United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F-98-008
October 1998
R.E.D. FACTS
Pesticide
Reregistration
Methylisothiazolinone
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. The Agency develops any
mitigation measures or regulatory controls needed to effectively reduce each
pesticide's risks. EPA then reregisters pesticides 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
3092, methylisothiazolinone. The Reregistration Eligibility Decision covers the
two active ingredients 5-chloro-2-methyl-3(2H)-isothiazolone and 2-methyl-
3(2H)-isothiazolone. These two active ingredients occur together in the
currently registered products in approximately a 3:1 ratio, respectively, and are
commonly referred to as methylisothiazolinone.
Use Profile
Methylisothiazolinone is used to control slime-forming bacteria, fungi,
and algae in pulp/paper mills, cooling water systems, oil field operations,
industrial process waters, and air washer systems and is incorporated into
adhesives, coatings, fuels, metal working fluids, resin emulsions, paints, and
various other speciality industrial products as a preservative. It is also used to
control the growth of mold, mildew, and sapstain on wood products.
Formulations include soluble concentrated liquids and soluble concentrated
solids. Products containing methylisothiazolinone are added to systems and
industrial products using manual pouring and metered pumping methods, dip
tanks and sprayers. Use practice limitations include National Pollutant
Discharge Elimination System (NPDES) license restrictions.
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Regulatory
History
Human Health
Assessment
Methylisothiazolinone was first registered in the U.S. in 1977 as an
antimicrobial with various uses. There are currently 85 products registered
including one technical product.
In 1987 the Agency issued the Antimicrobial Data Call-in Notice to
registrants with pesticides containing methylisothiazolinone to obtain additional
chronic and subchronic toxicity data. A Phase 4 Data Call-In was issued on
November 3, 1992, requiring additional toxicity and environmental fate data.
Toxicity
In studies using laboratory animals, methylisothiazolinone has been
shown to be of moderate acute toxicity by the oral and inhalation routes. It is
highly acutely toxic when applied dermally or to the eye and is considered to be
corrosive.
In subchronic studies, the most significant toxicological effect was
microscopic lesions in the nasal turbinates from inhalation exposure.
Developmental and chronic feeding/carcinogenicity studies in rats resulted in
no significant effects and the Agency classified methylisothiazolinone as a
Group D chemical, not classifiable as to human carcinogen!city. Results from
mutagenicity studies were equivocal.
Dietary Exposure
Tolerances or residue limits are established for methylisothiazolinone in
adhesives, paper, and paper products which may contact food. These uses are
regulated by the U.S. Food and Drug Administration (FDA). There are no
other registered food uses of methylisothiazolinone.
Occupational and Residential Exposure
Based on current use patterns, handlers may be exposed to
methylisothiazolinone during and after normal use of the liquid and solid
soluble concentrate formulations. Persons in residential settings may be
exposed to products containing methylisothiazolinone. Therefore, an exposure
assessment was conducted based on the toxicological endpoint of the
respiratory effect from the subchronic inhalation study.
The open-pouring application of methylisothiazolinone is considered the
worst-case inhalation exposure scenario for applicators. The worst-case
scenario for persons exposed to methylisothiazolinone-treated products is the
paint application use.
Although exposures to workers in areas where products containing
methylisothiazolinone have recently been applied are expected, EPA believes
that these post-application exposures would be significantly less than those for
handlers applying the pesticide.
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There are no methylisothiazolinone products labeled for homeowner use.
Exposures to homeowners may occur from products, such as adhesives, paints
or paper products, treated with methylisothiazolinone. Again, the Agency
believes that these exposures would be minimal.
Human Risk Assessment
Methylisothiazolinone is moderately to highly acutely toxic in oral,
dermal, eye irritation, dermal irritation, and inhalation acute toxicity studies.
The use of methylisothiazolinone in the manufacture of paper,
paperboard, and adhesives which may contact food is regulated by FDA.
There are no other registered food uses.
The Agency concluded that the risks of short-term and intermediate-term
occupational exposure to pesticide handlers are acceptable. Margins of
Exposure (MOEs) for all uses were above 100. An MOE of less than 100 is of
concern to the Agency. Short-term risks of corrosivity can be adequately
managed through the use of personal protective equipment (PPE) and
monitoring, as necessary. The Agency further believes risks from secondary
occupational exposures, residential exposures, and post-application exposures
are comparatively less and also acceptable. However, protective measures are
being imposed including additional product specific PPE (when appropriate),
and baseline PPE.
Environmental Environmental Fate
Assessment Of the two chemicals (5 -chloro-2-methyl-3(2H)-isothiazolone and 2-
methyl-3(2H)-isothiazolone) that compose methylisothiazolinone, only 5 -
chloro-2-methyl-3(2H)-isothiazolone was susceptible to hydrolysis and only at
alkaline pH. 5-Chloro-2-methyl-3(2H)-isothiazolone was very mobile in most
soils. The degradation profile observed in an aqueous availability study is
similar to that observed in the hydrolysis studies.
Ecological Effects
Methylisothiazolinone is moderately to practically non-toxic to birds, and
moderately to highly toxic to freshwater and estuarine/marine organisms.
Ecological Effects Risk Assessment
While the hazard to aquatic organisms from methylisothiazolinone has
been characterized, a quantitative risk assessment has not been conducted. The
risks to aquatic environments from this use are regulated under the NPDES
permitting program of EPA's Office of Water. The Agency currently requires
that labels for all methylisothiazolinone products require that discharges to
aquatic environments comply with an NPDES permit.
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Risk Mitigation To lessen the potential human health risks posed by
methylisothiazolinone, EPA is requiring the following risk mitigation measures.
(1) The Agency is establishing active-ingredient based minimum PPE
for primary occupational handlers. Since all the MOEs generated
are based on units of exposure from the Pesticide Handlers
Exposure Database in which handlers wore chemical resistant
gloves, long-sleeve shirts, long pants, and shoes plus socks, these
PPE are required for occupational handlers of
methylisothiazolinone products.
(2) The acute dermal, inhalation and ocular toxicity of the end-use
products will be used to determine appropriate protection from the
corrosivity of methylisothiazolinone.
Additional Data EPA has required additional generic information describing the
Required hydrolysis of 5-chloro-2-methyl-3(2H)-isothiazolone at pH 9 to confirm its
regulatory assessments and conclusions.
The Agency also is requiring methylisothiazolinone product-specific data
including product chemistry and acute toxicity studies, revised Confidential
Statements of Formula (CSFs), and revised labeling for registration.
Product LabGling All methylisothiazolinone end-use products must comply with EPA's
Changes Required current pesticide product labeling requirements and with the following. Fora
comprehensive list of labeling requirements, please see the
methylisothiazolinone RED document.
Personal Protective (PPE) Requirements
(1) EPA is establishing the following minimum, baseline PPE:
Mixers, loaders, and others exposed to methylisothiazolinone
products must wear:
- Long-sleeve shirt and long pants,
- Chemical resistant gloves,
— Shoes plus socks.
(2) If the end-use product is classified as Toxicity Category I or II
for eye irritation potential, add to the above PPE:
—Protective eyewear
(3) If the end-use product is classified as Toxicity Category I or II
for acute dermal toxicity or skin irritation potential, add:
-Chemical-resistant apron
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(4) If the end-use product is classified as Toxicity Category I or II
for acute inhalation toxicity, add:
—Respirator (the type must be specified; EPA will assist
registrants in determining appropriate respirators during
product reregi strati on).
Labeling Clarifications
The following clarifications must be made on all end-use products labels,
where applicable.
(1) Use Profile Clarifications
Registrants must specify on labeling of products containing
methylisothiazolinone the complete directions for use for each use
pattern: site of application, type of application, timing of
application, equipment used for application, and the rate of
application (dosage).
(2) Use on Pilings
Methylisothiazolinone is to be used only on terrestrial-use pilings
not aquatic-use pilings. The phrase "terrestrial-use pilings" must
be used when referring to any type of piling.
(3) Water Treatment Systems
All uses of products containing methylisothiazolinone in water
treatment systems must clearly specify recirculating water
treatment systems. The term "recirculating" must be added before
all references to water treatment systems (e.g., water treatment,
cooling towers, etc.).
(4) Clarification of Oil Drilling Mud Use
To clarify the intent of the oil recovery drilling muds/packer fluids
use (as an aquatic or terrestrial non-food use pattern), the
following statement must be added to the labels for terrestrial non-
food oil drilling muds and packer fluids:
"For use in terrestrial wells only."
And the following statement must be added to the precautionary
labeling:
"Do not apply in marine and/or estuarine oil fields."
The following statement must be added to the labels for aquatic
non-food industrial oil drilling muds and packer fluids:
"For use in offshore wells only."
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For use in both terrestrial and offshore oil drilling muds and packer
fluids, the following statement must be added:
"This product may be used for terrestrial and off-shore oil
drilling muds and packer fluids."
Other Labeling Requirements
The Agency is requiring the following labeling statements to be
located on all end-use products containing methylisothiazolinone that are
intended primarily for occupational use.
(1) Application Restrictions
"Do not apply this product in a way that will contact
workers or other persons."
(2) User Safety Requirements
"Discard clothing or other absorbent materials that have been
drenched or heavily contaminated with this product's concentrate.
Do not reuse them. Follow manufacturer's instructions for
cleaning/maintaining PPE. If there are no such instructions for
washables, use detergent and hot water. Keep and wash PPE
separately from other laundry."
(3) 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."
(4) Skin Sensitizer Statement
"This product may cause skin sensitization reactions in
some people."
The use of currently registered products containing
Conclusion methylisothiazolinone in accordance with approved labeling and as described in
the Reregi strati on Eligibility Decision Document will not pose unreasonable
risks or adverse effects to humans or the environment. Therefore, all uses of
these products are eligible for reregi strati on.
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Methylisothiazolinone products will be reregistered once the required
product-specific data, generic data, revised Confidential Statements of
Formula, and revised labeling are received and accepted by EPA.
For MOTG EPA is requesting public comments on the Reregi strati on Eligibility
Information Decision (RED) document for methylisothiazolinone 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 Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs (OPP), US EPA, Washington, DC 20460, telephone 703-305-5805.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregi strati on Information System at
703-308-7224. They also are available on the Internet using ftp on
FTP.EPA.GOV, or using WWW (World Wide Web) on WWW.EPA.GOV.
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 45242-0419, telephone 513-
489-8190, fax 513-489-8695.
Following the comment period, the methylisothiazolinone RED
document also 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 EPA's pesticide reregi strati on program, the
methylisothiazolinone RED, or reregi strati on of individual products containing
methylisothiazolinone, 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 Pesticides Telecommunications Network (NPTN). Call toll-free 1-
800-858-7378, between 9:30 am and 7:30 pm Eastern Standard Time, Monday
through Friday.
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