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. 
T a e bl 1 : All owa bl e C oncen t ra f Ions ~ or R egis 't ere dU ses 0 fP I . p . t roplconazo e ID aID 

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. 

T a e bl 2 : U !Pl d ae t d P os t -RED L b I a e Ch anges ~ or R egis 't ere dU ses 0 fP I . P' t rOI llconazo e ID aID 

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. . " 

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

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

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. 

T bl 3 All bl C f ~ R 't dU fP I . S . a e . . owa e oncentra Ion or egis ere ses 0 roplconazo e ID taID 

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-lIse 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 the propiconazole Reregistration Eligibility 

Decision (RED) document. Subsequently, the registrant provided EPA with a dermal absorption 

study for the active ingredient 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 inhalation 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 techniques 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 residential 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 propiconazole 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 Assessment

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 

endpoints is to the dermal absorption. USEPA (2003) 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 Risk 

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 Risk 

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 Exposure 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. The 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 inhalation 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 inhalation unit exposure values for 

handlers applying a pesticide-treated stain using an airless sprayer were used. These dermal

and inhalation unit exposure values of 79 and 0.83 mg/lb a.i., respectively, represent a 

handler wearing short pants and a short sleeve shirt, with no gloves and no respiratory 

protection. 

For the brush/roller scenario, the PHED dermal and inhalation unit exposure values for 

handlers applying a pesticide-treated paint using a paint brush to paint a bathroom were used. 

These dermal and inhalation unit exposure values 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 estimated 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 128 lb/day stain, assuming paint has a density of 10 lb/gal and 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 17 lb/day stain assuming paint has a density of 10 lb/gal and stain 8.5 lb/day) of 

treated 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 the 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 

Ratea

Quantity 

Handled/ 

Treated 

per dayb

Unit Exposure

(mg/lb a.i.)

Absorbed Daily Dose 

(mg/kg/day) e

MOE f

DermalcInhalationd 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

0.0023 0.0003 13,000 110,000 12,000

Brush/Roller (Stain) 17 lbs 0.052 2.4E-4 580 120,000 580

Airless Sprayer 

(Paint) 0.35% a.i.

by weight

150 lbs

79 0.83

0.0059 0.0062 5,100 4,800 2,500

Airless Sprayer 

(Stain)

128 lbs 0.13 0.0053 220 5,600 210

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 shirts, short pants, and no gloves.

d No respiratory 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-term NOAEL = 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 is 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 value is 0.83 mg/lb 

a.i. The dermal unit exposure is 38 mg/lb a.i. for long pants, long sleeved shirts; and no 

gloves. 

Quantity handled/treated: The quantity handled/treated values were estimated based on 

information from various sources. The following assumptions were made:

For the roller/brush painting/staining scenarios, it was assumed that 5 gallons (or 50 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 airless sprayer painting/staining scenarios, it was assumed that 50 gallons (or 500 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 short- 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). The 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-Term Occupational Handlers Exposures and MOEs 

Exposure Scenario --

Application Method

Application 

Ratea

Quantity 

Handled/ 

Treated 

per dayb

Unit Exposure

(mg/lb a.i.)

Absorbed Daily Dose 

(mg/kg/day) e

MOE f

DermalcInhalationd 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 weight

50 lbs

180 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 1700 130

Intermediate-term Exposure Duration

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

by weight

50 lbs

180 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

500 lbs

38 0.83

0.0095 0.021 1100 480 330

Airless Sprayer 

(Stain)

425 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 respiratory 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 NOAELs = 30 and 10 mg/kg/day, 

respectively, 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 characterize 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 Standard 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 assessment 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 concerns 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: Final 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, November 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 Barcode 324052; dated February 1, 2006.

Sign-off Date : 08/23/11

DP Barcode No. : D393026