Page 2 of 22 I. EXECUTIVE SUMMARY

The Antimicrobial s Division ( AD ) has evaluated the proposed use of the new active ingredient 2

- (tert

- b utylamino)

- 4

- (ethylamino)

- 6

- (methylthio)

- s

- triazine (i.e. terbutryn ) as a n industrial microbiocide. Terbutryn was previously registered as a herbicide on February 1987, but the se registrations were later canceled after a FIFRA
1988 data call in was issued

. No terbutryn reregistration eligibility decision (RED)
document was issued.

Troy Corporation has initiated the request for new active ingredient registrations of terbutryn as a material preservative. Terbutryn is a solid at room temperature and as a

res ult the compound is not expected to volatilize. T erbutryn has a n estimated vapor pressure of 0.000225 Pa at 25 °C (1.68 x 10 - 6 mm Hg) (MRID 47810507)

. Terbutryn
Technical (5383

- RGI) is use d to formulate three industrial use products Troysan ®
Terbutec ( 5 3 83

- RGO )

, Polyphase® 710S (5383

- RUN)

, and Troysan®V662 (5383

- TBD)

.

The new proposed labels indicate that terbutryn is to be used as an industrial microbiocide for the preservation of paints, coatings, caulks, adhesives and similar
materials. EPA will examine exposure to occupational workers and residential handlers of products preserved with terbutryn.

EPA will assess exposure to occupational workers while mixing/loading liquid and wettable powder pesticide products used to preserve joint ce ments, coatings, paints, sealants, and stuccos. EPA has historically use d exposure to latex paint as a surrogate or

a reasonable worst case screening estimate for exposures to other preserved products such

as joint cements, coatings, sealants, and stuccos

. EPA has determined that t here is a potential for short

- term (ST) [ defined as 1

- 30 days ] and intermediate

- term (IT) [defined as 1 to 6 months] occupational and ST residential handler exposure s to latex paints

. EPA has not developed a post

- application inhalation exposure scenario for the use of paints because terbutryn is not expected to volatilize . In addition, a dermal post

- application exposure assessment to paint was not conducted because paint will dry soon after application

. Th is assessment uses t oxicological endpoints developed from a recent EPA toxicology memorandum for terbutryn ( U.S. EPA

, 2013 a ).

Conclusion s

• Occupation al applicator exposure was assessed u sing the highest labeled rate of
0. 11 % active ingredient (a.i.)

. The dermal margin of exposure ( MOEs ) for the
brush/roller and airless sprayer are not of concern (calculated dermal MOEs are more than the target MOE of 100 )

. The short

- term residential applicator dermal risks are not of concern for all residential handler scenarios for painting using a brush/roller
and the airless sprayer using the highest labeled application rate of 0. 11 % a.i

.Page 3 of 22 • S ince the inhalation toxicological endpoint is based on an oral no

- observable

- adverse

effect level (NOAEL) , an extra 10X uncertainty facto r ( UF ) is applied to account for extrapolation from the oral route to the inhalation route

. The inhalation MOEs do not exceed the level of concern (e.g., calculated MOEs are greater than the target MOE of 1,000 ) for occupational and residential exposures

.

• Occupational w orker s during the manufacturing process of mixing and load ing terbutryn preservatives into joint cements, coatings, sealants, and stuccos were assessed. Risks are not expected to be exceeded provided the worker wears dermal
and inhalation personal protective equipment (PPE). D ermal 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 filte rs . Inhalation PPE is only required for workers mixing/loading products that are formulated as wettable powder s.

• T he NOAEL used for the dermal risk assessment is based on an oral study; the calculated dermal exposures were adjusted for dermal absorption of 35%.

II. BACKGROUND

A. Action Requested

The Agency developed an assessment based on the new proposed uses and
calculated the short

- and intermediate risks to occupational and residential exposure s to terbutryn antimicrobial products

.

B. Use Profile

Table 1 presents the chemical identity of terbutryn. According to the information available terbutryn is a powder

, is not particularly soluble in water (22 mg/L)

, and has a melting point of 104oC. Terbutryn is a solid at room temperature and is not expected to
volatilize.

Table 1. Chemical Identity

Common Name Te r butryn

Chemical name 2

- (tert

- butylamino)

- 4

- (ethylanino)

- 6

- (methylthio)

- s

- triazine

PC Code 080813 CAS registry
number 886

- 50

- 0

Case No. NonePage 4 of 22 Table 1. Chemical Identity

Structure

Empirical
Formula C10H19N5S1

Table 2 presents the antimicrobial use sites of three industrial end

- use products: Troysan® Terbutec (5383

- RGO), Polyphase® 710S (5383

- RUN), and Troysan ® V662 (5383

- TBD)

. T he proposed antimicrobial labeled uses for these products are as a material preservative for joint cements, coatings, sealants, and stuccos.

Table 2: Proposed Antimicrobial Use Sites for Terbutryn *

Use Site Product/Formulation Application

Rate (% product) Application

Rate (% ai by weight)

Joint cements Troysan® Terbutec (powder )
99% a.i. 0.03

- 0. 1 0 0.03

- 0. 1 0

Polyphase® 710S ( l iquid)
14% a.i. 0.5

- 1.5 0.0 5

- 0. 1 2

Troysan ®V662 (liquid)
48% a.i. 0.05

- 0.2 0.04

- 0.11

Coatings Troysan® Terbutec (powder )
99% a.i. 0.02

- 0. 1 0 0.02

- 0. 1 0

Polyphase® 710S (Liquid)
14% a.i. 0.5

- 1.4 0.0 4

- 0. 11

Troysan ®V662 (liquid)
48% a.i. 0.05

- 0.2 0.04

- 0.11

Sealants Troysan® Terbutec (powder )
99% a.i. 0.02

- 0. 1 0 0.02

- 0. 1 0Page 5 of 22 Table 2: Proposed Antimicrobial Use Sites for Terbutryn *

Use Site Product/Formulation Application

Rate (% product) Application

Rate (% ai by weight) Polyphase® 710S (Liquid)
14% a.i. 0.5

- 1.5 0.0 4

- 0. 11

Troysan ® V662 (Liquid)
48% a.i. 0.05

- 0.2 0.096

- 0.24

Stuccos Troysan® Terbutec (powder )
99% a.i. 0.02

- 0. 1 0 0.02

- 0. 1 0

Polyphase® 710S (Liquid)
14% a.i. 0.5

- 1.5 0.0 4

- 0. 11

Troysan ® V662 (Liquid)
48% a.i. 0.05

- 0.2 0.04

- 0.11

* Based on proposed labels dated 1/16/12

C. Criteria for Conducting Exposure Assessments

An occupational and/or residential exposure assessment is required for an active ingredient if (1) certain toxicological criteria are triggered and (2) there is a potential for exposure to handlers (mixers, loaders, applicators) during use or to persons entering treated sites or exposed to vapors after application is complete. Dermal and inhalation

t oxicological endpoints are needed to assess short

- , and i ntermediate

- term worker

exposures . There is a potential for applicator exposure s to in

- can preservatives in paints
in occupational and residential settings

. In addition, an occupational w orker may become

expose d while mix ing /load ing active ingredients when formulating preservatives for joint cements, coatings, sealants, and stuccos products

.

In this document, representative scenarios were assessed by using unit exposure data to estimate occupational and residential handlers’ exposures. Unit exposures are estimates of the amount of exposure to an active ingredient a handler receives while performing various handler tasks and are expressed in terms of micrograms or milligr ams (1 mg = 1,000 μg) of active ingredient per pounds of product handled. A series of unit exposures have been developed that are unique for each scenario typically considered in assessments (i.e., there are different unit exposures for different types of application equipment, job functions, and levels of protection). Appendix A provides the calculations for unit exposure , exposure, and MOEs

.Page 6 of 22 D. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies, which comprise the Pesticide Handlers Exposure Database (PHED) and the Chemical Manufacturers Association (CMA) database have already had ethical reviews and can be
used in risk assessment s

.

III. SUMMARY OF HAZARD CONCERNS FOR TERBUTRYN

The Agency has reviewed all toxicity studies submitted for terbutryn in the

A gency hazard assessment memorandum ( U

. S

. EPA

, 201 3 a )

. Table 3 summarizes the applicable toxicological doses and endpoints used for this occupational and residential

assessment

. More detail description is provided in the hazard assessment memorandum.

Since the dermal No Observed Adverse Effect Level ( NOAEL ) was selected based on results of oral studies, calculated dermal exposures were adjusted for a dermal absorption value of 35% (MRID 00157844)

. The oral NOAEL was also selected for the inhalation route. Therefore, a 10X uncertainty factor has been included for the inhalation route based on the lack of an inhalation specific toxicity study. The body weight used for
both the derma l and inhalation assessment is 80 kg based on the Exposure Factors
Handbook (U

. S

. EPA

, 2011).

On December 23, 1987

, the Agency presented the study results of previously submitted terbutryn chronic toxicity /ca rcinogenicity studies to the FIFRA Scientific Advisory Panel (SAP). The SAP concluded that “tumors were induced at multiple sites only 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 SAP assigned terbutryn as an interim category C (a possible human carcinogen), but also
decided to reduce th e assigne d category to a category D if negative data from more 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 tha t exceeded the MTD. ”

In 2011, the agency reviewed a newly submitted 2

- year rat carcinogenicity study and concluded that although

, cancer was detected at the highest dose tested (600 ppm), the toxicological significance of pancreatic acinar adenoma results were questionable. The cancer effect (i) did not show a clear dose

- dependency manner; (ii) the effect was seen in male rats only; and (iii) the control group has incidences of acinar adenoma (21%) that are higher than the historical control incidences (2

- 14%) (U

. S

. EPA 2012 a ).

For all dermal and inhalation exposure scenarios, uncertainty factors (UF) of 10x for interspecies extrapolation and 10x for intraspecies variation (total UF of 100x) were used. The level of concern (LOC) for occupational and residential dermal and inhalation risks is for margins of exposure (MOEs) less than 100. In addition, a n extra 10X database uncertainty factor for route to route extrapolation was applied to the existing
inhalation LOC since it is based on the 90

- day ora l toxicity study

.Page 7 of 22 Table 3. Summary of Toxicological Doses and Endpoints for Terbutryn

Exposure
Scenario Dose Used in Risk Assessment, UF Special Level of
Concern for Risk
Assessment Study and Toxicological Effects

Short (1

- 30 days)
Incidental Oral NOAEL=10 mg/kg/day Residential/ Occupational MOE =
100

(10x for inter species variation, and 10X for
intra

- species variation) Rabbit Developmental Study

(MRID# 000152763)
LOAEL = 50 mg/kg/day
based upon decreased food consumption, increased food index, decreased body weight gain and stool changes in rabbits at 50 mg/kg

Intermediate

- Term (1

- 6 Months)
Incidental Oral NOAEL=10 mg/kg/day Residential/ Occupational MOE =
100

(10x for inter species variation, and 10X for
intra

- species variation) 6

- month dog study (MRID 00029152)
LOAEL = 25 mg/kg/day (based on mucosal thickening of various segments of the small intestine and submucosal lymphoid hyperplasia in the pyloric region of the stomach was observed)

Relative dermal absorption rate 35% (MRID 00157844)

Short (1

- 30 days)
Incidental Dermal BMDL = 18.5 mg/kg/day Residential/ Occupational MOE =
100

(10x for inter species variation, and 10X for
intra

- species variation) 90

- day Oral Toxicity Study in Rats

(MRID# 47810501)
LOAEL = 70 mg/kg/day
based upon decreased body weight and body weight gain.

Intermediate

– Term (1

- 6 Months)
Incidental Dermal BMDL = 18.5 mg/kg/day Residential/ Occupational MOE =
100

(10x for inter species variation, and 10X for
intra

- species variation) 90

- Day Oral Toxicity Study in Rats

(MRID 47810501)

LOAEL = 70 mg/kg/day based on decreased body weight and body weight gain.

Short , Intermediate, Long

- Term
Inhalation BMDL = 18.5 mg/kg/day Residential/ Occupational MOE =
1000

(10x for inter species variation, 10X for intra

species variation and
10X database uncertainty for route to route extrapolation) same as for dermal exposure above.

Cancer (oral, dermal, inhalation) Group C carcinogen; quantitative risk assessment is not needed.Page 8 of 22 IV. OCCUPATIONAL EXPOSURES AND RISKS

For terbutryn, p otential occupational handler exposures can occur while mixing/loading preservatives and applying paints

. Dermal and inhalation exposures are expected to occur for both settings

.

A. Occupational Handler Exposures and Risks

Due to the lack of product

- specific/chemical

- specific exposure monitoring data, surrogate data from the Estimates of Worker Exposure from The Pesticide Handler Exposure Database (PHED) Version 1.1 dated August 1998 (U

. S

. EPA, 1998) was used for unit exposures for wettable powders and th e Chemical Manufacturers Association (CMA) antimicrobial exposure study (U

. S

. EPA, 1999: DP Barcode D247642) w a s used for estimating liquid pour unit exposures (UE)

.

Based on use data and label instructions, the agency believes that terbutryn exposures

may occur over a s hort

- term (1

- 30 days) term or intermediate

- term (1

- 6 month) exposure

. The risk assessment (see Table 4 ) developed for occupational handlers are based on mixer/loader and applicator exposures.

a. Mixer/loaders

Worker exposure may occur while mixing dust/powder or liquid formulation by scenarios: open pour of wettable powders or liquid pour to preser ve joint cements, coatings (e.g., paints), sealants, and stuccos

. The term “open pour” refers to the resulting worker exposure from physically transferring a dust/powder or liquid from a drum into the material preservative slurry by pouring from large containers (often drums) to smaller containers. Worker exposure from transferring the preservative by connecting/ disconnecting a chemical metering pump from a tote or by gravity flow is often known as the “liquid pump” scenario

. The agency identified the following mixer/loader scenarios:

• Exposure while mixing/loading wettable powder products used to preserve joint

cements, coatings (e.g., paints) , sealants, and stuccos (wettable powder unit exposure data was used as surrogate data for the dust/powder formulation); and

• Exposure while mixing/loading liquid products used to preserve joint cements, coatings (e.g., paints) , sealants, and stuccos

.

Use of a liquid pump and water soluble packaging of wettable powders are examples of engine ering controls which are intended to limit and minimize mixer/loader exposure.

b. Applicators

An applicator is a worker applying the treated material. The Agency derived anticipated use patterns from current label s and based our decisions on the types of equipment and techniques used antimicrobial applications. The Agency identified the following mixer/loader scenarios:Page 9 of 22 • Application of preserved c oatings ( which are represented through the use
of latex p aint ) by p rofessionals ( b rush/ r oller); and

• Application of preserved c oatings ( which are represented through the used
of latex p aint ) by p rofessionals ( a irless s prayer ).

c. Data and Assumptions for Handler Exposure Scenarios

A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. The assumptions and factors used in the risk
calculations include:

• MOEs were calculated for the short

- and intermediate

- term durati on for dermal and inhalation exposures using the appropriate endpoints in Table 4.

• Since the short

- and intermediate

- term dermal endpoints are based on oral studies

, a dermal absorption factor of 35% was used to adjust the oral endpoint value to
estimate dermal exposure for short

- and intermediate

- term durations (Health Effects Division policy document, 2010: Interim Guidance: Estimating Dermal Absorption Factors for Use in Human Health Risk Assessments) . Since the short

and intermediate

- term inhalation endpoints are based on oral studies and no inhalation absorption data are available, toxicity by the inhalation route is
considered to be equivalent to that by the oral route.

• In October 2011, Exposure Factors Handbook updated the recommended body weight to 80 kg (U

. S

. EPA

, 2011). The agency use d the updated body weight of 80 kg for this assessment.

• For non

- cancer assessments, the agency traditionally assumes the maximum application rates allowed by labels in its risk assessments (see Table 2 ).

• The av erage occupational workday is assumed to be 8 hours.

• For the occupational assessment, t he dermal and inhalation unit exposure values were taken from the Pesticide Handler Exposure Database (U

. S

. EPA

, 1998). The specific unit exposures used in this assessment are described in the bulleted list
below.

i. Mixer/loaders

 For open mixing /loading of wettable powders

, the occupational PHED
dermal and inha lation unit exposure values were used (PHED scenario

4 )

. The wettable powder unit exposure data were used as surrogate data for the dust/powder formulation. The dermal UE s for workers wearing long

- sleeve shirt and long pants or full coveralls are 0.17 mg/lb a.i. with gloves and 3.7 mg /lb a.i. with out gloves

. Th e inhalationPage 10 of 22 UE is 0.043 mg/lb a.i. for baseline (no respirator) and 0.0043 mg/lb a.i.
for a half

- or full

- face respirator ( providing a 90% protection factor).

 F or liquid pour ( open mixing/loading )

, the CMA dermal and inhalation unit exposure values for were used

. T he dermal UE for workers wearing long

- sleeve shirt and long pants or full coveralls and gloves is 0.135 mg/lb a.i and t he inhalation UE for baseline (no respirator) is 0.00346 mg/lb a.i. There is no CMA ungloved dermal

UE for the liquid p our preservatives scenario; a dermal UE of 50.3 mg/lb a.i. was used for workers not wearing gloves, taken from the
C MA liquid pour cooling tower scenario.

ii. Applicators

For in

- can preservative products such as paint, applied by a professional painter, the agency used the UEs from the PHED surrogate table (1998) assuming that the painter wears long pants, long sleeves, and

no gloves for brush/roller and airless sprayer application methods (note:
aerosol cans are not com monly assessed unless they are specified on the label). Gloves or respirators are not a viable mitigation option for in

- can preservative products such as paints because it is not feasible to label these types of end

- use products with the biocide informatio n.

 For roller/brush scenarios, the occupational PHED dermal and inhalation unit exposure values for paintbrush applications (PHED scenario 22) were used (single layer of clothing). The dermal UE representing a single layer of clothing is 180 mg/lb a.i. f or ungloved replicates. The inhalation UE is 0.28 mg/lb a.i.

 For airless sprayer scenarios, the occupational PHED dermal and inhalation unit exposure values for airless sprayer application (PHED scenario 23) were used

. Th e dermal UEs representing a si ngle layer of clothing is 38 mg/lb a.i. for ungloved replicates. The inhalation UE is 0.83 mg/lb a.i.

• There are three basic risk mitigation approaches considered appropriate for controlling occupational exposure. These include administrative controls, use of personal protective equipment (PPE), and the use of engineering controls. Occupational handler ex posure assessments were completed by the agency using baseline, and PPE.

• The baseline clothing level for occupational exposure scenarios is generally an individual wearing long pants, a long

- sleeved shirt, shoes, socks, no chemical

resistant gloves, and no respirator. The first level of mitigation generally applied is PPE, whic h may include addition of chemical resistant

- gloves, an additionalPage 11 of 22 layer of clothing, and/or a respirator. Mitigation was achieved using PPE; engineering controls was not necessary.

The quantity handled/treated values were estimated based on informatio n from various sources. The following assumptions were made:

 For the open pour/liquid pour mixing/loading scenarios to support the p reservation of joint cements, coatings (e.g., paints) , sealants, and

stuccos: 20,000 lbs (approximately 2,000 gallons, wh ere material density is 10 lb/gal) (AD assumption).

 For the roller/brush painting scenario, it was assumed that 50 lbs (approximately 5 gallons of paint with a density of 10 lb/gal) of treated paint are used ( AD assumption ).

 For the airless sprayer painting scenario, it was assumed that 5 0 0 lbs (approximately 5 0 gallons of paint with a density of 10 lb/gal) of treated paint are used ( AD assumption ).

d

. Exposure Calculations and Results

For all dermal exposure scenarios, uncertainty factors of 10x for interspecies extrapolation and 10x for intraspecies variation (total UF of 100x) were used. Dermal

o ccupational exposure and risk resulting in MOEs greater than or equal to 100 will not

exc eed the agency ’s level of concern. Inhalation o ccupational exposure and risk resulting in MOEs greater than or equal to 1,000 will not exceed the agency’s level of concern.

Summaries of the risks for occupational handlers are included in Table 4

.

De rmal

The short

- and intermediate

- term dermal risks excee d the agency’s level of

concern only for baseline attire (i.e., long

- sleeve shirt, long pants, shoes, socks, and no gloves) for the mixer/loader occupational handler scenarios with both wettable pow der (dermal MOE 58) and liquid formulations (dermal MOE 4). With the addition of chemical resistant gloves for the mixing/loading scenarios, the short

- and intermediate

term dermal risks are > 100 and are thus not of concern. The baseline dermal MOEs (ung loved) are 420 for the brush/roller scenario and 190 for airless sprayer applicator
scenario and are thus not of concern.

Inhalation

The short

- and intermediate

- term inhalation risks do not exceed the agency’s level
of concern at baseline (no respirator) for any of the occupational handler scenarios ( t arget MOE of 1,000 )

.Page 12 of 22 Aggregate Risk Index (ARI) Method :

The ARI was devised as a way to aggregate MOEs that have dissimilar UF’s. MOEs for each route of concern are compared against UF’s which reflect the nature, source, and quality of the data, and the FQPA mandate to protect susceptible infants and children. The ARI method automatically considers each route’s potency when route

specific NOAELs are used. If the MOE/UF ratios for each route of exposure are treated as fractions, they can be adjusted to a common denominator of 1. The ARI is then
calculated as follows:

ARI= 1[1/(UF/MOE inhalation )+ 1/(UF/MOE dermal )]

The ARI is always compared against 1. This allows for direct comparisons
betwee n routes and between chemicals. As a general rule, an ARI greater than or equal to 1 is of little concern, but an ARI less than 1 suggests a risk of concern.

The short

- and intermediate

- term ARIs exceed the agency ’s level of concern only
for baseline attire (i.e., long

- sleeve shirt, long pants, shoes, socks, and no gloves) for the mixer/loader occupational handler scenarios with both wettable powder (ARI 0.43) and liquid formulations (ARI 0.04). With the addition of chemical resistant gloves for the mixing/loading scenarios, the short

- and intermediate

- term dermal risks do not exceed the

agency ’s level of concern (e.g., ARI>1).

B. O ccupational Postapplication Exposures and Risks

Dermal and inhalation exposures are expected to occur to b ystanders as a result of material preservative applications in industrial settings. Currently, no data are available to assess this scenario; however, exposures are expected to be less than handler exposure. Terbutryn is a solid at room temperature and as a result the compound is not expected to
volatilize since its vapor pressure is 1.68E

- 6 mm Hg (U.S. EPA 2013 b )

.Page 13 of 22 Table 4 . Short and Intermediate Term Risks Associated with Occupational Handlers using Terbutryn

Exposure
Scenario Method of Application Unit Exposure (mg/lb a.i.)

App.

Rate Quantity
Handled/ Treated per day Absorbed Daily Dose (mg/kg/day) d MOEs e Total ARI (LOC = ARI <1)

Dermal Inhalation Dermal Inhalation Dermal (LOC = MOE <100) Inhalation (LOC = MOE <1000) Baseline
Dermal +
Inhalation PPE

Gloves
Dermal +
Inhalation PPE

- Gloves
Dermal + PF10 Resp.
Inhalation Baseline

a P PE

Gloves b Baseline

a PF10 Resp. c Baseline

a PPE

Gloves

b Baseline

a PF10

resp. c Baseline

a PPE

Gloves

b Baseline

a PF10 Resp.

c

Mixing/Loading

Preservation of Joint Cements, Coatings (e.g. paints) , Sealants,

and Stuccos Open Pour
Wettable
Powder (PHED) 3.7 0.17 0.043 0.0043 0. 1 % ai by weight 20,000 lbs 0.32 0.0 15 0.01 1 0.001 1 58 1300 1700 N/A 0.43 1.5 N/A

Liquid Pour

(CMA) 50.3 0.135 0.00346 N/A 0. 11 % ai by weight 20,000 lbs 4.9 0.013 9.7E

- 4 N/A 4 1400 19,000 N/A 0.04 8.1 N/A

Applicators

Application of

Paint by
Professionals Brush/Roller (PHED) 180 N/A 0.28 N/A 0. 11 % ai by weight 50 lb 0.044 N/A 0.0002 N/A 420 N/A 94,000 N/A 4 N/A N/A

Airless Sprayer (PHED) 38 N/A 0.83 N/A 500 lb 0.093 N/A 0.0058 N/A 19 0 N/A 3200 N/A 2 N/A N/A

N/A= Not applicable. Bold = MOE exceeds the Agency’s level of concern.

a Baseline Dermal: Long

- sleeve shirt, long pants, no gloves. Baseline Inhal ation: No respirator.
b PPE Dermal with gloves: baseline dermal plus chemical

- resistant gloves.

c PF10 Elastomeric half face respirator with appropriate cartridges and/or filters. Confirmatory inhalation study required for inhalation MOEs <100.
d Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb ai) * absorption (1.0 for ST/IT inhalation and 0.35 for ST/IT dermal) * applic ation rate * quantity treated / Body weight ( 8 0 kg).

e MOE = NOAEL (mg/kg/day) / Absorbed Daily Dose [Where ST/IT NOAEL = 1 8.5 mg/kg/day for dermal and inhalation exposures].
f Total MOE =1 / [1/ ( D ermal UF ) + ( 1 / ( Inhalation UF ) ]

. The dermal UF=100 and the inhalation UF=1,000.14 of 22 V. RESIDENTIAL EXPOSURES AND RISKS

Based on the use patterns on the labels, the EPA has determined potential residential handler exposures are a result of secondary handler dermal and inhalation exposure from applying joint cement, coating (e.g., paints) , sealant, and stucco treated with terbutryn.

A. Residential Handler Exposures and Risks

T he representative residential handler scenario s assessed were the application of
in

- can preservative products such as paint , using a brush/rollers and airless sprayers (described in Table 5 ). The application of paint was assessed using PHED data and
equat ions outlined in Appendix A.

1. Data and Assumptions for Handler Exposure Scenarios

The assumptions and factors used for residential painter scenarios include:

Unit Exposure Values : Unit exposure values were taken from the PHED data presented
in HED ’s Residential SOPs (U

. S

. EPA, 201 2 b ).

• For the airless sprayer scenario

,

Dermal Unit Exposure Data Summary:

The recommended dermal unit exposures for applications of pesticid e

- containing paints or stains using an airless sprayer is based on a lognormal distribution fit with exposu re monitoring data from PHED . PHED monitored 15 applications of approximately 5 gallons of pesticide

- containing stain with an airless sprayer.
While another study was available that was also reasonably representative of

re sidential applications, PHED employed exposure monitoring methods that best represented the type of clothing a homeowner or amateur applicator would wear (i.e., shorts, short

- sleeve shirt, no chemical

- resistant gloves).

Inhalation Unit Exposure Data Summary:

The recommended inhalation unit exposures for applications of pesticide

containing paints or stains using an airless sprayer is based on a lognormal distribution fit with exposure monitoring data from Formella, T. (1995) [EPA MRID 43600102] and PHED . Forme lla, T. (1995) monitored 36 applications of approximately 5 gallons of pesticide

- containing paint inside and outside houses for approximately 22

- 81 minutes using an ai rless sprayer. PHED monitored 15 applications of approximately 5 gallons of pesticide

- con taining stain with an airless sprayer. Both studies were reasonably representative of residential applications with inhalation exposures of the same general magnitude, thus a composite data set was utilized.15 of 22 • For the brush scenario

,

Dermal Unit Exposure Data Summary: The recommended dermal unit exposures for applications of pesticide

- containing paints or stains using a brush is based on a lognormal distribution fit with exposure monitoring data from PHED. PHED monitored 15 applications of approxi mately 1 gallon of pesticide

- containing paint to an interior b athroom for approximately 34

- 94 minutes with 2

- or 4

- inch brushes. This was the only available study for this exposure scenario.

Inhalation Unit Exposure Data Summary:
The recommended inhalati on unit exposures for applications of pesticide

containing paints or stains using a brush is based on a lognormal distribution fit with exposure monitoring data from PHED. PHED monitored 15 applications of approximately 1 gallon of pesticide

- containing pai nt to an interior bathroom for approximately 34

- 94 minutes with 2

- or 4

- inch brushes.

Quantity handled/treated : The quantities handled/treated were estimated based on information from various sources and assumptions.

• For the airless sprayer in paint applications , it is assumed that 150 lbs (approximately 15 gallons) of treated paint will be used. This is based on the coverage of 200 ft 2 /gallon and a house size of 40 x 30 x 20 ft (surface area of 2,800 ft 2 ) (U.S. EPA, 201 2 b )

.

• For the brush/roller in p aint applications , it is assumed that 20 lbs (approximately 2 gallons) of treated paint will be used. This is based on the 90 th
percentile value of 8 gallons of latex paint used per year divided by the mean frequency of 4 painting events/year (U.S. EPA, 2 011, 201 2 b )

.

Duration of Exposure : The duration of exposure for most homeowner applications of paint products is believed to be best represented by the short

- term duration (1 to 30 days). The reason that short term duration was chosen is because the different scenarios (i.e.
methods of a pplication) are assumed to be episodic, not daily. In addition, homeowners are assumed to use different paint products with varying actives, not exclusively terbutryn treated products (U.S. EPA, 201 1 )

.

2. Exposure Calculations and Results

The result ing short

- term exposures and MOEs for the representative residential handler scenarios are presented in Table 5

.

Dermal16 of 22 The short

- term dermal risks do not exceed AD ’s level of concern for all
residential handler scenarios.

Inhalation

The short

- term inhalation risks do not exceed AD ’s level of concern for all of the
residential handler scenario s.

Aggregate Risk Index (ARI) Method :

The ARI was devised as a way to aggregate MOEs that have dissimilar UF’s.
MOEs for each route of concern are compared against UF’s which reflect the nature, source, and quality of the data, and the FQPA mandate to protect susceptible infants and children. The ARI method automatically considers each route’s potency when route

specific NOAELs are used. If the MOE/UF ratios for each route of exposure are treated as fractions, they can be adjusted to a common denominator of 1. An ARI less than 1
indicates a risk concern. The ARI is then calculated as follows:

ARI= 1[1/(UF/MOE inhalation )+ 1/(UF/MOE dermal )]

The short

- term ARIs do not exceed the agency ’s level of concern for all of the
residential handler scenarios.

Table 5. Short

- Term Terbutryn Residential Handlers Exposures, MOEs , and ARIs

Exposure
Scenario Method of Application Unit Exposure (mg/lb ai)

Application

Rate Quantity
Handled/
Treated per day Absorbed Daily Dose b (mg/kg/day) MOE c Aggregate Risk Index (ARI)

(LOC<1)

Dermal a Inhalati

on Dermal Inhalation Dermal (LOC = MOE <100) Inhalation ( LOC =
MOE <1000)

Painting Brush/roller 450 0.2 0.11% ai by weight 20 lbs (2 gal) 0.043 5.5E

- 5 430 4.4E+5 4.2

Airless

sprayer 160 0.56 0.11% ai by weight 150 lbs (15 gal) 0.12 0.0012 160 1.6E+4 1.5

Bold = MOE exceeds the Agency’s level of concern

. Revised based on latest HED residential SOPs (February 2012)

a All dermal unit exposures rep resent ungloved replicates. The brush/roller and airless sprayer unit exposures represent short sleeve and short pant replicates.
b Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb ai) * absorption (1.0 for ST inhalation and 0.35 for ST dermal) * application rate * quantity treated / Body weight ( 8 0 kg).

c MOE = NOAEL (mg/kg/day) / Absorbed Daily Dose [Where ST NOAEL = 10 mg/kg/day for dermal and inhalation exp osures]. RI= UF/MOE, ARI=1/[(1/ UF/MOE dermal+1/ UF/MOE inhale)]17 of 22 B. Residential Post

- application Exposures and Risks

Postapplication/bystander inhalation exposures for use of paints (vapor exposure
to adults and children) were not assessed because terbutryn is a solid at room temperature and therefore is not expected to volatilize since its vapor pressure is 1.68E

- 6 mm Hg (US
EPA 201 3 b ).

V I

. NON

- DIETARY AGGREGATE EXPOSURE

An aggregate risk assessment considers food uses, drinking water and residential

exposures. There are no registered food uses. For both children and adults, because the adverse effects in the studies used for dermal and inhalation endpoints (decreased bod y weight and body weight gain) and utilized for the residential risk assessment are different than the effects in the chronic study (decreased hemoglobin and erythrocytes) used in the chronic drinking water assessment, aggregation of chronic drinking water and residential risks is not appropriate.

The only risks that need to be aggregated would be residential applicator exposures. The Agency combined short

- term residential risks for dermal and inhalation applicator exposures because the toxicological e ffects were the same for both the dermal
and inhalation routes. R esidential applicator were aggregated for both dermal and inhalation exposures and are represented by ARIs and do not exceed the Agency’s level
of concern

.

VII. RISK CONCLUSIONS

• Exposure to commercial painters was assessed using the highest labeled rate of 0.11% active ingredient (a.i.). The calculated dermal margins of exposure (MOEs) for the brush/roller and airless sprayer scenario (420 and 190 respectively) were higher than
the level o f concern (100) and are therefore not of concern.

• Residential risks for the residential painter applying in

- can preservatives in paint were

not of concern . The short

- term residential applicator dermal risks are not of concern
for all residential handler scenarios for painting using a brush/roller and the airless sprayer using the highest labeled application rate of 0.11% a.i.

• S ince the inhalation toxicological endpoint is based on an oral no

- observable

- adverse

effect level (NOAEL) , an extra 10X database uncertainty factor (UF) is applied to account for extrapolation from the oral route to the inhalation route. Calculated inhalation MOEs for occupational handlers were in excess of the target MOE of 1000
and thus are not of co ncern.18 of 22 • Occupational exposures to workers during the manufacturing process of mixing and loading terbutryn into joint cements, coatings (e.g., paints) , sealants, and stuccos were assessed. Risks are not expected to be of concern provided the worker wears d ermal 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

ca rtridges and/or filters. Inhalation PPE is only required for workers mixing/loading products that are formulated as wettable powders.

VII I

. R EFERENCE

USEPA, 1997. Exposure Factors Handbook. Volume I

- II. Office of Research and Development. Washington , D.C. EPA/600/P

- 95/002Fa.

USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure from the Pesticide Handler Exposure Database Version 1.1. Washington, DC: U.S. Environmental Protection Agency.

USEPA

, 2000. Residential SOPs. EPA Office of Pesticide Programs Human Health Effects Division. Dated April 5, 2000.

U

. S

. EPA, 2011. Exposure Factors Handbook. EPA/600/R

- 10/030. October 2011. www.epa.gov/ncea.

U

. S

. EPA, 2012a. Memorandum from Jonathan Chen. Subject: Terbutryn 

### : Evaluation of

the Rat Combined Chronic Toxicity/Carcinogenicity Study

– “ Fankhauser, H. (2001) 24

- Month carcinogenicity and chronic toxicity study in rats. Syngenta Crop Protection AG, Stein, Switzerland. Laboratory Study No.: 951040, May 8, 2001. MRID 48348901. Unpublished.” DP Barcode: D386095.

USEPA, 2012 b

. Standard Operating Procedures for Residential Pesticide Exposure

Assessment. Health Effects Division. Office of Pesticide Programs. http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html#datacomp January 2012

.

U.S. EPA, 2013 a . Memorandum: Terbutryn: Toxicological Review and Hazard

A ssessment for the Proposed Uses as a Material Preservative. Memorandum from Jonathan Chen, PhD., Toxicologist to Stacey Grigsby, Product Manager. DP Barcode:
D407711.

U.S. EPA 2013 b . Memorandum: Review for 5383

- RGI . Memorandum from Chris Jiang,
Chemist t o Jacqueline Campbell

- McFarlane PM 34/ Stacey Grigsby, DP Barcode:

D 367948

.19 of 22 APPENDIX A
UNIT EXPOSURES20 of 22 Using surrogate unit exposure data, maximum application rates from labels, and EPA estimates of daily amount handled, exposures and risks to handlers were assessed. The exposure/risks were calculated using the following equations:

A D uses unit exposure to assess handler exposures to pesticides. Unit exposures are estimates of the amount of exposure to an active ingredient a handler receives while

pe rforming various handler tasks and are expressed in terms of micrograms or milligrams of active ingredient per pounds of active ingredient handled. A D has developed a series of unit exposures that are unique for each scenario typically considered in our

a ssessments (i.e., there are different unit exposures for different types of application equipment, job functions, and levels of protection). The unit exposure concept has been established in the scientific literature and also through various exposure moni toring guidelines published by the U.S. EPA and international organizations such as Health Canada and OECD (Organization for Economic Cooperation and Development).

Once the data for a given exposure scenario have been selected, the data are normalized ( i.e., divided by) by the amount of pesticide handled resulting in standard unit exposures (milligrams of exposure per pound of active ingredient handled). Following normalization, the data are statistically summarized. The distribution of exposure for

ea ch body part (e.g., chest, upper arm) is categorized as normal, lognormal, or “other” (i.e., neither normal nor lognormal). A central tendency value is then selected from the distribution of the exposure for each body part. These values are the arithmeti c mean for normal distributions, the geometric mean for lognormal distributions, and the median for all “other” distributions. Once selected, the central tendency values for each body part are composited into a “best fit” exposure value representing the e ntire body.

1. Daily Exposure

Daily dermal or inhalation handler exposures are estimated for each applicable handler task with the application rate, quantity treated/handled in a day, and the applicable dermal or inhalation unit exposure using the foll owing formula:

Daily Exposure: E = UE x AR x AT (Eq. 1)

Where:

E = Amount (mg or μg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption;

UE = Unit exposure value (mg ai/lb ai) derived from August 1998 PHED data or from CMA
1999 data ; AR = Maximum application rate based on a logical unit treatment, such as acres (A), square feet (sq. ft.), gallons (gal), or cubic feet (cu. ft). Maximum values are gene rally used (lb ai/A, lb ai/sq ft, lb ai/gal, lb ai/cu ft); and

AT = Normalized application area based on a logical unit treatment such as acres (A/day), square feet (sq ft/day), gallons (gal/day), or cubic feet (cu ft/day).

2. Daily Dose

The daily dermal or inhalation dose is calculated by normalizing the daily exposure by body weight and adjusting, if necessary, with an appropriate absorption21 of 22 factor. Since the short

- and intermediate

- term dermal endpoints are based on oral studies
a derm al absorption factor of 35% was used to estimate dermal exposure for short

- and
intermediate

- term durations. Since the short

- and intermediate

- term inhalation endpoints
are based on oral studies and no inhalation absorption data are available, toxicity by the
inhalation route is considered to be assumed to be 100% of the oral dose. Daily dose was calculated using the following formula:

Daily Dose: ADD = E x ABS (Eq. 2)

BW

Where:

ADD = Absorbed dose received from exposure to a chemical in a given scenario (mg active ingredient/kg body weight/day);

E = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption;
ABS = A measure of the amount of chemical that crosses a biological boundary such as lungs (% of the total available absorbed); and

BW = Body weight determined to represent the population of interest in a risk assessment (kg).

3. Margins of Exposure

Non

- cancer inhalation and dermal risks for each applicable handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the daily dose to the toxicological endpoint of concern.

Margins of Exposure: MOE = NOAEL or LOAEL (Eq. 3 )

ADD

Where:
MOE = Margin of exposure, value used to represent risk or how close a chemical exposure is to being a concern (unitless);
NOAEL or LOAEL = Dose level in a toxicity study, where no observed adverse effects (NOAEL) or where the lowest observed adverse effects (LOAEL) occurred in the study; and

ADD = Average daily dose or the absorbed dose received from exposure to a chemical in a given scenario (mg ai/kg body weight/day).

In addition to the target MOEs that were used for the anal ysis, a series of assumptions and exposure factors served as the basis for completing the handler risk assessment. Each general assumption and factor for both residential and occupational assessments is detailed below. Assumptions specific to the use site category are listed in each separate section of this document. The general assumptions and factors include:

• AD has patterned this risk assessment on a series of likely representative scenarios for each use site that are believed by AD to represent the v ast majority of terbutryn uses.

• Based on the adverse effects for female rats, the average body weight of 70 kg for handlers was used to complete the non

- cancer risk assessment. Exposure factors used to calculate daily exposures to handlers were based on a pplicable data, if available.22 of 22 When appropriate data were lacking, values from a scenario deemed similar were
used.

• The maximum application rates allowed by labels were assumed.