[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
