Document ID: EPA-HQ-OPP-2013-0364-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-05-07T04:00Z

Proposed Registration of the New Material Preservative Active
Ingredient, Terbutryn 

I  Proposed Decision: The Agency is proposing to register new
registrations for products containing the new active ingredient,
terbutryn.  The proposed label uses include material preservation in
joint cements, stuccos, sealants, paints, primers, sealers, and
industrial coatings. Terbutryn was initially registered by EPA in 1969
as an herbicide to control weeds in various grain crops. All terbutryn
product registrations in the U.S. were voluntarily canceled in
1990-1991.  Subsequently, Troy Chemical Corporation submitted
applications to EPA for material preservation uses. Terbutryn is an
alternative to formaldehyde as a material preservative and these
registrations are expected to lessen the chance of risks posed by
products that release formaldehyde to the extent these new products are
used. 

II.  Human Health Risk Assessment Summary:  The toxicological database
for terbutryn is complete.  Terbutryn is mildly irritating to eyes and
mildly or slightly irritating to skin.  Terbutryn is not a dermal
sensitizer.  Terbutryn is of moderate acute toxicity by oral, dermal, or
inhalation routes of exposure.  In subchronic and chronic toxicity
studies, decreased body weight, body weight gain, hematological effects
and decreased food index were observed.  Normochromic anemia evidenced
by significant decreases in erythrocyte count, hemoglobin, and
hematocrit was observed and noticed in some subacute and subchronic
studies.  In the chronic toxicity study, a statistically significant and
dose-related decrease in hemoglobin and erythrocytes in females was
considered as the primary adverse effect.  Mucosal thickening of the
small intestine and submucosal lymphoid hyperplasia in the pyloric
region of the stomach were noticed in the 6-month dog study.  

Acute Tox: Low to moderate acute toxicity via the oral, dermal, and
inhalation routes of exposure (Toxicity Categories III-IV).  Terbutryn
is not a dermal irritant or sensitizer.

Developmental Tox: Not teratogenic to either species (rabbit or rat),
based upon decreased food consumption increased food index, decreased
body weight gain and stool, changes in rabbits skeletal variations in
developing fetuses were present at doses causing maternal toxicity (i.e.
diarrhea, decreased body weight, decreased body-weight gain).

Repro. Tox: No reproductive effects were reported.

Neurotoxicity:  There is no neurotoxicity study available on technical
terbutryn.  However, no signs of neurotoxicity were observed in the
sub-chronic, chronic, developmental and reproductive toxicity studies
with terbutryn.  There is no evidence that the nervous system is a
target.

Carcinogenicity: The Scientific Advisory Panel (SAP) concluded “tumors
were induced at multiple sites on at the highest dose, which exceeded a
maximum tolerated dose (MTD).  Good dose-response data were not
available due to the large spread between doses.  Therefore the panel
believes that an interim category C is appropriate, but that this could
be reduced to a category D if negative data from ore appropriate doses
were submitted.  Furthermore, the panel does not believe a quantitative
risk assessment (for the carcinogenic effects) is justified since
positive tumor Data occurred only at doses that exceeded the MTD”.  

The FQPA Safety Factor : The data on developmental and reproductive
toxicity of terbutryn (two developmental toxicity studies and one
multi-generation reproduction toxicity study) showed no indication of
developmental or reproductive toxicity to offspring from in utero or
post-natal exposure to terbutryn. Also, there are no indications of
neurotoxicity of terbutryn from the

available subchronic, developmental, or reproductive toxicity data. The
Agency has no

residual uncertainties regarding age-related sensitivities for women of
child bearing age

or infants and children based on the absence of sensitivity observed in
the developmental and reproductive toxicity studies for terbutryn. In
addition, there are no residual uncertainties regarding exposure as
conservative model inputs have been used to estimate exposures to
terbutryn in drinking water.For these reasons, the default 10x FQPA
Safety Factor was reduced to 1x.

Aggregate Risk:  An aggregate risk assessment considers food, drinking
water and residential sources of exposure. There are no registered food
uses. For both children and adults, the adverse effects in the studies
used to assess residential dermal and inhalation risks (decreased body
weight and body weight gain) are different than the effects in the
chronic toxicity study (decreased hemoglobin and erythrocytes) used in
the chronic drinking water assessment, aggregation of chronic drinking
water and residential risks is not appropriate. A short- and
intermediate-term aggregate risk assessment was conducted for terbutryn
for both occupational handlers and residential handlers.  Dermal and
inhalation exposures for these populations were aggregated, as the
studies and endpoints selected for the dermal and inhalation routes are
the same. 

Drinking Water Assessment:  Drinking water consumption and risk were
based on a DEEM-FCID-NHANESIWWEIA (2003-2008) model run using the 18 ppb
EEC level and the cPAD of 0.001. The results indicate that, even with an
extremely conservative estimate of the terbutryn level in drinking
water, all infants were at 97% of the cPAD, children 1-2 were at 54% of
the cPAD, and the total U.S. population was at 38% of the cPAD. When the
somewhat more refined EEC of 9 ppb is modeled, these apparent risks
decline to 49%, 27%, and 19%, respectively.

Occupational and Residential Risk: Risk to commercial and residential
painters applying in-can preservatives in paint are not of concern.
Occupational exposures to workers during the manufacturing process of
mixing and loading terbutryn into joint cements, coatings (e.g.,
paints), sealants, and stuccos are not expected to be of concern
provided the worker wears dermal and inhalation personal protective
equipment (PPE). Dermal PPE would include chemical resistant gloves,
long-sleeve shirts and gloves for both liquid and wettable powder
products. Inhalation PPE would include half face respirator with
appropriate cartridges and/or filters. Inhalation PPE is only required
for workers mixing/loading products that are formulated as wettable
powders.

III.  Environmental Fate/Ecological Risk Assessment Summary:  

Environmental Fate: Persistence: Terbutryn is considered
moderately-persistent to persistent in aerobic and anaerobic conditions
with half-lives of 35-169 days and moderately persistent to persistent
in soil with a half-life of 67 days in aerobic soil. 

Mobility: Terbutryn is moderately mobile to immobile in aerobic and
anaerobic conditions with reported organic carbon partitioning
coefficients ranging from 1,490-12,442 L/KG-oc indicating a potential to
absorb on to particles and bind to sediments.

Mode of Degradation: Terbutryn degrades primarily by photodegradation in
shallow, clear, well-mixed water. Under other conditions, aerobic
metabolism is expected to be the primary route of degradation. Terbutryn
also degrades slowly under conditions of aerobic and anaerobic aquatic
metabolism. There is no evidence of degradation via hydrolysis.   The
major degradates include compounds with intact triazine rings and loss
of side chains.

Ecological risk: Birds: Submitted acute oral and subacute dietary
toxicity data for birds indicate that terbutryn is essentially nontoxic
acutely to birds and ducks. 

Mammals: Practically non-toxic to small mammals. No LOCs were exceeded. 

Terrestrial: There is no exposure to terrestrial organisms at the use
site (i.e., manufacturing facilities).  Additionally, in-service use of
joint cements, coatings (e.g., paints), sealants, and stuccos preserved
with terbutyrn is considered to have insignificant or minimal exposure
because application sites are not habitat for terrestrial organisms and
bioaccumulation in the food chain is not considered a route of concern.

Fish and Aquatic Invertebrate:  All RQs for fish and aquatic
invertebrates as well as aquatic plants were below LOC values, and
therefore the proposed use in paints does not create any apparent
ecological risks of concern.  The other proposed material preservative
uses are expected to have similar (e.g., stucco) or lower exposure and
therefore similar or lower environmental risks than the modeled outdoor
architectural paint scenario. 

 

IV.  Risk Mitigation: Workers involved in the manufacturing process of
mixing and loading terbutryn into joint cements, coatings (e.g.,
paints), sealants, and stuccos, must wear chemical resistant gloves,
long-sleeve shirts and gloves for both liquid and wettable powder
products. Inhalation PPE including half face respirator with appropriate
cartridges and/or filters is also necessary for workers involved in the
manufacturing process that use wettable powders.

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