### Proposed Registration of the New **Material Preservative Active Ingredient,**  **Terbutryn I**  **Proposed Decision**  : The Agency is proposing to register new registrations for product s containing the new active ingredient, t erbutry n. The proposed label uses include material preservation in joint cements, stuccos, sealants, paints, primers, sealers, and industrial coatings. Terbutry n was initiall y registered b y EPA in 1969 as an herbicide to control weeds in various grain crops. All terbutry

n product registrations in the U.S. were voluntarily canceled in 1990
- 1991. Subsequently , Troy Chemical Corporation submitted applications to EPA for material preservation uses. Terbutry n is an alternative to formaldehyde as a material preservative and these registrations are expe cted to lessen the chance of risks posed b y products that release formaldeh yde to the extent these new products are used. **II. Human Health Risk**  **Assessment Summary:** The toxicological database for terbutry n is complete. Terbutry

n is mildly

irritating to eyes and mildly or slightl y irritating to skin. Terbutry n is not a dermal sensitizer. Terbutry n is of moderate acute toxicity by oral, dermal, or inhalation routes of exposure. In subchronic and chronic toxicity studies, decreased body weight, body wei ght gain, hematological effects and decreased food index were observed. Normochromic anemia evidenced b y significant decreases in ery throcy te 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 erythrocy tes in females was considered as the primary adverse effect. Mucosal thickening of the small intestine and submucosal ly mphoid hy

perplasia in the pyloric r egion of the stomach were noticed in the 6
- month dog study. **Acute Tox:** Lo w to moderate acute toxicity via the oral, dermal, and inhalation routes of exposure (Toxicity Categories II I - IV). Terbutry n is not a dermal irritant or sensitizer
. **Developmental T ox:**  Not t eratogenic 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 tox icity (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 terbutry n. However, no signs of neurotoxicity

were observed in the sub
- chronic, chronic, developmental and reproductive toxicity

studies with terbutry

n. There is no evidence that the nervous s ys tem is a target. **Carcinogenicity:** The Scientific Advisory Panel (SAP) concluded “tumors were induced at multiple sites o n 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 onl y at doses that exceeded the MTD”.2

**The FQPA S**  **afety F**  **actor** : The data on deve l opmental and reproductive toxicity of terbutry

n (two developmental toxicity

studies and one multi
- generation reproduction toxicity study) showe d no indication of developmental or reproductive to xicity to offspring from in utero or p o st - natal exposure to terbutry

n. Also, there are no indications of neurotoxicity of terbutry

n from the available subchronic, developmental, or reproductive toxicity data
. The Agency

has no residual uncertainties regarding age
- re l ated sensitivities for women o f child bearing age or infants and children based on the absence of sensitivity observe d in the developmental and reproductive toxicity

studies for terbutry

n . In addition, there are no residual uncertainties regardi ng exposure as conservative model inputs have been used to estimate exposures to terbutry n 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 wat er 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 th an the effects in the chronic toxicity study (decreased hemoglobin and ery throcy tes) used in the chronic drinking water assessment, aggregation of chronic drinking water and residential risks is not appropriate. A short
- and intermediate
- term aggregate ris k assessment was conducted for terbutry n 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 sam e. **Drinking W**  **ater A**  **ssessment:** Drinking water consumption and risk were based on a DEEM
FC ID - NHANESIWWEIA (2003
- 2008) model run us i ng the 18 ppb EEC level and the cPAD of 0
. 001. The results indicate that , even with an extremely conservative estimate of th e terbutry n 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%, respective l y. **Occupational and Residential Risk:** Risk t o commercial and residential painters appl yi ng in
- can preservatives in paint are not of concern. Occupational exposures to workers during the manufacturing process of mixing and loadin g terbutry n 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
- s leeve 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 w ettable powders. **III. Environmental Fate/** **Ecological Risk Assessment Summary**  : **Environmental Fate:**  Persistence: Terbutry n is considered moderatel y - persistent to persistent in aerobic and anaerobic conditions with half
- lives of 35
- 169 day s and m oderatel y persistent to persistent in soil with a half
- life of 67 day s in aerobic soil. Mobility: Terbutry

n is moderatel y 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: Terbutry n degrades primarily

by photodegradation in shallow, clear, well
mixed water. Under other conditions, aerobic metabolism is expected to be the primary route of degradation. Terbutry

n also degrades slowly

under conditions of aerobic and anaerobic aquatic metabolism. There is no evidence of degradation via hydroly sis. The major degradates include compounds with intact triazine rings and loss of side chains.3

**Ecological risk**  **:** Birds: Submitted acute oral and subacute dietary t oxicity d ata for birds indicate that terbutry

n is essentially nontoxic acutel y to birds and ducks
. Mammals: Practically non - toxic to small mammals. N o L OC s were exceeded. Terrestrial: T here 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 terbuty rn is considered to have insignificant or mi nimal 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: A ll 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. **I V.**  **Risk Mitigation:** Workers involved in the manufacturing process of mixing and loading terbutry n into joint cements, coatings (e.g., paints), sealants, and stuccos, must wear c hemical resistant gloves, long
- sleeve shirts and gloves for both liquid and wettable powder products
. Inhalation PPE includ ing half face respirator with appropriate cartridges and/or filters is also necessary for workers involved in the manufact uring process that use wettable powders
.