3210 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

ACTION: Notice.

SUMMARY: This notice announces receipt

of applications to register pesticide

products containing active ingredients

not included in any previously

registered products pursuant to the

provisions of section 3(c)(4) of the

Federal Insecticide, Fungicide, and

Rodenticide Act (FIFRA), as amended.

DATES: Written comments must be

submitted by February 13, 1995.

ADDRESSES: By mail, submit written

comments identified by the document

control number [OPP–30378] and the

registration/file number, to: Public

Response and Program Resources

Branch, Field Operations Divisions

(7506C), Office of Pesticide Programs,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460. In

person, bring comments to:

Environmental Protection Agency, Rm.

1132, CM #2, 1921 Jefferson Davis Hwy.,

Arlington, VA.

Information submitted as a comment

concerning this notice may be claimed

confidential by marking any part or all

of that information as ‘‘Confidential

Business Information’’ (CBI).

Information so marked will not be

disclosed except in accordance with

procedures set forth in 40 CFR part 2.

A copy of the comment that does not

contain CBI must be submitted for

inclusion in the public record.

Information not marked confidential

may be disclosed publicly by EPA

without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

given above, from 8 a.m. to 4 p.m.,

Monday through Friday, excluding

holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Janet L. Andersen, Acting Director,

Biopesticides and Pollution Prevention

Division (7501W), Office of Pesticide

Programs, Environmental Protection

Agency, 401 M St., SW., Washington,

DC 20460. Office location and telephone

number: Rm. CS51B6, Westfield

Building North Tower, 2800 Crystal

Drive, Arlington, VA 22202, (703–308–

8712).

SUPPLEMENTARY INFORMATION: EPA

received applications as follows to

register pesticide products containing

active ingredients not included in any

previously registered products pursuant

to the provisions of section 3(c)(4) of

FIFRA. Notice of receipt of these

applications does not imply a decision

by the Agency on the applications.

Products Containing Active Ingredients

Not Included In Any Previously

Registered Products

1. File Symbol: 56336–RT. Applicant:

Consep, Inc., 213 Southwest Columbia

St., Bend, OR 97702. Product name:

Consep SPRA4 Peach Twig Borer

Pheromone Sprayable. Insecticide.

Active ingredients: (E)-5-decenyl acetate

at 46.20 percent and (E)-5-decenol at

9.60 percent. For tree nut crops and

other crops; for the control of peach

twig borer.

2. File Symbol: 56336–RL. Applicant:

Consep, Inc. Product name: Checkmate

Peach Twig Borer (PTB) Technical

Pheromone. Insecticide. Active

ingredients: (E)-5-decenyl acetate at 77

percent and (E)-5-decenol at 16.00

percent. For use in manufacturing or

formulation only.

3. File Symbol: 56336–RA. Applicant:

Consep, Inc. Product name: Check-mate

PTB Dispenser. Insecticide. Active

ingredients: (E)-5-decenyl acetate at 7.92

percent and (E)-5-decenol at 1.65

percent. For tree nut crops and other

crops; for the control of peach twig

borer.

Notice of approval or denial of an

application to register a pesticide

product will be announced in the

Federal Register. The procedure for

requesting data will be given in the

Federal Register if an application is

approved.

Comments received within the

specified time period will be considered

before a final decision is made;

comments received after the time

specified will be considered only to the

extent possible without delaying

processing of the application.

Written comments filed pursuant to

this notice, will be available in the

Public Response and Program Resources

Branch, Field Operation Division office

at the address provided from 8 a.m. to

4 p.m., Monday through Friday, except

legal holidays. It is suggested that

persons interested in reviewing the

application file, telephone the FOD

office (703–305–5805), to ensure that

the file is available on the date of

intended visit.

Authority: 7 U.S.C. 136.

List of Subjects

Environmental protection, Pesticides

and pests, Product registration.

Dated: January 6, 1995.

Janet L. Andersen,

Acting Director, Biopesticides and Pollution

Prevention Division, Office of Pesticide

Programs.

[FR Doc. 95–932 Filed 1–12–95; 8:45 am]

BILLING CODE 6560–50–F

[OPP–30000/59; FRL–4918–8]

Propoxur (Baygon, Sendran);

Proposed Decision Not to Initiate a

Special Review

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice; Proposed Decision Not

To Initiate a Special Review.

SUMMARY: This Notice announces EPA’s

proposed decision not to initiate a

Special Review of the insecticide

propoxur (Baygon, Sendran; 2-

isopropoxy-phenyl-N-methylcarbamate).

The Special Review was originally

proposed on the basis of potential

carcinogenic risks to applicators and

home residents from the registered uses.

After evaluating new exposure and

carcinogenicity data, and in light of

voluntary cancellation and label

amendment actions which eliminated

those uses posing the greatest concern,

EPA believes that the estimated risks do

not warrant initiation of Special Review.

DATES: Written comments must be

received on or before March 14, 1995.

ADDRESSES: Submit three copies of

written comments, bearing the

document control number ‘‘OPP–30000/

59,’’ by mail to: Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

comments to: Rm 1132, Crystal Mall

Building #2, 1921 Jefferson Davis

Highway, Arlington, VA 22202.

Information submitted in any

comment concerning this Notice may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI), and so marking on the cover of

each copy submitted. Information so

marked will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. Two complete copies

should be submitted with section(s)

claimed CBI clearly marked, and

numbered consecutively throughout the

text. The third copy should have the

claimed CBI section(s) excised and

numbered consecutively (as in the two

complete copies) without modifying the

remaining text. The propoxur public

docket has been open for public

inspection since February 1992. An

index of propoxur documents,

information supporting this proposed

action and any submitted comment or

part of a comment is available for public

inspection and copying in the Public

Docket, Rm. 1132 at the Virginia address

given above. Office hours are from 8
Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices 3211

a.m. to 4:30 p.m., Monday through

Friday, except legal holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Ann Sibold, Review Manager,

Environmental Protection Agency

(7508W), 401 M St., SW., Washington,

DC 20460. Office location and telephone

number: 2800 Crystal Drive, 3rd Floor,

Arlington, VA 22202, (703) 308–8033.

SUPPLEMENTARY INFORMATION: EPA

announces its proposed decision not to

initiate a Special Review of propoxur.

EPA has re-evaluated the concerns

raised in its March 22, 1988 preliminary

notification letter to registrants (Refs. 1),

along with other relevant information

and the regulatory actions taken since

the preliminary notification. Based on

this re-evaluation, EPA has determined

that a Special Review of propoxur is not

warranted at this time.

I. Introduction

A. Chemical Background

Propoxur is the common name for 2-

isopropoxy-phenyl-N-methylcarbamate,

a carbamate insecticide for the control

of insects and other arthropods inside

and outside of buildings and on pets.

The holders of the two U.S. technical

registrations of propoxur, Baygon and

Sendran, are Miles Inc., Agriculture

Division (formerly Mobay Corp.,

Agricultural Chemical Division), and

Miles Inc., Animal Health Division

(formerly Mobay Corp., Animal Health

Division) respectively. Miles Inc. is a

subsidiary of Bayer, AG, Germany.

Approximately 100 companies hold

active registrations for intermediate

and/or end-use products in which

propoxur is an active ingredient (a.i.).

There are approximately 200

registrations for formulations containing

propoxur, including 2 technical

products, Baygon (96 percent) and

Sendran (94 percent), and 19

formulation intermediates.

End-use propoxur products provide

contact kill and residual control of a

wide variety of common indoor insects,

such as ants and cockroaches. Propoxur

formulations are also sold for the

control of fleas and ticks on pets. In

addition, propoxur-containing products

are sold for limited outdoor uses. For

example, it is used in wasp and hornet

sprays, and application to and around

building surfaces and foundations,

patios, driveways, and sidewalks.

Propoxur products are sold as wettable

powders, emulsifiable concentrates,

aerosols, total-release aerosol foggers,

ready-to-use (RTU) liquids, granular

baits, enclosed baits, impregnated or

controlled release strips and shelf paper.

Wettable powders and emulsifiable

concentrates (diluted and mixed with

water) and RTU liquids can be applied

using a compressed air sprayer in both

household and non-household settings.

Pest Control Operators (PCOs) use

emulsifiable concentrates, wettable

powders, and granular products. Pet-use

products are sold as aerosol sprays,

collars, and dab-ons. There are a

number of propoxur insecticides which

contain other active ingredients such as

dichlorvos (DDVP), piperonyl butoxide,

pyrethrins, allethrin, and N-octyl

bicycloheptene dicarboximide. EPA

estimates that combined indoor and

outdoor household uses (applied by

both residents and PCOs) account for 80

to 92 percent of total propoxur usage in

the United States. PCOs apply

approximately 6 percent to 9 percent of

the total propoxur used in homes.

Residents of single family homes,

condominiums and apartments are the

primary users of propoxur products sold

as aerosols or RTU liquids. There is

limited use (up to about 8 percent) of

propoxur in commercial establishments.

B. Legal Background

1. Statute. A pesticide product may be

sold or distributed in the United States

only if it is registered or exempt from

registration under the Federal

Insecticide, Fungicide, and Rodenticide

Act (FIFRA) as amended (7 U.S.C. 136

et seq.). Before a product can be

registered it must be shown that it can

be used without ‘‘unreasonable adverse

effects on the environment’’ (FIFRA

section 3(c)(5)), that is, without causing

‘‘any unreasonable risk to man or the

environment, taking into account the

economic, social, and environmental

costs and benefits of the use of the

pesticide’’ (FIFRA section 2(bb)). The

burden of proving that a pesticide meets

this standard for registration is at all

times on the proponent of initial or

continued registration. If, at any time,

EPA determines that a pesticide no

longer meets this standard for

registration or reregistration, the

Administrator may cancel the

registration under sections 3 or 6 of

FIFRA.

2. Special Review process. EPA

initiates a Special Review when it

determines that a pesticide meets or

exceeds one or more of the risk criteria

set out in the regulations (40 CFR

154.7). The Special Review process is

described in 40 CFR part 154, published

in the Federal Register of November 27,

1985 (50 FR 49015). During a Special

Review, EPA: (1) announces and

describes EPA’s finding that use of the

pesticide meets one or more of the risk

criteria set forth in 40 CFR 154.7; (2)

establishes a public docket; (3) proposes

a regulatory decision; (4) solicits

comments from the public on the issues

and proposed regulatory decision of the

Special Review, and from the Secretary

of Agriculture and the FIFRA Scientific

Advisory Panel on the Agency’s analysis

and proposed decision; (5) reviews and

responds to all significant comments

submitted within the stated time frame;

and (6) makes a final regulatory decision

based on the risks and benefits

associated with each use of the

pesticide.

Prior to formal initiation of a Special

Review, a preliminary notification is

sent to registrants and applicants for

registration pursuant to 40 CFR 154.21

announcing that the Agency is

considering commencing a Special

Review.

If the Agency determines, after

issuance of a notification pursuant to 40

CFR 154.21, that it will not conduct a

Special Review, it is required under 40

CFR 154.23 to issue a proposed decision

to be published in the Federal Register.

This Notice is being issued under 40

CFR 154.23. A period of not less than

30 days is to be provided for public

comment on the Proposed Decision Not

To Initiate a Special Review.

Subsequent to receipt and evaluation of

comments on the Proposed Decision Not

To Initiate a Special Review, the

Administrator is required by 40 CFR

154.25 to publish in the Federal

Register a final decision regarding

whether or not a Special Review will be

conducted.

C. Regulatory Background

1. Data Call-In (DCI) Notices. EPA

issued DCI Notices to various propoxur

registrants in 1987, 1988, 1989, and

1992. Following these DCIs, registrants

either voluntarily cancelled or deleted

from labels certain uses, as follows: all

propoxur-containing dusts; all outdoor

uses (except for the following limited

uses: application to the exterior of

buildings and around foundations,

patios, driveways, and sidewalks);

ready-to-use (RTU) liquids applied with

trigger pump sprayers; and certain pet

uses including dips and shampoos.

Miles Inc., the registrant of technical

propoxur, submitted five acceptable

studies that EPA used in its exposure

assessments (PCO and post-application

exposures from crack and crevice

treatments using compressed air

sprayers, residential applicator (RA)

exposure using aerosol sprays, PCO

exposure from granular bait uses, and

applicator exposure from pet aerosols).

2. Notification of registrants. On

March 22, 1988, pursuant to 40 CFR

154.21(a), EPA issued a private

(‘‘Grassley-Allen’’) notification to

propoxur registrants that the Agency
3212 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

was considering a Special Review of

propoxur (Ref. 1). EPA was concerned

with propoxur’s potential cancer risk to

applicators when applying propoxur

indoors and outdoors, to occupants of

treated buildings, and from treating pets

with propoxur. EPA’s concern was

based on a 1984 study which reported

increases in the incidences of malignant

and benign tumors in the urinary

bladders of both male and female rats,

an increase in incidence of uterine

tumors in female rats, and the early

onset and increased incidence of

hyperplasia of the urinary bladder in

these rats. EPA classified propoxur as a

Group B2 (probable human) carcinogen.

EPA noted that data from the 1987 DCI

would be used to refine estimates of

risk, and that the registrants’ responses

to this notification would be considered

in its determination whether to initiate

a Special Review.

3. 1990 Notice of Intent to Suspend,

and 1991 Settlement Agreement. On

October 15, 1990, EPA sent a Notice of

Intent to Suspend (NOITS) to Miles Inc.

and the five manufacturing-use

producers for failure to comply with the

terms of the December 14, 1987 DCI

regarding certain exposure studies. The

requirements of the 1987 DCI were

legally binding only for those

companies who received the DCI. As a

result, only their products were subject

to the NOITS. Miles Inc. requested a

hearing concerning the NOITS, and

subsequently reached a settlement with

EPA on June 28, 1991. The agreement

noted that Miles Inc. had recently

submitted new studies to address the

data requirements for indoor

pressurized aerosol and granular bait

products. EPA agreed to issue a new DCI

requiring end-use registrants to submit

exposure studies not committed to by

Miles Inc., such as a trigger pump spray

study. If no other end-use registrant

committed to generate data to support

these uses, Miles Inc. would amend its

labels for its manufacturing-use

products to prohibit the unsupported

uses. On August 12, 1991, after

accepting the aerosol spray and PCO

granular bait studies submitted by Miles

Inc., EPA withdrew the NOITS on all of

the registered products of

manufacturing-use producers which

these two studies supported. RTU liquid

products applied with trigger-pump

sprayers subject to the NOITS remained

suspended. Subsequently, all registrants

with these products amended their

propoxur end-use product labels to

delete use of RTU liquids with triggerpump sprayers.

II. Estimation of Propoxur Cancer Risks

to RAs, PCOs, and Residents of Treated

Buildings

Since the 1988 notification to

registrants that EPA was considering a

Special Review of propoxur, the Agency

has refined its risk assessments. The

current risk assessment is discussed in

this unit.

A. Hazard Identification —

Carcinogenicity

1. Animal carcinogenicity studies— a.

Rat studies. In a 1984 2–year rat chronic

feeding/carcinogenicity study, propoxur

was administered in a standard

European diet (Altromin 1321) to SPF

Wistar rats, at concentrations of 0, 200,

1,000, or 5,000 ppm propoxur. At the 1–

year interim sacrifice, there was an

increased incidence of urinary bladder

epithelial hyperplasia in the two highest

dose groups of male and female rats.

There was also a urinary bladder

papilloma in 1 of the 10 highest dose

males. Animals that died, were

moribund, or were sacrificed at term

also had dose-related increases in the

degree and extent of urothelial

hyperplasia. Highly significant increases

in urinary bladder papillomas,

carcinomas and combined papillomas/

carcinomas (67 to 75 percent verses 0

percent in the controls) were observed

in male and female rats at the highest

dietary exposure level (5,000 ppm) in

this study. Bladder tumors are

considered to be relatively rare in

rodents, especially in the absence of

silica crystalline deposits. Additionally,

there was an increased incidence of

uterine carcinoma (not statistically

significant at p > 0.05) in females at the

highest dose level. However, it appeared

that this tumor had a tendency to

develop earlier and/or grow more

rapidly than the control group. The

urinary bladder findings of the 1984

carcinogenicity study were confirmed in

a subsequent 2–year study completed in

1988 with female Wistar rats on an

Altromin diet. There were significant

increases in urinary bladder papillomas

and combined papillomas/carcinomas at

the three highest dose levels tested

(3,000, 5,000 and 8,000 ppm) and in

carcinomas at the highest dose level.

The dose-related trends for papillomas,

carcinomas and combined papillomas/

carcinomas were also significant. Also,

the observed hyperplasia of the urinary

bladder was dose-and time-dependent.

However, a significant comparative pairwise increase in uterine tumors was not

observed in this study.

b. Mouse studies. In a 1982 2–year

mouse carcinogenicity feeding study,

male and female CF1/W74 mice were

fed propoxur at dose levels up to 6,000

ppm. No adverse effects on the bladder

were noted. Similarly, in a 1988 1–year

mouse feeding study, where up to 8,000

ppm propoxur in an Altromin diet was

administered to female NMRI mice, no

histopathological changes were

observed. In a 1992 B6C3F1 mouse

carcinogenicity/feeding study using up

to 8,000 ppm propoxur in an Altromin

diet, there was a dose-related increase in

bladder epithelial hyperplasia

(classified as minimal and diffuse in all

instances) at 2,000 and 8,000 ppm (not

at 500 ppm), but no indication of any

carcinogenic effect involving the urinary

bladder. However, the study did show a

dose-related trend of increased

incidence of hepatocellular adenomas in

males.

c. Other animal studies. In a 1988

study, female Syrian hamsters were fed

up to 8,000 ppm propoxur in an

Altromin diet for 1 year without

histopathological effects involving the

urinary bladder. In a 1984 1–year dog

feeding study, no adverse urinary

bladder effects were reported using dose

levels up to 1,800 ppm. Also, in a 1985

13–week oral gavage study with Rhesus

monkeys, no adverse urinary bladder

effects were noted after feeding 40 mg/

kg/day of propoxur.

2. Other studies— a. Metabolism and

biotransformation. Miles Inc. has

submitted results of a number of

biotransformation studies conducted on

different mammalian species (rat,

mouse, hamster, monkey, and human).

Propoxur is extensively metabolized

(more than 10 metabolites have been

identified) and many of the metabolites

are excreted in the urine. Because

propoxur is so completely metabolized,

there is very little or no parent

compound in urine. One of the

metabolites is 1,2-dihydroxybenzene

(‘‘M1’’ or catechol). In the rat,

approximately 7 percent to 20 percent of

propoxur is degraded to catechol.

Catechol, at high dose levels

administered by gavage, has been shown

to induce cancer in the glandular

stomach of rats. Three other metabolites

of propoxur of structural interest are: 2-

isopropoxyphenol (‘‘M2’’), 2-

isopropoxylphenyl-hydroxymethylcarbamate (‘‘M5’’), and 1-

hydroxy-2-isopropoxy-4-nitrobenzene

(‘‘M9A’’). ‘‘M9A’’ has a nitro-group

added to the phenyl ring of metabolite

‘‘M2,’’ and Miles Inc. has proposed that

it is formed in the stomach. In human

data (Ref. 2), the glucuronide conjugate

of ‘‘M2’’ was the predominant

metabolite found, with trace levels of

‘‘M9A.’’ Based on the Agency’s current

knowledge, none of the metabolites
Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices 3213

would appear to be of carcinogenic

concern.

b. Mutagenicity. Propoxur and its

metabolites, including catechol, have

not been shown to produce detectable

gene mutations, with the exception of

‘‘M5’’ (equivocal or weakly positive in

the Ames assay for Salmonella

typhimurium strain TA1535). While

propoxur appears to give no indications

of clastogenic activity in in vitro studies

submitted by Miles Inc., one published

study shows increased incidence of

sister chromatid exchange and

micronuclei in human lymphocytes

following in vitro exposure to propoxur.

Propoxur also induces S-phase mitosis

in bladder epithelial cells suggesting an

effect on cell proliferation. The ‘‘M1’’

metabolite, catechol, has been shown to

be genotoxic in several published

studies, including in vivo tests,

primarily via a clastogenic mechanism.

The presence of the ‘‘M9A’’ metabolite

suggests a possible nitrosation

mechanism; the N-nitroso derivative of

propoxur is a known mutagenic

compound. Overall, the indications are

that there is, at most, only weak

genotoxicity associated with propoxur

and/or its metabolites. It is noteworthy

that dietary exposure to propoxur has

been shown to result in an increased

incidence of S-phase in rat urinary

bladder epithelial cells (not a genotoxic

effect) suggesting that the rat urinary

bladder tumors may originate from

increased cell proliferation.

c. Effects of diet and urinary pH on

the bladder. Miles Inc. has submitted a

number of studies relating to the effects

of diet and urinary pH on the bladder.

In a 15–week feeding study, female

Wistar rats received 8,000 ppm

propoxur in Altromin diet, with or

without addition of 2 percent

ammonium chloride. Without the

ammonium chloride, the urinary pH

was more basic by approximately 2 pH

units. At termination, hyperplasia of the

urinary bladder was present in 8/14 rats

not receiving ammonium chloride and

in 1/15 rats receiving it. In two other

studies with rats given a casein semisynthetic diet (No. 1/0) and propoxur at

8,000 ppm for 4.8 or 14 weeks, and at

3,000 or 8,000 ppm propoxur for 100

weeks, no histopathologic changes in

the urinary bladder were reported.

These studies appear to support Miles

Inc.’s position that development of the

urinary bladder hyperplasia (and

subsequent tumor occurrence in rats) is

associated not only with administration

of propoxur but also with the diet and

possibly its effects on urinary pH.

3. Findings and recommendations of

EPA’s Scientific Advisory Groups. In the

September 4, 1986 Peer Review of

propoxur, the Peer Review Committee

reviewed the evidence of

carcinogenicity of propoxur from the

1984 rat feeding/carcinogenicity study,

and other toxicological data on the

chemical. The Peer Review Committee

reviewed the carcinogenic potential for

classification, and concluded that there

was sufficient evidence of

carcinogenicity to classify propoxur to

Group B2 (Probable Human

Carcinogen). The classification was

supported by the unusually high

incidence of bladder neoplasia, the

relative rarity of the bladder tumor in

rats, early onset of hyperplasia and

papilloma of the bladder, and the

somewhat uncommon finding of

bladder tumors in the absence of

crystalline (usually silica) deposits.

In the second Peer Review of

propoxur held on December 6, 1990, the

Carcinogenicity Peer Review Committee

reviewed the evidence for the Group C

Classification of propoxur by the

Carcinogen Assessment Group of EPA’s

Office of Research and Development.

The Peer Review Committee agreed to

defer discussion of the classification of

propoxur until the data from the 1988

rat carcinogenicity study had been

reviewed.

In the October 3, 1991 third Peer

Review of Propoxur, the Carcinogenicity

Peer Review Committee concluded ‘‘that

there was insufficient evidence to

change the classification of propoxur

(Group B2 carcinogen) and method of

quantification’’ at this time. However,

the Committee stated that if a speciesand diet-specific effect could be

established, and if the genotoxic mode

of action were dismissed for propoxur,

then ‘‘the use of the conventional lowdose quantitative risk assessment

method (Q1*) might not be appropriate.’’

The Committee suggested that ‘‘studies

designed to further investigate the

mechanism of action and genotoxic

potential’’ of propoxur be performed.

Specifically, the Committee suggested a

re-cutting of the bladder sections and

that a pathologist (with expertise in

bladder neoplasia) read these and reread the original bladder slides from the

1988 female rat study. The Committee

suggested that a pathologist look at

sections from all groups for uterine

pathology from the same study. The

Agency also suggested historical control

data from the registrant’s testing facility

and information on the diet composition

(Altromin 1321 compared to other

diets). In addition, to better understand

possible mechanistic considerations and

relate them to the Agency’s regulatory

position on propoxur, Miles Inc. was

advised to clarify propoxur’s genotoxic

potential and to resolve the discrepancy

created by the two dietary regimens.

Miles Inc. has responded, in part, to

the suggestions of the third

Carcinogenicity Peer Review

Committee. The Agency has discussed

with the registrant the mechanisms by

which the urinary bladder tumors are

triggered and the possible relationship

of uterine tumors to dietary propoxur.

The findings will be evaluated by the

Carcinogenicity Peer Review Committee

after all the suggested data have been

submitted. EPA does not expect that the

peer review will conclude that the

carcinogenicity of propoxur is a more

serious concern than today’s document

concludes.

4. Evaluation of carcinogenicity

data—Hazard finding. Following the

October, 1991 Peer Review, EPA reevaluated (Ref. 3) the rat urinary bladder

tumor rates from the l984 2–year feeding

study. As there was no statistical

evidence of increasing mortality with

increasing doses of propoxur, the unit

risk estimate could be obtained using a

linearized Multi-Stage model for each

sex group of rats. The resulting unit risk

estimates for both males and females

were then combined to obtain a

geometric mean. The Agency estimated

the human equivalent potency (Q1*) of

propoxur to be 3.7 × 10-3 (mg/kg/day)-1.

The Q1* represents the 95 percent upper

bound confidence limit of tumor

induction likely to occur from a given

dose of a carcinogen. It is emphasized,

that if the mechanism(s) by which the

urinary bladder tumors develop in rats

involves a threshold level, and/or if

these tumors are species-specific, then

the risk to humans would be less than

indicated by this Q1*.

5. Uncertainties in propoxur’s role In

carcinogenesis. To date, there is no clear

indication as to how propoxur produces

hyperplasia and tumors. Bladder tumors

are rare in rats, particularly in the

absence of crystalline (silica) deposits. It

has been suggested that silica deposits

may in some way participate in bladder

tumor formation, especially in the

presence of a diet that may alter the pH

of urine in the bladder. It is emphasized

that there is no indication of silica

deposits in the urinary bladders of rats

fed propoxur. However, there may be

other factors associated with induction

of hyperplasia or the formation of

tumors, such as enhancement of the

cellular response to growth factors. In

addition, the role and relative

contributions of the parent compound

and its metabolites to the process are

unknown.

Miles Inc. has taken the position that

propoxur is non-genotoxic, and that an

‘‘epigenetic’’ mechanism, such as that
3214 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

involving dietary exposure to sodium

saccharin, is likely to be responsible for

the formation of rat urinary bladder

tumors in chronic animal feeding

studies. Chronic dietary exposure to

sodium saccharin at appropriate levels

leads to urothelial hyperplasia and

subsequent bladder tumors in rats.

However, silica microcrystals are found

in the urinary bladder of rats fed sodium

saccharin and these are absent in rats

fed propoxur.

Miles Inc. recently reported on the

results of a preliminary scanning

electron microscopy study designed to

determine if silica crystalline deposits

occur in the urinary bladders of

propoxur-treated rats and their possible

role in inducing hyperplasia and tumors

as mediated by the diet and urinary pH.

No silica crystalline deposits were

observed. The registrant has maintained

its previous position of a non-genotoxic

mechanism for propoxur-induced cell

proliferative response in the rat bladder,

but added that propoxur may act like a

mitogen (that is, it promotes increased

cell division, but does not, by itself,

alter cell DNA). It is not known whether

a complex interaction of weak or

moderate genotoxic activity, cell

proliferation and cytotoxicity in the

urinary bladder results in tumor

formation, or whether cell proliferation

alone can cause this effect. Miles Inc.

has indicated that it is studying whether

there are genotoxic effects in the urinary

bladder. In the absence of this

information, which might indicate a

threshold effect, and for purposes of this

risk assessment, EPA has used the linear

multistage model that it typically uses.

The Agency has received data from

Miles Inc. which indicates the elevated

incidence (8/48 or 16.7 percent) of

uterine carcinomas observed at 5,000

ppm in a 2–year rat study was within

the range (0/50 to 10/50) observed for

historical control groups in a series of

32 chronic feeding studies in rats. The

overall incidence of uterine carcinomas

and/or adenocarcinomas was 163/2,107,

or 7.7 percent.

Until propoxur is reviewed again by

the Carcinogenicity Peer Review

Committee and concludes differently,

propoxur remains classified as a B2

carcinogen for which the carcinogenic

potency has been quantified at 3.7 × 10-3

(mg/kg/day)-1.

B. Exposure

The estimates of exposure for Pest

Control Operators (PCOs), Residential

Applicators (RAs), and residents of

treated homes are discussed below and

displayed in Table 1 below.

1. Applicator exposure. The main

routes of human exposure to propoxur

are through dermal contact with and

inhalation of residues. Residues may be

found on surfaces to which propoxur

has been applied. However, propoxur

may volatilize or evaporate during and

following application, and be deposited

onto other, untreated interior surfaces of

a building. Inhalation exposure occurs

from contact with propoxur vapors or

dust during and following application of

propoxur products. PCOs and RAs are

exposed primarily during the mixing,

loading, and application of propoxur

products to the interior or around the

exterior of buildings. Kennel workers

and pet owners are exposed while

treating animals. Residents of treated

buildings are exposed to airborne and

surface residues following application.

EPA assessed human exposure to

propoxur using data obtained from

several sources, including studies

submitted by Miles Inc. in response to

the 1987 DCI, data from the technical

literature, and surrogate data. The

exposure data and the related estimates

are discussed below.

a. Crack and crevice study of PCO

exposure. Crack and crevice treatments

are among the most popular propoxur

uses for indoor pest control. In response

to the December 14, 1987 Data Call-in

(DCI) requirement, Miles Inc. submitted

an acceptable crack and crevice study of

PCO exposure (Ref. 4), in which Miles

Inc. monitored the dermal and

inhalation exposures of three PCOs as

they treated five homes each. In this

study, PCOs used a compressed air

sprayer to apply a wettable powder

formulation of propoxur, diluted to 1.1

percent active ingredient (a.i.), to cracks

and crevices and as a limited broadcast

treatment. The PCOs wore chemicalresistant gloves, cotton/polyester

coveralls over a long sleeved shirt and

long pants, and leather boots. Dermal

exposure was monitored using gauze

patches inside and outside clothing.

Levels of residues on PCOs’ hands were

measured using an ethanol handwash.

Inhalation exposure was measured by

using personal sampling devices located

in the applicator’s breathing zone.

(Inhalation exposure was found to be

negligible compared to dermal.)

(1) Wettable powders. To estimate

PCO exposure to wettable powders, EPA

supplemented the crack and crevice

data with additional assumptions as

follows: the average PCO weighs 70 kg,

works 8 hours per day over a 20–year

working-life of a 70–year life-span, and

handles 924 oz. a.i. per year. Dermal

absorption was assumed to be 50

percent. Dermal exposure was estimated

at 5.2 × 10-3 mg/kg/day (Ref. 5).

(2) Ready-to-Use (RTU) liquids. EPA

determined that RTU liquid products

are applied at rates similar to the

wettable powder formulations, and

residues are not expected to be higher

or more persistent than those from the

wettable powder formulation. For this

reason, EPA determined the results of

the crack and crevice exposure

assessment for wettable powders should

be used to estimate PCO exposure

during application of RTU liquids (Refs.

5, 6 and 7). Thus, exposure was

estimated at 5.2 × 10-3 mg/kg/day.

b. Granular bait study. Granular baits

are formulated as dry pellets, usually

containing 2 percent propoxur. They

can be scattered on paper, pasteboards,

or on the floor at a rate of about 4 oz

per 500 to 1,000 square feet areas. Baits

are used near baseboards, in closets,

under sinks and refrigerators, around

structures, patios, sidewalks and other

places where insects may be. Miles Inc.

submitted an acceptable study of PCO

exposure to granular products. In this

study, PCOs wore gloves, long-sleeved

shirts, cotton trousers, and baseball caps

over normal clothing which consisted of

denim or cotton trousers, long-sleeved

shirts and shoes while applying 2

percent granular baits by hand to a 2 to

3 foot wide band around driveways,

sidewalks, patios, and flower beds, at

the prescribed label rate of 4 oz per

1,000 square feet (0.08 oz. a.i./1000 sq.

ft.). The granules were applied by three

PCOs, each of whom carried a 5 pound

carton of the bait in one hand while

scattering the material with the other

hand. Dermal exposure was measured

using gauze patches worn both inside

and outside the clothing and on the

front of the cap. Hand exposure was

measured from an ethanol handwash.

Airborne residues were determined by

drawing air from the breathing zone

through filters using calibrated personal

sampling pumps. Propoxur residues

were not detected in most of the

samples analyzed for dermal or

respiratory exposure. Similarly,

propoxur was not detected in hand

washes after removal of the protective

gloves. Because of the large numbers of

samples with non-detectable values,

EPA determined under these conditions

that the exposure would be negligible

for PCOs (Refs. 6, 7, and 8).

c. Aerosol pet spray study. A number

of pressurized aerosol spray products

are formulated for use directly on dogs

and cats. The amount of a.i. in the

products varies from 0.25 percent to 1

percent propoxur. In response to the

1987 DCI requirement, Miles Inc.

submitted an acceptable aerosol pet

spray study (Ref. 10). In this study,

exposures of five workers using a 0.025

percent aerosol spray of propoxur were

measured at each of three different
Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices 3215

locations as each worker applied the

spray to 20 dogs. All treatments were

conducted indoors. Each dog was

treated for 1 to 2 minutes. The elapsed

time for each replicate ranged from 45

to 90 minutes per worker. Each worker

wore a shirt with long or short sleeves

and pants, but no other protective

clothing. Urine was collected from each

subject over a 24 hour period and

analyzed for the propoxur metabolite

isopropoxyphenol (IPP) (This is the

same as 2-isopropoxyphenol or M2

discussed in Unit II.A.2.(a) of this

document.) After reviewing the

literature, EPA concluded that the total

absorbed dose of propoxur is

determined by adjusting the amount of

IPP excreted by the following factors:

the percent of propoxur excreted, the

percent IPP is of all metabolites, and the

relative molecular weights of the parent

and the metabolite IPP (Refs. 10, 11, and

12).

(1) Kennel workers. An exposure

estimate is not presented here because

the Agency does not believe pet aerosol

products are routinely used by kennel

workers. The Agency believes that

kennels are more likely to use shampoos

or dips because they are more effective

in getting rid of fleas and ticks.

Shampoos are preferred to other

formulations because they wash away

dirt, fleas, and ticks in addition to the

pesticidal action. Also, they are believed

to be easier on the animal. Aerosols and

trigger-pump sprays are sometimes used

when a pet owner declines to have a pet

shampooed or dipped. There are no

propoxur shampoos or dips registered,

and as noted elsewhere in this

document, propoxur may no longer be

applied with trigger-pump sprayers.

(2) Pet owners. In order to calculate

lifetime exposure for pet owner

applicators, EPA supplemented the

mean exposure data from the aerosol

exposure study with the following

additional assumptions. Pet owners

were assumed to weigh 70 kg, wear long

sleeved shirts and long pants during

application, and treat 1 dog four times

per year over a 70–year lifetime (Refs. 6,

7, 12, 13, and 14). Exposure was

estimated at 6.4 × 10-3 mg/kg/day per

application day.

d. Aerosol spray study of Residential

Applicator (RA) exposure. In response

to the 1987 DCI, Miles Inc. submitted a

study of residential applicator exposure

(Ref. 15). In this study, a 16 oz. aerosol

can containing 1 percent a.i. was

sprayed into cracks, crevices,

baseboards, under sinks, and in other

places where insects might be found. A

total of 15 sets of data were collected.

Applicators wore long sleeved shirts,

long pants, shoes, and baseball caps.

Dermal exposure data were gathered

from gauze patches attached both

outside and inside the clothing and on

the cap. Hand exposure data were

gathered from an ethanol handwash.

Respiratory exposure data were gathered

from microfilters contained in a cassette

attached to the lapel of the applicator.

(1) RA exposure to aerosols. EPA used

additional assumptions to calculate

exposure as follows: the RA weighs 70

kg, breathes 1.7 m3 of air per hour, uses

up the entire can of aerosol with each

use, uses four cans per year, and during

application wears a short sleeve shirt,

shorts, and shoes, which EPA believes

is a reasonable clothing scenario.

Residues below the level of detection

were assumed to be present at one-half

the level of detection. The RA was

assumed to apply propoxur every year

from age 18 to age 70. RAs were exposed

for 1 hour per application through

dermal and inhalation exposure.

(Respiratory exposure estimates were

found to be negligible compared to

dermal exposure.) Dermal absorption

was assumed to be 50 percent because

a homeowner applicator is assumed to

remain in the residence following

application. Exposure was calculated at

2.1 × 10-4 mg/kg/day (Refs 6, 7, 16, 17,

18, and 19).

(2) Outdoor uses. EPA also considered

RA exposures for outdoor application of

propoxur aerosols, which are designed

to eradicate hornet and wasp nests

around buildings and homes. These

insects commonly nest in eaves of

buildings and underneath building

structures with overhangs. These

products are generally equipped with a

delivery system that will allow the

operator to apply the aerosol at a safe

distance from the nest. An applicator of

these formulations of propoxur is likely

to be exposed for a shorter time than

would occur with indoor use products.

It is also likely that the volatile

formulations would dissipate more

quickly than similar formulations used

indoors. Thus, the exposure and

corresponding risk from outdoor aerosol

uses can be expected to be lower than

is estimated for those used in indoor

treatments (Ref. 15).

(3) RTU liquid application by RAs.

EPA has used the aerosol spray study to

calculate the maximum exposure RAs

incur when applying RTU liquids with

a compressed air sprayer to cracks and

crevices. EPA assumed that the RA

would wear a short sleeved shirt, shorts,

shoes, and no gloves and would apply

an RTU liquid four times per year. Only

dermal exposure data were used to

calculate exposure, because inhalation

was considered to be negligible.

Exposure was estimated at 2.1 × 10-4

mg/kg/day. If the RA applicator wears

clothing similar to a PCO, that is, long

sleeved shirt, long pants, and gloves,

exposure would be less (Refs. 6, 7, 12,

16, 17, 18, 19, 20, and 21).

(4) Granular products applied by RAs.

Some granular products are registered

for use in and around the home

(including limited outdoor application

to driveways, sidewalks, patios, and

foundations). These products are

applied indoors by pouring from a paper

container into a tray which is then

placed under refrigerators, by lightly

applying the product to floor under

sinks or refrigerators, or by application

to cracks and crevices that are

inaccessible to children. They are not

applied by general broadcast treatment

indoors or in large quantities. While

there are no quantitative data addressing

this use scenario, EPA believes that

potential dermal exposure would not

exceed that received from an aerosol

spray can while wearing a long sleeve

shirt and long pants. Respiratory

exposure would be negligible (Ref. 9).

Exposure from the limited outdoor

applications is not expected to be

greater than indoor exposure. The

limited outdoor use still permitted

(application to sidewalks, patios,

foundations, and driveways) is expected

to present negligible exposure to RAs.

e. Other applicator exposure

estimates. PCO and RA exposures from

total release aerosol foggers,

impregnated strips, shelf paper,

enclosed or containerized baits, pet dabons, and tick and flea collars have not

been estimated but are believed to be

negligible (Ref. 6).

2. Post application exposure.

Residents of homes are exposed from

post-application exposures, through

dermal and inhalation routes of

exposure. Home residents may also be

exposed while treating household pets.

a. Crack and crevice study of postapplication exposure. In response to the

1987 DCI, Miles Inc. submitted an

acceptable study of post application

residential exposure following a crack

and crevice and limited structural

surface treatment by commercial

applicators in five homes using Baygon

70 WP insecticide diluted to a label rate

of 1.1 percent a.i. (Ref. 22). The material

was applied as a coarse spray to cracks,

crevices, baseboards and other areas

treated for insect control using a

compressed air sprayer. An average of

1.2 oz of a.i. was applied to each house.

Surface residues and air levels of

propoxur were measured at intervals of

up to 48 hours after treatment. Eighteen

samples of each of three types of

surfaces were monitored: vinyl tile

squares represented floors and counters,
3216 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

nylon carpet squares represented carpet

and fabric squares represented furniture.

Transferable residues were measured by

wiping the sample surfaces with gauze

pads. Residue levels from different

rooms were pooled for each type of

material. The maximum geometric mean

of all the measured surface residues for

a given surface type was used to

represent the measured residue for that

surface, at the specified time intervals.

Airborne residues were determined by

drawing air through a sampling

apparatus for 1 hour periods at

designated intervals. Exposures were

calculated for three age categories of

residents: an infant, a 12 year old child,

and an adult. The infant was assumed

to weigh 7.5 kg, have a body surface

area of 4.8 ft2, and have a respiratory

volume of 0.5 m3/hr. The child was

assumed to weigh 40.5 kg, have a body

surface area of 14.8 ft2, and have a

respiratory volume of 0.9 m3/hr. The

adult was assumed to weigh 70 kg, have

a body surface area of 21 ft2, and have

a respiratory volume of 1.0 m3/hr. In

addition, they were assumed to be

exposed 24, 15, and 15 hours/day,

respectively. Assumptions about

clothing were not specified; rather

dermal exposure was expected to occur

over 50 percent of the body surface.

Individuals were assumed to contact a

50 square foot contact area in a 4–hour

interval. Exposure was assumed to

occur 365 days/year.

(1) Crack and crevice. To calculate

exposure following application of

wettable powders to cracks and

crevices, EPA assumed that 64 oz. of a

1.1 percent solution by weight (total of

0.73 oz.) would be applied once a year

for cleanout treatment and 16 oz. of a

0.5 percent solution by weight (total of

0.083 oz.) would be applied 11 times a

year for maintenance treatments.

Residents were assumed to be exposed

365 days per year over a 70–year

lifetime. Dissipation was assumed to be

60 percent, and dermal absorption was

assumed to be 50 percent of the residue

on skin surfaces, because dermal

absorption increases with length of time

exposed (Refs. 7, 18, 23, and 24).

To calculate concentrations of

propoxur in the air of treated houses,

EPA pooled air concentration data for

all rooms to yield an average air

concentration of 5.1 μg/m3. Absorption

by the inhalation route was assumed to

be 100 percent. The hours/day of

inhalation exposure were the same as

for dermal exposure. Total dermal and

inhalation exposure was calculated at

2.8 × 10-4 mg/kg/day (Ref. 23).

EPA realizes exposure could also arise

from an oral route. For example,

residues could settle on food

preparation surfaces or on food. Another

potential source of oral exposure could

arise from residues on toys or other

similar items. In 1989, EPA reviewed

the Miles study which measured

amounts of propoxur found on surfaces

following crack and crevice residential

treatment, but the exposure assessment

did not address potential oral exposure.

At this time EPA does not have a

methodology to derive estimates of oral

exposure based on residues on these

surfaces, food, or toys (Ref. 22). EPA

believes that if it were possible to

quantify oral exposure resulting from

residential use of propoxur, it is

unlikely it would greatly change the

exposure estimates for this chemical.

(2) RTU liquids. Using the wettable

powder exposure assessment, EPA also

estimated post application exposure

following 12 applications per year of a

0.5 percent RTU product by a PCO (Ref.

23). Reducing this exposure threefold,

EPA estimated post application

exposure following four applications

per year of a 0.5 percent RTU liquid

propoxur product by an RA. Exposure

was estimated at 9.3 × 10-5 mg/kg/day

(Ref. 19).

(3) Aerosols. Miles Inc. elected not to

submit an aerosol spray study for postapplication human exposure to aerosol

products, so EPA used the post

application exposure data from the

crack and crevice spray study as a

surrogate. EPA adjusted the crack and

crevice data to reflect the quantity of a.i.

applied during application of a 16 oz.

can of 1 percent propoxur aerosol four

times per year for 70 years. Total dermal

and inhalation exposure was estimated

at 5.7 × 10-5 mg/kg/day (Refs. 20 and

25).

(4) Total release aerosol foggers. To

estimate post application exposure from

total release aerosol foggers, EPA used

the assumptions of the exposure

assessment developed for post

application exposure following aerosol

use. Thus, the total release aerosol

fogger (and also the aerosol) exposure

assessment is based on the crack and

crevice data. EPA believes it is

reasonable to use the crack and crevice

data to estimate total release aerosol

fogger exposure for the following

reasons. First, the crack and crevice

study showed that residues are found

throughout the house even though a

limited area was treated. A similar

distribution of residues would be

expected with total release aerosol

foggers. Second, the total amount of

material released in a total release

aerosol fogger is much less than the total

amount applied in a crack and crevice

application. Third, residues would be

deposited on surfaces that people rarely

contact, such as ceilings. Exposure

(dermal and inhalation) was estimated

at 5.7 × 10-5 mg/kg/day (Refs. 6, 20, and

25).

b. Pest strip study. After Miles Inc.

submitted an unacceptable post

application exposure study (Ref. 26),

EPA updated a 1985 exposure

assessment for impregnated strips. This

assessment was based on a study in the

technical literature (Ref. 27).

(1) Pest strips. EPA assumed that

dermal exposure is negligible and 100

percent of propoxur inhaled by the

individual is absorbed. Furthermore, the

individual was assumed to be exposed

24 hours/day, 365 days/year for 70 years

of an average lifetime, and the strips

replaced when efficiency diminishes

(Refs. 6, 7, and 28). EPA believes these

exposure estimates are conservative

because the only remaining registrations

for pest strips are in areas where human

exposure is minimal, such as

communications boxes. Inhalation

exposure was estimated at 1.1 × 10-4 mg/

kg/day.

(2) Tick and flea collars. The

registrants were not required to submit

data on residents’ post application

exposure to the propoxur found in tick

and flea collars. Using data from the

impregnated strips study, EPA

estimated exposure to residents from

surrogate data based on propoxur pest

strips (Ref. 26) and dogs. EPA assumed

that respiratory absorption is 100

percent, and the exposure is constant

over a 70-year lifetime. Inhalation

exposure was estimated at 6.3 × 10-6 mg/

kg/day (Refs. 6, 7, and 28).

c. Other post application exposure

estimates. Residents’ (including

children’s) post application exposures

from shelf paper, enclosed or

containerized baits, and other pet

products, including dab-ons and

aerosols, have not been estimated but

are believed to be negligible (Refs. 6 and

19). EPA believes post application

exposure to granular products will not

exceed that from aerosol and would

probably be much less. (Ref. 9)
Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices 3217

TABLE 1.—PROPOXUR USES AND EXPOSURE ESTIMATES FOR PCOS, RAS, KENNEL WORKERS, PET OWNERS, AND

RESIDENTS OF TREATED HOMES

Use Applicator Exposure (mg/kg/

day)

Resident Post Application Exposure (mg/

kg/day)

Crack and Crevice.

PCO Application ........................................................................................... 5.2 × 10-3a 2.8 × 10-4a,b

RA Application .............................................................................................. 2.1 × 10-4a 9.3 × 10-5a,b

Aerosols.

RA Application .............................................................................................. 2.1 × 10-4a 5.7 × 10-5a,b

Granular Baits.

PCO Application ........................................................................................... negligible negligible

RA Application .............................................................................................. negligible negligible

Pet Aerosols.

Pet Owner Application .................................................................................. 6.4 × 10-3 negligible

Total Release Aerosol Foggers.

RA Application .............................................................................................. negligible 5.7 × 10-5a,b

Pest Strips.

RA Application .............................................................................................. negligible 1.1 × 10-4

Shelf Paper.

RA Application .............................................................................................. negligible negligible

Enclosed or Containerized Baits.

PCO Application ........................................................................................... negligible negligible

RA Application .............................................................................................. negligible negligible

Pet Dab-ons.

RA Application .............................................................................................. negligible negligible

Pet Tick and Flea Collars.

RA Application .............................................................................................. negligible 6.3 × 10-6

a Dermal absorption is assumed to be 50 percent.

b Dermal contact area is assumed to be 50 sq. ft.

C. Risk Assessment

1. Non-dietary exposure. Using the

exposure estimates discussed above and

the Q1* for propoxur, EPA determined

the excess lifetime cancer risks to

applicators and residents of treated

homes. The risks are displayed in Table

2 below. Total residential risks do not

exceed the Agency’s level of concern.

The Agency’s policy for applicator risk

is that risk should be as close to

negligible as possible. The risk for PCOs

applying propoxur to cracks and

crevices is 5.4 × 10-6. Labels require

PCOs to wear coveralls, long sleeved

shirts, long pants, boots, and chemical

resistant gloves. The Agency believes

there are no other reasonable protective

clothing requirements which can be

required to reduce the risk further.

Thus, this level of risk is in compliance

with the Agency’s worker risk policy. In

addition, the Agency recently adopted a

policy to incorporate a unified

interspecies scaling factor (Ref. 29)

when estimating the Q1*. This factor

adjusts the Q1* by a ratio of body

surface to body weight. Its exact value

depends on the animal test species

used. The risks set forth in the following

Table 2 have not been calculated using

this new scaling factor. If they had, the

risk would be approximately one third

lower.

TABLE 2.—PROPOXUR USES AND EXCESS LIFETIME CANCER RISKS FOR PCOS, KENNEL WORKERS, RAS, PET OWNERS,

AND RESIDENTS OF TREATED HOMES.

Use Applicator Risk Resident Post Application Risk Total Residential Riska

Crack and Crevice.

PCO Application ................................................ 5.4 × 10-6 1.0 × 10-6 1.0 × 10-6

RA Application .................................................. 7.8 × 10-7 3.4 × 10-7 1.1 × 10-6

Aerosols.

RA Application .................................................. 7.8 × 10-7 2.1 × 10-7 9.9 × 10-7

Granular Baits.

PCO Application ................................................ negligible negligible negligible
3218 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

TABLE 2.—PROPOXUR USES AND EXCESS LIFETIME CANCER RISKS FOR PCOS, KENNEL WORKERS, RAS, PET OWNERS,

AND RESIDENTS OF TREATED HOMES.—Continued

Use Applicator Risk Resident Post Application Risk Total Residential Riska

RA Application .................................................. negligible negligible negligible

Pet Aerosols.

Pet Owner Application ...................................... 2.6 × 10-7 negligible 2.6 × 10-7

Total Release Aerosol Foggers.

RA Application .................................................. negligible 2.1 × 10-7 2.1 × 10-7

Pest Strips.

RA Application .................................................. negligible 4.1 × 10-7 4.1 × 10-7

Shelf Paper.

RA Application .................................................. negligible negligible negligible

Enclosed or Containerized Baits.

PCO Application ................................................ negligible negligible negligible

RA Application .................................................. negligible negligible negligible

Pet Dab-ons.

RA Application .................................................. negligible negligible negligible

Pet Tick and Flea Collars.

RA Application .................................................. negligible 2.3 × 10-8 2.3 × 10-8

a When application is by PCO, total residential risk includes only risk from post application exposure as the PCO is assumed to have left the treated house.

When application is by RA, total residential risk includes both RA risk and post application risk, as the RA is assumed to stay in the treated house.

2. Evaluation of the use of propoxur

in food handling establishments.

Propoxur is registered to control pests in

food-handling establishments. For

example, propoxur products are labeled

for crack and crevice application in food

areas of food handling establishments. If

applications in these areas result in

residues of propoxur on food, a food

additive regulation would be required to

be established under section 409 of the

Federal Food, Drug and Cosmetic Act

(FFDCA) to cover expected levels of

residues on treated food and allow their

legal entry into interstate commerce.

Miles Inc. filed a petition (9H5199,

dated 10/16/78) which stated that crack

and crevice applications in food areas of

handling establishments resulted in

residues on food. Miles, Inc. further

proposed a food additive regulation of

0.2 ppm propoxur on all foods.

Section 409 of the FFDCA contains a

provision called the Delaney Clause

which specifically provides that, with

limited exceptions, no additive is

deemed safe if it has been found to

induce cancer in man or animals. (21

U.S.C. 348(c)(5)).

The Delaney Clause has been

interpreted as baring the establishment

of food additive regulations for any

pesticides that have been found to

induce cancer in animals or humans,

regardless of the level of risk.(Les v.

Reilly 968 F2d935 (9th Cir 1992) Cert

Denied, 113 S. Ct. 1361 (1993).

Because propoxur has been

determined to induce cancer within the

meaning of the Delaney clause (Ref. 30),

the necessary food additive regulation

cannot be established. In accordance

with EPA’s policy and regulations, (see

40 CFR 152.112(g)) requiring

coordination of its FIFRA and FFDCA

authorities, EPA will propose

cancellation of the use of propoxur in

food areas of food handling

establishments in the near future.

3. Risk to children. In 1993 the

National Academy of Sciences (NAS)

reported on pesticides in the diets of

infants and children (Ref. 31). While it

did not consider specifically children’s

risks arising from exposure to propoxur,

it raised a number of issues about

children’s risk from exposure to

pesticides in general. This section will

discuss some of these issues as they

relate to the risk assessment set forth in

this document.

a. Hazard assessment. The NAS study

notes that children may be more or less

susceptible to the effects of pesticides.

In terms of the propoxur hazard

assessment, a question may be raised

about whether children metabolize

propoxur differently or whether

children are more or less sensitive to

propoxur’s toxic end point—

proliferation of urinary bladder

epithelial cells. The studies reviewed

for the propoxur hazard assessment

were largely performed and accepted by

the Agency before the results of the NAS

study were available. They do not

address these issues. EPA’s general

approach when addressing gaps in

scientific knowledge is to build

conservatism into risk assessments to

protect children and other sensitive

populations. EPA used its conservative

(in terms of protecting human health)

model of estimating carcinogenic

potency. It represents the 95 percent

upper bound confidence limit of tumor

induction likely to occur from a given

dose. EPA has chosen this approach to

provide a margin of safety for

uncertainties in characterizing the

carcinogenic response, for the existence

of more sensitive individuals, such as

children, in the exposed population and

for possible synergism of pesticides and

metabolites. For this reason, EPA

believes the estimates of cancer risk are

conservative. In the review of the

toxicology studies in unit II.A. of this

document, EPA has noted the

possibility that the Carcinogenicity Peer

Review Committee may re-evaluate

propoxur after all the suggested data

have been submitted. EPA does not

expect that the peer review will

conclude that the carcinogenicity of

propoxur is a more serious concern than

today’s document concludes.

For the future, EPA is taking

additional steps to determine whether

children are more or less susceptible to

the effects of pesticides. EPA is in the
Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices 3219

process of planning new research and

reviewing its risk assessment methods

so that it can better evaluate how these

residues affect children.

b. Dietary exposure. The NAS Report

raised a concern about children’s

exposure to pesticide residues in the

diet. As noted in unit II.C.2. of this

document, EPA will propose that the

use of propoxur in food handling

establishments will be cancelled in the

near future.

c. Non-dietary exposure. The NAS

Report also pointed out that non-dietary

sources of pesticides should be

considered when estimating total

exposure of children. The propoxur

exposure assessment considers children

and infant’s exposure explicitly in

assessing post application exposure. For

example, the post application exposure

assessment considered, for both infants

and children separately, different ratios

of skin to body weight, different

respiratory volumes, and different times

spent in a treated house. In terms of the

propoxur exposure assessment, a

question may be raised about children’s

exposure to residues from ingested

household dust, pets wearing flea

collars, or sprayed pets. Presently, EPA

does not have a methodology for

measuring ingested household dust.

EPA believes exposure from flea collars

is primarily inhalation, this source of

exposure is captured in the exposure

assessment, and the risk is small (10-8).

Children’s exposure to pets treated with

aerosol sprays has not been specifically

measured. However, the pet owner

applicator exposure assessment assumes

pets will be treated four times per year

for every year of a 70–year lifetime. EPA

believes it is unlikely that children will

be routinely treating household pets for

fleas, and thus believes this exposure

estimate is very conservative.

For the future, EPA is initiating a

residential research strategy to support

development of exposure monitoring

and assessment of test guidelines, based

on the unique behavior of infants and

children, including dermal contact with

treated surfaces, hand-to-mouth contact,

and object-to mouth contact as well as

other modes of exposure. The goal is to

develop comprehensive guidelines for

assessing exposure to pesticides both

inside residences and in other settings,

such as yards. EPA would like to set

appropriate times for returning to

treated residences. The research strategy

will also compare exposures of the

suburban child and the inner city child

who may be exposed to structural

pesticide residues carried by ventilation

systems. EPA is also working with

industry to establish a Task Force to

conduct studies and collect more data

on residential exposures.

d. Children’s risk. Overall, EPA

believes the conservative assumptions

built into the hazard and exposure

assessments have given good estimates

of risk to the general population, and in

so doing have also been protective of

children. EPA is planning additional

research in this area. If, in the future,

based on new data or methodologies,

the risk picture changes, EPA will

reconsider this proposed decision not to

initiate this Special Review.

D. Unsupported Uses, Risk Reduction,

and Amendments to DCIs

No registrant of propoxur end-use

products committed to generate trigger

pump sprayer data in response to the

1992 DCI. EPA believes that the liquid

is likely to drip from the sprayer onto

the applicator’s fingers, and without

data, this exposure and risk cannot be

quantified and could be of concern.

Accordingly, registrants have either

voluntarily cancelled this use pattern or

have amended their labels to delete use

of ready-to-use liquids with trigger

pump sprayers.

IV. Comments Received on the

Preliminary Notifications

Comment. In a letter dated March 22,

1988, EPA notified the registrants that it

was considering a Special Review of

propoxur based on carcinogenicity

concerns and the estimated risks posed

to PCOs and the general public. In

responses dated April 26, 1988 and May

16, 1988, Miles Inc. stated that it already

has committed to support the continued

registration of propoxur products in

response to the 1987 DCI; that EPA

should consider all data before deciding

on initiating a Special Review of

propoxur; and that the bladder

carcinogenic effect was species-specific

for the rat and Miles Inc. would provide

additional data to support its claim.

Miles Inc. also urged the Agency not to

initiate its Special Review of propoxur

without first reviewing the data to be

generated by Miles Inc. to satisfy the

data requirements outlined in the 1987

propoxur DCI. Also, Miles Inc.

suggested that EPA review its cancer

classification of propoxur as a Group B2

carcinogen.

Response. EPA has concluded its

review of the studies submitted by Miles

Inc. to comply with the 1987 DCI. The

effects of the voluntary cancellation of

and label amendments deleting use of

RTU liquids with trigger pump sprayers

were considered. EPA has determined

that the risks to PCOs and the general

public for the remaining registrations of

propoxur are likely to present negligible

short-term or long-term human risk. In

addition, the registrant has submitted

some additional information relating to

the carcinogenicity of propoxur. When

all the requested data has been

submitted, EPA will reconvene a peer

review panel to review all the

carcinogenicity data relating to

propoxur.

V. EPA’s Proposed Decision Regarding

Special Review

EPA notified propoxur registrants in

1988 that the Agency was considering a

Special Review of propoxur. Because of

propoxur’s Group B2 (probable) human

carcinogen classification and widespread uses of the pesticide in homes,

EPA was concerned with the potential

long-term health hazards from

prolonged exposures associated with the

application of certain indoor

formulations. However, since then, EPA

has refined the risk assessment. In

addition, registrants have cancelled

those product registrations and deleted

or amended label uses for which EPA

had risk concerns. For these reasons, the

Agency now concludes that the

remaining uses of propoxur products are

likely to present negligible short-term or

long-term human risk. Therefore, the

Agency is proposing not to initiate a

Special Review of propoxur at this time.

EPA based its regulatory decision on

propoxur entirely on the available

information in its exposure database

and the result of its risk assessments,

which are based on conservative

assumptions and the conservative

linearized multi-stage model of

carcinogenic potency. EPA has

concluded that it can issue this

regulatory decision in the absence of

more conclusive data to resolve the

question of diet and species specificity

of propoxur in inducing bladder effects

in animals, or to resolve the issue on

propoxur’s suggested activity as a nongenotoxic or ‘‘threshold’’ carcinogen.

The Agency believes that the issues

surrounding the mechanism of

carbamate-induced carcinogenicity are

complex, and may be a subject of

considerable scientific debate for the

future.

VI. Executive Order 12898 on

Environmental Justice

In accordance with the Executive

Order on Environmental Justice, EPA

has reviewed this proposed decision

and found it does not result in any

adverse environmental effects

(including human health, social and

economic effects) on minority

communities and low-income

communities.
3220 Federal Register / Vol. 60, No. 9 / Friday, January 13, 1995 / Notices

VII. Public Record and Opportunity for

Comment.

EPA has established a public docket

(OPP–30000/59) for the propoxur PreSpecial Review. This public record

includes: (1) this Notice; (2) any other

notices pertinent to the propoxur

Special Review; (3) non-Confidential

Business Information (CBI) documents

and copies of written comments

submitted to EPA in response to the preSpecial Review registrant notification,

(4) any other Notice regarding propoxur

submitted at any time during the PreSpecial Review process by persons

outside government; (5) a transcript of

all public meetings held by EPA for the

purpose of gathering information on

propoxur; (6) memoranda describing

each meeting held on propoxur between

EPA personnel and persons outside

government during the Pre-Special

Review process; and (7) a current index

of materials in the public docket.

Additional information about the docket

may be found in the section on

addresses at the beginning of thisnotice.

EPA is providing a 60–day period for

registrants, applicants, and interested

persons to comment on the risks

associated with indoor and pet uses of

propoxur products, and on EPA’s

proposed decision not to initiate a

Special Review of propoxur. Written

comments must be submitted by March

14, 1995, and must be identified by the

docket number (OPP–30000/59).

Comments should be sent to the address

provided at the beginning of this notice.

VIII. References

The documents referred to in this Notice

are listed below. Copies are available in the

Public Docket. Information about the Public

Docket is available in the ADDRESSES unit

at the beginning of this notice.

(1) Letter from D. Campt, Director, Office

of Pesticide Programs, to propoxur

registrants, dated March 22, 1988.

(2) Eben, A. ‘‘Studies on Transformation of

Propoxur in Humans,’’ dated June 1, 1987,

Accession Number 406297–4, Data

Evaluation Report (DER) No. 6858.

(3) Memorandum from B. Fisher, HED, to

B. Backus, HED, titled Propoxur (Baygon)

Qualitative Risk Assessment, Revised and

Quantitative Risk Assessment-Two-Year SPF

Rat Dietary Study, dated April 21, 1992.

(4) Memorandum from D. Jaquith, HED, to

D. Edwards, RD, titled Review of Propoxur

Exposure Studies Submitted by Mobay

Corporation in Response to Data-Call-In

Notice (HED Project Nos. 9–1935, 9–1936, 9–

1937, 9–1938, 9–1939) and Current Estimates

of Exposure for Other Scenarios, dated

February 7, 1990.

(5) Memorandum from E. Budd, HED, to J.

Gallagher, SRRD, titled Propoxur:

Carcinogenic Risk Assessment for Pest

Control Operators Treating Indoor Sites

(Utilizing Dermal Absorption Data) (Crack

and Crevice Study) dated January 24, 1991,

updated August 14, 1992.

(6) Memorandum from E. Budd, HED, to D.

Chen, SRRD, titled Propoxur: Quantitative

Risk Assessments for Remaining End-Use

Formulations Listed in OREB Memorandum

of November 6, 1992, dated February 8, 1993.

(7) Memorandum from D. Jaquith, HED, to

D. Chen, SRRD titled Refinement of Exposure

Analysis for Propoxur, dated November 6,

1992.

(8) Memorandum from D. Jaquith, HED, to

D. Edwards, RD, titled Review of Repeated

Exposure Study Addressing Application of a

2 percent propoxur bait (HED Project No. 1–

1471) dated November 15, 1991.

(9) Memorandum from D. Jaquith, HED, to

A. Sibold, SRRD, titled Exposures to

Propoxur from Granular Baits Applied in and

around Homes dated May 24, 1994.

(10) Memorandum from D. Jaquith, HED, to

D. Edwards, RD, titled Review of Repeat

Exposure Study for Propoxur Pet Spray

Products (HED Project No. 2–0491) dated July

15, 1992.

(11) Memorandum from Byron Backus,

HED, to McCall/Whitby, HED, titled Used of

Measurements of 2-Isopropoxyphenol in

Human Urine Samples to Determine

Exposure and Absorption of Propoxur, dated

June 28, 1994.

(12) Memorandum from David Jaquith,

HED, to Deborah McCall, HED, titled

Response to Questions from SRB Regarding

Propoxur, dated July 13, 1994.

(13) Memorandum from E. Budd, HED to

D. Chen, SRRD, titled Propoxur: Carcinogenic

Risks for Individuals Apply a 0.25 Percent

Aerosol Spray to Pets. dated August 14, 1992.

(14) Memorandum from Deborah McCall,

HED to Ann Sibold, SRRD, titled Propoxur:

Revisions to Carcinogenic Risk Estimates for

Commercial Workers and Homeowners

Exposed to Pet Sprays, dated July 25, 1994.

(15) Memorandum from D. Jaquith, HED, to

D. Chen, SRRD, titled Review of Repeat

Exposure Study for Propoxur Aerosol Spray

(HED Project No. 1/1208), dated July 29,

1991.

(16) Memorandum from K. Whitby, HED,

to D. Chen, SRRD, titled Propoxur (Baygon)

Carcinogenic Risk for Homeowners Applying

1 percent Aerosol Spray Products, dated

September 1, 1992.

(17) Memorandum from D. Jaquith, HED, to

D. Chen, SRRD, titled Classification of

Propoxur Use Sites and Expansion of

Exposure Matrix for Aerosol Uses, dated

August 11, 1992.

(18) Memorandum from D. Jaquith, HED, to

D. Chen, SRRD, titled Errors in Exposure

Analysis for Propoxur, dated November 18,

1992.

(19) Memorandum from Deborah McCall,

HED, to Ann Sibold, SRRD, titled Propoxur:

Revised Lifetime Risk Numbers for Ready-toUse Sprays, dated August 12, 1994.

(20) Memorandum from D. Jaquith, HED, to

D. Chen, SRRD, titled Post-Application

Exposures of Residents to Propoxur Applied

as an Aerosol Spray, dated November 1,

1991.

(21) Memorandum from David Jaquith,

HED, to Deborah McCall, HED, titled

Clarification of Resident Applicator

Exposures from Ready to Use (RTU)

Formulations of Propoxur, dated August 5,

1994.

(22) Memorandum from D. Jaquith, HED, to

D. Edwards, RD, titled Review of Study

Estimating Resident Exposure to Propoxur

Following Crack and Crevice Treatment (HED

project No. 9–1936) dated November 15,

1989.

(23) Memorandum from E. Budd, HED, to

D. Chen, SRRD, titled Propoxur: Revised

Carcinogenic Risk Assessment for Residents

of Homes Following Crack and Crevice

Treatments (Utilizing Refined Exposure

Analysis Provided OREB in Memoranda of

November 6, 1992 and November 18, 1992),

dated December 8, 1992.

(24) Memorandum from D. Jaquith, HED, to

J. Gallagher, SRRD, titled Adjustments to Post

Application Exposure Assessment for

Residents of Homes treated with Propoxur

(HED Proj. No. 1–0222), dated February 27,

1991.

(25) Memorandum from E. Budd, HED, to

D. Chen, SRRD, titled Propoxur: Revised

Carcinogenic Risk Assessment for Residents

of Homes Following Treatments with a 1

percent Aerosol Product (Utilizing Refined

Exposure Analysis Provided by OREB in

Memoranda of 11/6/92 and 11/18/92), dated

December 8, 1992.

(26) Memorandum from S. Knott, HED, to

D. Edwards, RD, titled review of Post

Application Exposure from Indoor Pest Strips

Containing Propoxur (HED Project No. 9–

1540) dated August 2, 1989.

(27) Jackson, M.D. and Lewis, R.G., (1981)

Insecticide Concentrations in Air after

Application of Pest Control Strips. Bull

Environm Contam Toxicol 27:122–125.

(28) Memorandum from C. Lunchick, EAB,

to Jay Ellenberger, RD, and Robert Zendzian,

HED, titled Exposure Assessment for

Propoxur (Baygon) dated January 8, 1985.

(29) Memorandum from Penelope FennerCrisp, HED, to Bill Burnam, Hugh Pettigrew,

and Kerry Dearfield, titled Deriving Q*s

Using the Unified Interspecies Scaling

Factor, dated July 8, 1994.

(30) Memorandum from Stephanie Irene,

HED to Louis P True, Jr., SRRD, and Stephen

Johnson, RD, titled Propoxur - Carcinogencity

in Animals, dated December 14, 1994.

(31) National Research Council (U.S.).

Committee on Pesticides in the Diets of

Infants and Children, Pesticides in the Diets

of Infants and Children. copyright 1993 by

the National Academy of Sciences.

List of Subjects

Environmental protection, chemcals,

pesticides and pest.

Dated: December 30, 1994.

Lynn R. Goldman,

Assistant Administrator for Prevention,

Pesticides and Toxic Substances.

[FR Doc. 95–934 Filed 1–12–95; 8:45 am]

BILLING CODE 6560–50–F