United States
Environmental Protection
Agency
Office of Prevention, Pesticides
And Toxic Substances
(H-7508W)
EPA-738-F-93-001
March 1993
R.E.D. FACTS
Pesticide
Reregistration
Use Profile
Hydroxytetracycline
Monohydrochloride
and Oxytetracycline
Calcium
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 Document, or RED. This fact
sheet summarizes the information in the RED for hydroxytetracycline
monohydrochloride and oxytetracycline calcium.
Oxytetracycline is an antibiotic drug produced by a micro-organism.
Two related compounds, hydroxytetracycline monohydrochloride and
oxytetracycline calcium, are registered as pesticides, for use in preventing
the growth of or killing bacteria, fungi and mycoplasma-like organisms.
These pesticides are used primarily to control fire blight of pears, pear
decline, bacterial spot on peaches and nectarines, lethal yellowing of
coconut palm, and lethal decline of pritchardia palm; and as an antifoulant
added to marine paints to prevent the growth of barnacles.
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Regulatory
History
Human Health
Assessment
Oxytetracycline calcium is formulated as a wettable powder and is
applied as a foliar application using ground or aircraft equipment.
Hydroxytetracycline monohydrochloride is formulated as a soluble
concentrate/solid and is applied either by tree injection or as an additive to
paints.
Oxytetracycline has been available in the United States as a drug for
therapeutic use in humans since 1950. It also is used in veterinary medicine
to prevent infections in fowl, cattle and swine.
Oxytetracycline first was registered as a pesticide in 1974. EPA
issued a Registration Standard for Oxytetracycline, hydroxytetracycline
monohydrochloride and Oxytetracycline calcium in December 1988 (NTIS
PB89-138556). The Agency assessed the data submitted in response to the
Registration Standard in developing this RED.
At present, five end-use products are registered containing
hydroxytetracycline monohydrochloride or Oxytetracycline calcium as active
ingredients. There are no active registrations for products containing
Oxytetracycline, the third active ingredient covered in the 1988 Registration
Standard. For this reason, the RED does not apply to Oxytetracycline per
se, but only to the two derivatives.
Toxicity
EPA has waived all toxicological data requirements for
hydroxytetracycline monohydrochloride and Oxytetracycline calcium. The
toxicity of all three oxytetracyclines is expected to be similar, and data
generated on one compound can be used to assess exposure/risks of the
other two. Sufficient information is available on their effects in humans,
supplemented by the laboratory animal studies summarized below.
Hydroxytetracycline monohydrochloride and Oxytetracycline calcium
are of low acute toxicity through the oral route of exposure, and have been
placed in Toxicity Category IV indicating the lowest degree of toxicity for
this effect. Subchronic feeding studies in rats showed no adverse effects. In
two-year chronic toxicity studies in rats and dogs, the No Observed Effect
Level was the highest dose tested.
Carcinogenicity studies show some equivocal evidence of cancer in
male and female rats administered extremely high doses. However, EPA
has classified Oxytetracycline as a "Group D" carcinogen—one that is "not
classifiable as to human carcinogenicity."
One developmental toxicity study in rats showed a high incidence of
maternal deaths and fetotoxicity; however, excessive dose levels were used.
No adverse effects were demonstrated in another similar study.
In humans administered Oxytetracycline to treat infectious diseases
caused by various microorganisms, a variety of adverse effects have been
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reported including toxic and irritative effects, hypersensitivity and other
biological effects.
Dietary Exposure
Tolerances or maximum residue limits are established for residues of
oxytetracycline in or on pears at 0.35 ppm and peaches (including
nectarines) at 0.1 ppm. Please see 40 CFR 180.337. Tolerances of 0.1
ppm in or on tomatoes and cherries are pending. The 1988 Registration
Standard concluded that EPA had adequate data to support the registered
pear and peach uses, but also concluded that the tolerance for peaches
should be raised to 0.35 ppm.
Because oxytetracycline is used in veterinary medicine, tolerances for
residues in animals have been established by FDA. Please see 21 CFR 520,
522, 524 and 558. No Codex Maximum Residue Limits (MRLs) and no
Canadian or Mexican tolerances are established or proposed for
oxytetracycline.
Occupational and Residential Exposure
When oxytetracycline calcium is applied to pears, peaches and
nectarines using foliar application methods, pesticide mixers, loaders, and
applicators can be exposed; fieldworkers also can be exposed, post-
application. Worker exposure from trunk injection of hydroxytetracycline
monohydrochloride to agricultural and ornamental trees is expected to be
negligible.
Because the toxicity data for oxytetracycline do not meet EPA criteria
that would trigger requirements for these studies, no occupational or
residential exposure monitoring data are required. However,
oxytetracycline has produced allergic reactions in some patients, and
resistance to the drug could result from human exposure. Therefore, EPA
will require labeling on pesticide products containing hydroxytetracycline
monohydrochloride and oxytetracycline calcium to lessen these potential
risks.
Human Risk Assessment
The risks to people from dietary and occupational exposure to
pesticides containing hydroxytetracycline monohydrochloride and
oxytetracycline calcium are considered negligible. Chronic dietary risks
posed by all food uses of these pesticides are well below the level that would
reasonably cause concern.
During use and/or post-application, workers may be exposed to
relatively greater amounts of these pesticides than the general public.
However, label requirements will address concerns with potential allergic
responses in oxytetracycline-sensitive people, as well as the potential
development of resistance to oxytetracycline.
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Environmental
Assessment
Additional Data
Required
Product Labeling
Changes Required
Environmental Fate
EPA has waived all environmental fate data requirements for
hydroxytetracycline monohydrochloride and oxytetracycline calcium because
of their limited pesticidal use patterns and the availability of published
literature.
Ecological Effects
Acute toxicity studies in the published literature indicate that
oxytetracycline is practically non-toxic to birds, fish, aquatic invertebrates
and non-target insects such as honey bees.
Ecological Effects Risk Assessment
Due to their low toxicity and the low estimated environmental
concentration resulting from their use as pesticides, it is unlikely that
hydroxytetracycline monohydrochloride and oxytetracycline calcium pose
undue risks to avian or aquatic organisms or honey bees.
EPA is requiring product-specific acute toxicity and product chemistry
studies for reregistration of these pesticides.
The labels of all registered pesticide products containing
hydroxytetracycline monohydrochloride and oxytetracycline calcium must
comply with EPA's current pesticide labeling requirements. The Agency
soon will issue a Pesticide Registration (PR) Notice providing instruction on
changing labels of agricultural products in keeping with the Worker
Protection Standard. That PR Notice also will apply to these products.
End-use products must bear the following additional or revised label
statements in the Human Hazards section:
• Labels of products registered for use on agricultural crops by foliar
application methods must include the restricted entry statement,
"Entry into treated orchards (or "areas") is prohibited for 12 hours
following application."
• Labels of products registered for use on agricultural crops by foliar
applications must include the protective clothing statement,
"Prolonged or frequently repeated exposure may cause allergic
reactions in some individuals. Do not breathe dust or spray mist.
Wear a MSHA/NIOSH approved TC-21C dust/mist filtering
respirator, long sleeved shirt, pants, shoes, and chemical-resistant
gloves while handling or applying this product. Wash thoroughly
after handling or applying."
Regulatory Use of the active ingredients hydroxytetracycline monohydrochloride
Conclusion anc^ oxytetracycline calcium in accordance with approved labeling will not
result in unreasonable adverse effects to human health or the environment,
and all registered pesticide products containing these active ingredients are
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eligible for reregistration. These products will be reregistered once the
required product-specific data and revised labeling are received and accepted
by EPA.
For MorG EPA is requesting public comments on the Reregistration Eligibility
Information Document (RED) for hydroxytetracycline monohydrochloride and
oxytetracycline calcium 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 (7506C), Office of Pesticide Programs (OPP), US EPA,
Washington, DC 20460, telephone 703-305-5805.
Following the comment period, the hydroxytetracycline
monohydrochloride and oxytetracycline calcium 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 hydroxytetracycline monohydrochloride
and oxytetracycline calcium or about EPA's pesticide reregistration
program, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-308-8000.
For information about reregistration of individual products containing these
active ingredients, please contact Ben Chambliss, Product Manager,
Registration Division (7505C), OPP, US EPA, Washington, DC 20460,
telephone 703-305-6900.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 8:00 am and 6:00 pm Central Time, Monday
through Friday.
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