Number range CHAPTER

![](media/image1.wmf){width="1.2in" height="1.2in"}

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION,

PESTICIDES AND

TOXIC SUBSTANCES

[MEMORANDUM]{.underline}

DATE: September 29, 2005

SUBJECT: **Para-tertiary amylphenol (4-t-amylphenol) and its sodium and
potassium salts**: AD Risk Assessment for the Reregistration Eligibility
Decision (RED) Document. Chemical Nos. 064101, 064111, 064112. Case No.
3016. DP Barcode: D316280

FROM: Deborah Smegal, MPH, Toxicologist/Risk Assessor

#  Myron Ottley, Ph.D., Toxicologist

Tim McMahon, Ph.D. Senior Toxicologist

Siroos Mostaghimi, Ph.D. Environmental Engineer

Najm Shamim, Ph.D. Chemist

Srinivas Gowda, Microbiologist/Chemist

David C. Bays

Jonathan Chen, PhD., Toxicologist

Antimicrobials Division (7510C)

THRU: Norm Cook, Chief

Risk Assessment and Science Support Branch

Antimicrobials Division (7510C)

TO: Killian Swift, Risk Manager Reviewer

Team 36, Reregistration

Antimicrobials Division (7510C)

Attached is the Revised Risk Assessment for Para-tertiary amylphenol
(4-t-amylphenol) and its sodium and potassium salts for the purpose of
issuing a Reregistration Eligibility Decision (RED). The disciplinary
science chapters and other supporting documents for the 4-t-amylphenol
RED are also included as attachments as follows:

4-t-Amylphenol: Report of the Antimicrobials Divisions's Toxicology
Endpoint Selection Committee (ADTC), July 2005

Toxicology Science Chapter for the Reregistration Eligibility Decision
Document, From M. Ottley/D. Smegal to K. Swift, September 2005 D316279

Occupational and Residential Exposure Assessment for t-Tert-Amylphenol
and Salts. S. Mostaghimi . September 2005. D316290

Product Chemistry of Para-Tertiary-Amylphenol, para-tertiary-amylphenol,
sodium salt and para-tertiary-amylphenol, potassium salt. From A. N.
Shamim to T. McMahon. D316275

Revised Environmental Fate Assessment of 4-tert-Amylphenol and its
Potassium and Sodium salts for the Reregistration Eligibility Decision
(RED) Document. From S. Gowda, Microbiologist to M. Hartman. September
29 2005, D322006

Ecological Hazard and Environmental Risk Assessment for
4-tert-amylphenol and salts to be included in the RED. D. Bays to A.
Heyward and K. Swift. October 2005, D316278

Incident Reports Associated with 4-tert-amylphenol. J. Chen. May 2005,
D316276

Dietary Exposure Assessments for the Reregistration Eligibility
Decision. R. Quick. September 29, 2005. D316295.

[**1.0** **EXECUTIVE SUMMARY** 4](#executive-summary)

[**2.0** **PHYSICAL AND CHEMICAL PROPERTIES**
11](#physical-and-chemical-properties)

[**3.0.** **ENVIRONMENTAL FATE** 12](#environmental-fate)

[**4.0** **HAZARD CHARACTERIZATION** 13](#hazard-characterization)

[4.1 Hazard Profile 13](#hazard-profile)

[4.2 FQPA Considerations 16](#fqpa-considerations)

[4.3 Dose-Response Assessment 17](#dose-response-assessment)

[4.4 Endocrine Disruption 18](#endocrine-disruption)

[**5.0** **EXPOSURE ASSESSMENT AND CHARACTERIZATION**
19](#exposure-assessment-and-characterization)

[5.1 Summary of Registered Uses 19](#summary-of-registered-uses)

[5.2 Dietary Exposure and Risk 19](#dietary-exposure-and-risk)

[5.3 Drinking Water Exposure and Risk
21](#drinking-water-exposure-and-risk)

[5.4 Residential Exposure/Risk Pathway
22](#residential-exposurerisk-pathway)

[5.4.1 Residential Handler 22](#residential-handler)

[5.4.2 Postapplication Residential Exposure
23](#postapplication-residential-exposure)

[**6.0** **AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION**
26](#aggregate-risk-assessments-and-risk-characterization)

[6.1 Short- and Intermediate-Term Aggregate Risk
27](#short--and-intermediate-term-aggregate-risk)

[6.2 Long-Term Aggregate Risk 28](#long-term-aggregate-risk)

[**7.0** **CUMULATIVE EXPOSURE AND RISK**
28](#cumulative-exposure-and-risk)

[**8.0** **OCCUPATIONAL EXPOSURE AND RISK**
28](#occupational-exposure-and-risk)

[**9.0** **INCIDENTS** 30](#incidents)

[**10.0** **ENVIRONMENTAL RISK** 31](#environmental-risk)

[**11.0** **DEFICIENCIES/DATA NEEDS** 36](#deficienciesdata-needs)

[**12.0** **REFERENCES** 37](#references)

# **1.0 EXECUTIVE SUMMARY** 

4-tertiary-amylphenol (4-t-amylphenol), and salts (potassium and sodium)
are active ingredients in disinfectant, food-contact sanitizer and
deodorizer products used in agricultural, food handling,
commercial/institutional/industrial, residential and public access, and
medical settings, primarily used on hard, non-porous surfaces. Number
range CHAPTER The majority of the products are virucidal, fungicidal,
tuberculocidal, bactericidal, pseudomonacidal, or staphylocidal. Number
range CHAPTERExamples of registered uses for 4-t-amylphenol and salts
include application to hard surfaces (e.g., walls, floors, tables,
fixtures), textiles (e.g., clothing, diapers, mattresses, bedding),
carpets, medical instruments, and agricultural equipment. Additionally,
there are registered uses for fogging in occupational settings and air
deodorization in both occupational and residential settings.
Concentrations of 4-t-amylphenol and salts in products range from
0.0027% to 10%. The products are formulated as soluble concentrates,
ready-to-use liquid solutions, pressurized sprays, and impregnated
wipes.

A potential outdoor use, wood protection to treat unseasoned forest
products, is apparently no longer supported by any registrant. In
addition, the registrant is no longer supporting uses in potable human
drinking water systems.

**Hazard:** Number range CHAPTERThe toxicology database for
4-t-amylphenol, in terms of guideline studies, is largely incomplete.
Studies from the open literature provide limited information, and more
data are needed to put together a complete profile.

4-t-Amylphenol is a primary dermal irritant (Category I) and is in
Category III for acute oral toxicity based on guideline studies. It also
appears to be an eye irritant (Category I), and may be in Category III
for acute dermal toxicity according to data from the open literature.
However, acceptable guideline acute studies are not available for
dermal, inhalation, primary eye irritation or dermal sensitization, and
the literature data protocols were inadequate. Literature studies also
indicate it is a skin sensitizer and possible depigmentation agent. In
short-term studies, 4-t-amylphenol produced clinical signs along with
decreased food consumption and body weight in a developmental toxicity
study, but no systemic effects in a 13-week dermal study. The structural
abnormalities and developmental delays that occurred in the
developmental study, occurred at higher dose levels than the maternal
effects, suggesting that increased quantitative susceptibility concerns
are not warranted; however, the minimal maternal effects (reversible
clinical signs) seen in the presence of the developmental effects
increases concern for qualitative susceptibility. Neither a
developmental study in rabbits nor a reproduction study was available to
provide confirmation. Number range CHAPTERAvailable data suggest that
4-t-amylphenol has endocrine disrupter capabilities (uterotrophic and
estrogenic effects) and increased bilirubin production in babies. In
addition, this chemical is listed on a European list of "Chemicals
purported to be endocrine disruptors".

4-t-Amylphenol was negative for carcinogenicity in a subchronic skin
painting study from the open literature. However, guideline studies for
carcinogenicity are not available. All mutagenicity tests were negative.

**Toxicity Endpoints:** The toxicity endpoints used in this document to
assess potential risks include acute and chronic dietary reference doses
(RfDs), and short-, intermediate- and/or long-term incidental oral,
dermal and inhalation doses. The Antimicrobials Division's endpoint
selection committee (ADTC) selected endpoints in April 2005. Since the
toxicological endpoints selected for 4-tert-amylphenol and
4-tert-amylphenol salts are identical, a separate assessment was not
conducted for each active ingredient.

[Acute and Chronic RfDs]{.underline}: The acute RfD is 0.67 mg/kg/day
for females (13-50 years, based on adverse developmental effects
(skeletal effects and decreased fetal body weight) at 500 mg/kg/day in a
rat developmental study. The chronic RfD is 0.17 mg/kg/day based on
clinical signs of toxicity and decreased body weight and food
consumption at 200 mg/kg/day in a rat developmental study. An
uncertainty factor of 300 (10X for interspecies extrapolation, 10X for
intraspecies variability, and 3X for database uncertainties) was applied
to the NOAEL to obtain the acute and chronic RfDs. A **database
uncertainty factor of 3x** is applied to non-occupational risk
assessments for 4-t-amylphenol, due to the number and significance of
the data gaps including lack of repeated oral toxicity studies. An
additional Food Quality Protection Factor (FQPA) safety factor is
applied, which is discussed below.

[Incidental oral endpoints:]{.underline} The short- and
intermediate-term incidental oral NOAEL is 50 mg/kg/day from a rat oral
developmental toxicity study that noted clinical signs, decreases in
body weight and body weight gain, coupled with decreased food
consumption at 200 mg/kg/day. The target margin of exposure (MOE) is
3,000 (includes 10X FQPA factor).

[Dermal endpoints:]{.underline} The short- and intermediate-term dermal
NOAEL is 25 mg/kg/day, which is based on the lack of systemic effects
identified up to and including a dose of 25 mg/kg/day in a rat
subchronic dermal toxicity study. Uncertainty factors or "target"
margins of exposure (MOE) for 4-t-amylphenol dermal exposures are 100
for occupational scenarios and 1,000 for residential scenario (includes
10X FQPA factor). It should be noted that 4-t-amylphenol caused dermal
irritant effects following repeated dermal exposure at 10 mg/kg/day, and
may also be a potential dermal sensitizer.

[Inhalation endpoints:]{.underline} The short-, intermediate- and
long-term inhalation NOAEL is 50 mg/kg/day from a rat oral developmental
toxicity study that noted clinical signs, decreases in body weight and
body weight gain, coupled with decreased food consumption at 200
mg/kg/day. In the absence of data, it was conservatively assumed that
inhalation absorption is equivalent to oral absorption (i.e., 100%). For
inhalation exposures, the uncertainty factors are 300 for occupational
scenarios and 3,000 for residential scenarios (includes 10X FQPA
factor).

**FQPA Safety Factor**. The ADTC committee concluded that the hazard
based FQPA safety factor should be **retained at 10X.** The toxicology
data base is not complete with respect to assessing the increased
susceptibility to infants and children as required by FQPA for
4-t-amylphenol. The rat prenatal developmental study showed no
quantitative evidence of increased susceptibility (i.e., developmental
NOAELs/LOAELs were the higher than those for maternal effects). However,
there was qualitative evidence of increased susceptibility as the fetal
effects (i.e., skeletal abnormalities, decreased body weight gain) were
considered to be more severe than the maternal toxicity (reversible
clinical signs). In addition, there is an absence of developmental
toxicity data in the rabbit, and an absence of reproductive toxicity
data. Furthermore, studies in the open literature suggest that
4-t-amylphenol may be an endocrine disruptor. It increased non-pregnant
uterine weight in rats and was associated with elevated blood levels of
bilirubin in children exposed to 4-t-ampyphenol and other phenols in
disinfectant. These studies, while not indicative, are suggestive of a
basis for increased concern for reproductive and/or developmental
effects due to exposure to 4-t-amylphenol. In addition, this chemical is
listed on a European list of "Chemicals purported to be endocrine
disruptors".

Based on Agency policy, a RfD modified by a FQPA safety factor is a
population adjusted dose (PAD)[^1] FQPA Safety Factor. The Agency
calculated an acute PAD and a chronic PAD, and uses this value to
estimate acute and chronic dietary risk.

**Dietary Exposure and Risk:** Number range CHAPTERThe Agency has
conducted a dietary exposure and risk assessment for use of
4-t-amylphenol in a ready-to-use disinfecting solution. A counter top
that is treated with this product may come into contact with food, which
in turn may be ingested. This is considered to be an indirect food use.
4-t-ANumber range CHAPTERmylphenol (also known as phenol,
4-1,1-dimethylpropyl) (CAS No. 80-46-6) has a tolerance exception in
40CFR 180.940 (c) as a food-contact sanitizer for use in food-processing
equipment and utensils with a not to exceed limit of 80 ppm. However,
the maximum ingredient percentage for 4-t-amylphenol in food handling
establishments from the various labeled ready-to-use products is 0.054 %
a.i (540 ppm), which exceeds the current tolerance exemption limitation.
The Agency estimates that use of this product results in 4-t-amylphenol
food residues of Number range CHAPTER340 ppb (µg/kg).

When assessing acute and chronic (non-cancer) dietary risk, AD
considered potential dietary exposure to the U.S. population including
infants and children, as well as to females of childbearing age (13-50
years). AD expresses dietary risk estimates as a percentage of the aPAD
or chronic PAD. Dietary exposures that are less than 100% of the aPAD or
cPAD are below the Agency's level of concern.

[Acute Dietary Risk]{.underline}. AD has determined that, based on the
assumptions and models used, the acute dietary risk from exposure to
4-t-amylphenol does not exceed the Agency's level of concern for females
of childbearing age, the only subpopulation examined. The dietary risk
estimate is **2.7% of the acute PAD**.

[Chronic Dietary Risk]{.underline}. In the absence of data, screening
level estimates used for the acute dietary risk analysis are used to
assess potential chronic dietary exposure. The risk analysis assumes
daily exposure from the hard surface disinfection of counter tops. The
chronic non-cancer dietary analysis indicates all risk estimates are
below the Agency's level of concern for all population subgroups. The
highest dietary risk estimate is **42% of the chronic PAD**, for infants
and children, assuming 10% of the residues are transferred to food. The
Agency requires confirmatory data for this transfer rate because 100%
residue transfer indicates risks of concern.

**Water Exposure and Risk:** There are no currently registered outdoor
uses of 4-t-amylphenol and its salts that are being supported by the
registrant. The Number range CHAPTERpotential outdoor uses, wood
protection to treat unseasoned forest products, and use in potable human
drinking water systems are apparently no longer supported by any
registrant. 4-t-AmylpNumber range CHAPTERhenol's use as a general
disinfectant allows for the possibility of surface water contamination.
However, the estimated value for biodegradation indicates it may
biodegrade linearly within days in the aquatic environment, although
ultimate biodegradation (mineralization) may take months. The sodium and
potassium salts of 4-t-amylphenol are estimated to biodegrade within
days to weeks. Because of the possibility of biodegradation in water and
soils, 4-t-amylphenol and its salts are not likely to contaminate
surface and ground waters. Thus, a quantitative drinking water
assessment was not conducted for these chemicals.

**Residential (Non-Occupational) Exposure and Risk:** Number range
CHAPTERSome products containing 4-t-amylphenol are labeled for
residential use as disinfectants and deodorizers. These products are for
use on hard surfaces (e.g., floors, walls, bathroom fixtures, trash
cans, household contents), textiles (e.g., clothing, diapers, and
bedding), and carpets. Additionally, there are products which can be
used to deodorize air in the home. Number range CHAPTERThere are no
residential uses for products containing sodium 4-tert-amylphenate or
potassium 4-tert-amylphenate**.** The following scenarios were
considered for residential handlers: application of hard surface
disinfectants via (1) mopping; (2) wiping; (3) trigger pump spray; and
(4) aerosol spray.

The Agency also evaluated potential postapplication exposures to
products that contain 4-t-amylphenol. Postapplication scenarios
evaluated, which were considered to be representative of all possible
exposure scenarios, included: contact with treated hard
surfaces/flooring by children (incidental oral and dermal exposure),
dermal contact with treated textiles and diapers, incidental ingestion
of treated textiles, and postapplication/bystander inhalation exposure
from use of disinfecting/deodorizing products. Duration of exposure is
short-term (1-30 days) and intermediate-term (1-6 months) for all
residential scenarios assessed, except for the diaper use, which is also
considered to be a long-term scenario (\> 6 months). The scenarios were
evaluated based on the Residential Exposure Assessment Standard
Operating Procedures (SOPs), product label maximum application rates,
related use information, Agency standard assumptions, inhalation and
dermal unit exposure data from the proprietary Chemical Manufactures
Association (EPA 1999, CMA, 1992), and Pesticide Handlers Exposure
Database (PHED). In addition, the Multi-Chamber Concentration and
Exposure Model (MCCEM) was used to estimate postapplication inhalation
exposure to air deodorizer. At this time, EPA does not have available
chemical-specific handler or postapplication exposure studies that meet
Agency guidelines.

*Residential Handler Risk Summary.* For the residential handler dermal
and inhalation risk assessment, short- and intermediate-term risks for
all scenarios evaluated are above the respective target MOEs for all
scenarios (i.e., dermal MOEs were \>1,000 and inhalation MOEs were
\>3,000), and thus are not of concern.

[]{.mark}

*Postapplication Residential Risk Summary.* For the residential
postapplication scenarios assessed in this document, risk estimates that
exceed the Agency's level of concern (i.e., dermal MOEs \<1,000,
inhalation MOEs \<3,000, and oral MOEs \<3,000) are:

-   Incidental oral exposure from children mouthing treated textiles
    (oral MOE=650);

-   Dermal exposure from children wearing treated clothing (Dermal MOE =
    0.86 with a 100% transfer factor and Dermal MOE = 17 with a 5%
    transfer factor);

-   Dermal exposure from children wearing a treated diaper (Dermal MOE =
    59 with a 100% transfer factor and Dermal MOE = 1,200 with a 5%
    transfer factor, which is above the target MOE);

-   Dermal exposure from children playing on a treated hard surface in a
    daycare center (Dermal MOE = 940);

-   Dermal exposure from adults wearing treated clothing (Dermal MOE =
    140 with a 100% transfer factor; however, with a 5% transfer factor
    the Dermal MOE = 2,700, which is above the target MOE). The Agency
    will require confirmatory data to support a 5% transfer factor.

As noted previously, 4-t-amylphenol also caused dermal irritant effects
following repeated dermal exposure at 10 mg/kg/day, and may also be a
potential dermal sensitizer. Since the MOEs are based on systemic
effects at 25 mg/kg/day, the Agency intends to consider the potential
for irritation and sensitization in recommended labeling language of
pesticide products containing 4-t-amylphenol, and additional dermal
toxicity data on a diluted end-use formulation.

**Aggregate Exposure and Risk**: In order for a pesticide registration
to continue, it must be shown that the use does not result in
"unreasonable adverse effects on the environment". Section 2 (bb) of
FIFRA defines this term to include "a human dietary risk from residues
that result from a use of a pesticide in or on any food inconsistent
with standard under section 408\..." of FFDCA. As mandated by the FQPA
amendments to FIFRA and the Federal Food, Drug and Cosmetic Act (FFDCA),
the Agency must consider total aggregate exposure from food, drinking
water and residential sources of exposure to 4-t-amylphenol.

Oral and inhalation exposure and risk estimates were combined for the
aggregate risk assessment because the toxicity endpoint is identical for
both routes of exposure. Dermal residential exposures were not
aggregated with the oral or inhalation exposures due to different
toxicological endpoints for oral (clinical signs and body weight
changes), and dermal (no systemic effects at the highest dose tested).
Acute and chronic aggregate assessments were not conducted because there
are no significant impacts to drinking water sources from the indoor
uses of 4-t-amylphenol, nor are there long-term residential uses. Thus,
only short- and intermediate-term aggregate assessments were conducted.

[Short and Intermediate Term.]{.underline} Short- and intermediate-term
aggregate risks are considered together since the exposure and toxicity
endpoints are identical for both durations. For children, the short- and
intermediate-term aggregate assessment includes average dietary exposure
(food) and estimated incidental oral exposures from residential uses
such as hard surface disinfection. In addition, inhalation exposures
from the postapplication of an air deodorizer use were aggregated with
the oral exposures since the toxicity endpoint is the same and it is
possible that the scenarios could co-occur. For adults, the aggregate
assessment includes dietary (oral) and residential inhalation exposures
from wiping a hard surface disinfectant, in addition to postapplication
inhalation exposure from the air deodorizer.

The aggregate oral and inhalation risks are not of concern for adults,
as the total aggregate MOE is 13,000 which is greater than the target of
3,000. For children, the aggregate risk estimates are also above the
target MOE of 3000 (MOE=3,200), and thus are not of concern. As noted
previously, incidental oral exposure to treated textiles are not
included in the aggregate assessment because oral MOE is already of
concern (MOE=650 versus target \>3000). It should be noted that several
conservative assumptions were used in this assessment.

A dermal aggregate assessment was not conducted. However, as noted
previously, short- and intermediate dermal risks are already of concern
for residents for the treated textile and diaper use, and dermal contact
with residues from hard surface disinfectant use. The Agency will
request confirmatory data to verify these risk estimates.

[Long-Term Aggregate]{.underline}. A long-term aggregate assessment was
not conducted because the only long-term residential use (diaper use)
results in dermal exposure, which has a different toxicological effect
than the chronic dietary oral exposure.

**Occupational Exposure and Risk**. Number range CHAPTERBased on
examination of product labels describing uses for the product, it has
been determined that exposure to handlers can occur in a variety of
occupational environments. Additionally, postapplication exposures are
likely to occur in these settings. The representative scenarios selected
by AD for assessment were evaluated using maximum application rates as
recommended on the product labels for 4-t-amylphenol.

To assess the handler risks, AD used surrogate unit exposure data from
both the proprietary Chemical Manufacturers Association (CMA)
antimicrobial exposure study and the Pesticide Handlers Exposure
Database (PHED). Additionally, the MCCEM (Multi- Chamber Concentration
and Exposure Model) was used to estimate postapplication/bystander
exposures.

For the occupational handler dermal and inhalation risk assessment, the
short- and intermediate- and long-term risks calculated at baseline
exposure (no gloves and no respirators) were above target MOEs for all
scenarios (i.e., dermal MOEs were \>100 and inhalation MOEs were \>300).
Note, however, that the high pressure spray application method in the
agricultural use site category was assessed using gloved data.

[]{.mark}

For most of the occupational scenarios, postapplication dermal exposure
is not expected to occur or is expected to be negligible based on the
application rates and chemical properties of the chemical.
Postapplication/bystander inhalation exposures, however, were assessed
for entry into a building after a fogging application. The
representative building selected was a poultry barn. The calculated
inhalation MOEs were above the target MOE of 300 for all fogging
postapplication scenarios.

**Other Food Quality Protection Act (FQPA) Considerations**

[Cumulative Effects]{.underline}. Section 408 of the FFDCA stipulates
that when determining the safety of a pesticide chemical, EPA shall base
its assessment of the risk posed by the chemical on, among other things,
available information concerning the cumulative effects to human health
that may result from dietary, residential, or other non-occupational
exposure to other substances that have a common mechanism of toxicity.
The reason for consideration of other substances is due to the
possibility that low-level exposures to multiple chemical substances
that cause a common toxic effect by a common mechanism could lead to the
same adverse health effect as would a higher level of exposure to any of
the other substances individually. A person exposed to a pesticide at a
level that is considered safe may in fact experience harm if that person
is also exposed to other substances that cause a common toxic effect by
a mechanism common with that of the subject pesticide, even if the
individual exposure levels to the other substances are also considered
safe. EPA does not have, at this time, available data to determine
whether 4-t-amylphenol and its salts have a common mechanism of toxicity
with other substances.

[Endocrine Disruption]{.underline}. Available data for 4-t-amylphenol
suggest is has endocrine disruptor capabilities in mammals (uterotrophic
and estrogenic effects) and increased bilirubin production in babies. It
has been shown to affect the reproductive process of carp. The Food
Quality Protection Act (FQPA; 1996) requires that EPA develop a
screening program to determine whether certain substances (including all
pesticides and inerts) \"may have an effect in humans that is similar to
an effect produced by a naturally occurring estrogen, or such other
endocrine effect\....\" Following the recommendations of its Endocrine
Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system. EPA also adopted EDSTAC's recommendation
that the Program include evaluations of potential effects in wildlife.
For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations.
As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disruptor Screening
Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency's EDSP have been developed and validated,
4-t-amylphenol and its potassium and sodium salts may be subjected to
additional screening and/or testing to better characterize effects
related to endocrine disruption.

**Environmental Hazard and Risk.** The registrant has not submitted any
ecological effects data to support this RED for 4-tert-amylphenol and
its salts. The only data that was available was found in the
peer-reviewed literature. None of these studies met current guideline
requirements and therefore, could not be used in a risk assessment.
There is a concern about the possibility of endocrine disruption in
fish, since 4-t-amylphenol is considered an ecoestrogen. This was
documented in several studies on carp (*Cyprinus carpio*), whose
findings were included in the ecotoxicity chapter. However, since this
chemical is restricted to indoor uses only, the possibility for exposure
of fish to 4-t-amylphenol would be limited. The registrant does have to
submit three ecological effects studies on the acute toxicity of this
chemical. These include an avian acute oral toxicity test, preferably
using the bobwhite quail, (850.2100/71-1), a freshwater fish acute
toxicity test, preferably using the rainbow trout, (850.1075/72-1), and
an acute freshwater invertebrate test (850.1010/72-2). These tests are
required in order to document potential acute toxicity to these
organisms in the unlikely event that exposure to 4-t-amylphenol and its
salts does occur.

# **2.0 PHYSICAL AND CHEMICAL PROPERTIES**

The physical and chemical properties of 4-t-amylphenol and its sodium
and potassium salts are provided in Table 1.

Structure for 4-t-amylphenol:

![](media/image2.wmf)

![](media/image3.wmf)

+--------------+-----------------------+---------------+--------------+
| **Table 1    |                       |               |              |
| Physical and |                       |               |              |
| Chemical     |                       |               |              |
| Properties** |                       |               |              |
+==============+=======================+===============+==============+
| Number range | 4-t-amylphenol        | Sodium        | Potassium    |
| CHA          |                       | 4-ter         | 4-tert       |
| PTERProperty |                       | t-amylphenate | -amylphenate |
+--------------+-----------------------+---------------+--------------+
| PC Chemical  | 064101                | 064111        | 064112       |
| Code         |                       |               |              |
+--------------+-----------------------+---------------+--------------+
| Cas Number   | 80-46-6               | 31366-95-7    | 53404-18-5   |
+--------------+-----------------------+---------------+--------------+
| Molecular    | C~11~H~16~O           | C~11~H~15~NaO | C~11~H~15~KO |
| Formula      |                       |               |              |
+--------------+-----------------------+---------------+--------------+
| Synonyms     | Para-tert-amylphenol, |               |              |
|              | Number range          |               |              |
|              | CHAPTER1-hydrox       |               |              |
|              | y-4(2-methyl-2-butyl) |               |              |
|              |                       |               |              |
|              | benzene;              |               |              |
|              | p-(1,1-d              |               |              |
|              | imethylpropyl)phenol; |               |              |
|              | p-(alpha,             |               |              |
|              | alpha-dimethylpropyl) |               |              |
|              |                       |               |              |
|              | phenol                |               |              |
+--------------+-----------------------+---------------+--------------+
| Molecular    | 164.25                | 186.23        | 202.34       |
| Weight       |                       |               |              |
+--------------+-----------------------+---------------+--------------+
| Melting      | 95^o^C                | 205^o^C       | 206^o^C      |
| Point        |                       | (estimated)   |              |
+--------------+-----------------------+---------------+--------------+
| Boiling      | 263^o^C               | 485^o^C       | 486^o^C      |
| Point        |                       | (estimated)   |              |
+--------------+-----------------------+---------------+--------------+
| Vapor        | 1.16 x 10^-3^ mm Hg   | 7.7 x10^-10^  | 7.7 x10^-10^ |
| Pressure     |                       | (estimated)   | mm Hg        |
|              | at 25^o^ C            |               |              |
|              |                       | at 25^o^C     | at 25^o^C    |
|              |                       |               | (estimated)  |
+--------------+-----------------------+---------------+--------------+
| Solubility   | 113.4 mg/L            | 4595 mg/L     | 3811 mg/L at |
| (water)      |                       | (estimated)   | 25^o^C       |
|              |                       |               | (estimated)  |
+--------------+-----------------------+---------------+--------------+
| Henry Law    | 2.03 x 10^-6^         | 4.10 x        | 5.38 x       |
| Constant     | atm-m^3^/mol          | 10^-14^       | 10^-14^      |
| (HLC)        | (estimated)           | atm-m^3^      | atm-m^3^     |
|              |                       | /mole         | /mole        |
|              |                       | (estimated)   | (estimated)  |
+--------------+-----------------------+---------------+--------------+
| Log K~oc~    | 3.57 (estimated)      | 3.57          | 3.57         |
|              |                       |               | (estimated)  |
+--------------+-----------------------+---------------+--------------+
| Log K~ow~    | 3.91                  | 1.23          | 1.23         |
|              |                       |               | (estimated)  |
+--------------+-----------------------+---------------+--------------+
| Physical     | White Solid           | Solid         | Solid        |
| State        |                       |               |              |
+--------------+-----------------------+---------------+--------------+
| Persistence  | 3.073 hours (measured | 4.67 hours    | 4.67 hours ( |
| in Air (t~½~ | against hydroxy       | (measured     | measured     |
| in Air)      | radical)              | against       | against      |
|              |                       | hydroxy       | hydroxy      |
|              |                       | radical       | radical)     |
+--------------+-----------------------+---------------+--------------+

# **3.0. ENVIRONMENTAL FATE**

Detailed information on environmental fate is presented in the attached
memo from S. Gowda (September 2005). A brief summary is provided below.

The environmental fate assessment for 4-t-amylphenol and its potassium
and sodium salts is based on US EPA=s Estimation Programs Interface
(EPI) Suite. EPI Suite provides estimations of physical/chemical
properties and environmental fate properties.

4-t-Amylphenol may be bioaccumlative (log K~OW~ 3.91) and is likely to
pose a concern for aquatic organisms. It is expected to have moderate to
slight mobility in soils based upon the estimated Koc value of 3799.
Estimated value for biodegradation probability indicates that it may
biodegrade linearly within days in aquatic medium. However, ultimate
biodegradation (mineralization) may take months. It is volatile and may
vaporize into the atmosphere. The estimated half life in the air for
4-t-Amylphenol is about three hours which indicates that it is not
persistent in air. Because of the possibility of biodegradation in water
and soils, it is not likely to contaminate surface and ground waters.

4-t-Amylphenol, potassium salt, is not likely to be bioaccumlative ( log
K~OW~ 1.23) and may not pose a concern for bioconcentration in aquatic
organisms. It may be expected to have moderate to slight mobility in
soils as its estimated Koc value is 3799. Estimated probability of
biodegradation of 4-t-Amylphenol, potassium salt, in soils and water
indicates that it is likely to biodegrade within days to weeks.
Therefore, it may be unlikely that soil and water contamination would
take place. It has low volatility and its estimated half life in air is
about 4.68 hours and is not likely to be persistent in air.

4-t-Amylphenol, sodium salt, is not likely to be bioaccumlative ( log
K~OW~ is 1.23) and may not pose a concern for bioconcentration in
aquatic organisms. It may be expected to have moderate to slight
mobility in soils as its estimated Koc value is the same as the parent
molecule, 4-t-Amylphenol. Probability for sodium 4-tert-amylphenate
biodegradation is the same as the parent molecule, 4-t-amylphenol.
Hence, it is not likely to persist in soils and water, and surface and
ground water contamination is not likely to occur. It has low volatility
and its estimated half life in air is about 4.68 hours and is not likely
to be persistent in air.

# **4.0 HAZARD CHARACTERIZATION**

##  4.1 Hazard Profile 

The toxicology database for 4-t-amylphenol, in terms of guideline
studies, is largely incomplete. Studies from the open literature provide
useful information, but more data are needed to put together a complete
profile.

A detailed hazard assessment for 4-t-amylphenol and its salts is
presented in the attached memorandum (memo from M. Ottley/D. Smegal,
September 2005). 4-t-Amylphenol is a primary dermal irritant (Category
I) and is in Category III for acute oral toxicity based on guideline
studies. It also appears to be an eye irritant (Category I), and may be
in Category III for acute dermal toxicity according to data from the
open literature. However, acceptable guideline acute studies are not
available for dermal, inhalation, primary eye irritation or dermal
sensitization, and the literature data protocols were inadequate.

In short-term studies, 4-t-amylphenol produced clinical signs along with
decreased food consumption and body weight in a developmental toxicity
study, but no systemic effects in a 13-week dermal study. The structural
abnormalities and developmental delays that occurred in the
developmental study, occurred at higher dose levels than the maternal
effects, suggesting that increased quantitative susceptibility concerns
are not warranted; however, the minimal maternal effects (reversible
clinical signs) seen in the presence of the developmental effects
increases concern for qualitative susceptibility. Neither a
developmental study in rabbits nor a reproduction study was available to
provide confirmation.

Available data suggest that 4-t-amylphenol has endocrine disrupter
capabilities (uterotrophic and estrogenic effects) and increased
bilirubin production in babies. In addition, this chemical is listed on
a European list of "Chemicals purported to be endocrine disruptors" (IEH
2005). When taken with the lack of available developmental and
reproductive toxicity data, concerns for FQPA issues are heightened.

No dermal penetration studies were available for 4-t-amylphenol, and an
extrapolation between the 13-week dermal study and the oral
developmental study does not seem possible, for the purposes of
estimating dermal absorption.

4-t-Amylphenol was negative for carcinogenicity in a subchronic skin
painting study from the open literature. However, guideline studies for
carcinogenicity are not available. All mutagenicity tests were negative.
Tables 2 and 3 highlight key toxicological studies for 4-t-amylphenol.

  ------------------------- ---------- ------------------------- ------------
  **Table 2 Acute Toxicity                                       
  Studies for                                                    
  4-t-Amylphenol                                                 
  Technical**                                                    

  Guideline No./ Study Type MRID No.   **Results**               **Toxicity
                                                                 Category**

  870.1100 Acute oral       46616601   LD50 \>2000 mg/kg for     III
  toxicity                             males and females         

  870.1200 Acute dermal     NA         No adequate acute         \[ \]
  toxicity                             toxicity studies were     
                                       provided or identified in 
                                       the open literature.      

  870.1300 Acute inhalation NA                                   \[ \]
  toxicity                                                       

  870.2400 Acute eye        NA                                   \[ \]
  irritation                                                     

  870.2500 Acute dermal     46616602   Corrosive following 4     I
  irritation                           hour application; scar    
                                       tissue noted 14 days      
                                       after treatment           

  870.2600 Skin             NA                                   
  sensitization                                                  
  ------------------------- ---------- ------------------------- ------------

+-------------+-----------------+-------------------------------------+
| **Table 3   |                 |                                     |
| Toxicity    |                 |                                     |
| Profile of  |                 |                                     |
| 4-t         |                 |                                     |
| -Amylphenol |                 |                                     |
| Technical** |                 |                                     |
+=============+=================+=====================================+
| Number      | **MRID No.      | **Results**                         |
| range       | (year)/         |                                     |
| CHAPTER     | Classification  |                                     |
| **Guideline | /Doses**        |                                     |
| No./ Study  |                 |                                     |
| Type**      |                 |                                     |
+-------------+-----------------+-------------------------------------+
| 870.3250    | MRID 42470301   | NOAEL = 2.5 mg/kg/day               |
|             | (1993)          |                                     |
| 90-Day      |                 | LOAEL = 10 mg/kg/day based on       |
| dermal      | 0, 2.5, 10, 25  | dermal effects                      |
| toxicity    | mg/kg/day       |                                     |
|             |                 |                                     |
|             | not acceptable, |                                     |
|             | no systemic     |                                     |
|             | toxicity        |                                     |
|             | demonstrated    |                                     |
+-------------+-----------------+-------------------------------------+
| 870.3700a   | 41920002 (1991) | **Maternal** NOAEL = 50 mg/kg/day   |
|             |                 |                                     |
| Prenatal    | Acceptable      | LOAEL = 200 mg/kg/day based on      |
| de          |                 | clinical signs and decreased body   |
| velopmental | 0, 50, 200, 500 | weight, weight gain, and food       |
| in rodents  | mg/kg/day       | consumption                         |
|             |                 |                                     |
|             |                 | **Developmental** NOAEL = 200       |
|             |                 | mg/kg/day                           |
|             |                 |                                     |
|             |                 | LOAEL = 500 mg/kg/day based on      |
|             |                 | decreased fetal body weight and     |
|             |                 | increased incidence of bent ribs    |
+-------------+-----------------+-------------------------------------+
| Gene        | 414384-01       | Negative, with or without           |
| Mutation    | (1990)          | activation                          |
|             |                 |                                     |
| 870.5265    | Acceptable      |                                     |
|             |                 |                                     |
| *Salmonella | 1, 3.2, 10,     |                                     |
| t           | 31.6, and 100   |                                     |
| yphimurium* | ug/plate       |                                     |
| reverse     |                 |                                     |
| mutation    |                 |                                     |
| assay       |                 |                                     |
+-------------+-----------------+-------------------------------------+
| Gene        | 415727-01       | Negative with and without metabolic |
| Mutation    | (1990)          | activation. The few positive        |
|             |                 | results in control plates are       |
| 870.5300    | Acceptable      | consistent with historical control  |
|             |                 | data for the laboratory and test    |
| *In vitro*  | non-activated   | system.                             |
| mammalian   | conditions - 5, |                                     |
| cell gene   | 10, 20, 30, and |                                     |
| mutation    | 40 g/ml;       |                                     |
| test        | activated       |                                     |
|             | conditions - 2, |                                     |
|             | 4, 6, 8, and 10 |                                     |
|             | ug/ml           |                                     |
+-------------+-----------------+-------------------------------------+
| Number      | Number range    | Negative                            |
| range       | CHAPTER417108   |                                     |
| CHAPTERC    | (1990)          |                                     |
| ytogenetics |                 |                                     |
|             | Acceptable      |                                     |
| 870.5395    |                 |                                     |
|             | 62.5 (M), 250   |                                     |
| Mammalian   | (M+F), 1000     |                                     |
| erythrocyte | (M+F), and 4000 |                                     |
| mi          | mg/kg (F)       |                                     |
| cro-nucleus |                 |                                     |
| test        |                 |                                     |
+-------------+-----------------+-------------------------------------+

[Skin Sensitization.]{.underline} Number range CHAPTERP-tert-amylphenol
has been reported to be a skin sensitizer and depigmenting agent (BIBRA
Working Group, 1990). Stevenson (1984), however, reported p-t-amylphenol
to have a "low depigmenting potential" because none of 129 men who had
been exposed to the compound during its manufacture exhibited
depigmentation.

[Developmental Toxicity.]{.underline} The data base for developmental
toxicity is adequate only for non-food uses of 4-t-amylphenol.
Additional data are required for indirect food use. The one study
provided, a prenatal developmental toxicity study in rats, indicated a
lower NOAEL and LOAEL for maternal toxicity (i.e., 50 and 200 mg/kg-day)
than for developmental toxicity (i.e., 200 and 500 mg/kg-day), and the
developmental effects were not frankly teratogenic. Thus, there is no
quantitative indication that the fetus is more susceptible than the
pregnant female.

[Mutagenicity.]{.underline} The data base for mutagenicity is considered
adequate based on EPA's 1991 mutagenicity guidelines and indicates that
p-tert-amylphenol is not mutagenic or genotoxic. In a submitted
bacterial study (MRID No. 414384-01) and a study identified in the
published literature (Zeiger et al. 1988), p-t-amylphenol was not
mutagenic to the bacteria in the presence or absence of mammalian
metabolic activation. An assay using cultured mouse lymphoma cells also
proved negative (MRID No. 415727-01). Finally, a mouse micronucleus test
using male and female CD-1 mice also was negative (MRID No. 417108).

[Number range CHAPTEREndocrine Disruption.]{.underline} 4-t-Amylphenol
is listed on a European list of "Chemicals purported to be endocrine
disruptors" (IEH 2005). In the open literature (Yamasaki et al. 2003),
an increase in non-pregnant uterine weight was observed in rats
following 4-t-amylphenol exposure. Another study (Soto et al. 1995)
suggested that 4-t-amylphenol may have estrogenic effect. Wysowski et
at. (1978) reported elevated blood levels of bilirubin in children
exposed to 4-t-amylphenol and other phenols in disinfectant. These
studies, while not indicative, are suggestive of a basis for increased
concern for reproductive and/or developmental effects due to exposure to
4-t-amylphenol.

Number range CHAPTERSoto et al. (1995) have found p-t-amylphenol to be
estrogenic in the E-SCREEN assay, which assesses the estrogenicity of a
compound by measuring its proliferative effect on estrogen-sensitive
cells. The cell number achieved by similar inocula of MCF-7 cells
(estrogen-sensitive human breast cancer cells) in the absence of
estrogens (negative control) and in the presence of 17-estradiol
(positive control) is compared with the number of cells achieved with a
range of concentrations of the test chemical. For 4-t-pentylphenol, a
concentration of 10 M was the lowest concentration needed for maximal
cell yield. For the positive control 17-estradiol, the lowest
concentration needed was 30 pM. The relative proliferative effect (RPE)
is calculated as 100 x (PE-1) of the test compound divided by (PE-1) of
17-estradiol. A value of 100 indicates that the compound tested is a
full agonist of the estradiol; a value of 0 indicates that the compound
lacks estroenicity at the doses tested. Intermediate values suggest that
the compound is a partial agonist of 17-estradiol. For 4-t-pentylphenol,
and RPE of 105 was estimated.

Number range CHAPTERRoutledge and Sumpter (1997) demonstrated estrogenic
activity of 4-tert-amylphenol using an estrogen-inducible strain of
yeast (*Saccharomyces cerevisiae*) that expresses the human estrogen
receptor. Using the natural estrogen 17-estradiol for comparison, the
data indicated that both the position (para \> meta \> ortho) and
branching (tertiary \> secondary = normal) of the alkyl group affect
estrogenicity. In this assay, 4-t-amylphenol was found to be
100,000-fold less potent than17-estradiol.

## 4.2 FQPA Considerations 

Under the Food Quality Protection Act (FQPA), P.L. 104-170, which was
promulgated in 1996 as an amendment to the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and
Cosmetic Act (FFDCA), the Agency was directed to \"ensure that there is
a reasonable certainty that no harm will result to infants and
children\" from aggregate exposure to a pesticide chemical residue. The
law further states that in the case of threshold effects, for purposes
of providing this reasonable certainty of no harm, \"an additional
tenfold margin of safety for the pesticide chemical residue and other
sources of exposure shall be applied for infants and children to take
into account potential pre- and post-natal toxicity and completeness of
the data with respect to exposure and toxicity to infants and children.
Notwithstanding such requirement for an additional margin of safety, the
Administrator may use a different margin of safety for the pesticide
residue only if, on the basis of reliable data, such margin will be safe
for infants and children.\"

Number range CHAPTERThe toxicology data base is not complete with
respect to assessing the increased susceptibility to infants and
children as required by FQPA for 4-t-amylphenol. The rat Number range
CHAPTERprenatal developmental study showed no quantitative evidence of
increased susceptibility (i.e., developmental NOAELs/LOAELs were the
higher than those for maternal effects). However, there was qualitative
evidence of increased susceptibility (i.e., fetal effects (skeletal
abnormalities, decreased body weight gain) were considered to be more
severe than the maternal toxicity (reversible clinical signs) observed
at the same dose level). In addition, there is an absence of
developmental toxicity data in the rabbit, and an absence of
reproductive toxicity data.

Number range CHAPTERIn the open literature (Yamasaki et al. 2003), an
increase in non-pregnant uterine weight was observed in rats following
4-t-amylphenol exposure. Another study (Soto et al. 1995) suggested that
4-t-amylphenol may have estrogenic effect. Wysowski et at. (1978)
reported elevated blood levels of bilirubin in children exposed to
4-t-ampyphenol and other phenols in disinfectant. These studies, while
not indicative, are suggestive of a basis for increased concern for
reproductive and/or developmental effects due to exposure to
4-t-amylphenol.

On the basis of a lack of guideline studies, qualitative evidence of
sensitivity in the developmental toxicity study, and the suggestive
evidence in the open literature of possible endocrine effects, the ADTC
has determined that the **FQPA Safety Factor should be retained (10x) at
this time.**

## 4.3 Dose-Response Assessment 

The doses and toxicological endpoints selected for various exposure
scenarios are summarized below.

+---------------+---------------+--------------+-----------------------+
| **Table 4.    |               |              |                       |
| Toxicological |               |              |                       |
| Endpoints**   |               |              |                       |
+===============+===============+==============+=======================+
| **Exposure    | **Dose Used   | **FQPA SF    | **Study and           |
| Scenario**    | in Risk       | and Endpoint | Toxicological         |
|               | Assessment,   | for Risk     | Effects**             |
|               | UF**          | Assessment** |                       |
+---------------+---------------+--------------+-----------------------+
| Acute Dietary | NOAEL = 200   | FQPA SF =    | Developmental         |
|               |               | 10x          | Toxicity Study in     |
| (Females 13 - | mg/kg/day     |              | Rats                  |
| 50 years)     |               | **a          |                       |
|               | UF = 100      | PAD=**[acute | LOAEL = 500           |
|               |               | RfD]         | mg/kg/day, based on   |
|               | DB=3x         | {.underline} | skeletal effects and  |
|               |               |              | decreased fetal body  |
|               | **Acute       | FQPA SF      | weight                |
|               | RfD**=0.67    |              |                       |
|               | mg/kg/day     | **=** 0.067  |                       |
|               |               | mg/kg/day    |                       |
+---------------+---------------+--------------+-----------------------+
| Chronic       | NOAEL = 50    | FQPA SF =    | Developmental         |
| Dietary       |               | 10x          | toxicity study in the |
|               | mg/kg/day     |              | rat                   |
| (all          |               | **cPA        |                       |
| populations)  | UF = 100      | D=**[chronic | LOAEL = 200 mg/kg/day |
|               |               | RfD]         | based on clinical     |
|               | DB=3x         | {.underline} | signs of toxicity,    |
|               |               |              | decreased body weight |
|               | **Chronic     | FQPA SF      | and body weight gain, |
|               | RfD**=0.17    |              | and decreased food    |
|               | mg/kg/day     | = 0.017      | consumption           |
|               |               | mg/kg/day    |                       |
+---------------+---------------+--------------+-----------------------+
| Incidental    | Maternal Oral | **Target     | Developmental         |
| Oral,         |               | MOE** =      | toxicity study in the |
|               | NOAEL = 50    |              | rat                   |
| Short- and    | mg/kg/day     | 3000         |                       |
| Inte          |               | (            | LOAEL = 200 mg/kg/day |
| rmediate-Term |               | residential) | based on clinical     |
|               |               | (10x inter-  | signs of toxicity,    |
|               |               | and          | decreased body weight |
|               |               | i            | and body weight gain, |
|               |               | ntra-species | and decreased food    |
|               |               | ex           | consumption           |
|               |               | trapolation, |                       |
|               |               | 10X FQPA, 3x |                       |
|               |               | database     |                       |
|               |               | uncertainty) |                       |
+---------------+---------------+--------------+-----------------------+
| Short-, and   | Dermal NOAEL  | **Target     | Subchronic dermal     |
| Intermediate  | = 25          | MOE** =      | toxicity study in     |
| -Term         |               |              | Rats                  |
|               | mg/kg/day for | 1000         |                       |
| Dermal        | systemic      | (            | Systemic LOAEL = not  |
|               | effects       | residential) | identified. No        |
|               |               | (10x inter-  | systemic effects      |
|               |               | and          | identified up to and  |
|               |               | intraspecies | including 25          |
|               |               | factors and  | mg/kg/day (HDT).      |
|               |               | 10x FQPA)    |                       |
|               |               |              | Dermal LOAEL= 10      |
|               |               | 100          | mg/kg/day for dermal  |
|               |               | (o           | effects and           |
|               |               | ccupational) | irritation. Dermal    |
|               |               |              | NOAEL=2.5 mg/kg/day   |
+---------------+---------------+--------------+-----------------------+
| Short-,       | Oral          | **Target     | Developmental         |
| I             |               | MOE** =      | toxicity study in the |
| ntermediate-, | NOAEL = 50    |              | rat                   |
| and Long-Term | mg/kg/day     | 300          |                       |
|               |               | (o           | LOAEL = 200 mg/kg/day |
| Inhalation    |               | ccupational) | based on clinical     |
|               |               | 3000         | signs of toxicity,    |
|               |               | (            | decreased body weight |
|               |               | residential) | and body weight gain, |
|               |               | (10x inter-  | and decreased food    |
|               |               | and          | consumption.          |
|               |               | intraspecies |                       |
|               |               | ex           |                       |
|               |               | trapolation, |                       |
|               |               | 10x FQPA, 3x |                       |
|               |               | database     |                       |
|               |               | uncertainty, |                       |
|               |               | and          |                       |
|               |               | ro           |                       |
|               |               | ute-specific |                       |
|               |               | e            |                       |
|               |               | xtrapolation |                       |
|               |               | factor)      |                       |
+---------------+---------------+--------------+-----------------------+
| Cancer        | No cancer     |              |                       |
|               | data          |              |                       |
|               | available for |              |                       |
|               | 4             |              |                       |
|               | -t-amylphenol |              |                       |
+---------------+---------------+--------------+-----------------------+

[Database Uncertainty Factor]{.underline}. For oral and inhalation risk
assessments, the ADTC applied an additional uncertainty factor of 3x at
this time, due to the number and significance of the data gaps for
conduct of these risk assessments. A 3x factor was not needed for the
dermal route as an acceptable route-specific study was available.

## 4.4 Endocrine Disruption 

The Food Quality Protection Act (FQPA; 1996) requires that EPA develop a
screening program to determine whether certain substances (including all
pesticides and inerts) \"may have an effect in humans that is similar to
an effect produced by a naturally occurring estrogen, or such other
endocrine effect\....\" Following the recommendations of its Endocrine
Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system. EPA also adopted EDSTAC's recommendation
that the Program include evaluations of potential effects in wildlife.
For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations.
As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disruptor Screening
Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency's EDSP have been developed, 4-t-amylphenol and its
potassium and sodium salts may be subjected to additional screening
and/or testing to better characterize effects related to endocrine
disruption.

As noted previously, the available data suggest that 4-t-amylphenol has
endocrine disrupter capabilities (uterotrophic and estrogenic effects)
and increased bilirubin production in babies.

# **5.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION**

Dietary exposure to 4-t-amylphenol can occur from use as a disinfectant
and food-contact sanitizer. Residential exposure can occur from
4-t-amylphenol-containing products, such as hard surface disinfectants.
Postapplication exposure can occur in adults and children from dermal
contact with treated textiles and diapers, as well as in children from
hand-to-mouth incidental oral exposure from treated surfaces.
Occupational exposure to 4-t-amylphenol can occur from
mixing/loading/application activities in various use sites, including
agricultural premises, food handling,
commercial/institutional/industrial premises and medical premises.

## 5.1 Summary of Registered Uses 

4-t-Amylphenol, and salts (potassium and sodium) are active ingredients
in disinfectant, food-contact sanitizer and deodorizer products used in
agricultural, food handling, commercial/institutional/industrial,
residential and public access, and medical settings, primarily used on
hard, non-porous surfaces. Number range CHAPTERExamples of registered
uses for 4-tert-amylphenol and salts include application to hard
surfaces (e.g., walls, floors, tables, fixtures), textiles (e.g.,
clothing, diapers, mattresses, bedding), carpets, medical instruments,
and agricultural equipment. Additionally, there are registered uses for
fogging in occupational settings and air deodorization in both
occupational and residential settings. Concentrations of
4-tert-amylphenol and salts in products range from 0.0027% to 10%. The
products are formulated as soluble concentrates, ready-to-use liquid
solutions, pressurized sprays, and impregnated wipes. The application
rates used in this assessment were the maximum application rates as
recommended on the product labels.

## 5.2 Dietary Exposure and Risk 

Estimates of dietary risk are based upon the detailed analysis in the
Dietary Exposure Assessment memorandum (memo from R. Quick to K. Swift,
September 2005, D316295) and are summarized here for completeness.
4-t-Number range CHAPTER Amylphenol and its potassium salt are
antimicrobials that can be used as disinfectants or sanitizers on
counter tops, tables, refrigerators, on animal premises; and in mushroom
premises. There are other registered uses for these chemicals that
include but are not limited to odor elimination in rooms, beauty parlors
and medical premises. There are 32 registered products that contain
4-t-amylphenol or its potassium and sodium salts as active ingredients
that may result in dietary exposure. 4-t-ANumber range CHAPTERmylphenol
(also known as phenol, 4-1,1-dimethylpropyl) (CAS No. 80-46-6) has a
tolerance exception in 40CFR 180.940 (c) as a food-contact sanitizer for
use in food-processing equipment and utensils with a not to exceed limit
of 80 ppm.

The use of antimicrobial chemicals on food or feed contact surfaces,
agricultural commodities, in animal premises and poultry premises
including hatcheries and application to food-grade eggs may result in
pesticide residues in human food. The Agency must determine the risk to
human health that may occur from exposure to these chemicals.

Number range CHAPTERRefrigerators counter tops, sinks and stoves are use
sites on registered labels. These surfaces that have been treated with
the 4-t-amylphenol products may bear small residues of the
4-t-amylphenol products after rinsing with potable water; i.e., rinsing
with potable water may not remove all residues deposited on the treated
surfaces from the proposed uses. Residues from treated surfaces can
migrate to food coming into contact with the treated and rinsed surfaces
and can be ingested by humans.

In the absence of residue data for residues of 4-t-amyphenol on treated
food contact surfaces, the Agency estimated residue levels that may
occur in food from the application rates on food contact surfaces. To
estimate the Estimated Daily Intake (EDI), the Agency has used an FDA
model. The maximum ingredient percentage for 4-t-amylphenol in food
handling establishments from the various labeled ready-to-use products
is 0.054 % a.i (540 ppm). The Agency estimates that use of this product
results in 4-t-amylphenol food residues of Number range CHAPTER340 ppb
(µg/kg). The Agency assumed that food can contact 2000 cm^2^ of treated
surfaces, and that 10% of the pesticide migrates to food based on the
Agency Residential SOPs. The use of the 10% transfer rate instead of the
use of a 100% transfer rate that is used in the FDA Sanitizer Solution
Guidelines requires the submission of confirmatory data to establish the
reliability of the use of the10% transfer rate. These daily estimates
were conservatively used to assess both acute and chronic dietary risks,
which are shown below in Table 5.

+---------------+---------------+--------+---------------+-----------+
| **Table 5.    |               |        |               |           |
| Summary of    |               |        |               |           |
| Dietary       |               |        |               |           |
| Exposure and  |               |        |               |           |
| Risk for      |               |        |               |           |
| 4-t           |               |        |               |           |
| -amylphenol** |               |        |               |           |
+===============+===============+========+===============+===========+
| **Population  | **Acute       |        | **Chronic     |           |
| Subgroup**    | Dietary**     |        | Dietary**     |           |
+---------------+---------------+--------+---------------+-----------+
|               | **Dietary     | **^%   | **^Dietary    | **^%\ c   |
|               | Exposure      | \ aPAD | \ Exposure^** | PAD\ b^** |
|               | (mg/kg/day)   | \ b^** |               |           |
|               | ^a^**         |        | **^(mg/       |           |
|               |               |        | kg/day)\ a^** |           |
+---------------+---------------+--------+---------------+-----------+
| adult male    | 0.0015        | NA     | 0.0015        | 9         |
+---------------+---------------+--------+---------------+-----------+
| females       | 0.0018        | 2.7    | 0.0018        | 10.6      |
| (13-50 years) |               |        |               |           |
+---------------+---------------+--------+---------------+-----------+
| inf           | 0.0072        | NA     | 0.0072        | 42        |
| ants/children |               |        |               |           |
+---------------+---------------+--------+---------------+-----------+

NA=not applicable

a\-- acute and chronic exposure analysis based on body weights of 70 kg,
60 kg, and 15 kg for adult males, females and children, respectively.

b\-- %PAD = dietary exposure (mg/kg/day) / aPAD or cPAD, where aPAD=
0.067 mg/kg/day for females of child bearing age; and cPAD=0.017
mg/kg/day for all populations

Dietary exposures from general agricultural premise use, poultry
hatcheries, mushroom houses and greenhouse and hydroponic uses are
expected to be much lower than the dietary exposures resulting from the
surface disinfectant and sanitizing uses.

Agricultural premise uses involve the application of a pesticide
chemical to the hard surface interior surfaces of the interior of barns
and poultry houses. These uses involve application to the physical
structure of the premises (including floors and walls) and also include,
but not limited to, watering troughs, feed troughs, animal halters,
ropes and forks.

Poultry hatcheries are not used in the production of eggs for food-grade
eggs for human consumption. Hatchery eggs are used for the production of
chicks. Sanitizer chemicals could penetrate the egg shell and become a
residue in the developing chick. Any residues that did penetrate the egg
shell and occur in the chick would not be expected to be detectable in
birds that are ready for consumption because of growth dilution in the
growing birds. The use of p-tertiary amylphenol products in poultry
hatcheries appears to be a non-food use.

4-t-Amylphenol is used for cleaning and sanitizing non-food contact
surfaces between crops in mushrooms. Surfaces that are treated include
tanks, air conditioners, air ducts, fans and breezeways, compost wharf,
concreted surfaces, inside and outside walls of mushroom houses, lofts,
floors, spawning machines, tampers, casing rings, storage sheds and
track alleys before spawning. Thus, the use of 4-t-amylphenol products
in mushroom houses appears to be a non-food use.

Food commodities can be grown in greenhouses and on hydroponic farms.
The food commodities can be grown in a growing media or hydroponically
in water. There is a label restriction against application to crop, soil
or growing media in which a crop grows or will be grown. There is also a
label instruction that requires a potable water rinse before treated
surfaces contact the crop or the substrate in which the crop is or will
be grown. A potable water rinse for treated surfaces will likely remove
a part, but not all of the residues from treated surfaces. The growing
structures could be made of wood, plastic, concrete or metal. The
greatest potential for residues adhering to treated surfaces would be
expected to be from the use of wood structures. Wood is porous and
residues would likely be absorbed into the treated surfaces. This would
also be true to a lesser extent on concrete surfaces. Metal surfaces
would not be porous and rinsing well or scrubbing would likely remove
most or all pesticide residues.

## 5.3 Drinking Water Exposure and Risk 

There are no currently registered outdoor uses of 4-t-amylphenol and its
salts that are being supported by the registrant. The Number range
CHAPTERpotential outdoor uses, wood protection to treat unseasoned
forest products, and use in potable human drinking water systems are
apparently no longer supported by any registrant. 4-t-AmylpNumber range
CHAPTERhenol's use as a general disinfectant allows for the possibility
of ground and surface water contamination. It has been found in an
effluent sample from a municipal waste water treatment plant. However,
the estimated value for biodegradation indicates it may biodegrade
linearly within days in the aquatic environment, although ultimate
biodegradation (mineralization) may take months. It is also volatile
based on its vapor pressure of 0.00116 mmHg, and has a moderate to
slight mobility in soils based on its estimated Koc value of 3799. The
sodium and potassium salts of 4-t-amylphenol are also slightly to
moderately mobile in soils, and are estimated to biodegrade within days
to weeks. Because of the possibility of biodegradation in water and
soils, 4-t-amylphenol and its salts are not likely to contaminate
surface and ground waters. Thus, a drinking water assessment was not
conducted for these chemicals.

## 5.4 Residential Exposure/Risk Pathway 

Details of the residential exposure assessment can be found within the
companion memorandum (memorandum from S. Mostaghimi, September 2005). A
summary of the residential assessment is presented below.

### 5.4.1 Residential Handler 

[Exposure Scenarios]{.underline}

4-t-Amylphenol is a disinfectant, sanitizer and deodorizer, that is used
in agricultural, food handling, commercial/institutional/industrial,
residential and medical settings. It is used as a hard surface
disinfectant (e.g., walls, floors, tables, fixtures), textiles (e.g.,
clothing, diapers, mattresses, bedding), carpets, medical instruments
and agricultural equipment. The following representative residential
handler scenarios were evaluated:

\(1\) mopping hard surfaces,

\(2\) wiping hard surfaces,

\(3\) using trigger pump equipment to treat hard surfaces and/or
textiles, and

\(4\) application to air using an aerosol spray can

4-t-amylphenol and salt products are widely used disinfectants and have
a large number of use patterns that are difficult to completely capture
in this assessment. As such, AD has selected representative scenarios
for each use site that are believed to be representative of the vast
majority of 4-t-amylphenol and salt uses, based on end-use product
application methods and use amounts.

[Exposure Data and Assumptions]{.underline}

There are no chemical-specific exposure data to assess paint
applications with a brush, roller, airless sprayer or aerosol can.
However, surrogate data are available for mopping, wiping, trigger pump
spray and aerosol can application methods. Dermal and inhalation
exposures were assessed for mopping and wiping using proprietary
Chemical Manufacturers Association (CMA) data (CMA 1992, USEPA 1999).
These data are based on individuals mopping floors and receiving
exposure via contact with the mop or with the bucket, or using a finger
pump sprayer to apply the product and then wipe the surfaces with a
paper towel. Dermal and inhalation exposures were assessed for trigger
pump spray and aerosol application methods using *PHED Version 1.1*
values found in the *Residential Exposure SOPs* (U.S. EPA, 1997a, 2001).
The surrogate exposure data in PHED are based on test subjects applying
an aerosol insecticide to baseboards in kitchens. The dermal and
inhalation exposures from these techniques have been normalized by the
amount of active ingredient handled and reported as unit exposures (UE)
expressed as mg/lb ai handled.

In addition, product label maximum application rates, related use
information, and Agency standard values were used to assess residential
handler exposures. For example, it was assumed that one gallon of
diluted solution is used for mopping floors, while 0.5 liters (0.13
gallons) are used in the wiping and trigger pump spray scenario. For
aerosol can spray, it was assumed that one 16 oz can of product is used
in a day. The residential handler scenarios are assumed to be of short-
and intermediate-term duration (1-30 days and 1-6 months)

[Risk Characterization]{.underline}

A summary of the residential handler exposures and risk are presented on
Table 6. The non-cancer risk estimates are expressed in terms of the
MOE. For residential handlers that handle products containing
4-t-amylphenol and its salts, short-term, and intermediate-term MOEs
were above the target MOEs (i.e., \>1000 for dermal and \>3000 for
inhalation) and thus, do not exceed the Agency's level of concern for
any of the residential handler scenarios evaluated.

+---------------+---------+-----------+--------------+---------------+
| **Table 6**   |         |           |              |               |
|               |         |           |              |               |
| **Estimates   |         |           |              |               |
| of Exposures  |         |           |              |               |
| and Risks to  |         |           |              |               |
| Residential   |         |           |              |               |
| Handlers of** |         |           |              |               |
|               |         |           |              |               |
| **4           |         |           |              |               |
| -t-Amylphenol |         |           |              |               |
| and salts     |         |           |              |               |
| (Short- and   |         |           |              |               |
| Intermediat   |         |           |              |               |
| e-Duration)** |         |           |              |               |
+---------------+---------+-----------+--------------+---------------+
| **Scenario**  | *       | **I       | **Dermal     | **Inhalation  |
|               | *Dermal | nhalation | MOE^c^**     | MOE^d^**      |
|               | Dose**  | Dose**    |              |               |
|               |         |           | **(Target    | **(Target     |
|               | **(m    | **(mg/kg/ | MOE\>1000)** | MOE\>3000)**  |
|               | g/kg/da | day)^b^** |              |               |
|               | y)^a^** |           |              |               |
+---------------+---------+-----------+--------------+---------------+
| \(1\) Mopping | 0.00128 | 4.        | 20,000       | 1,200,000     |
|               |         | 25x10^-5^ |              |               |
+---------------+---------+-----------+--------------+---------------+
| \(2\) Wiping  | 0.00666 | 1.        | 3,800        | 320,000       |
|               |         | 56x10^-4^ |              |               |
+---------------+---------+-----------+--------------+---------------+
| \(3\) Trigger | 0.00198 | 2.        | 13,000       | 2,300,000     |
| Pump Spray    |         | 16x10^-5^ |              |               |
+---------------+---------+-----------+--------------+---------------+
| \(4\) Aerosol | 0.00233 | 2.        | 11,000       | 2,000,000     |
| Spray         |         | 54x10^-5^ |              |               |
+---------------+---------+-----------+--------------+---------------+

^a^ Dermal Dose (mg/kg/day) = \[Unit Dermal Exposure (mg/lb ai) \* Use
Rate (lb ai/lb product or lb ai/gal product) \* Amount Handled per Day
(lb product/day)\] / Body Weight (kg).

^b^ Inhalation Dose (mg/kg/day) = \[Unit Inhalation Exposure (mg/lb ai)
\* Use Rate (lb ai/lb product or lb ai/gal product) \* Amount Handled
per Day (lb product/day)\*inhalation absorption (1.0)\] / Body Weight
(kg)

^c^ Dermal MOE = Dermal NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day).
Where the NOAEL is 25 mg/kg/day from the subchronic rat dermal toxicity
study.

^d^ Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose
(mg/kg/day). Where the inhalation NOAEL of 50 mg/kg/day is from an oral
rat developmental study. In the absence of data, inhalation absorption
is assumed to be equivalent to oral absorption

### 5.4.2 Postapplication Residential Exposure 

> Residential postapplication exposures result when bystanders (adults
> and children) come in contact with 4-t-amylphenol and its salts in
> areas where pesticide-treated end-use products have recently been
> applied (e.g., treated hard surfaces/floors), or when children
> incidentally ingest the pesticide residues through mouthing the
> treated end products/treated articles (i.e., hand-to-mouth or
> object-to-mouth contact).
>
> Number range CHAPTERFor the purposes of this screening level
> assessment, postapplication scenarios have been developed that
> encompass multiple products, but still represent a high end exposure
> scenario for all products represented. Representative postapplication
> scenarios assessed include:
>
> • contacting treated hard surfaces/floors (dermal and incidental oral
> exposure to children),
>
> • wearing treated clothing (dermal exposure to adults and children),
>
> • wearing diapers treated with a trigger-pump spray (dermal exposure
> to children),
>
> • mouthing treated textiles such as clothing and blankets (incidental
> oral exposure to children), and
>
> • postapplication/bystander inhalation exposures from use of
> disinfecting/deodorizing products (vapor exposure to adults and
> children).

[Exposure Data and Assumptions]{.underline}

> Typically, most products used in a residential setting result in
> exposures occurring over a short-term time duration (1 -- 30 days). If
> the products are used on a routine basis (i.e., once a week) and the
> active ingredient has a long indoor half-life, exposures may occur
> over an intermediate-term time duration (30 days -- 6 months). At this
> time, AD does not have residue dissipation data or reliable use
> pattern data, including the frequency and duration of use of
> antimicrobial products in the residential setting. Even though AD does
> not believe that the use patterns of many residential products result
> in intermediate-term exposure, they are assessed to provide an upper
> bound estimate of exposure. AD does believe, however, that
> intermediate-term exposure to children may occur in day care centers
> where disinfecting products are used more frequently.
>
> A number of conservative assumptions were used in assessing
> postapplication risks including maximum application rate from the
> label. In addition Number range CHAPTERquantities handled/treated were
> estimated based on information from various sources, including the
> Draft Standard Operating Procedures (SOPs) for Residential Exposure
> Assessments (USEPA 2000, 2001) and the AD Draft Residential SOP use
> table. In certain cases, no standard values were available for some
> scenarios. Assumptions for these scenarios were based on AD estimates
> and could be further refined from input from affected sectors. In the
> absence of data, for both the textile and diaper scenarios, it was
> assumed that either 100% or 5% of 4-t-amylphenol could transfer and be
> available for dermal contact. The Agency will require data to confirm
> the actual transfer factor of 4-t-amylphenol
>
> Number range CHAPTERNo postapplication air concentration data have
> been submitted for 4-t-amylphenol to determine potential vapor
> inhalation risk. Therefore, the Multi-Chamber Concentration and
> Exposure Model (MCCEM v1.2) was used to present a screening-level
> estimate of the potential inhalation risk to adults and children for
> the air deodorizer use. MCCEM estimates average and peak indoor air
> concentrations of chemicals released from products or materials in
> houses, apartments, townhouses, or other residences. The data
> libraries in MCCEM contain information about Number range
> CHAPTERresidential settings. MCCEM estimates inhalation exposures to
> chemicals, calculated as single day doses, chronic average daily
> doses, or lifetime average daily doses. (All dose estimates are
> potential doses; they do not account for actual absorption into the
> body.)
>
> [Risk Characterization]{.underline}
>
> A summary of the residential postapplication exposures and risks are
> presented on Table 7. The non-cancer risk estimates are expressed in
> terms of the MOE. The target MOEs are \>1000 for dermal exposures, and
> \>3000 for incidental oral and inhalation exposures.

**Dermal Risks**. Number range CHAPTERThe child short- and
intermediate-term dermal MOEs for contact following hard surface
disinfection is above the target MOE of 1,000 for residential settings
(MOE = 3,700) and slightly below the MOE for daycare centers (MOE =
940). Number range CHAPTER The short- and intermediate-term MOEs for
dermal contact with treated clothing is of concern for young children
(MOEs are \<1 assuming a 100% transfer factor; MOE=17 assuming a 5%
transfer factor). For adults, the dermal MOE is below the target MOE of
1,000 using a 100% transfer factor (MOE = 140) and above the MOE using
the 5% transfer factor (MOE = 2,700). The Number range CHAPTERdermal MOE
for a children wearing treated diapers is only of concern (MOE=59) using
a transfer factor of 100%, but it not of concern when using a transfer
factor of 5%. The Agency requires confirmatory data for a 4-t-amylphenol
transfer factor from clothing and diapers. In addition, it should be
noted that 4-t-amylphenol caused dermal irritant effects following
repeated dermal exposure, and may also be a potential dermal sensitizer.
The Agency intends to consider these effects in the labeling of
pesticide products containing 4-t-amylphenol, and request additional
dermal toxicity data on the diluted end-use formulated product.

> **Incidental Oral Risks**. Number range CHAPTERThe short- and
> intermediate-term incidental oral MOEs following hard surface
> disinfection are above the target MOE of 3,000 for residential
> settings (MOE = 61,000) and daycare centers (MOE = 15,000), and thus
> are not of concern. However, the oral MOE for children mouthing
> treated textiles exceeds the Agency's level of concern (MOE=650
> compared to target MOE\>3000).
>
> **Inhalation Risks.** Number range CHAPTERFor both adults and
> children, the calculated inhalation MOEs are greater than the target
> MOE of 3,000 (MOE=27,000 and 7,500, respectively), for inhalation
> exposures following use of an air deodorizer.

+----------------+-------------+--------------+-----------------------+
| **Table 7**    |             |              |                       |
|                |             |              |                       |
| **Summary of   |             |              |                       |
| Short- and     |             |              |                       |
| Inter          |             |              |                       |
| mediate-Term** |             |              |                       |
|                |             |              |                       |
| **Residential  |             |              |                       |
| P              |             |              |                       |
| ostapplication |             |              |                       |
| Exposures and  |             |              |                       |
| Risks**        |             |              |                       |
+================+=============+==============+=======================+
| **Scenario**   |             | **Dose ^a^** | **MOE^b^**            |
|                |             |              |                       |
|                |             | **(          | **(Target MOE\>1000   |
|                |             | mg/kg/day)** | dermal;**             |
|                |             |              |                       |
|                |             |              | **\>3000 oral and     |
|                |             |              | inhalation)**         |
+----------------+-------------+--------------+-----------------------+
| **Dermal       |             |              |                       |
| Exposure**     |             |              |                       |
+----------------+-------------+--------------+-----------------------+
| Hard surface   | Residential | 0.0067       | 3,700                 |
| Disinfection   | Setting     |              |                       |
+----------------+-------------+--------------+-----------------------+
|                | Daycare     | 0.0267       | 940                   |
|                | center      |              |                       |
+----------------+-------------+--------------+-----------------------+
| Treated        | Adults      | 0.0092 (5%   | 2,700                 |
| clothing       |             | transfer)    |                       |
|                |             |              | **140**               |
|                |             | 0.185 (100%  |                       |
|                |             | transfer)    |                       |
+----------------+-------------+--------------+-----------------------+
|                | Children    | 1.45 (5%     | **17**                |
|                |             | transfer)    |                       |
|                |             |              | **\<1**               |
|                |             | 28.9 (100%   |                       |
|                |             | transfer)    |                       |
+----------------+-------------+--------------+-----------------------+
| Treated        | Children    | 0.0212 (5%   | 1,200                 |
| Diapers        |             | transfer)    |                       |
|                |             |              | **59**                |
|                |             | 0.424 (100%  |                       |
|                |             | transfer)    |                       |
+----------------+-------------+--------------+-----------------------+
| **Incidental   |             |              |                       |
| Oral           |             |              |                       |
| Exposure**     |             |              |                       |
+----------------+-------------+--------------+-----------------------+
| Hard surface   | Residential | 0.000817     | 61,000                |
| Disinfection   | Setting     |              |                       |
+----------------+-------------+--------------+-----------------------+
|                | Daycare     | 0.00155      | 32,000                |
|                | center      |              |                       |
+----------------+-------------+--------------+-----------------------+
| Treated        | Children    |              | **650**               |
| clothing       |             |              |                       |
+----------------+-------------+--------------+-----------------------+
| **Inhalation   |             |              |                       |
| Exposure**     |             |              |                       |
+----------------+-------------+--------------+-----------------------+
| Air Deodorizer | Adults      | 0.00186      | 27,000                |
+----------------+-------------+--------------+-----------------------+
|                | Children    | 0.00666      | 7,500                 |
+----------------+-------------+--------------+-----------------------+

^a^ Dose calculations for each scenario above are outlined in the
attached Occupational/Residential Assessment (memo from S. Number range
CHAPTER Mostaghimi, May 2005).

^b^ MOE= NOAEL (mg/kg/day) / PDR (mg/kg/day). Oral and inhalation NOAEL
is 50 mg/kg/day; dermal NOAEL is 25 mg/kg/day

# **6.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION**

# 

In order for a pesticide registration to continue, it must be shown that
the use does not result in "unreasonable adverse effects on the
environment". Section 2 (bb) of FIFRA defines this term to include "a
human dietary risk from residues that result from a use of a pesticide
in or on any food inconsistent with standard under section 408\..." of
FFDCA. As mandated by the FQPA amendments to FIFRA and the Federal Food,
Drug and Cosmetic Act (FFDCA), the Agency must consider total aggregate
exposure from food, drinking water and residential sources of exposure
to 4-t-amylphenol. Aggregate exposure is the total exposure to a single
chemical (or its residues) that may occur from dietary (i.e., food and
drinking water), residential, and other non-occupational sources, and
from plausible exposure routes (oral, dermal, and inhalation).

Typically, aggregate risk assessment are conducted for acute (1 day),
short-term (1-30 days), intermediate-term (1-6 months) and chronic (6
months to lifetime) exposures. However, acute and chronic aggregate
assessments were not conducted because there are no significant impacts
to drinking water sources, nor are there long-term residential uses.
Thus, only short- and intermediate-term aggregate assessments were
conducted. Oral and inhalation exposure and risk estimates were combined
for the aggregate risk assessment because these endpoints are based on
the same toxicity study (oral developmental study) and effects of
concern (clinical signs and changes in body weight and food
consumption). Dermal exposures were not aggregated with the oral or
inhalation exposures due to different toxicological endpoints for oral
(clinical signs and body weight changes), and dermal (no systemic
effects at the highest dose tested). Number range CHAPTER

In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at
[[http://www.epa.gov/pesticides/trac/science/aggregate.pdf]{.underline}](http://www.epa.gov/pesticides/trac/science/aggregate.pdf)
). Steps for deciding whether to perform aggregate exposure and risk
assessments are listed, which include: identification of toxicological
endpoints for each exposure route and duration; identification of
potential exposures for each pathway (food, water, and/or residential);
reconciliation of durations and pathways of exposure with durations and
pathways of health effects; determination of which possible residential
exposure scenarios are likely to occur together within a given time
frame; determination of magnitude and duration of exposure for all
exposure combinations; determination of the appropriate technique
(deterministic or probabilistic) for exposure assessment; and
determination of the appropriate risk metric to estimate aggregate risk.

## 6.1 Short- and Intermediate-Term Aggregate Risk 

Aggregate short and intermediate term risk assessments are designed to
provide estimates of risk likely to result from exposures to the
pesticide or pesticide residues in food, water, and from residential (or
other non-occupational) pesticide uses. Short- and intermediate-term
aggregate risks are considered together because the exposure and
toxicity endpoints are identical for incidental oral, and inhalation
residential exposures for both durations. For children, the short- and
intermediate-term aggregate assessment includes average dietary exposure
(food) and estimated incidental oral exposures to children from
residential uses such as hard surface disinfection. In addition,
inhalation exposure from the postapplication of an air deodorizer use
was aggregated with the oral exposures since the toxicity endpoint is
the same. For adults, the aggregate assessment includes dietary (oral)
and residential inhalation exposures from wiping a hard surface
disinfectant, in addition to postapplication inhalation exposure from
the air deodorizer.

Aggregate risks were calculated using the total MOE approach outlined in
OPP guidance for aggregate risk assessment (August 1, 1999, Updated
"Interim Guidance for Incorporating Drinking Water Exposure into
Aggregate Risk Assessments"). The assumptions and equations are
presented in the footnotes on Table 8.

[Oral and Inhalation Aggregate Risks]{.underline}. Table 8 presents a
summary of the short- and intermediate-term aggregate risk MOEs. The
aggregate oral and inhalation risks are not of concern for adults, as
the total aggregate MOE is 13,000 which is greater than the target of
3,000. For children, the aggregate risk estimates are also above the
target MOE of 3000 (MOE=3,200) and thus are not of concern. It should be
noted that several conservative assumptions were used in this
assessment. As noted previously, incidental oral exposure to treated
textiles are not included in the aggregate assessment because the oral
MOE is already of concern (MOE=650 vs target \>3000).

[Dermal Risk Results]{.underline}. A dermal aggregate assessment was not
conducted because the toxicity effects for the dermal exposure route are
not the same as the oral/inhalation exposure route. However, as shown
previously on Table 7, short- and intermediate dermal risks are already
of concern for residents for the treated textile and diaper use.

+-----------------------+-------------+-------+----------+---+----------+
| **Table 8**           |             |       |          |   |          |
|                       |             |       |          |   |          |
| **Summary of Short-   |             |       |          |   |          |
| and Intermediate-Term |             |       |          |   |          |
| Aggregate Risk        |             |       |          |   |          |
| Estimates**           |             |       |          |   |          |
+=======================+=============+=======+==========+===+==========+
| **Exposure Scenario** | **Dose      |       | **Total  |   |          |
|                       | ^a^**       |       | MOE^b^** |   |          |
|                       |             |       |          |   |          |
|                       | **(m        |       | *        |   |          |
|                       | g/kg/day)** |       | *(Target |   |          |
|                       |             |       | MOE\     |   |          |
|                       |             |       | >3000)** |   |          |
+-----------------------+-------------+-------+----------+---+----------+
|                       | **Child**   | **Ad  | *        |   | *        |
|                       |             | ult** | *Child** |   | *Adult** |
+-----------------------+-------------+-------+----------+---+----------+
| **Oral Exposure**     |             |       |          |   |          |
+-----------------------+-------------+-------+----------+---+----------+
| Dietary Exposure      | 0.0072      | 0     | 6940 (c) | 2 |          |
|                       |             | .0018 |          | 8 |          |
|                       |             | (a)   |          | , |          |
|                       |             |       |          | 0 |          |
|                       |             |       |          | 0 |          |
|                       |             |       |          | 0 |          |
|                       |             |       |          | ( |          |
|                       |             |       |          | c |          |
|                       |             |       |          | ) |          |
+-----------------------+-------------+-------+----------+---+----------+
| Hard surface          | 0.00155     | NA    | 32,000   |   | NA       |
| Disinfection          |             |       |          |   |          |
| \--Daycare center     |             |       |          |   |          |
+-----------------------+-------------+-------+----------+---+----------+
| **Inhalation          |             |       |          |   |          |
| Exposure**            |             |       |          |   |          |
+-----------------------+-------------+-------+----------+---+----------+
| Handler of hard       | NA          | 0.0   | NA       |   | 320,000  |
| surface               |             | 00156 |          |   |          |
| disinfectant\--wiping |             |       |          |   |          |
+-----------------------+-------------+-------+----------+---+----------+
| Air Deodorizer        | 0.00666     | 0.    | 7,500    |   | 27,000   |
|                       |             | 00186 |          |   |          |
+-----------------------+-------------+-------+----------+---+----------+
| Total Aggregate Dose  | 0.0154      | 0.    | *        |   | **       |
| and MOE               |             | 00316 | *3,240** |   | 13,000** |
+-----------------------+-------------+-------+----------+---+----------+

NA= Not applicable

(a) Chronic dietary exposure for females 13-50 years.

(b) Number range CHAPTERMOE = NOAEL (mg/kg/day) / potential dose rate
    (mg/kg/day) \[Where short-and intermediate-term oral NOAEL = 50
    mg/kg/day\]. Target MOE = 3,000.

(c) Risk estimates are equivalent to percent of the PAD of 42% for child
    and 10.6% for adults.

## 6.2 Long-Term Aggregate Risk 

A long-term aggregate assessment was not conducted because the only
long-term residential use (diaper use) results in dermal exposure, which
has a different toxicological effect than the chronic dietary oral
exposure.

# **7.0 CUMULATIVE EXPOSURE AND RISK**

Another standard of section 408 of the FFDCA which must be considered in
making an unreasonable adverse effect determination is that the Agency
considers \"available information" concerning the cumulative effects of
a particular pesticide\'s residues and \"other substances that have a
common mechanism of toxicity."

For the purposes of this tolerance action, therefore, EPA has not
assumed that 4-t-amylphenol and its potassium and sodium salts have a
common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA's Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common
mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/.

# **8.0 OCCUPATIONAL EXPOSURE AND RISK** 

AD has assessed the exposures and risks to occupational workers that
handle 4-t-amylphenol (memorandum from S. Number range
CHAPTERMostaghimi, September 2005). This section summarizes the results
of the occupational exposure assessment.

Based on examination of product labels describing uses for the product,
it has been determined that exposure to handlers can occur in a variety
of occupational settings. Additionally, postapplication exposures are
likely to occur in these settings. The representative scenarios selected
by AD for assessment were evaluated using maximum application rates as
recommended on the product labels for 4-t-amylphenol.

**Occupational Handlers.** The Agency has determined that there is
potential for dermal and inhalation worker exposure to 4-t-amylphenol at
various use sites including agricultural premises, food handling,
commercial/institutional/industrial premises, and medical premises. The
occupational exposure scenarios, and estimated risks are presented on
Table 9.

To assess the handler risks, AD used surrogate unit exposure data from
both the proprietary Chemical Manufacturers Association (CMA)
antimicrobial exposure study and the Pesticide Handlers Exposure
Database (PHED).

For the occupational handler dermal and inhalation risk assessment, the
short- and intermediate- term risks calculated at baseline exposure (no
gloves and no respirators) were above target MOEs for all scenarios
(i.e., dermal MOEs were \>100 and inhalation MOEs were \>300). Note,
however, that the high pressure spray application method in the
agricultural use site category was assessed using gloved data.

+--------+---+---------+--------+----------+---------+---------+---------+
| *      |   |         |        |          |         |         |         |
| *Table |   |         |        |          |         |         |         |
| 9**    |   |         |        |          |         |         |         |
|        |   |         |        |          |         |         |         |
| **S    |   |         |        |          |         |         |         |
| hort-, |   |         |        |          |         |         |         |
| Inter  |   |         |        |          |         |         |         |
| mediat |   |         |        |          |         |         |         |
| e-Term |   |         |        |          |         |         |         |
| Risks  |   |         |        |          |         |         |         |
| for    |   |         |        |          |         |         |         |
| Occupa |   |         |        |          |         |         |         |
| tional |   |         |        |          |         |         |         |
| Hand   |   |         |        |          |         |         |         |
| lers** |   |         |        |          |         |         |         |
+========+===+=========+========+==========+=========+=========+=========+
| **Ex   | * |         | *      | **       | **MOE   |         |         |
| posure | * |         | *Appli | Quantity | c**     |         |         |
| Scen   | M |         | cation | Ha       |         |         |         |
| ario** | e |         | Rate   | ndled/** |         |         |         |
|        | t |         | (lb    |          |         |         |         |
|        | h |         | ai/    | *        |         |         |         |
|        | o |         | gal    | *Treated |         |         |         |
|        | d |         | lon)** | per day  |         |         |         |
|        | o |         |        | (ga      |         |         |         |
|        | f |         |        | llons)** |         |         |         |
|        | A |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | l |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | c |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | t |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | o |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | * |         |        |          |         |         |         |
|        | * |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        |   |         |        |          | **B     | **PPE   | **B     |
|        |   |         |        |          | aseline | Gloves  | aseline |
|        |   |         |        |          | Dermal  | Dermal  | Inhal   |
|        |   |         |        |          | (a)**   | (b)**   | ation** |
|        |   |         |        |          |         |         |         |
|        |   |         |        |          | **      | **      | **      |
|        |   |         |        |          | (Target | (Target | (Target |
|        |   |         |        |          | MOE\    | MOE\    | MOE\    |
|        |   |         |        |          | >100)** | >100)** | >100)** |
+--------+---+---------+--------+----------+---------+---------+---------+
| **     |   |         |        |          |         |         |         |
| Agricu |   |         |        |          |         |         |         |
| ltural |   |         |        |          |         |         |         |
| Pr     |   |         |        |          |         |         |         |
| emises |   |         |        |          |         |         |         |
| and    |   |         |        |          |         |         |         |
| Equip  |   |         |        |          |         |         |         |
| ment** |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Appli  | L |         | 0.0034 | 10       | 270     | No Data | 150,000 |
| cation | o |         |        |          |         |         |         |
| to     | w |         |        |          |         |         |         |
| hard   | P |         |        |          |         |         |         |
| su     | r |         |        |          |         |         |         |
| rfaces | e |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | H |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
|        | w |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | H |         |        | 40       | No Data | 5,100   | 210,000 |
|        | i |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | h |         |        |          |         |         |         |
|        | P |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | H |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
|        | w |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | M |         |        | 2        | 3,600   | No Data | 220,000 |
|        | o |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | W |         |        | 0.26     | 690     | No Data | 59,000  |
|        | i |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | T |         |        | 0.26     | 10,000  | 24,000  | 3,      |
|        | r |         |        |          |         |         | 000,000 |
|        | i |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | P |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | m |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | S |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | y |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Fogger | L |         | 0.163  | 15,000   | 120     | No Data | 4,500   |
|        | i |         | lb     | ft2      |         |         |         |
|        | q |         | a      |          |         |         |         |
|        | u |         | i/gal/ |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | d |         | 6,000  |          |         |         |         |
|        | P |         | ft2    |          |         |         |         |
|        | o |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | o |         |        |          |         |         |         |
|        | f |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | o |         |        |          |         |         |         |
|        | l |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | b |         |        |          |         |         |         |
|        | l |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | c |         |        |          |         |         |         |
|        | o |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | c |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | t |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | t |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| **Food |   |         |        |          |         |         |         |
| Hand   |   |         |        |          |         |         |         |
| ling** |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Appli  | L |         | 0.0025 | 2        | 1,800   | No Data | 1,      |
| cation | o |         |        |          |         |         | 000,000 |
| to     | w |         |        |          |         |         |         |
| indoor | P |         |        |          |         |         |         |
| hard   | r |         |        |          |         |         |         |
| su     | e |         |        |          |         |         |         |
| rfaces | s |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | H |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
|        | w |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | M |         |        | 2        | 4,900   | No Data | 290,000 |
|        | o |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | W |         |        | 0.26     | 940     | No Data | 80,000  |
|        | i |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | T |         |        | 0.26     | 7,300   | 17,000  | 2,      |
|        | r |         |        |          |         |         | 100,000 |
|        | i |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | P |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | m |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | S |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | y |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| **     |   |         |        |          |         |         |         |
| Commer |   |         |        |          |         |         |         |
| cial/I |   |         |        |          |         |         |         |
| nstitu |   |         |        |          |         |         |         |
| tional |   |         |        |          |         |         |         |
| Prem   |   |         |        |          |         |         |         |
| ises** |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Appli  | L |         | 0.005  | 2        | 920     | No Data | 510,000 |
| cation | o |         |        |          |         |         |         |
| to     | w |         |        |          |         |         |         |
| indoor | P |         |        |          |         |         |         |
| hard   | r |         |        |          |         |         |         |
| su     | e |         |        |          |         |         |         |
| rfaces | s |         |        |          |         |         |         |
|        | s |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | H |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
|        | w |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | d |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | M |         |        | 2        | 2,400   | No Data | 150,000 |
|        | o |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | W |         |        | 0.26     | 470     | No Data | 40,000  |
|        | i |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | i |         |        |          |         |         |         |
|        | n |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        | T |         |        | 0.26     | 7,100   | 17,000  | 2,      |
|        | r |         |        |          |         |         | 100,000 |
|        | i |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | g |         |        |          |         |         |         |
|        | e |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | P |         |        |          |         |         |         |
|        | u |         |        |          |         |         |         |
|        | m |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | S |         |        |          |         |         |         |
|        | p |         |        |          |         |         |         |
|        | r |         |        |          |         |         |         |
|        | a |         |        |          |         |         |         |
|        | y |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Air    |   | Aerosol | 0.074% | 3 16 oz  | 4,100   | 9,700   | 1.      |
| D      |   | Spray   | ai by  | cans     |         |         | 200,000 |
| eodori |   |         | weight |          |         |         |         |
| zation |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| **M    |   |         |        |          |         |         |         |
| edical |   |         |        |          |         |         |         |
| Pr     |   |         |        |          |         |         |         |
| emises |   |         |        |          |         |         |         |
| and    |   |         |        |          |         |         |         |
| Equip  |   |         |        |          |         |         |         |
| ment** |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Appli  |   | Low     | 0.005  | 2        | 920     | No Data | 510,000 |
| cation |   | P       |        |          |         |         |         |
| to     |   | ressure |        |          |         |         |         |
| indoor |   | H       |        |          |         |         |         |
| hard   |   | andwand |        |          |         |         |         |
| su     |   |         |        |          |         |         |         |
| rfaces |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
|        |   | Mopping |        | 45       | 110     | No Data | 6,500   |
+--------+---+---------+--------+----------+---------+---------+---------+
|        |   | Wiping  |        | 0.26     | 470     | No Data | 40,000  |
+--------+---+---------+--------+----------+---------+---------+---------+
|        |   | Trigger |        | 0.26     | 7,100   | 17,000  | 2,      |
|        |   | Pump    |        |          |         |         | 100,000 |
|        |   | Spray   |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+
| Air    |   | Aerosol | 0.074% | 3 16 oz  | 4,100   | 9,700   | 1,      |
| D      |   | Spray   | ai by  | cans     |         |         | 200,000 |
| eodori |   |         | weight |          |         |         |         |
| zation |   |         |        |          |         |         |         |
+--------+---+---------+--------+----------+---------+---------+---------+

\(a\) Baseline Dermal: Long-sleeve shirt, long pants, no gloves.

\(b\) PPE Dermal with gloves: baseline dermal plus chemical-resistant
gloves.

c MOE = NOAEL (mg/kg/day) / Daily Dose \[Where short-and
intermediate-term NOAEL = 25 mg/kg/day for dermal exposure and short-,
and Number range CHAPTERintermediate-term inhalation NOAEL =50 mg/kg/day
for inhalation exposure\]. Target MOE is 100 for dermal exposure and 300
for inhalation exposure.

**Postapplication Exposure and Risk.** For most of the occupational
scenarios, postapplication dermal exposure is not expected to occur or
is expected to be negligible based on the application rates and chemical
properties of the chemical. Postapplication/bystander inhalation
exposures, however, were assessed for entry into a building after a
fogging application. The representative building selected was a poultry
barn. The Agency used the MCCEM (Multi- Chamber Concentration and
Exposure Model) to estimate postapplication/bystander exposures.

The calculated inhalation MOEs were above the target MOE of 300 for all
fogging postapplication scenarios.

# **9.0 INCIDENTS**

A detailed summary of the human incident data is presented in the
memorandum from J. Chen D316276, July 2005. Below is a brief summary of
this information. Number range CHAPTERThe Agency consulted the following
databases for poisoning incident data for 4-t-amylphenol and its salts,
and other similar phenolic disinfectant compounds:

(1) **[OPP Incident Data System (IDS)]{.underline}** - The Incident Data
    System of The Office of Pesticide Programs (OPP) of the
    Environmental Protection Agency (EPA) contains reports of incidents
    from various sources, including registrants, other federal and state
    health and environmental agencies and individual consumers,
    submitted to OPP since 1992. Reports submitted to the Incident Data
    System represent anecdotal reports or allegations only, unless
    otherwise stated. Typically no conclusions can be drawn implicating
    the pesticide as a cause of any of the reported health effects.
    Nevertheless, sometimes with enough cases and/or enough
    documentation risk mitigation measures may be suggested.

(2) Number range CHAPTER**[Poison Control Centers]{.underline}** - as
    the result of a data purchase by EPA, OPP received Poison Control
    Center data covering the years 1993 through 1998 for all pesticides.
    Most of the national Poison Control Centers (PCCs) participate in a
    national data collection system, the Toxic Exposure Surveillance
    System, which obtains data from about 65-70 centers at hospitals and
    universities. PCCs provide telephone consultation for individuals
    and health care providers on suspected poisonings, involving drugs,
    household products, pesticides, etc.

(3) Number range CHAPTER**[California Department of Pesticide
    Regulation]{.underline}** - California has collected uniform data on
    suspected pesticide poisonings since 1982. Physicians are required,
    by statute, to report to their local health officer all occurrences
    of illness suspected of being related to exposure to pesticides. The
    majority of the incidents involve workers. Information on exposure
    (worker activity), type of illness (systemic, eye, skin, eye/skin
    and respiratory), likelihood of a causal relationship, and number of
    days off work and in the hospital are provided.

(4) Number range CHAPTER**[National Pesticide Telecommunications Network
    (NPTN)]{.underline}** - NPTN is a toll-free information service
    supported by OPP. A ranking of the top 200 active ingredients for
    which telephone calls were received during calendar years 1984-1991,
    inclusive, has been prepared. The total number of calls was
    tabulated for the categories human incidents, animal incidents,
    calls for information, and others.

Number range CHAPTERThere are some reported incidents associated with
exposure to end-use products containing 4-tert-amylphenol. Dermal,
ocular and inhalation are the primary routes of exposure. Dermal
exposure is considered as a very important route of exposure. Most of
the incidents are related to irritation reaction. The most common
symptoms reported for cases of inhalation exposure were respiratory
irritation/burning, irritation to mouth/throat/nose, coughing/choking,
shortness of breath, dizziness, flu-like symptoms, and headache. Eye
pain, burning of eyes, conjunctivitis, blurring vision, and acute
inflammation have been reported in ocular exposure incidents.
Neurological effects, such as dizziness, headache and blurred vision
have also been reported.

# **10.0 ENVIRONMENTAL RISK**

A detailed ecological hazard and environmental risk assessment for
4-t-amylphenol and its salts is presented in the attached memorandum
(memo from D. Bays, October 2005). A brief summary is presented below.

[Environmental Modeling/Exposure]{.underline}. The limited environmental
exposure resulting from indoor uses of 4-t-amylphenol and its salts is
not anticipated to cause adverse effects to terrestrial or aquatic
organisms.

[Ecological Hazard and Risk]{.underline}. The registrant has not
submitted any ecological effects data to support this RED. The only data
that was available was found in the peer-reviewed literature. None of
these studies met current guideline requirements and therefore, could
not be used in a risk assessment. There is a concern about the
possibility of endocrine disruption in fish, since 4-t-amylphenol is
considered an ecoestrogen. This was documented in several studies on
carp (*Cyprinus carpio*), whose findings were included in the
ecotoxicity chapter. However, since this chemical is restricted to
indoor uses only, the possibility for exposure of fish to 4-t-amylphenol
would be limited. The registrant does have to submit three ecological
effects studies on the acute toxicity of this chemical. These include an
avian acute oral toxicity test, preferably using the bobwhite quail,
(850.2100/71-1), a freshwater fish acute toxicity test, preferably using
the rainbow trout, (850.1075/72-1), and an acute freshwater invertebrate
test (850.1010/72-2). These tests are required in order to document
potential acute toxicity to these organisms in the unlikely event that
exposure to 4-t-amylphenol and its salts does occur.

The acute toxicity data for 4-t-amylphenol are summarized on Table 10.
As shown in Table 10, acute toxicity for freshwater fish ranged from
2.50 mg/L to 16 mg/L in the fathead minnow. The first study was
conducted using criteria similar to OPP/OPPTS guidelines and would have
more weight than the second study which did not provide any information
on how the study was conducted. Therefore, the data indicates that
4-t-amylphenol is moderately toxic to coldwater species, such as the
fathead minnow. The fathead minnow is considered to be less sensitive
than the bluegill. Also shown in Table 10, acute toxicity to shrimp was
LC50 = 1.7 mg/L. This indicated that 4-t-amylphenol was moderately toxic
to shrimp. The study does not meet current guideline requirements and
could not be used in a risk assessment.

+--------------+------------+--------+------------------+-------------+
| **Table 10.  |            |        |                  |             |
| Acute        |            |        |                  |             |
| Toxicity of  |            |        |                  |             |
| 4-t-         |            |        |                  |             |
| amylphenol** |            |        |                  |             |
| **and        |            |        |                  |             |
| salts**      |            |        |                  |             |
+==============+============+========+==================+=============+
| **Organism** | *          | **To   | **Comments**     | **          |
|              | *Results - | xicity |                  | Reference** |
|              | LC50       | Cate   |                  |             |
|              | (mg/L)     | gory** |                  |             |
|              | (95%       |        |                  |             |
|              | Confidence |        |                  |             |
|              | Limit)**   |        |                  |             |
+--------------+------------+--------+------------------+-------------+
| **Freshwater |            |        |                  |             |
| Fish**       |            |        |                  |             |
+--------------+------------+--------+------------------+-------------+
| Fathead      | 2.50       | mode   | \- 96h test      | Holcombe, G |
| minnow       | (1.87 -    | rately | duration;        | W et al.    |
| (*Pimephales | 3.34)      | toxic  |                  | 1984        |
| promelas*)   |            |        | \- flow-through  | Environ     |
|              |            |        | bioassay         | Pollut ser  |
|              |            |        |                  | A Ecol Biol |
|              |            |        | -caused necrosis | 35:367-81   |
|              |            |        | in fish          |             |
+--------------+------------+--------+------------------+-------------+
| Fathead      | 16         | Sl     | \- No            | Russon, C L |
| minnow       |            | ightly | information      | et al. 1997 |
| *(Pimephales |            | toxic  | available on the | Environ.    |
| promela*s)   |            |        | test parameters  | Toxicol.    |
|              |            |        |                  | Chem 16:948 |
+--------------+------------+--------+------------------+-------------+

+--------------+------------+--------+------------------+-------------+
| **Mari       |            |        |                  |             |
| ne/Estuarine |            |        |                  |             |
| Inv          |            |        |                  |             |
| ertebrates** |            |        |                  |             |
+--------------+------------+--------+------------------+-------------+
| Shrimp       | 96h LC50 = | Mode   | \- 96h test      | McLeese, D  |
| (*Crangon    | 1.7 mg/L   | rately | duration;        | W 1981      |
| sep          |            | toxic  |                  | Chemosphere |
| temspinosa*) |            |        | \- aerated       | 10(7):723   |
|              |            |        | gently and       |             |
|              |            |        | changed at 49    |             |
|              |            |        | hours            |             |
+--------------+------------+--------+------------------+-------------+

**Endocrine Disruption Effects in Fish.** EPA is required under the
FFDCA, as amended by FQPA, to develop a screening program to determine
whether certain substances (including all pesticide active and other
ingredients) \"may have an effect in humans that is similar to an effect
produced by a naturally-occurring estrogen, or other such endocrine
effects as the Administrator may designate.\" Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system. EPA also
adopted EDSTAC\'s recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effects in humans, FFDCA authority to
require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP). When the appropriate
screening and/or testing protocols being considered under the Agency\'s
EDSP have been developed, 4-t-amylphenol and its salts may be subjected
to additional screening and/or testing to better characterize effects
related to endocrine disruption.

4-t-Amylphenol was estrogenic in a number of different fish models from
the *in vitro* rainbow trout ER competitive binding assay (MED) to *in
vivo* medaka full life cycle tests (Seki et al., 2003) as summarized in
the table below. Many types of estrogenic or endocrine disruptive
responses were observed such as increased expression of vitellogening
(Vtg) mRNA and protein, sex reversal, and reduction of P450 11-β
hydoxylase levels. The estrogenic LOEC varied among models, while it
took a 4-t-amylphenol concentration of -3.7/-3.3 log M to increase Vtg
mRNA expression in trout liver slices *in vitro*, a concentration of
only -6.5 log M increased Vtg protein levels in medaka full life cycle
tests. Efficacy of the 4-t-amylphenol estrogenic response was nearly
equal to the maximum response elicited by exposure to 17-estradiol
(E~2~). The effect of 4-t-amylphenol exposure on cell viability was
measured in a number of these studies and was found to occur at
concentrations above the estrogenic LOEC, although the toxic
concentration of 4-t-amylphenol was never more than an order of
magnitude greater than the estrogenic LOEC. While there are only a small
number of studies of the estrogenic effects 4-t-amylphenol the relative
estrogenic potency of 4-t-amylphenol appeared to be an order of
magnitude higher in fish than in mammals. This chemical is also on a
European list of "Chemicals purported to be endocrine Disrupters" (IEH,
2005; page 85 in the Consumer Products table which references Miller et
al., 2001 and Schultz et al., 2000, and a priority list produced by an
European consulting firm).

Examples of 4-t-amylphenol affecting the reproductive processes of carp
have been reported in the peer-reported literature. Since the use
pattern for this chemical is restricted to indoor uses, exposure to
fish, such as carp, should be limited. Therefore, no additional testing
for endocrine disruption effects on fish is necessary at this time.

+------------+--------------+----------+----------------+-------------+
| **Table    |              |          |                |             |
| 11:        |              |          |                |             |
| Examples   |              |          |                |             |
| of         |              |          |                |             |
| 4-t-       |              |          |                |             |
| amylphenol |              |          |                |             |
| Affecting  |              |          |                |             |
| the        |              |          |                |             |
| Endocrine  |              |          |                |             |
| System in  |              |          |                |             |
| Fish**     |              |          |                |             |
+============+==============+==========+================+=============+
| Organism   | Results      | Toxicity | Comments       | Reference   |
|            |              | Category |                |             |
+------------+--------------+----------+----------------+-------------+
| Male       | caused       | id       | \- test        | Gimeno et   |
| common     | formation of | entified | concentration  | al. 1997    |
| carp       | oviducts in  | as an    | 0.14 mg/L      |             |
| (*Cyprinus | male fish    | eco      |                | Environ Sci |
| carpio*)   | and reduced  | estrogen | \- exposed     | Technol     |
|            | the number   |          | embryos and    | 31(10):     |
|            | of           |          | fingerlings at | 2884-2890.  |
|            | primordial   |          | various ages   |             |
|            | germ cells   |          |                |             |
|            | in gonads    |          |                |             |
+------------+--------------+----------+----------------+-------------+
| Male       | 30-day EC50  | id       | \- 120 male    | Gimeno, S.  |
| common     | for oviduct  | entified | carp tested    | et al.      |
| carp       | formation =  | as       |                | 1998a       |
| (*Cyprinus | 63 ug/L      | causing  | \- nominal     |             |
| carpio*)   |              | e        | concentrations | Aquatic     |
|            | NOEC for     | ndocrine | of 100, 320, & | Toxicology  |
|            | oviduct      | di       | 1000 ug/L were | (Amsterdam) |
|            | formation =  | sruption | tested         | 43:77-92.   |
|            | \<36 ug/L    | effects  |                |             |
|            | primordial   |          | \- 160 day     |             |
|            | germ cells   |          | test duration  |             |
|            | lower in     |          |                |             |
|            | treated fish |          | \-             |             |
|            | NOEC for     |          | intermittent   |             |
|            | vitellogenin |          | flow through   |             |
|            | induction    |          | system         |             |
|            | =90-256 ug/L |          |                |             |
+------------+--------------+----------+----------------+-------------+
| Cultured   | vitellogenin | id       | -six month old | Smeets, J.  |
| h          | induction in | entified | hepatocytes    | M. et al.   |
| epatocytes | carp         | as       | with fully     | 1999.       |
| from       | hepatocytes  | causing  | mature testes  | Toxicol.    |
| geneticall | with LOEC    | e        | containing     | Sci. 50(2): |
| y-uniform, | ranging from | ndocrine | mature sperm   | 206-213.    |
| all male,  | 5-50 uM,     | di       |                |             |
| F1-hybrid  | cytotoxic at | sruption |                |             |
| progenies  | 100uM        | effects  |                |             |
| of common  |              |          |                |             |
| carp       |              |          |                |             |
| (*Cyprinus |              |          |                |             |
| capio*)    |              |          |                |             |
+------------+--------------+----------+----------------+-------------+
| Trout RTH  | Estrogenic   | I        | \- relative    | Hornung et  |
| 149        | LOEC= -6 log | dentifid | potency is     | al. 2003    |
|            | M; IC50=     | as       | 0.036          |             |
| R          |              | causing  | approximately  |             |
| ecombinant | 7.6x10^-7^ M | e        | 75% of maximum |             |
| trout-ER   |              | ndocring | E2             |             |
|            |              | di       |                |             |
|            |              | sruption |                |             |
|            |              | effects  |                |             |
+------------+--------------+----------+----------------+-------------+
| Partial    | Estrogenic   | Id       | \- oviduct     | Gimeno et   |
| life cycle | LOEC= -6.2   | entified | development in | al. 1996    |
| carp       | log M        | as       | male           |             |
| (*Cyprinus |              | causing  |                |             |
| carpio*)   |              | e        |                |             |
|            |              | ndocrine |                |             |
|            |              | di       |                |             |
|            |              | sruption |                |             |
|            |              | effects  |                |             |
+------------+--------------+----------+----------------+-------------+
| Partial    | Estrogenic   | Id       | \- sex         | Yokota et   |
| life cycle | LOEC= 5.8    | entified | reversal;      | al. 2005    |
| Medaka     | log M        | as       | Inhibition of  |             |
| (*Oryzias  |              | causing  | P450 11B       |             |
| latipes*)  |              | e        | hydroxylase    |             |
|            |              | ndocrine | mRNA levels    |             |
|            |              | di       |                |             |
|            |              | sruption |                |             |
|            |              | effects  |                |             |
+------------+--------------+----------+----------------+-------------+
| Full life  | Estrogenic   | Id       | \- Vtg         | Seki et al. |
| cycle      | LOEC= -6.5;  | entified | induction at   | 2003        |
| Medaka     | cytotoxicity | as       | -6.5 log M     |             |
| (*Oryzias  | = -5.2 F~0~  | causing  |                |             |
| latipes*)  | and -5.8     | e        |                |             |
|            | F~1~         | ndocrine |                |             |
|            |              | di       |                |             |
|            |              | sruption |                |             |
|            |              | effects  |                |             |
+------------+--------------+----------+----------------+-------------+
| Rainbow    | Estrogenic   | Id       |                | Tapper et   |
| trout      | LOEC=        | entified |                | al. 2005    |
| cytosol ER |              | as       |                |             |
| c          | \- 5 log M;  | causing  |                |             |
| ompetitive | IC5          | e        |                |             |
| binding    | 0=2.2x10^-4^ | ndocrine |                |             |
|            | M; RBA       | di       |                |             |
|            | 0.004%       | sruption |                |             |
|            |              | effects  |                |             |
+------------+--------------+----------+----------------+-------------+
| Male       | Estrogenic   | Id       | \- relative    | Tapper et   |
| rainbow    | LOEC=        | entified | potency =      | al. 2005    |
| trout      |              | as       | 0.004%         |             |
| liver      | \- 3.7 log   | causing  | approximately  |             |
| slice/Vtg  | M;           | e        | 75% of maximum |             |
| gene       | IC5          | ndocrine | E2             |             |
| expression | 0=1.8x10^-4^ | di       |                |             |
|            | M;           | sruption |                |             |
|            | c            | effects  |                |             |
|            | ytotoxicity= |          |                |             |
|            | -3 log M     |          |                |             |
+------------+--------------+----------+----------------+-------------+
| Male       | elevated     | id       | \- 3 month     | Gimeno et   |
| common     | levels of    | entified | test duration  | al. 1998b   |
| carp       | v            | as       |                | Aquatic     |
| (*Cyprinus | itellogenin, | causing  | \- nominal     | Toxicology  |
| carpio*)   | inhibition   | e        | concentrations | (Amsterdam) |
|            | of           | ndocrine | of 32, 100,    | 43:93-109.  |
|            | sper         | di       | 320 and 1000   |             |
|            | matogenesis, | sruption | ug/L were      |             |
|            | d            | effects  | tested         |             |
|            | isappearance | and      |                |             |
|            | of           |          |                |             |
|            | spermatozoa  | no       |                |             |
|            | and          | m        |                |             |
|            | s            | ortality |                |             |
|            | permatogenic | or       |                |             |
|            | cysts,       | growth   |                |             |
|            | reduced      | effects  |                |             |
|            | diameter of  |          |                |             |
|            | seminiferous |          |                |             |
|            | lobules,     |          |                |             |
|            | reduced      |          |                |             |
|            | spermatocrit |          |                |             |
|            | values and   |          |                |             |
|            | early        |          |                |             |
|            | appearance   |          |                |             |
|            | of           |          |                |             |
|            | ovo-testes   |          |                |             |
|            |              |          |                |             |
|            | LOAEL= 0.032 |          |                |             |
|            | mg/L         |          |                |             |
+------------+--------------+----------+----------------+-------------+

E2= 17-estradiol; ;Vtg = vitellogening; RBA = relative binding affinity

Vitellogenin, an egg yolk pre-cursor protein is produced in female trout
liver and transported to the gonad for the production of eggs. Male
trout retain ER in the liver and the ability to produce vitellogenin,
and can be induced to do so upon exposure to estrogen (Number range
CHAPTER17-estradiol; E~2~), or estrogenic chemicals.

**Environmental Risk Assessment**

The indoor uses of 4-tert-amylphenol and its salts considered in this
RED make it unlikely that any appreciable exposure to terrestrial or
aquatic organisms would occur when 4-t-amylphenol and its salts are used
according to label directions. Even though there is a low potential for
risk due to the lack of expected environmental exposure from the
registered uses of this product, three acute toxicity studies (avian
acute oral toxicity test \[850.2100/71-1\] preferably using the bobwhite
quail; freshwater fish acute toxicity test \[850.1075/72-1\] preferably
using the rainbow trout; and an acute freshwater invertebrate test
\[850.1010/72-2\]), will need to be submitted by the registrant in order
to determine potential toxicity to birds and aquatic organisms in the
unlikely event that exposure does occur.

**Endangered Species Considerations**

The Agency has developed the Endangered Species Protection Program to
identify pesticides whose use may cause adverse impacts on endangered
and threatened species, and to implement mitigation measures that
address these impacts. The Endangered Species Act requires federal
agencies to ensure that their actions are not likely to jeopardize
listed species or adversely modify designated critical habitat. To
analyze the potential of registered pesticide uses to affect any
particular species, EPA puts basic toxicity and exposure data developed
for risk assessments into context for individual listed species and
their locations by evaluating important ecological parameters, pesticide
use information, the geographic relationship between specific pesticide
uses and species locations, and biological requirements and behavioral
aspects of the particular species. A determination that there is a
likelihood of potential impact to a listed species may result in
limitations on use of the pesticide, other measures to mitigate any
potential impact, or consultations with the Fish and Wildlife Service
and/or the National Marine Fisheries Service as necessary.

Based on the low likelihood of environmental exposure from the
registered indoor uses of 4-t-amylphenol and its salts to fish, aquatic
invertebrates, and aquatic plants, adverse impacts to endangered species
are not expected from the registered uses of 4-t-amylphenol and its
salts.

# **11.0 DEFICIENCIES/DATA NEEDS**

[Hazard Data Gaps.]{.underline} TNumber range CHAPTERhere are several
data gaps for 4-t-amylphenol. The existing acute toxicity data
iincomplete and 4 new acute toxicity studies using the technical grade
active ingredient must be conducted. The current hazard database is
inadequate to support the indirect food use of 4-t-amylphenol. The ADTC
(2005) identified the following data gaps for 4-t-amylphenol:

> Acute toxicity testing: 870.1200 (acute dermal), 870.1300 (acute
> inhalation), 870.2400 (primary eye irritation, and 870.2600 (dermal
> sensitization)
>
> 90 oral subchronic study in the rat, modified to examine endocrine
> disrupter effects

Developmental toxicity study in the rabbit

> 2-generation reproduction study in the rat or other available
> information on reproductive toxicity
>
> Repeat dose inhalation toxicity study of at least 28 days duration

Because 4-t-amylphenol appears to cause severe dermal irritation and is
a sensitizer following repeated dermal exposure, a dermal toxicity study
with the diluted end-use formulated product would be helpful to ensure
that clothing and diapers containing 4-t-amylphenol will not be
irritating to skin.

[Dietary Data Gaps.]{.underline} In the absence of chemical-specific
data, the Agency used a 10% migration factor for the dietary assessment.
The Agency requests confirmatory data to support the 10% migration
factor.

Confirmatory data are needed to show whether residues would be absorbed
into treated surfaces, especially **wood** surfaces, of feeding devices
and not be removed by scrubbing with soap and rinsing with water. If the
antimicrobial residues are absorbed into the wood, these residues would
be available for livestock ingestion. This finding [could]{.underline}
entail the need to generate data for large animals including livestock
and poultry metabolism studies, analytical methods for livestock and
poultry tissues and residue data for livestock and poultry.

[Ecological Data Gaps.]{.underline} For indoor uses, an acute oral
toxicity study using the technical grade of the active ingredient (TGAI)
is required to establish the toxicity of 4-tert-amylphenol and its salts
to birds. The preferred test species is either mallard duck (a
waterfowl) or northern bobwhite quail (an upland game bird). Two avian
acute toxicity studies were found in the Agency's files for
4-tert-amylphenol or its salts. The tests were conducted in 1974 using
the bobwhite quail (MRID \# 240116618) and mallard duck (MRID \#
011504216). The tests were conducted using antiquated procedures and do
not meet the current guideline requirements. The results showed moderate
toxicity, which makes it important that a test using current guideline
requirement be conducted by the registrant. **Avian acute oral toxicity
testing (850.2100/71-1), preferably using the bobwhite quail, is
required to support the currently registered uses of 4-tert-amylphenol
and it salts.**

Freshwater fish toxicity studies using the TGAI are required to
establish the toxicity of 4-tert-amylphenol to fish. Data are generally
required for only one species. Testing in two fish species is required
for stable chemicals with high volume effluents (e.g., including, but
not limited to, egg washing, fruit and vegetable rinses, swimming pools
or materials preservatives) and if the LC~50~ in the first species is
greater than (\>) 1 ppm. The preferred test species are rainbow trout (a
coldwater fish) and bluegill sunfish (a warmwater fish), although other
test species identified in the OPPTS Guideline (i.e., OPPTS 850.1075
(e)(4)(i)(A)) may also be used. No freshwater fish acute toxicity
studies were identified from peer-reviewed literature. Two fish studies
were found in the agency's files, but no studies have been submitted to
support registration of 4-tert-amylphenol. The first study (MRID \#
240116619) was conducted in 1974 and tested both rainbow trout and
bluegill sunfish in the same study. The second study(MRID \# 444742-08)
was conducted in 1992 using zebra fish, but only tested one
concentration of TGAI. Neither of these studies meets current guideline
requirements and cannot be used in a risk assessment. **Freshwater fish
acute toxicity testing (850.1075/72-1) on one species preferably the
rainbow trout is required to support the currently registered uses of
4-tert-amylphenol and its salts.**

A freshwater aquatic invertebrate toxicity test using the TGAI is
required to establish the toxicity of a pesticide to aquatic
invertebrates. The preferred test species is *Daphnia magna* or *Daphnia
pulex*. No toxicity studies were identified for these species in
peer-reviewed literature. No studies have been submitted by registrants
to support the registered uses of 4-tert-amylphenol and its salts.
**Freshwater invertebrate acute toxicity testing (850.1010/72-2) is
required for the currently registered uses of 4-tert-amylphenol and its
salts**.

[Residential/Occupational Data Gaps.]{.underline} Confirmatory worker
exposure data are necessary, due to the significant limitations of the
existing exposure data used in this assessment. The Agency is requesting
worker exposure studies that evaluate both dermal (Guideline 875.1200)
and inhalation (Guideline 875.1400) exposure for indoor uses. The Agency
also requires confirmation of descriptions of human activity (875.2800)
associated with the uses assessed in this document. In addition, the
Agency requests confirmatory data to support the assumption that only 5%
of 4-t-amylphenol is transferred from treated-textiles/diapers to skin.

[Environmental Fate Data Gaps]{.underline}: 4-t-Amylphenol and its
potassium and sodium salts are registered as indoor use products and
minimum environmental fate data required by EPA for an indoor use
product is hydrolysis (161-1). However, no hydrolysis data as indicated
in the U.S. Environmental Protection Agency's Environmental Fate Data
Requirements published in Pesticide Assessment Guidelines, Subdivision
N, Number range CHAPTER§161-1 have been submitted to the Agency for
these chemicals.

# **12.0 REFERENCES**

BIBRA, Working Group (1990): Para-tertiary-Amylphenol. Toxicity Profile
BIBRA Toxicology International. 3 pp.

MRID No. 00417108

Edwards, C.N. 1990. Assessment of Clastogenic Action on Bone Marrow
Erythrocytes in the Micronucleus Test. Prepared by Life Science Research
Ltd., Suffolk, UK. Study No. 90/NLL033/0533. Submitted by Nipa
Laboratories, Inc., Wilmington, DE.

Gimeno, S., Gerritsen, A., Bowmer, T., and Komen, H. (1996).
Feminization of male carp. *Nature* 384, 221-222.

Gimeno, S., Komen, H., Venderbosch, P.W., and Bowner, T. (1997)
Disruption of sexual differentiation in genetic male carp (*Cyprinus*
*carpio*) exposed to an alkyphenol during different life stages.
Environ. Sci. Technol. 31(10): 2884-2890.

Gimeno, S., Komen, H., Gerritsen, A.G., and Bowner, T. (1998a):
Feminisation of young males of the common carp, *Cyprinus carpio*,
exposed to 4-tert-pentyphenol during sexual differentiation. Aquatic
Toxicology (Amsterdam) 43: 77-92.

Gimeno, S., Komen, H., Jobling, S., Sumpter, J., and Bowner, T. (1998b):
Demasculinisation of sexually mature male common carp, *Cyprinus
carpio*, exposed to 4-tert-amylphenol during spermatogenesis. Aquatic
Toxicology (Amsterdam) 43: 93-109.

Holcombe, G.W., Phipps, G.L., Knuth, M.L., and Felhabert, T. (1984) The
acute toxicity of selected substituted phenols, benzenes and benzoic
acid ester to fathead minnows *Pimephales promelas*. Environ. Pollut.
Ser. A Ecol. Biol. 35(4): 367-381.

Hornung, M., Ankley GT, and Schmieder, P. (2003). Induction of an
estrogen-responsive reporter gene in rainbow trout hepatoma cells
(RTH-149) at 11 or 18C. Environ Toxicol Chem. 22, 866-871.

MRID No. 41572701

Lloyd, J.M. 1990. Investigation of Mutagenic Activity in the TK+/- Mouse
Lymphoma Cell Mutation System. Prepared by Life Science Research Ltd.,
Suffolk, UK. Study No. 90/NLL034/0395. Submitted by Nipa Laboratories,
Inc., Wilmington, DE.

Number range CHAPTERMRID No. 41438401

May, K. 1990. Nipacide PTAP (para-tertiary amylphenol): Assessment of
Mutagenic Potential in Histidine Auxotrophs of *Salmonella typhimurium*.
Prepared by Life Science Research Ltd., Suffolk, UK. Study No. 90/0109.
Submitted by Nipa Laboratories, Inc., Wilmington, DE.

MRID 42470301

Siglin 1992. Ninety-One Day Dermal Toxicity Study in Rats with Nipacide
PTAP. Springborn Laboratories.

Number range CHAPTERTapper, M., Sheedy, B., Denny, J., and Schmieder, P.
(2005) Rainbow trout estrogen (ER) binding and ER-mediated vitellogenin
production in a trout liver slice assay. \[Measurements made at the
EPA/ORD/NHEERL/Midcontinent Ecology Division (MED)- Duluth, MN\]

MRID No. 46616601. Tuffnell, P.P. Phenol, 4-(1,1-dimethylpropyl)- Acute
Oral Toxicity in the Rat. Safepharm Laboratories Ltd., Derby U.K.,
Laboratory Test No. 47/2097. July 23, 1992. Unpublished.

MRID No. 46616602. Tuffnell, P.P. Phenol, 4-(1,1-dimethylpropyl)- Acute
Dermal Irritation Test in the Rabbit. Safepharm Laboratories Ltd., Derby
U.K., Laboratory Test No. 47/2098. July 25, 1992. Unpublished.

IEH (2005) *Chemicals Purported to be Endocrine Disrupters: A
Compilation of Published Lists* (Web Report W20), Leicester, UK, MRC
Institute for Environment and Health, available at
http://www.le.ac.uk/ieh/

McLeese, D.W. (1981) Lethality and accumulation of alkyphenols in
aquatic fauna. Chemosphere 10(7): 723.

Routledge, E. J. and Sumpter, J. P. (1997) Structural features of
alkylphenolic chemicals associated with estrogenic activity. J. Biol.
Chem. 272(6): 3280-3288.

Russon, C.L., Bradbury, S.P., Broderius, S.J., Hammermeister, R.A., and
Drummond, R.A. (1997) \[no title given\] environ. Toxicol. Chem. 16:948.

Seki, M., Yokota, H., Matsubara, H., Maeda, M., Tadokoro, H., Kobayashi,
K. (2003). Fish full life cycle testing for the weak estrogen
4-t-pentylphenol on medaka (Oryzias latipes). *Environ Toxicol Chem* 22,
1487-1496.

Number range CHAPTERMRID No. 41920002

Siglin, J.C. 1991. Nipacide PTAP, Teratology Study in Rats. Prepared by
Springborn Laboratories, Inc., Spencerville, OH. Study No. 3227.3.
Submitted by Nipa Laboratories, Inc., Wilmington, DE.

Smeets, J.M., Van, H.I., Giesy, J.P., Seinen, W., and van den, B.M.
(1999): Estrogenic potencies of several environmental pollutants, as
determined by vitellogenin induction in a carp hepatocyte assay.
Toxicol. Sci. 50(2): 206-213.

Soto, et al. (1995) The E-SCREEN assay as a tool to identify estrogens:
An update on estrogenic environmental pollutants. Environ. Health
Perspect. 103 (Suppl. 7): 113-122.

Stevenson,C.J. (1984): Environmentally induced vitiligo (leukoderma)
from depigmenting agents and chemicals. J. Toxicol. Cutaneous Ocul.
Toxicol. 3(3): 299-308.

Number range CHAPTERUSEPA. 1999. Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study. Memorandum from
Siroos Mostaghimi, Ph.D., USEPA, to Julie Fairfax, USEPA. Dated November
4, 1999. DP Barcode D247642.

U.S Environmental Protection Agency (EPA) 2001. Residential SOPs Policy
Update 12, Number range CHAPTEREPA Office of Pesticide Programs--Human
Health Division. Dated April 5, 2000.

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide:
ECOTOXicology Database System. Version 3.0. Available:
http://www.epa.gov/ecotox/

Wysowski, D.K. et al. (1978) Epidemic neonatal hyperbilirubinemia and
use of a phenolic disinfectant detergent. Pediatrics 61: 165-170.

Yamasaki, K., et al. (2003) Immature rat uterotrophic assay of 18
chemicals and Hershberger assay of 30 chemicals. Toxicology 183: 93-115.

Yokota, H., Abe.T., Nakai, M., Murakami, H., Eto, C., Yakabe, Y. (2005)
Effects of 4-tert-pentylphenol on the gene expression of P450
11β-hydroxylase in the gonad of medaka. *Aquatic Toxicology* 71,
121-132.

Zeiger,E., Anderson,B., Haworth,S., Lawlor,T., and Mortelmans,K. (198):
Salmonella mutagenicity tests. 4. results from the testing of 300
chemicals. Environ. Mol. Mutagen 11: 1-158.

[^1]: 1 ^1^ PAD = Population Adjusted Dose = [Acute or Chronic
    RfD]{.underline}

    FQPA Safety Factor