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Page 2 of 60 Creosote Registration Review Team

Human Health & Environmental Effects Nat han 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

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Page 3 of 60 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD a cute p opulation a djusted d ose ASRI a ctivated sludge r espiration i nhibition
atm

- m 3 /mole a tmospheric pressure

- c ubic meter per mole AWPA American Wood Protection Association BCF b ioconcentration f actor °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese h amster o vary CMA Chemical Manufacturers Association CO 2 c arbon dioxide COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose DCI data call

- in EC 50 m edian (or 50 percent) e ffect c oncentration EC 05 5 p ercent e ffect c oncentration ECOTOX ECOTOXicology EDI e stimated daily i ntake EDSP E ndocrine 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 Feder al Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol g rams per mole GLN guideline number HPV h igh production v olume IDS Incident Data System Koc o rganic carbon normalized soil

- water partition coefficient Kd s oil

- water partition coefficient Kow o ctanol

- water partition coefficient LC 50 m edian (or 50 percent) l ethal c oncentration LD 50 m edian (or 50 percent) l ethal d ose LOAEC l owest

- o bserved

- a dverse

- e ffect

- c oncentration LOEC l owest

- o bserved

- e ffect

- c oncentration LOAEL lowest

- observed

- adverse

- e ffect

- l evel Log K ow l ogarithm of the octanol

- water partition coefficient
μg m icrogram ml/g m illiliter p er g ram mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercuryDocket Number EPA

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Page 4 of 60 MOE m argin of e xposure MRID Master Record Identification Number MRL m aximum r esidue l imit N/A n ot a pplicable

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

- l evel OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co

- operation and Development OPP Office of Pesticide Programs PAD p opulation a djusted d ose PAI p ure active i ngredient PDM Probabilistic Dilution Model % p ercent PC Code Pesticide Chemical Code PCF p ounds p er c ubic foot pH power of h ydrogen or power of the con centration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary i rritation s core pKa p ower of the acid dissociation constant or negative base

- 10 logarithm of the acid dissociation constant of a solution ppb p arts p er b illion
ppm p arts p er m illion PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship RED Rere gistration Eligibility Decision SAR s tructure a ctivity r elationship SF s afety f actor SSTS Section Seven Tracking System TEP t ypical e nd

- u se p roduct TGAI t echnical grade active i ngredient TMDL total maximum daily l oads UF uncertainty factor UV/VIS ultraviole t/v isible light a bsorption % w / w p ercent weight per weight. WP w ettable powder WWTPs w astewater treatment plantsDocket Number EPA

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Page 5 of 60 

### Table of Contents
1 Introduction

................................ ................................ ................................ ............................. 7 1.1 Statutory and Regulatory Authority

................................ ................................ ................. 7 1.2 Updates to the Work plan

................................ ................................ ................................ . 7 1.3 Case Overview

................................ ................................ ................................ ................. 8 1.4 Chemical Identification and Properties

................................ ................................ .......... 10 1.5 Us e/Usage Description

................................ ................................ ................................ ... 11 1.5.1 Registrations

................................ ................................ ................................ ........... 11 1.5.2 Summary of Registered Uses

................................ ................................ .................. 12 1.5.3 Usage Information

................................ ................................ ................................ .. 12 1.6 Regulatory History

................................ ................................ ................................ ......... 12 1.6.1 Tolerance Information

................................ ................................ ............................ 13 1.7 Incidents

................................ ................................ ................................ ......................... 13 1.7.1 Human He alth

................................ ................................ ................................ ......... 13 1.7.2 Ecological

................................ ................................ ................................ ............... 13 2 Anticipated Data Needs

................................ ................................ ................................ ........ 13 3 Human Health Risk Assessment

................................ ................................ ........................... 17 3.1 Existing Toxicological Endpoints

................................ ................................ .................. 17 3.2 Dietary Exposure

................................ ................................ ................................ ............ 18 3.2.1 Food

................................ ................................ ................................ ........................ 18 3.2.2 Drinking Water

................................ ................................ ................................ ....... 18 3.3 Occu pational and Residential Exposures

................................ ................................ ....... 18 3.3.1 Occupational Handler Exposure

................................ ................................ ............. 19 3.3.2 Occupational Post

- Application Exposure

................................ ............................... 19 3.3.3 Residential Handler Exposures

................................ ................................ ............... 20 3.3.4 Residential Post

- Application Exposures

................................ ................................ . 20 3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 20 3.4.1 Aggregate Exposures

................................ ................................ .............................. 20 3.4.2 Cumulative Exposures

................................ ................................ ............................ 20 4 Environmental Risk Assessment

................................ ................................ ........................... 20 4.1 Environmental Fate Assessment

................................ ................................ .................... 21 4.1.1 Water Quality

................................ ................................ ................................ .......... 22 4.2 Environmental Exposure Pathways

................................ ................................ ................ 24 4.3 Ecological Effects Analysis

................................ ................................ ........................... 24 4.3.1 Available Ecotoxicity Endpoints

................................ ................................ ............ 24 4.3.2 Open literature

................................ ................................ ................................ ........ 25 4.4 Exposure Analysis Plan

................................ ................................ ................................ .. 25 4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 25 4.4.2 Screening Level Down

- the

- Drain Analysis

................................ ............................ 25 5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 25 6 Optional Label Changes

................................ ................................ ................................ ........ 26 7 Next Steps

................................ ................................ ................................ ............................. 27 8 References

................................ ................................ ................................ ............................. 28

Appendix A T oxicology Profile

................................ ................................ ............................... 29 Appendix B Environmental Fate

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Page 6 of 60 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 52 Appendix D Physical and Chemical Properties

................................ ................................ ....... 56 Appendix E Comments Received Concerning the Preliminary Work Plan

............................ 57

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review: Creosote

................................ ................................ ................................ ................................ .......... 8 Table 2

– Anticipated Registration Review Schedule

................................ ................................ .. 10 Table 3

– Chemical Identification of Creosote

................................ ................................ ............. 10 Table 4

– Physical

- Chemical Properties for Creosote

................................ ................................ .. 11 Table 5

– Summary of Creosote Registered Uses

................................ ................................ ........ 12 Table 6

– Studies Anticipated as Needed for the Registration Review of Creosote

..................... 15 Table 7

– Data Needs Required by the September 22, 2011 Data Call

- In for the Creosote RED

. 16 Table 8

– Existing Toxicological Endpoints

................................ ................................ ................. 17 Table 9

– Occupational Handler Exposure Scenarios for Creosote

................................ .............. 19 Table 10

– Available Creosote Ecological Effects Endpoints

................................ ...................... 24Docket Number EPA

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Page 7 of 60 

## 1 Introduction

This document is the United States Environmental Protection Agency ’s ( USEPA, EPA or “the
agency ”) Final Work Plan ( F WP) for creosote . The F WP document explains what EPA's Office of Pesticide Programs (OPP) knows about coal tar creosote highlighting anticipated data and assessment needs, identifying the 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 200 8 Registration Eligibility Decision (RED), the creosote case included the following chemicals: coal tar creosote (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 w ere cancelled in February of 2013

. 1 As such, this registration 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 public participatio n component to solicit input from interested stakeholders. The agency intends, by sharing 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 t o receive as it moves toward a decision on
creosote

. 

## 1.1 Statutory and Regulatory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continu e to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the agency periodically re evaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided
at http://www2.epa.gov/pesticide

- reevaluation/registration

- review

- process

.
The agency is implementing the regi stration review 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 the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 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 registration review decision.



## 1.2 Updates to the Work plan

1 “Product Cancellation Orders for Certain Pesticide Registrations”, 78 FR 8513

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Page 8 of 60 Since the publication of the Creosote Prelim inary Work Plan (PWP), the agency has made the following updates:

• Updated the timeline in Table 2, the “Anticipated Registration Review Table.”

• Corrected the creosote application rate in Table 5.

• Updated neurotoxicity language in Appendix A

.

• Revised section 1.5.1 Registrations with the correct number of registrants.

• Updated section 3.1 with description of naphthalene as an endpoint.

• Revised section 4.1.1 with updated information on impaired water bodies.

• Revised Table 8 and Appendix A to reflect that the inhalation toxicological endpoint NOAEL is 4.7 mg/m3 and the LOAEL is 48 mg/m3

.

• Deleted “ Guidance for Commenters” section.

• Updated Section 7, “Next Steps.”

• Updated Appendix A with characterization of subchronic toxicity, 90

- Day Inhalation S tu dies.

• Added Appendix E, which includes the agency’s response to comments submitted regarding the PWP.

• Corrected formatting and typographical errors.

The agency received two submission s during the public comment period on the initial docket. See Appendix E for the agency’s response to th e s e comment s

.

Comments received did not result in a modification to t he anticipated data needs for the creosote work plan

. This document makes final the work plan for the creosote registration review process.



## 1.3 Case Overview
The PWP for creosote was published on March 30, 2015, and the 60

- day comment period ended on May 29, 2015. The agency received two submission s during the public comment period on the initial docket. Documents associated with this registration review case can be viewed
at http://www.regulations.gov in docket EPA

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. Tables 1 and 2 b elow summarize the issues relevant to this registration review case and the anticipated registration review schedule

.

Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review : Creosote

Risk Assessment A ssessment 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 detail s)

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

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Page 9 of 60 Risk Assessment A ssessment 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 detail s)

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 Post

Application 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

Resident ial 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 1.6.1 ) 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 Review. For data called in through the post

Reregistration Eligibility Decision (RED) Data Call

- In (DCI ), see Table 7

. 1 Data already required by the 2011 post

- RED Creosote DCI.Docket Number EPA

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Page 10 of 60 Table 2

– Anticipated Registration Review Schedule
Anticipated Activity Target Date * Completion Date Phase 1: Opening the Docket Open Docket and 60

- Day Comment Period for Preli minary Work Plan 2015

- 03 2015

- 03

- 30 Close Public Comment Period 2015

- 05 2015

- 05

- 29 Phase 2: Case Development

Issue Final Work Plan 2015

- 09 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 Pro posed 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).



## 1.4 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 0139 : creosote (PC Code 0 25004 )

.

Table 3

– Chemical Identification of Creosote

Chemical Name Creosote Chemical Classification Poly cyclic 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

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Page 1 1 of 60 USEPA’s document, “Guidance for Reregistration of Pesticide Products Containing Coal Tar Creosote” recognizes that “hundreds 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 (EPA 2008). These two fractions of creosote are derived by carbonizing coal through 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 information relevant to risk assessment 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 MRID Unless Specified

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 48480902 Product is liquid
830.7220 Boiling point ( o C) >180 48490902

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

830.7550 Octanol

- water partition coefficient at 25 o C (Log K ow ) 3.25 48480902

830.7840 Solubility in water (mg/L) 313 48480902

830.7950 Vapor pressure (mmHg) 11.1 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

. 

## 1.5 Use/Usage Description

1.5.1 Registrations

There are five creosote registrants holding a total of seventeen industrial wood preservative product registrations for wood protection as well as treating wood to be used in marine environments.

Currently there are 1 6 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 preservatives. Wood treated with these pre servatives 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. Indoor applications of creosote are prohibited as well as application to wood intended for use in interiors or for use in contactDocket Number EPA

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Page 12 of 60 with food, feed, or drinking water. These restrictions were imposed on creosote registrations as part of the a gency’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)

. 

### 1.5.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses 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

- 2 0 lb s /ft 3



### 1.5.3 Usage Information

According to the Kline Biocides Report for 2004/2005, c reosote 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).



## 1.6 Regul atory Histor y Creosote has been registered as a heavy duty wood preservative since 1948. Since creosote is derived from the distillation of coal tar, consists of hundreds of compounds, and has a variable composition, the American Wood Protection Associatio n (AWPA) established standards to differentiate between th e different 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 contribute d benefits to society and were eligible for reregistration provided the mitigation measures and associated label changes identified in the 2008 RED were implemented and required data were submitted. As mentioned in Section 1.5.1

, restrictions were imposed on creosote registrations as part of the a gency’s Special Review process

.
A post

- RED Generic

- Data Call

- In (GDCI) and Product

- Specific

- Data

- Call

- In (PDC I) were issued on September 22, 2011. For the status of these data, see Table 7

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### 1.6.1 Tolerance Information

For the active ingredient creosote, EPA has not established tolerances in raw agricultural commodities or processed food and feed products under the Federal Food, Drug and Cosmetic Act (FFDCA) Section 408. There are also no tolerance exemptions for creosote under FFDCA Section 408. Creosote has not been cleared as a food additive by the US Food and Drug Administration (US FDA) under FFDCA Section 409.



## 1.7 Incidents

1.7.1 Huma n 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, 201 5 covering the period from January, 1997 to January, 7, 2015. Over 28 incident reports exist in the Aggregate Incident Summary report. The last reported incident was i n August 2011. The associated human health effects include irritation effects to eyes, respiratory (chemical pneumonia), and ski n (blisters, erythema, and irritation). Other human health effects include muscle stiffness, dizziness, headache, fever and malaise. Whether these deleterious health effects result from exposure 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 report in registration review.



### 1.7.2 Ecological

As of December 22, 2014, the EPA/OPP Incident Data System (IDS) contains one aggregate incident summary from a creosote treatment facility in Pittsburg h , 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 A nticipated Data Needs

Several studies were required by the DCI following 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 review of creosote . Table 7 outline s the data requirements required by the post

- RED DCI issued on September 22, 2011

. The agency anticipates reviewing any data received in response to the post

- RED DCI as well as data requested for this registration review prior to conducting the registrati on review risk assessments for creosote

. The ecological toxicity studies anticipated to be required for registration review could be conducted using the leachate from the leaching study required by the post

– RED DCI in order to provide information for a ro bust assessment. Alternatively, information on effects on various taxa from monitoring studies conducted near aquatic sites could be submitted to allowDocket Number EPA

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Page 14 of 60 the agency to determine risks from in situ use of creosote. This information would need to address acu te and chronic effects in the water column as well as in sediments.Docket Number EPA

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Page 15 of 60 Table 6

– Studies Anticipated as Needed for the Registration Review of Creosote

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario

850.2100 1 Avian acute oral TGAI 12

Ecological

All Terrestrial environment 850.3020 Honey bee, acute contact toxicity 12 850.1010 Freshwater invertebrate, acute

TEP: Leachate from creosote pilings or railroad ties 24

Aquatic environment 850.1025

or 850.1055 Estuarine/marine bivalve, acute 12

850.1035 Estuarine/marine invertebrate, acute 12 850.1075 Estuarine/marine fish, acute 18 850.1075 Freshwater fish, acute 18 850.1300 Freshwater invertebrate, life cycle 12 850.1350 Estu arine/marine invertebrate, life cycle 12 850.1400 2 Freshwater fish, early life

- stage 12 850.1400 2 Estuarine /marine fish, early life

- stage 12 850.4225 3 Seedling emergence, semi

- aquatic plants 12 850.4400 Aquatic plants, vascular 12 850.4500 4 Algal toxicity (3 spp.) 12 850.4550 4 Cyanobacteria toxicity 12

870.7800 9 Immunotoxicity P1/P13 and P2 blends 12 Occupational worker Dermal and inhalation exposure to wood treatment workers None 5 ,6,7 Whole sediment, chronic, freshwater (2 spp.) TEP: Leachate from creosote pilings or railroad ties 24 Ecological Aquatic environment None 6, 7,8 Whole sediment, chronic, estuarine/marine 24

1 The anticipated DCI will provide that OECD TG 233 using the "LD 50
- slope test" or "limit dose test" can be used instead of OCSPP 850.2100 for certain species and conditions (e.g., causes no delayed effects, causes no regurgitation). Details on the species and conditions under which TG 233 would not fulfill the anticipat ed data requirement are described
at http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/review_avian_acute_oral _oecd_tg223.htm

2 The anticipated DCI will provide that t esting must be conducted with the most sensitive organism (either fres hwater or estuarine/marine vertebrates, or freshwater or estuarine/marine invertebrates), as determined from the results of the acute toxicity tests (acute EC 50 freshwater invertebrates; acute LC 50 /EC 50 estuarine and marine organisms; acute freshwater fish LC 50 ).
3 Test guidelines 850.4100 and 850.4225 were merged and harmonized into OCSPP 850.4100 in a Federal Register Notice dated June 27, 2012 (FRL

- 9333

- 1).

4 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850

– Ecological Effects Tests

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Av ailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

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Page 16 of 60 5 The anticipated DCI will provide that t he two species to be used to conduct this test are Hyallela a zteca and Chironomus dilutes. The anticipated DCI will provide that f or Hyallela

a zteca, c onduct study according to ORD Study Method EPA 600/R

- 099

- 064 but with 12 replicates per treatment (4 for 28

- d survival and growth and 8 for the remainder of the test) with 10 neonates per replicate , and f or Chironomus dilutus, conduct study according to ORD Study Method: EPA 600/R

- 099

- 020 but with 10 replicates per treatment with 20 neonates per replicate.

6 The preferred sediment is formulated, guidance for the formulated sediment can be found in OECD 218 Sediment

- Water Chironomid Toxicity Test using Spiked Sediment.

7 The anticipated DCI will require that a protocol must be approved by the a gency prior to t he initiation of the study.
8 The anticipated DCI will provide that t he species to be used to conduct this test is Leptocheirus plumulosus and to c onduct the study according to ORD Study Method: EPA 600/R

099

- 020 but with 10 replicates per treatment with 20 neonates per replicate

. 9 Studies should be conducted by the oral route.

Table 7

– Data Needs Required by the September 22, 2011 Data Call

- In for the Creosote RED

GLN Study Name Status of DCI 875.1100 Dermal exposure (outdoor) To comply with the data requirements , the registrant submitted a draft protocol study for Exposure of Workers to Creosote During Pressure Treatment of Lumber for review

. The agency is reviewing the protocol for this observational study. If the protocol and results from the ensuing study are approved, this study would satisfy the exposure study requirements for the creosote case (GLNs 875.1 1 00, 875.1200, 875.1300, 875.1400 , and 875.1600)

. 875.1200 Dermal exposure (indoor) 875.1300 Inhalation exposure (outdoor) 875.1400 Inhalation exposure (indoor)

875.1600 Applicator exposure monitoring data reporting 875.1700 Product use information No data have been submitted; this s tudy is outstanding

. Special Study

– Leaching Leaching s tudy for release of creosote components from creosote impregnated wood No data have been submitted; this s tudy is outstanding

.
Special Study

– Sediment Sediment concentration, Aquatic Structures No data have been submitted; this s tudy is outstanding

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Page 17 of 60 

## 3 Human Health Risk Assessment

The agency anticipates the need to conduct a new human health risk assessment for creosote based upon the updated exposure study data required by the 2011 post

- RED DCI

. Additional ly, immuno toxi city data are anticipated to be required to conduct this risk assessment for registration review. Because creosote is currently registered for use in occupational settings, occupational handlers have the potential to be exposed by the dermal and inhalation routes through the pressure treatment process.

EPA plans to estimate cancer and non

- cancer risk s to occupational handlers as a result of inhalation and dermal ex posure to creosote during the pressure treatment process

. 

## 3.1 Existing Toxicological Endpoints

Table 8 p resents the endpoints used in the agency’s most recent human health risk assessment for creosote in support of the 2008 RED. An i mmunotoxicity study is identified as a n anticipated data need for the registration review for creosote. Based on worker risk es timates available at the time of the 2008 RED, naphthalene was used as a surrogate for creosote, as it was the only detectable component fr o m monitoring performed at pressure treatment facilities. All available information including existing toxicology studies, valid scientific literature, and the studies that are expected to be required for registration review will be considered in establishing the endpoints to be used in the registration review risk a ssessment. A detailed description of the existing database of toxicity studies is provided in Appendix A

.

Table 8

– Existing Toxicological E ndpoints

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 = 4.7 mg/m 3 MOE = 100 90

- day inhalation toxicity study with P2 creosote (MRID 43600901); decreased body weight and weight gain, altered hematology a n d clinical chemistry, increased absolute and relative weight of the liver a n d thyroid, and increased incidence of lesions of the nasal cavity at 48 mg/m 3Docket Number EPA

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Page 18 of 60 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

Inhalation

– naphthalene (short

- , intermediate

- , and long

- term) LOAEL = 52 mg/m 3 MOE = 300 Two year inhalatio n 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 3

Dermal absorption Absorption value of 5%, determine d 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 preservative s . These uses are not expected to result in direct or indirect dietary (food) exposure. T he use of creosote as a wood preservative is not expected to result in exposures to creosote in drinking waters; therefore, a drinking water assessment is not required at this time.



### 3.2.1 Food

No dietary exposure is expected from the registered uses of creosote

. Therefore, the agency does not anticipate the need to conduct a dietary 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 not 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 will mainly be due to the presence of PAH

containing materials in water storage and distribution systems ( EPA , Technical Factsheet on: Polycyclic Aromatic Hydrocarbons).



## 3.3 Occupational and Residential Exposures
The agency anticipates the need to revise the 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 neithe r permitted to be purchased nor expected to be applied by potential residential users. Since no residential handler uses are expected from the use of creos o te , a residential risk assessment is not required. Additionally, EPA will not be assessing residen tial post

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### 3.3.1 Occupational Handler Exposure

The agency conducted an occupational assessment for the RED for creosote on September 5, 2008 (EPA 2008 c ). The occupational assessment was based on doses for occupational wood pressure treatment workers using chemical

- specific dermal and inhalation monitoring data submitted by the Creosote Council III (MRID 45323401).

As a result of the risks of concern identified in the RED, the agency identified label change s intended to reduce exposure to creosote workers in wood treatment facilities. In an effort to determine if those mitigation measures are effective in reducing exposure, the agency issued a post

- RE D DCI requiring that new exposure monitoring studies be conducted at wood treatment facilities using personal protective equipment (PPE) and engineering controls identified in the 2008 RED.

The agency recently received a n observational protocol 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 that will help the agency to determine new exposures based on the new engineeri ng control measures specified in the RED. The scenario outlined in Table 9 would encompass the typical worker exposure scenarios for a variety of job functions within a wood treatment facility

. For example, for pressure treatment facilities, workers operate and monitor application system valves and controls, open and close cylinder doors, and supervise 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 onto charge trams; move charges into and out of treatment cylinders; remove charge leads and bands from treated wood; distribute treated wood to load

- out a rea, and load treated wood for shipment. Workers also perform various labor and cleanup duties in treatment and drip pad area including: sweeping and pressure

- washing drip pad and tracks; removing and shredding all bands from treated stacks of lumber; pick ing up and disposing treated wood waste; 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 Inhalation Short, Intermediate, and Long Term



### 3.3.2 Occupational Post

- Application Exposure

There is potential exposure to linem e n and other workers installing or maintaining creosote treated utility poles. Railroad workers may also be exposed during the installation of railroad ties. Because m echanical installation (e.g. railroad ties) and/or the use of appropriate PPE are recommended to reduce exposure/contact with creos ote treated wood ( EPA 2008c)

, t he ag ency does not anticipate the need to conduct an occupational post

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### 3.3.3 Residential Handler Exposures

C reosote , which is a restricted use pesticide, is neither permitted to be purchased nor expected to be applied by potential res idential users. Therefore, residential exposure is not expected from the wood preservative uses of creosote and a residential risk assessment is not anticipated to be needed for this registration review

.


### 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. R ailroad ties are used for fuel for co

- ge neration plants and there would be no residential exposure for that particular use. However, railroad ties may resold for

use in residential s ettings (e.g. landscaping )

. Such reuse of creosote

- treated wood is not subject to regulation by EPA under FIFRA; however, l andscape retaining walls are not expected to be areas of frequent contact , and any contact with landscaping timbers is expected to be episodic in nature. Addit ionally, old railroad ties would likely have significantly less transferable creosote th a n freshly treated wood ( EPA. 2008c )

. As a result

, the agency does not anticipate significant exposure to occur and will not conduct a residential post

- application ris k assessment.



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

C reosote is not registered for any food use, and it was also determined that cr eosote is not likely to impact the diet or drinking water

. Additionally, r esidential exposures are not expected. Therefore, an aggregate exposure and risk assessment is not anticipated to be needed for
creosote.



### 3.4.2 Cumulative Exposures A cumulative exposure and risk assessment for creosote was not perform ed for the 2008 RED

. EPA has not made a common mechanism of toxicity f inding 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 tha t creosote has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism 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 registration review will allow the a gency to determine potential acute and chronic risks to aquat ic 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 dete rmination for the antimicrobial uses of creosote. The registration review risk assessment will allow the a gency to determine whether each use has 'no effect' or 'mayDocket Number EPA

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Page 21 of 60 affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its de signated critical habitat, the a gency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (t he Services), as appropriate.

The a gency conducted a preliminary environmental risk assessment for the 2008 RED (EPA 2008 a, b ). The uses assessed were railroad ties and aquatic structures. Because no guideline ecotoxicity studies have been submitted, t he assessment was based on the limited ecotoxicity data information available in the open literature.

The 2008 risk assessment concluded that

, a lthough there are many PAHs in creosote, many occur only in minor amounts. The agency identif ied eight 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 aquatic organisms and detection in available monitoring data.

Although the literature is not compre hensive for any of the eight PAHs for acute and chronic toxicity to freshwater and estuarine/marine fish, pelagic and benthic invertebrates, and aquatic plants, the a gency concluded that there are potential risk s 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 site. One year after pilings we re installed in Sooke Basin, an assemblage of invertebrate organisms inhabited the creosote

- treated pilings, suggesting minimal long

- term impacts to some non

- listed species.

Laboratory and field investigation found a major detrimental impact on hatching an d 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 likel y to vary locally, depending on abiotic and biotic factors such as current speed, amount of structure per unit area, air and water temperature, salinity, and the aquatic species occurring in the immediate 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 movement of PAHs into the aquatic environment.



## 4.1 Environmental Fate Assessment

C reosote 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 identifiable substances) consisting of simple PAH s , multi

- aromatic fused rings, cyclic nitrogen

- containing heteronuclear compounds, and phenolic substa nces. It is estimated that about 85 percent of the creosote mixture consists of PAHs and the remainder consists of cyclic heteronuclear nitrogen andDocket Number EPA

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Page 22 of 60 oxygen

- containing molecules. Since the PAHs constitute 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

, creosote normally does not contaminate the air. The major route of exposure is from PAHs leaching from treated wood into surrounding soil or water column s.
Degradation of the PAH components can occur by both abiotic and biotic mechanisms. PAHs do not undergo abiotic hydrolysis based on the chemical structure and the lack of hydrolyzable functional groups. However, PAH s can readily photodegrade in water because these compounds absorb UV light. P hotooxidized products of PAHs can be stable and persist 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 aerobic conditions, therefore degradation will be slower in anaerobic sediments. D egradation also occurs more readily for the PAHs that have fewer rings (2

- and 3

- ring compounds) versus the 4

- or 5

- ring compounds (Karthikeyan an d 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 molecu lar weight are more mobile than those of higher molecular weight

. However, even the low er molecular weight compounds have limited movem ent in soil ( Villholth, 1999)

. PAH residues around treated wood (railroad ties, utility poles) are expected to be highe r than those further from treated wood. In water, PAHs with more rings (e.g. acenaphthe ne) are more likely to sorb to sediment and bioconcentrate in aquatic organisms than those with fewer rings

, including naphthalene, 1

- methyl naphthalene, and 2

- methyl naphthalene (Godsy et al., 1992)

. L eaching from treated wood tends to occur in the first 7 days and is higher under flooded conditions (Bestari et al., 1998 a )

. For more information on the environmental fate of creosote,

see Appendix B.



### 4.1.1 Water Quality
Based on the Office of Water (OW) website, t otal Maximum Daily Loads (TMDL) have not been developed for creosote as a mixture. 2 Additional information on impaired water bodies and TMDLs from individual PAHs may be found at EPA’s website

. 3 While impairments from individual PAHs do exist, none can be conclusively linked to the use of creosote.

The OW identifies several PAHs contained in creosote as causes for impairment. These P AHs include naphthalene, 2

- methylnaphthalene, and Indeno[1,2,3

- Cd]Pyrene

. 4 Naphthalene is listed as a cause of water body impairment for one stream in California, two streams in New Hampshire, and one stream in Washington State unde r section 303(d) of the Clean Water Act

. 5 However, for streams with naphthalene concerns, there were differences in the listed number of

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

3 http://www.epa.gov/owow/tmdl/

4 http://iaspub.epa.gov/tmdl_waters10/attains_n ation_cy.cause_detail_303d?p_cause_group_id=885

5 http://iaspub.epa.gov/tmdl_waters10/attains_impaired_waters.control?p_cause_name=NAPHTHALENEDocket Number EPA

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Page 23 of 60 PAHs of concern. For the New River in California, naphthalene was listed as the only PAH of concern and the source of contamination was unknow n. 6 However, for the New Hampshire (Cocheco and Lamprey Rivers) and in the Washington Stream, other PAHs were also listed as impairments. The source of naphthalene impairment for the Cocheco River is unknown, and the stream appears to receive storm sewer drainage and overflows that may contain PAHs from sources other than creosote. 7 The Lamprey River also contains storm sewage outflows and oil and gas activities that have the potential to contain PAHs, but the source of some PAHs was unknown. 8 The Duwam ish Waterway in Washington includes impairments for numerous PAHs with no known source. 9

2

- Methylnaphthalene is listed as a cause of water body impairment for the Los Angeles harbor in California, three streams in New Hampshire, and one stream in Washing ton State unde r section 303(d) of the Clean Water Act

. 10 For the Los Angeles Harbor (Consolidated slip), several PAHs were listed as impairments with an unknown source of contamination. 11 In addition to the Cocheco and Lamprey Rivers in New Hampshire above, the Ashuelot River at the Fisk Mill h ydro electric plant 12 is also impaired because of numerous PAHs with an unknown source. 13 The Duwamish Waterway in Washington (see above) includes impairments for numerous PAHs with no known source. 14

Indeno[1,2,3

- Cd] Pyrene is listed as a source of impairment for four water bodies in New Hampshire and two water bodies in Washington State. 15 In addition to the Ashuelot and Cocheo Rivers in New Hampshire discussed above, the Taylor River at Rice Dam Pond 16 and at Taylor Ri ver Refuse Pond 17 have impairments for numerous PAHs with an unknown source. For

6 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=CAR7231000019990205102948&p_cycl e=&p_report_type = 7 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=NHEST600030608

- 01&p_cycle=&p_report_type = 8 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=NHEST600030709

- 01&p_cycle=&p_report_type = 9 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=WANONE_47122F3F4_NW&p_cycle= &p_report_type = 10 http://iaspub.epa.gov/tmdl_waters10/attains_impaired_waters.control?p_cause_name=2

- METHYLNAPHTHALENE

11 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=CAB4051200020000229082107&p_cyc le=&p_report_type = 12 http://lowimpacthydro.org/lihi

- certificate

- 46

- ashuelot

- lower

- robertson

- hydroelectric

- projects

- ferc

- s

- 7791

- and

8235/ , hydroelectric dam on the Ashuelot River

13 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=NHIMP802010403

- 04&p_cycle=&p_report_type = 14 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=WANONE_47122F3F4_NW&p_cycle= &p_report_type = 15 http://iaspub.epa.gov/tmdl_waters10/attains_impaired_waters.control?p_cause_name=INDENO[1,2,3

- CD]PYRENE

16 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=NHIMP600031003

- 19&p_cycle=&p_report_type = 17 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=NHLAK600031003

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Page 24 of 60 Washington, in addition to the Duwamish Waterway listed above, Eagle Harbor also has PAH impairments from an unknown source. 18



## 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 surrounding treated railroad ties and other treated wood and might be transported into the aquatic environment via various environmental
pa thways, including runoff and leaching. Creosote

- treated wood used directly in the aquatic environment will leach PAHs directly into surface waters and sediments. H eavier PAHs reaching the aquatic environments are expected to bind to organic matter and se diments and potentially expose benthic invertebrates. Lighter PAHs will mostly occur in the water column and may potentially expose fish, aquatic invertebrates, 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 Exposure Pathways of Antimicrobial Pesticides ” are located in the docket at www.regulations. gov (EPA

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- 0002). For “ In

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



## 4.3 Ecological Effects Analysis

4.3.1 Available Ecotoxicity Endpoints

E cotoxicity studies conducted in accordance with the 850 OCSPP Harmonized Test Guidelines to address the data requirements for pesticide registration are not currently available for creosote. Some supplemental data are available in the OPP Ecotoxicity D atabase for creosote. The anticipated ecotoxicity data requirements for creosote are specified in more detail in Appendix C. Available endpoints, and data gaps for each receptor group, are listed below. For a co mplete list of the ecotoxicity data anticipated to be required in registration review, see Table 6

.

Table 10

– Available Creosote Ecological E ffects 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

--

18 http://iaspub.epa.gov/tmdl_waters10/attains_waterbody.control?p_list_id=WA1224819475188_47122G5C0&p_cy cle=&p_report_type =Docket Number EPA

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Page 25 of 60 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

-- Nontarget insects TGAI Acute Data gap

--
1 These studie s are considered supplemental. Data are anticipated to be required. 

### 4.3.2 Open literature

O pen literature studies also will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched when the risk assessment is prepared. A ny acute or chronic endpoints more sensitive than what is currently available will be used in the risk assessment and risk characterization. Information on the a gency’s use of open literature is foun d on th e a gency’s website : http://www.epa.gov/pesticides/science/efed/policy_guidance/ team_authors/endangered_species_ reregistration_workgroup/esa_evaluation_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 (EE Cs) in the aquatic environment

. Resulting exposure estimates will be compared to the toxicity endpoints to determine if levels of concern are exceeded for each receptor group.



### 4.4.2 Screening Level Down

- the

- Drain Analysis

The a gency does not anticipate the need for a Down

- the

- Drain (DtD) assessment because the

c reosote treated wood at the site of the treatment is dried with a drain pad underneath and any leaked chemical is recycled for use. Remaining chemical in the pad (if any) must be treated as a hazardous w aste 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 nu merous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,Docket Number EPA

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Page 26 of 60 reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive lo ss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the 2008 RED for creosote , EPA reviewed t hese 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 Disruptor Scree ning Program (EDSP).

EPA has developed the EDSP to determine whether 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 other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estro gen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effe ct.
Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert in gredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 19 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 o r likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 20



## 6 Optional Label Changes

Th e agency invites any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/ or improve label clarity.

19 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

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- 2009

- 0477

- 0074 for the final second list of

chemicals.

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## 7 Next Steps

A DCI will be developed regarding the data needs listed under the “Anticipated Data Needs” section of this document. The agency expects to issue the DCI by September 2016

.Docket Number EPA

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## 8 References

Bestari, K.T. Jim et al. 1998a. Distribution 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.

Cha pman, P.J. et al. 1995. Fossil Fuel Biodegradation: Laboratory Studies. Environ. Health Perspec. 103, Supplemental 5:80

- 83.

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

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

EPA. 2008b. Reregistration Eligibility Decision 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: Polycyclic Aromatic Hydrocarbons (PAHs)

. http://www.epa.gov/ogwdw/pdfs/factsheets/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 microcosms: a review. Journal of Hazardous Substance Research. 3:3

- 19.

Kirso, U. et al. 1991. Ph otochemical oxidation of PAH and heteroaromatic analogues in different model conditions. Polycyclic Aromatic Hydrocarbons: Proceedings of the Thirteenth International Symposium on Polynuclear Aromatic Hydrocarbons.

Kline, 2005. Specialty Biocides North Am erica 2004

- 2005, Volume II: United States, Kline and Company, Inc.

Villholth, K.G. 1999. Colloid characterization and colloidal phase partitioning of polycyclic aromatic hydrocarbons in two creosote

- contaminated aquifers in Denmark. Environ. Sci. Technol. 33:691

- 699.Page 29 of 60 

# Appendix A T oxicology Profile

The agency anticipate s the need to require immunotoxicology data for creosote

. 

## Acute Toxicity for Product Labeling

Acute toxicity studies available for labeling purposes have been summarized in Table s 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 430321 01 LD 50 male= 2451 mg/kg ; female = 18 93 mg/kg III

870.1200/ Acute dermal toxicity 430321 02 LD 50 male and female: > 2000 mg/kg III

870.1300/ Acute inhalation toxicity 430321 03 LC 50 > 5 mg/L IV

870.2400/ Acute eye irritation 430321 04 Irritation clearing in 8

- 21 days I I

870.2500/ Acute dermal irritation 430321 05 Erythema to day 14 I II

870.2600/ Skin sensitization 430321 06 Study unacceptable * Y
*Even though dermal sensitization studies were unacceptable, it is assumed that 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 I II

870.2500/ Acute dermal irritation 43032305 No irritation after 7 days I II

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 30 of 60 

## Subchronic Toxicity

T here are dermal subchronic (90

- day) toxicity 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 treatment

related effects from dermal application of P1/P13 creosote on b ody 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 test

article 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 guideline requir ement (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 given dermal applications of P2 creosote in corn oil at dosage levels of 0, 4, 40 or 400 mg/kg bw/day. There was no mortality observed in this study at any dose lev el. Body weight in high dose males was decreased 7

- 8% during weeks 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 decreased during weeks 2

- 4 and week 6 by 4

- 10% vs

c ontrol. Only slight dermal irritation was observed in high dose males. No effects were observed on hematology or clinical chemistry. Treated skin in the 400 mg/kg/day dose groups (male and female) was observed with increased incidence of dermal inflam m at ion. 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 were not ed in any of the treated groups.

This study is classified as acceptable and satisfies the guideline 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 Inha lation Toxicity Studies

There are 90

- day inhalation toxicity studies available for the P1/P13 blend (MRID 43601001) and P2 blend (MRID 43600901). These studies are summarized below.

Executive Summary (P1/P13 blend) : In a subchronic inhalation toxicity st udy with P1/P 13 creosote (MRID # 43601001), 20 Sprague

- Dawley rats/sex/group were treated for thirteen weeks, five days a week, six hours pe r day with P1/P13 Creosote CTM via whole body exposurePage 31 of 60 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 between 2.2 and 3.0 microns with a geometric standard deviation between 1.91 and 1.99. Subsequent to the exposure peri od 10 animals/sex/group were a llowed to recover for 6 weeks. During the study one male rat of the mid dose group (49 mg/m 3 ) died from myocardial degeneration that resulted in heart failure. One male and one female rat in the highest dose group had similar lesions observed at terminal necropsy. . Significant trea tment

- related findings in the mid and high dose animals after the exposure period included decreased body weight gains of both sexes (resolved by the end of recovery period), altered hematological parameters (decreased hemoglobin, hematocrit, numbers of er ythrocytes, increased numbers of reticulocytes, polychromasia, poikilocytosis, anisocytosis

- both sexes) and biochemical parameters (increased serum cholesterol levels

- both sexes, phosphorous levels

- males only). Macroscopic discolouration of the lung s, which persisted throughout the recovery period, was correlated with the presence of black pigment granules within alveolar macrophages of animals of all treatment groups. An increase in liver/brain weights (statistically significant only in the females ), increased lung/trachea/body weight ratios and the presence of small cystic spaces containing basophilic mucoid material in the nasal cavity epithelium was still evident after the recovery period in both sexes.

Male and female rats of the low dose group were 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 low dose animals showed recovery.

Based on the results of this study, the systemic LOAEL is 49 mg/m 3 for both sexe s, based on cardiac pathology, decreased body weight gain, altered hematology and clinical chemistry, and gross pathological findings in the lungs. The syste mic NOAEL is 5.4 mg/m 3 (0.005 mg/L) for P1/P13.

This study is classifi ed as acceptable (guideline) and satisfies the guideline requirement ( OCSPP 870.3465) for a subchronic inhalation toxicity study in rats . No additional data 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 for 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 ani mals (low dose female; mid dose male) were sacrificed in extremis and the cause of morbidity was not related 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 cholesterol levels, m/f). In both sexe s macroscopic discolouration of the lungs persisted through the recovery period and correlated with the presence of black pigment granules within alveolar macrophages. Both sexes showed increased absolute and relative liver and thyroid weights and increas ed lung/trachea/body weight ratios.Page 32 of 60 Absolute and relative thyroid weights of high dose animals actually increased after the recovery period. An increased incidence of lesions of the nasal cavity epithelium (chronic inflammation) was noted following treat ment (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 hypertrophy occurred in all male g roups 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 cell hypertrop hy was slightly increased in low and mid dose females after the recovery period. Slightly increased incidence of mild poikilocytosis was observed in all treatment groups (m/f) including the low dose group and control, which persisted through the recovery p eriod. 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 a n d clinical chemistry, increased absolute and relative weight of the liver a n d 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 a cceptable (guideline) and satisfies the guideline requirement (O CSPP 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 toxicity study using P1/P1 3 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 the high dose (although mean fetal weight was not affected). Cesarean section observations showed significantly increased resorptions and post

implantation 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 L OAEL is 175 mg/kg/day, based on decreased body weight gain and food consumption during the study.

No treatment

- related malformations (external, visceral or skeletal) were observed in any of the fetuses at 25 mg/kg bw/day. At 50 mg/kg bw /day, 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 significant increased incidence of developmental malformations, (ii) increased incidence of cardiovascular, vertebral and digital malformations, compared to lower dose levels, concurrent controls or historical co ntrols (2429 and 2898 fetuses examined viscerally and skeletally respectively) and (iii) an increased incidence of malformations at this dose level in spite of increased fetal loss (resorptions) (Beck and Lloyd,Page 33 of 60 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 (decreased body weight gain and food 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 developmental toxicity LOAEL is 175 mg/kg/day, based on increased post

- implantation loss, increased mean resorptions, decreased live fetuses p er litter, and increased developmental malformations.

In a developmental toxicity study in rabbits (MRID 44839802), artificially inseminated New Zealand White Rabbits (20/dose) were administered 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 rabbits vs. 0 control), reduced live fetuses (28 vs. 50 in control), and decreased implantation sites were noted in maternal rabbits. There was no sig nificant 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 effects 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 creosote. 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 dose levels of 0, 25, 75, and 225 mg/kg/day. Although decreases in body weigh t and food consumption were observed at all dose levels, food efficiency appeared affected only at the high dose of 225 mg/kg/day. Thus, the cesarean section effects observed at this dose (decreased implantations/dam, increased pre

- and post

- implantation l oss, increased resorptions, decreased uterine weight) could be secondary to the decreased food efficiency observed at this dose. This distinction is a fine one, however, based on results with P1/P13 creosote in which no decrease in food efficiency was obs erved at a dose of 175 mg/kg, but increased resorptions, increased post

- implantation loss, and decreased live fetuses per litter were observed at 175 mg/kg. The Maternal NOAEL in this study is determined to be 75 mg/kg/day, and the LOAEL 225 mg/kg/day, ba sed 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 [craniorachischisis, hydrocephaly and malpositioned eye (same pup)] observed at the 75 mg/kg bw/day dose level, and hydrocephaly at the 225 mg/kg bw/day dose level compared to none observed in lower do se levels, concurrent 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 fe tuses examined at this level for visceral and skeletal malformations was approximately 50% of those examined at the mid

- dose level. The developmental toxicity NOAEL is determined to be 25 mg/kg/day in this study, based on the incidences of malformations o bserved at 75 mg/kg/day which exceeded both concurrent and historical control incidence.Page 34 of 60 This study is classified as acceptable and satisfies the guideline requirement (83

- 3) for a developmental toxicity study in rats with P 2 creosote. No additional dat a are anticipated to be required. 

## Reproductive Toxicity

T here is one study available for reproductive toxicity of the 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 reproduction t oxicity 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 contributed to the decreased fertility observed in this study. S ystemic effects observed in this study for parental animals included a dose

- related decrease in body weight during the pre

- mating period at all dose levels. Salivation w as observed at 75 mg/kg/day and above in the F1 generation. Effects in offspring incl uded a dose

- related decrease in growth of the F0 generation starting at 25 mg/kg/day (as shown by decreased pup weight). For the F0 pups, mean number of live pups per litter was decreased at 75 and 150 mg/kg/day, and percent live pups at 175 mg/kg/day was also decreased. 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 weight. Decreased fertility and pregnancy indices were observed in the F1 female parental 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 s tudy, the Parental Systemic NOAEL is < 25 mg/kg/day, and the parental systemic LOAEL is 25 mg/kg/day, based on decreased pre

- mating body weight. The developmental NOAEL in this study is < 25 mg/kg/day, and the developmental LOAEL is 25 mg/kg/day, based on a dose

related 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 guideline requirement ( 870.3800 ) for a developmental toxicity study in rats with P1/P13 creosote. No additional data are anticipated to be required. 

## Chronic Toxicity /Carcinogenicity

T he chronic toxicity/carcinog enicity data base submitted to the a gency for creosote consists of a six

- month initiation/promotion study of creosote conducted in mice (MRID 44844401), and a published study by Culp et al. (1998)

. The six month initiation/promotion study was not designed for purposes of deriving a quantitative risk estimate of carcinogenic potency. The study of Culp et al. (1998) did examine tumors induced by coal tar mixtures and was ued for quantitative cancer assessmentPage 35 of 60 Executive Summary (P1/P13 blend) : In a submitted dermal carcino genicity study (MRID 44844401), North American P1/P13 creosote composite (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 undiluted creosote to the shaved backs of the mice. Acetone was utilized as a solvent throughout 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

- tetradecanoyl p horbol

- 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 wit h DMBA and TPA, and acetone controls groups with DMBA and 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 irrita

tion and clinical signs including severe erythema, slight edema, eschar, and exfoliation. Increased incidences of thickened skin (7

- 11/30, p < 0.01), scabbing (16

- 20/30, p < 0.01), acut e inflamma tion (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 application site during necropsy compared to the DMBA/ace tone controls (0/30). Dermal treatment with c reosote did n ot result in a significant decrease in survival, although 6 mice died during 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 initiation phase were decreased by 6

- 8% by the end of the 2

- week treatment regimen; however, they gained weight 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 consumptio n in the experimental groups was generally greater than in the solvent control groups.

Increased incidences of enlarged lymph nodes were seen with 50% (6/30, p < 0.05), and 100% creosote (5

- 9/30, p < 0.05

- 0.01) during the promotion phase with DMBA as in itiator 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 increased (15

- 19/30, p < 0.01) with 50% and 100% creosote in the promotion phase compar ed to the controls (1/30).

The LOAEL is 50 μL of 50% or 25,000 μg/day twice/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 fo r 26 weeks.

Topical treatment of male Crl:CD

- 1 ® mice for 2 weeks in the initiation 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 con trol, 0%; creosote/TPA treated, 80

- 90%, p < 0.01). Treatment twice a week for 26 weeks during the pro motion phase with 50 μL of 500 μg/μL or undiluted creosote following the DMBA initiation phase resulted in tumor incidences of 100% compared to 3% in the D MBA/acetone control. Topical treatment with undiluted creosote in both the initiation and promotion phases resulted in a 100% tumor incidence compared to 0% in the acetone control group. Creosote acted as an initiator, promoter, and complete carcinogen u nder the conditions of this study.Page 36 of 60 This carcino genicity study in the mouse is a cceptable/ n onguideline. The study had numerous deficiencies that limited the information obtainable on possible systemic toxic effects, but the data demonstrated unequivocally the oncogenic nature of creosote when applied to the skin of Crl CD

- 1 ® mice. The deficiencies did not affect this outcome of the study, which was designed to assess the skin tumor initiating, promoting, and complete carcinogenicity of creo sote.

Executive Summary ( two coal tar mixtures and pure benzo[a]pyrene (BaP) ) : In an oral

carc inogenicity study conducted by Culp et al. (199 8 ), the carcinogenicity of two coal tar mixtures and pure benzo[a]pyrene (BaP) was studied. Coal tar mixture 1 (CTM

- 1) was a composite of coal tar samples from seven coal gasification plant waste sites and wa s dosed at 0.0, 0.01, 0.03, 0.1, 0.3, 0.6, and 1.0% of diet. Coal tar 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 with pure BaP at 0, 0.0005, 0.0025, and 0.01 % in diet. A control group received solvent control in diet. Each group consisted of 48 mice

. In mice exposed to coal tar, coal tar acted as a systemic carcinogen and induced a dose

- related increase in hepatocellular adenomas and carcinomas, 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 increased sharply between the 0.1 and 0.3% doses. However, there was not a proportional increase in forestomach tumors above 0.3% because these mice died from adenocarcinomas of the small intestine. Tumors of the eso phagus, observed in BaP treated mice, were not observed in the 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, forest omach, 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 dose d with ≥ 0.3% CTM

- 1 or CTM

- 2 had significantly 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 and/or carcinomas of the forestomach, esophagus

an d tongue. The incidence of forestomach tumors increased steeply between 5 and 25 ppm, equivalent to 20.5 and 104 μg BaP/day. Tumors of the esophagus were not observed in the CTM1 or CTM

- 2 treated groups. Lung and hepatocellular tumors, observed in CTM t reated 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, respectively, fed 100 ppm BaP. It should be noted that all animals in 100 ppm group died before termination of the study.Page 37 of 60 This carcinogenicity study in the mouse is acceptable/nonguideline. The study contained information useful for deriving a quantitative estimate of cancer potency for creosote. 

## Mutagenicity

In consideration of the available evidence that creosote is a positive mutagen, the a gency waived the requirement for the standard mutagenicity battery, and instead required dominant lethal testing of both the P1/P13 and P2 blends , which 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 assay (MRID not available), male HSD:Sprague

- Dawley CD rats were treated orall y 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 wer e 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 with one or more dead implantations, proportion of females with two or more dead implantations 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 mat ed females, was also determined.

Creosote P1/P 13 was tested to toxic doses. In the dominant lethal study, all rats in the top two treatment groups but none in the low dose group showed decreased activity following dosing and all rats in the high dose group had dyspnea. Two animals in the low dose group and two in the high dose gr oup had material around the nose and mouth. Other pharmacotoxic signs were limited to a few animals in the high dose group and included lacrimation, deposition of the test material around the eyes, increased salivation and anogenital staining. One high do se rat died following the fourth dose. A dose

- related decrease in body weight in the low

- , mid

- , and high

dose animals, compared to the solvent controls, was seen during the dosing period, and this initial weight loss was not recovered in mid

- and high

- do se rats during the ten week mating period. Statistically significant differences from control values were seen in a number of endpoints throughout the study; however, 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 implantations per female, the percentage of females with
≥ one implantation, the percentage of females with ≥ two implantations and the percent dead impl antations per total implantations. These increases were seen at the low and mid doses but not at the high dose. Also, the vehicle control values in mating group nine were unusually low compared to those in the other weekly mating groups (there were 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) and values for percentage of females with ≥ one an d two dead implantations and the percent dead implantations per total impla ntations were depressed). The results, although statistically significant, are thus not considered biologically significant. Positive and solvent control valuesPage 38 of 60 were appropriate e xcept where noted for the vehicle controls in mating group nine. Based on the results of this study, there was no evidence that Creosote P1/P13 induced dominant lethals in any germ cell stage in male rats as tested in this study. No additional data are a nticipated 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 19 3.75 mg/kg body weight/day in a volume of 2.5 mL/kg. Actual doses by chemical analysis 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 d ays 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 l utea per female, preimplantation losses per female, live implantations per female, dead implantations per female, proportion of females with one or more dead implantations, proportion of females with two or more dead implantations and dead implantations/to tal 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 treatment 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 lacrimation, deposition of the test material around the eyes and increased saliva tion in one high

- dose male, labored breathing in one low

- dose male and two high

- dose males, and material around nose and mouth in two low

- dose, one medium

dose and four high

- dose males. Reduced food consumption was seen in all high

- dose rats. No dosing

- or test material

- related deaths occurred during the study. A dose

- related decrease in body weight in the low

- , mid

- , and high

- dose animals, compared to the solvent controls, 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 signifi cant differences from solvent control values (p ≤ 0.05) were seen for a number of end points 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 increase 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 implants. In the tenth mating group (exposure to the test material at the spermatogonial stem cell stage), an apparently dose

- related in crease 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 percentage of dead implantations per total implantations. The increases reached stati stical significance at the highest dose for the first two endpoints. Positive and solvent control values were appropriate. The data in this study, while indicating a positive effect at week 10 of treatment, are not considered to be treatment

related, bas ed on the conclusion that while dead implantations per female was significantly increased at the highest dose tested at mating week 10, the number of live implants/female was not significantly reduced (<5% lower than control). In addition, no dominant let hal effects were seen at weeks 8 or 9, which would also sample spermatogonial cells. Therefore, creosote P2 isPage 39 of 60 considered to be negative for dominant lethal effects in rats. No additional data are anticipated to be required. 

## Other Toxicological Effects

Neurotoxicity

There are no current a gency guideline neurotoxicity studies available for creosote. The existing experimental animal studies on the P1/P13 and P2 blends of creosote submitted to and evaluated by the agency indicate no evidence of neurotoxicity for either the P1/P13 or P2 blends of
creosote. Data from the 2002 ATSDR Toxicological profile for Creosote showed increased brain

- to

- body weight ratios after exposure 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 o f male and female rats for 96 weeks in the diet to 143 and 394 mg/kg/day, respectively. Acute exposure of male and female rats to 600 and 313 mg/kg beechwood creosote resulted in convulsions. In rats exposed by inhalation for 5 weeks to 690 mg/m 3 creosote or for 13 weeks to 140 mg/m 3 creosote, no neurological effects were noted. No effects were noted in mice exposed by inhalation to 690 mg/m 3 creosote for 13 weeks.

A more recent published case study of toxicity from inhalation of creosote vapors showed evidence of neurotoxicity (Heimstra et al., J Med Case Reports. 2007; 1: 102 ). In this instance, neurotoxicity was observed in a 56 year old female who had chronically inhaled creosote vapor. Symptoms included proximal muscle weakness, ataxia, a wide

- bas ed gait, blunted affect, and evidence of memory impairment. These symptoms may have been secondary to renal impairment from creosote vapor inhalation which was directly diagnosed, but they are also consistent with those from other aromatic hydrocarbons. H owever, the dose which resulted in neurotoxicity is unknown, and is only of a single individual.

Based on the current registration of creosote as a restricted use pesticide for non

- food uses only, neurotoxicity data are not anticipated to be required, as the available data indicate no evidence of neurotoxicity, or neurotoxicity only at doses significantly higher than the endpoints currently selected for regulation of creosote risk.

Dermal Absorption

Dermal absorption of creosote was assessed through rev iew 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 sk in preparations (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 intended for terrestrial, fresh water, and marine use and has the greatest potential for dermal exposure. A protocol was submitted to the agency a nd approved prior to conduct of these studies.Page 40 of 60 Executive Summary (P1/P13 blend) : In a n in vivo dermal penetration study (MRID 47179501) AWPA P1

- P13 Creosote (98.5% a.i.) spiked with eight radiolabeled target chemicals (approx. 43% of the chemicals in cre osote) was applied 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 wa s eight hours. At the end of 8 hours, animals were removed from the metabolism cages, and the application sites were washed with 2% Ivory soap solution followed by a water rinse and then a dry natural sponge. Four rats were then euthanized (0 hours post

- exposur e) while the other four rats were returned to the metabolism cages for further excreta collection. These four rats were sacrificed at 496 hours post

- exposure.

The mean percent recovery of the radioactivity 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

- exposure group and 56.822% (±8.294%) for the 496

- hr post

- exposure group. The mean percent absorbed dose was 6.342% (±0.808%) at 0 hours post

exposure 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 aft er removal 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 penetrati on study intended to clarify the results for the 496 post

exposure group in the initial main study, AWPA P1

- P13 Creosote (98.5% a.i.) spiked with eight radiolabeled target chemicals was applied to the shaved dorsal skin (10.5 cm 2 ) of four male Sprague

- Dawl ey 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 study, the O

- ring, which demarcated t he application area, was applied without glue following the dose application, and was removed at the end of the 8

- hr exposure. In the main study, the O

- ring had been glued to the skin one day prior to dose application and remained in place until study term ination.

In the supplemental study, the mean percent recovery of the radioactivity in the applied dose was 92.775% (±2.70%) at 496 hours post

- exposure. The majority 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 absorbed 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 signi ficant amount of radioactivity in the body wrap after 8 hours adds uncertainty as to the actual available 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 fe cal excretion of radioactivity from 8 hours onward. Therefore, the data are not conclusive of a reduced dermal absorption based on the contention that the O

- ring or the glue had an influence on dermal absorption.

In a preliminary plasma kinetic (dermal bioavailability) study, neat creosote 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 sacrificed 168 hours post

- d osing (160 hours post

-Page 41 of 60 exposure). None of the twelve target creosote chemicals 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 concent ration were evaluated, this was part of an agreement in study design between the agency and the registrant. No additional data are anticipated to be required.

In an in vitro dermal absorption study using rat and 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 preparations mounted in individual 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

- application. The skin was washed 8 hours post

application and the study terminated. The amount of the applied dose absorbed was considered to be the amount of radioactivity measured in the receptor fluid.

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 derm al 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 dermal absorption of creosote, using available in vivo dermal absorption data: b ased on (1) the lack of data demonstrating that the concentration of the creosote solution did not exceed solubility limits and therefore did not have an artefactual influence on the magnitude of absorption in the in vitro test system, and (2) the continued absorption observed after eight hours in the in vivo study [the O

- ring influence could not be conclusively demonstrated to be acting as a depot for radioactivity]), the agency’s conclusion was to use the value of 34% from the in vivo 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 for all uses of antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for Antimicrobial Pesticide Data Requirements (78 FR, no. 89, 26978, May 8, 2013)

. It is an anticipated data requirement for registration review. The expected data call

- in notice will provide that t he registrant can address this d ata requirement by submitting a study according to the OCSPP 870.7800 guideline, citing information from the scientific literature that adequately addresses immunotoxicity of creosote , or submitting a request for waiver of this study using the agency’s pub lished guidance, available
at: http://www.epa.gov/pesticides/regulating/part158

- tox

- data

- requirement.pdf

.Page 42 of 60 Toxicology References for Appendix A

MRID 43032101: North A merican P1/P13 Creosote: Acute Oral Toxicity Study in Rats. Study

c onducted by IRDC, Mattawan, MI for the Cre osote Council II. Unpublished. HED document no. 011033.

MRID 43032102: North American P1/P13 Creosote: Acute Dermal 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: Acute Inhalation Toxicit y 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 Irritation Study in Rabbits. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished

. HED document no. 011033.

MRID 43032105: North American P1/P13 Creosote: Primary 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: Dermal Sensitization Study (Buehler) in the Albino Guinea Pig. Study conducted by IRDC, Mattawan, 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 Cr eosote Council II. Unpublished. HED document no. 011033.

MRID 43032302: North American P2 Creosote: Acute Dermal Toxicity Study in Rats. Study

co nducted by IRDC, Mattawan, MI for the Creosote Council II. Unpublished.

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

MRID 43032304: North American P2 Creosote:Eye Irritation Study in Rats. Study conducted by IRDC, Mattawan, MI for the Cr eosote Council II. Unpublished. HED document no. 011033.

M RID 43032305: North American P2 Creosote: Primary Dermal Irritation Test in Rabbits.Study conducted by IRDC, Mattawan, MI for the Cr eosote Council II. Unpublished. HED document no. 011033.

MRID 43032306: North Amer ican P2 Creosote: Dermal Sensitization Study (Buehler) in the Albino Guinea Pig. Study conducte d by IRDC, Mattawan, MI for the Creosote Council II. Unpublished. HED document no. 011033.Page 43 of 60 MRID 43601001: North American P1/P13 Creosote: Thirteen Week Subchronic Inhalation Toxicity Study on North Ameri can P1/P13 Creosote CTM in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 67 1

- 016 (1995). Unpublished.

MRID 43600901: North American P2 Creosote: Thirteen Week Subchronic Inhalation Toxicity Study on North American P2 Creosote 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. Repo rt No. 671

- 013 (1995). Unpublished.

MRID 43616201: North American P2 Creosote: 90 Day Sub chronic Dermal Toxicity Study in Rats. Study conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No. 671

- 014 (1993). Unpublished.

MRID 43584201: Nor th American P1/P13 Creosote: Developmental 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. St udy 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 Creosote: 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: F asano, W. (2007) AWPA P1

- P13 Creosote: In vitro kinetics in rat and human skin. E.I. du Pont de Nemours 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 Registry (1990): Toxicological Profile for Creosote. U.S. Department of Health and Human Services: Public Health Service. McMahon, Timothy F.: Creosote: Endpoint Selection Report. February 2008. Unpublished.

Culp, S.J., Ga ylor, D.W., Sheldon, W.G., Goldstein, L.S., and Beland, F.A. (1996): DNA adduct measurements in relation to small intestine and forestomach tumor incidence during the chronic feeding of coal tar or benzo[a]pyrene to mice. Polycyclic Aromatic Compounds 11, 161

- 168.Page 44 of 60 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 tar 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.

Heimstra, T.F., Bellamy, C., and Hughes, J.H. (2007): Coal tar creosote abuse by vapour inhalation presenting with renal impairment and neurotoxicity: a case report. J. Med. Case Reports 1: 102

McMahon, Timothy F.: Creosote: Endpoint Selection 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/Fertility Study in Rats. Study conducted by IRDC, Mattawan, MI for Koppers Industries , Pittsburgh, PA. Report no. 672

- 006. Unpublished.Page 45 of 60 

# Appendix B Environmental Fate

The agency does not anticipate the need to require 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 a gency conducted an open literature search for environmental fate and transport studies on the creosote mixture and based the as sessment on the PAH constituents only. In this appendix , the a gency is summarizing the contents of the RED.

The environmental fate and transport of creosote as addressed here focuses pr imarily on the likely exposure of PAHs into three environmental compartments: 1) leaching of creosote mixture into surface and ground waters from the railroad ties and utility 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. Microbial degradation and volatility are expected to be more rapid for those PAHs with fewer rings. Photodegradation in water is also a primary route of dissipation for those PAHs in water.

Water and Sediment

Hydrolysis

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

Aqu eous Photoly s is

PAHs can readily photodegrade in water because these compounds absorb UV light. Howe ver, photooxidized products of PAHs can be stable, and can persist in air/water and soils and become an environmental concern as these photooxidized 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 significant route of dissipation. In general, the potential for b ioconcentration of PAHs increases as the number of rings increases , but sorption to sediment and the lack of water solubility may limit the actual bioconcentration of higher molecular weight compounds. Most of the bioconcentration data for creosote PAHs was associated with Superfund sites and environmental spills and not laboratory studies that were specifically targeted to measure biocon cen tration based on known water concentrations

. Southworth et al.Page 46 of 60 (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.

Creoso te Behavior with Sediment and Ground Water

Mueller et al. (1993) studie d the removal of Group 1, 2, and 3 PAHs 21 from contaminated
gr oundwater in Florida over 32 days. Group 1 PAHs include known carcinogens (only member is benzo(a)pyrene (5

- rings), Group 2 PAHs include “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 naphthalene. Shocken and Gibson (1984) demonstrated degradation of acenaphthene and 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 that PAHs were not detected in ground water at depths >12 meters at the same abandoned wood treatment site. Mueller e t al. (1991) determined that lower

- molecular weight PAHs in groundwater degraded faster (half

- lives of ~3 days) while higher molecular

- weight PAHs degraded slower (half

- lives of ~14 days).

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

Some of the PAHs, particularly those that have 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 naphthalene (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. However, i f the octanol/ water coefficients (K ow ) is high, and if the PAHs are desorbed from the soils/sediments to which they are bound, some of these PAHs can become bioaccumulative to the benthic organisms.

Volatility from Soil

F ew studies are reported in the op en literature on field volatilities 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 measurable fluxes of acenaphthene and fluorene (3

- ring PAHs) were only detected using a soil cover with low organic content, indicating sorption.

Aerobic Soil Metabolism

21 Carex Canada, http://www.carexcanada.ca/en/polycyclic_aromatic_hydrocarbons/Page 47 of 60 Most of the PAHs have a tendency to biodegrade un der aerobic conditions. It has been reported that over eighty percent of biodegradation 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 biodegr adation. A number of aerobic soil metabolism studies on PAHs conducted at various contaminated sites as well as in simulated microcosms reported that low molecular weight PAHs generally metabolized in aerobic conditions and the greater the oxic environmen t, the higher the biodegradation level. Chapman et al. (1995) determined that 72 % of low

molecular weight PAHs were degraded after washing creosote

- contaminated soil. Hurst et al. (1996) found that after 7 days, 45 and 55 % of PAHs mineralized in 2 and 21 % oxygen, respecti vely.

A n a erobic Soil Metabolism

Genther et al. (1997) studied the anaerobic soil metabolism of PAHs and demonstrated that only anthraquinone (3

- rings) and 2

- methyl anthracene (3

- rings) demonstrated any degradation under anaerobic conditions.

Volatility from Treated Wood

Exposure to air do e s not seem to be an important factor in the environmental behavior for most PAHs. While Gevao et al. (1998) showed that acenaphthene, fl uorene, phenanthrene, anthracene, and fluoranthene volatilized at a faster rate at 30 ° C than at 4 ° C

, 85 percent of these components remained in the wood after seven weeks. The rate of volatilization was slow for acenaphthene (half

- life, one year) and fl uoranthene (half

- 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 microbial populations.

Leaching from Treated Wood

Guideline d ata on leaching of creosote components from treated wood were required in a post

RED DCI ( GDCI

- 025004

- 30249 ) and have not been submitted. 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., 1998 a )

. In a terrestrial microcosm, 95 % of PAHs in Ponderosa pine blocks were present 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, and 5

- ring compounds were found in soil

.Page 48 of 60 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. Microbio l. 1649

- 1655.

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

- 1006.

Bestari, K.T. Jim et al. 1998b. Distribution and composition of polycyclic aromatic hydrocarbons within experimental microcosms treated with creosote

- impregnated douglas fir pilings. Environ. Toxicol. Chem. 17(12):2369

- 2377.

Bieri, R.H. et al. 1986. Polycyclic aromatic hydrocarbons in surface se diments 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 Environmental Fate of 129 Priority Pollutants, EPA

440

- 4

- 79

- 029a,b.

Elder, J.F. and P. Dresler. 1988. Accumulation and bioconcentration of polycyclic aromatic hydrocarbons in a nearshore estuarine environment near a Pensacola (Florid a) creosote contamination site. Environmental Pollution. 49:117

- 132.

Electric Power Research Institute (EPRI). 1992. Document EPRI TR

- 01000870.

Ehrlich, G.G. et al. 1982. Groundwater. 20(4):703

- 710.

Flyvberg, J.E. et al. 1993. J. Contamin. Hydrolo gy. 12:133

- 150.

Fowler, M.G. et al. 1993. Preliminary results from a field experiment investigating the fate of some creosote components in a natural aquifer. Org. Geochem. 22:641

- 649.

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

- 659.

Gevao, B. a nd 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. Environ. Sci. Tech. 19(10):955

- 961.

Grbic

- Galic, D. et al. 1991. Anaerobic degradation of aromatic hydrocarbons and aerobic degradation of trichloroethylene by subsurface microorganisms. In: Organic Substances and Sediments in Water, R.A. Baker, Ed., Lewis Publishers, Michigan:239

- 266.Page 49 of 60 Harris, J.C. 1982. Handbook of Chemical Property 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 hy drocarbons 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. Aqueous Pha se Biodegradation Kinetics of 10 PAH Compounds. Environmental Engineering Science 20(3) :207

- 218.

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

Lindhardt, B. and T.H. Christensen. 1996. Volatilisation of aromatic hydrocarbons from soil : part II, fluxes from coal tar contaminated soils residing below the soil surface. Water Air Soil Pollution. 92:375

- 389.

Long, E.R. et al. 1995. Incidence of adverse biological effects within ranges of chemical concentrations in marine and estuarine s ediments. Environ. Management. 19:81

- 97.

Mabey, W. et al. 1982. Aquatic Fate Process for 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, Flo rida; 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 porewater partitioning of polycyclic aromatic hydrocarbons in three cores fr om 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 industrialized estuary. Environ. Sci. Technol. 19:597

- 603.

Middaugh, D.P. et al. 1991. Archives of Environ. Contamin. pp. 244

- 254.

Mihelcic, J.R. et al. 1988. Appl. Environ. Microbiol. 54:1182

- 1187.

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

- 1293.

Miller, M.M. et al. 1985. Environ. Sci. Technol. 19:522

- 529.

Mississippi State University. 1981. Cooperative Agreement Number 12

- 156.Page 50 of 60 Mueller, J.G. et al. 1991. Biodegradation of creosote in contaminated groundwater: chemical and biological assessment. Applied and Environmental Microbiology. 57(5): 1277

- 1285.

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

- 698.

National Oceanic and Atmosp heric Administration (NOAA). 1988. A Selected Summary of Data of Chemical Contaminants in Sediments Collected During 1984

- 1987, NTIS.

Neff, J.M. et al. 1976. Marine Biology. Volume 38:279

- 289.

Padma, T.V. et al. 1999. Toxicity of creosote water

- solub le fractions generated from contaminated sediments t the bay mysid. Ecotoxicology and Environmental Safety. 42:171

- 176.

Politzer, I.R. et al. 1985. Impact on Human Health of Petroleum in the Marine Environment, American Petroleum Institute (API), Washi ngton, 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 oxidation of the polycyclic aromatic hydrocarbons acenaphthene and acenaphthylene. Appl. Environ. Microbiol. 48(1):10

- 16.

Smith, J.H. et al. 1978. Environmental Pathways of Selected Chemicals in Fresh Water Systems: Part II. Laboratory Studies: 304. EPA

- 600/7

- 78

- 074, USEPA, Athens, Georgia.

Southwor th, R.G. 1977. Aquatic Toxicology, ASTM 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. Sedime nt bioassessment in Halifax Harbour. Environmental Toxicology and Chemistry. 11:1567

- 1581.

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- 289.Page 51 of 60 Wan, M.T. 1994. Utility right

- of

- way contaminants: polycyclic aromatic hydrocarbons. J. Envir on. Quality. 23:1297

- 1304.

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

- 37.

Zepp, R.G. et al. 1980. Assessing the photochemistry of organic pollutants in aquatic environments. In, Dynamics, Exposure and Hazard Assessment of Toxic Chemicals. R. Haque, Ed. Ann Arbor Sci. Publ. Inc., Ann Arbor, Michigan: 69

- 110.Page 52 of 60 

# Appendix C Ecotoxicology Profile

The ecotoxicity database is incomplete. The agency anticipates the need to require ecotoxicity data for registration review (for 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 insects to support the u se of creosote as a wood preservative. The guideline for an acute toxicity test (850.3020) is not satisfied. At this time, t he

a gency 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

a cute toxicity testing with freshwater fish (cold

- water and warm

- water species) is not satisfied.
D ata are anticipated to be needed for the ecological 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 (marine creosote) is highly to very highly toxic toPage 53 of 60 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 freshwater 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 very highly toxic to estuarine/marine organisms. These data can be used to help characterize the toxicity of creosote to estuarine/marine organisms, but they do not satisfy the guidelines for fish (850.1075), bivalve (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035). These data are anticipated to be needed for the ecological risk assessment for liste d 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 anticipated to be needed for one fish and one invertebrate species. The expected DCI will provide that t esting 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 freshw ater 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. T he guideline for a freshwater invertebrate life cycl e test (850.1300) or estuarine/marine mysid life cycle test (850.1350) is notPage 54 of 60 satisfied. These data are included as studies anticipated 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 guidelines for testing with duckweed, a vascular sp. (85 0.4400), three algal spp. (850.4500), and cyanobacteria (850.4550) are not satisfied. A seedling emergence toxicity test with rice also is needed; the guideline (850.4225) is not satisfied. These data are anticipated to be needed for the ecological risk assessment for listed and nonlisted plants.

Benthic Invertebrates, chronic

No sediment

- toxicity data are available for creosote. Based on environmental fate properties discussed in Appendix B, creosote is expected to accumulate and persist in aquatic sedi ments. 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 invertebrates. There currently is no guideline number for this test.Page 55 of 60 Ecotoxici ty References for Appendix C

40228401 EPA. 1986. Acute Toxicity Handbook of Chemicals 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. 19 73. Toxicity of C & P Creosote to rainbow trout. Fish Toxicity Lab. Report, Animal Biology Lab., EPA

- PR, ARC, Beltsville, MD. ID No. MB 189.

TN 0542 EPA. 1973. Toxicity of C & P Creosote 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., Washing ton, DC.Page 56 of 60 

# Appendix D Physical and Chemical Properties

The creosote product chemistry information is summarized in Table D 1

.

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

.Page 57 of 60 

# Appendix E Comments Received Concerning the Preliminary Work Plan

On March 30, 2015, EPA opened a 60

- day public comment period on the PWP for the registration review of cre osote. The comment period ended on May 29, 2015. During the public comment period the agency received two submission s. Table E1 below lists the submitter s

.

Table E1. Submitters of Comments on the “Creosote Preliminary Workplan”

California Regional Water Quality Control Board, San Francisco Bay Region Creosote Council III (CCIII)

Submitter: California Regional Water Quality Control Board, San Francisco Bay Region

1.) Comment: “ Because approved creosote uses have caused or contributed to impairment of a number of water bodies, we commented on the previous creosote registration review in 2004; these comment letters are attached, as they remain relevant to this registration review. Five water bodies in the San Francisco region alone remain on the Clean Water Act Section 303(d) list of impaired waters due to polycyclic aromatic hydrocarbons (PAHs) likely attributable to creosote use. We request that all §303(d) listings for PAHs nationwide be included in the current reg istration review. We appreciate that the current registration review (preliminary workplan) recognizes potential impacts on herring from creosote

- treated pilings. However, Section 4 of the workplan appears to indicate that EPA is focused on literature pertaining on ly to the eight PAHs identified thus far as potential concerns to aquatic organisms. We request that all scientific literature related to acute and chronic toxicity associated with any PAHs be reviewed in order to better understand the water quality im pact s of these chemical mixes. ”

AD Response : The agency has previously responded to the aforementioned comment s received from the San Francisco Bay Regional Water Quality Control Board in 2008. A copy of the response will be placed in the docket for reference

. With regards to the PAHs to be considered in the creosote risk assessment, EPA is focused on risks to aquatic organisms exposed to the material leached from treated wood structures. The composition of the leachate was not known in 2008, and thus the major PAHs in creosote were used for the risk
assessment. As stated in Table 7 of the Creosote PWP, EPA is requiring a “ Leaching study for release of creosote components from creosote impregnated wood ” to identify the composition of the leachate. The lea chate identified in that study is the test material to be used in the ecotoxicity studies being required in Table 6. The risk assessment planned in Registration Review will use the information from these studies to assess acute and chronic risks. Any rel evant open literature also will be used to characterize risks of creosote leached from wood structures.Page 58 of 60 Submitter: Creosote Council III (CCIII)

1.) Comment : “ Page 10, paragraph 1.4

– Use/Usage Description. The Preliminary Work Plan states that there are six creosote registrants holding a total of 17 registrations. This is no longer the case. There are now five creosote registrants (listed above), which collectively hold 15 creosote registrations. Of those, 14 are for end

- use products, and 1 is for a manufactu ring

- use product. ”

AD Response : The agency has amended section 1.5.1 to say there are five registrants. The agency’s database shows 17 active registrations for the five registrants. Of these registrations, 16 are end use products and one is a manufacturin g use product. Two registrations were previously owned by KMG Bernuth, and have been transferred to Koppers Inc.

2.) Comment: “ Page 11, Table 5

– Summary of Creosote Registered Uses. The correct creosote application rate is 6

- 20 lbs/ft 3 , not 6

- 12 lbs/ft 3 as the table indicates.”

AD Response : The agency thanks the CCIII for this information. Table 5 has been revised to reflect th e correct application rate

.
3.) Comment: “ Page 12, Section 2, Anticipated Data Needs

– As EPA is aware, CCIII already is in the pro cess of developing creosote wood treater worker exposure data and creosote ecological toxicity data. A draft protocol for the worker exposure study and a randomized list of candidate wood

- treating plant sites have been provided to the Antimicrobials Division for its review. Formal validation for analytical chemistry methods is nearly complete. Approval for the study has been received from the EPA and Canadian PMRA institutional review boards. Site visits with workers, union representatives, plant management, and the Study Director and Quality Assurance consultant are underway. The formal study is expected to begin within 60

- 90 days, if not sooner.

AD Response : The agency thanks the CC III for these study updates.

4.) Comment: “ Table 6

– Studies Anticipated as Needed for the Registration Review of Creosote The majority of studies listed in Table 6 of the Preliminary Work Plan are aquatic toxicity studies, and as noted in the Plan, these gui delines studies are not available. CCIII has conducted an environmental assessment at the installation site of new creosote

- treated harbor pilings. The assessment includes toxicity studies on surface water, column water, and sediment. The Council is submitting reports of those studies and supporting analytical chemistry to the Agenc y under separate cover. (See item 7.0 below) CCIII requests that EPA reconsider its need for the aquatic toxicity, phytotoxicity, and leachate studies listed in Table 6 of the Preliminary Work Plan following review of the environmental studies that the Council is submitting at this time. Also, CCIII seeks a waiver for the avian acute oral toxicity and the honey bee acute oral toxicity testing requirements listed in Table 6. The description of these studies in Appendix C, Ecotoxicity Profile, of the Preliminary Work Plan indicates that both studies are to be conducted by the oral route of exposure and that aPage 59 of 60 honeybee study of creosote residue on wood is not needed at this time . It is not clear to the Council how honeybees or birds would come into contact with liquid creosote since that material is used only in creosote wood treating plants and is contained in tankage or pressure vessels at all times. For this reason the Council is requesting a waiver from the requirements to conduct acute toxicity studies in birds and honeybees.”

AD Response : When the CCIII is ready to submit this data, the EPA will consider it. To submit existing studies that ha ve not been previously submitted , CCIII can respond to the registration review DCI with option four

, “ s ubmitting an existing s tudy” . T he agen cy will assess whether the Moss Landing data identified in this comment and in comment number seven satisfy the data requirements identified in Table 6. With regards to the waiver request for the avian acute oral toxicity, the study is required for all antimicrobial active ingredients and t he data are used to determine if precautionary labeling is needed. The bee study is required for all antimicr obial active ingredients with a wood preservative use pattern

. T he CCIII can submit formal waiver request s once the registration review DCI is issued and the agency will consider the waiver request s at that time.

5.) Comment: “ Page 14 Table 7

– Data Required by the September 22, 2011 Data Call

- In for the Creosote RED. The Agency notes in the Preliminary Work Plan that no data have been submitted for Product Use Information, Guideline 875

- 1700. The registrants would like clarification from the Agency o n this data requirement since it appears that no guideline is available for Product Use Information. ”

AD Response : T he EPA needs product use information on how the pesticide under review is actually used and applied in the field or around the home. For product use information guidance, please see guidance for guidelines ( GLN ) 875.2700 and GLN 875.2800 . The following link to the Mar ch 1998 Post Application Exposure Guidelines presented to the Scientific Advisory Panel provide s guidance for these guidelines ( Chapters 11 and 12 ) : http://www.epa.gov/scipoly/ sap/meetings/1998/march/contents.htm

. In the absence of precise data, ranges or estimates are acceptable if a supporting rationale is provided.

6.) Comment: “ Page 15, Table 8

– Existing Toxicological Endpoints

. The NOAEL listed in Table 8 for Inhalation (shor t

- , intermediate

- , and long

- term) is 0.0047mg/m 3 and the MOE = 100. The table goes on to say that this NOAEL is based on the CCIII report (MRID 43600901) for a 90

- day inhalation study of P2 creosote in rats. Table 6 also states that toxicological effects i n that study were observed at a creosote exposure of 0.048mg/m 3 . The measured exposure concentrations in that inhalation study, however, were 0, 4, 7, 48 and 102mg/m 3 and the NOAEL was 4.7 mg/m 3 , not 0.0047mg/m3, as stated in Table 8. The toxicological effects listed in Table 8 were observed at an ex posure of 48mg/m 3 , not 0.48mg/m 3 .”

AD Response: The agency thanks the CCIII for these corrections. Table 8 and Appendix A have been revised to reflect that t he NOAEL is 4.7 mg/m 3 and that th e LOAEL is 48 mg/ m 3

.
7.) Comment: “ In January 1994 the Moss Landing Harbor District in Moss Landing, California began replacement of aging pilings with new creosote

- treated pilings. During pilingPage 6 0 of 60 installation, samples of surface water (creosote sheen), column water, and sediment were collected at new piling sites and at a reference control site. The water samples and sediment elutriate were tested in a seven

- day static renewal toxicity test with Mysidopsis bahia

. Sediment samples were tested in a 10

- day static acute toxic ity test with Ampelisca abdita. The work was conducted in five phases over a 16 month period. Extensive chemical characterization of samples was performed with each sampling. The reports for this work, “Environmental Assessment of the Impact of Creosote

- Tr eated Pilings on Seawater and Sediment Collected at Moss Landing Harbor,” are being submitted to the Agency for document processing. ”

AD Response: Please see the agency’s response to CCIII’s fourth comment in this Appendix.

8.) Comment: “ Page 28, Subchronic Toxicity, 90

- Day Inhalation Studies

... The text in this section of the Preliminary Work Plan goes on to state that ‘ cardiac pathology (i.e., hemorrhage, lymphocytic infiltration and cardiomyopathy) was noted in all animals of all groups (including controls) and this condition may have been exacerbated by treatment with creosote in the mid

- and high dose animals. ’ This is an overstatement of what was reported in the study. Cardiac pathology was seen in three animals at terminal sacrifice. Hemorrhage and lympho cytic infiltration (inflammation) occurred without cardiac pathology in the respiratory tissue and liver of other animals. No animal had cardiac lesions following the recovery period. The Study Director made the following statement in the study report, ‘ On e exposure

- related mortality occurred during this study. One Group III male died during study week 4 of complications involving heart lesions identified in the histopathologic evaluation. The relative significance of this one mortality should not be overst ated. This was one animal that died out of twenty males at an early stage of the study. Although the animal appeared in good health at the start of the study, it started losing body weight during the week prior to death. It is possible that this animal had an unknown preexisting condition which was aggravated by the exposure conditions leading to the fatal heart lesions”.

AD Response: The agency thanks the CCIII for this comment. Appendix A’s summary of the inhalation study has been amended to reflect the cardiac pathology effects observed in the study

.