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[Federal Register Volume 60, Number 9 (Friday, January 13, 1995)]
[Notices]
[Pages 3210-3220]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-934]

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ENVIRONMENTAL PROTECTION AGENCY
[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.

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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 [[Page 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 [[Page 3212]] 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 trigger-pump 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 pair-wise 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-hydroxy-methylcarbamate 
(``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 [[Page 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 semi-synthetic 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 species- and diet-specific effect could 
be established, and if the genotoxic mode of action were dismissed for 
propoxur, then ``the use of the conventional low-dose 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 re-read 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 re-evaluated (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  x  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 
[[Page 3214]] 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  x  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 chemical-resistant 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  x  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  x  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 [[Page 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  x  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  x  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  x  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 dab-ons, 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 post-application 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, [[Page 3216]] 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 g/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  x  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  x  10-5 mg/kg/day (Ref. 
19).
    (3) Aerosols. Miles Inc. elected not to submit an aerosol spray 
study for post-application 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  x  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  x  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  x  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  x  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)

                                                                        
[[Page 3217]]                                                           
   Table 1.--Propoxur Uses and Exposure Estimates for PCOs, RAs, Kennel Workers, Pet Owners, and Residents of   
                                                  Treated Homes                                                 
----------------------------------------------------------------------------------------------------------------
                                                     Applicator Exposure (mg/ Resident Post Application Exposure
                        Use                                  kg/day)                      (mg/kg/day)           
----------------------------------------------------------------------------------------------------------------
Crack and Crevice..................................                                                             
                                                                                                                
   PCO Application.................................       5.2  x  10-3a                 2.8  x  10-4a,b         
                                                                                                                
   RA Application..................................       2.1  x  10-4a                 9.3  x  10-5a,b         
                                                                                                                
Aerosols...........................................                                                             
                                                                                                                
   RA Application..................................       2.1  x  10-4a                 5.7  x  10-5a,b         
                                                                                                                
Granular Baits.....................................                                                             
                                                                                                                
   PCO Application.................................         negligible                    negligible            
                                                                                                                
   RA Application..................................         negligible                    negligible            
                                                                                                                
Pet Aerosols.......................................                                                             
                                                                                                                
   Pet Owner Application...........................        6.4  x  10-3                   negligible            
                                                                                                                
Total Release Aerosol Foggers......................                                                             
                                                                                                                
   RA Application..................................         negligible                  5.7  x  10-5a,b         
                                                                                                                
Pest Strips........................................                                                             
                                                                                                                
   RA Application..................................         negligible                   1.1  x  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  x  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  x  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.                                          
----------------------------------------------------------------------------------------------------------------
                                                                                             Total Residential  
            Use                 Applicator Risk        Resident Post Application Risk             Riska         
----------------------------------------------------------------------------------------------------------------
                                                                                                                
Crack and Crevice.........                                                                                      
                                                                                                                
   PCO Application........        5.4  x  10-6                  1.0  x  10-6                   1.0  x  10-6     
                                                                                                                
  RA Application..........        7.8  x  10-7                  3.4  x  10-7                   1.1  x  10-6     
                                                                                                                
Aerosols..................                                                                                      
                                                                                                                
   RA Application.........        7.8  x  10-7                  2.1  x  10-7                   9.9  x  10-7     
                                                                                                                
Granular Baits............                                                                                      
                                                                                                                
   PCO Application........         negligible                    negligible                     negligible      
                                                                                                                
[[Page 3218]]                                                                                                   
                                                                                                                
   RA Application.........         negligible                    negligible                     negligible      
                                                                                                                
Pet Aerosols..............                                                                                      
                                                                                                                
   Pet Owner Application..        2.6  x  10-7                   negligible                    2.6  x  10-7     
                                                                                                                
Total Release Aerosol                                                                                           
 Foggers..................                                                                                      
                                                                                                                
   RA Application.........         negligible                   2.1  x  10-7                   2.1  x  10-7     
                                                                                                                
Pest Strips...............                                                                                      
                                                                                                                
   RA Application.........         negligible                   4.1  x  10-7                   4.1  x  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  x  10-8                   2.3  x  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 [[Page 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 wide-spread 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 non-genotoxic 
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. 
[[Page 3220]] 

VII. Public Record and Opportunity for Comment.

    EPA has established a public docket (OPP-30000/59) for the propoxur 
Pre-Special 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 pre-Special Review 
registrant notification, (4) any other Notice regarding propoxur 
submitted at any time during the Pre-Special 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-to-Use 
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 Fenner-Crisp, 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
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