United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508 C)
EPA-738-F99-013
November, 1999
R.E.D. FACTS
Niclosamide
Pesticide
Reregistration
Use Profile
All pesticides sold or distributed in the United States must be registered
by EPA, based on scientific studies showing that they can be used without
posing unreasonable risks to people or the environment. Because of advances
in scientific knowledge, the law requires that pesticides which were first
registered before November 1, 1984, be reregistered to ensure that they meet
today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human health
and environmental effects of each pesticide. To implement provisions of the
Food Quality Protection Act of 1996, EPA considers the special sensitivity of
infants and children to pesticides, as well as aggregate exposure of the public
to pesticide residues from all sources, and the cumulative effects of pesticides
and other compounds with common mechanisms of toxicity. The Agency
develops any mitigation measures or regulatory controls needed to effectively
reduce each pesticide's risks. EPA then reregisters pesticides that meet the
safety standard of the FQPA and 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. The
decisions for Niclosamide and. TFM were combined into one publication
because the use patterns are very similar and the compounds are often used
together. This fact sheet summarizes the information in the RED document for
reregistration case 2455, 2-amino ethanol salt of 2',5'-dichloro-4'-nitro
salicylanilide (Niclosamide).
Niclosamide is used as (1) a lampricide'to control sea lamprey larvae in
tributaries to the Great Lakes, the Finger Lakes and Lake Chaniplain and (2) a
molluscicide to control freshwater snails which carry the vectors for diseases
which affect fish and humans. Less than 400 pounds of active ingredient
niclosamide is used each year in lamprey and freshwater snail treatments.
Niclosamide has been used as a human and veterinary drug for treatment of
parasites.
-------
Formulations include a 70% wettable powder (WP) and two granular
formulations. The WP is applied by metered pump from the back of a boat or
by backpack sprayer. The 3.2% granular product is applied with a backpack
blower device that spreads the granules over a wide surface area.
Regulatory Niclosamide was first registered as a pesticide in the U.S. in 1964 by the
History U.S. Department of Agriculture (USD A), the Agency's predecessor for
pesticide regulation under FIFRA. Currently, five niclosamide products are
registered with EPA: a 70% WP for sea lamprey control, two Special Local
Needs labels with the 70% WP, one 3.2% granular formulation, and one 5%
granular formulation. The registrant, has requested voluntary cancellation of
the 5% granular product.
Human Health
Assessment
Toxicity
Niclosamide has acute oral LD50 values of > 1000 mg/kg (Toxicity
Category HI). The acute dermal toxicity is minimal, as indicated by a LD50 >
2000 mg/kg (Toxicity Category IE). It produced slight skin irritation (Toxicity
Category IV) and caused eye irritation (unclassified Toxicity Category based
on short time interval of eye examination). It was a moderate skin sensitizer.
The acute inhalation data are not available.
Niclosamide showed no evidence of causing developmental toxicity,
mutagenicity or carcinogenicity.
Dietary Exposure
People are unlikely to be exposed to residues of niclosamide through the
diet due to: the low amount of compound used, the United States Fish and
Wildlife Service restrictions against removing irrigation and drinking water
from streams during treatment, and the rapid dissipation of residues in fish and
water. The Special Local Needs Labels for the use in ornamental fish ponds are
also not likely to result in any dietary exposure. Tolerances have not have been
established and are not required for niclosamide.
Occupational and Residential Exposure
Occupational and residential risk assessments were not conducted for
niclosamide based on the low volume used. Protective measures currently on
niclosamide labels were considered adequate for the products being
reregistered. All products are Restricted Use Pesticides and all labels require
double layers of clothing and respirators. Industrial hygiene and medical
monitoring programs are required routinely for all handlers of products
containing niclosamide.
-------
Human Risk Assessment
Risk assessments were not conducted for niclosamide based on the
extremely low volume and infrequency of use. Niclosamide use is closely
regulated by the US Fish and Wildlife Service and by the states which issued
Special Local Need labels.
Environmental Niclosamide is applied to freshwater tributaries and is therefore expected to
Assessment have little impact on terrestrial plants and animals. Applications are designed to have
minimal effects on fish, but other aquatic animals are expected to be impacted.
Environmental Fate
• In addition to dilution and dispersion, sorption to sediments and suspended
particulates and possibly photodegradation (in clear shallow waters), are the major
routes of dissipation of niclosamide. Neither hydrolysis nor volatilization from soil
or water surfaces should be major fate processes for this compound;
• In most aquatic environments, niclosamide will adsorb to suspended solids and
sediment and this binding is reversible.
• It is unclear what role, if any, aerobic and anaerobic microbial degradation plays in
the dissipation of niclosamide in the a.quatic environment.
• Accumulation in fish is not expected.
Ecological Effects
• Avian acute- moderately toxic (LD50 60 mg/kg)
• Avian subacute dietary- practically nontoxic (LC50. > 5,419 mg/kg diet()
• Mammalian acute- practically nontoxic (LD50 > 1,000 mg/kg)
• Pish (freshwater acute)- highly toxic to very highly toxic (LC50 0.03 - 0.23 mg/L)
• Invertebrates acute- slightly to very highly toxic (EC^ 0.034-50 mg/L)
• Invertebrates chronic-(NOAEC 0.03 mg/L; LOEC 0.05 mg/L)
• Aquatic plants- toxic (0.04 to > 1,450 mg/L)
Environmental Risk Characterization
• The effects of niclosamide at the treatment site are likely to be mitigated by
photodegradation and the flushing action of the stream/river.
At the predicted treatment levels, acute high risk, acute restricted use, and
endangered species levels of concern are exceeded for aquatic animals. Although
niclosamide is likely to have an immediate effect on the aquatic community, the data
• suggest that most organisms recover quickly and the treatment area community
structure returns to pre-treatment conditions within weeks or months. This recovery
is site specific and may take much longer in certain environments. Certain species
-------
may be significantly impacted, most notably the indigenous lamprey species. In
general, however, native lamprey species have tended to populate the upper reaches
of tributary streams, whereas the sea lamprey is more likely to inhabit lower reaches
of the stream. Thus, nontarget species that may have been affected in the treatment
area are repopulated through downstream migration from untreated areas.
Furthermore, retreatment of the stream will not occur for at least 3 to 5 years.
Additionally, a genuine effort is made to document where sensitive populations
reside, and steps are undertaken to avoid treatments at concentrations known to be
toxic to these organisms. The long-term effects remain uncertain to more sensitive
species, such as indigenous lampreys, and to aquatic communities downstream from
the treatment sites where chronic effects may be more likely.
Risk Mitigation The use practices of niclosamide have been refined over the past several years
in order to lower the impacts of these applications on non-target organisms and to
lower occupational and non-occupational exposure to people. Niclosamide is a
Restricted Use Pesticide and the labels refer users to the US Fish and Wildlife
Service's Manual for Pesticide Applications. Additional mitigation required by the
Agency includes minor clarifications of label language. Aerial applications were
prohibited on some of the current labels and will be prohibited on all new labels in
order to lessen chances of nontarget human and other terrestrial animal exposures to
these restricted use compounds.
i
Additional Data EPA is requiring the following additional generic studies for niclosamide to
RGQUired confirm its regulatory assessments and conclusions:
Photodegradation in Water Guideline # 835-2240 (161-2)
Aerobic Aquatic Metabolism Guideline # 835-4300 (162-4)
Anaerobic Aquatic Metabolism Guideline #835-4400 (162-3)
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 reregistration.
i
i
|
Product Labeling All niclosamide end-use products must comply with EPA's current pesticide
Changes Required product labeling requirements. For a comprehensive list of labeling requirements,
please see attached labeling table from the Niclosamide RED document.
j'
Regulatory The use of currently registered products containing niclosamide in
Conclusion accordance with approved labeling for sea lamprey control or in ornamental fish
aquaculture will not pose unreasonable risks or adverse effects to humans or the
environment. Therefore, uses of several niclosamide products are eligible for
reregistration.
-------
The registrant has requested cancellation of the 5% granular product used to
kill snails which carry the vector for Swimmer's Itch.
The use of the 70% WP as a molluscicide in Puerto Rico against snails which
carry the vector for Schistosomiasis is considered to be ineligible pending additional
use information and exposure data.
Niclosamide products will be reregistered for all other uses 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 Decision (RED)
Information document for niclosamide during a 60-day time period, as announced in a Notice of
Availability published in the Federal Register. The document is entitled
Reregistration Eligibility Decision: 3-Trifluoro-Methvl-4-Nitro-Phenol CASE 3082
and Niclosamide CASE 2455. To obtain a copy of this 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
Service Center for Environmental Publications (EPA/NSCEP), PO Box 42419,
Cincinnati, OH 45242-2419, telephone 1-800-490-9198; fax 513-489-8695.
Following the comment period, the niclosamide RED document also will be
available from the National Technical Information Service (NTIS), 5285 Port Royal
Road, Springfield, VA 22161, telephone 1-800-553-6847, or 703-605-6000.
For more information about EPA's pesticide reregistration program, the
niclosamide RED, or reregistration of individual products containing niclosamide,
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 internet address is ace.orst.edu/info/nptn.
-------
a
o
I
I
"3
•a
i-a
•S3
£
'3
i
•§•
u
§
P
S
•d
P
, •&
- ts
o t, w> a o
<-> "3 8 *o o
'
a
P
El
ng
sly
Re
TO
1
1rt
l-s
S "8
8 S
OH 73
'S S
3
-------
Chan
ft
2
1
3
I
P4
•8
g?
«
S
S
&
•H
Required La
§
-------
•3
a
a
S
«^
Is
Directions
ng
uired La
§•
£?
3
CO
endations"
Safety R
"U
••3
P.
'S
I
g
c
tel
cti
mi
tv «
JB &
4-j TO
2 |
te
leas
irri
te, an
ties th
•1
g
..
-------
acement on La
I
Ji
s
M
u
S
'a
3
i
i
I
f
CJ
VI
QJ
Pi
se
a
1
ll
IB g 1 | S
S111JE
tn fll *? „
1
cu
o
p
-------
------- |