 1966 under 7F0622; CDL:090813-H)
229
-------
BIBLIOGRAPHY
MRID
CITATION
00023664 Monsanto Company (1966) Results of Analysis of Field Treated Soybeans. (Unpublished
study received Dec 1, 1966 under 7F0622; CDL:090813-I)
00023665 Monsanto Company (1966) Results of Analysis of Field Treated Corn. (Unpublished study
received Dec 1, 1966 under 7F0622; CDL: 090813-J)
00024526 Monsanto Company (1971) Chemical Residue Studies on Peanuts, Peanut Hulls and Peanut
Vines. (Unpublished study received Mar 5, 1975 under 3F1334; CDL:093569-B)
00025262 Monsanto Company (1966) Results of Analysis of Field Treated Soybeans: [Alachlor],
(Unpublished study received Sep 11, 1968 under 9F0740; CDL:091280-B)
00026221 Monsanto Company (19??) Summary on Metabolism of CP 50144 in Soybeans and Corn.
(Unpublished study received Dec 1, 1966 under 7F0622; CDL:090813-M)
00026995 Monsanto Company (1969) Reasonable Grounds in Support of the Petition for Residue
Tolerance: [Lasso], (Unpublished study received on unknown date under 2G1176;
CDL: 09543 3-F)
00027139 Weidner, C.W. (1974) Degradation in Groundwater and Mobility of Herbicides. Master's
thesis, Univ. of Nebraska, Dept. of Agronomy. (Unpublished study received Jul 19, 1978
under 201-403; submitted by Shell Chemical Co., Washington, D.C.; CDL:234472-0)
00027140 Lavy, T.L. (1974) Mobility and Deactivation of Herbicides in SoilWater Systems: Project
A-024-NEB. (Available from: National Technical Information Service, Springfield, VA:
PB-238 632; unpublished study received Jul 19, 1978 under 201-403; prepared by Univ. of
Nebraska, Water Resources Research Institute, submitted by Shell Chemical Co., Washington,
D C.; CDL:234472-P)
00028549 McAllister, W.A.; Forbis, A.D. (1978) Acute Toxicity of Technical Alachlor (AB-78-200) to
Daphnia magna. (Unpublished study received Dec 28, 1979 under 524-285; prepared by
Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto Co., Washington, D.C.;
CDL:241535-A)
00028550 Thompson, C.M.; Forbis, A.D. (1978) Acute Toxicity of Lasso (MCB/ Cg) (AB-78-111) to
Rainbow Trout (Salmo gairdneri). (Unpublished study received Dec 28, 1979 under 524-285;
prepared by Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto Co.,
Washington, D.C.; CDL:241535-B)
00028551 Thompson, C.M.; Forbis, A.D. (1978) Acute Toxicity of Lasso (MCB/ Cg) (AB-78-111) to
Bluegill Sunfish (Lepomis macrochirus). (Unpublished study received Dec 28, 1979 under
524-285; prepared by Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto
Co., Washington, D.C.; CDL: 241535-C)
230
-------
BIBLIOGRAPHY
MRID
CITATION
00028553 Thompson, C.M.; Forbis, A.D. (1978) Acute Toxicity of Lasso EC (MCB) (AB-78-167B) to
Rainbow Trout (Salmo gairdneri). (Unpublished study received Dec 28, 1979 under 524-285;
prepared by Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto Co.,
Washington, D.C.; CDL:241535-E)
00028554 Thompson, C.M.; Forbis, A.D. (1978) Acute Toxicity of Lasso EC (MCB) (AB-78-167) to
Bluegill Sunfish (Lepomis macrochirus). (Unpublished study received Dec 28, 1979 under
524-285; prepared by Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto
Co., Washington, D.C.; CDL:241535-F)
00028555 McAllister, W.A.; Forbis, A.D. (1978) Acute Toxicity of Lasso EC (MCB) (AB-78-167) to
Daphnia magna. (Unpublished study received Dec 28, 1979 under 524-285; prepared by
Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto Co., Washington, D.C.;
CDL:241535-G)
00028556 Lauer, R.; Arras, D.D.; Stranz, J.L.; et al. (1979) Residues of Alachlor and Atrazine in Field
Treated Sorghum following Preor Postemergent Applications with Lasso(R) or a Lasso(R) +
Atrazine Tank Mix: Report No. MSL-1033. Rev. (Unpublished study received Mar 25, 1980
under 524-285; prepared in cooperation with ABC Laboratories, Inc., submitted by Monsanto
Co., Washington, D.C.; CDL:099326-A)
00028557 Monsanto Company (19??) Analytical Residue Method for Alachlor in Sorghum Forage,
Fodder and Grain. Two undated methods. (Unpublished study received Mar 25, 1980 under
524-285; CDL: 099326-B)
00028558 Monsanto Company (19??) Reasonable Grounds in Support of the Request: [Lasso],
(Unpublished study received Mar 25, 1980 under 524-285; CDL:099326-C)
00031524 Thompson, C.M.; Forbis, A.D.; Oleson, F.B.; et al. (1979) Acute Toxicity of Lasso(R)
NF-79-WB (AB-79-068) to Rainbow Trout (Salmo gairdneri): Static Acute Bioassay Report #
24007. (Unpublished study received Jan 17, 1980 under 524-EX-49; prepared in cooperation
with Analytical Bio Chemistry Laboratories, Inc., submitted by Monsanto Co., Washington,
D C.; CDL:241619-E)
00031525 Thompson, C.M.; McAllister, W.A.; Oleson, F.B.; et al. (1979) Acute Toxicity of Lasso(R)
NF-79-WB (AB-79-069) to Bluegill Sunfish (Lepomis macrochirus): Static Acute Bioassay
Report # 24008. (Unpublished study received Jan 17, 1980 under 524-EX-49; prepared in
cooperation with Analytical Bio-Chemistry Laboratories, Inc., submitted by Monsanto Co.,
Washington, D.C.; CDL:241619-F)
00031526 Thompson, C.M.; Forbis, A.D.; Oleson, F.B. (1979) Acute Toxicity of Lasso(R) NF-79-WB
(AB-79-070) to Daphnia magna: Static Acute Bioassay Report # 24009. (Unpublished study
231
-------
BIBLIOGRAPHY
MRID
CITATION
received Jan 17, 1980 under 524-EX-49; prepared in cooperation with Analytical Bio
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00068044 Wilson, G.R.; Dubelman, S. (1981) Residues of Alachlor in Sorghum Forage, Stover, and
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residue method for bifenox (Modown) in sorghum; Analytical residue method for propazine in
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00075709 Daly, I.W.; Hogan, G.K.; Plutnick, R.; et al. (1981) An Eighteen Month Chronic Feeding
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43140001 Schneider, R. (1994) Radiolabeled Validation of the Alachlor Enforcement Method for the
Determination of Alachlor Metabolites Producing 2,6-Diethylaniline (DEA) and
2-(l-Hydroxyethyl)-6-ethylaniline (HEEA) in Animal Products: Lab Project Number:
MSL-13254: 1227. Unpublished study prepared by The Agricultural Group of Monsanto Co.
159 p.
43267501 Ireland, B.; Acquavella, J.; Farrell, T. et al. (1994) Evaluation of Ocular Health among
Alachlor Manufacturing Workers. Unpublished study prepared by Monsanto Co. and
University of Iowa. 20 p.
251
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43369201 Asbury, K.; Wilson, A. (1994) Determination of CP 50144-Derived Radioactivity in Rat: Lab
Project Number: 93043: ML/93/197: 1264. Unpublished study prepared by Monsanto
Environmental Health Laboratory. 29 p.
43442001 Schneider, R.; Sidhu, R. (1994) Alachlor Residues in Rotational Crops Following
Preemergence and Postemergence Sequential Applications of Micro-Tech Herbicide to Field
Corn: Lab Project Numbers: 92-24-R-5: 41254: 92-24-R-5A. Unpublished study prepared by
Monsanto Company. 443 p.
43482301 Asbury, K.; Lau, H.; Hopkins, W.; et al. (1994) In vitro Metabolism of Alachlor
2,6-Diethyl-2-Methylthioacetanilide (Alachlor Secondary Sulfide), Alachlor Sec-Amide, and
2,6-Diethylaniline by Rat and Human Nasal Turbinates and Liver: Lab Project Numbers: EHL
92214: ML-93-14: R.D. 1287. Unpublished study prepared by Monsanto Co. 47 p.
43504101 Kinnet, M.; Lau, H.; Ruecker, F. (1994) Effects of Acute Alachlor Exposure of Hepatotixicity
(sic) and Cell Proliferation in the F344 Rat: Lab Project Number: 92198: ML/92/517.
Unpublished study prepared by Monsanto Environmental Health Lab. 90 p.
43507401 Hall, L.; Wilson, A. (1993) A Study of the Distribution and Localization of Diethylaniline
(DEA) in Rats and Mice Using Whole-Body Autoradiography: Lab Project Number: R.D.
1230: 89081/ML-89-128: EHL 89081. Unpublished study prepared by Monsanto Co. 27 p.
43507601 Roloff, M.; Thake, D.; Heydens, W. (1994) Oncogenicity Study of Alachlor Administered in
Feed to CD-I Mice for 18 Months: Lab Project Number: MSL-13847: EHL 91166:
ML-92-001. Unpublished study prepared by Monsanto Environmental Health Lab and
Experimental Pathology Labs, Inc. 1636 p.
43590001 Branch, D.; Thake, D. (1995) Gastric Tumor Promotion Study of Alachlor in Long-Evans
Rats: Lab Project Number: ML-93-137: EHL 93049: RD 1295. Unpublished study prepared
by Monsanto Co. 463 p.
43590002 Curtiss, S.; Cabonce, M.; Oakley, L.; et al. (1995) Study of the Effects of Alachlor on Cellular
Stress Response Genes in Rat Nasal Turbinate Tissue: Lab Project Number: ML-94-160: EHL
94081: 1295. Unpublished study prepared by Monsanto Co. 61 p.
43641602 Asbury, K.; Lau, H; Wilson, A. (1995) A Study of the Effect of Alachlor and Selected
Metabolites on Cytotoxicity Markers in Nasal Tissue of the Long-Evans Rat: Lab Project
Number: EHL 94070: ML-94-169: MSL 14187. Unpublished study prepared by Monsanto
Co. 37 p.
43641603 Vandenberghe, Y.; Kervyn, S. (1995) Effect of Alachlor on Glutathione Levels of Cultured
Adult Rat Hepatocytes: Lab Project Number: XX-95-043. Unpublished study prepared by
Searle European Development Centre. 40 p.
252
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43641604 Lau, H.; Asbury, K.; McClanahan, R. (1995) Characterization of Covalent Adducts Formed
with Nasal Tissue Protein Following Dietary Administration of (Carbon-14) Alachlor to
Female Long-Evans Rats: Lab Project Number: EHL 94064: ML-94-161. Unpublished study
prepared by Monsanto Co. 72 p.
43706001 Hall, L. (1991) A Study of the Distribution and Localization of Dimethylaniline in Rats and
Mice Using Whole-Body Autoradiography: Lab Project Number: MSL-11227: ML-89-129:
EHL-89082. Unpublished study prepared by Monsanto Environmental Health Lab. 47 p.
43729501 Couch, R.; Hard, G.; Iatropoulos, M. et al. (1995) Effects of Butachlor on the Cell
Proliferation and Mucosal Thickness in the Gastric Tissue of Female Rhesus Monkeys: Lab
Project Number: MSL-14039: WS-93-164: WS-93-165. Unpublished study prepared by
American Health Foundation and White Sands Research Center. 308 p.
43729502 Branch, D.; Thake, D. (1994) Gastric Tumor Initiation/Promotion Study of Butachlor in
Sprague-Dawley Rats: Lab Project Number: ML-92-365: 92142: 1266. Unpublished study
prepared by Monsanto Co. 741 p.
43729503 Reisch, C.; Thake, C.; Wilson, A. (1994) A study of the Effect of Butachlor on Cell
Proliferation in Selected Tissues of the Mouse: Lab Project Number: EHL-93064: ML-93-153:
1266. Unpublished study prepared by American Health Foundation and Monsanto Co. 97 p.
43750801 Thake, D.; Hotz, K.; Reisch, C. et al. (1995) A Study of the Mechanism of Butachlor Induced
Carcinogenicity in Female Sprague-Dawley Rats: Lab Project Number: EHL-92049:
ML-92-146: 1266. Unpublished study prepared by Monsanto, American Health Foundation,
Daiyo-Kai Institute of Medical Science, and others. 1308 p.
43774701 Schneider, R. (1995) Terrestrial Field Dissipation of Alachlor and its Metabolites at Hickman,
California: Lab Project Number: MSL-13960: SARS-93-CA-65: 41125. Unpublished study
prepared by Stewart Agricultural Research Services, Inc. and ABC Labs, Inc. 406 p.
43774702 Phillips, M.; Hall, B. (1995) The Aerobic/Anaerobic Degradation of Radiolabeled Alachlor in
River/Ditch/Pond Waters and Their Associated Sediments: Lab Project Number: IRI 383873:
MSL 14156: 1321. Unpublished study prepared by Inveresk Research International. 104 p.
43774703 Bowman, J.; Hurshman, B. (1994) Acute Toxicity of MON 5775 to Daphnia magna: Final
Report: Lab Project Number: 41728: AB-94-155: R.D. 1321. Unpublished study prepared by
ABC Labs, Inc. 26 p.
43774704 Bowman, J.; Downing, J.; Hurshman, B. (1995) Acute Toxicity of MON 5775 to Rainbow
Trout (Oncorhynchus mykiss): Amended Final Report: Lab Project Number: 41729:
AB-94-156: 1321. Unpublished study prepared by ABC Labs, Inc. 26 p.
253
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43774705 Bowman, P.; Hurshman, B. (1994) Acute Toxicity of MON 5760 to Dahnia magna: Final
Report: Lab Project Number: 41730: AB-94-153: 1321. Unpublished study prepared by ABC
Labs, Inc. 26 p.
43774706 Bowman, J.; Hurshman, B. (1995) Acute Toxicity of MON 5760 to Rainbow Trout
(Oncorhynchus mykiss): Final Report: Lab Project Number: 41731: AB-94-154: 1321.
Unpublished study prepared by ABC Labs, Inc. 27 p.
43774707 Forbis, A. (1995) Chronic Toxicity of Alachlor to Daphnia magna Under Flow-Through Test
Conditions: Final Report: Lab Project Number: 41517: AB-94-061: 1321. Unpublished study
prepared by ABC Labs, Inc. 39 p.
43862601 Rhodes, J.; Muckerman, M. (1995) Early Life-Stage Toxicity of Alachlor to the Rainbow
Trout (Oncorhynchus mykiss) Under Flow-Through Conditions: Lab Project Number: 42187:
AB-94-280: R.D. 1331. Unpublished study prepared by ABC Labs, Inc. 339 p.
43878501 Acquavella, J.; Riordan, S.; Anne, M.; et al. (1995) An Update of Mortality and Cancer
Incidence among Alachlor Manufacturing Workers: Epidemiology Report #9501. Unpublished
study prepared by Monsanto Co. and The University of Iowa. 33 p.
43889401 Hotz, K. (1995) Effect of MON 5775 on Cell Proliferation in the Nasal Tissue of Male F-344
Rats: Lab Project Number: ML-95-070: 95034: R.D. 1335. Unpublished study prepared by
Monsanto Co. 19 p.
43889402 Iatropoulos, M.; Wang, C. (1995) Evaluation of Cell Proliferation and Measurement of
Mucosal Thickness in Gastric Fundi of Rats from Study SB-92-383: Lab Project Number:
AH-95-071: R.D. 1335: SB-92-383. Unpublished study prepared by American Health
Foundation. 20 p.
43889403 Stegeman, S.; Kier, L.; Garret, S.; et al. (1995) Mouse Bone Marrow Micronucleus Assay of
MON 5775: Lab Project Number: ML-95-069: EHL 95030: RD 1335. Unpublished study
prepared by Ceregen, Unit of Monsanto Co. 54 p.
43889404 Kraus, L.; Hopkins, W.; Kinnett, M.; et al. (1995) Elimination, Absorption, Tissue
Distribution, and Metabolism of Alachlor Ethane Sulfonate (MON 5775) in Long-Evans Rats
Following Oral Administration: Lab Project Number: ML-95-066: EHL 95031: MSL 14489.
Unpublished study prepared by Ceregen, Unit of Monsanto Co. 52 p.
43908101 Holson, J. (1995) A Developmental Toxicity Study of MON 5775 in Rats: Lab Project
Number: WIL-50237: WI-95-068: R.D.1335. Unpublished study prepared by WIL Research
Labs, Inc. 292 p.
254
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44032103 Stegeman, S.; Kier, L.; Albin, L.; et al. (1995) Mouse Bone Marrow Micronucleus Assay of
Alachlor: Lab Project Number: ML-95-231: EHL 95082: RD 1348. Unpublished study
prepared by Monsanto Co., Ceregen Unit. 58 p.
44105503 Kirby-Smith, W.; Eisenreich, S.; Howe, J.; et al. (1993) The Effects in Estuaries of Pesticide
Runoff from Adjacent Farm Lands (Alachlor, Terbufos, Permethrin): Lab Project Number:
CF813415: 1357: R.D. 1357. Unpublished study prepared by Duke University Marine Lab.;
University of Minnesota; and University of North Carolina. 220 p.
44405301 Blumhorst, M. (1997) Soil Adsorption/Desorption of (carbon 14) Alachlor Sulfonic Acid
Metabolite (ESA) by the Batch Equilibrium Method: Lab Project Number: 97-24-M-l:
115S12: MSL-14976. Unpublished study prepared by EPL Bio-Analytical Services, Inc. 106
P-
44492301 Most, J. (1995) Alachlor (Pure) Physico-Chemical Properties: Lab Project Number:
MSL-14400: MTO 41 A/942653: PC27-94-6-V-0. Unpublished study prepared by Huntingdon
Research Centre, Ltd. 67 p. {OPPTS 830.7050}
44492302 Monsanto Co. (1998) Monsanto Response to the Draft Health Effects Division Science
Chapter for the Alachlor RED Dated 4 November 1997: Lab Project Number: R.D. NO. 1400.
Unpublished study. 39 p.
44524301 Graves, W.C.,Swigert, J.P., and Krueger, H.O., (1998) Alachlor: A 96-Hour Flow-Through
Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus), Project/Study
number 139A-195/WL-96-189, an unpublished report of a study conducted by Wildlife
International, Inc. for Monsanto Life Sciences Company. Guideline Series 72-3
44524302 Graves, W.C.,Swigert, J.P., and Krueger, H.O., (1998) Alachlor: A 96-Hour Flow-Through
Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahiz), Project/Study number
139 A-l 96/WL-96-190, an unpublished report of a study conducted by Wildlife International,
Inc. for Monsanto Life Sciences Company. Guideline Series 72-3
44524303 Graves, W.C.,Swigert, J.P., and Krueger, H.O., (1998) Alachlor: A 96-Hour Flow-Through
Acute Toxicity Test with the Eastern Oyster (Crassostrea virginica), Project/Study number
139 A- l 97/WL-96-191, an unpublished report of a study conducted by Wildlife International,
Inc. for Monsanto Life Sciences Company. Guideline Series 72-3
44592401 Hackett, A. (1998) Surface Drinking Water Monitoring Program for Acetochlor and Other
Corn Herbicides: Lab Project Number: 94-27-R-3: 94-310: MSL-15395. Unpublished study
prepared by Monsanto Company and Stone Environmental, Inc. 233 p
255
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Coupe, R.H., Goolsby, D.A., Iverson, J.L., Zaugg, S.D., and Markovchick, D.J., 1995,
Pesticide, nutrient, streamflow and physical property data for the Mississippi River and major tributaries, April
1991-September 1992: U.S. Geological Survey Open-File Report 93-657, 116 p
Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of the EPA food-chain
(Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Environ. Tox. Chem. 13:1383-
1391.
Goolsby D.A. and E.M. Thurman. 1991. Herbicides in rivers and streams of the upper Midwestern United
States. To be published in: Proc. 46th Ann. Meeting Upper Mississippi River Conservation Committee.
Goolsby, D.A., R.C. Coup, and D.J. Markovchick. 1991. Distribution of selected herbicides and nitrate in the
Mississippi River and its major tributaries., April through June, 1991. U. S. Geological Survey Water
Resources Investigations Report p91-4163.
Goolsby, D.A., and Battaglin, W.A., 1993, Occurrence, distribution, and transport of agricultural chemicals in
surface waters of the Midwestern United States, in Goolsby, D.A., Boyer, L.L., and Mallard, G.E., eds.,
Selected papers on agricultural chemicals in water resources of the Midcontinental United States: U.S.
Geological Survey Open-File Report 93-418, p. 1-25
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metabolites in surface water, ground water, and rainwater in the Midwestern United States. P. 583-591.
Proceedings 1995 Annual Conference. June 18-22, 1995. Anaheim, CA. American Water Works Association.
Goolsby, D.A., Battaglin, W.A., Fallon, J.D., Aga, D.S., Kolpin, D.W., and Thurman, E.M., 1996, Persistence
of herbicides in selected reservoirs in the Midwestern United States—Some preliminary results: Iowa
Groundwater Quarterly, v. 7, no. 2, p. 11-16 (reprinted from U.S. Geological Survey Open-File Report 93-418)
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for estimation of their magnitude in the environment. In F. Coulston and F. Korte, eds., Environmental Quality
and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ, Stuttgart, West Germany, pp. 9-28.
Holden, L.R. and J. A. Graham, 1992. Results of the National Alachlor Well Water Survey. Environ. Sci.
Technol. 26:935-943
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Keck, P. 1991. 1991 Missouri River Monitoring Study. Missouri River Public Water Supplies Association.
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agricultural chemicals in near-surface aquifers of the midcontinental U.S.A. Groundwater Quality: Remediation
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using highly sensitive analytical methods and tritium. J. Environ. Qual. 24:1125-1132.
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in near-surface aquifers of the Midwestern United States.
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Carolina Rural Supply Wells: Land Use factors and Persistence. J. Environ. Qual., 24:426-431
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Groundwater. Environ. Sci. Technol. 29:1557-1563.
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Environ. Contam. Toxicol., 58:934-938
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of pesticide use on ground water in North Carolina. North Carolina Dept. of Ag. 2109 Blue Ridge Rd.,
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Intentionally Blank Page
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, I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
% PR0^° WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 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 III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its Attachments
1 through 6; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3 (for both generic and product specific data), the Requirements Status and
Registrant's Response Form, (see section III-B); or
3. Why you believe EPA should not require your submission of data in the manner
specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with its
requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension. We have provided a list 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 under the Paperwork Reduction Act by OMB Approval No. 2070-0107
and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
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 Formsdnsert A) with
Instructions
3 - Generic Data Call-In and Product Specific Data Call-In Requirements Status and
Registrant's Response Forms (Insert B) with Instructions
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data Requirements
for Reregi strati on
5 - List of Registrants Receiving This Notice
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
product(s) containing the subject active ingredient(s).
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and
Registrant's Response Forms (Insert B) (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.
II-B. SCHEDULE FOR SUBMISSION OF DATA
Section I
Section II
Section III
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
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You are required to submit the data or otherwise satisfy the data requirements specified
in the Requirements Status and Registrant's Response Forms (Insert B) within the time frames
provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test
standards outlined in the Pesticide Assessment Guidelines for those studies for which guidelines
have been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, VA 22161 (Telephone number:
703-605-6000).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the study
will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend deadlines
for complying with data requirements when the studies were not conducted in accordance with
acceptable standards. The OECD protocols are available from OECD, 2001 L Street, N.W.,
Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone number 202-785-
0350).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160],
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3fcY2yB^ 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-Infs). or any other agreements entered into
with the Agency pertaining to such prior Notice. Registrants must comply with the requirements
of all Notices to avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
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).
III-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.
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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.
III-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 III-C. A discussion of options relating to requests for data waivers is
contained in Section III-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 (Insert A), and the Requirements Status and Registrant's Response
Formfflnsert B).
The Data Call-In Response Fonnsf Insert A) must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Fonnsf Insert B) 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 Fonnsf Insert A) and the
Requirements Status and Registrant's Response Fonnsf Insert B) 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
product(s) containing the active ingredient that is the subject of this Notice. If you wish to
voluntarily cancel your product, you must submit completed Generic and Product Specific Data
Call-In Response Fonnsf Insert A), indicating your election of this option. Voluntary cancellation
is item number 5 on both Data Call-In Response Formfs). If you choose this option, these are the
only forms that you are required to complete.
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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 (Insert B), 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 (Insert B). You must also complete a
Data Call-In Response Form (Insert A) by signing the certification, item number 8. 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, aH 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.
To apply for the Generic Data Exemption you must submit a completed Data Call-In Response
Form (Insert A), Attachment 2 and all supporting documentation. The Generic Data Exemption is
item number 6a on the Data Call-In Response Form (Insert A). If you claim a generic data
exemption you are not required to complete the Requirements Status and Registrant's Response
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Form (Insert A). 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 product(s), 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 III-C.l. of this Notice and comprise options 1 through 6 of item
9 in the instructions for the Requirements Status and Registrant's Response Form (Insert B) and
item 6b on the Data Call-In Response Form (Insert A). If you choose item 6b (agree to satisfy the
generic data requirements), you must submit the Data Call-In Response Form (Insert A) and the
Requirements Status and Registrant's Response Form (Insert B) 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 III-D.l. 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 (Insert B). 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 III-C.2. A discussion of options relating to
requests for data waivers is contained in Section III-D.2.
Two forms apply to the product specific data requirements one or both of which must be used
in responding to the Agency, depending upon your response. These forms are the Data-Call-in
Response Form (Insert A), and the Requirements Status and Registrant's Response Form (Insert
B), for product specific data. The Data Call-In Response Form (Insert A) must be submitted as
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part of every response to this Notice. In addition, one copy of the Requirements Status and
Registrant's Response Form (Insert B) also must be submitted for each product listed on the Data
Call-In Response Formdnsert A) 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 Call-In
Response Formdnsert A) and Requirements Status and Registrant's Response Form (Insert B) (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
product(s) containing the active ingredient that is the subject of this Notice. If you wish to
voluntarily cancel your product, you must submit a completed Data Call-In Response Formdnsert
A), indicating your election of this option. Voluntary cancellation is item number 5 on both the
Generic and Product Specific Data Call-In Response Formsdnsert B). 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.
b. Satisfying the Product Specific Data Requirements of this Notice.
There are various options available to satisfy the product specific data requirements of this
Notice. These options are discussed in Section III-C. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the product specific Requirements Status and
Registrant's Response Formdnsert B) 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 Formdnsert A). 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.
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 Formdnsert B). If you choose this option, you must submit the Data Call-In Response
Formdnsert A) and the Requirements Status and Registrant's Response Formdnsert B) 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.
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III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-In Response Form (Insert A) 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 (Insert B)
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 guidelines
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. In 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 Registrant's Response
Form (Insert B) and/or footnotes to the form. If you wish to use a protocol which differs from the
options discussed in Section II-C 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 II-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
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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 report.
The time frames in the Requirements Status and Registrant's Response Form (Insert B) 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 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
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EPA (by selecting this option) to exercise its discretion not to suspend your registration(s),
although you did 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 Certification with Respect to Citations of Data (in PR Notice 98-5)
(EPA Form 8570-34) . 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 (Insert A) and a Requirements Status and
Registrant's Response Form (Insert B) 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 do submit, the required data in the specified time frame. In such cases,
the Agency generally will not grant a time extension for submitting the data.
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must determine that
the study satisfies the requirements imposed by this Notice. You may only submit a study that has
not been previously submitted to the Agency or previously cited by anyone. Existing studies are
studies which predate issuance of this Notice. Do not use this option if you are submitting data to
upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the Agency
will require you to comply with this Notice, normally without an extension of the required date of
submission. The Agency may determine at any time that a study is not valid and needs to be
repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly met:
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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 data means any laboratory worksheets, records, memoranda, notes, or exact copies
thereof, that are the result of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report of that study. In the event
that exact transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the exact copy or exact
transcript may be substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments." The
term "specimens", according to 40 CFR 160.3, means "any material derived from a test
system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all GLP-required
quality assurance and quality control information pursuant to the requirements of 40
CFR Part 160. Registrants also must certify at the time of submission of the existing
study that such GLP information is available for post May 1984 studies by including an
appropriate statement on or attached to the study signed by an authorized official or
representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline relevant
to the study provided in the FIFRA Accelerated Reregi strati on Phase 3 Technical
Guidance and that the study has been conducted according to the Pesticide Assessment
Guidelines (PAG) or meets the purpose of the PAG (both documents available from
NTIS). A study not conducted according to the PAG may be submitted to the Agency
for consideration if the registrant believes that the study clearly meets the purpose of the
PAG. The registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in addition to
certifying that the purposes of the PAG are met by the study, clearly articulate the
rationale why you believe the study meets the purpose of the PAG, including copies of
any supporting information or data. It has been the Agency's experience that studies
completed prior to January 1970 rarely satisfied the purpose of the PAG and that
necessary raw data 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.
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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 a 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 entitled "Standard Format for Data Submitted
under FIFRA".
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
aU deficiencies in the study identified by EPA. You must provide a clearly articulated rationale of
how the deficiencies have been remedied or corrected and why the study should be rated as
acceptable to EPA. Your submission must also specify the MRID number(s) of the study which
you are attempting to upgrade and must be in conformance with PR Notice 86-5 entitled
"Standard Format for Data Submitted under FIFRA."
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 MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all data
submissions intended to upgrade studies. Additionally, your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those
criteria, as well as a certification regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA, that study must have
been previously classified by EPA as acceptable, or it must be a study which has not yet been
reviewed by the Agency. Acceptable toxicology studies generally will have been classified as
"core-guideline" or "core-minimum." For 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.
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If you are citing a study of which you are not the original data submitter, you must submit a
completed copy of EPA Form No. 8570-34, Certification with Respect to Citations of Data.
2. Product Specific Data
If you acknowledge on the product specific Data Call-In Response Form (Insert A) 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 (Insert B) 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 (Insert B). These six options are listed
immediately below with information in parentheses to guide registrants to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the Agency
by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing study
that has been submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1. Developing Data — The requirements for developing product specific data are the same
as those described for generic data (see Section III.C.l, 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 III.C.l,
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 III.C.l., 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 III.C.l., Option 4) apply to this option for product specific data.
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Option 5. Upgrading a Study — The same requirements described for generic data (see Section
III.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 III.C.l., 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 (Insert A) and the
Requirements Status and Registrant's Response Form (Insert B), and in the generic data
requirements section (III.C.l.), as appropriate.
III-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.
a. Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response
Form (Insert B). 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 product(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,
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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 product(s) 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.
(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 product(s): (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.
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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 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 productfs). vou 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 (Insert B). 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.
SECTION IV. CONSEQUENCES OF FATT JTRF TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
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1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any option
chosen to address the data requirements (e.g., any required action or information
pertaining to submission or citation of existing studies or offers, arrangements, or
arbitration on the sharing of costs or the formation of Task Forces, failure to comply
with the terms of an agreement or arbitration concerning joint data development or
failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies, as
required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or failure of a
registrant on whom you rely for a generic data exemption either to:
a. Inform EPA of intent to develop and submit the data required by this Notice on a
Data Call-In Response Form (Insert A) and a Requirements Status and Registrant's
Response Form (Insert B).
b. Fulfill the commitment to develop and submit the data as required by this Notice; or
c. Otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
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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 product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may be
suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act.
You 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.
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,
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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 Call-In Response Forms (Insert A)and
completed Requirements Status and Registrant's Response Forms (Insert B), 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
Formsdnsert A) 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
Reregi strati on Division
Attachments
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
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 Reregi strati on
5 - List of Registrants Receiving This Notice
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ALACHLOR DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have
product(s) containing alachlor.
This Product Specific Data Call-In Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregi strati on
of alachlor. This attachment is to be used in conjunction with (1) the Product Specific
Data Call-In Notice, (2) the Product Specific Data Call-In Response Form (Attachment
2), (3) the Requirements Status and Registrant's Form (Attachment 3), (4) EPA's
Grouping of End-Use Products for Meeting Acute Toxicology Data Requirement
(Attachment 4), (5) the EPA Acceptance Criteria (Attachment 5), (6) a list of registrants
receiving this DCI (Attachment 6) and (7) the Cost Share and Data Compensation Forms
in replying to this alachlor Product Specific Data Call-In (Attachment 7). Instructions and
guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for alachlor are
contained in the Requirements Status and Registrant's Response. Attachment 3. The
Agency has concluded that additional data on alachlor are needed for specific products.
These data are required to be submitted to the Agency within the time frame listed. These
data are needed to fully complete the reregistration of all eligible alachlor products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and
procedures established by this Notice, please contact Veronica Dutch at (703) 308-8585.
All responses to this Notice for the Product Specific data requirements should be
submitted to:
Veronica Dutch
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508C
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: alachlor
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ALACHLOR DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s)
containing alachlor.
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 reregi strati on of alachlor.
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) the EPA Acceptance Criteria (Attachment 5), and (6) the Cost Share and Data
Compensation Forms in replying to this alachlor Generic Data Call In (Attachment F).
Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for alachlor
are contained in the Requirements Status and Registrant's Response. Attachment C. The
Agency has concluded that additional product chemistry data on alachlor are needed.
These data are needed to fully complete the reregistration of all eligible alachlor 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 Kathryn Boyle at (703) 305-6304.
All responses to this Notice for the generic data requirements should be submitted to:
Kathryn Boyle, Chemical Review Manager
Reregistration Branch III
Special Review and Registration Division (7508C)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: alachlor
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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" (Insert A) and are to be used by registrants to respond to generic and product
specific Data Call-Ins as part of EPA's Reregi strati on 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."(Insert A) 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 out the forms.
EPA has developed these forms individually for each registrant, and has preprinted
these forms with a number of items. DO NOT 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 2137, 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.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE
FORMS
INSERT A
Generic and Product Specific Data Call-in
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
Item 3. ON BOTH FORMS: This item identifies the type of Data Call-In. The date
of issuance is date stamped.
Item 4. ON BOTH FORMS: This item identifies 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 Call-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 both 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 (Insert B)
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 and 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.
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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.
INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE
FORMS
INSERT B
Generic and Product Specific Data Call-in
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 (Insert B) that indicates how you will
satisfy those requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
Item 7a 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."
Item 7b. For each end use product (EUP) for which you wish to maintain registration,
you must agree to satisfy the data requirements by responding "yes."
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); do 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.
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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.
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE
FORMS
INSERT B CONTINUED
Generic and Product Specific Data Call-in
Item 8. 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 initialed
and dated in the space provided for the certification.
Item 9. ON BOTH FORMS: Enter the date of signature.
Item 10. 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 that 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 canceled
this product. For these cases, please supply all relevant details so that EPA can ensure that its records are correct.
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Instructions For Completing The "Requirements Status and Registrant's
Response Forms" (Insert B) 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 reregi strati on 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 2137, 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.
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INSTRUCTIONS FOR COMPLETING Till "REQUIREMENTS STATUS
AND REGISTRANT'S RESPONSE FORMS" (Insert B)
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.
Item 3. 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 (ID#) 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, Subpart c.
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 to be submitted in connection with the study.
As noted in Section III 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 (Insert B).
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INSTRUCTIONS FOR COMPLETING Till "REQUIREMENTS STATUS
AND REGISTRANT'S RESPONSE FORMS" (Insert B) continued
Generic and Product Specific Data Call-In
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:
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
0
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 End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical Grade
Active Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PAI/PAIRA Pure Active Indredient or Pute Active
Ingredient Radiolabelled
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PAIRA
Pure Active Ingredient Radiolabeled
PAIRA/M
Pure Active Ingredient Radiolabeled and Metabolites
PAIRA/PM
Pure Active Ingredient Radiolabeled and Plant
Metabolites
TEP
Typical End-Use Product
TEP %
Typical End-Use Product, Percent Active Ingredient
Specified
TEP/MET
Typical End-Use Product and Metabolites
TEP/PAI/M
Typical End-Use Product or Pure Active Ingredient
and Metabolites
TGAI
Technical Grade Active Ingredient
TGAI/PAI
Technical Grade Active Ingredient or Pure Active
Ingredient
TGAI/PAIRA
Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabeled
TGAI/TEP
Technical Grade Active Ingredient or Typical End-Use
Product
MET
Metabolites
IMP
Impurities
DEGR
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 Call-In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for
submission of product specific studies begins from the date stamped on the
letter transmitting the Reregi strati on 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.
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Option 1. ON BOTH FORMS: (Developing Data') I 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 sharing 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.
Option 3. ON BOTH FORMS: (Offer to Cost Shared I have made an offer to
enter into an agreement with one or more registrants to develop data
jointly. I am also submitting a completed "Certification of offer to
Cost Share in the Development of Data" form. I am submitting
evidence that I have made an offer to another registrant (who has an
obligation to submit data) to share in the cost of that data. I am
including a copy of my offer and proof of the other registrant's receipt
of that offer. I am identifying the party which is committing to submit
or provide the required data; if the required study is not submitted on
time, my product may be subject to suspension. I understand that
other terms under Option 3 in the Data Call-In Notice apply as well.
However, for Product Specific Data, I understand that this
option is available only for acute toxicity or certain efficacy data and
only if the Agency indicates in an attachment to this Data Call-In
Notice that my product is similar enough to another product to qualify
for this option.
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Option 4. ON BOTH FORMS: (Submitting Existing Data') I will submit an
existing study by the specified due date that has never before been
submitted to EPA. By indicating that I have chosen this option, I
certify that this study meets all the requirements pertaining to the
conditions for submittal of existing data outlined in the Data Call-In
Notice and I have attached the needed supporting information along
with this response.
Option 5. ON BOTH FORMS: (Upgrading a Study') I will submit by the
specified due date, or will cite data to upgrade a study that EPA has
classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all
the requirements pertaining to the conditions for submitting or citing
existing data to upgrade a study described in the Data Call-In Notice.
I am indicating on attached correspondence the Master Record
Identification Number (MRID) that EPA has assigned to the data that
I am citing as well as the MRID of the study I am attempting to
upgrade.
Option 6. ON BOTH FORMS: (Citing a Study') 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 my own data. In either case, I will provide the MRID 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" (Insert B) for generic data.
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(Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
(Low Volume/Minor Use Waiver Requesf) 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.
(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" (Insert B) for product specific data.
Option 7. (Waiver Requesf) 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 Notice. In
this case, I must, within 30 days-of my receipt of the Agency's written
decision, submit a revised "Requirements Status" form specifying the
Option 7.
Option 8.
Option 9.
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option chosen. I also understand that the deadline for submission of
data as specified by the original Data Call-In notice will not change.
Item 10. 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.
Item 11. ON BOTH FORMS: Enter the date of signature.
Item 12. 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 may provide additional information that does not fit on this form in a signed letter that 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 product. For these cases, please supply all relevant details so that the Agency can ensure that its records are correct.
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EPA'S BATCHING OF ALACHLOR PRODUCTS FOR MEETING ACUTE
MAMMALIAN TOXICITY DATA REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregi strati on of products containing Alachlor as
the active ingredient, the Agency has batched products which can be considered similar
for purposes of acute toxicity. Factors considered in the sorting process include each
product's active and inert ingredients (identity, percent composition and biological
activity), type of formulation (e.g., emulsifiable concentrate, aerosol, wettable powder,
granular, etc.), and labeling (e.g., signal word, use classification, precautionary labeling,
etc.). Note that the Agency is not describing batched products as "substantially similar"
since some products within a batch may not be considered chemically similar or have
identical use patterns.
Using available information, batching has been accomplished by the process described
in the preceding paragraph. Notwith-standing the batching process, the Agency
reserves the right to require, at any time, acute toxicity data for an individual product
should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit
or cite a single battery of six acute toxicological studies to represent all the products
within that batch. It is the registrants' option to participate in the process with all other
registrants, only some of the other registrants, or only their own products within a
batch, or to generate all the required acute toxicological studies for each of their own
products. If a registrant chooses to generate the data for a batch, he/she must use one
of the products within the batch as the test material. If a registrant chooses to rely
upon previously submitted acute toxicity data, he/she may do so provided that the data
base is complete and valid by today's standards (see acceptance criteria attached), the
formulation tested is considered by EPA to be similar for acute toxicity, and the
formulation has not been significantly altered since submission and acceptance of the
acute toxicity data. Regardless of whether new data is generated or existing data is
referenced, registrants must clearly identify the test material by EPA Registration
Number. If more than one confidential statement of formula (CSF) exists for a product,
the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
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In deciding how to meet the product specific data requirements, registrants must
follow the directions given in the Data Call-In Notice and its attachments appended to
the RED. The DCI Notice contains two response forms which are to be completed and
submitted to the Agency within 90 days of receipt. The first form, "Data Call-In
Response," asks whether the registrant will meet the data requirements for each
product. The second form, "Requirements Status and Registrant's Response," lists the
product specific data required for each product, including the standard six acute
toxicity tests. A registrant who wishes to participate in a batch must decide whether
he/she will provide the data or depend on someone else to do so. If a registrant
supplies the data to support a batch of products, he/she must select one of the
following options: Developing Data (Option 1), Submitting an Existing Study (Option
4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6). If a
registrant depends on another's data, he/she must choose among: Cost Sharing (Option
2), Offers to Cost Share (Option 3) or Citing an Existing Study (Option 6). If a
registrant does not want to participate in a batch, the choices are Options 1, 4, 5 or 6.
However, a registrant should know that choosing not to participate in a batch does not
preclude other registrants in the batch from citing his/her studies and offering to cost
share (Option 3) those studies.
Twelve active products were found which contain Alachlor as the active ingredient.
These products have been placed into the "no batch" category in accordance with the
active and inert ingredients, type of formulation and current labeling.
The following product(s) may cite acute data as follows:
- EPA Reg. No. 524-344 may be supported by acute oral, acute dermal and/or acute
inhalation data generated with EPA Reg. Nos. 524-403 or 524-316.
No
Batch
EPA Reg. No.
% Active Ingredient
Formulation
Type
241-311
Alachlor 34.5
Imazaquin 2.2
Liquid
241-329
Alachlor 32.4
Imazaquin 1.9
Liquid
524-296
o
LO
\—1
Solid
524-314
45.1
Liquid
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No
Batch
EPA Reg. No.
% Active Ingredient
Formulation
Type
524-315
O
o
Liquid
524-316
O
O
Liquid
524-329
Alachlor 27.2
Atrazine 15.5
Liquid
524-341
Alachlor 27.6
Glyphosate 14.8
Liquid
524-344
41. 5
Microencap
Liquid
524-403
65. 0
Microencap
Solid
524-418
Alachlor 25.2
Atrazine 14.3
Related atrazine
compounds 0.8
Microencap
Liquid
524-422
Alachlor 31.7
Trifluralin 3.9
Liquid
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This page has been inserted as a place marker and is replaced by an electronically
generated PDCI List of Registrants page number 1 in the actual Printed version of the
Red document
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Pesticide Registration Forms are available at the following EPA
internet site:
http://www.epa.gov/opprd001/forms/.
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat
reader)
Instructions
1. Print out and complete the forms. (Note: Form numbers that are bolded can
be filled out on your computer then printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the
existing policy.
3. Mail the forms, along with any additional documents necessary to comply
with EPA regulations covering your request, to the address below for the
Document Processing Desk.
DO NOT fax or e-mail any form containing 'Confidential Business
Information' or 'Sensitive Information.'
If you have any problems accessing these forms, please contact Nicole Williams at
(703) 308-5551 or by e-mail atwilliams.nicole@epamail.epa.gov.
The following Agency Pesticide Registration Forms are currently available via the
internet:
at the following locations:
8570-1
Application for Pesticide
Registration/Amendment
http://www.epa. aov/opprdOO l/forms/8570-1 .pdf.
8570-4
Confidential Statement of Formula
http://www.epa.aov/opprd001/forms/8570-4.pdf.
8570-5
Notice of Supplemental Registration
of Distribution of a Registered
Pesticide Product
http://www.epa.aov/opprd001/forms/8570-5.pdf.
8570-17
Application for an Experimental Use
Permit
http://www.epa.aov/opprd001/forms/8570-17.pdf.
8570-25
Application for/Notification of State
Registration of a Pesticide To Meet a
Special Local Need
http://www.epa.aov/opprd001/forms/8570-25.pdf.
8570-27
Formulator's Exemption Statement
http://www.epa.aov/opprd001/forms/8570-27.pdf.
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8570-28
Certification of Compliance with
Data Gap Procedures
http://www.epa.2ov/opprd001/forms/8570-28.pdf.
8570-30
Pesticide Registration Maintenance
Fee Filing
http://www.epa.aov/opprd001/forms/8570-30.pdf.
8570-32
Certification of Attempt to Enter
into an Agreement with other
Restraints for Development of Data
http://www.epa.aov/opprd001/forms/8570-32.pdf.
8570-34
Certification with Respect to
Citations of Data (in PR Notice
98-5)
http://www.epa.aov/opppmsdl/PR Notices/pr98-5.pdf.
8570-35
Data Matrix (in PR Notice 98-5)
http://www.epa.gov/opppmsdl/PR_Notices/pr98-5.pdf.
8570-36
Summary of the Physical/Chemical
Properties (in PR Notice 98-1)
http://www.epa.aov/opppmsdl/PR Notices/pr98-l.pdf.
8570-37
Self-Certification Statement for the
Physical/Chemical Properties (in PR
Notice 98-1)
http://www.epa.aov/opppmsdl/PR Notices/pr98-l.pdf.
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Pesticide Registration Kit
www.epa.gov/pesticides/registrationkit/.
Dear Registrant:
For your convenience, we have assembled an online registration kit which
contains the following pertinent forms and information needed to register a
pesticide product with the U.S. Environmental Protection Agency's Office of
Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the
Federal Food, Drug and Cosmetic Act (FFDCA) as Amended by the Food
Quality Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program—Storage and Disposal
Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through
Irrigation Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy
Statement
f. 90-1 Inert Ingredients in Pesticide Products; Revised Policy
Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation
Amendments
h. 98-1 Self Certification of Product Chemistry Data with
Attachments (This document is in PDF format and requires the
Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR Notices.
3. Pesticide Product Registration Application Forms (These forms are in
PDF format and will require the Acrobat reader.)
a. EPA Form No. 8570-1, Application for Pesticide
Regi strati on/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption
Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of
Data
e. EPA Form No. 8570-35, Data Matrix
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4. General Pesticide Information (Some of these forms are in PDF format
and will require the Acrobat reader.)
a. Registration Division Personnel Contact List
Biopesticides and Pollution Prevention Division (BPPD) Contacts
Antimicrobials Division Organizational Structure/Contact List
b. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data
Requirements (PDF format)
c. 40 CFR Part 156, Labeling Requirements for Pesticides and
Devices (PDF format)
d. 40 CFR Part 158, Data Requirements for Registration (PDF
format)
e. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data
(November 27, 1985)
Before submitting your application for registration, you may wish to consult
some additional sources of information.
These include:
1. The Office of Pesticide Programs' Web Site
2. The booklet "General Information on Applying for Registration of
Pesticides in the United States", PB92-221811, available through the
National Technical Information Service (NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000. Please note that EPA is
currently in the process of updating this booklet to reflect the changes in the
registration program resulting from the passage of the FQPA and the
reorganization of the Office of Pesticide Programs. We anticipate that this
publication will become available during the Fall of 1998.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue
University's Center for Environmental and Regulatory Information
Systems. This service does charge a fee for subscriptions and custom
searches. You can contact NPIRS by telephone at (765) 494-6614 or
through their Web site.
4. The National Pesticide Telecommunications Network (NPTN) can
provide information on active ingredients, uses, toxicology, and chemistry
of pesticides. You can contact NPTN by telephone at 1-800-858-7378 or
through their Web site at ace.orst.edu/info/nptn/.
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The Agency will return a notice of receipt of an application for registration or
amended registration, experimental use permit, or amendment to a petition if the
applicant or petitioner encloses with his submission a stamped, self-addressed
postcard. The postcard must contain the following entries to be completed by OPP:
Date of receipt
EPA identifying number
the Product Manager assignment
Other identifying information may be included by the applicant to link the
acknowledgment of receipt to the specific application submitted. EPA will stamp
the date of receipt and provide the EPA identifying File Symbol or petition number
for the new submission. The identifying number should be used whenever you
contact the Agency concerning an application for registration, experimental use
permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are
properly coded and assigned to your company, please include a list of all synonyms,
common and trade names, company experimental codes, and other names which
identify the chemical (including "blind" codes used when a sample was submitted
for testing by commercial or academic facilities). Please provide a CAS number if
one has been assigned.
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List of Available Related Documents
The following is a list of available documents for Dicofol that may further assist
you in responding to this Reregi strati on Eligibility Decision document. These
documents may be obtained by the following methods:
Electronic
File format: Portable Document Format (.PDF) Requires Adobe® Acrobat or
compatible reader. Electronic copies are available on our website
at www.epa.gov/REDs, or contact Kathryn Boyle at (703) 305-
6304.
1. PR Notice 86-5.
2. PR Notice 91-2 (pertains to the Label Ingredient Statement).
3. A full copy of this RED document.
4. A copy of the fact sheet for Alachlor
The following documents are part of the Administrative Record for Alachlor and
may included in the EPA's Office of Pesticide Programs Public Docket. Copies of
these documents are not available electronically, but may be obtained by contacting
the person listed on the Chemical Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
The following Agency reference documents are not available electronically, but
may be obtained by contacting the person listed on the Chemical Status Sheet of
this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
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