United States
Environmental Protection
Agency
/
EPA-7387^95-028
Office of Prevention, Pesticides
And Toxic Substances , _
(7508W) . AUG I 5 1996
R.E.D. FACTS
PROMETRYN
Pesticide
Re registration
Use Profile
All pesticides sold or used 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 years ago be reregistered to ensure that they meet
today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks. EPA then reregisters pesticides that can be used without
posing undue hazards to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this
and explains why in a Reregistration Eligibility Decision Document, or
RED. This fact sheet summarizes the information in the RED document for
reregistration case 0467, prometryn,
Prometryn is a substituted thiomethly triazine herbicide registered for
the control of several annual grasses and broadleaf weeds in terrestrial food
and feed crops cotton, celery, pigeon peas and dill. Prometryn's mechanism
of action inhibits the electron transport in target broadleaves and grasses.
Prometryn was first registered in 1964 by Ciba Crop Protection. Prometryn
is also manufactured by the Verolit Chemical Manufacturer, Ltd.
Prometryn's major use sites are cotton and celery.
Other names for prometryn are Prometryne, Caparol, Gesagard,
Primatol Q, and Prometex. Prometryn is formulated as a single active
ingredient in wettable powder, crystalline, and flowable concentrate.
Prometryn is also formulated in a multiple active ingredient product which
combines a flowable concentrate with monosodium methanearsonate.
Currently there are 17 registered products (includes two Special Local Need
registrations) that contain from 8 to 97 percent prometryn. There are no
homeowner use products registered. .
-------
Regulatory Prometryn was first registered in the United States in 1964 as a
Historv herbicide for the control of weeds in cotton, celery, pigeon peas, and dill. A
Registration Standard was issued in March 1987 (NTIS# PB87-184826),
and required product and residue chemistry, toxicology, fish and wildlife,
plant protection, and environmental fate data. Additionally, the Special
Review and Reregi strati on Division issued two Data Call-Ins, one
September 30, 1991, requesting Tier III non-target phytotoxicity field
studies and Spray Drift information, and the second, September 2, 1992,
requesting hexachlorobenzene (HCB) and penta-chlorobenzene (PCB) data
to determine the potential presence of the impurities in technical prometryn.
Lacking appropriate guidance for conducting Tier EH testing and because of
our new policy, the Agency has decided to assess risk and make
reregistration decisions based on Tier n laboratory data. Therefore, the
Agency placed Tier EH study requirements on reserve. The Reregistration
Eligibility Decision document reflects the reassessment of the data
submitted in response to the Registration Standard and both Data Call-Ins.
Human Health Toxicity
Assessment ^ studies using laboratory animals, prometryn technical has been
shown to be slightly to practically non-toxic for oral, dermal, inhalation and
has been placed in Tox Category Ed (next to lowest in the four categories)
for these. Additionally, pertaining to acute eye and dermal irritation,
prometryn technical is considered to be slight to practically non toxic,
respectively and has been categorized as being in Categories HI and IV for
these. Prometryn is not considered a sentizer.
In a subchronic 28-day feeding study using rats showed that
macroscopic and microscopic pathological findings appeared in the high
dose animals and were limited to the G.I. tract along with clinical signs and
marked decreases in body weights! were also seen in these animals. In a 21-
-day dermal toxicity study with rabbits, no local or systemic toxicity was
observed at the highest dose levels (1000 mg/kg/day).
In three chronic toxicity/carcinogenicity studies with mice, rats and
dogs showed that prometryn was not oncogenic. Prometryn was classified
as a Group E Carcinogen (no evidence of human carcinogenic potential)
because prometryn did not alter the spontaneous tumor profile for the
strains of mice and rats tested. The dog study, however, was not considered
because, even though there were some effects, under the conditions .of the
study, the effects were not oncogenic.
A developmental toxicity study with rats showed the highest dose
level caused maternal and developmental toxicity. In another study also
conducted with rabbits resulted in effects at the highest dose level, ,
including increased abortions and decrease in body weight parameters.
-------
A 2-generation reproductive study with rats showed effects at the
highest dose level including decrease in body weight and corresponding
food consumption. Nevertheless, the statistically significant decrease in
pup body weight (also at the high dose level) was considered to be
lexicologically significant because of its potential negative impact on post-
natally developing systems such as the neuro- and immune systems.
In four mutagenicity studies (ames samonella test, chromosomal
aberration, bacterial DNA repair, and unscheduled DNA synthesis test)
prometryn was found to be negative.
A series of (radiolabeled) general metabolism studies with rats
showed the greatest distribution of prometryn first in the blood followed by
the spleen and then in the lungs.
Dietary Exposure
People may be exposed to residues of prometryn through the diet.
Tolerances or maximum residue limits have been established for a variety
of crop and animal commodities (see 40 CFR 180.222(a) and (b)).
Food and Feed additive tolerances are established for residues of
prometryn in or on the following raw agricultural commodities: celery (0.5
ppm); corn fodder (field, pop, and sweet, 0.25 ppm); corn forage (field,
pop, and sweet, 0.25 ppm); fresh corn (sweet K +CWHR, 0.25 ppm); corn
grain (0.25 ppm); cotton[forage](l ppm); cottonseed (0.25 ppm); and
pigeon peas (0.25 ppm). A tolerance with regional registration is
established in or on dill (0.03 ppm).
The Agency has determined that a risk assessment for the uses of
prometryn can be conducted using tolerance-level residues of prometryn,
per se in cottonseed, pigeon peas, celery and dill.
The Agency has assessed the dietary risk posed by prometryn
considering tolerance level residues to calculate the Theoretical Maximum
Contribution (TMRC) for the overall US population and 22 subgroups. No
refinements using anticipated residues or percent crop treated were applied.
Two analysis were conducted, one included the commodity (com) for
which revocation of tolerance is recommended and the other did not include
the proposed revocation of tolerances on corn. Both chronic analyses
indicated a negligible chronic dietary risk from the use of prometryn.
The RfD was determined to be 0.04 mg/kg/day based on a NOEL of
3.75 mg/ kg/day from a chronic toxicity study in dogs. The LEL was
determined to be 3.75 mg/kg/day based on bone marrow atrophy and
degenerative changes in the liver and kidneys. An uncertainty factor of 100
was used to account for inter- and intra- species variability.
An acute dietary analysis has been recommended. The endpoint for
acute dietary risk assessment is the NOEL of 12 mg/kg/day from a rabbit
-------
developmental study, while the LEL was based on increased resorptions,
abortion and significant changes in other reproductive parameters at
72 mg/kg body weight/day.
Occupational Exposure
Based on current use patterns, handlers (mixers, loaders, and
applicators) may be exposed to prometryn during and after application in
agricultural settings. There are no data to evaluate post-application
exposure because post-application data were not required in the
Registration Standard and subsequent DCI's, because at the time no
toxicological criteria had been triggered. There are no residential uses for
prometryn and no exposure risk is expected to homeowners.
There are toxicological eiidpoints of concern for prometryn. The
endpoint for both short-term and intermediate-term occupational exposure
is a NOEL of 12 mg/kg/day taken from a rabbit developmental study
indicating increased resorption, abortion, and significant changes in other
reproductive parameters at the LEL. The LEL is 72 mg/kg/day and the
Agency deemed a 15% factor appropriate for estimating dermal exposure.
Although no dermal absorption study with prometryn was ever
conducted, the Agency determined that a 7% absorption value is a
reasonable upper limit for dermal absorption. The 7% is based on a
comparison between an oral rabbit developmental study and a 21-day
dermal rabbit study. However, uncertainties and concerns exist regarding
the use of 7% in conducting the risk assessment because the parameters
typically measured in a 21-day dermal study are not extensive (i.e., no
clinical chemistries) and the effects observed including increased abortion
and increased post-implantation loss in the developmental study are
significant. Thus, the Agency has decided to use a more protective
absorption rate of 15%.
The Agency has determined that there is an exposure potential for
handlers during the usual use-patterns associated with prometryn.
Exposures to mixers, loaders and applicators are likely when liquid (used in
aerial application) and wettable powder (used in aerial and groundboom
applications) formulations are used. In the same manner, the Agency has
determined that there is a potential for exposure to persons entering treated
sites after application is complete with special concern for lay-by
applications to celery, since such applications can be made over the crop
and celery is often thinned by hand.
Human Risk Assessment
To mitigate the risks posed to handlers, the Agency is requiring that
all wettable powder formulations be encased in soluble packets. To
mitigate the risks associated with mixing and loading liquid formulations to
support aerial applications, the Agency is requiring minimum (baseline)
PPE of a chemical resistent apron and a respirator equipped with a dust/mist
-------
filter. Additionally,^lo.protectffield workers, the Agency is requiring a 24-
hour REI for uses on celery and a 12-hour REI for all other uses. The
Agency is also requiring interim spray drift advisory measures be placed on
all labels, and is requiring a confirmatory post-application/ reentry study for
celery to assess the impact posed to reentry workers.
Environmental
Assessment Environmental Fate
The laboratory mobility data for prometryn indicate that prometryn
has the potential to leach into ground water and will be most mobile in
sandy, alkaline soils which contain little organic matter or clay. Prometryn
was detected in ground water from an irrigation well in California.
However, in California, Arizona and New Mexico, prometryn labels
instruct potential users not to apply the product to sand or loamy sand soils.
Also, prometryn was not detected in ground water during a retrospective
ground-water monitoring study performed by the registrant in Missouri, at a
site which was underlain by sandy loams and loamy sands.
Ecological Effects
Because prometryn is registered for the control of weeds in terrestrial
feed and food crops; cotton, celery, pigeon peas and dill, it is expected that
exposure to nontarget organisms can result from direct applications, spray
drift, and runoff from treated areas. Studies indicate that prometryn poses
an acute risk to nonendagered and endangered terrestrial and aquatic plants,
a chronic risk to birds, and an acute risk to endangered small mammals.
Prometryn is currently not classified as a restricted use pesticide.
Although the restricted use risk quotients are at the threshold for small
mammals, fresh water invertebrates and estuarine/marine organisms, the
Agency has determined that the numbers do not warrant the chemical's
reclassification at this time.
Ecological Effects Risk Assessment
The Agency is requiring labelling prohibiting the use of prometryn on
sand and sandy loam soils. However, in light of the registrant's stewardship
and the data-in-house, the Agency has determined that ground water and
surface .water label advisories are not necessary at this time.
All of the ecological effects data required are fulfilled with the
exception of an avian reproduction (upland gamebird) study and a fish early
life stage study. These studies are needed to fully assess prometryn's. risk
assessment to birds and fish.
In order that the use of prometryn will not endanger sensitive
terrestrial and aquatic plant species and to reduce potential risks, the
Agency is requiring all products to carry environmental hazard labeling.
Additionally, in the future, when the Agency implements the Endangered
-------
Additional Data
Required
Guideline 13 2-1 (a)
Guideline 132-l(b)
Guideline 133-3
Guideline 165-2
Species Protection Program, limitations may be imposed on the use of
prometryn to protect threatened and endangered species.
The Agency is requiring the following generic data for prometryn to
confirm its regulatory assessment and conclusions:
o Guideline 71-4(a) Avian reproduction (upland gamebird)
o Guideline 72-4(a) Fish early life-stage
o Guideline 85-2 Dermal absorption
o A confirmatory post-application/reentry study for celery. The study
shall consist of:
Foliar dislodgeable residue dissipation,
Soil residue dissipation, and
Dermal exposure to be conducted
concurrently.
Limited field rotational crop study (for leafy
vegetables).
Additionally, the Agency is requiring product-specific data including
product chemistry and acute toxicity studies, revised Confidential
Statements of Formula (CSFs), and revised labeling for reregistration.
Product Labeling The labels of all registered pesticide products containing prometryn must
Changes Required comply with the Agency's current pesticide labeling requirement and with
the additional requirements summarized below.
Worker Protection Requirements
Personal Protective Equipment (PPE) Requirements
For Occupational Use
The minimum (baseline) PPE for all prometryn occupational handlers
of prometryn end-use products is:
"Applicators and other handlers must wear:
~ long sleeve shirt and long pants,
~ Chemical resistant gloves, and
— Shoes plus socks."
For the liquid-formulation end-use products that contain instructions for
aerial applications, the Agency is requiring the following additional
minimum (Baseline) PPE for mixers and loaders supporting aerial
application:
"In addition, mixers and loaders supporting aerial applications must wear:
— Chemical resistant apron, and
- Respirator (a dust/mist filtering respirator (MSHA/NIOSH
approval number prefix TC-21C)).
-------
Entry Restictions j j
For Occupational-Use
A 24-hour restricted entry interval (REI) is required for celery and a
12-hour (REI) is required for all other uses. The PPE required for early
entry is:
—Coveralls over long-sleeve shirt and long pants,
—Chemical-resistant gloves,
—Shoes plus socks.
Other Labeling Requirements
For Occupational Use:
"Do not apply this product in a way that will make contact with
workers or other persons, either directly or through drift. Only
protected handlers may be in the area during application."
Engeneering Controls:
"When handlers use closed systems (including water-soluble packets),
enclosed cabs, or aircraft in a manner that meets the requirements listd
in the Worker Protection Standard (WPS) for agricultural pesticides
(40 CFR 170.240(d)(4-6), the handler PPE requirements may be
reduced or modified as specified in the WPS."
User Safety Requirements:
"Follow manufacturer's instructions for cleaning/maintaining PPE. If
no such instructions for washables, use detergent and hot water. Keep
and wash PPE separately from other laundry."
User Safety Recommendations:
• "Users should wash hands before eating, drinking, chewing gum,
using tobacco, or using the toilet."
• "Users should remove clothing immediately if pesticide gets
inside. Then wash thoroughly and put on clean clothing."
• "Users should remove PPE immediately after handling this
product Wash the outside of gloves before removing. As soon as
possible, wash thoroughly and change into clean clothing."
Soil Incorporation Statement
Registrants may add the following statement to their labeling in the
Agricultural Use Requirements box immediately following the restricted
entry interval:
"Exception: If the product is 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."
-------
Jt
T
Environmental Hazard:
For all prometryn end-use products, use this precautionary statement:
"Do not apply directly to water or to areas where the
surface water is present or to intertidal areas below the
mean high water mark. Do not contaminate water when
disposing of equipment washwater or rinsate. Drift and
runoff may be hazardous to aquatic organisms in
neighboring areas. Do not apply where runoff is likely to
occur. Do not apply when weather conditions favor drift
from treated areas."
Rotational Crops:
Labels must specify a plant-back-interval (FBI) of 8 months for
rotational crops.
Spray Drift Label Advisory:
For prometryn products that can be applied aerially, the following
statement must be placed on each label:
. "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 spraying decisions."
The following drift management requirements must be followed to
avoid off-target drift movement from aerial applications to agricultural
crops. These requirements do not apply to forestry applications, public
health uses or to applications dry formulations:
1. "The distance of the outer most nozzles on the boom must not
exceed 3/4 the lenght of the wingspan or rotor."
2. "Nozzles must always point backward parallel with the air
stream and never be .pointed downwards mure 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.
The following aerial drift reduction advisory information must be contained
in the product labeling:
[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' jinder unfavorable environmental conditions (see
Wind, Temperature and Humidity, and Temperature Inversions).
Controlling Droplet Size
• Volume - Use high flow rae nozzles to apply the highest practical
spray volume. Nozzles with higher rated flows produce larger droplets.
• 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.
Boom Length
For some use patterns, reducing the efffective boom length to less
than 3/4 of the wingspan or rotor length may further reduce drift without
reducing swath width.
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.
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.).
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.
-------
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.
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.
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).
The use of currently registered products containing prometryn in
accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products abiding to the requirements imposed in the RED document are
eligible for reregistration. .
Prometryn products will be reregistered once the required product
specific data, revised Confidential Statements of Formula, and revised
labeling are received and accepted by EPA.
For More EPA is requesting public comments on the Reregistration Eligibility
Information Decision Document (RED) for prometryn 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 or to submit written comments, please contact the
Pesticide Docket, Public Response and Program Resources Branch, Field
Operations Division (H-7506C), Office of Pesticide Programs (OPP),
US EPA, Washington, DC 20460. Telephone 703-305-5805.
Regulatory
Conclusion
10
-------
Following the comment period, the prometryn RED will be available
from the National Technical Information Service (NTIS), 5285 Port Royal
Road, Springfield, VA 22161, telephone 703-487-4650.
For more information about prometryn or about EPA's pesticide
reregi strati on program, please contact the Special Review and
Reregistration Division (H-7508W), OPP, US EPA, Washington, DC
20460, telephone 703-308-8000. For information about reregi strati on of
individual products containing prometryn, please contact Robert Taylor,
Product Manager, Registration Division (H-7505C), OPP, US EPA,
Washington, DC 20460, telephone 703-305-6800.
-------
I -
,-f
------- |