Page 1 of 31 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460

OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVENTION

PC Code: 0 38501

DP Barcode: D429589

Date: December 9, 2015

MEMORANDUM

SUBJECT: Registration Review: Combined Problem Formulation and Environmental Fate

, Ecological Preliminary Risk Assessment and Endangered Species Assessment for Diphenylamine

TO: Roy Johnson , Chemical Review Manager

Jill Bloom

, Team Leader Risk Management and Implementation Branch 5

Pesticide Re

- Evaluation Division (7508P)

FROM: Andrew Sayer, Ph.D., Biologist Cheryl Sutton, Ph.D., Environmental Scientist

Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

REVIEWED

BY: T h om as Steeger, Ph.D., Senior Advisor

James N. Carleton, Ph.D., Senior Fate Scientist

Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

THROUGH: Jean Holmes, D.V.M., M.P.H., Branch Chief

Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

The Environmental Fate and Effects Division (EFED) has c ompleted a combined problem

formulation and preliminary environmental fate and ecolo gical risk assessment in support of the Registration Review of diphenylamine ( PC Code 038501 ; CAS No: 122

- 39

- 4 ) as a plant growth regulator

.

EFED examined the most recen t environmental fate and ecological risk assessment written in support of the 1997 Reregistration Eligibility Decision ( RED ) for diphenylamine in association with updated toxicity, exposure, and usage information to determine if additional data are needed to support the Registration Review of diphenylamine . In addition, EFED considered the latest Agency science policies and risk assessment methodologies

. Because the database was- Page 2 of 31

- determined to be sufficient to assess the ecological risk for the sole registered use of diphenylamine , the preliminary risk assessment has been combined with the problem formulation

for R egistration R eview

. EFED’s understanding of the underlying fate and effects of diphenylamine have not changed since the earlier assessment in 1997 and no additional data are required at this time given the limited use of the compound as a post

- harvest treatment ; therefore, this preliminary risk assessment does not differ substantially from the previous

, and the reader is

referred t o the earlier document for a more detailed discussion of the available data.

Risk Conclusions

Diphenylamine is plant

- growth regulator registered for use as a post

- harvest treatment on appl es to prevent fruit scald. The chemical is classified as an indoor/food use pesticide, and is applied using truck or bin drenching, or thermal fogging. Diphenylamine is hydrolytically stable, but readily degrades via photolysis in water and through atmospheric oxidation. It transforms in

aerob ic soil, but forms dimers and polymers that may be more stable than the parent compound. It is only slightly mobile in soil, but may volatilize from soils and surface water.

Diphenylamine is classified as moderately toxic to freshwater fish , aquatic

- pha se amphibians,

and freshwater invertebrates on an acute exposure basis, and practically non

- toxic to birds

, reptiles and terrestrial

- phase amphibians on an acute oral and subacute dietary exposure basis. Diphenylamine is practically non

- toxic to mammals o n an acute exposure basis, but effects have been observed in chronic studies and include reduction in mean body weights, body weight gains, changes in hematological parameters, splenic/kindey lesions, and increased signs of clinical toxicity. No studies h ave been submitted for estuarine/marine organisms, terrestrial invertebrates, terrestrial and aquatic plants ; however, minimum exposure of these taxa to didphenylamine given its current limited use as a post

- harvest treatment is expected . Chronic

studies h ave not been submitted for taxa other than mammals. No additional relevant data were identified in the open literature

.

The results of this preliminary risk assessment are similar to those identified in the environmental fate and ecological risk assessment written in support of the R ED for diphenylamine in 1997

. Diphenylamine is classified as an “ indoor / food ” use chemical and EPA does not generally conduct quantitative ecological risk assessments for indoor /food use chemicals for which there are no significant exposure pathways to non

- target organisms

. G iven

the use pattern s ( i.e ., truck or bin drenching with collection of drench water, or thermal fogging in an enclosed, sealed indoor space) , the environmental fate properties (rapid photolysis, rapid

biotic transformation in soil , and rapid atmospheric oxidation of volatilized compound), and the limited amount of diphenylamine that will be available for environmental expo sure as a direct result of these application methods , the likelihood of adverse effects on ecological systems from the post

- harvest treatment use is considered to be minimal. Discharge of effluent containing diphenylamine is regulated by National Pollutant Discharge Elimination System (NPDES) permits. Disposal of drench water collected following application is not assessed here, as it is regulated under NPDES.- Page 3 of 31

- Based on the low likelihood of exposure, EFED has made a No Effect (NE) determination for Federally threatened or endangered ( hereafter referred to as “listed” ) species and their designated

critical habitat

.

Uncertainties

There is some degree of uncertainty surrounding the environmental fate of diphenylamine

. Although more data are availab le than typically are for indoor / food use pesticide s
, which require only hydrolysis data, there is not a full environmental fate dataset. Additionally, complete information regarding the transformation products via biotic metabolism is not available.

How ever, risk uncertainty associated with the lack of environmental fate data is offset by the fact

that potential environmental exposure is expected to be minimal due to diphenylamine’s use as a post

- harvest treatment . Exposure potential is further reduced by diphenylamine’s lability to photolytic and atmospheric oxidative degradation processes , particularly if the chemical is

vented into the atmosphere as a vapor following thermal fogging. Although there is uncertainty concerning the environmental fate of the comp o und and its exposure potential associated with
post

- use disposal, drench wastes disposal is regulated under the NPDES permitting system and

has not been further evaluated in this assessment

.

Provided that use of diphenylamine as currently specif ied on the label s does not change, no

additional data are recommended at this time.

## Combined Problem Formulation

, Environmental Fate

, Ecological Preliminary Risk Assessment and Endangered Species

Assessment for the Registration Review of Diphenylamine

CAS 122

- 39

- 4 PC Code 038501

November 20 , 2015

Prepared b y Andrew Sayer, Ph.D., Biologist Cheryl Sutton , Ph.D., Environmental Scientist U.S. Environmental Protection Agency Office of Pesticide Programs

Environmental Fate and Effects Division (EFED)

Environmental Risk Branch IV 1200 Pennsylvania Ave., NW

Mail Code 7507P Washington, DC 20460 Reviewed by Thomas Steeger, Ph.D., Senior Science Advisor James Carleton, Ph.D., Senior Fate Scientist Jean Holmes, D.V.M., M.P.H., Branch Chief- Page 5 of 31

- 

## Table of Contents

1. Executive Summary

................................ ................................ ................................ .............. 7

2. Problem Formulation

................................ ................................ ................................ ......... 8

2.1. Conclusions from Previous Risk Assessments

................................ ................................ 8

2.1.1. Ecological Risk Assessment

................................ ................................ ...................... 9

2.1.2. Drinking Water Exposure Assessments

................................ ................................ .. 9

2.1.3 Clean Water Act Programs

................................ ................................ .......................... 9

2.2. Nature of Regulatory Action

................................ ................................ ...................... 10

2.3. Stressor Source and Distribution

................................ ................................ .............. 10

2.3.1. Nature of the Chemical Stressor

................................ ................................ .......... 10

2.3.2. Overview of Pesticide Usage

................................ ................................ ................ 10 2.4. Receptors

................................ ................................ ................................ ................... 11

2.4.1. Aquatic and Terrestrial Effects

................................ ................................ ........... 11 2.4.2. Ecosystems Potentially at Risk

................................ ................................ ......... 11

2.5. Assessment Endpoints

................................ ................................ ................................ 12 2.6. Risk Hypotheses

................................ ................................ ................................ ......... 12 2.6.2. Potential Exposure Pathways and Effects

................................ .......................... 13 2.7. Analysis Plan

................................ ................................ ................................ .............. 13 2.7.1. Measures of Exposure

................................ ................................ ........................ 13

2.7.1.1 Measures of Aquatic and Terrestrial Exposure

................................ ................................ ........ 13 2.7.2. Measures of Effect

................................ ................................ .............................. 13 2.8. Preliminary Identification of Data Gaps

................................ ............................ 14 3. Analysis

................................ ................................ ................................ .............................. 14

3.1. Use Characterization

................................ ................................ ................................ .. 14

3.2. Exposure Characterization

................................ ................................ ........................ 15

3.2.1. Environmental Fate and Transport Characterization

................................ ...... 15

3.2.1.1. Transport and Mobility

................................ ................................ ................................ ............ 17

3.2.1.3. Field Studies

................................ ................................ ................................ ............................ 17

3.2.1.4. Bioaccumulation

................................ ................................ ................................ ...................... 17

3.2.1.5. Transformation Products

................................ ................................ ................................ .......... 18 3.2.2. Measures of Aquatic Exposure

................................ ................................ ............ 18

3.2.2.1. Estimated Environmental Concentrations in Surface

................................ ............................... 18

3.2.2.2. Monitoring Data

................................ ................................ ................................ ....................... 19 3.2.3. Measures of Terrestrial Exposure

................................ ................................ ....... 19

3.3. Ecological Effects Characterization

................................ ................................ .......... 19

3.3.1. Aquatic Organisms

................................ ................................ ............................... 19

3.3.2. Terrestrial Organisms

................................ ................................ .......................... 20

3.3.3. Review of Incident Data

................................ ................................ ....................... 22

4. Risk Characterization

................................ ................................ ................................ ......... 23

4.1. Risk Description

................................ ................................ ................................ .......... 23

4.2.1. Risks to Aquatic Organisms

................................ ................................ ................. 23

4.2.1.1. Freshwater Fish, Invertebrates, and Amphibians

................................ ................................ ..... 23 4.2.2. Risks to Terrestrial Organisms

................................ ................................ ............ 23

4.2.2.1. Birds, Reptiles, and Terrestrial

- phase Amphibians

................................ ................................ .. 23

4.2.2.2. Mammals

................................ ................................ ................................ ................................ . 24

4.2.2.3. Terrestrial Invertebrates

................................ ................................ ................................ ........... 24

4.2.2.4. Te rrestrial Plants

................................ ................................ ................................ ...................... 24- Page 6 of 31

- 5. Endocrine Disruptor Screening Program (EDSP)

................................ ........................... 24

6. Conclusions

................................ ................................ ................................ .......................... 25

7. References

................................ ................................ ................................ ............................ 25

8. Appendix A. Submitted Studies for Diphenylamine

................................ ....................... 27

9. Appendix B. Text from Memo (with CBI Redacted) from the DPA Task Force in Response to Use Questions from EPA

................................ ................................ ....................... 29

List of Tables

T ABLE 1. C HEMICAL P ROFILE OF D IPHENYLAMINE

. ................................ ................................ ................................ ................. 10

T ABLE 2. C HEMICAL P ROPERTIES AND E NVIRONMENTAL F ATE P ARAMETERS OF D IPHENYLAMINE

. ................................ ................... 15

T ABLE 3: D IPHENYLAMINE A CUTE T OXICITY V ALUES FOR A QUATIC O RGAMISMS

. ................................ ................................ .......... 20

T ABL E 4. D IPHENYLAMINE A CUTE T OXICITY V ALUES FOR B IRDS AND M AMMALS

. ................................ ................................ .......... 22- Page 7 of 31

- 1

. Executive Summary

Diphenylamine is a plant growth regulator used only for post

- harvest treatment of apples for control of scald, a physiological disorder that causes browning of th e skin in storage rendering the apple unacceptable for fresh market. Diphenylamine prevent s the oxidation of alpha

farnesene, a volatile compound which naturally occurs in apples and leads to spoilage

. It is

classified as an indoor/food use chemical and does not have outdoor (field) or residential labeled applications.

Applications are made post

- harvest by either truck or bin drenching, which are conducted

outdoors . Additionally, a drench or spray application is sometimes utilized as bins of fru it are moved beneath a conveyor; alternatively thermal fogging conducted in an enclosed, seal ed indoor space may be used

. D rench wastes are collected and disposed of after re

- use and a determination that the material is no longer suitable for re

- use. Dis posal of the drench waste is governed by NPDES permitting requirements . V enting of the chemical in vapor phase following indoor fogging is not expected to lead to non

- target exposure due to expected degradation of diphenylamine in the atmosphere . Given th ese use practices and the fate of the vapor phase

material , there are no significant environmental release pathways that would be expected to

affect non

- target plants or animals

.

Diphenylamine is hydrolytically stable at environmental pH’s, but readily degrades via aqueous photolysis and through atmospheric oxidation. It is susceptibl e to biotic transformation in

aerobic soil; h owever, th is process may lead to the form ation of dimers and polymers that may be more stable than the parent compound. It is only slightly mobile in soil, but may volatilize from either dry or moist soils, as well as from surface water ; volatilized material would then be subject to atmospheric oxidation

.

Diphenylamine is classified as moderately toxic to freshwater fish , aquatic

- phase amphibians and

freshwater invertebrat es on an acute exposure basis, and practically non

- toxic to birds , reptiles

and terrestrial

- phase amphibians on an acute oral and subacute dietary exposure basis. Diphenylamine is practically non

- toxic to mammals on an acute exposure basis, but effects

observed in a reproduction stud y with rats include reduction in mean body weights and body weight gains, changes in hematological parameters, splenic/kindey lesions, and increased signs

of clinical toxicit y ( e.g ., bluish colored fluid in the cage and bluish colored staining of the coat in both sexes, and swelling of mammary gland(s) or palpable later al

- ventral masses, primarily in females)

. No studies have been submitted for estuarine/marine organisms, ter restrial invertebrates, terrestrial and aquatic plants. Chronic studies have not been submitted for taxa

other than mammals

.

The results of this screening

- level risk assessment are similar to those identified in the environmental fate and ecological risk assessment written in support of the RED for diphenylamine in 1997. Diphenylamine is an indoor / food use chemical and EPA does not generally conduct quantitative ecological risk assessments for indoor use chemicals for which there are no routes of exposure to non

- target organisms

. G iven the patterns of diphenylamine use ( i.e ., truck or bin drenching with collection of drench water, or thermal fogging in an enclosed, sealed indoor space), the likelihood of exposure t hat would in turn lead to adverse effects on- Page 8 of 31

- ecological systems from the post

- harvest treatment use is considered to be minimal. P otential aquatic and terrestrial exposure to diphenylamine from drench water disposal would be mitigated by rapid aqueous pho tolysis, rapid biotic transformation in soil, volatilization, and atmospheric oxidation of any volatilized compound

. Discharge of effluent containing diphenylamine is regulated by National Pollutant Discharge Elimination System (NPDES) permits as indicate d on end use product labeling

. (At this time, some of the relevant diphenylamine product labels do not cite the NPDES permits, but the registrants have agreed to add the appropriate statements. ) Exposure from the d isposal of drench water collected follow ing post

- harvest treatment application is not assessed here, as it is regulated under NPDES.

Based on the low likelihood of environmental exposure from the indoor /food use pattern, the NPDES permit for the drench water disposal, and the environmental fate properties of diphenylamine

, EFED conclude s that the post

- harvest use of diphenylamine on apples will have

'No Effect' (NE) on f ederally listed endangered or threatened terrestrial or aquatic species, or their designated critical habitats, as identified by the U.S. F ish and Wildlife Service and the

N ational M arine F isheries S ervice

. EPA anticipates conducting no further analysis of potential risks to endangered or threaten ed species from diphenylamine for this use unless the Agency

obtains dat a or information that would otherwise inform the Agency’s determination.

2

. Problem Formulation

The purpose of problem formulation is to provide the foundation for the environmental fate and ecological risk assessment being conducted for the l abeled uses of diphenylamine ( PC Code

038501 ; CAS No: 122

- 39

- 4 )

. The problem formulation sets the obje ctives for the risk assessment and provides a plan for analyzing the data and characterizing the risk ( USEPA 1998)

.

As part of the Registration Review process, a Problem Formulation (PF) for this risk assessment

has been developed simultaneously with the conduct of the Registration Review Preliminary

Risk Assessment (PRA) itself, as it was determined that given the current uses available data a re suffici ent to conduct the risk assessment at this time

. A separate Problem Formulation document

will not be issued for diphenylamine

.

2.1. Conclusions from Previous Risk Assessments

Most recently, i n 2008, EFED assessed the ecological risk of a new diphenylamine product that used a post

- harvest thermal fogging application technique to treat apples for scald during storage (DP340287), which was the same as the technique EFED reviewed previously for another diphenylamine product in June 2004 (DP303521 ). Both reviews concluded that the thermal fogging method of application would reduce potential exposures of terrestrial and aquatic

environments to diphenylamine when compared with drench applications in open air facilities with discharge of spent drench material to orchards, and would reduce overall environmental loadings. Based on the limited potential exposure from the thermal fogging application technique, the potential risks to terrestrial and aquatic non

- target organisms, including federally

listed s pecies , was determined to be even lower than that associated with the drench application. The ecological risk assessment written in support of the 1997 Reregistration Eligbility Decision- Page 9 of 31

- (RED) document for diphenylamine was issued in July 1997 (USEPA 1997 ). Conclusions are presented below.

2.1.1. Ecological Risk Assessment

The major environmental fate and ecological risk conclusions presented in the RED were as

follows:

• Diphenylamine is stable towards hydrolysis at environmental ly relevant pH value s. It has

a moderate solubility in water, a relatively high octanol/water partition coefficient (K ow )

, and a high vapor pressure. The high rate of aqueous photolysis and the susceptibility of the chemical in aerobic environments indicate that if diphenylamine were to reach surface waters, the parent compound would be short lived. However, aerobic biotic transformations result in dimers and polymers that may be more stable than the parent compound.

• Diphenylamine is moderately toxic to fish , aquatic

- phase amphibians, and aquatic

invertebrates on an acute exposure basis . It is practically non

- toxic to birds, reptiles and

terrestrial

- phase amphibians on an acute and subacute exposure basis and it is practically

non

- toxic to mammals on an acute oral exposure basis

.

• Diphenylamine is classified as an indoor / food use chemical and EPA does not generally

conduct quantitative ecological risk assessments for indoor /food use chemicals for which

there are no significant exposure routes for non

- target organisms

. However , give n the use patterns and the limited amount of diphenylamine that will be available for environmental

exposure as a direct result of these application methods, the likelihood of adverse effects on ecological systems is considered to be minimal. Discharge of effluent containing diphenylamine is regulated by National Pollutant Discharge Elimination System (NPDES) permits.

2.1.2. Drinking Water Exposure Assessments

A drinking water assessment (DWA) has not been conducted for diphenylamine, as the compound has been ca tegorized in the past as an indoor / food use, for which a DWA was not required.

2.1.3 Clean Water Act Programs

Diphenylamine is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Loads (TMDLs) or water quality criteria have been developed for diphenylamine (USEPA 2015).- Page 10 of 31

- 2. 2. Nature of Regulatory Action

The PRA is con ducted as part of the Agency’s Registration R eview process for pesticide active ingredients

. In 1996, FIFRA was amended by the Food Quality Protection Act (FQPA), and the Agency was mandated to implement a new program for the periodic review of pesticides, i.e

., Registration Review. The Registration Review program is intended to ensure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to

meet the statut ory standard of no unreasonable adverse effects to human health and the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the new Registration Review program, EPA periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely.

2. 3

. Stressor Source and Distribution

2. 3

. 1

. Nature of the Chemical Stressor

Diphenylamine is a plant growth regulator used for post

- harvest treatment of apples for scald

control

. It is classified as an indoor/food use chemical and does not have outdoor (field) or residential labeled applications. Diphenylamine works as an antioxidant to prevent the oxidation

of alpha

- farnesene, a volatile compound which is present in apples and caus es cold storage scald on the outside of the fruit (Ingle and D'Souza, 1989).

The chemical profile of diphenylamine is provided in Table 1

. As described in Section 3.2.1.4

, this screening

- level ecological risk assessment focuses on diphenylamine parent only

.

Table 1 . Chemical Profile of Diphenylamine

. Common name s Diphenylamine , DPA

IUPAC name /CAS name N

- phenylaniline /N

- phenylbenzenamine

Registered Product Name s No Scald DPA EC

- 283 ( 31% a.i.; EPA Registration 2792

- 45 )

ecoFOG

- 100 ( 10% a.i.; EPA Reg. No. 64864

- 53)

Chemical name D iphenylamine

Structure

SMILES Notation N(c(cccc1)c1)c(cccc2)c2 Pesticide type Plant Growth Regulator (no longer used as a fungicide)

Chemical class Bridged Diphenyl ( http://www.alanwood.net/pesticides/class_pesticides.html )

CAS number 122

- 39

- 4 Empirical formula ( C 6 H 5 ) 2 NH

Molecular mass 169.23 g mol

- 1

2. 3 .2

. Overview of Pesticide Usage- Page 11 of 31

- Diphenylamine is a plant growth regulator used as a post

- harvest treatment to prevent scald on apples going to storage. Based on information provided by the Biologic and Economic Analysis Division (BEAD) in the BEAD Chemical Profile (BCP), diphenylamine application is made as a
post

- harvest treatment with dipping, drenching, spraying, and thermal fogging (USEPA 2015). However, the registrants for diphen ylamine stated in a 2015 memo to EPA (from the Diphenylamine [ DPA ] Task Force ; see Appendix B ) that tank dipping is no longer used and is

not being supported as a labeled use. Additional use details are provided in Appendix B , which

consists of text from the DPA Task Force memo (with C onfidential B usiness I nformation redacted) in response to use questions recently posed by EPA . Use details were also previously provided in the 1997 RED chapter (USEPA 1997). A pplications are made post

- harvest by either

tru ck or bin drenching, which are conducted outdoors and utilize a drench or spray application as

bins of fruit are moved beneath on a conveyor; alternatively, thermal fogging is conducted in an enclosed, seal ed indoor space

. Based on information in the BCP, diphenylamine end

- use products are formulated as an emulsifiable concentrate, soluble concentrate, or pressurized gas. Additional use information is presented in Section 3.1

.

Following post

- harvest drenching, t he disposal of the collected drench water containing diphenylamine may include transfer to and storage in lagoons

, or distribut ion to land ( e.g ., t o orchard roads for dust abatement or to fields)

. E xposure and risk resulting from disposal of drench water collected following applicati on are not assessed here, as such disposal is regulated

under NPDES permits as indicated on end use product labels. Appendix B contains additional information on the disposal of drench waste under NPDES regulations

.

2. 4

. Receptors

2. 4 .1

. Aquatic and Terrestrial Effects

A receptor is a biological entity that is exposed to a stressor (USEPA 1998 ) and EPA relies on surrogate species to assess the potential for adverse effects to aquatic and terrestrial receptors from the use of a pesticide

. Consiste nt with the process described in the Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs (USEPA 2004), this risk assessment uses a surrogate species approach in its evaluation of diphenylamine. Toxicity data generated fro m surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate potential effects on a variety of species (receptors) included under these taxonomic groupings.

Acute and chronic toxicity data from studi es submitted by pesticide registrants along with data from the available open literature are used to evaluate potential direct effects of diphenylamine to aquatic and terrestrial receptors. The open literature studies are located through EPA’s database

ECO TOX ( http://cfpub.epa.gov/ecotox/ ), which provides a source for locating single chemical toxicity data for aquatic life, terrestrial plants, and wildlife.

2. 4 .2

. Ecosystems Potentially at Risk

Ecosys tems at potential risk are often extensive in scope; therefore, it is not possible to identify such ecosystems in other than general terms in a screening

- level assessment. In general terms,- Page 12 of 31

- terrestrial ecosystems potentially at risk are treated areas and a reas immediately adjacent to

treated areas

. For diphenylamine, this includes terrestrial areas on which treated wastewater is disposed and areas adjacent to that. Aquatic ecosystems potentially at risk include water bodies adjacent to or downstream from treated areas and may include natural or impounded lentic
systems, i.e. , ponds, lakes, and reservoirs, and lotic (flowing) waterways, i.e. , streams and rivers. Within water bodies, the water column, sediment, and pore water are all compartments of potentia l concern. Due to the limited use of diphenylamine as a post

- harvest treatment on apples, and the lack of significant exposure pathways directly related to the post

- harvest use as a drench or thermal fog, ecosystem s potentially at risk are highly limited in scope. After use and

re

- use, drench waste water is collected and disposed of according to NPDES permitting requirements . Additionally, venting of the chemical in vapor phase following indoor fogging is not expected to lead to non

- targ et exposure due to expected degradation of diphenylamine in the atmosphere (via rapid oxidation or photolysis) , there are no significant release pathways

.

2. 5

. Assessment Endpoints

Assessment endpoints represent the actual environmental values that are to be protected, defined by ecological entitities (species, community, etc. ) and their attributes or characteristics (USEPA 1998). Typically, ecological entities assessed include the following: birds, amphibians, reptiles, mammals, freshwater fish, terres trial and aquatic invertebrates, and terrestrial and aquatic plants. The assessed attributes for any of these entities may include growth, survival, and/or reproduction. If risks are identified for given species/taxa based on a screening

- level assessment, then such risks might be expected to translate to higher levels of biological organization. For diphenylamine, however, use patterns and environmental fate data suggest it will not be sufficiently available in the environment to be a cause of concern for ecological entities.

2. 6

. Risk Hypotheses

For diphenylamine, the following risk hypothesis is employed for the ecological risk assessment:

The exposure pathway of diphenylamine used in accordance with the label has low potential to result in adverse effects on the survival, growth, and reproduction of non

target terrestrial and aquatic organisms.

Additional discussion can be found in Section 4.1 , Risk Characterization.- Page 13 of 31

- 2. 6 .2

. Potential Exposure Pathways and Effects

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant concentrations

. An exposure pathway is the means by which a pesticide moves in the

environment from a so urce to an ecological receptor

. For an ecological pathway to be complete, it must include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure. The potential exposu re pathways and effects of the registered use of diphenylamine are mediated by the fact that the compound i s exclusively an indoor/food use ( post

- harvest treatment of apples )

. T he normally

assessed routes of environmental exposure are not relevant for diphenylamine

. The two diphenylamine appl ication method s ar e truck or bin drenching, with collection of drench water ; and thermal fogging, which is done in an enclosed, sealed indoor space. Additionally, any

d iphenylamine released to the air as a vapor in limited amounts following venting of storage

space s where thermal fogging is conducted is expected to rapidly degrade via atmospheric oxidation and photolysis. The disposal of drench water containing diphenylamine may lead to

non

- target organism exposure if such water is stored in lagoons or distributed to land , f or example to orchard roads for dust

- abatement purposes. However, exposure resulting from disposal of drench water collected following post

- harvest application is not assessed here, as such dispo sal is regulated under NPDES as indicated on end use product labels

. Furthermore,

n either application method is expected to result in spray drift. Appendix B contains additional information on the disposal of drench waste under NPDES permits

.

2. 7

. Analysis Plan

2. 7 .1

. Measures of Exposure

2.7.1.1 Measures of Aquatic and Terrestrial Exposure

Standard exposure modeling is not applicable to the indoor / food use registered for diphenylamine, precluding the need for the determination of estimated environmental concentrations (EEC). The sole registered use of diphenylamine as a post

- harvest treatment on apples is not anticipated to result in aquatic exposure from either the thermal fogging application (an indoor use in a sealed, enclosed room) or from the outdoor (truck and bin) drenching use,

after which the drench waste is collected and subsequently disposed of in accordance with NPDES permit s

.

Exposure estimates using the Screening Tool for Inhalation Risk (STIR, v. 1.0, 11/23/2010) and Screening Imbibition Program (SIP, v. 1.0) were not conducted for diphenylamine due to the

indo or /food use pattern , low acute and sub

- acute toxicity to avian taxa, short at mospheric

oxidation hal f

- life, and NPDES permit regarding the disposal of drench water.

2

. 7 .2

. Measures of Effect

Measures of effect are obtained from a suite of registrant

- submitted guideline studies which were conducted with a limited number of surrogate test species. The test species are not intended to be representative of the most sensitive species but rather wer e selected based on their ability to- Page 14 of 31

- thrive under laboratory conditions. The acute measures of effect used in this screening

- level

assessment are the LD 50 (Lethal Dose), LC 50 (Lethal Concentration), and EC 50 (Effects Concentration). These are measures of acute toxicity which result in 50% of the respective effect in tested organisms. The biological endpoint for the chronic measure of exposure is the NOAEL (No Observed Adverse Effect Level). Toxicity studies were submitted for freshwater fish and

invertebr ates, birds, and mammals. The endpoints used for risk characterization were derived from studies which underwent review and were classified as “acceptable” (conducted under guideline conditions and considered to be scientifically valid) or “supplemental” ( conditions deviated from guidelines but the results were considered to be scientifically valid).

2.8

. Preliminary Identification of Data Gaps

The database on the environmental fate and transport properties of diphenylamine is complete with respect to the required studies for indoor/food use pesticides, for which only hydrolysis data are required to be submitted to EPA

. Acceptable studies were submitted for hydrolysis

, aqueous photolysis, aerobic soil metabolism and adsorption/leaching . A submitted anaerobic aquatic metabolism study was classified as not acceptable. Since the compound is used only for post

harvest treatment of apples as an indoor / food use (fumigation in storage) or as a drench with recycled and collected treatment wate r, environmental fate data requirements are limited to hydrolysis data

. Additional data on photolysis and metabolism of diphenylamine are also available, but are not required for this post

- harvest use.

There are no ecological effects data gaps for dipheny lamine with respect to the required studies for indoor/food use pesticides

. No studies have been submitted for estuarine/marine organisms, terrestrial invertebrates, terrestrial and aquatic plants. Chronic studies have not been submitted

for taxa other t han mammals. However, given the current use pattern, these data were not deemed to be necessary to complete the risk assessment. Only acute studies are required for fish and aquatic invertebrates because of the indoor / food use.

3

. Analysis

3.1

. Use Characterization

Diphenylamine is used as a post

- harvest treatment as a plant growth regulator to prevent scald on apples going to storage. Applications are made post

- harvest by either truck or bin drenching,

which is conducted outdoors and utilize s drench or spray application as bins of fruit are moved beneath on a conveyor , with collection and subsequent disposal of drench wastes in accordance with NPDES permits . A lternatively, application may be done via thermal fogging conducted in an enclosed, s eal ed indoor space. Additional information on use provided by the DPA Task Force is presented in a memo in Appendix B

. As stated in the memo,

“ The application rate is application of 100 gallons of product to 30 bins of apples. The application rate rang es from 1000

– 2200 ppm with an average 1500 ppm. The number of apple bins typically treated in one day depends on the region of the country and apple production. Application can range from 1000

- 5000 apple bins/day with an average of 2500 apple bins/day c ould be treated depending on the size of the packing house. ”- Page 15 of 31

- Based on information in the memo, “ The typical thermal fogging room can hold from a minimum of 500 apple bins to a maximum of 6,000 apple bins with an average room holding 1,800 apple

bins .” The DPA Task Force also stated in the memo, “ The primary application is drench which is >50% of applications followed by thermal fogging at approximately 25% of applications. Over the few years, more facilities have been converting to thermal fogging and it is expected to

continue .” The registrants reiterated this information orally during a teleconference following the Office of Pesticide Programs’ (OPP) receipt of the memo in response to OPP’s questions on

use.

3.2

. Exposure Characterization

3.2. 1. Environmental Fate and Transport Characterization

Diphenylamine is moderately soluble in water, and has a moderately high vapor pressure, indicating that it has intermediate to high volatility under field conditions and may volatilize in

the environment i f present on dry, non

- adsorbing surfaces

. Based on its Henry’s Law Constant, diphenylamine may also volatilize from water. While diphenylamine is stable to hydrolysis, it degrades rapidly via aqueous photolysis

, with a half

- life of 4.4 hours. Its estima ted atmospheric

oxidation half

- life is 0.6 hours , estimated using a quantitative structure

- activity relationship (QSAR) software (EPI Suite v.4.11)

. Diphenylamine transforms rapidly in aerobic soil (half

- life <1 day), although it forms more structurally c omplex dimers and polymers via metabolism (most of which contained dimeric diphenylamine with an additional unit of aniline)

, which may be more stable than the parent compound. Degradation in aerobic soil occur s to some extent, and one of the products of aerobic metabolism is CO 2 (18% of the applied by study termination at 1 year)

. Unextracted residues (up to 58% of the applied by 184 days) were also formed in laboratory metabolism studies. In soils, parent diphenylamine is only s lightly mobile, based on organic carbon partition coefficient ( K oc ) values in five soils and using the FAO soil mobility

classification scheme ( FAO, 2000). Chemical property and environmental fate data for diphenylamine are presented in Table 2

.

Table 2 . Chemical Properties and Environmental Fate Parameters of Diphenylamine

. Chemical/Fate Parameter Value Description/Comments Source (MRID) /

Classification

Selected Physical/Chemical Parameters

Chemical name diphenylamine

˗ ˗

Molecular mass 169.23 g mol

- 1

˗ USEPA 199 7

Vapor pressure (25 ° C) 6.39 x 10

- 4 Torr Intermediate to high volatility possible from dry,

non

- sorbing surfaces. USEPA 199 7

Water solubility (25 ° C) 39.4 mg/L USEPA 199 7

Octanol

- water partition coefficient (Log K OW ) 3.59 USEPA 199 7- Page 16 of 31

- Chemical/Fate Parameter Value Description/Comments Source (MRID) /

Classification

Henry’s Law Constant (25°C) 3.6 x 10

- 6 atm

- m 3 /mole Calculated from MW, VP,

WS . Indicates the compound

may volatilize from moist

soil or water surfaces. ˗

Atmospheric oxidation half

life (hours; 25°C) 0.64 Estimated value. Based on reaction with hydroxyl

radicals. No reaction with

ozone. EPI Suite

v.411 /AopWin

v1.92

Persistence

Hydrolysis half

- life (d ays ) pH 5, 25 ° C pH 7, 25 ° C pH 9, 25 ° C 316

352

358 Essentially s table to hydrolysis. 42660001 (Acceptable)

Aqueous photolysis half

- life

@ 25 ° C ; pH 7 (hours) 4.4 Rapidly photodegrades in clear, shallow water. 42958201 (Acceptable)

Soil photolysis half

- life
(25 ° C) No data. D ata are not required.

˗

Aerobic soil metabolism

half

- life ( days; 25°C) <1 Transformed to dimers and polymers possibly more stable than the parent. High unextracted residues by day

3. 42964201 (Acceptable)

Anaerobic soil metabolism

half

- life (25°C) No data. D ata are not required.

˗

Aerobic aquatic metabolism

half

- life (25°C) No data. D ata are not required.

˗

Anaerobic aquatic

metabolism half

- life (25°C) No data. D ata are not required. 43080901 (Not Acceptable)

Mobility

Freundlich soil

- water partition coefficients (K F ); 21.4 (loamy sand) 13.8 (loam) 4.9 (silt loam) 16.4 (silty clay loam) 151.6 (clay) ˗ 43412701 (Acceptable)

Organic carbon

- normalized

soil partition coefficients (K FOC ) 3622 (loamy sand) 3962 (loam) 1212 (silt loam) 6593 (silty clay loam) 5143 (clay) Slightly mobile in soils. 43412701 (Acceptable)

Field Dissipation

Terrestrial field dissipation

half

- life No data Data are not required.

˗

Fish Bioconcentration- Page 17 of 31

- Chemical/Fate Parameter Value Description/Comments Source (MRID) /

Classification

Fish bioconcentration factors (steady

- state); depuration

rate No data Data are not required.

˗

3 .2.1.1

. Transport and Mobility

In a batch equilibrium study of diphenylamine conducted on five soils, diphenylamine was only slightly mobile in soil based on the K
oc values (MRID 43412701)

. In aged soil columns, diphenylamine residues were somewhat mobile in silt loam soil columns (with < 1.9% found in the last two segments and the leachate) , and slightly mobile in loamy sand, loam and clay soil

columns (with 0.11

- 0.48% of t he applied in the last two column segment or leachates) . Because

this chemical is used indoors or with collected drench waste

, there is a low likelihood that it will runoff to surface waters. However, if collected drench material is applied to orchard roa ds or other outdoor surfaces, rather than held in lined storage lagoon s , there is a potential for diphenylamine to reach surface waters via runoff events. The susceptibility of the chemical to aqueous photolysis and to biotic degradation in aerobic environ ments indicate that if it were to

be released to soils or reach surface waters, the parent compound has a high likelihood of being readily dissipated.

There is also a potential for transport via volatilization, based on diphenylamine’s vapor pressure

as well as the high level of volatiles (up to 70% of the applied) detected in the submitted anaerobic aquatic metabolism study. However, v olatilized diphenylamine is expected to rapidly degrade through atmospheric oxidation

, and possibly aqueous photolysis i f it is present on particulate matter along with sufficient moisture

.

3.2.1.2

. Degradatio n

Diphenylamine rapidly degrade d in water via photolysis ( half

- life of 4.4 hours ) in laboratory

studies , forming several major transformation products (MRID 42958201). In aerobic loam soil (MRID 42964201), diphenylamine transformed with a metabolism half

- life of <1 day, but formed dimers and polymers that are structurally more complex and may be more stable than the parent compound (USEPA 1997). Inform ation on the biotic metabolism of diphenylamine in anaerobic soil or aquatic environments is not available.

3.2.1.3

. Field Studies

F ield dissipation data have not been submitted and are not required for diphenylamine based on

the current label use.

3.2.1.4

. Bioaccumulation

Bioconcentration in fish data have not been submitted and are not required for diphenylamine

based on the current label use.- Page 18 of 31

- 3.2.1.5. Transformation Products

Submitted studies did not fully characterize transformation products

. In the aquatic photolysis study, several major transformation products were formed: carbazole (maximum of 51.7% at 10.5 hours, decreasing to non

- detectable by 72

- 192 hours); hydroxydiphenylamine (OH

- DPA; maximum of 16.3% at 36 hours, decreasing to 6.8% by 192 hours); and an hydroxylated tricyclic compound (first detected at 4 hours, increasing to 93.2% by 192 hours). Minor transformation products (not identified) were a total maximum of 5.9% of the applied.

In the aerobic soil metabolism study, 12 tran sformation products ( < 18.9% of the applied) were isolated, but were not identified. Additionally, some mineralization occurred, as CO 2 was 17.9% of the applied after 365 days. Unextracted residues were > 46.4% of the applied by day 3, and

were a maximum of 57.9% at 184 days. Additional information about transformation products was obtained from an aged column leaching study (43413001), in which four degradates were identified in column soil samples. These included N,N

- diphenylformamide (DPF), 4

- nitro

- N

p henylbenzenamine (NDPA), and two diphenylamine dimers (DPA

- 1, DPA

- 2).

3.2.2

. Measures of Aquatic Exposure

3.2.2. 1. Estimated Environmental Concentrations in Surface

Water

Standard exposure modeling was not conducted for diphenylamine and estimated environmental concentrations (EEC) were not determined

. The registered use of diphenylamine as a post

harvest treatment on apples is not anticipated to result in aquatic exposure from either the fogging application (an indoor use in a sealed , enclosed room ) or from the outdoor (truck and bin) drenching use , after which the drench waste is collected and subsequently disposed of in accordance with NPDES permits

. As stated by the DPA Task Force in a memo to the Agency (see Appendix B ),

“ Based on NPDES requirements, waste materials can be disposed of in lined lagoons, as dust abatement liquids or land applied. For the lined lagoon disposal, the waste solution is added to imperviously lined, in

- ground, engineered structures, which rely largely u pon evaporation for water removal. Dust abatement is the application of wastewater to unpaved bin storage lots and unpaved roads (i.e., orchard roads) for the purpose of dust suppression. Land application is an engineered system for applying wastewater to a vegetated land surface. DPA waste solutions are not discharged directly to surface

waters.”

Thus, while there is the potential for aquatic exposure in surface water from storage in lined lagoons, or from use of the drench waste for dust abatement or lan d application, these applications are regulated by NPDES

. It is noted, however, that potential aquatic exposure from such applications would be mitigated by aqueous photolysis, volatilization, and atmospheric oxidation of any volatilized compound.- Page 19 of 31

- 3.2.2. 2

. Monitoring Data

EFED conducted a search ( September 2015) of the United States Geological Services (USGS) National Water Quality Assessment (NAWQA) Program database ( http://cida.usgs.gov/nawqa_q ueries_public/ ) and the California Department of Pesticide Regulation (CDPR) surface water and sediment database ( http://cdpr.ca.gov/docs/emon/surfwtr/surfcont.htm )

. Based on the search resu lts, n o monitoring data are available for diphenyl amine

.

3.2.3. Measures of Terrestrial Exposure

Standard exposure modeling was not conducted for diphenylamine and estimated environmental concentrations (EEC) were not determined. The registered use of diphenylamine as a post

harvest treatment on apples is not anticipated to result in terrestrial expos ure from either the fogging application (an indoor use in a sealed, enclosed room) or from the outdoor (truck and bin) drenching use, after which the drench waste is collected. Disposal of drench waste, which may be stored in lagoons or applied to orchard fields and roads for dust abatement, is regulated by NPDES permit. Given the pattern of diphenylamine use, the likelihood of adverse effects on ecological systems from terrestrial exposure is considered to be minimal.

3.3. Ecological Effects Characteriz ation

A detailed description of the available ecotoxicity data for diphenylamine is provided in the Environmental Fate and Ecological Risk Assessment written in support of the RED for diphenylamine (USEPA 1997). Since the completion of that assessment, no new ecological

effect s data have been submitted to EPA

.

Since this is an indoor / food use chemical, and given the pattern of diphenylamine use, the likelihood of adverse effects on ecological systems is considered to be minimal. No further data

are re quired. Discharge of effluent containing diphenylamine for manufacturing use is regulated by NPDES.

3.3.1. Aquatic Organisms

Only acute studies are required for fish and aquatic invertebrates because of the indoor / food use. An overview of submitted aqua tic organism studies can be seen in Table 3

.

Freshwater Fish

One study with r ainbow trout ( Oncorhynchus mykiss ) using the technical grade active ingredient ( TGAI ) was submitted to establish the toxicity of diphenylamine to freshwater fish (MRID 43879001). The 96

- hr LC 50 is 2.2 mg a

. i

. /L (parts per million; ppm )

, classifying diphenylamine as moderately toxic to freshwater fish on an acute exposure basis. Sublethal effects occurred at the three hightest treatment groups and included lethargy, erratic swimming, discoloration, loss of equilibrium, and lying on the bottom of the test chamber.- Page 20 of 31

- Freshwater Invertebrates

One study with the w ater flea ( Daphnia magna ) using the TGAI was submitted to establish the toxicity of diphenylamine to freshwater invertebrates for the food use (MRID 43878301). The

48

- hr LC 50 is 1.2 ppm classifying diphenylamine as moderately toxic to freshwater invertebrates on an acute exposure basis. No sublethal effects were reported.

Estuarine/Marine Fish

Estuarine/marine fish acute toxicity data are not required for diphenylamine bec ause of the

indoor /food use

. No additional data were identified through ECOTOX.

Estuarine/Marine Invertebrates

Estuarine/marine invertebrate acute toxicity are not required for diphenylamine because of the

indoor /food use

. No additional data were identi fied through ECOTOX.

Chronic Effects

A freshwater fish early life

- stage and freshwater invertebrate life

- cycle test using TGAI are not required for diphenylamine because of the indoor /food use. No additional data were identified through ECOTOX.

Aquatic Plants and Algae

No data are available to assess the acute toxicity of diphenylamine to aquatic plants and algae. According to 40 CFR § 158

- Subpart G, plant data are not required for contained pesticide

treatments.

Table 3 : Diphenylamine Acute Toxicity Values for Aquatic Orgamisms.

Study Type Species Test Material Endpoints (mg a.i./L) (Study Duration) Toxicity Classification (MRID) (Study Classification) Acute toxicity to

freshwater

vertebrates Rainbow trout ( Oncorhynchus mykiss ) TGAI (100% a.i.) LC 50 =2.2 mg a.i./L (96

- hour test) Moderately toxic (43879001) (Acceptable)

Acute toxicity to

freshwater

invertebrates Water flea ( Daphnia magna ) TGAI (100% a.i.) EC 50 =1.2mg a.i./L (48

- hour test) Moderately toxic (43878301) (Acceptable)

3.3.2. Terrestrial Organisms

An overview of submitted terrestrial organism studies can be seen in Table 4

.

Birds

Only acute oral and subacute dietary studies are required for birds due to the indoor /food use. One acute oral toxicity study with the Bobwhite q uail ( Colinus virginlanus ) using TGAI was conducted to establish the toxicity of diphenylamine to birds (MRID 43878901) as well as to reptiles and terrestrial

- phase amphibians for which birds serve as surrogates . The 14

- day LD 50 is- Page 21 of 31

- >2

, 2 5 0 mg a.i./kg

- bw (ppm) classifying diphenylamine as practically non

- toxic to birds on an acute exposure basis

. R educ ed weight gain, however, was reported for males in the 2,25 0 ppm
treatment group.

A study with the m allard d uck ( Anas platyrhynchos ) using TGAI was conducted to establish the

subacute dieta ry toxicity of diphenylamine to birds (MRID 438 971 01) , reptiles and terrestrial

phase amphibians . The 5

- day LC 50 is >5

, 20 5 mg a.i./kg

- diet classifying diphenylamine as practically non

- toxic to birds on a subacute dietary exposure basis. No mortalities or signs of toxicity were observed in the control or treatment groups.

Chronic Effects

Avian reproduction studies using TGAI are not required for diphenylamine because of the

intended indoor /food use and its reported low acute toxicity to avian taxa. No additional data were identified through ECOTOX.

Terrestrial Invertebrates

Terrestrial invertebrate studies are not required due to the indoor /food use of diphenylamine. No additional data were identified through ECOTOX.

Mammals

A cute oral and chroni c mammalian toxicity studies with Sprague

- Dawley rats ( Rattus norvegicus ) exposd to TGAI (99.9% a.i.) were submitted

. In the acute study, the LC 50 was reported to be 2.72 g/kg/day classifying diphenylamine as practically non

- toxic on an acute exposure bas is ( Accession Number 00148523 )

.

A two

- generation Sprague

- Dawley rat reproductive study was conducted (MRID 42638101 )

. Compound

- related systemic t oxicity was observed in a dose

- r elated manner among both sexes and generations at all dose levels. In general, females were more affected than males and F 1 animals were more affected than F 0 animals. Kidney, spleen, and liver appeared to be the target

organs as evidenced by weight differences relative to control animals at 399 mg/kg/day in ma les

, 131 and 448 mg/kg/day in females

, and gross and microscopic findings at all d ose levels in both

sexes. The systemic toxicity NOAEL was less than 40 /46 mg/kg/day in males and females, respectively. The LOAEL was 40/ 46 mg/kg/day in males and females, respectively, based on

gro ss pathological findings in the spleen (enlarged, discolored, congestion, and hemosiderosis)

, and on microscopi c findings in the kidney (brown pigment in the proximal convoluted tubule), liver (hepatic hypertrophy and brown pigment in the Kupf fer cells), and spleen (congestion and hemosiderosis).

Terrestrial and Aquatic Plants

According to 40 CFR § 158

- Subpart G, t errestrial and aquatic plant studies are not required due

to the indoor /food use of diphenylamine. No additional data were identified through ECOTOX.- Page 22 of 31

- Table 4

. Diphenylamine Acute Toxicity Values for Birds and Mammals

.

Study Type Species Test Material Endpoints Toxicity

Classification (MRID) (Study Classification)

Acute oral toxicity

to birds Bobwhite quail ( Colinus virginianus ) TGAI (100% a.i.) LD 50 >2250 mg a.i./kg bw

14

- day test Practically non

- toxic ( 43878901 ) (Acceptable)

Subacute dietary toxicity to birds Mallard duck ( Anas platyrhynchos ) TGAI (100% a.i.) LC 50 >5205 mg a.i./kg diet

5

- day test Practically non

- toxic ( 43879101 ) (Acceptable)

A cute oral toxicity

to mammals Sprague Dawley rats

( Rattus norvegicus ) TGAI (99.9% a.i.) LD 50 =2.72 g/kg/day

14

- day test Practically non

- toxic ( 00148523 ) (Acceptable)

Chronic

mammalian

toxicity Sprague Dawley rats

( Rattus norvegicus ) TGAI (99.8 % a.i.) Males

NOAEL <40 mg/kg/day
LOAEL ≤40 mg/kg/day

Females

NOAEL <46 mg/kg/day LOAEL ≤46 mg/kg/day

52

- week test Endpoints: gross pathological findings in the spleen (enlarged and

discolored, congestion, and hemosiderosis), kidney abnormalities

(brown pigment in proximal convoluted

tubule), and liver

abnormalities (hypertrophy and brown pigment in

Kupffer cells)

( 42638101 ) (Acceptable)

3.3.3. Review of Incident Data

The ecological incident information system (EIIS) is a database maintained by the Office of Pesticide Programs; the database contains ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an inciden t, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents a re categorized according to the certainty that the incident resulted from pesticide exposure.

Based on the 40 CFR §159.184, information on all known “major” incidents must be submitted to the Agency by the registrant(s). All ecological incidents consid ered “minor” only need to be aggregately reported in Aggregate Incident Reports (AIR) as quarterly counts of incidents by the registrant(s). Both EIIS and AIR were searched in September 2015 and no incidents for diphenylamine have been reported . Because of uncertainties regarding the extent to which incidents are reported to EPA, the absence of incident reports cannot be construed as the absence

of incidents.- Page 23 of 31

- 4. Risk Characterization

Diphenylamine is moderately toxic to freshwater fish , aquatic

- phase amphibians, and freshwater invertebrates. It is practically non

- toxic to birds, reptiles and terrestrial

- phase amphibians on an acute and subacute exposure basis. EFED generally does not conduct quantitative ecological

risk assessments f or indoor /food use chemicals for which there are no exposure pathways to non

target organisms

. Given the pattern of diphenylamine use, and the lack of significant exposure pathways associated with the post

- harvest treatment, the likelihood of adverse effects on ecological systems is considered to be minimal. Although t his is an indoor /food use chemical, disposal of drench wastes containing diphenylamine following the post

- harvest use is regulated by NPDES permit.

4.1. Risk Description

Diphenylamine is an indoor / food use chemical and it is not expected to be persistent or mobile in the environment as it is subject to rapid abiotic and biotic routes of degradation. A detailed description though of the available environmental fate and eco logical effect data for diphenylamine is provided in the Environmental Fate and Ecological Risk Assessment written in support of the RED for diphenylamine (USEPA 1997).

4.2.1. Risks to Aquatic Organisms

4.2.1.1. Freshwater Fish, Invertebr ates, and Amphibians

The susceptibility of the chemical to aqueous photolysis and to biotic degradation in aerobic environments indicate that if it were to be released to soils or reach surface waters, the parent compound has a high likelihood of being re adily dissipated. Although d iphenylamine is moderately toxic to aquatic animals, the likelihood of exposure from the indoor /food use and as a result of the environmental fate properties of the compound is considered low

. No data are

available to assess t he toxicity of diphenylamine to estuarine/marine organisms as such data are not required for indoor uses; however, given the environmental fate profile of the compound and the chemical’s indoor use, the likelihood of exposure and hence risk is considered l ow.

4.2.2. Risks to Terrestrial Organisms

4.2.2.1. Birds, Reptiles, and Terrestrial

- phase Amphibians

Diphenylamine is practically non

- toxic to birds, reptiles and terrestrial

- phase amphibians on an

acute oral and subacute dietary exposure basis. Since this is an indoor / food use chemical, EPA

does not conduct avian risk assessments for such use s . However, given the pattern of diphenylamine use and the environmental fate properties of diphenylamine , the likelihood of exposure that could le ad to adverse effects on ecological systems is considered to be minimal.- Page 24 of 31

- 4.2.2.2. Mammals

Diphenylamine is practically non

- toxic to mammals on an acute exposure basis and given the chemical’s environmental fate profile and use , the likelihood of adverse effects from exposure is

consider low

.

4.2.2.3. Terrestrial Invertebrates

Although t errestrial invertebrate testing is not required for diphenylamine because of the

chemical’s use pattern , the likelihood of exposure is considered low

.

4.2.2.4. Terres trial Plants

Diphenylamine represents a relatively lo w likelihood of exposure to non

- target plants based on

its current use. Non

- target plant testing is not required for diphenylamine because of the

indoor /food use pattern. Release of the chemical into the air will result in rapid photolytic and atmospheric oxidative degradation processes with little exposure to non

- target terrestrial plants.

5. Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous 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, reproductive, and general or systemic toxici ty. 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 loss,

and sex rati os 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 Registration Review for diephenylamine, EPA reviewed th ese 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), diphenylamine is subject to the endocrine screening part of the Endocrine Disruptor Screening 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 substan ce to interact with the estrogen, 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 wh ere 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 th e dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between- Page 25 of 31

- 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 ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of known or likely endocrine disruptors. Diphenylamine is not on

either list

. 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 s creening battery, please visit our

website. 2

6

. Conclusions

The risk hypothesis articulated in the problem formulation stated that “ t he exposure pathway of diphenylamine used in accordance with the label has low potential to result in adverse effects on the survival, growth, and reproduction of non

- target terrestrial and aquatic organisms. ” This hypothesis is supported by t he results of this preliminary risk assessment w ritten in support of Registration Review , as well as the environmental fate and ecological risk assessment written previously in support of the RED for diphenylamine in 1997

. Based on the low likelihood of exposure from the indoor /food use pattern, low tox icitiy to non

- target organisms, the NPDES permit for the drench water disposal, and the environemental fate properties, the Agency concludes that the registration of the dipheylamine on post harvest apples will have 'no effect' (NE) on endangered or threat ened terrestrial or aquatic species, or their designated critical habitats, as listed by the FWS and the NOAA’s NMFS. EPA anticipates conducting no further analysis of potential risks to endangered or threatened species from diphenylamine for this use

unl ess the Agency obtains data or information that would otherwise inform the Agency’s

determination.

7. References

Food and Agriculture Organization of the United Nations. 2000. FAO PESTICIDE DISPOSAL SERIES 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence processes in the soil. Editorial Group, FAO

Information Division: Rome. http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger

. 1994

. Literature review and evaluation of the

EPA food

- chain (Kenaga) nomogram, and instrument for estimating pesticide residues o n plants

. Environmental Toxicology and Chemistry 13 (9):1383

- 1391.

Hoerger, F., and E.E. Kenaga

. 1972

. Pesticide residues on plants: Correlation of representative data as a basis for estimation of their magnitude in the environment

. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ, Stuttgart, West Germany, pp. 9

- 28.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

2 http://w ww.epa.gov/endo/- Page 26 of 31

- Ingle, M. and M. C. D'Souza. 1989. Physiology and control of superficial scald of apples: a

review. Hort Science 24:28

- 31.

USEPA. 2015. BEAD Chemical Profile (BCP) for Registration Review: Diphenylamine (038501). United States Environmental Protection Agency (USEPA). Biological and Economic Analysis Division. Office of Pesticide Programs. June 11, 2015.

USEPA. 2 014

. Estimation Program Interface (EPI)

Suite TM

. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

USEPA. 2009 a

. Water models. Available online at http://www.epa.gov/oppefed1/models/water/

.

USEPA. 2009 b

. ECOTOXicology Database, v. 4.0

. Accessed on 12 April 2012

. Available online

at http://cfpub.epa.gov/ecotox/

.

USEPA. 2009 c . Guidance for Selec ting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version 2.1

. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs,

Environmental Fate and Effects Div ision, October 22, 2009. Online

at: http://www.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/guidance

selecting

- input

- p arameters

- modeling

USEPA. 2006 c , TerrPlant v. 1.2.2 User’s Guide

. Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, D.C

. December 26, 2006.

USEPA. 2004

. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Agency

. Endangered and Threatened Species

Effects Determinations

. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C

. Available online at http://www.epa.gov/oppfead1/endanger/consultation/ecorisk

- overview.pdf

.

USEPA. 1997. Environmental Fate Science Chapter for the Registration Elegibility Document for Diphenylamine. (D P Barcodes D231687, D208697, D208687, Dl98487) U.S. Environmental Protection Agency, ( formerly the ) Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Environmental Fate and Effects Division, July 1997

.

USEPA. 1998. Guidelines for Ecological Risk Assessment

. EPA/630/R

- 95/002F

. Published in 63 FR 26846; May 14, 1998

. U.S. Environmental Protection Agency, Washington, DC

. April, 1998.

USEPA. 1993 b . Wildlife Exposure Factors Handbook

. EPA/600/R

- 13/187a

. Office of Research and Development, Washington, D.C.- Page 27 of 31

- USEPA. 1992. Pesticides in Ground Water Database: A Compilation of Monitoring Studies:

1971

- 1991: National Summary. U.S. Environmental Protection Agency, Washington,

DC.

Willis, G.H. and L.L. McDowell

. 1987

. Pes ticide persistence on foliage

. Reviews of Environmental Contamination and Toxicology 100: 23

- 73.

8. Appendix A

. Submitted Studies for Diphenylamine

Environmental Fate S tudies

MRID ? Citation

42660001 2059358

2059359

2059361

s u mmary Baur, L. (1993) Hydrolysis of (carbon 14)

- Ring

- Diphenylamine in Water at pH 5, 7, and 9: Lab Project Number: XBL 92084: RPT00119. Unpublished study prepared by XenoBiotic Labs, Inc. 82 p.

161

- 2 Photodegradation

- wat er

42958201 2059360

s u mmary Baur, L.; Robinson, R. (1993) Aqueous Photolysis of (carbon 14)

- Ring

Diphenylamine: Lab Project Number: XBL 92087: RPT00123. Unpublished study prepared by XenoBiotic Laboratories, Inc. 106 p.

162

- 1 Aerobic soil metabolism

42964201 2059360

summary 2059361 Liu, D. (1993) Aerobic Soil Metabolism of (carbon 14)

- Ring

- Diphenylamine: Lab Project Number: XBL 92082: RPT00139. Unpublished study prepared by XenoBiotic Labs, Inc. 98 p.

162

- 3 Anaerobic aquatic metabolism

43080901 2059360

summary 2059361 Liu, D. (1993) Anaerobic Aquatic Metabolism of (carbon 14)

- Ring

Diphenylamine: Lab Project Number: 92083: RPT00140. Unpublished study prepared by XenoBiotic Labs, Inc. 102 p.

163

- 1 Leach/adsorption/desorpt ion

43412701 2059360

summary 2059361 Reynolds, J. (1994) Adsorption and Desorption of (carbon 14)

- Ring

Diphenylamine in Four Soils and One Sediment: Lab Project Number: 92086: RPT00163. Unpublished study prepared by XenoBiotic Lab., Inc. 123 p.

43413001 2059360

summary 2059361 Kammerer, R. (1994) Aged Leaching of ((carbon 14)

- Ring) Diphenylamine in Four Soils: Lab Project Number: XBL94011: RPT00184. Unpublished study prepared by XenoBiotic Lab., Inc. 139 p.

Non

- Guideline Studies

44775201 Morrissey, M. (1999) Diphenylamine (Purified Active Ingredient): Determination- Page 28 of 31

- of UV

- Visible Absorption Spectrum: Final Report: Lab Project Number:
COVANCE 6524

- 115. Unpublished study prepared by Covance Laboratories Inc. 23 p. {OPPTS 830.7050}
Ecological Effects St udies

71

- 1 Avian Single Dose Oral Toxicity

MRID Citation Reference

43878901 2059364 Palmer, S.; Beavers, J. (1995) Diphenylamine: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 436

- 102: DLR54: 436/100295/QLD.NC/CHP1053 . Unpublished study prepared by Wildlife International Ltd. 41 p.

71

- 2 Avian Dietar y Toxicity

MRID Citation Reference

43879101 2059366 Palmer, S.; Beavers, J. (1995) Diphenylamine: A Dietary LC50 Study with the Mallard: Lab Project Number: DLR52: 436

- 101: 436/100295/MLCSDT.WC/CHP105. Unpublished study prepared by Wildlife International Ltd. 74 p.

72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

107141 Pitcher, F. (1972) No Scald DPA: Rainbow Trout (Salmo gairdneri)|: Test No. 499. (U.S. Agricultural Research Service, Pesticides Regulation Div., Animal Biology Laboratory; unpublished study; CDL:130356

- A)

43055201 Arce, G. (1993) Letter Sent to Office of Pesticide Programs dated December 10, 1993 concerning results of a range

- finding fish toxicity study. Prepared by Elf Atochem N. America, Inc. 11 p.

43879001 2059365 Drottar, K.; Swigert, J. (1995) Diphenylamine Technical: A 96

- Hour Flow

- Through Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report: Lab Project Number: SDR20: 436A

- 101: 436/100295/RBT

- 96H2/CHP105. Unpublished study prepared by W ildlife International Ltd. 99 p.

72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

43878301 2059363 Drottar, K.; Swigert, J. (1995) Diphenylamine Technical: A 48

- Hour Flow

-- Page 29 of 31

- Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Final Report: Lab Project Number: SDR20: 436A

- 102: MP

- DPAP

- MA. Unpublished study prepared by Wildlife International Ltd. 97 p.

9. Appendix B . Text from Memo (with CBI Redacted) from the DPA Task Force in Response to Use Questions from EPA

DPA TASK FORCE RESPONSE TO EPA QUESTIONS REGARDING

DIPHENYLAMINE

Are all applications indoors?

No, truck and bin drenching is done outside. Thermal fogging is perf ormed inside a sealed, enclosed room but the applicators and thermofoggers are in an open area outside of the room.

• Describe how typical apple treatments for the allowed application methods such as thermal fogging, tank dipping, drenching, conveyor floodi ng, and spraying of apples are performed. Are all of these methods still used, allowed on labels, and supported for registration review? Explain the truck drenching use.

The vast majority of DPA application is to apple bins. Each bin contains approxima tely 900 pounds of apples. Very little application to apples outside of bin would be performed.

Thermal fogging is done in an enclosed storage room. The bins are placed in the chamber and the chamber is closed. DPA solution is mixed outside then “fog ged” into the storage room using the appropriate equipment.

Drenching or conveyor flooding (either chain or track drenching) is done by direct spray of the DPA solution on the apple bins in a stationary position or as the apples move past the spray nozzl es on a chain or track driven conveyor belt.

Truck drenching can be compared to a car wash. The truck pulls forward so that the front of bed is under the spray nozzle and the truck pulls forward until all bins in the truck bed are

treated. The truck remains stationary in a draining area allowing the spray material to drain before putting bins in storage. Truck drenching may be done on as few as 20 bins and up to

96 bins.

Tank dipping is no longer used and will not be supported.

• Where does the us ed liquid go after use? How is used material disposed of? Does any waste material containing diphenylamine go down the drain of a storage facility or food processing facility? Are the drainage wastes covered by a NPDES permit or prohibited by label langua ge? Is waste material applied outdoors such as to holding ponds, land application, or discharged directly to surface water.- Page 30 of 31

- Liquids are collected after application and generally recycled for further applications. None of the waste material containing DP A goes down the drain of a storage facility or food processing facility. All discharges are in accordance with NPDES permits and the regulatory authority in each particular State or region. Based on NPDES requirements, waste materials can be disposed of i n l ined lagoons , as dust abatement liquids or land applied. For the lined lagoon disposal, the waste solution is added to imperviously lined, in

- ground, engineered

structures, which rely largely upon evaporation for water removal. Dust abatement is the application of wastewater to unpaved bin storage lots and unpaved roads (i.e., orchard roads) for the purpose of dust suppression. Land application is an engineered system for applying

wastewater to a vegetated land surface. DPA waste solutions are not di scharged directly to

surface waters.

• How much is applied in a typical facility in one day (min, max, average)? How many apples are typically treated per day (min, max, average)?

The application rate is application of 100 gallons of product to 30 bins of apples. The application rate ranges from 1000

– 2200 ppm with an average 1500 ppm. The number of apple bins typically treated in one day depends on the region of the country and apple production. Application can range from 1000

- 5000 apple bins/day wit h an average of 2500 apple bins/day could be treated depending on the size of the packing house. Washington State is the largest producer and generally has large packing facilities which would be at the upper end of the range. In other regions of the cou ntry with less apple production, the daily number of bins treated would be at the lower end of the range.

• What is the typical size of the room treated for the thermal fogging treatment (min, max, average)?

The typical thermal fogging room can hold fro m a minimum of 500 apple bins to a maximum of 6,000 apple bins with an average room holding 1,800 apple bins.

• What is the total usage (lbs) per year for the last 5

- 10 years?

The total annual usage based on sales for DECCO and Pace is found in Tables 1 a nd 2. As this is confidential business information, it should be maintained as confidential.

• Are drench wastes still disposed of in the field? Please describe.

As noted above, both dust abatement disposal and land applications are approved by NPDES

pe rmits.

• What are the main methods of application used now? Is it almost all fogging, or are the other methods (involving water) still used?

The primary application is drench which is > 50% of applications followed by thermal fogging at approximately 25% of applications. Over the few years, more facilities have been converting to thermal fogging and it is expected to continue. The change to thermal fogging- Page 31 of 31

- over the last few years can be seen in the DECCO and Pace sales information found in

Confidential Tables 1 and 2.

• Are any drench or spray applications to apples conducted in outside environments (eg trucks, bins, etc)?

As discussed above, truck and bin drench and spray applications are conducted outdoors in areas designated for the application and permitting the collection of any runoff from the sprayed bins. Thermal fogging is done indoors.

• When using foggers with room venting before reentry, explain the configuration of exhaust air piping and potential deposition near the site

.

In general, room fogging is achieved by entry of the fog through a portal in the lower part of the chamber approximately 3 feet above the floor. Room cooling systems and hum idifiers are turned off 12 hours prior to fumigation and during fumigation. All room air circulation fans are turned off prior to fumigation to allow DPA permeation throughout the room and turned on one hour after treatment. Venting is done through ceilin g vents. Room cooling systems and humidifiers may be turned on several hours after completion of fumigation as all fogger should have been removed by that time. Venting is to the outside.

• Is it your understanding that after the required room venting times on the label, no PPE is needed or used in practice?

That is correct.

• Are you aware your label mentions not to use paper wraps impregnated with DPA, but there are no registrations for wraps, or are wraps still used?

Paper wraps impregnated with DPA are not produced or used. This appears to be a carryover

from much older labels and should be removed.

• Some labels allow a second treatment with prolonged storage (eg> 4 months), but some labels are silent on retreatment. What is the actual pract ice?

Retreatment is found on one registrants’ label (Pace). Use of a second treatment is permitted but is very seldom done, if at all.