July 9, 2012 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D.C

. 20460

William Goodwine

Janssen Pharmaceutic a NV

1125 Trenton-Harbourton Road Titusville, New Jersey 08560 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Subject: Updated Reregistration Labeling Requirements for Propiconazole Products Used as Paints and/or Stains

Dear Mr. Goodwine:

I am writing to inform you of changes to the reregistration labeling requirements for Janssen

Pharmaceutica NV' s propiconazole products used in paints and stains. In the 2006 RED the Agency assumed a 100% dermal penetration rate for propiconazole used in paints and stains. As

a result, risks exceeded the Agency's level of concern for occupational handlers using paints and

stains that contain propiconazole. To mitigate the risks identified in the RED, the Agency presented label language that, among other things, would prohibit the use of propiconazole in paints and stains above a concentration of 0.125% by weight.

In April 2009 Janssen Pharmaceutica NV submitted a dermal penetration study indicating dermal absorption rates of 1 % and 26.6% for paints and stain, respectively. This study was submitted in anticipation of the requirement for a dermal penetration study through the post-RED data call-in (DCI) which has since been issued on September 13,2011 (GDCI-122101-31121). Based on the

results of the 2009 dermal penetration study, the Agency updated the paints and stains portion of

the propiconazole risk assessment (attached). This letter presents the allowable concentrations

and updated reregistration label requirements for registered products containing propiconazole

for which updated dermal penetration data have been submitted or cited.

Paints

Table 1 presents the allowable concentrations for registered products containing propiconazole

for use in paints for which updated dermal penetration data have been submitted or cited.

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Labeled Use Allowable Concentration

In-Can Preservative for Paints/Coatings and Building Materials! 1.2% Paints/Dry Film Preservative of Coatings and Building Materials 1.2% (applied via airless sprayer)
Paints/Dry Film Preservative (application via airless sprayer 1.25% prohibited)

I Because products sold to the consumer are not labeled pesticide products restrictions to application methods are not feasible. Therefore, the MOE for application via airless sprayer was used to calculate the maximum application rates.

Table 2 presents the label changes in the 2006 RED that, based on the updated risk assessment,

are no longer necessary for registered paint/dry film products containing propiconazole for which updated dermal penetration data have been submitted or cited.



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Description Amended Labeling Language Placement on Label

Manufacturing Use Products

For all "+his j3Faeuet**m~'** Rat ee feFffiulatee iRta j3aiRts aRe staiRS Directions for Use Manufacturing Use YRless the ma*imum eaReeRtFatiaR af j3Faj3ieaRailiale is less thaR

Products ,1 f\ 1") <::01'. l.

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End-Use Products Intended for Occupational Use (wpS and Non-WPS)

Application "9a Rat**aj3j3I~'** maFe thaR fRegistFaRt, iRseFt amauRt eEiyal ta Directions for Use l

Restrictions For 0.125% e)' 'Height] j3eF galiaR as a j3reseFVati'/e fer j3aiRts aRe products labeled/or**~**
use as material preservatives

ThiS labeling language IS no longer reqUired.

Stains

Table 3 presents the allowable concentration for registered products containing propiconazole for

use in stains for which updated dermal penetration data have been submitted or cited.



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# . Labeled Use Allowable Concentration

In-Can Preservative for Penetrating Stains (Solvent-Basedi 0.15% Penetrating Wood Preservatives and Wood Preservative Stains 0.15% (applied via airless sprayer)
Penetrating Wood Preservatives and Wood Preservative Stains 0.34% (application via airless sprayer prohibited)

L Because products sold to the consumer are not labeled pesticide products, restrictions to application methods are not feasible.
Therefore, the MOE for application via airless sprayer was used to calculate the maximum application rates.

Table 4 presents the updated label changes for registered stain products containing propiconazole

for which updated dermal penetration data have been submitted or cited; these label changes supersede those presented in the 2006 RED.Table 4: Updated Label Changes for Registered Uses of Propiconazole in Stain

Description Amended Labeling Language Placement on Label

Manufacturing Use Products

For all "This product may not be formulated into an in-can preservative Directions for Use Manufacturing Use for stains unless the maximum concentration ofpropiconazole is

Products less than or equal to 0

. 15 % by weight."

End- lI se Products Intended for Occupational Use (WPS apd Non

- WPS)

Application "Do not apply more than [Registrant, insert amount equal to Directions for Use

Restrictions For 0.15 % by weight] per gallon as a preservative for stains or in products labeledfor stains where application via airless sprayer is not prohibited."

use as material preservatives or where application of

stain via airless

sprayer IS NOT prohibited Application "Do not apply more than [Registrant, insert amount equal to Directions for Use

Restrictions For 0.34 % by weight] per gallon in stains. Do not use airless products labeledfor sprayer."

use in stains where application of stain

via airless sprayer is prohibited

This letter will be placed in reregistration public docket EPA-HQ-OPP-2005-0497 at www.regulations.gov and you are encouraged to submit a copy of this letter along with your 8-

month response to the PDCI. Please contact Rebecca von dem Hagen of my staff with any questions regarding this letter. She may be reached at vondem-hagen.rebecca@epa.gov or (703)

305-6785. 

# /lkatJ---

Mark Hartman, Chief Regulatory Management Branch II

Antimicrobials Division

cc: Christina Scheltema and Julia Stokes, Pesticide Re-evaluation Division

Lance Wormell and Rebecca von dem Hagen, Antimicrobials Division

### 2

Executive Summary

Potential risks to painters were identified in t he propiconazole Reregistration Eligibility Decision (RED) document. Subsequently

, the registrant provided EPA with a dermal absorption study for the active ingr edient in paint and stain matrices to refine the potential risks identified in the RED. The results provided herein is a refinement to the paint assessment provided in the

RED

. Based on the new dermal absorption data, the potential total dermal and inhal ation MOEs for the residential application of paints and stains using brush/roller and airless sprayers are not of concern. The potential dermal and inhalation MOEs for the occupational applications of paints and stains using the same application techniqu es are not of concern, except for the airless spraying of the propiconazole

- treated stain where the MOEs are 47 for dermal, 570 for inhalation, and 43 for the total (total MOE is the sum of the dermal and inhalation routes because both exposure routes are assessed using the same oral endpoint). The target MOE is 100.

1.0 Background

Some products containing propiconazole can be used as a material preservative in a variety of products, including paints and stains, which can result in exposure to residenti al and occupational users while painting. The propiconazole RED identified potential risks to painters when assuming a 40 percent dermal absorption for the active ingredient. Subsequent to the

RED

, the registrant conducted a dermal absorption study of pr opiconazole in paints and stains. The resulting dermal absorption values for propiconazole in treated paints and stains are 1 and 26.6 percent, respectively. The assessment herein provides an updated risk assessment based on
these new data.

2.0 Assessme nt

2.1 Toxicological Endpoint

Table 1 summarizes the toxicological endpoints used in the dermal and inhalation
assessment for propiconazole (USEPA, 2003). The modification from the selected toxicological endpoint s is to the dermal absorption. USEPA (2 003) had originally selected a dermal absorption of 40 percent for the active ingredient . Subsequently, the registrant performed a dermal absorption study using the active ingredient in paint and stain. The dermal absorption for propiconazole in treated paints and stains is 1 and 26.6 percent , respectively (DP 365243 . MRID
No. 477365

- 03 ).

Table 1. Summary of Dermal and Inhalation Toxicological Doses and Endpoints for

Propiconazole for Use in Human Risk Assessments

Exposure
Scenario Dose Used in Ris k

Assessment, UF Special FQPA SF* and

Level of Concern for

Risk Assessment Study and Toxicological Effects

Short

- Term (1

- 30 days)

Dermal &
Inhalation Oral NOAEL= 30

mg ai/kg /day Residential MOE = 100

Occupational MOE = 100 Acute Neurotoxicity Study

- Rats

. Clinical toxicity: piloerection, diarrhea, tip toe at 100 mg/kg

### 3

Table 1. Summary of Dermal and Inhalation Toxicological Doses and Endpoints for

Propiconazole for Use in Human Risk Assessments

Exposure
Scenario Dose Used in Ris k

Assessment, UF Special FQPA SF* and

Level of Concern for

Risk Assessment Study and Toxicological Effects

Intermediate

- Term (1

- 6 months) and Long

- Term
Dermal &
Inhalation (>6 months) Oral NOAEL= 10

mg ai/kg/day Residential MOE = 100

Occupational MOE = 100 24 Month Oncogenicity Study

- Mice. Liver toxicity (increased liver weight in males and increase in liver lesions (masses/raised areas/ swellings/nodular areas mainly)

Dermal Absorption Dermal absorption 1% in paints and 26.6% in stains (MRID 47736503, DP365243)

Cancer (Oral, dermal

, inhalation) Group C, possible human carcinogen

UF = uncertainty factor, FQPA SF = special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, MOE = margin of exposure, LOC = Level of concern.



### 2.2 Exposur e and Risk Assessment

2.2.1 Residential Handler Exposures and Risks

The residential handler scenarios described in USEPA (2006) were assessed to determine dermal and inhalation exposures to painters. Th e dermal portion of the 2006 assessment is updated herein to account for the new dermal absorption data of 1 percent for paints and 26.6 percent for stains. Inhalation MOEs are also provided to update the total MOE. The total MOE is appropriate because the endpoints for both the dermal and inhala tion routes are being assessed via the oral toxicological endpoint.

Unit Exposure Values : Unit exposure values were taken from the PHED data presented in HED’s Residential SOPs (USEPA, 2000 ).

For the airless sprayer scenario, the PHED dermal and inhala tion unit exposure value s for
handler s applying a pesticide

- treated stain using an airless sprayer were used. Th e s e dermal
and inhalation unit exposure value s of 79 and 0.83 mg/lb a.i. , respectively, represent a handler wearing short pants and a short sle eve shirt, with no gloves and no respiratory protection

. For the brush/roller scenario

, the PHED dermal and inhalation unit exposure value s for
handler s applying a pesticide

- treated paint using a paint brush to paint a bathroom w ere used.

Th e s e dermal an d inhalation unit exposure value s of 230 and 0.284 mg/lb a.i. , respectively, represent a handler wearing short pants and a short sleeve shirt, with no gloves and no respiratory protection

.

Quantity handled/treated : The quantities handled/treated were esti mated based on information from various sources, including AD’s standard assumptions.

### 4

For the airless sprayer in paint /stain applications, it is assumed that 15 gallons (or 150 lb/day paint and 12 8 lb/day stain , assuming paint has a density of 10 lb/gal a nd stain 8 .5 lb/gal ) of treated paint

/stain will be used per day.

For the brush/roller in paint /stain applications, it is assumed that 2 gallons (or 20 lb/day, paint and 1 7 lb/day stain assuming paint has a density of 10 lb/gal and stain 8 .5 lb/day ) of

t reated paint

/stain will be used per day.

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

- term duration (1 to 30 days of consecutive exposure ). This is because painting by homeowners is assumed to be episodic, not daily. In addition, homeowners are assumed to use different products with varying actives, not exclusively propiconazole treated products.

Results

The resulting short

- term exposures and MOEs for th e representative residential handler scenarios are presented in Table 2. The calculated dermal , inhalation, and total MOEs were above the target MOE of 100 for all scenarios , and therefore not of concern ( all MOEs >1000 ).

Table 2 Short

- Term Residential Handlers Exposures and MOEs

Exposure Scenario

-- Application Method Application

Rate a Quantity

Handled/
Treated per day b Unit Exposure

(mg/lb a.i.) Absorbed Daily Dose (mg/kg/day) e MOE f

Dermal c Inhalation d Dermal Inhalation Dermal (Target =
100) Inhalation

(Target =
100) TOTAL

MOE g (Target = 100)

Brush/Roller (Paint) 0.35% a.i.

by weight 20 lbs 230 0.284 0.0 023 0.0003 13,000 110,000 12,000

Brush/Roller (Stain) 17 lbs 0.0 5 2 2.4E

- 4 5 8 0 120,000 58 0

Airless Sprayer (Paint) 0.35% a.i.

by weight 150 lbs

79 0.83 0.0059 0.0062 5,10 0 4,800 2,500

Airless Sprayer (Stain) 12 8 lbs 0.1 3 0.0053 22 0 5,600 2 1 0

a Application rates are the maximum application rates determined from EPA registered labels for propiconazole.

b Amount handled per day values are estimates based on AD’s standard assumptions.

c All dermal unit exposures are modified to represent painters wearing short

- sleeve shirt s , short pants , and no gloves

. d No respirator y protection.

e Absorbed Daily dose (mg/kg/day) = [unit ex posure (mg/lb a.i.) * application rate (% a.i. weight) * quantity treated

(lb/day) * absorption factor (0. 01 for paint and 0.266 for stain for dermal; and 1.0 for inhalation)]/ Body weight (70 kg).

f MOE = NOAEL / Absorbed Daily Dose. [Where short

- term N OAEL = 30 mg/kg/day for dermal and inhalation]. Target MOE is 100.

g Total MOE = 1/((1/Dermal ST MOE) + (1/Inhalation ST MOE)). The target MOE is 100.



### 2.2. 2 Occupational Handler Exposures and Risks

The occupational handler scenarios described in USEPA (2006) were assessed to determine dermal and inhalation exposures to painters. The dermal portion of the 2006 assessment is updated herein to account for the new dermal absorption data of 1 percent for

### 5

paints and 26.6 percent for stains. Inhalation MOEs are also provided to update the total MOE. The total MOE is appropriate because the endpoints for both the dermal and inhalation routes are being assessed via the oral toxicological endpoint.

Unit Exposure Values (UE): Dermal unit exposure values were taken from the Pesticide Handler Exposure Database (USEPA, 1998).

For roller/brush scenarios, the occupational PHED dermal and inhalation unit exposure values for paintbrush applications were used. The inhalation exposure value is 0.28 mg/lb
a.i. The dermal unit exposure i s 180 mg/lb a.i. long pants, long sleeved shirts, and no gloves.

For airless sprayer scenarios, the occupational PHED dermal and inhalation unit exposure values for airless sprayer application were used

. The inhalation exposure val ue is 0.83 mg/l b a.i. The dermal unit exposure is 38 mg/lb a.i. for long pants, long sleeved shirts; and no glove s

.

Quantity handled/treated : The quantity handled/treated values were estimated based on information from various sources. The following ass umptions were made:

For the roller/brush painting /staining scenario s , it was assumed that 5 gallons ( or 5 0 lbs of paint and 42.5 lbs of stain assuming a density of 10 lb/gal paint and 8.5 lb/gal stain ) of treated paint

/stain are used per day

. For the airl

ess sprayer painting/staining scenario s , it was assumed that 50 gallons (or 50 0 lbs of paint and 425 lbs stain assuming a density of 10 lb/gal paint and 8.5 lb/gal stain ) of treated paint /stain are used.

Duration of Exposure : The MOEs were calculated for the short

- and intermediate

- term durations for occupational handlers using the appropriate endpoints in Table 1.

Exposure Calculations and Results

The resulting exposures and MOEs for the representative occupational handler scenarios are presented in Table 3 for both sh ort

- and intermediate

- term durations

. The difference between the paint and stain applications is the density (10 lbs for paint and 8.5 lbs for stain) and the dermal absorption values (1 percent for paint and 26.6 percent for stain). T he difference between
the short

- and intermediate

- term assessments is the NOAEL of 30 mg/kg/day for short

- term and
a NOAEL of 10 mg/kg/day for intermediate

- term. The calculated total MOEs were above the target MOE of 100 for all scenarios, except for the airless sprayer application of stain where the
total MOE is 43.

### 6

Table 3. Short

- and Intermediate

- T erm Occupational Handlers Exposures and MOEs

Exposure Scenario

-- Application Method Application

Rate a Quantity

Handled/
Treated per day b U nit Exposure

(mg/lb a.i.) Absorbed Daily Dose (mg/kg/day) e MOE f

Dermal c Inhalation d Dermal Inhalation Dermal (Target =
100) Inhalation

(Target =
100) TOTAL

MOE g (Target = 100)

Short

- term Exposure Duration

Brush/Roller (Paint) 0.35% a.i.

by we ight 50 lbs 18 0 0.284 0.0045 0.0007 6700 43,000 5800

Brush/Roller (Stain) 42.5 lbs 0.10 0.0006 290 50,000 290
Airless Sprayer (Paint) 0.35% a.i.

by weight 500 lbs

38 0.83 0.0095 0.021 3200 1400 990

Airless Sprayer (Stain) 425 lbs 0.21 0.018 140 17 00 130

Intermediate

- term Exposure Duration

Brush/Roller (Paint) 0.35% a.i.

by weight 5 0 lbs 18 0 0.284 0.0045 0.0007 2200 14,000 1900

Brush/Roller (Stain) 42.5 lbs 0.10 0.0006 98 17,000 98
Airless Sprayer (Paint) 0.35% a.i.

by weight 5 0 0 lbs

38 0.83 0.0095 0.021 1100 480 330

Airless Sprayer (Stain) 4 2 5 lbs 0.21 0.018 47 570 43

a Application rates are the maximum application rates determined from EPA registered labels for propiconazole.
b Amount handled per day values are estimates based on AD’s standard assumptions.

c All dermal unit exposures represent workers wearing long

- sleeve shirt, long pants , and no gloves

. d No respirator y protection.

e Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) * application rate (% a.i. weight) * quantity treated

(lb/day) * absorption factor (0.01 for paint and 0.266 for stain for dermal; and 1.0 for inhalation)]/ Body weight (70 kg).

f MOE = NOAEL / Absorbed Daily Dose. [Where short

- and intermediate

- term oral NOAEL s = 30 and 10 mg/kg/day

,

re spectively, for both dermal and inhalation]. Target MOE is 100.

g Total MOE = 1/((1/Dermal MOE) + (1/Inhalation MOE)). The target MOE is 100.



### 3.0 Limitations and Uncertainties

The following limitations and uncertainties are listed below to characteriz e the

assessment.

The Surrogate dermal and inhalation unit exposure values were taken from the Pesticide Handler Exposure Database (USEPA, 1998). The quantities handled/treated were estimated based on information from various sources, including HED’s Sta ndard Operating Procedures (SOPs) for Residential Exposure Assessments (USEPA 2000 and 2001). The maximum propiconazole in paint rate of 0.35 percent by weight is used in the
assessment. Use data could be used to refine the assessment of the intermediate

- term duration, if available and if lower rates are more commonly used.

### 7

4 .0 Conclusion

The original RED assessment for paint did not provide a distinction between paints and stains. The registrant has provided dermal absorption to refine the risk as sessment which included tests for both paints and stains. Therefore, the assessment herein also presented the assessment of each separately. The estimated dermal, inhalation, and total MOEs for residential and occupational painters do not trigger risk co ncerns except for the intermediate

- term occupational scenario for airless sprayers for stains. This scenario is characterized by a total MOE of 43 (target MOE is 100). The risk driver for the total MOE is the dermal route

. The brush application for the intermediate

- term occupational stain use is at the target MOE (i.e., the total MOE is 98).

5 .0. References

DP 365243

. 

### Propiconazole

– Toxicological Review and Dermal Absorption Factor Determination for the Proposed Increase in Application Rate for Use in Paints and Stains. DER memorandum from Jenny J. Tao, Toxicologist to Stacey Grigsby, Chemical Review Manager, dated November 23, 2009.

MRID No. 47736503. McClanahan, R. (2008) Propiconazole in Paints and Stains

– In Vivo Dermal
Penetration in Rats: F inal Report. Project Number: 021081/1, 021801, T002914/06. Unpublished study prepared by Ricerca Biosciences, LLC. 118 p.



### 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.

USEPA. 2001. HED Science Advisory Council for Exposure. Policy Update, Novemb er 12. Recommended Revisions to the Standard Operating Procedures (SOPs) for Residential Exposure Assessment, February 22, 2001.

USEPA. 2003. Propiconazole

– 3 rd 

### Report of the Hazard Identification Assessment Review Committee. Dated December 17, 2003 . TXR No. 0052277.

USEPA 2006. Propiconazole : Revised Occupational and Residential Exposure Assessment of the Antimicrobial Uses to Support the Reregistration Eligibility Decision (RED) Document. PC Code: 122101. Reregistration Case No. 3125. DP Ba rcode 324052; dated February 1, 2006.

Sign

- off Date : 08/23/11
DP Barcod e No. : D393026