Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 2 of 54 Creosote Registration Review Team

Human Health & Environmental Effects Nathan Mottl Tim McMahon Siroos Mostaghimi Jim Breithaupt Bill Erickson

Health Effects Division Kristin Rury

Risk Management Sandra O’Neill Rose Kyprianou Tom Luminello

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 3 of 54 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD acute population adjusted dose ASRI activated sludge respiration inhibition
atm-m 3 /mole atmospheric pressure-cubic meter per mole AWPA American Wood Protection Association BCF bioconcentration factor °C degrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese hamster ovary CMA Chemical Manufacturers Association CO 2 carbon dioxide COC concentration-of-concern cPAD chronic population adjusted dose DCI data call-in EC 50 median (or 50 percent) effect concentration EC 05 5 percent effect concentration ECOTOX ECOTOXicology EDI estimated daily intake EDSP Endocrine Disruptor Screening Program E-FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Federal Food, Dr ug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol grams per mole GLN guideline number HPV high production volume IDS Incident Data System Koc organic carbon normalized soil-water partition coefficient Kd soil-water partition coefficient Kow octanol-water partition coefficient LC 50 median (or 50 percent) lethal concentration LD 50 median (or 50 percent) lethal dose LOAEC lowest-observed-adverse-effect-concentration LOEC lowest-observed-effect-concentration LOAEL lowest-observed-adverse-effect-level Log K ow logarithm of the octanol-water partition coefficient μg microgram ml/g milliliter per gram mg/kg milligram per kilogram mg/kg/day milligram per kilogram per day mg/L milligram per liter mm Hg millimeter of mercuryDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 4 of 54 MOE margin of exposure MRID Master Record Identification Number MRL maximum residue limit N/A not applicable
nm nanometers NOAEC no-observed-adverse-effect-concentration NOAEL no-observed-adverse-effect-level OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co-operation and Development OPP Office of Pesticide Programs PAD population adjusted dose PAI pure active ingredient PDM Probabilistic Dilution Model % percent PC Code Pesticide Chemical Code PCF pounds per cubic foot pH power of hydrogen or power of the concentration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary irritation score pKa power of the acid dissociation constant or negative base-10 logarithm of the acid dissociation constant of a solution ppb parts per billion ppm parts per million PWP Preliminary Work Plan QSAR quantitative structure-activity relationship RED Reregistration Eligibility Decision SAR structure activity relationship SF safety factor SSTS Section Seven Tracking System TEP typical end-use product TGAI technical grade active ingredient TMDL total maximum daily loads UF uncertainty factor UV/VIS ultraviolet/visible light absorption % w/w percent weight per weight. WP wettable powder WWTPs wastewater treatment plantsDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 5 of 54 

### Table of Contents

1 Introduction .................................................................................................................. ........... 7 1.1 Statutory and Regulatory Authority ................................................................................. 7 1.2 Case Overview ................................................................................................................. 8 1.3 Chemical Identification and Properties ............................................................................ 9 1.4 Use/Usage Description ................................................................................................... 10 1.4.1 Registrations ........................................................................................................... 10 1.4.2 Summary of Regist ered Uses .................................................................................. 11 1.4.3 Usage Information .................................................................................................. 11 1.5 Regulatory History ......................................................................................................... 11 1.5.1 Tolerance Information ............................................................................................ 11 1.6 Incidents ..................................................................................................................... .... 12 1.6.1 Human Health ......................................................................................................... 12 1.6.2 Ecological ............................................................................................................... 12 2 Anticipated Data Needs ........................................................................................................ 12 3 Human Health Risk Assessment ........................................................................................... 15 3.1 Existing Toxicological Endpoints .................................................................................. 15 3.2 Dietary Exposure ............................................................................................................ 1 6 3.2.1 Food ........................................................................................................................ 1 6 3.2.2 Drinking Water ....................................................................................................... 16 3.3 Occupational and Residential Exposures ....................................................................... 16 3.3.1 Occupational Handler Exposure ............................................................................. 16 3.3.2 Occupational Post-Appli cation Exposure ............................................................... 17 3.3.3 Residential Handler Exposures ............................................................................... 17 3.3.4 Residential Post-Applic ation Exposures ................................................................. 18 3.4 Aggregate and Cumulative Exposure ............................................................................. 18 3.4.1 Aggregate Exposures .............................................................................................. 18 3.4.2 Cumulative Exposures ............................................................................................ 18 4 Environmental Risk Assessment........................................................................................... 18 4.1 Environmental Fate Assessment .................................................................................... 19 4.1.1 Water Quality .......................................................................................................... 20 4.2 Environmental Exposure Pathways ................................................................................ 20 4.3 Ecological Effects Analysis ........................................................................................... 21 4.3.1 Available Ecotoxicity Endpoints ............................................................................ 21 4.3.2 Open literature ........................................................................................................ 22 4.4 Exposure Analysis Plan .................................................................................................. 22 4.4.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 22 4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 22 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 22 6 Optional Label Changes ........................................................................................................ 23 7 Guidance for Commenters .................................................................................................... 23 7.1 Preliminary Work Plan ................................................................................................... 23 7.1.1 Trade Irritants .......................................................................................................... 23 7.1.2 Water Quality .......................................................................................................... 24 7.1.3 Environmental Justice ............................................................................................. 24 7.1.4 Additional Information ........................................................................................... 24Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 6 of 54 8 Next Steps .................................................................................................................... ......... 25 9 References .................................................................................................................... ......... 26

Appendix A Toxicology Profile ............................................................................................... 27 Appendix B Environmental Fate ............................................................................................. 43 Appendix C Ecotoxicology Profile .......................................................................................... 50 Appendix D Physical and Chemical Properties ....................................................................... 54

List of Tables Table 1 – Summary of Anticipated Risk Assessments and Data Needs for Registration Review: Creosote ...................................................................................................................... .................... 8 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 9 Table 3 – Chemical Identification of Creosote ............................................................................... 9 Table 4 – Physical-Chemical Properties for Creosote .................................................................. 10 Table 5 – Summary of Creosote Registered Uses ........................................................................ 11 Table 6 – Studies Anticipated as Needed fo r the Registration Review of Creosote ..................... 13 Table 7 –Data Needs Required by the September 22, 2011 Data Call-In for the Creosote RED . 14 Table 8 – Existing Toxicological Endpoints ................................................................................. 15 Table 9 – Occupational Handler Expo sure Scenarios for Creosote .............................................. 17 Table 10 – Available Creosote Ecological Effects Endpoints ...................................................... 21Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 7 of 54 

## 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the agency”) Preliminary Work Plan (PWP) for creosote. The PWP document explains what EPA's Office of Pesticide Programs (OPP) knows about co al tar creosote highlig hting anticipated data and assessment needs, identifying th e types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing creosote’s review. At the time of the 2008 Registration El igibility Decision (RED ), the creosote case included the following chemicals: coal tar creo sote (PC Code 025004), creosote oil (PC Code 025003), and coal tar (PC Code 022003). The last EPA registrations for both creosote oil and coal tar were cancelled in February of 2013. 1 As such, this registra tion review case will assess registrations only for coal tar creosote (PC Code 025004), herein referred to as creosote.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The agency intends, by sh aring this information in the docket, to inform the public of what it knows about creosote and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision on creosote. The agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will he lp the agency’s decision-making process for this chemical.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time. Th rough the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www2.epa.gov/pesticide-reevalua tion/registration-review-process.

The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial

1 “Product Cancellation Orders for Certain Pesticide Registrations”, 78 FR 8513-8522 (February 6, 2013).Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 8 of 54 comment period, the agency will develop and commit to a Final Work Plan (FWP) and anticipated schedule for the creosote case.



## 1.2 Case Overview
The docket for creosote (case 0139) has been esta blished at http://www.regulations.gov in docket number EPA-HQ-OPP-2014-0823, documents associated with this registration review can be viewed at this docket. Tables 1- 2 below summarize the issues releva nt to this registration review case and the anticipated regi stration review schedule.

Table 1 – Summary of Anticipated Risk Asse ssments and Data Needs for Registration Review: Creosote

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment (N/A = Not Applicable) Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 6 for details)

Dietary (food) No (see Section 3.2.1) N/A None None

Dietary (drinking water) No (see Section 3.2.2) N/A None None

Occupational Handler Yes 9/5/2008 Updated Immunotoxicity Worker Exposure Study 1

Occupational PostApplication No (see Section 3.3.2) N/A None None (Post application job functions have been redefined as handlers)

Residential Handler No (see Section 3.3.3) N/A None None

Residential Post Application No (see Section 3.3.4) N/A None None

Aggregate No (see Section 3.4.1) N/A None None

Cumulative No (see Section 3.4.2) N/A None None

Tolerance Review No (see Section 1.5.1) N/A None None

Ecological Yes (see Section 4) 3/27/2008 Updated Ecotoxicity - see Table 6

* Table 1 is a summary of the anticipated risk assessments and data needs for Registration Revi ew. For data called in through t he postReregistration Eligibility Decision (RED) Data Call-In (DCI), see Table 7.

1 Data already required by the 2011 post-RED Creosote DCI.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 9 of 54 Table 2 – Anticipated Regi stration Review Schedule

Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2015-03 2015-03 Close Public Comment Period 2015-05 Phase 2: Case Development

Issue Final Work Plan 2015-09

Issue Data Call-In (DCI) 2016-09

Receive Data to be Considered in Risk Assessment 2018-09

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2020-03

Close Public Comment Period 2020-04
Phase 3: Registration Review Decision and Implementation
Open 60-Day Public Comment Period for Proposed Decision 2020-09

Close Public Comment Period 2020-11

Issue Final Decision 2121-03

Begin Post-Decision Follow-up 2121
Total (years) 6 *The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredient in this case).



## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be a ssessed in case 0139: creosote (PC Code 025004).

Table 3 – Chemical Identification of Creosote

Chemical Name Creosote Chemical Classification Polycyclic aromatic hydrocarbons (PAHs)
PC Code 025004
CAS Number 8001-58-9

Molecular Formula Not applicable (Mix of compounds
Molecular Weight (grams/mole) Not applicable (Mix of compounds

Molecular Structure Not applicable (Mix of compounds

Creosote consists primarily of liquid, solid PAHs , other hetero nuclear aromatic substances, and some tar acids and bases.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 10 of 54 USEPA’s document, “Guidance for Reregistrati on of Pesticide Products Containing Coal Tar Creosote” recognizes that “hundred s of individual chemicals have been identified in coal tar creosote.” There are two major types of creosote, P1/P13 fraction which is used in the treatment of utility poles and pilings and P2 fraction which is used in the treatment of railroad ties/crossties and is more viscous than the P1/P13 blend (E PA 2008). These two fractions of creosote are derived by carbonizing coal thr ough high temperature distillation and collecting the coal tar fractions that are comprised of light oil, middle oil, and heavy (oil) anthracene.

The creosote product chemistry in formation relevant to risk a ssessment is summarized in Table 4, and the details of the product chemistry information are discussed in Appendix D .

Table 4 – Physical-Chemical Properties for Creosote

Guideline No. Parameter Creosote Reference/Comments

830.7050 UV/Visible Absorption Not available for mixture PAHs absorb UV light but no spectrum available for mixture
830.7200 Melting point ( o C) Not applicable MRID 48480902 Product is liquid 830.7220 Boiling point ( o C) >180 MRID 48490902

830.7370 Dissociation constant (pKa) Not applicable MRID 48480902 No acid or base functional
groups

830.7550 Octanol-water partition coefficient at 25 o C (Log K ow ) 3.25 MRID 48480902
830.7840 Solubility in water (mg/L) 313 MRID 48480902
830.7950 Vapor pressure (mmHg) 11.1 MRID 48480902 24.4 o C
None Henry's law constant at 25 o C (atm-m 3 /mol) Not calculated Product is a mixture with various chemical and physical properties

atm-m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury.



## 1.4 Use/Usage Description

1.4.1 Registrations
There are six creosote registrants holding a total of seventeen industrial wood preservative product registrations for wood protection as well as treating wood in marine environments.

Currently there are 16 end-use products (EUP) registered for pressure treatment of wood, as well as in fresh water and marine environments, and one manufacturing use product (MUP) containing directions for further formulation into wood preser vatives. Wood treated with these preservatives is specified for commercial and industrial uses at outdoor sites.

Creosote formulations intended for use as a wood treatment are classified as restricted use pesticides (RUPs) for sale and use by certified applicators only. I ndoor applications of creosote are prohibited as well as application to w ood intended for use in interiors (with certain exceptions) or for use in contac t with food, feed, or drinking wa ter. These restrictions wereDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 11 of 54 imposed on creosote registrations as part of the Agency’s Special Review process as indicated in the U.S.EPA Position Document 4 for Wood Preservative Pesticides: Creosote, Pentachlorophenol and Inorganic Arsenicals (1984, amended 1986)

. 

### 1.4.2 Summary of Registered Uses

Table 5 presents a summary of the registered us es of creosote that will be assessed in this registration review. Creosote is applied by pressure treatment.

Table 5 – Summary of Creosote Registered Uses

Use Application Method Application Rate

Wood or Wood Structure Protection Treatments

Pressure Treatment to Forest Products Pressure Treatment 6-12 lb/cu ft



### 1.4.3 Usage Information

According to the Kline Biocides Report for 2004/2005, creosote is one of the leading wood preservatives for railroad ties. In 2004, U.S. consumption of creosote was estimated at 785 million pounds, and was forecasted to grow at an average volume rate of 0.2% over the subsequent five years (Kline, 2005).



## 1.5 Regulatory History
Creosote has been registered as a heavy duty wood preservative since 1948. Since creosote is derived from the distillation of coal tar, cons ists of hundreds of compoun ds, and has a variable composition, the American Wood Protection Asso ciation (AWPA) established standards to differentiate between the diffe rent blends of creosote. The industry refers to these different blends of creosote as P1/P13 and P2.

The agency completed a RED for creosote in 2008. EPA determined that creosote products contributed benefits to society and were elig ible for reregistration provided the mitigation measures and associated label changes iden tified in the 2008 RED were implemented and required data were submitted. As mentioned in Section 1.4.1, restrictions were imposed on creosote registrations as part of th e Agency’s Special Review process.

A post-RED Generic-Data Call -In (GDCI) and Product-Specific -Data-Call-In (PDCI) were issued on September 22, 2011. For the status of these data, see Table 7.


### 1.5.1 Tolerance Information

For the active ingredient creoso te, EPA has not established tole rances in raw agricultural commodities or processed food and feed products for creosote under the Federal Food, Drug andDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 12 of 54 Cosmetic Act (FFDCA) Section 408. There are al so no tolerance exemptions for creosote under FFDCA Section 408. Creosote has not been clear ed as a food additive by the US Food and Drug Administration (US FDA) under FFDCA Section 409.



## 1.6 Incidents

1.6.1 Human Health

EPA conducted an epidemiology and incidents report on March 9, 2008 for the RED (EPA 2008d). For registration review, EPA conducted a search for creosote in the Incident Data System (IDS) on January 7, 2015 covering the pe riod from January, 1997 to January, 7, 2015. Over 28 incident reports exist in the Aggregate Incident Summa ry report. The last reported incident was in August 2011. The associated human health effects include irritation effects to eyes, respiratory (chemical pneumonia), and skin (blisters, erythema, and irritation). Other human health effects include muscle stiffness, di zziness, headache, fever and malaise. Whether these deleterious health effects result from expos ure to creosote specifically, or to one or more other chemicals typically found as contaminants, is not clear. EPA will be conducting a more comprehensive incident repor t in registration review.



### 1.6.2 Ecological

As of December 22, 2014, the EPA/OPP Incident Data System (IDS) contains one aggregate incident summary from a creosote treatment f acility in Pittsburgh, PA. Employees found a dead pigeon and a dead sparrow in 1999 and 3 dead pigeons between November 2002 and January 2003. The dead birds were found in a building housing machinery used to pressure-treat creosote. The report states that the company does not feel that these bird mortalities were related
to creosote.


## 2 Anticipated Data Needs

Several studies were required by the DCI followi ng the assessment of creosote in the 2008 RED. In addition to the already-required RED DCI data , the following studies as listed in Table 6 are expected to be needed for the registration re view of creosote. Ta ble 7 outlines the data requirements required by the post-RED DCI issued on September 22, 2011. The agency anticipates reviewing any data received in re sponse to the post-RED DCI as well as data requested for this registration review prior to co nducting the registration re view risk assessments for creosote. The ecological toxicity studies an ticipated to be required for registration review could be conducted using the leachate from th e leaching study required by the post–RED DCI in order to provide information for a robust assess ment. Alternatively, information on effects on various taxa from monitoring studies conducted n ear aquatic sites could be submitted to allow the agency to determine risks from in situ use of creosote. This information would need to address acute and chronic effects in the water column as well as in sediments.Docket Number EPA-HQ-OPP-2014-0823www.regulations.govPage13of54Table 6 – Studies Anticipated as Needed for the Registration Review of CreosoteGLNStudy NameTest SubstanceTime Frame(Measured inmonths fromDCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) TriggeringAnticipated DataRequirementApplicableExposureScenario850.21001Avian acute oralTGAI12EcologicalAllTerrestrialenvironment850.3020 Honey bee, acute oral toxicity 12850.1010 Freshwater invertebrate, acuteTEP: Leachate from creosotepilings or railroad ties24Aquaticenvironment850.1025or850.1055Estuarine/marine bivalve, acute 12850.1035 Estuarine/marine invertebrate, acute 12850.1075 Estuarine/marine fish, acute 18850.1075 Freshwater fish, acute 18850.1300 Freshwater invertebrate, life cycle 12850.1350 Estuarine/marine invertebrate, life cycle 12850.14002Freshwater fish, early life-stage 12850.14002Estuarine/marine fish, early life-stage 12850.42253Seedling emergence, semi-aquatic plants 12850.4400 Aquatic plants, vascular 12850.45004Algal toxicity (3 spp.) 12850.45504Cyanobacteria toxicity 12870.7800 Immunotoxicity P1/P13 and P2 blends 12 Occupational workerNone5,6,7Whole sediment, chronic, freshwater (2 spp.)TEP: Leachate from creosotepilings or railroad ties24EcologicalAquaticenvironmentNone6, 7,8Whole sediment, chronic, estuarine/marine 241The anticipated DCI will providethat OECD TG 233 using the "LD50- slope test" or "limit dose test"can be used instead of OCSPP 850.2100for certain species and conditions(e.g., causes no delayed effects,causes no regurgitation). Details on the species and conditions under which TG 233 would notfulfill the anticipated data requirement are describedat http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/review_avian_acute_oral_oecd_tg223.htm2The anticipated DCI will provide that testing must be conducted with the most sensitive organism (either freshwater or estuarine/marine vertebrates, or freshwater orestuarine/marine invertebrates), as determined from the results of the acute toxicity tests (acute EC50freshwater invertebrates; acute LC50/EC50estuarine and marine organisms; acutefreshwater fish LC50).3Test guidelines 850.4100 and 850.4225 weremerged and harmonized into OCSPP 850.4100 ina Federal Register Notice dated June 27, 2012 (FRL-9333-1).4On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 –Ecological Effects Tests – including renumbering and other designations or changes forsome guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPAHQ-OPPT-2009-0154-00285The anticipated DCI will providethat the two species to be usedto conduct this test are Hyallela azteca and Chironomus dilutes. The anticipated DCI will provide that for Hyallelaazteca, conduct study according to ORD Study Method EPA 600/R-099-064 but with 12 replicates per treatment (4 for 28-d survivaland growth and 8 for the remainder of the test)with 10 neonates per replicate, and for Chironomus dilutus, conduct study according to ORD Study Method: EPA 600/R-099-020 butwith 10 replicates per treatment with 20neonates per replicate.6The preferred sediment is formulated, guidance for the formulated sediment can befound in OECD 218 Sediment-Water ChironomidToxicity Test using Spiked Sediment.Docket Number EPA-HQ-OPP-2014-0823www.regulations.govPage14of547The anticipated DCI will require that a protocol must be approved by the agency prior to the initiation of the study.8The anticipated DCI will providethat the species to be usedto conduct this test is Leptocheirus plumulosus and to conduct the study according to ORD Study Method: EPA 600/R099-020 but with 10 replicates per treatment with 20 neonatesper replicate.Table 7 –Data Needs Required by the September 22, 2011 Data Call-In for the Creosote REDGLNStudy NameStatus of DCI875.1100 Dermal exposure (outdoor)In place of these studies, the registrantsubmitted a draft protocol study for Exposure of Workers to Creosote DuringPressure Treatment of Lumber for review. The agency is reviewing the protocol for this observational study. If theprotocol and results from the ensuing study are approved, this study would satisfy the exposure study requirements forthe creosote case (GLNs 875.1100, 875.1200, 875.1300, 875.1400, and 875.1600).875.1200 Dermal exposure (indoor)875.1300 Inhalation exposure (outdoor)875.1400 Inhalation exposure (indoor)875.1600Applicator exposuremonitoring data reporting875.1700 Product use information No data have been submitted; this study is outstanding.SpecialStudy –LeachingLeaching study for release ofcreosote components fromcreosote impregnated woodNo data have been submitted; this study is outstanding.SpecialStudy –SedimentSediment concentration,Aquatic StructuresNo data have been submitted; this study is outstanding.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 15 of 54 

## 3 Human Health Risk Assessment

The agency anticipates the need to conduct a ne w human health risk assessment for creosote based upon the updated exposure study data requi red by the 2011 post-RED DCI. Additionally, immunotoxicity data are anticipated to be re quired to conduct this risk assessment for registration review. Because creoso te is currently registered fo r use in occupational settings, occupational handlers have the poten tial to be exposed through the pressure treatment process.

EPA plans to estimate cancer and non-cancer ri sks to occupational ha ndlers as a result of inhalation and dermal exposure to creosote during the pressure treatment process.



## 3.1 Existing Toxicological Endpoints

Table 8 presents the endpoints used in the agency ’s most recent human health risk assessment for creosote in support of the 2008 RED. An immunot oxicity study is identif ied as an anticipated data need for the registration review for creoso te. All available information including existing toxicology studies, valid scientific literature, and the studies that are expected to be required for registration review will be consid ered in establishing the endpoints to be used in the registration review risk assessment. A detailed description of the existing database of toxicity studies is provided in Appendix A .

Table 8 – Existing Toxicological Endpoints

Exposure Scenario Dose Used in Risk Assessment

(mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

Dermal (short-term) Oral NOAEL=50 MOE = 100 Developmental Toxicity study in the rat (MRID 43584201); decreased body weight and food consumptions in maternal rats at 175 mg/kg/day

Dermal (Intermediate-term) Dermal NOAEL = 40 mg/kg/day MOE = 100 90-day dermal toxicity study in the rat (MRID 43616201); increased incidence of dermal inflammation and decreased body weight gain at 400 mg/kg/day

Dermal (long-term) Oral LOAEL = 25 mg/kg/day MOE = 300 2-generation reproduction toxicity study in the rat (MRID 42893201 ); decreased pre-mating body weight at 25 mg/kg/day

Inhalation –creosote (short-, intermediate-, and long-term) NOAEL = 0.0047mg/m 3 MOE = 100 90-day inhalation toxicity study with P2 creosote (MRID 43600901); decreased body weight and weight gain, altered hematology and clinical chemistry, increased absolute and relative weight of the liver and thyroid, and increased incidence of lesions of the nasal cavity at 0.048 mg/m 3

Inhalation – naphthalene (short-, intermediate-, and long-term) LOAEL = 52 mg/m 3 MOE = 300 Two year inhalation toxicity study in the mouse; National Toxicology Program (1992a), as cited in USEPA: IRIS Toxicological Review of naphthalene (1998), based on nasal lesions in the respiratory and olfactory epithelium at 52 mg/m 3Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 16 of 54 Exposure Scenario Dose Used in Risk Assessment

(mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

Dermal absorption Absorption value of 5%, determined from the results of in vivo / in vitro testing in rats and in vitro testing using human skin (MRIDs 47179501 and 47179502).



## 3.2 Dietary Exposure

A dietary (food and drinking water) exposure assessment is not required for creosote at this time. The only Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)-registered uses of creosote are as wood preservatives. These uses are not expected to result in dir ect or indirect dietary (food) exposure. The use of creosote as a wood preservative is not expected to result in exposures to creosote in drinki ng waters; therefore, a drinking water assessment is not required at this time.



### 3.2.1 Food

No dietary exposure is expected fr om the registered uses of creo sote. Therefore, the agency does not anticipate the need to conduct a di etary exposure assessment for creosote.



### 3.2.2 Drinking Water
EPA does not anticipate the need to conduct a drinking water assessment because dietary exposure from drinking water is no t expected to occur from the registered uses of creosote. PAHs in raw water will tend to adsorb to any particulate matter and be removed by filtration before reaching the tap. PAHs in tap water wi ll mainly be due to the presence of PAHcontaining materials in water st orage and distribution systems (EPA, Technical Factsheet on: Polycyclic Aromatic Hydrocarbons).



## 3.3 Occupational and Re sidential Exposures
The agency anticipates the need to revise th e occupational assessment conducted in support of the 2008 RED. This is needed to account for new exposure monitoring studies required by the 2011 post-RED DCI. As a restricted use pesticide, creosote is neither permitted to be purchased nor expected to be applied by pot ential residential users. Sin ce no residential handler uses are expected from the use of creosote, a residential risk assessment is not re quired. Additionally, EPA will not be assessing residential post-application exposures.



### 3.3.1 Occupational Handler Exposure

The agency conducted an occupational assessm ent for the RED for creosote on September 5, 2008 (EPA 2008c). The occupational assessment was based on doses for occupational wood pressure treatment workers using chemical-sp ecific dermal and inha lation monitoring data submitted by the Creosote Council III (MRID 45323401).Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 17 of 54 As a result of the risks of concern identified in the RED, the agency identified label changes intended to reduce exposure to creosote workers in wood treatment facilitie s. In an effort to determine if those mitigation measures are effect ive in reducing exposure, the agency issued a post-RED DCI requiring that new exposure mon itoring studies be conducted at wood treatment facilities using personal protectiv e equipment (PPE) and engineeri ng controls identified in the 2008 RED.

The agency recently received an observational pr otocol from the Creosote Council III for a wood pressure treatment dermal and inhalation study. The agency expects to receive the completed study during registration review th at will help the agency to determine new exposures based on the new engineering control measures specified in the RED. The scenario outlined in Table 9 include the typical worker expos ure scenarios for a variety of job functions within a wood treatment facility.

For example, for pressure treatment facilities, workers operate and mon itor application system valves and controls, open and close cylinder doors, and supervis e the insertion and removal of charges (loads of dried or debarked poles) of timber from the treatment cylinders. Workers operate forklifts used to load untreated wood ont o charge trams; move ch arges into and out of treatment cylinders; remove char ge leads and bands from treated wood; distribute treated wood to load-out area, and load treated wood for sh ipment. Workers also perform various labor and cleanup duties in treatment and dr ip pad area including: sweeping and pressure-washing drip pad and tracks; removing and shredding all bands from treated stacks of lumber; picking up and disposing treated wood wast e; cleaning cylinders; and, handling hazardous waste ( EPA 2008c)

.
Table 9 – Occupational Handler Exposure Scenarios for Creosote

Scenario Exposure Route(s) Duration Occupational Exposures
Pressure Treatment Workers Dermal and Inha lation Short, Intermediate, and Long Term



### 3.3.2 Occupational Post-Application Exposure
There is potential exposure to lin emen and other workers installing or repairing creosote treated utility poles. Railroad workers may also be e xposed during the installa tion of railroad ties. Because mechanical installation (e.g. railroad ties) and/or the use of appropriate PPE are recommended to reduce exposure/cont act with creosote treated wood ( EPA 2008c), the agency does not anticipate the need to conduct an o ccupational post-applicati on exposure assessment.



### 3.3.3 Residential Handler Exposures
Creosote, which is a restricted use pesticide, is neither permitted to be pur chased nor expected to be applied by potential residentia l users. Therefore, residential exposure is not expected from the wood preservative uses of creosote and a resident ial risk assessment is not anticipated to be needed for this registration review.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 18 of 54 

### 3.3.4 Residential Post-Application Exposures
There are no approved pesticide uses of creosote to treat wood for residential use. The agency recognizes that materials such as utility poles or railroad ties may be sold for reuse after their original intended use has ended. Railroad ties are used for fuel for co-generation plants and there would be no residential exposure for that particular use. However, railroad ties may resold for use in residential setti ngs (e.g. landscaping). Such reuse of creosote-treated wood is not subject to regulation by EPA under FIFRA; however, lands cape retaining walls are not expected to be areas of frequent contact, and any contact with la ndscaping timbers is expected to be episodic in nature. Additionally, old railroad ties would likel y have significantly less transferable creosote than freshly treated wood ( EPA. 2008c ). As a result, the agency does not anticipate significant exposure to occur and will not conduct a reside ntial post-application risk assessment.



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

Creosote is not registered for a ny food use, and it was also determ ined that creosote is not likely to impact the diet or drinking water. Add itionally, residential expos ures are not expected. Therefore, an aggregate exposure and risk asse ssment is not anticipated to be needed for
creosote.



### 3.4.2 Cumulative Exposures
A cumulative exposure and risk assessment for creosote was not performed for the 2008 RED. EPA has not made a common mechanism of toxicity finding for creosote. Creosote is a complex mixture of chemical substances that may act by various mechanisms to produce toxicity. For the purposes of this registration review, therefore, EPA has not assumed that creosote has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mech anism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

The ecological risk assessment planned during re gistration review will allow the agency to determine potential acute and chronic risks to aquatic organisms exposed to creosote and its’ degradates and impurities transported from antimicrobial use sites into the terrestrial and aquatic environments. The agency has not yet conducted a risk assessment that supports a complete endangered species determination for the antimicrobi al uses of creosote. The registration review risk assessment will allow the agency to determ ine whether each use has 'no effect' or 'may affect' federally listed threaten ed or endangered species (liste d species) or their designated critical habitats. When an assessment concludes th at a pesticide’s use 'may affect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fi sheries Services (the Services), as appropriate.

The agency conducted a preliminary environmen tal risk assessment for the 2008 RED (EPA 2008 a,b). The uses assessed were railroad ties and aquatic structures. Because no guidelineDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 19 of 54 ecotoxicity studies have been submitted, the assessment was based on the limited ecotoxicity data information available in the open literature.

The 2008 risk assessment concluded that, although there are many PAHs in creosote, many occur only in minor amounts. The agency identified ei ght PAHs of potential concern in the aquatic environment from leaching of creosote-treated wood based on several factors including total amount of PAH, toxicity to a quatic organisms and detection in available monitoring data.

Although the literature is not comprehensive for any of the eight PAHs for acute and chronic toxicity to freshwater and estuarine/marine fis h, pelagic and benthic inve rtebrates, and aquatic plants, the agency concluded that there are poten tial risks to fish and invertebrates from the use of creosote-treated wood in aquatic and railroad structures.

Further, based on findings from a field study in the Sooke Basin (Vancouver Bay, Canada), PAH accumulation in sediments may be sufficiently high to pose a risk to benthic organisms in the immediate vicinity of creosote-treated pilings for at least a year. Although survival and spawning were not affected, short-term adverse effects on growth of mussels were reported immediately around pilings at the Sooke Basin field si te. One year after p ilings were installed in Sooke Basin, an assemblage of invertebrate or ganisms inhabited the creosote-treated pilings, suggesting minimal long-term impacts to some non-listed species.

Laboratory and field inves tigation found a major detrimental impact on hatching and development of fish (herring) eggs attached to aquatic pilings, even from pilings that were 40 years old, suggesting that some sensitive species may be adversely affected by creosote-treated pilings.

Impacts of creosote-treated aquatic pilings are likely to vary locally, depending on abiotic and biotic factors such as current speed, amount of st ructure per unit area, air and water temperature, salinity, and the aquatic speci es occurring in the immediat e area of the structures.

Creosote treated railroad structures are likely to have less direct impact than the treated aquatic structures, but there is the potential for move ment of PAHs into the aquatic environment.



## 4.1 Environmental Fate Assessment

Creosote or the P1/P13 and P2 fractions of creosote are obtained from the carbonization of bituminous coal and are mixtures of organic molecules (about 200-250 id entifiable substances) consisting of simple PAHs, multi-aromatic fused rings, cyclic nitrogen-containing heteronuclear compounds, and phenolic substances. It is esti mated that about 85 perc ent of the creosote mixture consists of PAHs and the remainder c onsists of cyclic heteronuclear nitrogen and oxygen-containing molecules. Since the PAHs c onstitute the majority of the percent mass of creosote, they are the focus of this environmental fate assessment.

Most of the PAHs are non-volatile; therefore, cr eosote normally does not contaminate the air. The major route of exposure is from PAHs leaching from treated wood into surrounding soil or water columns.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 20 of 54 Degradation of the PAH components can occur by both abiotic and biotic mechanisms. PAHs do not undergo abiotic hydrolysis based on the chemi cal structure and the lack of hydrolyzable functional groups. However, PAHs can readily photodegrade in water because these compounds absorb UV light. Photooxidized products of PAHs can be stable and persis t in air/water and soils and may become an environmental concern as these photooxidized products are also bioaccumulative (Kirso, 1991).

Biotic degradation occurs more readily under ae robic conditions, therefor e degradation will be slower in anaerobic sediments. Degradation also occurs more readily for the PAHs that have fewer rings (2- and 3- ring compounds) versus the 4- or 5-ring compounds (Karthikeyan and Bhandari, 2001, Bouwer et al., 1996 , Chapman et al., 1995).

The mobility of PAHs is dependent on the size of the individual compound. PAHs that have lower molecular weight are more mobile than th ose of higher molecular weight. However, even the lower molecular weight compounds have li mited movement in soil (Villholth, 1999). PAH residues around treated w ood (railroad ties, utility poles) are expected to be higher than those further from treated wood. In water, PAHs w ith more rings (e.g. acenaphthene) are more likely to sorb to sediment and bioc oncentrate in aquatic organisms than those with fewer rings, including naphthalene, 1-methyl naphthalene, and 2-methyl napht halene (Godsy et al., 1992). Leaching from treated wood tends to occur in th e first 7 days and is higher under flooded conditions (Bestari et al., 1998a). For more in formation on the environmental fate of creosote, see Appendix B



### 4.1.1 Water Quality
The only PAH in creosote that is identified as a cause of water body impairment is naphthalene. Naphthalene is identified as a cause of impair ment for two streams in New Hampshire, one stream in Washington State, and one stream in Virginia under section 303(d) of the Clean Water Act. 2 However, no Total Maximum Daily Loads (TMDL) have been developed for creosote as a mixture. 3 More information on impaired water bodies and TMDLs can be found at EPA’s website. 4



## 4.2 Environmental Exposure Pathways

PAHs leaching from treated wood are the primary source of environmental exposure to nontarget organisms. PAHs may leach into the soil surr ounding treated railroad ties and other treated wood and might be transported into the aquatic environment via various environmental pathways, including runoff and leaching. Creosote -treated wood used dire ctly in the aquatic environment will leach PAHs directly into su rface waters and sediments. Heavier PAHs reaching the aquatic environments are expected to bind to organic matter and sediments and

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

4 http://www.epa.gov/owow/tmdl/Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 21 of 54 potentially expose benthic invertebrates. Lighter PAHs will mostly occur in the water column and may potentially expose fish, aquatic inverteb rates, and aquatic plants to those PAHs.

Based on antimicrobial use patterns, the agency developed conceptual models (CMDs) depicting potential routes of environmental exposure to terrestrial and aquatic receptor groups. The

“ Conceptual Models for Environmental Expos ure Pathways of Antimicrobial Pesticides ” are located in the docket at www.regulati ons.gov (EPA-HQ-OPP-2014-0638-0002). For “ In

‐ Use Service of Wood Treated Wood Products ” see page 29 in that document.



## 4.3 Ecological Effects Analysis

4.3.1 Available Ecotoxicity Endpoints
Ecotoxicity studies conducted in accordance with the 850 OCS PP Harmonized Test Guidelines to address the data requirements fo r pesticide registration are not cu rrently available for creosote. Some supplemental data are available in the OPP Ecotoxicity Database for creosote. The anticipated ecotoxicity data requirements for creo sote are specified in more detail in Appendix C . Available endpoints, and data gaps for each receptor group, are listed below. For a complete list of the ecotoxicity da ta anticipated to be required in registration review, see Table 6.

Table 10 – Available Creosote Ecological Effects Endpoints

Receptor

Group Test Material Risk Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC50 = 570 μg ai/L TN 2401 1 Chronic Data gap --

Freshwater invertebrates TGAI Acute EC50 = 76 μg ai/L TN 2392 1 Chronic Data gap --

Freshwater benthic invertebrates TGAI Chronic Data gap --

Estuarine/marine fish TGAI Acute LC50 = 720 μg ai/L 40228401 1 Chronic Data gap --
Estuarine/marine

invertebrates TGAI Acute EC50 = 18 μg ai/L 40228401 1 Chronic Data gap --

Estuarine/marine benthic invertebrates TGAI Chronic Data gap --

Algae TGAI EC 50 NOAEC Data gap --

Aquatic vascular plants TGAI EC 50 NOAEC Data gap --

Semi-aquatic plants TGAI EC 50 NOAEC Data gap --

Birds TGAI Acute Data gap -- Dietary Data gap --Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 22 of 54 Nontarget insects TGAI Acute Data gap --

1 These studies are considered supplemental . Data are anticipated to be required.


### 4.3.2 Open literature
Open literature studies also will be iden tified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when the risk assessment is prepared. Any acute or chronic endpoints more sensitive than what is currently available w ill be used in the risk assessment and risk characterization. Informati on on the agency’s use of open literature is found on the agency’s website: http://www.epa.gov/pesticides/science/efed/pol icy_guidance/team_authors/endangered_species_ reregistration_workgroup/esa_ev aluation_open_literature.htm.



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available models will be used to determine the estimated environmental concentration (EECs) in the aquatic environment. Resulting exposure estimates will be co mpared to the toxicity endpoints to determine if levels of concer n are exceeded for each receptor group.



### 4.4.2 Screening Level Down-the-Drain Analysis
The agency does not anticipate the need for a Down-the-Drain (DtD) assessment because the creosote treated wood at the site of the treatment is dried with a drain pad underneath and any leaked chemical is recycled for use. Remaining ch emical in the pad (if any) must be treated as a hazardous waste and disposal (if any) must be conducted according to a state pesticide or environmental control agency, or by guidance from a hazardous waste representative.


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the 2008 RED for creo sote, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), creosote is subject to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily requiredDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 23 of 54 determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 5 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website. 6



## 6 Optional Label Changes

The agency invites comment on any label amendments that could be considered to eliminate the anticipated need for EPA to requi re certain data, reduce the possibi lity that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions , and/or improve label clarity.



## 7 Guidance for Commenters

7.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the creosote registration review case.



### 7.1.1 Trade Irritants
Through the registration review process, the ag ency intends to solic it information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting fr om lack of MRLs or disparities between U.S. tolerances and

5 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

6 http://www.epa.gov/endo/Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 24 of 54 MRLs in key export markets, providing as much specificity as possible re garding the nature of the concern.



### 7.1.2 Water Quality
The agency invites submission of wa ter quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Im paired Water Body and Other Water Quality Data in OPP’s Registration Review Risk A ssessment and Management Process 7 in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments.



### 7.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to creo sote compared to th e general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.



### 7.1.4 Additional Information

Stakeholders are also specifically asked to provid e available information a nd data that will assist the agency in refining its risk assessments, including any species-spec ific ecological effects determinations.

As mentioned in Section 1.5, the agency determined in the 20 08 RED that creosote products contribute benefits to society a nd were eligible for reregistra tion. In registration review, EPA plans to update the benefits and alternatives assessments for creosote. Stakeholders are encouraged to provide updated information on benefits and altern atives during the PWP comment period.

The agency is interested in rece iving the following information:

1. Confirmation on the following label information: A. Sites of application B. Geographic limitations on use 2. Use or potential use distribution 3. State or local use restrictions 4. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the agency 5. Monitoring data

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htmDocket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 25 of 54 

## 8 Next Steps

After the 60-day comment period closes in May 2015, the agency will review and respond to any comments received in a timely manner, and then i ssue a Final Work Plan for the creosote case.Docket Number EPA-HQ-OPP-2014-0823 www.regulations.gov

Page 26 of 54 

## 9 References

Bestari, K.T. Jim et al. 1998a. Distribut ion and composition of polycyclic aromatic hydrocarbons within experimental microcosms treated with liquid creosote. Environ. Toxicol. Chem. 17(12):2359-2368.

Bouwer, E.J. et al. 1996. Annals of New York Academy of Sciences. pp. 103-115.

Chapman, P.J. et al. 1995. Fossil Fuel Biodegrad ation: Laboratory Studies. Environ. Health Perspec. 103, Supplemental 5:80-83.

EPA 2002. ECOTOX User Guide: ECOTOXicology Da tabase System. Version 3.0. Available: http://www.epa.gov/ecotox/

EPA. 2008a. Updated Ecological Risk Assessment for Creosote. W. Erickson, AD/RASSB, March 27, 2008.

EPA. 2008b. Reregistration Eligibility Deci sion for Creosote (Case 0139). EPA 739-R-08-007.

EPA. 2008c. Creosote Occupational/Residential Exposure Assessment. PC Codes 022003, 025003, and 025004, Case 0139, Antimicrobials Division, 9/5/2008, Timothy Leighton, Ph.D.

EPA. 2008d. Epidemiology and Incidents Reports Associated with Creosote. Cases 0139, Antimicrobials Division, 3/9/08.

EPA. Technical Factsheet on: Polycyc lic Aromatic Hydrocarbons (PAHs). http://www.epa.gov/ogwdw/pdfs/fa ctsheets/soc/tech/pahs.pdf

Godsy, E.M. et al. 1992. Ground Water. 30(2):232-242.

Karthikeyan, R. and A. Bhandari. 2001. Anaerobic biotransformation of aromatic and polycyclic aromatic hydrocarbons in soil micr ocosms: a review. Journal of Hazardous Substance Research. 3:3-19.

Kirso, U. et al. 1991. Photochemical oxidati on of PAH and heteroaromatic analogues in different model conditions. Polycyclic Ar omatic Hydrocarbons: Proceedings of the Thirteenth International Symposium on Polynuclear Aromatic Hydrocarbons.

Kline, 2005. Specialty Biocides North Ameri ca 2004-2005, Volume II: United States, Kline and Company, Inc.

Villholth, K.G. 1999. Colloid characterization and colloidal phase part itioning of polycyclic aromatic hydrocarbons in two creosote-contami nated aquifers in Denmark. Environ. Sci. Technol. 33:691-699.Page 27 of 54 

# Appendix A Toxicology Profile

The agency anticipates the need to requi re immunotoxicology data for creosote. 

## Acute Toxicity for Product Labeling

Acute toxicity studies available for labeling purposes have been summarized in Tables A1 and A2 for the two creosote blends: P1/P13 and P2.

Table A1 – Acute Toxicity Studies for Creosote P1/P13 blend

Guideline No./ Study Type MRID No. Results Toxicity Category
870.1100/ Acute oral toxicity 43032101 LD 50 male= 2451 mg/kg; female = 1893 mg/kg III

870.1200/ Acute dermal toxicity 43032102 LD 50 male and female: > 2000 mg/kg III

870.1300/ Acute inhalation toxicity 43032103 LC 50 > 5 mg/L IV

870.2400/ Acute eye irritation 43032104 Irritation clearing in 8-21 days II

870.2500/ Acute dermal irritation 43032105 Erythema to day 14 III

870.2600/ Skin sensitization 43032106 Study unacceptable* Y

*Even though dermal sensitization studies were unacceptable, it is assumed th at both blends are dermal sensitizers.
Table A2 – Acute Toxicity Studies for Creosote P2 blend

Guideline No./ Study Type MRID No. Results Toxicity Category
870.1100/ Acute oral toxicity 43032301 LD 50 male= 2524 mg/kg; female = 1993 mg/kg III

870.1200/ Acute dermal toxicity 43032302 LD 50 male and female: > 2000 mg/kg III

870.1300/ Acute inhalation toxicity 43032303 LC 50 > 5.3 mg/L IV

870.2400/ Acute eye irritation 43032304 Irritation clearing within 7 days III

870.2500/ Acute dermal irritation 43032305 No irritation after 7 days III

870.2600/ Skin sensitization 43032306 Study unacceptable* Y

*Even though dermal sensitization studies were unacceptable, it is assumed that both blends are dermal sensitizers.Page 28 of 54 

## Subchronic Toxicity

There are dermal subchronic (90-day) toxic ity studies for the P1/P13 (MRID 43616101) and P2 (MRID 43616201) blends of creosote. These studies are summarized below.

90-Day Dermal Toxicity Studies

Executive Summary (P1/P13 blend) : In a 90-day dermal toxicity study (MRID # 43616101), 10 Charles River Crl:CD BR rats (10/sex/dose) were given dermal applications of P1/P13 creosote in corn oil mixture at dosage levels of 0, 4, 40 or 400 mg/kg bw/day. There were no treatmentrelated effects from dermal application of P1/P13 creosote on body weight, food consumption, ophthalmology, hematology, clinical chemistry, or organ weights at any dose level tested. Mortality (death of one male rat at 400 mg/kg/day) was observed on day 79 of the study. No testarticle related microscpoic lesions were noted at the application site on the skin at any dose level. Based on the results of this study, the systemic LOAEL was determined to be 400 mg/kg bw/day for both male and female rats, based on mortality. The systemic NOAEL was determined to be 40 mg/kg/day.

This study is classified as acceptable and satisfies the guidelin e requirement (OCSPP 870.3250) for a subchronic dermal toxicity study in rats for P1/P13 creosote. No additional data are anticipated to be required.

Executive Summary (P2 blend) : In a 90-day dermal toxicity study (MRID # 43616201), Charles River rats ( 10/sex/dose) were give n dermal applications of P2 cr eosote in corn oil at dosage levels of 0, 4, 40 or 400 mg/kg bw/day. There wa s no mortality observed in this study at any dose level. Body weight in high dose males was decreased 7-8% during w eeks 9-12 of the study, and bodyweight gain decreased 15% in high dose males for the treatment period. Food consumption in high dose males was decrease d during weeks 2-4 and week 6 by 4-10% vs control. Only slight dermal irritation was observe d in high dose males. No effects were observed on hematology or clinical chemistry. Treated sk in in the 400 mg/kg/day dose groups (male and female) was observed with increased incidence of dermal inflammation. Based on the results of this study, the systemic LOAEL is 400 mg/kg/day, based on decreased body weight gain in male rats. The systemic NOAEL is 40 mg/kg/day. For females, the NOAEL is set at 400 mg/kg bw/day since no systemic toxic effects we re noted in any of the treated groups.

This study is classified as acceptable and satisfies the guidelin e requirement (OCSPP 870.3250) for a subchronic dermal toxicity study in rats for P2 creosote. No additional data are anticipated to be required.

90-Day Inhalation Toxicity Studies

There are 90-day inhalation t oxicity studies available fo r the P1/P13 blend (MRID 43601001) and P2 blend (MRID 43600901). These studies are summarized below.

Executive Summary (P1/P13 blend) : In a subchronic inhalati on toxicity study with P1/P13 creosote (MRID # 43601001), 20 Sprague-Dawley ra ts/sex/group were treated for thirteen weeks, five days a week, six hours per day w ith P1/P13 Creosote CTM via whole body exposurePage 29 of 54 at doses of 0, 5.4, 49 and 106 mg/m 3 (0.005, 0.049 and 0.106 mg/L in air, respectively) measured gravimetrically. The aerosol MMAD was be tween 2.2 and 3.0 microns with a geometric standard deviation between 1.91 and 1.99. Subsequent to the exposure period 10 animals/sex/group were allowed to recover for 6 weeks. During the study one male rat of the mid dose group (49 mg/m 3 ) died from myocardial degenerati on that resulted in heart failure. One male and one female rat in the highest dos e group had similar lesions observed at terminal necropsy. Cardiac pathology (ie: hemorrhage, ly mphocytic infiltration and cardiomyopathy) was noted in all animals of all groups (including controls) and this condition may have been exacerbated by treatment with creo sote in the mid and high dose animals. Significant treatmentrelated findings in the mid and high dose animal s after the exposure pe riod included decreased body weight gains of both sexes (resolved by the e nd of recovery period), altered hematological parameters (decreased hemoglobin, hematocrit, nu mbers of erythrocytes, increased numbers of reticulocytes, polychromasia, poikilocytosis, anisocytosis -both sexes) and biochemical parameters (increased serum cholestero l levels - both sexes, phosphorous levels - males only). Macroscopic discolouration of the lungs, whic h persisted throughout the recovery period, was correlated with the presence of black pigment granules within alveolar macrophages of animals of all treatment groups. An incr ease in liver/brain wei ghts (statistically signi ficant only in the females), increased lung/trachea/ body weight ratios and the presence of small cystic spaces containing basophilic mucoid materi al in the nasal cavity epitheli um was still evident after the recovery period in both sexes.

Male and female rats of the low dose group we re observed to have mild poikilocytosis and anisocytosis while the females only showed the occasional cyst of the epithelium in the nasal cavity. All hematological findings in lo w dose animals showed recovery.

Based on the results of this study, the systemic LOAEL is 49 mg/m 3 for both sexes, based on cardiac pathology, decreased body weight gain, alte red hematology and clinical chemistry, and gross pathological findings in the lu ngs. The systemic NOAEL is 5.4 mg/m 3 (0.005 mg/L) for P1/P13.

This study is classified as accep table (guideline) and satisfies the guideline requirement (OCSPP 870.3465) for a subchronic inhalation toxicity study in rats. No additional da ta are anticipated to be required.

Executive Summary (P2 blend) : In a 13-week inhalation toxicity study (MRID # 43600901), 20 Sprague-Dawley rats/sex/group were treated fo r 5 days/week, 6 hours/day with P2 Creosote CTM via whole body exposure at doses of 0, 4.7, 48 or 102 mg/m 3 (0, 0.005, 0.048 or 0.102 mg/L ) in air measured gravimetrically. The aerosol size MMAD was between 2.4 and 2.9 microns with a geometric standard deviation between 1.85 and 1.91. Subsequent to the exposure period 10 rats/sex/group were allowed to recover from treatment for 6 weeks.

During the exposure period, two animals (low dose female; mid dose male) were sacrificed in extremis and the cause of morbidity was not rela ted to treatment. Significant treatment-related findings in mid and high dose animals included decreased terminal body weight and body weight gain (m/f), altered hematological parameters (decreased hemoglobin content, hematocrit, erythrocyte and platelet counts; increased reticulocyte counts and mild poikilocytosis, m/f) and biochemical parameters (increased serum choles terol levels, m/f). In both sexes macroscopicPage 30 of 54 discolouration of the lungs persisted through the recovery period and correlated with the presence of black pigment granules within alve olar macrophages. Both sexes showed increased absolute and relative liver and thyroid weights and increased lung/trachea /body weight ratios. Absolute and relative thyroid weig hts of high dose animals actually increased after the recovery period. An increased incidence of lesions of th e nasal cavity epithelium (chronic inflammation) was noted following treatment (all treatment groups, m/f) but appeared to lessen in incidence and severity during the recovery period (mainly the high dose group, m/f). During exposure an increased incidence of thyroid follicular epithelial cell hypertr ophy occurred in all male groups including control and in the high dose female group. At recovery the male incidence remained similar to that observed at exposure while the incidence in females of the high dose group had declined. The incidence of thyroid follicular ce ll hypertrophy was slightly increased in low and mid dose females after the recovery period. Sligh tly increased incidence of mild poikilocytosis was observed in all treatment groups (m/f) in cluding the low dose group and control, which persisted through the recovery pe riod. Low dose animals exhibited lesions of the nasal cavity epithelium which had resolved after the recovery period. Based on the results of this study, the systemic LOAEL is 48 mg/m 3 , based on decreased body weight and weight gain, altered hematology and clinical chemistry, increased ab solute and relative weight of the liver and thyroid, and increased incidence of lesions of the nasal cavity. The systemic NOAEL is set at 4.7 mg/m 3 (0.0047mg/L ) for P2 Creosote CTM in rats.

This study is classified as accep table (guideline) and satisfies the guideline requirement (OCSPP 870.3465) for a subchronic inhalation toxicity study in rats for P2 creosote. No additional data are anticipated to be required. 

## Developmental Toxicity

There are developmental toxicity studies available for the P1/P13 blend (MRID 43584201 and MRID 44839802) and the P2 blend (MRID 43584202). These studies are summarized below.

Executive Summary (P1/P13 blend) : In a developmental toxic ity study using P1/P13 creosote (MRID # 43584201), pregnant female Sprague-Dawley rats (30/dose) were administered P1/P13 creosote at dose levels of 0, 25, 50, and 175 mg/ kg/day on gestation days 6 through 15 inclusive. Decreased body weight and food consumption were observed in dams at the 175 mg/kg/day dose level. Decreased uterine weight was observed in dams at the high dose, which is reflected partly by the decreased live fetuses per litter at th e high dose (although mean fetal weight was not affected). Cesarean section observations show ed significantly increased resorptions and postimplantation loss as well as decreased number of live fetuses per litter at the 175 mg/kg/day dose. Based on the results of this study, the maternal NOAEL is 50 mg/kg/day, and the maternal LOAEL is 175 mg/kg/day, based on decreased b ody weight gain and food consumption during the study.

No treatment-related malformations (external, viscer al or skeletal) were observed in any of the fetuses at 25 mg/kg bw/day. At 50 mg/kg bw/d ay, the overall incidence of malformations on a fetal and litter basis were statistically elevated compared to controls. However, these individual malformations were not seen at higher dose levels and/or fell within the range of historical control data. At 175 mg/kg/day there was (i) an overall signif icant increased incidence of developmental malformations, (ii) increased inci dence of cardiovascular , vertebral and digitalPage 31 of 54 malformations, compared to lower dose levels, c oncurrent controls or historical controls (2429 and 2898 fetuses examined viscerally and skeletally respectively) and (iii) an increased incidence of malformations at this dose le vel in spite of increased feta l loss (resorptions) (Beck and Lloyd, 1963) thus resulting in fewer fetuses availa ble for teratogenic examination. Although the incidence of fetal malformations observed at 175 mg/kg/day dose level in rats was low and could be related to maternal stress (d ecreased body weight gain and f ood consumption), the teratogenic potential of P1/P13 Creosote cannot be ruled out. Based on these data, the developmental toxicity NOAEL is 50 mg/kg/day, and the deve lopmental toxicity LOAEL is 175 mg/kg/day, based on increased post-implantati on loss, increased mean resorpti ons, decreased live fetuses per litter, and increased developmental malformations.

In a developmental toxicity study in rabbits (MRID 44839802), artificial ly inseminated New Zealand White Rabbits (20/dose) were administer ed creosote P1/P13 in corn oil by gavage on gestation days 6 through 18. Doses were 0, 1, 9, and 75 mg/kg/day. At the 75 mg/kg/day dose level, increased abortions (3 rabb its vs. 0 control), reduced live fe tuses (28 vs. 50 in control), and decreased implantation sites were noted in matern al rabbits. There was no significant effect of creosote P1/P13 treatment on offspring in this study. The Maternal NOAEL in this study is determined to be 9 mg/kg/day based on effect s noted at 75 mg/kg/day. The Developmental NOAEL is determined to be 75 mg/kg/day, and the LOAEL > 75 mg/kg/day.

This study is classified as acceptable and satisfies the guideline requirement (83-3) for a developmental toxicity study in rats with P1/P13 cr eosote. No additional data are anticipated to be required.

Executive Summary (P2 blend) : In a developmental toxicity study (MRID # 43584202), pregnant female Sprague-Dawley rats (30/dose) were administered P2 creosote by gavage on gestation days 6 through 15 inclusive at dos e levels of 0, 25, 75, and 225 mg/kg/day. Although decreases in body weight and food consumption were observed at all dose levels, food efficiency appeared affected only at th e high dose of 225 mg/kg/day. Thus , the cesarean section effects observed at this dose (decreased implantations/d am, increased pre- and post-implantation loss, increased resorptions, decreased uterine weight ) could be secondary to the decreased food efficiency observed at this dose. This distin ction is a fine one, however, based on results with P1/P13 creosote in which no decrease in food efficiency was observed at a dose of 175 mg/kg, but increased resorptions, increased post-implanta tion loss, and decreased live fetuses per litter were observed at 175 mg/kg. The Maternal N OAEL in this study is determined to be 75 mg/kg/day, and the LOAEL 225 mg/kg/day, based on decreased food efficiency observed in maternal rats at 225 mg/kg/day.

With regards to assessing the teratogenic potential of P2 Creosote in rats, no treatment-related malformations (external, visceral or skeletal) were observed at the 25 mg/kg bw/day dose level. The single incidences of malformations [crani orachischisis, hydrocephaly and malpositioned eye (same pup)] observed at the 75 mg/kg bw/day dos e level, and hydrocephaly at the 225 mg/kg bw/day dose level compared to none observed in lower dose levels, conc urrent controls or historical controls (2429 and 2898 fetuses examined viscerally and skeletally respectively) were considered treatment-related. It should be noted that at 225 mg/kg bw/day one whole litter was resorbed and the number of fetuses examined at th is level for visceral and skeletal malformations was approximately 50% of those examined at th e mid-dose level. The developmental toxicityPage 32 of 54 NOAEL is determined to be 25 mg/kg/day in this study, based on the incidences of malformations observed at 75 mg/kg/day which ex ceeded both concurrent and historical control incidence.

This study is classified as acceptable and satisfies the guideline requirement (83-3) for a developmental toxicity study in rats with P2 creo sote. No additional data are anticipated to be required. 

## Reproductive Toxicity

There is one study available fo r reproductive toxicity of th e P1/P13 creosote blend (MRID 42893201). This study is summarized below. Based on the available data showing similarity in toxicity between the P1/P13 and P2 blends, a reproductive study with P2 creosote is not anticipated to be needed.

Executive Summary (P1/P13 blend) : In a two-generation repr oduction toxicity study (MRID 42893201), Charles River Crl:CD rats, 26/sex/ group, were dosed by gavage with P1/P13 creosote in corn oil at doses of 0, 25, 75, and 150 mg/kg/day. Pre-mating treatment phase lasted approximately 17 weeks, which may have contribute d to the decreased fertility observed in this study. Systemic effects observed in this study for parental animals included a dose-related decrease in body weight during th e pre-mating period at all dose levels. Salivation was observed at 75 mg/kg/day and above in the F1 generation. Effects in offspring included a dose-related decrease in growth of the F0 generation st arting at 25 mg/kg/day (as shown by decreased pup weight). For the F0 pups, mean number of liv e pups per litter was decreased at 75 and 150 mg/kg/day, and percent live pups at 175 mg/kg/day was also decr eased. In the F1 pups, the percent live pups was decreased at 75 and 150 mg /kg/day, but pup growth was affected only at 150 mg/kg/day as shown by decreased mean pup we ight. Decreased fert ility and pregnancy indices were observed in the F1 female parent al rats at all dose levels, but this was not interpreted as a treatment-related effect, as it was more likely related to the fact that the critical weight for fertility was exceeded by the 17-week pre-mating interval. Based on the results of this study, the Parental Systemic NOAEL is < 25 mg/kg/day, and the parental systemic LOAEL is 25 mg/kg/day, based on decreased pre-ma ting body weight. The developmental NOAEL in this study is < 25 mg/kg/day, and the developm ental LOAEL is 25 mg/kg/day, based on a doserelated decrease in pup body weight for the F0 pups from days 14-21. The reproductive NOAEL is < 25 mg/kg/day, and the reproductive LOAEL is 25 mg/kg/day, based on reduced pregnancy and fertility indices in F1 female parental rats.

This study is classified as acceptable and satisfies the guidelin e requirement (870.3800) for a developmental toxicity study in rats with P1/P13 cr eosote. No additional data are anticipated to be required. 

## Chronic Toxicity/Carcinogenicity

The chronic toxicity/carcinogenicity data base submitted to the agency for creosote consists of a six-month initiation/promotion study of cr eosote conducted in mice (MRID 44844401), and a published study by Culp et al. (1998). The si x month initiation/promotion study was not designed for purposes of deriving a quantitative risk estimate of carcinogenic potency. ThePage 33 of 54 study of Culp et al. (1998) did examine tumors induced by coal tar mixtures and was ued for quantitative cancer assessment

Executive Summary (P1/P13 blend) : In a submitted dermal carcinogenicity study (MRID 44844401), North American P1/P13 creosote com posite (100.0%, lot no. P1/13-009-A) was administered to groups of 30 male Crl:CD-1 ® mice by applying 50 μL aliquots of 1%, 50% or 100% corresponding to 10 μg/μL, 500 μg/μL, or und iluted creosote to the shaved backs of the mice. Acetone was utilized as a solvent th roughout the study and was used as the solvent control. 9,10-Dimethyl-1,2-benzanthracene (DMBA) was utilized as a tumor initiator, and 12-0- tetradecanoylphorbol-13-acetate (TPA) was used as a tumor promoter in the study. Creosote was tested as a tumor initiator with TPA as promotor , as a promotor with DMBA as initiator, and as both initiator and promotor (complete carcinogen). A positive control group with DMBA and TPA, and acetone controls groups with DMBA a nd TPA were included. The initiation phase consisted of 5 applications/week for 2 weeks followed by a two week rest period, and then promotion (2 applications/week for 26 weeks).

Creosote treatment at 50% and 100% especially during the promotion phase caused skin irritation and clinical signs includi ng severe erythema, slight ed ema, eschar, and exfoliation. Increased incidences of thickened skin (7- 11/30, p < 0.01), scabbing (16-20/30, p < 0.01), acute inflammation (12-18/30, p < 0.01), ulceration (6 -10/30, p < 0.05-0.01), and epithelial hyperplasia (13-23/30, p < 0.01) were seen at the applica tion site during necropsy compared to the DMBA/acetone controls (0/30). Dermal treatment with creosote did not result in a significant decrease in survival, although 6 mice died duri ng treatment in the DMBA/100% creosote group compared to none in the acetone control groups . Group mean body weights of males treated with 100% creosote during the initi ation phase were decreased by 6-8% by the end of the 2-week treatment regimen; however, they gained weig ht rapidly over the next week and no further decreases in weight or weight gain were seen with creosote treatment compared to the acetone controls. Food consumption in th e experimental groups was generally greater than in the solvent control groups.

Increased incidences of enla rged lymph nodes were seen w ith 50% (6/30, p < 0.05), and 100% creosote (5-9/30, p < 0.05-0.01) during the promo tion phase with DMBA as initiator and with 100% creosote as both initiator and promotor (6-9/30, p < 0.05- 0.01) compared to 0/30 in the solvent controls. Incidences of enlarged spleen were also in creased (15-19/30, p < 0.01) with 50% and 100% creosote in the promotion pha se compared to the controls (1/30).

The LOAEL is 50 μL of 50% or 25,000 μg/day tw ice/week applied to the skin for 26 weeks, based on skin toxicity, enlarged lymph nodes and enlarged spleen. The NOAEL was 50 μL of 1% or 500 μg/day applied to the skin twice/week for 26 weeks.

Topical treatment of male Crl:CD-1 ® mice for 2 weeks in the init iation phase of the study with all concentrations of creosote followed by treatment with TPA resulted in increased incidences of neoplasms, chiefly skin papillomas (acetone /TPA control, 0%; creo sote/TPA treated, 80-90%, p < 0.01). Treatment twice a week for 26 week s during the promotion phase with 50 μL of 500μg/μL or undiluted creosote following th e DMBA initiation phase resulted in tumor incidences of 100% compared to 3% in the DM BA/acetone control. To pical treatment with undiluted creosote in both the initiation and promotion phases resulted in a 100% tumorPage 34 of 54 incidence compared to 0% in the acetone control group. Creosote ac ted as an initiator, promoter, and complete carcinogen under the conditions of this study.

This carcinogenicity study in the mouse is acceptable/nonguideline. The study had numerous deficiencies that limited the information obtaina ble on possible systemic toxic effects, but the data demonstrated unequivocally the oncogenic natu re of creosote when a pplied to the skin of Crl CD-1 ® mice. The deficiencies did not affect th is outcome of the study, which was designed to assess the skin tumor initiating, promoti ng, and complete carcinogenicity of creosote.

Executive Summary (two coal tar mixtures and pure benzo[a]pyrene (BaP)) : In an oral carcinogenicity study conducted by Cu lp et al. (1998), the carci nogenicity of two coal tar mixtures and pure benzo[a]pyrene (BaP) was st udied. Coal tar mixture 1 (CTM-1) was a composite of coal tar samples from seven coal gasification plant waste sites and was dosed at 0.0, 0.01, 0.03, 0.1, 0.3, 0.6, and 1.0% of diet. Coal ta r mixture 2 (CTM-2) was a composite of coal tars from three waste sites with high BaP content and was dosed at 0.0, 0.01, 0.03, 0.1, 0.3% of diet. An additional group was dosed w ith pure BaP at 0, 0.0005, 0.0025, and 0.01 % in diet. A control group received solven t control in diet. Each gr oup consisted of 48 mice. In mice exposed to coal tar, coal tar acted as a systemic carcinogen a nd induced a dose-related increase in hepatocellular adenomas and carci nomas, alveolar/bronchiolar adenomas and carcinomas, forestomach squamous epithelial papillomas and carcinomas, small intestine adenocarcinomas, histiocytic sarcomas, hemangiosarcomas in multiple organs, and sarcomas in several tissues.

The incidence of forestomach tumors increa sed sharply between the 0.1 and 0.3% doses. However, there was not a proporti onal increase in forestomach tumors above 0.3% because these mice died from adenocarcinomas of the small in testine. Tumors of the esophagus, observed in BaP treated mice, were not observed in th e CTM1 or CTM-2 treated groups. Lung and hepatocellular tumors observed in the CTM1 and CTM2 groups were not observed in BaP treated animals.

Multiple neoplasms were noted in liver, lung, fo restomach, and the small intestines of exposed mice. Liver neoplasms occurred in 1, 0, and 4 mice fed 0.03, 0.1 and 0.3% CTM-1, respectively. Lung neoplasms occurred in 21, 11 and 13 mice fed 0.3%, 0.6%, 1.0% CTM-1, respectively. Eight mice in the 0.3% CTM-2 group had multiple lung neoplasms. Forestomach carcinomas were found in 2 and 1 mice fed 0.6% or 1.0% CTM-1, respectively. Adenocarcinomas were found in the small intestines (jejunum) of 2 and 12 mice fed 0.6% and 1.0% CTM-1, respectively. Groups dosed with  0.3% CTM-1 or CTM-2 had signi ficantly reduced survival.

In those mice exposed to benzo(a)pyrene, BaP appeared to act as a point-of-contact carcinogen, causing an increased incidence of papillomas a nd/or carcinomas of the forestomach, esophagus and tongue. The incidence of forestomach tumo rs increased steeply between 5 and 25 ppm, equivalent to 20.5 and 104 μ g BaP/day. Tumors of the esophagus were not observed in the CTM1 or CTM-2 treated groups. Lung and hepa tocellular tumors, observed in CTM treated mice, were not observed in mice fed BaP.

Multiple neoplasms of the forestomach occurred in 8 and 21 mice fed 25 and 100 ppm BaP, respectively. Multiple neoplasms of the esophagus and tongue were noted in 6 and 3 mice,Page 35 of 54 respectively, fed 100 ppm BaP. It should be noted that all animals in 100 ppm group died before termination of the study.

This carcinogenicity study in the mouse is acceptable/nonguideline. The study contained information useful for deriving a quantitativ e estimate of cancer potency for creosote. 

## Mutagenicity

In consideration of the available evidence that creosote is a positive mutagen, the agency waived the requirement for the standard mutagenicity battery, and instead required dominant lethal testing of both the P1/P13 and P2 blends, whic h is designed to assess heritable mutations. The executive summaries of these studies are shown below.

Executive Summary (P1/P13 blend) : In a rat dominant lethal a ssay (MRID not available), male HSD:Sprague-Dawley CD rats were treated orally once per day for five consecutive days with Cresosote P1/P13 at target doses of 725, 362.5 or 181.25 mg/kg body weight/day in a volume of 2.5 mL/kg. Actual doses determined by chemical analysis were 857.5, 330.5 and 230.8 mg/kg/day. Twenty-one rats were dosed at the two lower doses and 26 rats at the highest dose. The vehicle was corn oil. Seven days after the initial dosing, each male was mated with two untreated females per week for 10 weeks. Females were sacrificed 13 days after the midweek of the presumptive mating day and the following data collected: total implantations per female, corpora lutea per female, preimplantation losses per female, live implantations per female, dead implantations per female, proportion of females w ith one or more dead implantations, proportion of females with two or more dead implantatio ns and dead implantations/total implantations (expressed as a percentage). The fertility index, computed as the number of fertile females (with corpora lutea present) pe r number of mated females, was also determined.

Creosote P1/P13 was tested to toxic doses. In the dominant lethal study, a ll rats in the top two treatment groups but none in the low dose group showed decreas ed activity following dosing and all rats in the high dose group had dyspnea. Tw o animals in the low dose group and two in the high dose group had material around the nose an d mouth. Other pharmacotoxic signs were limited to a few animals in the high dose group an d included lacrimation, deposition of the test material around the eyes, increased salivation and anogenital staining. One high dose rat died following the fourth dose. A dos e-related decrease in body weightin the low-, mid-, and highdose animals, compared to the solvent contro ls, was seen during the dosing period, and this initial weight loss was not recovered in mid- and high-dose rats during the ten week mating period. Statistically si gnificant differences from control values were seen in a number of endpoints throughout the study; howev er, with the exception of results from mating group nine, none were endpoints indicative of a dominant lethal effect. In mating group nine, statistically significant increases were seen in dead implantati ons per female, the percentage of females with
 one implantation, the percentage of females with  two implantations and the percent dead implantations per total implantations. These incr eases were seen at the low and mid doses but not at the high dose. Also, the vehicle contro l values in mating group nine were unusually low compared to those in the other weekly mating groups (there we re fewer preimplantation losses (0.85 per female) and fewer dead implantations (0.41 per female) than seen for the vehicle controls in the other mating groups (1.53 ± 0.37 and 0.85 ± 0.20 per female, respectively) andPage 36 of 54 values for percentage of females with  one and two dead implanta tions and the percent dead implantations per total implantations were de pressed). The results, although statistically significant, are thus not considered biologically significant. Positive and solvent control values were appropriate except where not ed for the vehicle controls in mating group nine. Based on the results of this study, there was no evidence that Cr eosote P1/P13 induced do minant lethals in any germ cell stage in male rats as tested in this study. No additional data are anticipated to be required.

Executive Summary (P2 blend) : In a rat dominant lethal assay (MRID not available), male HSD:Sprague-Dawley CD rats were treated orally once per day for five consecutive days with Creosote P2 at target doses of 775, 387.5 or 193.75 mg/kg body weight/day in a volume of 2.5 mL/kg. Actual doses by chemical analys is were 866.3, 431, or 199.3 mg/kg body weight/day. Twenty-one rats were dosed at the two lower doses and 26 rats at the highest dose. The vehicle was corn oil. Seven days after the initial dosing, each male was mated with two untreated females per week for 10 weeks. Females were sacrificed 13 days after the midweek of the presumptive mating day and the following data collected: total implantations per female, corpora lutea per female, preimplantation losses per female, live implantations per female, dead implantations per female, proportion of females w ith one or more dead implantations, proportion of females with two or more dead implantatio ns and dead implantations/total implantations (expressed as a percentage). The fertility index, computed as the number of fertile females (with corpora lutea present) per number of mated females, was also determined.

Creosote P2 was tested to an adequate dose. All rats in all treatmen t groups showed decreased activity following dosing. Other clinical signs, limited to a few animals in which there was a back-up of test material during dosing, were la crimation, deposition of the test material around the eyes and increased salivation in one high-dos e male, labored breathing in one low-dose male and two high-dose males, and material around no se and mouth in two low-dose, one mediumdose and four high-dose males. Reduced food cons umption was seen in all high-dose rats. No dosing- or test material-related deaths occurr ed during the study. A dose-related decrease in body weight in the low-, mid-, and high-dose anim als, compared to the solvent controls, was seen during the dosing period, and this initial weight loss was not recovered in mid- and highdose rats during the ten week ma ting period. Statistica lly significant differences from solvent control values (p  0.05) were seen for a number of endpoints during the first nine weekly mating intervals but, with one exception, not in endpoints considered indicative of dominant lethality. The one exception was a significant in crease in the number of dead implants over the solvent control value in the sixth mating group at the lowest Creosote P2 dose. This increase was not considered biologically relevant because no significant increases were seen at higher doses or in other endpoints concerning dead impl ants. In the tenth mating group (exposure to the test material at the spermatogonial stem cell stag e), an apparently dose-related increase was seen in the number of dead implantations per female, the percentage of females with  1 dead implant, the percentage of females with  2 dead implants and the percen tage of dead implantations per total implantations. The increase s reached statistical significance at the highest dose for the first two endpoints. Positive and solv ent control values we re appropriate. The data in this study, while indicating a positive effect at week 10 of treatment, are not considered to be treatmentrelated, based on the conclusion that while dead implantations per female was significantly increased at the highest dose te sted at mating week 10, the numb er of live implants/female wasPage 37 of 54 not significantly reduced (<5% lower than control) . In addition, no dominant lethal effects were seen at weeks 8 or 9, which would also sample sp ermatogonial cells. Therefore, creosote P2 is considered to be negative for dominant lethal e ffects in rats. No additional data are anticipated to be required.


## Other Toxicological Effects

Neurotoxicity

There are no current agency guideline neurotox icity studies available for creosote. Of the existing studies available, there is no evidence of neurotoxicity for either the P1/P13 or P2 blends of creosote, although there is va lid concern for some of the co mponents of creosote, which are known to be neurotoxic (i.e. naphthalene). Da ta from the ATSDR T oxicological profile for Creosote showed increased brain- to-body weight ratios after exposur e of male and female rats to beechwood creosote (used therapeutically in the past as a disinfectant and expectorant, and composed mainly of phenol, cresols, guaicol, xylenol , and creosol) to 257 mg/kg/day in the diet for 3 months in male rats, or exposure of female rats for 52 weeks to 297 mg/kg/day in the diet, or exposure of male and female rats for 96 weeks in the diet to 143 and 394 mg/kg/day, respectively. Acute exposure of male and fe male rats to 600 and 313 mg/kg beechwood creosote resulted in convulsions. Although signs of neur ologic involvement were evident, no treatmentrelated pathological find ings of the central nervous system were noted at necropsy in these studies. No additional data ar e anticipated to be required.

Dermal Absorption

Dermal absorption of creosote was assessed through review of submitted studies on the P1/P13 blend: An in vivo dermal absorption study in the rat (MRID 47179501), and an in vitro dermal absorption study using rat and human skin pr eparations (MRID 47179502). P1/P13 creosote was chosen as the test material for these studies by agreement between the agency and the registrant, as this blend is used for treatment of wood intend ed for terrestrial, fresh water, and marine use and has the greatest potential for dermal exposur e. A protocol was submitted to the agency and approved prior to conduct of these studies.

Executive Summary (P1/P13 blend) : In an in vivo dermal penetration study (MRID 47179501) AWPA P1-P13 Creosote (98.5% a.i.) spiked with eight radiolabeled ta rget chemicals (approx. 43% of the chemicals in creosote) was appl ied to the clipped dorso-lumbar skin (10.5 cm 2 ) of eight male Sprague-Dawley rats at a dose of 10.7 mg/cm 2 skin (10 μL/cm 2 , total radioactivity 16.7 μCi). The exposure duration was eight hours. At the end of 8 hours, animals were removed from the metabolism cages, and the application si tes were washed with 2% Ivory soap solution followed by a water rinse and then a dry natural sp onge. Four rats were then euthanized (0 hours post-exposure) while the other four rats were retu rned to the metabolism cages for further excreta collection. These four rats were sacr ificed at 496 hours post-exposure.

The mean percent recovery of the radioact ivity in the applied dose was 95.009% (±2.569%) and 96.609% (±3.628%) at 0 and 496 hours post-exposure, respectively. The majority of the administered dose was recovered from the skin wash sponges; the mean percent recovery was 59.283% (±12.54%) for the 0-hr post-expos ure group and 56.822% (±8.294%) for the 496-hrPage 38 of 54 post-exposure group. The mean percent abso rbed dose was 6.342% (±0.808%) at 0 hours postexposure and 33.959% (±8.445%) at 496 hours post-exposure, with a mean percent of 1.553% (±0.299%) and 0.005% (±0.003%), respectively, present in the skin after rem oval of the stratum corneum. Most of the absorbed dose had been excreted by 496 hours post-exposure, with a mean of 18.97% (±4.97%) of the dose eliminated in the urine and 12.60% (±4.11 %) eliminated in the feces.

In a supplemental dermal pene tration study intended to clarify the results for the 496 postexposure group in the initial main study, AWPA P1-P13 Creosote ( 98.5% a.i.) spiked with eight radiolabeled target chemicals was app lied to the shaved dorsal skin (10.5 cm 2 ) of four male Sprague-Dawley rats at a dose of 10.7 mg/cm 2 skin (10 μL/cm 2 , total radioactivity 18.9 μCi). The exposure duration was 8 hours. Animals were sacrificed at 496 hrs post-exposure (504 hrs post-dosing). In the supplemental absorption stud y, the O-ring, which dema rcated the application area, was applied without glue following the dose application, and was rem oved at the end of the 8-hr exposure. In the main study, the O-ring had been glued to the skinone day prior to dose application and remained in place until study termination.

In the supplemental study, the m ean percent recovery of the radi oactivity in the applied dose was 92.775% (±2.70%) at 496 hours post-exposure. The ma jority of the administered dose was recovered from the body wrap (34.228±6.328%), skin wash (22.240±7.818%), and O-ring (27.452±3.680%). Although the mean percent abso rbed dose was reported in this supplemental experiment as 8.853±1570%, with a mean percent of 0.005% present in the skin after removal of the stratum corneum, the presence of a significant amount of radioactivity in the body wrap after 8 hours adds uncertainty as to the actual availabl e dose. In addition, in the first experiment, dermal absorption was still evident after washing of the skin at 8 hours and monitoring of urinary and fecal excretion of radioactivity from 8 hours onward. Therefore, the data are not conclusive of a reduced dermal absorption based on the c ontention that the O-ring or the glue had an influence on dermal absorption.

In a preliminary plasma kinetic (dermal bioavail ability) study, neat creoso te was applied to the clipped dorso-lumbar skin (10.5 cm 2 ) of four male Sprague -Dawley rats (10 μL/cm 2 ) for an exposure duration of 8 hours; animals were sa crificed 168 hours post-dosing (160 hours postexposure). None of the twelve target creosote ch emicals analyzed in the plasma were detected above their detection limit.

This study in the rat is acceptable-non-guideline

. Although only one exposure duration and one exposure concentration were evaluated, this was part of an agreement in study design between the agency and the registrant. No additiona l data are anticipated to be required.

In an in vitro dermal absorption study using rat a nd human skin preparations (MRID 47179502), AWPA P1-P13 Creosote (98.5% a.i.) spiked with eight radiolabeled target chemicals was applied to 6 rat and 6 human skin prep arations mounted in individua l static diffusion cells at a nominal dose of 10,700 μg creosote/cm 2 (1 μCi/skin). Samples were collected from the receptor chambers at 0.5, 1, 2, 4, and 8 hours post-appli cation. The skin was washed 8 hours postapplication and the study terminat ed. The amount of the applied dose absorbed was considered to be the amount of radioactivity m easured in the receptor fluid.Page 39 of 54 The mean total recovery of the applied dose for the rat and human skin was 78.3% and 83.9%, respectively. The mean absorbed dose was 15.1% for the rat skin and 3.34% for the human skin. The mean rate of penetration was 85.3 μg equiv/cm 2 /hr for the rat skin and 19.7μg equiv/cm 2 /hr for the human skin. The mean rate of penetration and the mean total penetration for the rat skin were approximately 4.3 times and 4.4 times greater than that for the human skin, respectively.

This in vitro dermal absorption study is classified as unacceptable , based on several deficiencies in the study, including: evaluation of only one exposure duration; evaluation of only one dose level; no data on solubility as a rate-limiting factor for creosote dermal absorption; and lack of a 24 hour time point measurement.

The agency reached the following conclusion on de rmal absorption of creosote, using available in vivo dermal absorption data: based on (1) the lack of data demonstr ating that the concentration of the creosote solution did not exceed solubility limits and theref ore did not have an artefactual influence on the magnitude of absorption in th e in vitro test system, and (2) the continued absorption observed after eight hours in the in vivo study [the O-ring in fluence could not be conclusively demonstrated to be acting as a de pot for radioactivity]), the agency’s conclusion was to use the value of 34% from the in vi vo absorption study and recognize the 8-fold difference in absorption between human and rat skin from the in vitro study. Therefore, a value of 5% for dermal absorption was used (34% divided by 8 and rounded upward). 

## Immunotoxicity

An immunotoxicity study is a data requirement fo r all uses of antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for An timicrobial Pesticide Data Requirements (78 FR, no. 89, 26978, May 8, 2013). It is an antic ipated data requirement for registration review. The expected data call-in notice will pr ovide that the registrant can address this data requirement by submitting a study accordi ng to the OCSPP 870.7800 guideline, citing information from the scientific literature that adequately addresses immu notoxicity of creosote, or submitting a request for waiver of this study using the agency’s published guidance, available
at: http://www.epa.gov/pesticides/regulat ing/part158-tox-da ta-requirement.pdf

.Page 40 of 54 Toxicology References for Appendix A

MRID 43032101: North American P1/P13 Creosote: Acute Oral Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creo sote Council II. Unpublished. HED document no. 011033.

MRID 43032102: North American P1/P13 Creosote: Acute De rmal Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.

MRID 43032103: North American P1/P13 Creosote: Ac ute Inhalation Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.

MRID 43032104: North American P1/P13 Creosote: Eye Irr itation Study in Rabbits. Study conducted by IRDC, Mattawan, MI for the Creo sote Council II. Unpublished. HED document no. 011033.

MRID 43032105: North American P1/P13 Creosote: Prim ary Dermal Irritation Test in Rabbits. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.

MRID 43032106: North American P1/P13 Creosote: De rmal Sensitization Study (Buehler ) in the Albino Guinea Pig. Study conducted by IRDC, Ma ttawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.

MRID 43032301: North American P2 Creosote : Acute Oral Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creo sote Council II. Unpublished. HED document no. 011033.

MRID 43032302: North American P2 Creosote: Acute De rmal Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for th e Creosote Council II. Unpublished.

MRID 43032303: North American P2 Creosote: Acute I nhalation Toxicity Evaluation in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.

MRID 43032304: North American P2 Creosote:Eye Irritation Study in Ra ts. Study conducted by IRDC, Mattawan, MI for the Creosote C ouncil II. Unpublished. HED document no. 011033.

MRID 43032305: North American P2 Creosote: Primar y Dermal Irritation Test in Rabbits.Study conducted by IRDC, Mattawan, MI for the Creo sote Council II. Unpublished. HED document no. 011033.

MRID 43032306: North American P2 Creosote: Dermal Sensitization Study (Buehle r) in the Albino Guinea Pig. Study conducted by IRDC, Ma ttawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.Page 41 of 54 MRID 43601001: North American P1/P13 Creosote: Thir teen Week Subchronic Inhalation Toxicity Study on North American P1/P13 Creo sote CTM in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671-016 (1995). Unpublished.

MRID 43600901: North American P2 Cr eosote: Thirteen Week Subchron ic Inhalation Toxicity Study on North American P2 Creo sote CTM in Rats: Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671- 018 (1995). Unpublished.

MRID 43616101: North American P1/P13 Creosote: 90 -Day Subchronic Dermal Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671-013 (1995). Unpublished.

MRID 43616201: North American P2 Creosote: 90 Day Subchronic Dermal Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671- 014 (1993). Unpublished.

MRID 43584201: North American P1/P13 Creosote: Develo pmental Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671-020 (1995). Unpublished.

MRID 43584202: North American P2 Creosote: Developmental Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671-022 (1995). Unpublished.

MRID 44844401: A 6-Month Dermal Oncogenicity Study of Creosote in Mice. Study conducted by WIL Research Laboratories, Ashland, OH for Koppers Industries, Pittsburgh, PA. Report no. WIL-100005. Unpublished.

MRID 47179501: Fasano, W. (2007) AWPA P1-P13 Cr eosote: In vivo dermal absorption in the rat. E.I. du Pont de Nemours and Company, Haskell SM Laboratory for Health and Environmental Sciences, Newark, Delaware. Laboratory Project ID. DuPont-19622, July 2, 2007.

MRID 47179502: Fasano, W. (2007) AWPA P1-P13 Creo sote: In vitro kinetics in rat and human skin. E.I. du Pont de Ne mours and Company, Haskell SM Laboratory for Health and Environmental Sciences, Newark, Delaware. Laboratory Project ID: DuPont-21647, April 30, 2007.

Agency for Toxic Substances and Disease Regist ry (1990): Toxicologica l Profile for Creosote. U.S. Department of Health and Human Services : Public Health Service. McMahon, Timothy F.: Creosote: Endpoint Selection Repor t. February 2008. Unpublished.

Culp, S.J., Gaylor, D.W., Sheldon, W.G., Gold stein, L.S., and Beland, F.A. (1996): DNA adduct measurements in relation to small intestine a nd forestomach tumor incidence during the chronic feeding of coal tar or benzo[a]pyrene to mice. Polycyclic Aromatic Compounds 11, 161-168.Page 42 of 54 Culp, S.J., Gaylor, D.W., Sheldon, W.G., Goldstein, L.S., and Beland, F.A. (1998): A comparison of the tumors induced by coal ta r and benzo(a)pyrene in a 2-year bioassay. Carcinogenesis 19:1, pp. 117-124

Gaylor, D.W., Culp, S.J., Goldstein, L.S., and Beland, F.A. (2000): Cancer Risk Estimation for Mixtures of Coal Tars and Benzo[a]pyrene. Risk Analysis 20(1): 81-85.

McMahon, Timothy F.: Creosote: Endpoint Sele ction Report. February 2008. Unpublished.

Schneider, K., Roller, M., Kalberlah, F., and Schumacher-Wolz, U. (2002): Cancer Risk Assessment for Oral Exposure to PAH Mixtures. J. Appl. Toxicol. 22: 73-83.

USEPA, 1984: Wood Preservative Pesticides : Creosote, Pentachlorophenol, Inorganic Arsenicals. Position Document 4

York, Raymond G. (1994): Developmental Toxicity Study in New Zealand White Rabbits. Study conducted by IRDC, Mattawan, MI for Koppers Industries, Pittsburgh, PA. Report no. 672-002. Unpublished.

York, Raymond G. (1995): Two Generation Reproduction/Fer tility Study in Rats. Study conducted by IRDC, Mattawan, MI for Koppers Industries, Pittsburgh, PA. Report no. 672-006. Unpublished.Page 43 of 54 

# Appendix B Environmental Fate

The agency does not anticipate the need to requ ire environmental fate studies for registration review other than a wood leaching study called in through the post-RED DCI in 2011. In the RED, the agency conducted an open literature search for environmental fate and transport studies on the creosote mixture and based the assessment on the PAH constituents only. In this appendix, the agency is summarizi ng the contents of the RED.

The environmental fate and transport of creoso te as addressed here focuses primarily on the likely exposure of PAHs into three environmental compartments: 1) leaching of creosote mixture into surface and ground waters fr om the railroad ties and util ity poles; 2) migration into soil/sediments from the railroad ties and utility poles, and 3) bioaccumulation into the aqueous and benthic organisms.

The PAHs in creosote are primarily expected to sorb to soil and sediment because of limited water solubility and high carbon content. Microbia l degradation and volatility are expected to be more rapid for those PAHs with fewer rings. P hotodegradation in water is also a primary route of dissipation for those PAHs in water.

Water and Sediment

Hydrolysis

PAHs are fused aromatic polycyclic rings wh ich have no hydrolyzable hydrogens and the solubility of these compounds are very low in wate r. Therefore, hydrolysis is not an important route of dissipation for creosote.

Aqueous Photolysis

PAHs can readily photodegrade in water because these compounds absorb UV light. However, photooxidized products of PAHs can be stable, and can persist in air/water and soils and become an environmental concern as these photooxidize d products are also bioaccumulative (Kirso, 1991). The half-lives in water for various PAHs ranged from 3.6-375 minutes (freshwater, most <110 minutes), 28-146 minutes for benzo(a)pyrene (saltwater, most <72 minutes), and 0.58- 9,840 hours (numerous PAHs, most <48 hours).

Octanol-Water Partition Coefficient and Bioconcentration in Aquatic Organisms

Based on the log Kow (Log P) value of creosote of 3.25 (Table 4), bioconcentration of PAHs in aquatic organisms is a signifi cant route of dissipation. In general, the potential for bioconcentration of PAHs increas es as the number of rings incr eases, but sorption to sediment and the lack of water solubility may limit the act ual bioconcentration of higher molecular weight compounds. Most of the biocon centration data for creosote PAHs was associated with Superfund sites and environmental spills and not laboratory studies that were specifically targeted to measure bioconcentration based on k nown water concentrations. Southworth et al.Page 44 of 54 (1978) measured the bioconcentration in clams near a creosote spill. For the 2-ring and 4-5 ring PAHs, concentrations in clams increased while the concentrations of 3-ring compounds were stable or declined slightly. The concentration of 4-5 ring PAHs were the highest in clams.

Creosote Behavior with Sediment and Ground Water

Mueller et al. (1993) studied the removal of Group 1, 2, and 3 PAHs 8 from contaminated groundwater in Florida over 32 days. Group 1 PA Hs include known carcinogens (only member is benzo(a)pyrene (5-rings), Group 2 PAHs in clude “probable carcinogens” which range from 3- 5 rings, and Group 3 PAHs include numerous 4- and 5-ring compounds. Overall, 89.4-98 % of PAHs were removed by biodegradation and only 3.5-9.2 % remained at the end of the study. Over a 28-day period, Bouwer et al. (1996) studied the removal of 2-3 ring PAHs in sediment ground water and determined the effect of oxygen on mineralization. Mineralization for anthracene and phenanthrene ranged from 4 to 23 percent, ranged from 4 to 42 percent for benzene, and from 8 and 55 percent for naphtha lene. Shocken and Gibson (1984) demonstrated degradation of acenaphthene a nd acenaphthalene (3-ring compounds) into acenaphthenequinone (parent compound plus two ortho keto groups). Godsy et al. (1992) demonstrated lateral movement of <150 meters in ground water from an abandoned wood treatment site for most PAHs. Goerlitz et al. (1985) demonstrated th at PAHs were not dete cted in ground water at depths >12 meters at the same abandoned wood treat ment site. Mueller et al. (1991) determined that lower-molecular weight PAHs in groundwater degraded faster (half-lives of ~3 days) while higher molecular-weight PAHs degraded sl ower (half-lives of ~14 days).

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

Some of the PAHs, particularly those that ha ve a high molecular mass (higher number of the fused aromatic rings) have a higher tendency to adsorb to soil organic carbon. Such adsorption coefficients (K OC ) have been reported in literature (Knightes and Peters, 2003). The log Koc values range from 3.36 for naphthale ne (2-rings) to 5.18 for pyrene (4 rings). Some PAHs with a high K oc can bind strongly with the organic carbon of the soils/sediments and may not be bioavailable to the aquatic organisms. Ho wever, if the octanol/ water coefficients (K ow ) is high, and if the PAHs are desorbed from the soils/s ediments to which they are bound, some of these PAHs can become bioaccumulative to the benthic organisms.

Volatility from Soil

Few studies are reported in the ope n literature on field vol atilities for PAHs present in creosote. Lindhardt and Christensen (1996) measured the volatility of 11 PAHs from contaminated soil and determined that steady-state concentrations of naphthalene and methyl naphthalene (2-ring PAHs) were observed at 10-20 days, and measurab le fluxes of acenaphthene and fluorene (3-ring PAHs) were only detected using a soil cover wi th low organic content, indicating sorption.

Aerobic Soil Metabolism

8 Carex Canada, http://www.carexcanada.ca/en/p olycyclic_aromatic_hydrocarbons/Page 45 of 54 Most of the PAHs have a tendency to biodegrad e under aerobic conditions. It has been reported that over eighty percent of biode gradation occurs in the first month after the wood preservative application, with the exception of benz[a]pyrene and benzo[k]fluoranthene, which have shown resistance to biodegradation. A number of aerobic soil metabolism studies on PAHs conducted at various contaminated sites as well as in si mulated microcosms reported that low molecular weight PAHs generally metaboli zed in aerobic conditi ons and the greater th e oxic environment, the higher the biodegrada tion level. Chapman et al. (1995) determined that 72 % of lowmolecular weight PAHs were degraded after wash ing creosote-contaminated soil. Hurst et al. (1996) found that after 7 days, 45 and 55 % of PAHs mineralized in 2 and 21 % oxygen, respectively.

Anaerobic Soil Metabolism

Genther et al. (1997) studied th e anaerobic soil metabolism of PA Hs and demonstrated that only anthraquinone (3-rings) and 2-methyl anthracen e (3-rings) demonstrated any degradation under anaerobic conditions.

Volatility from Treated Wood

Exposure to air does not seem to be an important factor in the environmental behavior for most PAHs. While Gevao et al. ( 1998) showed that acenaphthe ne, fluorene, phenanthrene, anthracene, and fluoranthene volati lized at a faster rate at 30  C than at 4  C, 85 percent of these components remained in the wood after seven week s. The rate of volatilization was slow for acenaphthene (half-life, one year) and fluoranthene (hal f-life, one year). In most cases, the initial rates of dissipation are caused by partitioning between the wood and air and biodegradation in the presence of microbi al populations.

Leaching from Treated Wood

Guideline data on leaching of creosote component s from treated wood were required in a postRED DCI (GDCI-025004-30249) and have not been s ubmitted. The agency still anticipates the submission of these leaching data. Literature data indicate that leaching occurs primarily in the first 7 days in flooded conditions (Bestari et al., 1998a). In a terrestrial microcosm, 95 % of PAHs in Ponderosa pine blocks were presen t in wood after 2.5 months. In an aquatic microcosm, a leaching rate of 50 ug/cm 2 /day in freshwater was observed from marine-grade Douglas fir pilings (Bestari et al, 1998b). This study measured 15 of the 16 priority pollutant PAHs. In a terrestrial setting (Mississippi State University, 1981), 2-ring compounds were not found in soil around stakes but 3, 4, a nd 5-ring compounds were found in soil.Page 46 of 54 Environmental Fate References for Appendix B

Al-Bashir, B. et al. 1990. Appl. Microbiol. Biotech. 34:414-419.

Bauer, J.E. et al. 1985. Appl . Environ. Microbiol. 81-90.

Bauer, J.E. et al. 1988. Appl . Environ. Microbiol. 1649-1655.

Behymer, T.D. and R.A. Hites. 1985. Environ. Sci. Technol. 19(10):1004-1006.

Bestari, K.T. Jim et al. 1998b. Distribut ion and composition of polycyclic aromatic hydrocarbons within experimental microcos ms treated with creosote-impregnated douglas fir pilings. Environ. Toxicol. Chem. 17(12):2369-2377.

Bieri, R.H. et al. 1986. Polycyclic aroma tic hydrocarbons in surface sediments from the Elizabeth River subestuary. Int. J. Environ. Anal. Chem. 26:97-113.

Bouwer, E.J. and P.L. McCarty. 1983. Appl. Environ. Microbiol. 45:1295-1299.

Bruner, K.A. et al. 1994. J. Great Lakes Research. 20:725-734.

Callahan, M.A. et al. 1979. Water Related Envi ronmental Fate of 129 Priority Pollutants, EPA440-4-79-029a,b.

Elder, J.F. and P. Dresler. 1988. Accumulati on and bioconcentration of polycyclic aromatic hydrocarbons in a nearshore estu arine environment near a Pe nsacola (Florida) creosote contamination site. Envir onmental Pollution. 49:117-132.

Electric Power Research Institute (E PRI). 1992. Document EPRI TR-01000870.

Ehrlich, G.G. et al. 19 82. Groundwater. 20(4):703-710.

Flyvberg, J.E. et al. 1993. J. Contamin. Hydrology. 12:133-150.

Fowler, M.G. et al. 1993. Prelim inary results from a field experi ment investigating the fate of some creosote components in a natura l aquifer. Org. Geochem. 22:641-649.

Fukuda, K. et al. 1988. Chemosphere. 17(4):651-659.

Gevao, B. and K.C. Jones. 1998. Kinetics and potential significance of polycyclic aromatic hydrocarbon desorption from creosote-treated wood. Environ. Sci. Tech. 32:640-646.

Gile, J.D. et al. 1982. J. Agric. Food Chem. 30:295-301.

Goerlitz, D.F. et al. 1985. E nviron. Sci. Tech. 19(10):955-961.

Grbic-Galic, D. et al. 1991. Anaerobic de gradation of aromatic hydrocarbons and aerobic degradation of trichloroethyl ene by subsurface microorganisms. In: Organic Substances and Sediments in Water, R.A. Baker, Ed., Lewis Publishers, Michigan:239-266.Page 47 of 54 Harris, J.C. 1982. Handbook of Chemical Prope rty Estimation Methods. W.J. Lyman, W.F. Reehl, D.H. Rosenblatt, Eds. McGraw -Hill Book Company, New York: Chapters 7-8.

Hellou, J.G. et al. 1990. Polycyclic aromatic hydr ocarbons in muscle tissue of marine mammals from the Norhtwest Atlantic. Marine Pollution Bulletin. 21(10):469-473.

Howard, P.H., R.S. Boethling, W.F. Jarvis, W.M. Meylan, E.M. Michalenco, Eds. 1991. Handbook of Environmental Degradation Rates, Lewis Publishers, Inc. Chelsea, Michigan, USA.

Hurst, C.J. et al. 1996. Polycyclic aromatic hydrocarbon biodegradation as a function of oxygen tension in contaminated soil. J. Haz. Materials. 51:193-208.

Knightes, C.D. and C. A. Peters. 2003. A queous Phase Biodegradation Kinetics of 10 PAH Compounds. Environmental Engi neering Science 20(3):207-218.

Kuhn, E.P. et al. 1988. Appl. Environ. Microbiol. 54:490:496.

Lindhardt, B. and T.H. Christensen. 1996. Vo latilisation of aromatic hydrocarbons from soil: part II, fluxes from coal tar contaminated so ils residing below the soil surface. Water Air Soil Pollution. 92:375-389.

Long, E.R. et al. 1995. Incidence of adverse bi ological effects within ranges of chemical concentrations in marine and estuarine se diments. Environ. Management. 19:81-97.

Mabey, W. et al. 1982. Aquatic Fate Process fo r Organic Priority Pollutants. EPA Report No. 440/4-81-14.

Mattraw, H.C. and B.J. Frank. 1986. Movement and fate of creosote waste in ground water, Pensacola, Florida; U.S. Geological Survey toxic waste -- ground- water contamination program. U.S. Geological Survey Water Supply Paper No.: 2285.

McGroddy, S.E. and J.W. Farrington. Sediment por ewater partitioning of polycyclic aromatic hydrocarbons in three cores from Boston Harbor, Massachusetts. Environ. Sci. Technol. 29(6):1542-1550.

Merril, E.G. and T.L. Wade. 1985. Carbonized coal products as a source of aromatic hydrocarbons to sediments from a highly industr ialized estuary. E nviron. Sci. Technol. 19:597-603.

Middaugh, D.P. et al. 1991. Archiv es of Environ. Contamin. pp. 244-254.

Mihelcic, J.R. et al. 1988. A ppl. Environ. Microbiol. 54:1182-1187.

Mill, T. et al. 1981. Chemosphere. 10:1283-1293.

Miller, M.M. et al. 1985. E nviron. Sci. Technol. 19:522-529.

Mississippi State University. 1981. Cooperative Agreement Number 12-156.Page 48 of 54 Mueller, J.G. et al. 1991. Biodegradation of creosote in contaminat ed groundwater: chemical and biological assessment. Applied and Environmenta l Microbiology. 57(5):1277-1285.

Mueller, J.G. et al. 1993. Strategy using bior eactors and specially selected microorganisms for bioremediation of groundwater contaminated with creosote and pentachlorophenol. Environ. Sci. Technol. 27(4):691-698.

National Oceanic and Atmospheric Administ ration (NOAA). 1988. A Selected Summary of Data of Chemical Contaminants in Sediments Collected During 1984-1987, NTIS.

Neff, J.M. et al. 1976. Mari ne Biology. Volume 38:279-289.

Padma, T.V. et al. 1999. Toxicity of creo sote water-soluble fractions generated from contaminated sediments t the bay mysid. Ecotoxicology and Envi ronmental Safety. 42:171-176.

Politzer, I.R. et al. 1985. Impact on Human Hea lth of Petroleum in the Marine Environment, American Petroleum Institute (API), Washington, DC.

Priddle, M.W. and K.T.B. MacQuarrie. 1994. Dissolution of creosote in groundwater: an experimental and modeling investigation. Journal of Contaminant Hydrology. 15:27-56.

Rutherford, P.M., M.R. Gray, and M.J. Dudas. 1997. Desorption of [ 14 C]naphthalene from bioremediated soils contaminated with creosote compounds. 31:2515-2519.

Genther, B.R. et al. 1977. Arch. Environ. Contamin. Toxicol. 32:99-105.

Shocken, M.J. et al. 1984. Bacterial oxida tion of the polycyclic aromatic hydrocarbons acenaphthene and acenaphthylene. Appl . Environ. Microbiol. 48(1):10-16.

Smith, J.H. et al. 1978. Environmental Pathwa ys of Selected Chemicals in Fresh Water Systems: Part II. Laboratory Studies : 304. EPA-600/7-78-074, USEPA, Athens, Georgia.

Southworth, R.G. 1977. Aquatic Toxicology, AS TM ATP 667. L.L. Marking, R.A. Kimerle, Eds., American Society for Testing and Materials: 359-380, Philadelphia.

Southworth, G.R., J.J. Beauchamp, and P.K. Schmieder, 1978. Water Research. 12:973-977.

Spacie, A. et al. 1983. Uptake, depuration, and biotransformation of anthracene and benzo[a]pyrene in bluegill sunfish. Ecotoxicology and Environmental Safety. 7:330- 341.

Stegman, J.J. and J.M. Teal. 1973. Marine Biology. 22:37-44.

Tay K.L. et al. 1992. Sediment bioassessment in Halifax Harbour. Environmental Toxicology and Chemistry. 11:1567-1581.

Verasani, U. et al. 1978. Toxicol. Appl. Pharmacol. 44:277-289.Page 49 of 54 Wan, M.T. 1994. Utility right-of-way contaminan ts: polycyclic aromatic hydrocarbons. J. Environ. Quality. 23:1297-1304.

Wendt, P.H. et al. 1996. Wood pr eservatives leachates from docks in an estuarine environment. Arch. Environ. Contamin. Toxicol. 31:24-37.

Zepp, R.G. et al. 1980. Assessing the photoche mistry of organic pollutants in aquatic environments. In, Dynamics, Exposure and Ha zard Assessment of Toxic Chemicals. R. Haque, Ed. Ann Arbor Sci. Publ. Inc., Ann Arbor, Michigan: 69-110.Page 50 of 54 

# Appendix C Ecotoxicology Profile

The ecotoxicity database is incomplete. The agen cy anticipates the need to require ecotoxicity data for registration review (f or a complete list of the anticipated data, see Table 6).


### Terrestrial Organisms

Birds, acute oral

No data are available. A study is anticipated to be needed to determine the toxicity of creosote to birds. The guideline (850.2100) is not satisfied.

Nontarget Insects

Toxicity data are needed for beneficial ins ects to support the use of creosote as a wood preservative. The guideline for an acute toxicity test (850.3020) is not satisfi ed. At this time, the agency does not anticipate needing a honeybee study for toxicity of residues on wood (850.3030) to support the heavy duty wood preservative uses.


### Aquatic Organisms

Freshwater Fish, acute

No guideline data are available. Supplemental data available in the OPP chemical files for creosote indicate that creosote is moderately to highly toxic to fish. The guideline (850.1075) for acute toxicity testing with freshw ater fish (cold-water and warm-wat er species) is not satisfied. Data are anticipated to be needed for the eco logical risk assessment for listed and nonlisted freshwater fish.

Freshwater Fish Acute Toxicity

Test Species Test Material (% ai) LC50 (μg ai/L) Toxicity Category EPA Study ID

Rainbow Trout ( Oncorhynchus mykiss) Coal tar creosote (97) 600 Highly toxic TN 0571 Supplemental Marine grade creosote (nr) 570 Highly toxic TN 2401 Supplemental Bluegill ( Lepomis macrochirus ) Coal tar creosote (97) 1600 Moderately toxic TN 0542 Supplemental

Freshwater Invertebrates, acute

No guideline data are available. Supplemental data available in the OPP chemical files for creosote indicate that the material tested (mar ine creosote) is highly to very highly toxic toPage 51 of 54 daphnids. The guideline (850.1010) for acute toxicity testing with a freshwater invertebrate is not satisfied. The data are anticipated to be needed for the ecological risk assessment for listed and nonlisted freshwat er invertebrates.

Freshwater Invertebrate Acute Toxicity

Test Species Test Material (% ai) EC50 (μg ai/L) Toxicity Category EPA Study
ID

Waterflea ( Daphnia magna ) Marine creosote (nr) 76 Very highly toxic TN 2392 Supplemental
Marine creosote (nr) 240 Highly toxic TN 2393 Supplemental

Estuarine/Marine Fish and Invertebrates, acute

No guideline data are available. Supplemental data available in the OPP chemical files for creosote indicate that creosote is highly to ve ry highly toxic to estuarine/marine organisms. These data can be used to help characterize th e toxicity of creosote to estuarine/marine organisms, but they do not satisfy the guide lines for fish (850.1075), bivalve (850.1025 or 850.1055), and one additional inverteb rate sp. (850.1035). These da ta are anticipated to be needed for the ecological risk assessment for listed and nonlisted estuarine/marine fish and invertebrates.

Estuarine/Marine Fish and Invertebrate Acute Toxicity

Test Species Test Material (% ai) EC50 (μg ai/L) Toxicity Category EPA Study ID Sheepshead minnow ( Cyprinodon variegatus ) Coal tar creosote (97) 720 (juv.) 3500 (adult) Highly toxic 40228401 Supplemental Mysid shrimp ( Americamysis bahia ) Coal tar creosote (97) 18 Very highly toxic 40228401 Supplemental Eastern oyster ( Crassostrea virginica ) Coal tar creosote (97) 710 (adult) Highly toxic 40228401 Supplemental Pink shrimp ( Penaeus duorarum ) Coal tar creosote (97) 240 (adult) Very highly toxic 40228401 Supplemental

Fish and Aquatic Invertebrates, chronic

No data are available. Chronic data are an ticipated to be needed for one fish and one invertebrate species. The expect ed DCI will provide that testi ng must be done with the most sensitive species (either freshwater or estuarine/ marine) as determined from the results of the acute toxicity tests (acute EC50 freshwater invertebrates; acute LC50 freshwater fish; LC50/EC50 estuarine/marine species). The guideline for a freshwater or estuarine/marine fish early life-stage toxicity test (850.1400) is not satisfied. Th e guideline for a freshwater invertebrate life cycle test (850.1300) or estuarin e/marine mysid life cycl e test (850.1350) is notPage 52 of 54 satisfied. These data are included as studies anti cipated to be required in registration review (see Table 6).

Aquatic and Semi-aquatic Plants

No data are available. Data for vascular and non-vascular aquatic plants are anticipated to be needed to support wood preservative uses. The gu idelines for testing with duckweed, a vascular sp. (850.4400), three algal spp. (850.4500), and cy anobacteria (850.4550) ar e not satisfied. A seedling emergence toxicity test with rice al so is needed; the guideline (850.4225) is not satisfied. These data are anticipated to be n eeded for the ecological risk assessment for listed and nonlisted plants.

Benthic Invertebrates, chronic

No sediment-toxicity data are available for creo sote. Based on environmental fate properties discussed in Appendix B, creosote is expected to accumulate and persist in aquatic sediments. Because creosote persists in sediments (half-life > 10 days), chronic testing is anticipated to be needed for freshwater (2 spp.) and estuarine/marine (1 sp.) benthic inverteb rates. There currently is no guideline number for this test.Page 53 of 54 Ecotoxicity References for Appendix C

40228401 EPA. 1986. Acute Toxicity Handbook of Ch emicals to Estuarine Organisms. F.L. Mayer, Jr., Environmental Research Laboratory, Office of Research and Development, Gulf Breeze, FL. EPA/600/X-86/231

TN 0571 EPA. 1973. Toxicity of C & P Creosote to rainbow trout. Fish Toxicity Lab. Report, Animal Biology Lab., EPA-PR, AR C, Beltsville, MD. ID No. MB 189.

TN 0542 EPA. 1973. Toxicity of C & P Cr eosote to bluegill. Fish Toxicity Lab. Report, Animal Biology Lab., EPA-PR, ARC, Beltsville, MD. ID No. MB 189.

TN 2392 EPA. 1979. Marine Creosote: Daphnia magna Static Jar Test #2392. Biological Report of Analysis, Animal Biology Lab., Washington, DC.

TN 2393 EPA. 1979. Creosote: Daphnia magna Static Jar Test #2393 . Biological Report of Analysis, Animal Biology Lab., Washington, DC.

TN 2393 EPA. 1979. Marine Grade Creosote: Rainbow trout ( Salmo gairdneri ) Static Jar Test #2401. Biological Report of Analysis , Animal Biology Lab., Washington, DC.Page 54 of 54 

# Appendix D Physical and Chemical Properties

The creosote product chemistry inform ation is summarized in Table D1.

Table D-1 - Physical-Chemical Properties for Creosote

Guideline No. Parameter Creosote Reference/Comments

830.7050 UV/Visible Absorption Not available for mixture PAHs absorb UV light but no spectrum available for mixture
830.7200 Melting point ( o C) Not applicable MRID 48480902 Product is liquid 830.7220 Boiling point ( o C) >180 MRID 48490902

830.7370 Dissociation constant (pKa) Not applicable MRID 48480902 No acid or base functional
groups

830.7550 Octanol-water partition coefficient at 25 o C (Log K ow ) 3.25 MRID 48480902
830.7840 Solubility in water (mg/L) 313 MRID 48480902
830.7950 Vapor pressure (mmHg) 11.1 MRID 48480902 24.4 o C
None Henry's law constant at 25 o C (atm-m 3 /mol) Not calculated Product is a mixture with various chemical and physical properties

atm-m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury.