United States Prevention, Pesticides EPA-738-F-98-018
Environmental Protection And Toxic Substances December 1998
Agency (7508C)
R.E.D. FACTS
Alachlor
PGStJCJdG All pesticides sold or distributed in the United States must be registered
by EPA, based on scientific studies showing that they can be used without
posing unreasonable risks to people or the environment. Because of advances
in scientific knowledge, the law requires that pesticides which were first
registered before November 1, 1984, be reregistered to ensure that they meet
today's more stringent safety standards.
Under the Food Quality Protection Act of 1996, EPA must consider the
increased susceptibility of infants and children to pesticide residues and
determine the need for an additional safety factor for the protection of infants
and children. When establishing or reassessing tolerances, the Agency must
also consider aggregate exposures to a pesticide, that is, combining the
exposures that result from consuming pesticide residues in food and water, or
using pesticide products in and around the home. Additionally, the Agency
must assess the cumulative effect of pesticides and other chemicals that
demonstrate a common mechanism of toxicity. Mechanism of toxicity is
defined as the steps leading to an adverse health effect following exposure to a
chemical. A common mechanism of toxicity occurs when two or more
chemicals produce the same adverse health effect by the same sequence of
steps.
In evaluating pesticides for reregi strati on, the pesticide producers submit
to EPA a complete set of studies describing the human health and
environmental effects of each pesticide. Agency scientists review the
submitted studies to determine if the studies are scientifically valid. These
studies are the basis for the Agency's risk assessment. The Agency then
develops any mitigation measures or regulatory controls needed to effectively
reduce each pesticide's risks, and then reregisters those pesticides and/or uses
that can be used without posing unreasonable risks to human health or the
environment.
When a pesticide is eligible for reregistration, EPA explains the basis for
its decision in a Reregistration Eligibility Decision (RED) document. This fact
sheet summarizes the information in the RED document for reregistration case
0063, alachlor.
-------
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 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.
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 alachlor 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
-------
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
annually, 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
Qj* approach and the MOE approach for the evaluation of carcinogenic
potential. These are not directly comparable approaches. The Qt* 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 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 m 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 reregi strati on eligibility review considered the following
assessments to be appropriate:
-------
Assessment
Acute
Chronic
(non-carcinogenic)
Short-Term
Occupational
Intermediate-Term
MOE Approach5
Carcinogenic
MOE Approach
Carcinogenic
Occupational
Qj* Approach6
Carcinogenic
Residential
Exposure Route
Dietary
(food and water)
Dietary
(food and water)
Dermal + Inhalation
Dermal + Inhalation
Dietary
(food and water)
Dermal + Inhalation
Dietary
(food and water)
Dermal + Inhalation
NOEL1 for Use in
Estimating Risk
Not required - no evidence
of significant toxicity from
a one day or single event
exposure by the oral route
RfD2'3 = 0.01 mg/kg/day
NOEL= 150 mg/kg/day
Use of dermal absorption
factor (0.24) required.4
NOEL = 50 mg/kg/day
Use of dermal absorption
factor not required since
NOEL is from a dermal
study.4
NOEL = 0.5 mg/kg/day
(nasal)
NOEL = 14 mg/kg/day
(stomach)
Not appropriate - Exposure
assessment does not
indicate that use is long-
term and continuous.
Qt* = 0.08 (mg/kg/day)-1
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.
1 A NOEL (no observed 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.
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 tolerances. Based on this data, 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 also 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.
EPA has assessed the total carcinogenic dietary risk posed by alachlor by
both the Qj* approach and the MOE approach. Both approaches are discussed
below in the Aggregate Dietary 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 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 Qt* 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 Qt* 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 Qt* 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 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 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 Qt*
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 Qt* 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
-------
emerging plants, well before the plants are mature, mitigates the potential for
post-application exposure.
Environmental Environmental Fate
AsSGSSrnGnt The Environmental Fate Assessment 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).
Water Resources Assessment
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 label directions, 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 and indirectly on aquatic animals.
• Available information indicates that (surface) drinking water supply
systems will usually comply with the SDWA.
Ecological Effects
The available toxicity data for alachlor indicate that alachlor is:
Slightly to practically non-toxic to birds on an acute oral basis (LD50 of
1500mg/kg).
• Slightly toxic to mammals, based on a rat study (LD50 of 930 mg/kg).
• Slightly toxic to honey bees (LD50 >36 ug/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=0.35 ppb, LOEL=0.69 ppb, EC50=1.64ppb).
Therefore, a potential risk to nontarget terrestrial and aquatic plants, and
endangered plant species exists. The available information on the major
alachlor degradates indicates that the degradates appear to be less toxic to
aquatic organisms than the parent.
Ecological Risk Assessment
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.
Risk Mitigation To lessen the human health, ecological, water and food quality risk
posed by alachlor, the registrant has voluntarily agreed to reduce the maximum
single application rate from 6 Ib to 4 Ib ai/acre, and to classify alachlor as a
restricted use pesticide (RUP) for groundwater concerns. EPA is requiring
additional mitigation measures that will: protect non-target species, control
surface water and ground water contamination, and protect workers.
Additional Data EPA is requiring the following additional generic studies for alachlor to
Required confirm its regulatory assessments and conclusions:
• avian reproduction
• aquatic plant studies
• analytical methodologies
handler exposure studies
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, revised Confidential Statements of
Formula (CSFs), and revised labeling for reregi strati on.
Product Labeling All alachlor end-use products must comply with EPA's current pesticide
product labeling requirements. The following label changes are required: (For
10
-------
ChangGS RGCjUirGd 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 setbacks 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 (emulsifiable 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.
11
-------
For MorG EPA is requesting public comments on the Reregi strati on 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 reregi strati on program, the
Alachlor RED, or reregi strati on of individual products containing alachlor
please contact the Special Review and Reregi strati on 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/.
12
------- |