'nental Pro'
November 1984
&EPA
Pentachiorophenol
(Non-Wood Uses)
Special Review Position
Document 21 3
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PENTACHLOROPHENOL
NON-WOOD USES
POSITION DOCUMENT 2/3
U.S. Environmental Protection Agency
Office of Pesticides and Toxic Substances
Office of Pesticide Programs
401 M Street, SW
Washington, D.C.
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ACKNOWLEDGEMENTS
Lois Rossi, Review Manager, Registration Division
Michael Branagan, Review Manager, Registration Division
Thaddeus Czerkowicz, Microbiologist, Benefits and Use Division
Harry Day, Chemist, Hazard Evaluation Division
Don Eckerman, Economist, Benefits and Use Division
Karen Farmer, Secretary, Registration Division
Annie Hargrove, Secretary, Registration Division
Cara Jablon, Attorney Advisor, Office of General Counsel
Esther Saito, Science Integration Staff, Hazard Evaluation Division
Mary Wildermuth, Summer Intern, Registration Division
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TABLE OF CONTENTS
Page
Executive Summary i
Acknowledgements v
I. Introduction 1-1
A. General Background and Organization 1-1
B. Legal Background 1-2
C. Chemical Background 1-3
1. Chemical and Physical Characteristics 1-3
2. Use and Production 1-6
3. Tolerances 1-7
II. Risk Analysis and Assessments II-l
A. Analysis of Rebuttal Comments and Public II-l
Comments Concerning Fetotoxic and
Teratogenic Effects
1. Basis of Presumption II-l
2. Analysis of Specific Rebuttal and Public 11-10
Comments Concerning Fetotoxicity
3. Summary of Rebuttal Comments Concerning 11-19
Fetotoxicity Effects
B. Basis of Presumption and Analysis of Public 11-19
Comments Concerning Oncogenicity
1. Basis of Presumption 11-19
2. Analysis of Public Comments Concerning 11-23
Oncogenicity
3. Summary of Comments Concerning Oncogenicity
11-28
Ct Analysis of Rebuttal Comments Concerning Human
Exposure 11-28
D. Human Exposure Analysis 11-31
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E. Risk Assessment for Fetotoxicity and Oncogenicity
1. Risk Assessment for Fetotoxicity 11-43
2. Risk Assessment for Oncogenicity 11-46
F. Alternatives 11-50
III. Benefits Analysis III-l
A. Introduction III-l
B. Herbicidal Uses III-l
1. Greenhouses
2. Ornamental Lawns
3. Rights-of-Way
4. Commercial and Industrial Non-crop Areas
5. Domestic Dwellings, Medical Facilities/
Schools, Golf Courses, and Sand Traps
6. Wasteland Areas
7. Aquatic Areas and Drainage Ditch Banks
8. Alternatives and Economic Impacts
C. Antimicrobial Uses III-3
1. Working Solutions
2. Finished Product Preservatives
3. Working Solutions and Finished Product
Preservatives
4. Marine Anti-fouling Agents
5. Disinfection - Mushroom Houses
6. Construction Materials
D. Mossicide Use 111-10
E. Defoliant III-ll
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IV. Development of Regulatory Options IV-1
A. Introduction IV-1
B. Basis and Rationale for Developing Options IV-1
and Modifications
C. Discussion of Option 2, Modifications to the IV-2
Terms and Conditions of Registration
V. Proposed Regulatory Decisions - Risk/Benefit Use-by-
Use Analysis of Regulatory Options
V-l
A. Herbicidal V-l
B. Antimicrobial V-2
1. Working Solutions
2. Finished Product Preservatives
3. Working Solutions and Finish Product
Preservative
C. Marine Anti-fouling Agents V-7
D. Disinfection - Mushroom Houses V-8
E. Construction Materials V-8
F. Mossicide V-9
G. Defoliant V-10
VI. Bibliography VI-1
Appendix
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EXECUTIVE SUMMARY
Pentachlorophenol
Non-Wood Uses
Position Document 2/3
On October 18, 1978, EPA issued Notices of Rebuttable Presumption
Against Registration and Reregistration (RPAR) of pesticide
products containing pentachlorophenol (43 PR 48443). The
presumption against pentachlorophenol was based on validated
studies indicating its fetotoxicity.
In January, 1981, a Position Document 2/3 was issued that
addressed the risks and benefits and proposed regulatory action
of the wood preservative uses of pentachlorophenol, as well as
the inorganic arsenical compounds, creosote, coal tar, and
coal tar neutral oils (46 FR 13020).
Studies indicating the oncogenicity of the pentachlorophenol
contaminants, chlorinated dibenzo-p-dioxins (HxCDD) and
hexachlorobenzene (HCB), were also detailed thereby adding
the presumption of oncogenicity for pentachlorophenol.
In July, 1984 a Position Document 4 (PD-4) was issued on the
wood preservative uses of pentachlorophenol, the inorganic
arsenical compounds, creosote, coal tar, and coal tar neutral
oils. It set forth the Agency's final position on the regulation
and use of these chemicals as wood preservatives.
This document addresses the risks and benefits of the non-wood
uses of pentachlorophenol and its sodium and potassium salts.
The non-wood uses of pentachlorophenol can be divided into
these general categories: herbicides, antimicrobial
agents, disinfectants, mossicides, and defoliants.
Pentachlorophenol is registered for use on the following sites
as a non-specific, non-residual contact herbicide: greenhouses,
ornamental lawns, rights-of-way, commercial and industrial
non-crop areas, domestic dwellings, medical facilities, schools,
golf courses, wasteland areas, aquatic areas, and drainage
ditch banks.
Uses of pentachlorophenol as an antimicrobial agent to control
bacterial and fungal growth include: working solutions
(oil well flood waters, evaporative condenser cooling waters,
cooling tower waters, air washers); finished product preservatives
-------
(adhesives and sealants, latex paints, rubber articles,
defoaming agents, paper coatings, polyvinyl chloride emulsions
in food related products, zinc-silicone dioxide matrix coatings
in reusable bulk food storage containers, and water-based
gasketing compounds for food applications, photographic
developing solutions, cements in food can ends and seams,
feathers); working fluids and process chemicals in the textile
industry; pulp and paper mill solutions and products; leather
tannery solutions and products; and marine anti-foul ing agents
Pentachlorophenol is also used as a disinfectant in mushroom
houses and a mildewicide in a variety of construction materials,
As a mossicide, pentachlorophenol is used to control moss on
lawns and roofs.
Pentachlorophenol is also registered for use to treat soil to
control subterranean termites. This use is not considered in
this document. The subterranean termite control use of penta-
chlorophenol is under review by the Agency along with other
chemicals registered for this use.
In reaching a proposed regulatory decision regarding
the non-wood uses of pentachlorophenol, the Agency evaluated
rebuttal comments submitted in response to the PD-1 and public
comments submitted in response to the PD-2/3 published on the
wood uses of these chemicals.
The exposure data indicate that applicators of products
containing pentachlorophenol used for non-wood uses are subject
to primarily dermal exposure to hands. Some uses would result
in inhalation exposure as well.
Three of the currently registered uses have been identified
as food uses and require the establishment of tolerances under
Section 408 of the Federal Food, Drug and Cosmetic Act. These
uses are for mushroom houses, canning/sealing gaskets, and
on seed crops. There exists a potential for dietary
exposure as a result of these uses. Additionally, the use of
pentachlorophenol in the leather tanning industry could
result in dietary exposure. Fleshings from penta-treated hides
are sold to renderers who then in turn sell the fleshings for
incorporation into animal/poultry feed. The use of this feed
has resulted in penta residues being found in eggs and poultry.
The Agency has determined that the use of products containing
pentachlorophenol and its sodium and potassium salts for
non-wood uses poses a risk of fetotoxicity and, due to the
presence of the contaminants HxCDD and HCB, the risk of
oncogenicity to applicators. There are also potential risks
to the general population as a result of the uses that could
result in penta-residues in foods as described above.
An analysis of the benefits associated with each registered
ii
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use concludes that for the majority of uses viable, effective
alternatives are available and in use. Actual usage data are
not available for several uses.
The following regulatory options were considered by the
Agency in reaching the proposed regulatory decisions.
(1). Continuation of registration without changes.
(2). Continuation of registration with modification
to terms and conditions of registration.
(3). Cancellation of registration.
Specific risk reduction modifications selected for further
consideration under Option 2 are:
(1). Require protective clothing: impermeable gloves,
coveralls, respirators; require proper disposal of
protective clothing.
(2). Prohibit eating, drinking, and smoking during
application
(3). Restricted use classification
(4). Reduce contaminants in pentachlorophenol
Having evaluated the fetotoxic and oncogenic risks associated
with the non-wood uses of pentachlorophenol, the Agency has
determined that the benefits outweigh the risks for the use of
pentachlorophenol in oil well flood water and pulp and paper
mill solutions. The Agency proposes to continue the registration
for the use of pentachlorophenol as an anti-fungal agent in oil
well flood waters and in pulp and paper mill solutions but amend
the terms and conditions of registration to require that impermeable
gloves be worn during the handling of pentachlorophenol and
that the HxCDD content be required to be reduced to 1 ppm.
Having evaluated the fetotoxic and oncogenic risks associated
with the non-wood uses of pentachlorophenol, the Agency has
determined that the continued, unrestricted registrations of
the uses listed below is unjustifiable and that the risks out-
weigh the benefits for both Options 1 and 2. Therefore, the
Agency proposes to cancel the use of the products for all
uses listed below:
Herbicidal uses
- Greenhouses
- Ornamental lawns and edging
- Rights-of-way
- Commercial and industrial non-crop areas
iii
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- Domestic dwellings
- Public facilities
- Golf courses and sand traps
- Wasteland areas
- Aquatic areas
Antimicrobial Uses
- Working solutions including evaporative condensers, air
washers, cooling towers
- Finished product preservatives including adhesives/sealants,
canning and sealing cements, gaskets, photographic
developing solutions, and other uses including latex
paint/rubber, defoaming agents, paper coatings, polyvinyl
chloride emulsions, zinc-silicone dioxide coatings,
and feathers
- Working solutions and finished products preservatives
including textile/cordage, leather tannery, marine caulking/
marine paint
Disinfectant uses
- Mushroom houses
- Construction materials
Mossicide uses
- Roofs and lawns
Defoliant uses
- Seed crops
IV
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I. Introduction
A. General Background and Organization
The Federal Insecticide, Fungicide, and Rodenticide Act, as
amended, (FIFRA) and its regulations require the Environmental
Protection Agency (EPA) to review the risks and benefits of
uses of pesticides. On October 18, 1978, EPA issued Notices
of Rebuttable Presumption Against Registration and Reregistration
(RPAR) of pesticide products containing creosote, coal tar
and coal tar neutral oils, inorganic arsenical compounds,
and pentachlorophenol (43 FR 48443). The presumption against
pentachlorophenol was based on validated studies indicating
its fetotoxicity. Position Document 1 (PD 1) issued with
that Notice described these studies in detail.
In January, 1981, a Position Document 2/3 (PD 2/3)
addressed the risks and benefits of the wood preservative
uses of creosote, coal tar and coal tar neutral oils, the
inorganic arsenical compounds and pentachlorophenol (46 FR
13020). Studies indicating the oncogenicity of the penta-
chlorophenol contaminants, chlorinated dibenzo-p-dioxins
(HxCDD) and hexachlorobenzene (HCB) were also detailed
thereby adding the presumption of oncogenicity for penta-
chlorophenol.
In July, 1984 a Position Document 4 (PD 4) was issued on the
wood preservative uses of creosote, coal tar and coal tar
neutral oils, the inorganic arsenical compounds and penta-
chlorophenol (46 FR 13020). It set forth the Agency's final
position on the regulation and use of these chemicals as
wood preservatives.
The Agency's final decision on the wood preservative uses of
pentachlorophenol presented in the PD 4 required for all
wood preservative uses: an intermediate upper limit of 15
ppm HxCDD and TCDD below the limits of detection and, in 18
months, a 1 ppm HxCDD upper limit; a teratogenicity/feto-
toxicity label warning; disposal of protective clothing and
unused formulations; statements regarding personal hygiene
during and after application.
Modifications to the terms and conditions of registration
for pressure treatment, groundline, treatment of poles, home
and farm, sapstain control- millwork, plywood, and particle
board included: restricted use classification (all uses);
protective clothing, gloves, respirators (all uses); FIFRA
Mandatory Consumer Awareness Program (pressure treatment);
prohibitions on applying wood intended for use in interiors
or for use in contact with food, feed, or drinking water
(pressure treatment, home and farm); closed mixing and emptying
system (pressure treatment, sapstain control, millwork,
plywood, particle board); prohibit application indoors (home
and farm).
1-1
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This Position Document 2/3 addresses the risks and benefits
of the non-wood preservative uses of pentachlorophenol. The
non-wood preservative uses of creosote, coal tar and coal tar
neutral oils were discussed in Position Document 2/3
issued in August, 1984. The non-wood preservative uses of
the inorganic arsenical compounds will be considered in a
future Position Document 2/3.
This document contains five parts. Part I is this intro-
ductory section. Part II evaluates the potential risks asso-
ciated with the non-wood preservative uses of pentachloro-
phenol. Part II also includes descriptions and evaluations
of the risk evidence, exposure data, rebuttal submissions,
and the Agency's risk assessment. Part III estimates and
summarizes the economic benefits of the non-wood uses of
pentachlorophenol for each use category and describes the
assumptions and limits of these estimates. Part IV describes
the range of possible regulatory options and modifications to
reduce the risks so that they are exceeded by the benefits
of pentachlorophenol products and explains the Agency's se-
lection of some of these options for further consideration.
Part V presents the Agency's proposed regulatory decision
for each of the non-wood uses of pentachlorophenol.
B. Legal Background
To obtain a registration for a pesticide under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended,
an applicant for registration must show that the pesticide
satisfies the statutory standard for registration. That stan-
dard requires, among other things, that the pesticide perform
its intended function without causing "unreasonable adverse
effects on the environment" FIFRA §3(c)(5).
The term "unreasonable adverse effects on the environment"
is defined as "any unreasonable risk to man or the environment,
taking into account the economic, social and environmental
costs and benefits of the use of any pesticide" FIFRA §2(bb).
To register a pesticide, the Administrator must find that the
benefits of each use of the pesticide exceed the risks of use,
when the pesticide is used in accordance with commonly recog-
nized practice and in compliance with the terms and conditions
of registration.
The burden of proving that a pesticide satisfies the re-
gistration standard is on the proponents of registration and
continues as long as the registration remains in effect.
Under section 6 of FIFRA, the Administrator may cancel the
registration of a pesticide or modify the terms and conditions
of registration whenever it is determined that the pesticide
causes unreasonable adverse effects on the environment. The
1-2
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Agency created the RPAR process to facilitate the identification
of pesticide uses which may not satisfy the statutory standard
for registration and to provide an informal procedure to
gather and evaluate information about the risks and benefits
of these uses.
The regulations governing the RPAR process are set forth in
40 CFR 162.11. (The RPAR process has been recently named
the Special Review Process). Among other things, this section
provides that a rebuttable presumption against registration
shall arise if a pesticide meets or exceeds any of the risk
criteria set out in the regulations. The Agency announces
the commencement of the RPAR process by publishing a notice
in the Federal Register. After an RPAR is issued, registrants
and other interested persons are invited to review the data
and information to rebut the presumption by showing that the
Agency's initial determination of risk was in error, or by
showing that use of the pesticide is not likely to result in
any significant exposure to humans or the environment with
regard to the adverse effects in question. In addition to
submitting evidence to rebut the risk presumption, respon-
dents may submit evidence as to whether the economic, social
and environmental benefits of the use of the pesticide outweigh
the risks of use.
In determining whether the use of a pesticide poses risks
which are greater than the benefits, the Agency considers
possible changes to the terms and conditions of registration
which can reduce risks, and the impacts of such modifications
on the benefits of use. If the Agency determines that such
changes sufficiently reduce risks to the level where the
benefits outweigh the risks, it may conclude the RPAR process.
The Agency announces this type of conclusion to an RPAR review
by publication of a Notice of Determination in the Federal
Register. That Notice states and explains the rationale
for the Agency's regulatory position, provides that the
registrant may avoid cancellation by implementing the modifications
to the terms and conditions of registration set forth in the
Notice, and sets forth the hearing rights of the affected
parties.
C. Chemical Background
1. Chemical and Physical Characteristics
Pentachlorophenol is commonly called "penta". It is a buff
colored crystal which is produced in the United States by
chlorination of molten phenol in the presence of a catalyst.
The major commercial forms of penta are the unmodified phenol
and the sodium salt. The potassium salt is used to a lesser
extent. Figure 1 shows the structural formulae of these
forms of penta, while Table 1-1 contains the chemical and
physical properties of these compounds.
1-3
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FIGURE 1
Structure of Pentachlorophenol in
Cl
C1C !
x(
Cl
Cl
: — c'
O/COH
: — q
Cl
Cl
C1C '
Cl
its Various Forms
P
C— — C
f Jc-ONa
c~~\i
Pentachlorophenol Sodium Pentachlorophenate
C1C C-OK
\^/
£ - Cv
Cl Cl
Potassium Pentachlorophenate
TABLE 1-1
Physical Properties of Pentachlorophenol and
Sodium Pentachlorophenate
Type
Formula
Molecular
Weight
Specific
Pentachlorophenol
CgClsOH
266.4
1.9
Sodium Pentachlorophenol
CgClsONal^O
306.3
2.0
Gravity
Density 1.987
Vapor 0.00015 (25°C)
Pressure
Solubility
(g/100 g, e 25°C)
o Water
o Acetone
o Benzene
o Diacetone
Alcohol
o Ethanol
(95%)
o Methanol
o Isopropanol
o Ethylene
Glycol
<0.01
50
15
190
120
180
85
11
33
35
—
45
65
25
30
40
1-4
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Industrial production of penta is a two-stage process. In
the first stage, phenol is chlorinated at 105°C to yield
isomers of tri- and tetrachlorophenols. In the second stage,
the temperature is gradually increased to 130°C to keep the
reaction mixture molten, and the tri- and tetrachlorophenols
are further chlorinated to form pentachlorophenol. However,
not all of these precursor compounds react in the process;
some of the tetrachlorophenols survive and remain with the
penta through later processing. Technical grade penta,
therefore, contains from 4 to 12% tetrachlorophenols; in
fact, one of the three possible tetrachlorophenol isomers,
2,3,4,6-tetrachlorophenol, is listed as an active ingredient
in some penta products.
Dioxin and furan contaminants also form in the commercial
production of penta. The higher temperatures of the second
stage of penta production are favorable to the condensation of
the tri-and tetrachlorophenols to form hexa-, hepta-, and
octachlorodibenzo-p-dioxins (dioxins) and various chlorinated
dibenzofurans (furans). Figure 2 shows the structural formulae
of the basic molecules of these contaminants. Substitution
of chlorine atoms at one or more of the numbered positions
produces a member of the chlorinated dibenzo-p-dioxin (dioxin)
or chlorinated dibenzofuran (furan) chemical families.
FIGURE 2
9
Structure of
1
r\ f*
^xCV ^-^ X^v^
BC">->>C^ ^CX>-OC2
i U i i O i
7C /c\ /c J-3
6 4
Dibenzo-p-dioxin
Dioxin and Furan
9
1
f+
SC^C^C^ ^C^^C2
i O i i O i
7c>^> — c
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FIGURE 3
Structure of Hexachlorobenzene
O\
CC1
. /
2. Use and Production
Pentachlorophenol has a long history of use as a wood
preservative, disinfectant, herbicide, and antifungal agent.
As of 1977 , about 50 million pounds of penta were produced
annually in the United States and production was expected to
increase to 80 million pounds annually in the near future
(Josephson, 1977) . Approximately 80% of the pentachlorophenol
produced is used for wood preservative uses.
The registered non-wood uses of pentachlorophenol include
use as a herbicide, antimicrobial agent, disinfectant,
mossicide, and defoliant. Pentachlorophenol is also registered
for use to treat soil to control subterranean termites. This
use is not considered in this document. The subterranean termite
control use of pentachlorophenol is under review by the Agency
along with other chemicals registered for this use.
Pentachlorophenol is registered for use on the following
sites as a non-specific/ non-residual contact herbicide:
greenhouses, ornamental lawns, rights-of-way, commercial and
industrial non-crop areas, domestic dwellings, medical
facilities, schools, golf courses, sand traps, wasteland
areas, aquatic areas and drainage ditch banks.
Uses of pentachlorophenol as an antimicrobial agent to
control bacterial and fungal growth include: working solutions
(oil well flood waters, evaporative condenser cooling waters,
cooling tower waters, air washers); finished product preser-
vative (adhesives and sealants, latex paints, rubber articles,
defearning agents, paper coatings, polyvinyl chloride emulsions
in food related products, zinc-silicone dioxide matrix coatings
in reusable bulk food storage containers, and water-based
gasketing compounds for food applications, photographic
developing solutions, cements in food can ends and seams,
feathers); working fluids and process chemicals in the textile
industry; pulp and paper mill solutions and products; leather
tannery solutions and products; marine anti-fouling agents;
disinfectant in mushroom houses; mildewicides in a variety
of construction materials.
1-6
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As a mossicide, pentachlorophenol is used to control moss on
lawns and roofs.
Pentachlorophenol is registered as a defoliant aid in seed
crop harvesting of alfalfa, clover, birds foot trefoil, and
lespedeza.
3. Tolerances
The Agency has established no tolerances or exemptions
from the requirement of a tolerance and the FDA has not
established action levels for pentachlorophenol in or on raw
agricultural commodities.
The FDA has several regulations permitting the use of penta
and/or its salts in wood and non-wood packaging materials as
an indirect food additive.* Pentachlorophenol and its sodium
and potassium salts are cited in 21 CFR, Part 165.105 as
approved for use as an adhesive component. The salts are
limited to use as a preservative. In 21 CFR, Part 178.3120,
the potassium and sodium penta salts are designated for use
as optional adjuvant substances used in the production of
animal glue. Animal glue is used as a component of articles
intended for use in producing, manufacturing, packing,
processing, preparing/ treating, packaging, transporting, or
holding food. Sodium pentachlorophenate may also be used as
a component of paper and paperboard in contact with aqueous
and-fatty foods, with the restriction of its being used only
as a preservative for coating formulations (21 CFR, Part 176.170)
*According to CFR 21, Part 170, Section 170.3, "food additive"
includes all substances in which the intended use of which
results, or may reasonably be expected to result, directly
or indirectly, either in their becoming a component of food,
or otherwise affecting the characteristics of food. Material
used in the production of containers and packages is subject
to the definition if it may reasonably be expected to become
a component, or to directly or indirectly affect the charac-
teristics of food packed in the container. The general
provisions applicable to "indirect food additives" (Part
174, Section 174.5) are regulations prescribing conditions
under which food additive substances may be safely used and
predicate usage under conditions of good manufacturing practice.
The quantity of any food additive substance that may be
added to food as a result of use in articles that contact
food shall not exceed, where no limits are specified, that
which results from use of the substance in an amount not
more than reasonably required to accomplish the intended
physical or technical effect in the food-contact article; shall
not exceed any prescribed limitations; and shall not be intended
to accomplish any physical or technical effect in the food itself
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II. RISK ANALYSIS AND ASSESSMENTS
This portion of the Position Document is divided into five
sections. The first two sections discuss the basis for the
Agency's presumption, the rebuttal comments received in
response to PD 1 and the public comments received in response
to the Wood Preservatives Position Document 2/3, as they
apply to the non-wood uses of these chemicals.
The third and fourth sections address human exposure for the
various non-wood preservative uses of pentachlorophenol. The
final section presents the risk assessment.
In assessing the risks, two factors are considered: the
toxic effect (or effects) of the pesticide and whether the
amount of exposure is sufficient to cause the toxic effect(s).
The toxic effects of concern for pentachlorophenol were
described in the PD 1 as the basis for the rebuttable presumption.
A. Analysis of Rebuttal Comments and Public Comments Concerning
Fetotoxic and Teratogenic Effects
1. Basis of Presumption
In the studies summarized in the PD 1 on pentachlorophenol
and the PD 2/3 and PD 4 on the wood uses of pentachlorophenol,
fetotoxic effects were reported in rats exposed to purified
and commercial grade penta. Teratogenic effects were reported
in rats exposed to a mixture of two unspecified isomers of
hexachlorodibenzo-p-dioxin (HxCDD). Specifically, exposure
to penta contaminated with these HxCDD isomers resulted in
statistically significant increases in the incidence of
skeletal and soft tissue anomalies, growth retarded fetuses,
and embryonic resorptions in the litters of
treated dams. Teratogenic effects were also reported in mice
exposed to hexachlorobenzene (HCB). Exposure to this penta
contaminant produced significantly elevated maternal liver-to-
body weight ratios, decreased fetal body weights and caused a
significant increase in the number of abnormal fetuses per litter.
The results of these studies are summarized below.
Studies with Pentachlorophenol
Schwetz et a1. (1974) studied the effects of purified and
commercial grade penta on rat embryonal and fetal develop-
ment. Doses of 5, 15, 30, and 50 mg/kg/day of purified penta
and 5.8, 15, 34.7, and 50 mg/kg/day of commercial penta were
administered by gavage on gestation days 6 through 15 inclusive.
(Note that 5.8 and 34.7 mg/kg/day of commercial penta are
equivalent to 5 and 30 mg/kg/day of purified penta). Both
purified and commercial penta caused statistically significant
increases in fetal resorptions at the two higher doses (Table II-l)
II-l
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It is interesting that at 30 and 50 mg/kg/day, purified
penta had a more pronounced effect than the two highest doses
of commercial penta. For example, at 50 mg/kg/day purified
penta caused 100% incidence of fetal resorptions, while
commercial penta caused 58% resorptions. At 30 (purified)
and 50 (commercial) mg/kg/day, there were statistically
significant differences in the sex ratio of surviving fetuses:
in both cases, males were heavily predominant. These investi-
gators also found that administration of penta during early
organogenesis (days 8 through 11 of gestation) had a more
pronounced effect on fetal resorption than did its administration
during late organogenesis (days 12 through 15).
In this study, the no-observable-effect level (NOEL) for
fetal resorption was 5.8 mg/kg/day for commercial grade
penta and 15 mg/kg/day for purified penta. Measurements were
also taken on fetal body weight and crown-rump length, both
of which decreased with increasing dose. The NOEL for these
parameters was 15 mg/kg/day for both commercial grade and
purified penta.
TABLE II-l
Effect of Pentachlorophenol
on the Incidence of Fetal Resorptions3
Test Material &
Dose (mg/kg/dy)
Resorptions
Among Fetuses
% No.
Among Litters
% No.
Vehicle Controlb
Pentachlorophenol0
4.2 15/358
30.3 10/33
a.
b.
c.
d.
Commercial
5.8 7.1 15/212
15 8.8 17/194d
34.7 27.2 64/235d
50 58.1 108/186d
Purified
5 4.2 8/189
15 5.9 13/221
30 97.5 233/239d
50 100.0 229/229d
55.6
64.7
94.7
93.3
46.7
38.9
100.0
100.0
10/18
11/1 7d
18/19d
14/15d
7/15
7/18
20/20d
19/19d
From Schwetz et al. (1974).
2.0 ml/kg body weight corn oil per day.
Dosages were administered in corn oil (2.0 ml/kg).
Significantly different from control values by the binomial
expansion test, p<0.05.
II-2
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Schwetz et al. (1974) also investigated the fetal anomalies
in rats caused by penta. They studied the effects produced
by gavage of 5.8, 15, 34.7, and 50 mg/kg/day of commercial
grade penta, and 5, 15, and 30 mg/kg/day of purified penta.
In one experiment, they administered these amounts of penta
during days 6 through 15 of gestation; significant increases
in skeletal defects of the ribs, sternebrae, and vertebrae
were observed in the two highest dose groups of both purified
and commercial penta. The lowest dose of purified penta (5
mg/kg/day) caused an increase in delayed skull ossification.
In a second experiment, they gave 30.0 (purified) and 34.7
(commercial) mg/kg/day penta on days 8 through 11 of gestation
to one group of animals, and on days 12 through 15 to a
second group; significant increases in abnormal sternebrae
and skulls were observed in animals treated with purified
penta, and abnormal sternebrae were observed in animals
treated with commercial penta.
Larsen et al. (1975) fed 60 mg/kg !4C-penta to pregnant
Charles River rats (CD strain) on day 15 of gestation. They
detected negligible amounts (<0.3% of administered dose)
of 14C-pent.a in the placentae and fetuses up to 32 hours
after dosing. This indicated that the amount of penta that
passes through the placental barrier on day 15 is negligible.
In a separate experiment reported in the same paper, a single
oral dose of 60 mg/kg of unlabeled penta administered to
separate groups of animals on days 8, 9, 10, 11, 12, or 13 of
gestation had no significant effect on the rate of fetal
resorptions in the test animals as compared with controls.
However, significant reductions in fetal weight, another
fetotoxic effect, were reported on days 9 and 10.
Hinkle (1973) reported the absence of observed fetotoxic
effects of penta in the Golden Syrian hamster. Administration
of 1.25, 2.5, 5, 10, and 20 mg/kg of penta by gavage on days
6 through 10 of gestation caused no differences between
control and test animals in these parameters: maternal body
weight, fetal weight, litter size, and number of resorptions.
There was some (unspecified) increase in maternal toxicity
at the two highest doses. The author stated that penta was
found in detectable amounts (unspecified) in the untreated
animals as well as in their diet.
Fahrig (1978) observed decreases in litter size after
intraperitoneal injection of pregnant mice at day 10 of
gestation with 50 to 100 mg/kg penta. Control mice, on the
average, produced more than 6 fetuses/dam, whereas litter
sizes in the treated groups were about 4 fetuses/dam. Penta
was administered in a 10% solution of dimethylformamide; a
vehicle control was not reported. Litter size calculations
included dams that had no litters.
II-3
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It is clear from the above discussion that the higher doses
of penta can cause fetotoxic effects in experimental animals.
Based on the results of Schwetz et al. (1974), the Agency,
in PD 1, used 5.8 mg/kg/day of commercial penta as the NOEL
for fetotoxicity.
Schwetz et al. (1978), in a dietary study, randomly separated
7-week-old Sprague-Dawley (Spartan substrain) SPF derived
rats into test groups and allowed them to acclimatize for 1
week. There were 10 male and 20 female rats in each treatment
group and in the control group. The investigators mixed
penta (dissolved in anisole) with Purina Lab Chow to make a
1% preroix, from which test diets were prepared weekly and
fed to the treatment groups. (Table II-2 shows the composition
of the penta used in this study.) When adjusted weekly for
changing food consumption and body weights, this diet resulted
in doses of 3 and 30 mg/kg/day penta. All rats were observed
daily. Body weights were recorded on days 0, 29, and 62 of
the study, as well as 21 days after parturition. After 62
days on the test diet, each male was placed with two females
from the same treatment regimen for 15 days, which is three
estrus cycles in normal female rats. After the 15-day period,
the males were returned to individual cages and given the
appropriate dose-level diet. Females were maintained in
individual cages with ground corn-cob litter for nesting.
Treatment diets for females continued through 21 days following
parturition. After 21 days of lactation, the females and
their young were killed and necropsies were performed. One
male and one female of each litter were prepared for skeletal
examination. The adult male rats were sacrificed and examined
at the end of the study.
TABLE II-2
Composition of Dowicide® EC-7a
Component Amount ~
Phenols (as percent)
Trichlorophenol <0.1
Tetrachlorophenol 10.4 +0.2
Pentachlorophenol 90.4 +1.0
Dibenzo-p-dioxins
2,3,7 ,8-Tetrachloro-
Hexachloro-
Heptachloro-
Octachloro-
Dibenzof urans
Hexachloro-
Heptachloro-
Octachloro-
(as ppm)
<0.05
1.0 + 0.1
6.5 + 1.0
15.0 + 3.0
( a s ppm )
3.4 + 0.4
1.8 + 0.3
<1
a. From Schwetz et al. (1978).
II-4
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Indices of reproduction were evaluated by the Fisher exact
probability test, and body weights were analyzed by Dunnett's
test. The level of significance in all cases was P<0.05.
Statistically significant depression of parental body-weight
gain was reported at the 30 mg/kg/day dose for males at all
measurement periods, and for females at the last (62nd day)
period. At the 3 mg/kg/day dose, there was an apparent
trend toward decreased weights in both sexes at all periods
reported. This trend exists in the absence of significant
depression at any specific period.
At the 30 mg/kg/day dose, the neonatal weights of both sexes
compared to controls were significantly lower at all four
periods reported. The data for the 3 mg/kg/day dosage shows
a trend toward decreased weight (consistent with the high
dosage) which continues as the animals age. However, this
weight decrease at 3 mg/kg/day is not statistically significant
at any individual day.
Measured either as absolute weights or as liver-to-body
weight ratios, changes in maternal.liver weight at either
dosage were not significant compared to controls. Daily
inspection revealed no treatment-related effects on demeanor
or physical appearance in either adults or young.
Among the reproduction indices reported, neither the fertility
index nor the 24-hour survival index was significantly different
from controls at either dose. By Dunnett's test four indices
at 30 mg/kg/day were significantly less than control: gestation
survival, and 7-day, 14-day, and 21-day survival. Average
litter sizes were significantly less than controls on days
7, 14, and 21 at the 30 mg/kg/day dose. Gestation-period
length showed no significant treatment related effect.
At this 30 mg/kg/day dose there, was also a general trend
toward increased frequency of abnormalities in all parameters
reported. Statistically significant increases at this dose
were reported for lumbar spurs and fo'r vertebrae with split
centrum. At the 3 mg/kg/day level there was neither a trend
toward increased abnormalities nor any statistically significant
increases in any of the parameters reported.
Schwetz e_t al. (1978) is adequate to establish 3 mg/kg/day
as a provisional fetotoxicity NOEL for the penta analyzed.*
The test material (see Table II-2) was reported in the study
to contain 10-fold less hexachloro-, 30-fold less heptachloro-,
200-fold less octachlorodibenzo-p-dioxin, and 6- to 300-fold
less of the dibenzofurans than at least one of the currently
manufactured technical pentas.
* The term "provisional" is used because a teratogenicity study
which adequately demonstrating a fetotoxic no-effect level for
penta is not available at this time.
II-5
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Goldstein et al. (1977) fed female rats 20, 100, and 500
ppm of either technical or purified penta for 8 months. The
technical penta used for this study was reported to contain
only slightly less HxCDD and hexachlorodibenzofuran than the
levels reported for currently manufactured commercial penta.
Dosing at 20 ppm (about 1.5 mg/kg/day as interpolated from
food consumption data) resulted in a 15-fold increase over
the control in the activity of aryl hydrocarbon hydroxylase
(AHH). Purified penta, on the other hand, had no significant
effect on AHH induction at any dose tested. Glucuronyl
transferase activity was also significantly elevated at the
20 ppm treatment level by the technical penta used in this
study. The Agency is not aware of a meaningful toxic state
which can be associated, in this case, with the reported
levels of enzyme induction or elevation. However, elevated
AHH activity has been used as a "biochemical correlate"
(Goldstein, 1980) for the presence in biological samples of
some of the nonphenolic contaminants of technical penta. At
a level of 20 ppm neither technical nor purified penta in
this study affected the excretion of urinary porphyrins or
their precursors. The liver-to-body weight ratio was not
affected significantly at 20 ppm by either grade of penta.
Additional assessment of parental chronic toxicity allows
comparison of penta dose levels causing fetotoxicity with
those doses causing significant effects in adult animals.
A 2-year chronic feeding and oncogenicity study of penta in
rats (Schwetz e_t al. , 1978) shows a NOEL of 3 mg/kg/day for
bodyweight change and food consumption of the adults. In
addition, this study was unable to demonstrate a significant
increase of either benign or malignant tumors in either sex.
The 8-month rat (male and female) feeding study of Kimbrough
and Linder (1978), using the technical penta of the Goldstein
study (Goldstein et al., 1977), showed only "mild" histological
alterations (unspecified) in the liver at the 20 ppm dietary
concentration.
The results of 90-day feeding studies are also useful for
comparison with fetotoxic effects, which may occur with
relatively short exposure duration. In a 90-day rat feeding
study, Kociba £t al. (1973) used doses of 1, 3, 10, and 30
mg/kg/day. Several of the adult body weight gains were
significantly different from controls: males were higher,
females were lower. A comparison of the pooled dose mean
body weights with controls, however, failed to show a treatment
effect. The testes-to-body-weight ratios were lower than
controls at all doses and significantly lower at 10 and 1
mg/kg/day. Also, there was no clearly established NOEL for
serum glutamic pyruvic transaminase or alkaline phosphatase
elevations.
II-6
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The 90-day rat feeding study of Knudsen et al. (1974), performed
with an inadequately described technical penta, showed
significantly elevated alkaline phosphatase levels in females
at 1.1 mg/kg/day. Liver and kidney weights appeared to show
a dose-related increasing trend in both sexes. The liver
weight increase in females was significant at 2.5 and 10
mg/kg/day. Liver histopathology, specifically centrilobular
vacuolization, was present in both sexes at 10 mg/kg/day. At
2.5 mg/kg/day, this effect was marginally elevated in females
but absent in males.
A third 90-day rat feeding study (Johnson et a1., 1973) also
was performed with an incompletely described technical
penta. The NOEL was 3 mg/kg/day, based on increased liver
weight at higher doses.
Studies with Dioxins
Commercial penta contains several forms of chlorinated
dibenzo-p-dioxins (see Part I.C.2). Schwetz et al. (1973)
administered purified HxCDD (two unspecified isomers) and
octachlorodibenzo-p-dioxin (OCDD) by gavage to pregnant
Sprague-Dawley rats on days 6 through 15 of gestation. Doses
were 0.1, 1, 10, or 100 ug/kg/day HxCDD and 100 or 500 mg/kg/day
OCDD.
In these experiments with HxCDD, there were significant
increases over controls in fetal resorptions at the 10 and
100-ug/kg/day doses, as well as decreases in fetal body
weight and fetal crown-rump length. Subcutaneous edema was
observed at all doses except 0.1 ug/kg/day, which was considered
the no-effect dose. At the two highest doses, dilated renal
pelvis {at 10 and 100 ug/kg/day) and cleft palate (at 100
ug/kg/day) were also observed. In contrast, OCDD, at both
dose levels (100 and 500 mg/kg/day), produced no fetal resorp-
tions or other effects except for an increase in the incidence
of subcutaneous edema at the high dose level.
Significant increases over the controls in all of the terato-
genic parameters were observed at 100 ug/kg. For example,
cleft palate was observed in 47% (8/17) of the fetuses exposed
to HxCDD, compared with none (0/156) in the controls. Of the
treated fetuses, 12% (2/17) had dilated renal pelvis compared
with 0.6% (1/156) in the controls, and 31% (5/16) of the
treated fetuses had abnormal vertebrae, compared with 6%
(9/158) in the controls. In contrast, OCDD did not cause
teratogenicity at 100 mg/kg/day; although 500 mg/kg/day caused
subcutaneous edema, it produced no other observable effects.
Because of the extremely high doses of OCDD required to
produce an effect, the margins of safety for this dioxin
isomer are much greater than those for HxCDD.
II-7
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As the fetotoxicity NOEL (0.1 ug/kg/day) for HxCDD is lower
than that for teratogenicity for HxCDD, the Agency will use
the NOEL for fetotoxicity in the quantitative assessment of
risk. (Note that errors on pages 43 and 46 of PD 1 mistakenly
expressed this NOEL as 1.0 ug/kg/day.)
HxCDD is also responsible for some of the immunosuppressive
character of technical penta. In Holsapple et al. (1984),
daily exposure of adult female mice for 14 days to technical
grade penta at 10, 30, and 100 mg/kg (p.o.) suppressed the peak
(day 4) IgM antibody (Ab) response to sheep red blood cells (sRBC)
by 44%, 53%, and 72%, respectively. In contrast, similar exposure
to pure (dioxin-free) penta had no effect, thereby suggesting
that the suppression by technical penta was due to the
dibenzodioxins. Similar exposure to 1,2,3,6,7,8-HxCDD at 0.2,
1.0, and 4.0 ug/kg concentrations, corresponding to those
found in technical grade penta, indeed suppressed the peak
IgM Ab response to sRBC by 30%, 47%, and 62%, respectively. Direct
addition of 0.1 ug of either 1,2,3,6,7,8-HxCDD or 1,2,3,7,8,9-
HxCDD to spleen-cell suspensions of untreated mice was able
to suppress by greater than 80% the Ab response to sRBC.
Among the dioxin isomers, those chlorinated at the 2,3,7, and 8
positions are recognized as the isomers particularly toxic to
several species. Holsapple ejt a±. (1984) showed that subchronic
(14-day) exposure of their mice to 1,2,3,6,7,8-HxCDD (the major
dioxin in penta) produced significant elevations in liver
weight, microsomal protein, cytochrome P450, and in the
activity of aryl hydrocarbon hydroxylase (AHH). The induction
of AHH is a well-known biochemical response associated with
exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which,
for several species is the most toxic dioxin isomer. Furthermore,
the significantly decreased thymus weights among the mice
corresponds to the thymic atrophy observed in almost all species
exposed to 2,3,7,8-TCDD.
The immunosuppression by the hexadioxins is thought to be due
to the parent compound, as indicated by Holsapple et al.,
which showed that preincubation with crude liver homogenate
preparation (which readily activated cyclophosphamide)
abolished the activity of the hexadioxins, possibly by a
metabolic deactivation process.
Studies with Furans
As discussed in the chemical background section of this
document, chlorinated dibenzo-furans have also been shown to
be contaminants of pentachlorophenol products. The chemical
structures of the chlorinated dibenzo-furans and chlorinated
dibenzo-p-dioxins are similar and levels of contamination of
II-8
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the two chemicals parallel each other. Although no fetotoxic
studies have been done on the furans, because of their functional
similarity in short term testing (McConnel and Moore, 1979
and Poland et al., 1979), the chlorinated dibenzo-furans
are presumed to be fetotoxic and teratogenic as are the
dibenzo-p-dioxins.
Studies with Hexachlorobenzene (HCB)
Courtney e_t aJL. (1976) reported a teratogenic effect caused
by HCB in mice. Oral administration to CD-I mice on days 7
to 16 of gestation showed that HCB at 100 mg/kg/day produced
significantly elevated maternal liver-to-body weight ratios
and decreased fetal body weights. The number of abnormal
fetuses per litter increased significantly. In one of the
litters the abnormalities included some cleft palates.
Khera (1974) reported fetotoxic effects, which were limited
to dose-related sternal defects at doses of 40 mg/kg (days 6
to 21 of gestation) and to a significantly increased incidence
of uni- or bilateral fourteenth ribs. This latter effect
was dose- and duration-dependent and commenced at the lower
dose (10 mg/kg/day) during either days 6 to 16 or days 10 to
13 of gestation. There were no HCB-related effects on external
morphology. Khera did not observe visceral deformities and
histological examination was negative. The parameters of a
concurrent dominant lethal assay were all within the control
range. There was a NOEL of 60 mg/kg/day for maternal toxicity
(weight loss and convulsions) when HCB was administered on
gestation days 6-21 or for shorter periods.
Simon e_t al. (1979) also observed that HCB, when administered
at either 70 or 221 mg/kg/day for 5 days, would not induce
dominant-lethal mutations in rat. At these two doses, however,
HCB showed a dose-dependent decrease in the number of females
inseminated and impregnated.
Grant e_t al. (1977), in a four-generation rat reproduction
study, found that pregnancy, viability, lactation indices,
neonatal weight gain, and relative liver weight all had a
NOEL of 1.0 mg/kg/day dietary HCB. At a 4-fold higher dose,
several of the maternal animals died. No gross abnormalities
were observed in the young rats.
In several mammalian species penta is one of the metabolites
of hexachlorobenzene (HCB). Koss e_t a_l. (1978 ) dosed female
rats with HCB on alternate days at 50 mg/kg. These researchers
found a blood ratio of penta (as a metabolite of HCB) to HCB
of about 1:10 at steady-state. The mean blood concentration
of HCB in the general population is reported to be less than
1 ppb (Strassman-Sundy, 1980).
II-9
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2. Analysis of Specific Rebuttal and Public Comments
Concerning Fetotoxicity
The rebuttal and public comments that follow are rebuttals
submitted in response to the PD 1 on pentachlorophenol and
public comments submitted in response to the PD 2/3 on the
wood preservative uses of pentachlorophenol. The Agency
responses to each comment are also provided. These rebuttals
were previously published in the PD 2/3 (EPA, 1981) and the
PD 4 (EPA, 1984} on wood uses of pentachlorophenol respectively,
and are included in this document for completeness. The
number in parentheses after the title of each comment is an
internal number assigned to each comment received.
The following rebuttal comments were submitted in response
to the Position Document 1 on creosote, pentachlorophenol, and
the inorganic arsenicals.
Rebuttal Comment It Blood Concentrations of Penta After
Dosing (18)
Dow Chemical Company believes that the NOEL of 5.8 mg/kg/day
used in PD 1 is too low. In support of this opinion, the
rebutter provides calculations from a simulation model to
show that the theoretical average daily blood concentration
of penta after a single NOEL-dose of 60 mg/kg (Larsen et al.,
1975), when averaged over 4 days, is very close to the
theoretical average after 4 days of dosing at 15 mg/kg/day.
The rebutter states that:
Based on the similarity of these average blood concentrations
during the 4 critical days of gestation, and the fact
that 60 mg/kg administered singly is a no-effect-dose,
the actual no-effect-dose for repeated administration jj>
probably closer to 15 mg/kg per day than to j> mg/kg per d_ay_.
Agency Response; Although the hypothetical calculations
submitted by the rebutter are interesting, the Agency is not
convinced that the results calculated from a simulation model
of a single dose (Larsen et al., 1975) can rebut the empirical
results of experiments based on chronic administration.
Schwetz et al. (1974) clearly showed that doses of commercial
penta greater than 5.8 mg/kg/day are capable of producing
fetotoxic effects in rats. In addition to other possibly
relevant variables, the time-course of penta blood concentration
(which is very different in the two experiments) may partially
account for the difference in NOEL values.
11-10
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Rebuttal Comment 2; Terminology of Fetotoxic and Teratogenic
Effects (1, 18)
The American Wood Preservers Institute and Dow Chemical
Company state that the sole reference (Schwetz et. al.,
1974) cited in PD 1 as evidence for the teratogenicity of
penta in rats does not, in fact, support the conclusion of
teratogenic effects from this chemical in either humans or
rats. The rebutters claim that the distinctions between
teratogenicity, embryotoxicity, embryolethality, and fetotoxicity
are critical in the interpretation of the effects of penta.
They state that 1) teratogenic effects are typically irreversible
changes of a serious nature, 2) fetotoxic changes are
typically reversible and are of lesser toxicological
significance, and 3) embryolethality is a significant toxic
end-point, but does not result in the birth of a malformed
infant and is, therefore, not considered to be evidence of
teratogenicity.
Agency Response; Generally the term "teratogenic" is defined
as the tendency to produce physical and/or functional defects
in offspring exposed ir\ utero. The term "fetotoxic" has
traditionally been used to describe a wide variety of embryonic
and/or fetal divergences from the norm which cannot be classified
as gross terata (birth defects), or which are of unknown
significance. Types of effects which fall under the very broad
category of fetotoxic effects are death, reductions in fetal
weight, enlarged renal pelvis, and increased incidence of
supernumary ribs. It should be emphasized, however, that the
phenomena of terata and fetal toxicity as currently defined
are not separable into precise categories. Rather, the
spectrum of adverse embryonic/fetal effects is continuous,
and all deviations from the norm must be considered as examples
of developmental toxicity. Gross morphological terata represent
but one aspect of this spectrum, and while the significance
of such structural changes is more readily evaluated, such
effects are not necessarily more serious than certain effects
which are ordinarily classified as fetotoxic (fetal death
being the most obvious example).
In view of the spectrum of effects at issue, the Agency suggests
that it might be useful to consider developmental toxicity in
terms of three basic subcategories. The first subcategory
would be embryo or fetal lethality. This is, of course, an
irreversible effect and may occur with or without the occurrence
of gross terata. The second subcategory would be teratogenesis
and would encompass those changes (structural and/or functional)
11-11
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which are induced prsnatally, and which are irreversible.
Teratogenesis includes structural defects apparent in the fetus,
functional deficits which may become apparent only after birth,
and any other long-term effects (such as carcinogenicity)
which are attributable to _iri utero exposure. The third
category would be embryo or fetal toxicity as comprised of
those effects which are potentially reversible. This subcategory
would therefore include such effects as weight reductions,
reduction in the degree of skeletal ossification, and delays
in organ maturation.
Two major problems with a definitional scheme of this nature
must be pointed out, however. The first is that the rever-
sibility of any phenomenon is extremely difficult to prove.
An organ such as the kidney, for example, may be delayed in
development and then appear to "catch up." Unless a series
of specific kidney function tests are performed on the neonate,
however, no conclusion may be drawn concerning permanent
organ function changes. This same uncertainty as to possible
long-lasting after effects from developmental deviations is
true for all examples of fetotoxicity. The second problem
is that the reversible nature of an embryonic/fetal effect
in one species might, under a given agent, react in another
species in a more serious and irreversible manner. The
Agency must therefore consider all such deviations from
normal development in its risk assessment process, regardless
of any appearance of reversibilty.
The Agency agrees that the data of Schwetz e_t al. (1974)
should be cited as evidence for fetotoxic effects, rather
than for teratogenic effects. The Agency recognizes the
value of making distinctions between teratogenicity, embryo-
toxicity, embryolethality, and fetotoxicity in order to
scientifically categorize the effects of a toxic chemical.
However, from a regulatory standpoint, a fetotoxic effect may
represent as unacceptable a risk to the human fetus as would
a teratogenic effect. The studies reported in PD 1 described
terata (malformations), fetal resorptions, and increased
incidences of normal variants over controls. Any of these
adverse effects may engender concern that a sufficient margin
of safety may not exist between the test doses in animals
and the exposure levels in humans.
In the case of technical penta, when the NOEL for the feto-
toxicity of penta is considered in light of the exposure
values, the margins of safety (MOS's) are lower than those
obtained with the respective exposure figures and NOEL for
the fetotoxicity of HxCDD. Consequently, the MOS's for the
fetotoxicity of penta will be used in Part V to develop the
proposed regulatory decisions.
11-12
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Rebuttal Comment 3; Distinctions betwen Teratogenicity and
Embryotoxicity (1, 18)
The American Wood Preservers Institute and Dow Chemical Company
state the Agency is mistaken in using the study of Schwetz
e_t al. (1973) to establish the teratogenicity of HxCDD because
of the Agency's failure to distinguish between teratogenic
effects and reversible, less severe anomalies. They claim
these anomalies should be characterized only as embryotoxic
effects.
These rebutters state that the only finding in this study
indicative of a teratogenic event was the induction of cleft
palate. The rebutters point out that the other findings of
dilated renal pelvis, subcutaneous edema, and abnormal vertebral
development are evidence of embryotoxicity rather than
teratogenicity.
Agency Response: The 1973 paper of Schwetz e_t al. states
that, "By previously described definitions of teratogenicity
and embryotoxicity, HxCDD is teratogenic in the rat at 100
ug/kg dose level...." At this dose on days 6 through 15 of
gestation, cleft palate was produced in 47% (8/17) of the
rat fetuses. The rebutters offer no evidence that any of
the dose-related fetal anomalies described are reversible.
This study adequately demonstrates that HxCDD is a potential
cause of teratogenicity and other symptoms of developmental
toxicity. Discussions of the categories of developmental
toxicity (teratogenicity, embryotoxicity, fetotoxicity, etc.)
do not diminish the Agency's concern about a chemical or its
contaminants causing symptoms of developmental toxicity.
Rebuttal Comment 4; Relationship of Maternal Toxicty to
Fetotoxicity (1, 18)
The American Wood Preservers Institute and Dow Chemical Company
state that a 90-day toxicity study, a 2-year feeding study,
and a 1-generation reproduction each show a NOEL of 3 mg/kg/day.
This correspondence of the NOEL values cited for fetotoxicity
and maternal toxicity is presented as evidence of a low hazard
of fetotoxicity from penta. The rebutters suggest that the
observed fetal anomalies result indirectly from toxicity to
the mother, and not from direct toxicity to the fetus. Thus,
margins of safety which would protect the mother against
other toxicological manifestations would also protect the
developing embryo and fetus against adverse effects.
Agency Response; The rebutters have not demonstrated that
maternal toxicity is the cause of the observed fetotoxicity.
The concept that the fetotoxic effects of penta do not occur
at doses lower than those causing maternal toxicity is refuted
by the study of Schwetz et al. (1974). In this study there
was a significant increase in percent of fetal resorptions
at 15 mg/kg/day (commercial penta), a level which produced
11-13
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no maternal toxicity. Maternal toxicity did not appear
until a dose of 34.7 mg/kg/day was achieved. In addition,
it should be noted that the duration of exposure required to
manifest fetoxicity in an animal may be considerably less
than the time to demonstrate a chronic or life-time effect.
For this reason, a proper comparison of hazards involves
consideration of the duration and timing of exposure in
addition to the NOEL value comparison. The Agency believes
that the analysis of hazard to the fetus should be considered
in terms of an analysis of fetal exposure vs. fetotoxocity,
rather than exclusively in terms of a comparison of the
fetal hazard to that of some other hazard, such as maternal
toxicity.
Rebuttal Comment 5; Interpretation of Reduced Mouse Litter
Size (1, 18)
The American Wood Preservers Institute and Dow Chemical
Company contend that the study of Fahrig et al. (1978),
reporting decreases in litter size of female mice after intra-
peritoneal injection of 50 and 100 mg/kg penta, cannot be
relied upon for three reasons: 1) evidence of pregnancy was
not obtained, i.e., the absence of a litter may have been due
to lack of pregnancy, 2) a vehicle control was not used,
and 3) the route of administration (intraperitoneal injection)
bears no relationship to the routes of human exposure to
penta wood preservatives or to treated wood.
Agency Response; The Agency agrees that the Fahrig et al.
(1978) study is not primarily concerned with fetotoxic or
teratogenic effects. Indeed this study is basically an
examination of the mutagenic potency of the chlorophenols
and chlorophenol impurities. The conclusions of the study
are based upon the observed frequencies of various color
spots in the coats of mice. As such, the authors' comment of
"decreased litter size" is unaccompanied by supporting
data or procedural information which would normally be
essential to a study in which litter-size observation was
part of the formal protocol. Therefore, the Agency agrees
that "decreased litter size" should be considered an
ancillary comment rather than as supporting data.
The Agency also agrees that the lack of a vehicle control
makes accurate interpretation of the results of this study
difficult, as the toxicity of vehicle (dimethylformamide)
was not characterized by the authors.
Although the Agency generally does not use the results of
intraperitoneal experiments as the sole basis for an RPAR
notice, studies of this kind (e.g., Fahrig et. al., 1978) can
provide valuable supporting information.
11-14
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The following comments were submitted to the Agency in
response to the Position Document 2/3 on the wood preserving
uses of creosote, inorganic arsenicals, and pentachlorophenol.
Comment Issue ftlt Pentachlorophenol teratogenicity - evidence
of reproductive effects '
The Dow Chemical Company (32) questions the Agency's use of
data concerning "decreased litter size" (Fahrig et al. 1978)
to provide supporting information on pentachlorophenol
reproductive effects when the Agency has also concluded this
observation (on litter size) should only be considered as an
ancillary .comment.
The Dow Chemical Company (32) also states that the degree
of dilation of renal pelvis observed in fetuses treated with
HxCDD (Schwetz e_t al., 1973) was consistent with retardation
of kidney development (a reversible effect). Thus, HxCDD
should not be considered teratogenic on the basis of its effect
on the developing kidney (The Dow Chemical Company, 32).
Agency Response;
The Agency maintains that taking the Schwetz e_t al. (1973)
study into account, regardless of Fahrig et al. (1978),
establishes the teratogenicity of HxCDD. That is, the reversi-
bility of dilated renal pelvis can be properly ascertained
only upon postnatal examination, particularly for hydronephrosis,
an irreversible effect with which dilated renal pelvis may
be associated. Postnatal data were not included in the
Schwetz e_t al. (1973) study. However, production of cleft
palate (47% at 100 ug/kg/day) is evidence of HxCDD teratogenicity
(Van Ormer, 1982a).
The Agency reiterates the conclusion that "decreased litter
size" is an ancillary issue and has not used this data in
developing the current regulatory position.
Comment Issue #2; Pentachlorophenol teratogenicity/fetoxicity
- choice of proper NOEL
The Dow Chemical Company (32), the American Wood Preservers
Institute (AWPI) (36B) and The National Forest Products
Association (NPFA) (36B) contend that EPA's reduction of the
pentachlorophenol NOEL from 5.8 mg/kg/day (Schwetz et al.,
1974) to 3.0 mg/kg/day (Schwetz e_£ al., 1978) is unjustified.
These commenters state that the data used to establish this
fetotoxicity/teratogenicity NOEL utilized pentachlorophenol
which varied in purity from one set of animal data to another;
they argued that data based on "purified" pentachlorophenol are
not relevant to regulation of commercial pentachlorophenol.
They point out that although Schwetz et al. (1978) indicate a
NOEL between the two doses of 3.0 and 30.0 which were tested,
the Agency has identified 3.0 as the proper NOEL.
11-15
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Agency Response;
The Agency considers all relevant available data. Purified
pentachlorophenol data are not irrelevant to the regulation
of commercial pentachlorophenol. Because the Agency is not
aware of any teratogenicity study conducted according to Agency
guidelines on any current commercial pentachlorophenol, such
data provide the only basis for regulation.
The provisional NOEL value of 3.0 mg/kg/day was chosen from
a one-generation reproduction study (Schwetz e_t al. ,1978) ,
which reports a trend toward decreased neonatal weight at
3.0 mg/kg/day of purified pentachlorophenol, which is consistent
with the effects produced by the 30.0 mg/kg/day dosage, but
is not statistically significant at 3.0 mg/kg/day (Van Ormer,
1982b). A thorough discussion of the Agency's rationale for
the selection of a NOEL value of 3.0 mg/kg/day is presented
in the Wood Preservatives PD 2/3 (pages 347-353).
The teratogenicity study of Schwetz et al. (1974) is inadequate
to establish a fetotoxicity NOEL for either the commercial
or purified pentachlorophenol. There was a statistically
significant increase in skull bone delayed ossification at
the lowest dose of purified pentachlorophenol (5 mg/kg/day).
The study also lists increased incidence of delayed skull
ossification at the low dose (commercial grade pentachloro-
phenol, 5.8 mg/kg/day); lumbar spurs (commercial and purified
pentachlorophenol at 5.8 and 5.0 mg/kg/day, respectively);
and anomalous sternebrae (purified pentachlorophenol, 5.0
nig/kg/day) . Also, the commercial grade pentachlorophenol
produces some exencephaly (dose and incidence not listed)
which was reported in a public meeting as not significant
(Van Orraer, 1982a).
Comment Issue; #3: Pentachlorophenol - concern for the fetus
.in utero
The Dow Chemical Company (32) disagrees with the Agency's
PD 2/3 p. 257 contention that, from a regulatory standpoint,
a fetotoxic effect may represent as unacceptable a risk to
the human fetus as would a teratogenic effect.
Agency Response;
The Dow Chemical Company's (32) claim concerning the difference
between reversible (fetotoxic) and irreversible (teratogenic)
effects would mandate a difference in the required margin of
safety for the two effects, and implies that fetotoxic effects
have been shown to be reversible based on adequate postnatal
observation. The claim also implies that data exist on the
relative variability of the thresholds for these two types
of effects. The Agency is not aware of data on pentachloro-
phenol which show either the reversibility or the variability
of the measured fetotoxic effects, which (in any case) could
n-16
-------
appear in another species as a different type of functional
or behavioral deficit, e.g., retardation. Above all, the
Agency has concern for health of the embryo and fetus jji
utero, as well as concern that no reversible or irreversible
effects manifest after birth (Van Ormer, 1982a). Therefore,
a fetotoxic effect may represent as unacceptable a risk to
the human fetus as would a teratogenic effect.
Comment Issue #4: Pentachlorophenol fetotoxicity/teratogenicity
margin of safety
The AWPI (36B and 36F), the NFPA (36B and 36F) and the Dow
Chemical Company (32) state that the EPA's requirement for a
fetotoxic margin of safety (MOS) of 400 is unsupported and
excessive. They argue that there are data available on the
reversible nature of the fetotoxic effects of pentachlorophenol;
they claim that it is highly unlikely that any fetotoxic
effects would be evidenced if permissible exposures were limited
to one-tenth of the NOEL. Without submitting pentachlorophenol
postnatal data, the commentors reiterate the claim that fetotoxic
effects such as delayed ossification found in Schwetz ejt al.
(1974) can be reversible. An MOS as low as 100 is suggested
as appropriate.
Agency Response:
The assignment of an acceptable MOS is largely a risk/benefit
question, A fetotoxic effect such as delayed skull ossification
(reversible or irreversible) is merely the indication of an
effect in one species (A) which may extrapolate in another
species (B) into another type of effect, such as retardation.
In the field of teratogenicity, there is a relative lack of
ability to make qualitative extrapolation. Since the type
of response in species (B) cannot easily be predicted, regulation
must be based upon the absence of fetotoxic effects in the
species in question (A) by applying an MOS which reflects
this lack of qualitative correspondence between species
(i.e., by applying a margin of safety which includes components
for both qualitative and quantitative uncertainty). The
Agency is unaware of any pentachlorophenol data bearing on
the reversibility of effects such as delayed ossification
or dilated renal pelvis (Van Ormer, 1982a).
The Agency did not require an MOS of 400 for fetotoxic effects
in the PD 2/3 for pentachlorophenol. The measures proposed
in the PD 2/3 to reduce the oncogenic risk from pentachlorophenol
to an Agency-acceptable level would provide "margins of
safety greater than 400 for fetotoxicity." The assignment
of an acceptable MOS must be determined on a case by case,
use by use basis by weighing risks and benefits.
11-17
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The Scientific Advisory Panel (SAP) held an open meeting on
June 17-19, 1981, in Arlington, Virginia, to review the
Preliminary Notice of Determination concluding the RPAR for
the wood preservative chemicals. At this meeting the SAP
heard presentations by the Agency, the registrants, and other
interested members of the public. The Agency requested the
SAP to review several issues relating to the wood preservatives.
The SAP submitted its comments on the Preliminary Notice of
Determination and its recommendations on July 15, 1981. A
summary of the SAP comment relevant to the fetotoxicity of
pentachlorophenol and the Agency's response to that comment
is as follows:
Issue tl;
The Agency stated in the PD 2/3 that a no-observed effect
level (NOEL) for teratology could not be accurately determined
and asked the SAP if the occurrence of delayed skull ossification
at 5.0 mg/kg/day would preclude the establishment of a NOEL
at that level. The SAP commented that the establishment of
a NOEL is precluded both by the litter loss phenomenon and by
the delayed skull ossification at 5.0 mg/kg/day.
Agency Response
Although the Agency agrees with the SAP that an accurate
teratogenicity/fetotoxicity NOEL for pentachlorophenol cannot
be determined, in order to estimate the margins of safety for
teratogenicity/fetotoxic effects, the Agency has chosen a
provisional NOEL of 3 mg/kg/day based on a one-generation
reproduction study by Schwetz et al. (1978). Schwetz reported
a trend toward decreased neonatal weight at a dose of 3
nig/kg/day (Van Ormer, May 21, 1982). The margins of safety
(MOS) for pentachlorophenol were calculated on the basis of
the provisional NOEL of 3 mg/kg/day.
Issue 12;
On pages 273-274 of PD-2/3, the Agency addresses the role of
the wood preserving industry as a source of ambient background
levels of penta in the environment. In the absence of data
to the contrary the Agency's commonsense approach assumed that
the amount of ambient penta levels contributed by an industry
is related to the amount of penta used by that industry. The
wood preserving industry uses about 80% of the penta produced
in the U.S. Does the Panel agree with this approach? If not,
can the Panel suggest a feasible/appropriate method of more
accurately addressing the question of the source of environ-
mental penta?
11-18
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Panel Response
The Panel believes that it is essentially the Agency's responsi-
bility to develop a method of determining the source of environ-
mental penta. In general, the Agency's reasoning appears to
be sound. However, the Panel wishes to stress the need for
determining the use(s) of the remaining 20 per cent of the
penta produced in the U.S., in order that an accurate exposure
assessment can be made.
3. Summary of Rebuttal Comments Concerning Fetotoxic and
Teratogenic Effects
The rebuttal comments received do not rebut the presumption
of fetotoxicity for pentachlorophenol, nor the teratogenicity
and fetotoxicity caused by the contaminants HxCDD and HCB.
The one-generation study of Schwetz et a_l. (1978) has been
used to establish a provisional NOEL of 3.0 mg/kg/day for the
fetotoxicity of pentachlorophenol.
B. Basis of Presumption and Analysis of Rebuttal and
Public Comments Concerning Oncogenicity
1. Basis of Presumption
The Agency reviewed three studies concerning penta's possible
oncpgencity in the PD 1.
Innes et a_l. (1969) administered (by gavage) 46.4 rag/kg penta
to mice on days 7 through 28 of age, followed by 130 ppm (17
nig/kg/day) in the diet for 17 months. They reported that this
regimen caused no significant increase in tumor incidence in
the test animals when compared with controls.
In 1976, Schwetz £t a_l. reported that 1, 3, 10, and 30 mg/kg/day
of purified penta in the diet for 2 years did not increase
tumor incidence over control animals.
Boutwell and Bosch (1959) applied 0.3% dimethylbenzanthracene
in benzene as an initiator to the shaved backs of mice. As
a promoter, a solution of 20% penta in benzene was applied
similarly twice weekly for 15 weeks. The average number of
papillomas per survivor was 0.04 in the test group, slightly
less than the 0.07 observed in the controls. The number of
survivors with papillomas was 4% in the test group and 7% in
the control group.
These papers were reviewed by the Agency's Carcinogen
Assessment Group and were found to be negative with respect
to oncoaenie effects of oenta.
to oncogenic effects of penta
11-19
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Studies with Dioxins
In March 1980, the Agency received from the National Cancer
Institute (NCI) the final draft reports of two bioassay
studies dealing with the possible carcinogenicity of two
isomers of HxCDD. The results of one study, on the dermal
application of HxCDD to mice, were negative. The second
study involved oral administration of HxCDD to both rats and
mice. The doses ranged from 1.25 ug/kg/week to 10 ug/kg/week.
Under the conditions of this study, HxCDD increased the
incidences of benign and neoplastic liver tumors in mice of
both sexes and in females rats.
Squire Associates (1983) reviewed the NCI feeding study
and based on Dr. Squire's histopathological evaluations,
reported lower incidences of neoplastic nodules and carcinomas
in high dose female rats than the incidence reported by NCI
(1980) .
At the request of EPA, the National Toxicology Program (NTP)
then reviewed the histopathology slides to reexamine the
lesions in the liver tissues of the female rats. NTP (Hildebrandt,
1983) concluded that HxCDD administered to female rats causes
a toxic hepatitis and an increase in the incidence of neoplastic
nodules. The toxicity effects were characterized by cytomegalia,
karyomegaly, bile duct proliferation, and varying degrees of
cytoplasmic vacuolization (fatty change). In determining
the incidence of neoplastic nodules, Dr. Hildebrandt found
that although the cells in neoplastic nodules were often
very similar to foci of cellular alteration, two differentiating
features could be used; a) the degree of compressing adjacent
tissue (sometimes bulging from the surface), and b) perhaps
more importantly the degree of bile duct proliferation within
the focus of proliferating cells. A nodule (focus) of
proliferating cells compressing adjacent tissue and not
containing bile ducts was diagnosed as a neoplastic nodule.
A similar focus of cells that contained small bile ducts
and/or small proliferating bile ducts was diagnosed as a
focus of cellular alteration.
The nodules, or foci which Dr. Hildebrandt called neoplastic
nodules, were either devoid of bile ducts, contained a bile
duct at the periphery which was interpreted as entrapment, or
had only a hint of bile duct proliferation in one small region
of the nodule. Dr. Hildebrandt stated that there is some
subjectivity in the criteria he used to determine the number
of neoplastic nodules in the liver tissues. For example, a
few neoplastic nodules would have been diagnosed as foci of
cellular alterations if a reviewer was of the opinion that
neoplastic nodules have no bile ducts whatsoever.
11-20
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Dr. Hildebrandt found that two livers had a lesion that was
compatible with hepatocellular carcinoma.
The incidences of neoplastic nodules and carcinomas reported
by Dr. Hildebrandt as compared with the findings by NCI
(1980) and Squire Associates (1983) are summarized below.
TABLE II-3
Summary of Incidences of Neoplastic Nodules
and Carcinomas in Livers of Female Rats
Laboratory
Effect and Dose (ug/kg/wk)
Neoplastic Nodules
Carcinomas
Low Mid
1.25 2.5
High
5.0
Low
1.25
Mid
2.5
High
5.0
NCI, 1980
Squire Associates,
1983
Hildebrant
10/50 12/50 30/50
4/50 7/50 7/50
5/50 7/50 16/50
0/50 0/50 4/50
0/50 0/50 0/50
0/50 0/50 2/50
The NTP reevaluation (Hildebrant, 1983) shows incidences of
liver tumors in the range of 50% less than that of the original
1980 analysis (30 vs. 16 neoplastic nodules and two vs. four
hepatocellular carcinomas at the highest dose).
The Agency's Carcinogen Assessment Group (CAG) evaluated and
accepted the findings of NTP (Hildebrandt, 1983) and used
those data of incidences of neoplastic nodules and carcinomas
in female rats as part of the assessment of the carcinogenic
potency of HxCDD.
Other data which were used were contained in the original report
of the NCI (1980) bioassay and include incidences of tumors
for male rats male mice, and female mice. These data and the
data from the NTP reevaluation (Hildebrandt, 1983) are presented
in Tables II-4 and II-5.
The Carcinogen Assessment Group (McGaughy, 1984) summarized
and evaluated the results of the NCI bioassay. In the evalu-
ation it was stated that the bioassay showed positive results
for male and female rats (combined liver neoplastic nodules
or hepatocellular carcinomas) with the greater response in
the females. In the females, carcinomas appeared only in the
high-dose group, with a significant dose-response trend for
both neoplastic nodules and nodules and carcinomas combined.
In the male rats, there was also a trend for neoplastic
11-21
-------
nodules and carcinomas combined, but this was only marginally
significant. These results are presented in Table II-3,
which includes the recent NTP reevaluation of the female rat
liver slides. The review shows responses in the range of
50% less than that of the original analysis. The responses
for neoplastic nodules and combined nodules and carcinomas
are statistically significant.
In female mice, there was a dose-related trend in hepatocellular
carcinomas, but only the combined adenomas and carcinomas
were significant. In male mice, there was a minor trend in
hepatocellular adenomas, but no increase, statistical or
otherwise, in hepatocellular carcinomas (Table II-5).
Although no statistically significant increase in carcinomas
occurred in mice or rats of either sex, when neoplastic
nodules in the rats and hepatocellular adenomas in the rats
and hepatocellular adenomas in the mice were included in the
data, the results became significant for all groups. The
neoplastic nodules in the rats are viewed as evidence of a
progression response for cancer development; hepatocellular
adenomas in mice are interpreted as indications of potential
cancer, though the adenomas may be reversible.
Studies with Furans
Chlorinated dibenzofurans have been shown to be contaminants
of pentachlorophenol products. The chemical structures of
chlorinated dibenzofurans and chlorinated dibenzo-p-dioxins
are similar and levels of contamination of the two chemicals
parallel each other. Short term testing (McConnel and Moore,
1979 and Poland et al., 1979) of the furans indicated a
functional similarity with the dioxins. Although there are
no chronic long term studies, because of the structural
similarity and because of their functional similarity in
short term testing, chlorinated dibenzofurans could be
potential human oncogens as are the chlorinated dibenzodioxins.
Studies with Hexachlorobenzene (HCB)
In Cabral e_t al. (1977), six-week-old Syrian golden hamsters
were fed a diet containing 50, 100 or 200 ppm HCB (99.5%
pure) £d libitum for life. Although no hepatomas were observed
in the control group, the incidence of hepatomas in the
treated hamsters increased from 47% in the 50 ppm female
group to 85% in the 200 ppm female group. Similar results
were found in the male hamsters.
Cabral e_t al. (1979) studied the effects of the same dietary
levels in Swiss mice. Again, the treated groups (both male
and female) had significantly greater incidences of hepatomas
when compared to the controls. (See Section II-E for the
quantitative risk assessment.)
11-22
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2. Analysis of Specific Public Comments Concerning
Oncogenicity
No comments relevant to oncogenicity were received in response
to the PD 1 on pentachlorophenol since it was not a basis of
presumption in the PD 1. The comment that follows is a comment
submitted in response to the PD 2/3 on the wood preservative
uses of pentachlorophenol. The Agency response to each comment
are also provided. This comment was previously published in
the PD 4 (EPAf 1984) on wood uses of pentachlorophenol and
included in this document for completeness. The number in
parentheses after the title of the comment is an internal
number assigned to each comment received.
Comment Issue #1: Pentachlorophenol oncogenicity and dioxin
contamination
The American Wood Preservers Institute (AWPI) (36B) and the
National Forest Products Association (NFPA) (36B) claim that
the EPA's contention that technical pentachlorophenol presents
an oncogenic risk due to hexachlorodibenzo-p-dioxin (HxCDD)
and hexachlorobenzene (HCB) is incorrect. The AWPI and the
NFPA remark that pentachlorophenol does not contain the
2,3,7,8 TCDD dioxin, most frequently associated with adverse
human health effects; and pentachlorophenol's toxic effects
are manifested before any such evidence from HxCDD1s presence,
so that regulatory measures for pentachlorophenol will prevent
HxCDD exposure.
AWPI (36B) further contends that the oncogenic risk analysis
should be adjusted for the Science Advisory Board's (SAB)
(1978) report that 25% of total HxCDD is comprised of isomers
most likely to promote tumors. AWPI (36B) and NFPA'(36B)
comment that typically the HxCDD content in technical penta-
chlorophenol is well below the 15 ppm listed in the PD 2/3.
The AWPI (36B) and the NFPA (36B) also contend that the EPA's
use of the one-hit model to determine the carcinogenicity of
HxCDD based on the National Cancer Institute (NCI) gavage
assay (1980) is inappropriate because HxCDD is a "promoter"
rather than an "initiator" of cancer. They further comment
that Schwetz et al. (1978) and other investigators, including
Kimbrough and Linder (1978), indicate pentachlorophenol is
not an oncogen; any oncogenic potential of HxCDD is through
tumor promotion, not initiation. Thus, any HxCDD-related
carcinogenic activity would operate through a dose-response
mechanism, i.e., the greater the toxic dose above the NOEL,
the greater the promotion response. In addition, they claim
the absence of positive epidemiological data, together with
negative animal test results, support the "promoter" conclusion
(AWPI, 36B and NFPA, 36B).
11-23
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Agency Response; The regulation of both pentachlorophenol
and HxCDD is necessary because both pentachlorophenol and
HxCDD exposure can cause acute and chronic toxic effects (PD
2/3 on wood preservative uses, pp. 247-367). The oncogenic
risks associated with HxCDD exposure have been estimated in
the PD 4 on wood uses (Appendix B) to be of the order of
magnitude of 10~3 based on 15 ppm HxCDD in technical
pentachlorophenol even with the protective measures required.
Because the required protective measures (e.g., gloves,
protective clothing, respirators, etc.) which reduce the
acute toxicity and potential teratogenic/fetotoxic risks from
pentachlorophenol exposure do not reduce the potential
oncogenic risk from long-term exposure to HxCDD to levels
where benefits of use outweigh risks, this contaminant must
be regulated concurrently and independently. The Agency is
requiring an immediate upper limit of 15 ppm HxCDD, a level
cited by Rakshpal (1980), SAB (1978), and AWPI (1979) as
representative in technical pentachlorophenol, and requiring
that this contaminant be further reduced to an upper limit of
1 ppm. The potential oncogenic risk associated with
pentachlorophenol results from exposure to the contaminant
HxCDD and was discussed in the Wood Preservatives, PD 2/3
(pp.347-363).
Although HCB has also been shown to be an oncogen in laboratory
animals (PD 2/3 on wood uses, p. 345) the potential risks
from the HCB contaminant in technical pentachlorophenol are
negligible compared to those of HxCDD. The quantitative
oncogenic risk (PD 4 on wood uses) from pentachlorophenol is
based on the HxCDD contaminant alone, because the HCB slope
(potency) is significantly lower than the HxCDD slope, such
that including the HCB-related risk estimate would have only
a negligible effect on the total risk. This was also true
for the risk estimates calculated in the PD 2/3 on wood uses
(p. 363).
Buser and Bosshardt (1976) report that the forms of dioxins
most prevalent in commercial pentachlorophenol are hexa-,
hepta-, and octachlorodibenzo-p-dioxins (HxCDD, HpCDD and
OCDD, respectively). A small amount of tetrachlorodibenzo-
p-dioxin (TCDD) has also been found in pentachlorophenol
(Buser and Bosshardt, 1976) but proved not to be the extremely
toxic 2,3,7,8-isomer. Because the principal contaminants of
pentachlorophenol are the higher order dioxins, the oncogenic
potential of pentachlorophenol has been estimated using
information which includes the NCI bioassay of 1,2,3,6,7,8-
and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxins (Litt, May 24,
1982) .
11-24
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TABLE I1-4
HxCDD (Gavage) BIQASSAY (NCI, 1980):
OSBORNE-MENDEL RATS (2 years)-INCIDENCES OF NEOPLASriC NODULES
AND HEPATOCELLULAR CARCINCMAS
Vehicle
Tumor Control
MALE (700g)b
Number of animals examined 74
Hepatocellular carcinoma (HC) 0
Naoplastic nodule (NN) 0
HC + NN combined 0
Human equivalent dose (ug/kg/dy) 0
FEMALE (450g)d
Number of animals examined 75
Hepatocellular carcinoma (HC) 0
Neoplastic nodule (NN) 2(3%)
HC + NN combined 2(3%)
Human equivalent dose (ug/kg/dy) 0
a. 95% upper-limit estimate of linear term
area correction.
b. Analysis by tCI (1980)
c. p <0.05 versus vehicle-control
d. Reevaluation by Hildebrandt (1983)
e. p <0.001
Untreated Low-Dose Mid-Dose High-Dose Estimates^ of q^*
Control 1.25 2.5 5 (ug/kg/day)"1
75
0
2(3%)
2(3%)
0
73
0
1(1%)
1(1%)
0
in the multistage
49
0
0
0
0.04
50
0
5(10%)
5(10%)
0.03
model based
50
0
1(2%)
1(2%)
0.08
50
0
7(14%)c
7(14%)c
0.06
3(6%) 5.6 x 10-1
4(8%)c 5.9 x 10-1
01 C _
.ID
J\)
2(4%) 3.2 x 10"1
16(32%)e 3.3
18(36%)e 3.5
0 .12
on human equivalent dosages using surface
11-25
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TABLE II-5
HxCDD (Gavage) BIOASSAY ((CI, 1980):
B6C3F1 MICE (2 years) - INCIDENCES OF HEPATOCELLULAR CARCINOMAS
AND HEPATOCELLULAR ADENOMAS
Timor
Vehicle
Control
Untreated
Control
Low- Dose
1.25
Mid-Dase
2.5
High- Dose
5
Estimates'3 of q,*
(ug/kg/day)-l
(MALES)
Number of animals examined 73
Hepatocellular carcinoma (HC) 8(11%)
Hepatocellular adenoma (HA) 7(10%)
Conbined HA and HC 15(21%)
Human equivalent dose (ug/kg/dy) 0
(FEMALES)
Animal dose (ug/kg/wk)
Number of animals examined
Hepatocellular carcinoma (HC)
Hepatocellular adenoma (HA)
Combined HA and HC
Human equivalent dose (ug/kg/dy)
0
73
1(1%)
2(3%)
3(4%)
0
75
12(16%)
15(20%)
27(36%)
0
0
74
0
2(3%)
2(3%)
0
50
9(18%)
5(10%)
14(29%)
0.014
2.5
48
0
4(8%)
4(8%)
0.027
49
5(10%)
9(18%)
14(29%)
0.027
5.0
47
2(4%)
4(9%)
6(13%)
0.054
48
9(19%) 3.71
15(31%)b 6.99
24(50%)c 11.00
0.054
10
47
2(4%) 9.15 x 10-1
9(19%)b 2.61
10(23%)b 2.94
0.107
b
c
n equvaen ose uggy u _ « _ ».%/«.. _ ^z^. - "~~- - .. - —
95% upper-limit estimate of linear term in the multistage model based on human equivalent dosages using surface
area correction.
p <0.01 versus vehicle-control
p <0.001
11-26
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Although it may be that only 25% of the isomers of HxCDD
have been shown to cause tumors in laboratory animals, the
Agency assumes, for the purpose of developing regulations,
that there may be a structure-function relationship for
isomers of the same chemicals and takes a conservative regulatory
position in the absence of data to the contrary. The HxCDD
oncogenic risk estimate therefore reflects this position;
i.e., that 100% of the isomers of HxCDD which are contaminants
of pentachlorophenol and sodium pentachlorophenate are
potential human carcinogens.
Regarding AWPl's (36B) comment that the HxCDD content is
typically below 15 ppm, the Agency received data from several
manufacturers which indicated that the HxCDD concentrati-on in
technical pentachlorophenol could be as high as 23 ppm but
was usually approximately 15 ppm. The Agency chose 15 ppnr as
representative level for purpose of risk estimation in the Wood
Preservatives PD 2/3 as well as in the PD 4. The Agency has
received no data on HxCDD to the contrary.
The issue of whether the isomers of HxCDD are promoters
rather than initiators is not germane to model fitting. Seven
low-dose extrapolation models were used and the one with the
best data fit is the multistage model (Litt, May 24, 1982).
The multi-stage model has proven to be an appropriate choice
based on mathematical, theoretical and biological grounds
(Appendix to Water Quality Criteria Document; November 28,
1980 [45 FR 79318]). Further discussion of the multistage
model is provided in Section II-E of this document.
The Agency agrees that pentachlorophenol itself has not been
shown to be oncogenic in laboratory animals (PD 2/3 on wood
uses p. 344), but this does not negate the findings by NCI
(1980) that HxCDD, a contaminant in pentachlorophenol, has
been shown to cause tumors in laboratory animals. It. is the
Agency's position that exposure to pentachlorophenol containing
HxCDD presents a potential oncogenic risk to humans.
Epidemiological data submitted by AWPI (#81:30000/280
indicated no increased deaths or cases of cancer occurred
from exposure to pentachlorophenol (or inorganic arsenic) in
workers at a wood-treating plant in Hawaii. The Agency
reviewed these data and concluded the study was inadequate to
assess whether a cancer risk existed among the wood treaters
(Gibbs, 1983). Section V.A.2 (Comment #10) of the PD 4 on
wood uses discusses this evaluation more fully.
In the absence of adequate epidemiological data, the Agency
continues to assume that pentachlorophenol containing HxCDD
poses a potential unreasonable adverse effect. Animal data
exist which allow the quantitation of risks and provide an
adequate basis for regulation.
11-27
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A recent reevaluation of the NCI (1980) study showed liver
lesions from HxCDD dosed rats confirming that HxCDD is onco-
genic in laboratory animals. When compared to historical
controls, neoplasia incidence is increased among female rats
exposed to the highest dose [ NTP (Hildebrant), 1983]. There
is a clear indication that liver neoplasia in the female
rats was associated with HxCDD exposure (Moore, Nov. 4,
1983). Therefore, based on these findings, the Agency has
concluded that technical pentachlorophenol presents a potential
oncogenic risk to humans due to the HxCDD that is present.
3. Summary of Public Comments Concerning Oncogenicity
The comments received do not rebut the presumption of oncogen-
icity of commercial pentachlorophenol. The presumption of
oncogenicity is based on the determination of oncogenicity
for the contaminants HxCDD and HCB.
C. Analysis of Rebuttal Comments Concerning Human Exposure
The rebuttal comments that follow were submitted in response
to the PD 1 on pentachlorophenol. The Agency responses to
each comment are also provided.
Rebuttal Comment 1: Distinguish Between Cooling Tower Use
and Agriculture Use of Penta
The Cooling Tower Institute comments ask EPA to distinguish
between cooling tower use and agriculture use of penta. They
point out that penta-containing biocides are not consumer
products, only small quantities are used, personnel are well
trained, and little exposure to the public is likely. They
conclude EPA's registration requirements for cooling towers
should be different from agricultural use. They believe
restricted use classification should not apply to the use of
penta products in cooling towers.
Agency Response; EPA agrees that use of penta-containing
products for cooling tower use does not lead to public exposure
However, the commentors did not present a conclusive reason
for not restricting the use of penta-containing products. In
some cases, penta products are added by a metering device,
but in most cases they are added by hand. Dermal exposure is
potentially high, particularly if gloves are not worn.
Rebuttal Comment 2; Penta in Ionic Form (Non-Volatile) has
Insignificant Inhalation Exposure
Dr. Donald Crosby of the University of California at Davis
comments that much of the penta in cooling tower water is in
11-28
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the ionic form and does not volatilize: also, people are not
in direct proximity to the cooling towers during their
operation. With regard to tanneries and pulp mills, he states
the penta is in a non-volatile form and could not directly
contribute to significant inhalation exposure.
Agency Response; EPA agrees that penta in cooling tower
water and pulp mill slurries is mostly non-volatile and would
not contribute to significant inhalation exposure. The personnel
who add the penta-containing biocide, would,however, be
subject to potentially dermal exposure, particularly if gloves
are not worn.
Rebuttal Comment 3; Non-Volatility of Penta in Ionic Form and
Concern over Exposure Numbers (Assumptions)
Betz Laboratories echoed Dr. Crosby's comments on the non-
volatility of penta in its ionic form and its resulting in
insignificant inhalation exposure. Betz also claims exposure
to 100 ml of cooling water is excessive as is exposure to air
containing penta for two hours/day. The same remarks apply
to the use of penta in pulp/paper mills.
Agency Response; The Agency agrees that two hours/day may be
excessive. The Agency is basing penta exposure on actual use
time rather than time spent in the area. Regardless, the
actual penta available for volatilization is low.
Rebuttal Comment 4; O.M. Scott & Son's Co. Granular 2% Penta
Lawn Treatment Product
O.M. Scott & Son's Company comment that their granular penta-
containing (2%) lawn treatment product to remove moss from
lawns is safe as directed and does not lead to significant
exposure.
Agency Response; Because of the low concentration and the
granular form of the lawn treatment product, the Agency expects
minimal exposure if used as directed. The particles are large
and dermal contact would not be expected to result in significant
dermal absorption. However, there is concern about exposure
to children and animals playing in the treated yard.
Rebuttal Comment 5; Use in Drilling Muds, Cooling Towers,
Pulp Industry, Joint Compounds
Dow Chemical Company claims that penta use in drilling muds,
as a biocide, is safe and effective. Similarly, they contend
that penta use in cooling towers and the pulp industry is
safe. Dow also claims that use of penta in joint compounds
is necessary to prevent mildew during drying.
11-29
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Agency Response; Use of penta in pulp nills and oil well
waters results in negligible human exposure. However,
the use of penta in cooling towers, condensers, and air
washers may result in high dermal exposure. The use of penta
in wall and joint adhesives could result in volatilization
of penta into interiors resulting in inhalation exposure.
Rebuttal Comment 6; Blumberg Co., Inc. Product for Tanning
Presents No Inhalation Hazard
The Blumberg Company, Inc. states that use of their penta-
containing product in the tanning industry does not present
an inhalation hazard.
Agency Response; EPA agrees that the inhalation hazard is low
because penta is in an ionic form in the tannery baths used.
However, dermal exposure, particularly in the handling of hides
in solution, can be high. Ther-e have been instances where
penta entered the food chain from fleshings taken from hides
and sold to rendering plants. Renderers then sold the fleshings
for incorporation into animal/poultry feed. The use of this
feed resulted in penta contamination of eggs and poultry.
Rebuttal Comment 7; Exposure time in Cooling Tower Use
The Chapman Chemical Company claims the time of exposure to
penta from cooling towers has been overestimated. Minimal
possible contact time is the actual case.
They also claim exposure from home use of penta-containing
products can be lessened by more appropriate warning labels.
Agency Response; As mentioned in the Agency's response to
Rebuttal Comment 3, the Agency agrees that the possible time
of contact with penta in a cooling tower area is less than
two hours/day. The Agency is basing penta exposure on an
actual use time rather than time spent in the area. Inhalation
exposure is not significant.
11-30
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D. Human Exposure Analysis
1. Introduction
The PD-1 on pentachlorophenol provided exposure estimates for
wood and non-wood uses. The non-wood uses addressed in the
PD-1 included cooling towers, pulp/paper mills, and tanneries.
This exposure assessment will address these uses as well as
several others not included in the PD-1. Also, additional
information obtained since publication of the PD-1 is used to
improve the exposure assessment, particularly with regard to the
estimates of the number of applicators/persons exposed to penta and
sodium pentachlorophenol (Na-penta) and their current use patterns.
Information presented below discusses how the exposure figures
for each use were derived. The exposure estimates as well as the
assumptions used in calculating the estimates are summarized
in Table II-6.
2. Herbicidal
The use of pentachlorophenol as a herbicide has been
discontinued though current registrations still exist. Exposure
would be considered high because penta is applied by hand spray.
Exposure during mixing/loading and spraying is very high because
of the high concentration of penta. Also, the absorption will
be high when mixing/loading because it usually is in solvent
which leads to high dermal absorption.
3. Anti-Microbial
a. Working Solutions
Oil Well Water
The application of sodium penta (Na-penta) is made with a
metering pump. The final concentration of Na-penta is about
40 ppm, but the user of the product applies Na-penta at the
rate of 1000 ppm. Because no dermal or inhalation exposure
is expected, exposure from this use is negligible.
Evaporative Condensers
For this site, Na-Penta is applied as a solution. No infor-
mation on concentration of the product was available, but
a similar use concentration of 2,4,5-trichlorophenol contains
17.5 %A.I. (Reese, 1978). Assuming a similar concentration,
and the fact that it is added by hand, a worker could be exposed
to 6 ml* of concentrate/use. The Na-Penta is generally added
* The 6 ml value represents a mean value from an experiment
by Dow Chemical in which liquid pick-up on the skin was measured.
11-31
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once/week. The exposure estimate is calculated as follows:
6 ml x 0.175 (% AI) x 1000 mg/gm/70kg=
15 mg/kg/day x 50 days =750 mg/kg/yr
The desired concentration in the water is about 150 ppm.
It is not anticipated that further contact with the water
or significant vaporization will take place. There are an
estimated 500 applicators.
Air Washers, Cooling Towers
The exposure estimated for both of these sites was calculated
to be identical to those for the evaporative condenser use.
There are an estimated 10,000 applicators exposed due to the
use of Na-Penta in air washers and 100,000-1,000,000 applicators
due to the use in cooling towers.
b. Finished Product Preservative
Adhesive/Sealants
Pentachlorophenol is used as a component in the formulation of
sealers and adhesives as a preservative. A formulation containing
90% Na-Penta including isomers is added to the adhesive/sealer to
the extent of .25 - 1% weight for weight (w/w). There are an
estimated 20 workers involved in formulations of these products and
gloves/dust masks are used. For the formulators involved in
adding penta, an exposure estimate can be made assuming no
inhalation exposure and an applicator will have both hands (no
gloves) covered with dust. The exposure estimate is calculated
as follows:
200* mg x 0.9 (% AI)/70kg - 2.6mg/kg/day X 250 days = 650 mg/kg/yr
Canning/Sealing and Gaskets
Na-Penta is formulated into cements for use in canning
and sealing food and other containers. The Food and Drug
Administration (FDA) allows a maximum of 0.05% (w/w) Na-penta
in the sealing materials.
The formulation used contains 90% Na-Penta, including 11 isomers.
It is added to sealing or gasket material by the applicator.
There are an estimated 20 workers directly involved in this use
of penta.
*This value was taken from an experiment conducted by Zoecon
Corporation. The experiment showed that 200 mg completely
whitened all surfaces of the hands of an adult male with a fine
powder.
11-32
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Assuming an applicator will cover both hands (no gloves)
with dust daily and no inhalation exposure, the dermal exposure
would be (Noren, 1983):
200 mg x .9 (%AI)/70 kg *
2.6 mg/kg/day x 250 days =650 mg/kg/yr
Photographic Solutions
Pentachlorophenol is not currently used in photographic solutions.
No exposure figures are available for this use. However, a
qualitative assessment would indicate the potential dermal
exposure could be high due to the film developing process.
-------
For the soak, pickle/tan, fat liquor, and finish operations,
100 ml of daily dermal contact is assumed. The exposure estimate
calculation is as follows for the soak operation:
100 ml x 300 ppm cone. /70kg = .0004 mg/kg/day
The calculations are the same for the pickle/tan, fat liquor,
and finish operations except that the concentrations in ppm are
150, 85, 400 and the daily dermal exposures are .0002, .0001,
and .0005 mg/kg, respectively.
For the biocide application, the daily dermal contact is
assumed to be 200 mg of formulation/day. The calculation for
exposure for this operation is:
200 mg x .9(% AD/70 kg * 2.6 mg/kg
There is a potential for dietary exposure to penta as a
result of its use in the tanning industry. Fleshings from
penta-treated hides are sold to Tenderers who then in turn sell
the fleshings for incorporation into animal/poultry feed.
Marine Anti-Fouling Agents
Pentachlorophenol is added to marine caulking/sealer. The
concentration of penta for this use is 5%. Approximately 1650
gallons of penta-containing marine sealer are produced in the
United States annually/ involving about 6-8 workers.
It is estimated that plant workers will contact 100% penta
as dust and that 200 mg will cover the hands (Noren, 1983).
Assuming 1650 gallons are produced annually at 70 gallons/batch,
there are 24 batches made per year. The exposure estimate is
calculated as follows:
200 mg/70 kg = 2.8 mg/kg/day x 24 batches * 67 mg/kg/yr
Since manufacturing is done using a fume hood, inhalation
exposure is considered negligible.
Approximately 850 gallons of penta-containing marine sealer
are used in the U.S. Assuming contact with 6000 mg of 5% (AI)
penta product/yr, the estimated exposure is:
6000 mg(0.05)/70kg * 4.2 mg/kg/yr
The use of pentachlorophenol in marine paints was discontinued
in 1981, but the use is still registered. No exposure estimates
are available.
11-34
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d. Mushroom Houses
Dry 100% AI Na-Penta is used in a 1700 ppm solution for
spray application for mushroom house exteriors, as a tool
disinfectant dip, and around the grounds of mushroom houses.
Spraying is done 0.5 hr/day from 15-52 days/yr.
Assuming dermal contact with 200 mg of dry Na-Penta, the
dermal exposure estimate is:
200 mg/70kg = 3 mg/kg/day x 50 days/yr = 150 mg/kg/yr
Because the solution is only sprayed or used outside and
in a salt solution, inhalation exposure is expected to be
negligible because in the salt form vaporization is negligible.
However, spray application does produce inhalable particles
which can be inhaled or swallowed. In the Wood Preservative,
Position Document 2/3, it was determined that the Na-Penta air
concentration near a sapstain operation was 70 ug/m3. since
the sapstain solution is about three times the mushroom house use
rate (5000 ppm vs. 1700 ppm), the air concentration near the
spraying can be estimated at about 24 ug/m3. The inhalation
exposure estimate is:
24 ug/m3 x 1.8 m3/hr x .5 hr/day/70kg =
0.3 mg/kg/day x 50 days =15 mg/kg/yr
e. Mossicide
Pentachlorophenol is commonly used in the Pacific Northwest
to control moss growth on roofs. Two different penta products
are used: Na-Penta (28.2% AI) and pentachlorophenol (40% AI).
The penta products, 28.2% and 40%, are made-up into solutions
of 2.1% and 4%, respectively.
For mixing/loading, dermal contact is assumed to be 6 ml
of concentrate. The exposure estimates are as follows:
Penta: 6 ml (.04) x 1000 mg/gm/70kg = 34 mg/kg/use
Na-Penta: 6 ml (.282) x 1000 mg/gm/70kg = 24 mg/kg/use
For brush or spray application, dermal contact is assumed
to be 12 ml of concentrate. The exposure estimates are as follows:
Penta: 12 ml (.04) x 1000 mg/gm/70kg = 8 mg/kg/use
Na-Penta: 12 ml (.021) x 1000 mg/gm/70kg « 4 mg/kg/use
11-35
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For spray application, there will be some inhalation
exposure. The roof spraying operation will take 2 hours.
Inhalation exposure is estimated to be:
Penta: 560 ug/m3 x 1.8 m3/hr/1000ug/mg x 2 hr/70kg =
.02 mg/kg/use
Na-Penta: .02 x 300/560 = 0.01 mg/kg/use
Penta is added to granular formulations containing
fertilizer/filler, and applied with a lawn spreader. The
concentration of penta used is 1%. Since little handling of the
formulation takes place, exposure is estimated to be negligible.
f. Defoliant
Alfalfa grown for seed production is treated with
pentachlorophenol, which acts as a dessicant. The single
formulation for this use is a 40% AI product to be diluted at
the rate of 2-3 quarts/5-10 gallons of oil per acre. Penta is
not currently used on alfalfa. Therefore, no applicator exposure
information is available. Potential dietary exposure to
pentachlorophenol as a result of this use may occur. There
are no established tolerances for this use.
11-36
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TABLE 11-6
SUMMARY OF EXPOSURE ANALYSIS FOR NON-WOOD USES OF PENfACHLOROPHENOL
EXPOSURE (ug/kg/)
PERSONS DAILY " YEARLY
USE ASSUMPTIONS USED IN ANALYSIS EXPOSED DERMAL INHALATION DERMAL INAHALATION
HERBICIDE USE V
1. Greenhouses Low Usage — no exposure data available —
2. Ornamental lawns and edging
3. Rights-of-Vfey
4. Commercial and industrial non-crop areas
5. Domestic dwellings, public facilities,
golf courses and sand traps
6. Wasteland areas
7. Aquatic Areas
1/Pentachlorophenol use as a herbicide has been essentially discontinued because more effective
substitutes are available.
11-37
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TABLE I1-6
SUMMARY OF EXPOSURE ANALYSIS FOR NOW-WOOD USES OP PENTACHLOROPHBNOL
USE
ASSUMPTIONS USED IN ANALYSIS
EXPOSURE (ug/kg)*
PERSONS DAILY ~ YEARLY
EXPOSED DERMAL INHALATION DERMAL INAHALATION
ANTI-MICROBIAL
Working Solutions
1. Oil Vtell Water
2. Evaporative
Condensers
3. Air Washers
4. Cooling Towers
a. 15-39 pgn use cone. NA-Penta
b. metering pump used in application
c. Estimated Application Frequency:
2 hr/day, 25 day/yr
17.5% use cone. NA-Penta
(similar to 2,4,5 Trichlorophenol
(Reese, 1978))
applied as solution
concentrate added by hand
6 ml concentrate/use
150 ppm desired concentration
Estimated Application Frequency:
1 hr/day, 50 day/yr
b.
c.
d.
e.
f.
a.
b,
c,
d.
e.
f.
a,
b,
c,
d,
e,
f.
NEGLIGIBLE EXPOSURE
500
15,000
750,000
10,000
17.5% use cone. NA-Penta
(similar to 2,4,5 Trichlorophenol
(Reese, 1978))
applied as solution
concentrate added by hand
6 ml concentrate/use
150 ppn desired concentration
Estimated Application Frequency:
1 hr/day, 50 day/yr
17.5% use cone.. NA-Penta 100,000
applied as solution
concentrate added by hand, some
sites use pump device
6 ml concentrate/use
150 ppn desired concentration
Estimated Application Frequency:
1 hr/day, 50 day/yr
15,000
750,000
15,000 750,000
*dermal absorption factors not incorporated
11-38
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TABLE I1-6
SUMMARY OF EXPOSURE ANALYSIS FOR NON-WOOD USES OF PENrACHLOROPHENOL
USE
ASSUMPTIONS USED IN ANALYSIS
PERSONS
EXPOSED
EXPOSURE (ug/kg)
DAILY
YEARLY
DERMAL INHALATION DERMAL INAHALATION
ANTI-MICROBIAL
Finished Product
Preservatives
1. Adhesives/Sealants a
b
2. Canning/Sealing
3. Gaskets
90% NA-Pentsa and isomers 20
.25-1% w/w in product
c. negligible end use exposure
d. formulators use gloves and
dust masks
e. formulators: 200 mg to cover hands
f. Estimated application frequency:
1/6 hr/day, 250 day/yr
a. 90% NA-Penta and isomers 20
b. .05% max w/w in product (FDA)
c. no gloves
d. formulators: 200 mg to cover hands
e. Estimated application frequency:
1/6 hr/day, 250 day/yr
4. Photo Developing Solutions
5. Latex paint/Rubber, Defoaming agents,
Paper coatings, polvinyl chloride
emulsions, zinc-silicone dioxide
coatings, feathers.
*dermal absorption factors not incorporated
2,600
650,000
2,600
650,000
-low usage no exposure data available—
— no exposure data available
-low usage no exposure data available—
11-39
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TABLE II-6
SUMMARY CF EXPOSURE ANALYSIS FOR NON-WOOD USES OF PENTACHLOROPHENDL
USE
ASSUMPTIONS USED IN ANALYSIS
PERSONS
EXPOSED
EXPOSURE (ug/kg)*
DAILY
YEARLY
DERMAL INHALATION DERMAL INAHALATION
ANTI-MICROBIAL
Wbrking Solutions and Finished Product Preservatives
1. Textile/Cordage a. Solid beads 100% NA-Penta
b. Manually added to treating
solution
c. Rape content: .3% NA-Penta
d. formulators: 200 mg to cover hands
e. Estimated application frequency:
1/20 hr/day, 250 day/yr
15
2. Pulp/Paper Mills
Leather Tannery
Soak
Pickle/Tan
Fat Liquor
Finish
Biocide/
Application
a. 1-700 ppm NA-Penta use cone.
b. metering ptrop used 5,000
a. 300 ppm Na-Penta 35
b. daily contact with 100 ml
c. Estimated application frequency:
7 hr/day, 250 day/yr
a. 150 ppm Na-Penta 700
b. daily contact with 100 ml
c. Estimated application frequency:
7 hr/day, 250 day/yr
a. 85 ppm Na-Penta 160
b. daily contact with 100 ml
c. Estimated application frequency:
7 hr/day, 250 day/yr
a. 400 ppm Na-Penta 300
b. daily contact with 100 ml
c. Estimated application frequency:
7 hr/day, 250 day/yr
a. 900,000 ppm Na-Penta 100
b. daily contact with 200 mg
c. Estimated application frequency:
1/6 hr/day, 250 day/yr
2,600
650,000
NEGLIGIBLE EXPOSURE—
.4 100
.2
50
.1
25
.5
125
2,600
650,000
^dermal absorption factors not incorporated
11-40
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TABLE: n-e
SUMMARY OF EXPOSURE ANALYSIS FOR NON-VOX) USES OF PENTACHLOROPHENOL
USE
ASSUMPTIONS USED IN ANALYSIS
EXPOSURE (ug/kg)*
PERSONS DAILY YEARLY
EXPOSED DERMAL INHALATION DERMAL INAHALATION
ANTI-MICROBIAL
Marine Anti-Fouling Agents
1. Marine Calking
a. Manufacturing
b. Use
2. Marine Paints
Mushroom Houses
8
a. 100% Penta
b. product cone, is 5%
c. 200 mg 100% penta can cover hands
d. Estimated application frequency:
1.5 hr/day, 4 day/yr
e. Manufacturing addition uses fume food
a. 5% Penta 850
b. Applied with brush or towel
c. 6 gms/yr
d. Estimated application frequency:
4 hr/day, 1 day/yr
Low Usage
a. 1700 ppn\ Na-Penta 500
b. sprayed on house exterior,
tool disinfectant dip, around
grounds of houses
c. 200 mg dry Na-Penta
d. air concentration near spraying:
24 ug/m^ (comparing to sapstain
operation)
e. Estimated application frequency:
.5 hr/day, 50 day/yr
2,800 —
67,000
4,200
4,200
-low usage no exposure data available
3,000 300 150,000 15,000
Construction Materials Low Usage
"dermal absorption factors not incorporated
11-41
-low usage no exposure data available
-------
TABLE II-6
SUMMARY OP EXPOSURE ANALYSIS FOR NDW-WDOD USES OP PENTACHLOROPHEN3L
EXPOSURE (ug/kg)*
USE
MOSSICIDE
1. Roofs
Mix 1
Miv 9
ASSUMPTIONS USED IN ANALYSIS
a. 40% Na-Penta in organic solvent
a. 7ft. 74 Ma— Pent- a in unt-f>r
PERSONS
EXPOSED
N.A.
N.A.
DAILY
DERMAL INHALATION
34,000
•>A .nnn
YEARLY
DERMAL INAHALATION
34 ,000
•)A nnn
Application 1
Application 2
2. Lawns
b. contact w/ 6 ml cone, for mixing/
loading
c. Estimated application frequency:
1 day/yr,
a. 4% Na-Penta in organic solvent
a. 2.1% Na-Penta in water
b. can brush or spray
c. spray has inhalation exposure
d. dermal contact with 12 ml
e. roof spraying—2 hr
f. Estimated application frequency:
1 day/yr
a. 1% granular Penta
b. applied with lawn spreader
N.A. 8,000 20(spray) 8,000 20(spray)
N.A. 4,000 10(spray) 4,000 10(spray)
-NEGLIBIBLE EXPOSURE
DEFOLIANT
Seed (non-food):
Alfalfa, Clover,
Bird foot trefoil,
and Lespedeza
Low Usage
*dermal absorption factors not incorporated
N.A. = data not available
11-42
no exposure data available —
-------
E. Risk Assessment for Fetotoxic and Oncogenic Effects
1. Risk Assessment for Fetotoxic Effects
The Agency has calculated individual values of the Margin
of Safety (MOS) for the fetotoxicity risk assessment of penta
and its major contaminants for the population sub-groups exposed.
The MOS value is the ratio of the NOEL for fetotoxicity in
animal experiments to the appropriate sub-group exposure value.
The following absorption factors are assumed in calculating
the MOS values (Zendzian, 1982):
Dermal absorption
penta and its salts = 1%
penta in organic solvent = 50%
HxCDD = 50%
Inhalation Absorption = 100%
The following NOEL values have been used in the MOS cal-
culations for penta and two of its major contaminants:
Penta: 3,000 ug/kg/day = 3 mg/kg/day (Schwetz e_t al. , 1978)
HxCDD: 0.1 ug/kg/day (Schwetz e_t al. , 1973)
HCB: 1,000 ug/kg/day = 1 mg/kg/day (Grant e_t a_l. , 1977)
MOS Values based on the accompanying exposure values are
presented in the Table II-7 assuming no protective clothing
(gloves). MOS values for HxCDD are given for both 15 ppm and
1 ppm because technical penta generally contains 15 ppm HxCDD
but as required by the PD 4 on the wood preservative use of
pentachlorophenol the HxCDD contamination will be required to
be reduced to 1 ppm. Exposures to the HCB in penta have been
determined by the Agency to range below 3.4xlO~3 ug/kg/day
and thus HCB MOS values are all above 10,000. Therefore, the
MOS values for exposure to HCB in penta are not tabulated.
11-43
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TABLE II-7
Margins of Safety for Fetotoxic Effects of Penta and HxCDD
Use
Penta
MOS
HxCDD
MOS
15 ppro 1 ppm
HERBICIDAL
-no exposure data available-
ANTI-MICROBIAL
Working Solutions
1. Oil Well Water
2. Evaporative
Condensers
3. Air Washers
4. Cooling Towers
-negligible exposure-
20
20
20
0.87
0.87
0.87
13
13
13
Finished Product
Preservatives
120 5.1 77
120 5.1 77
•low usage no exposure data available-
•low usage no exposure data available-
1. Adhesives/Sealant
2. Canning/Sealing
3 . Gaskets
4. Photo Developing
Solutions
5. Latex paint/Rubber, low usage—no exposure data available—
defoaming agents,
paper coatings
emulsions, zinc-
silicone dioxide
coatings, feathers
Working Solutions
and Finished Product
Preservatives
1. Textile/Cordage
2. Pulp/Paper Mills
3. Leather Tannery
Soak
Pickle/Tan
Fat Liquor
Finish
Biocide/
Application
120
>10,000
>10,000
>10,000
>10,000
120
5.1 77
•negligible exposure-
>10,000 >10,000
>10,000 >10,000
>10,000 >10rOOO
>10,000 >10,000
5.1 77
11-44
-------
TABLE I1-7
Margins of Safety for Fetotoxic Effects of Penta and HxCDD
Use
Penta
MOS
HxCDD
MOS
15ppm Ippm
4. Marine Anti-
Foul ing Agents
Marine Caulking
Manufacturing 110
Use 71
4.8
3.2
72
48
Marine Paints low usage no exposure data available
Mushroom Houses
Construction
Materials
MOSSICIDE
ROOfS
Mix 40%
Mix 28 .2%
Application
4%
2.1%
Lawns
DEFOLIANT
Alfalfa
9.1 3.7 56
low usage noe exposure data available-
.18
13.0
.75(brush)
,75(spray)
75(brush)
60(spray)
0.39
0.56
5.9
8.3
1.7(spray) 25(spray)
1.7(brush) 25(brush)
3.3(spray) 50(spray
3.3(brush) 50(brush)
negligible Exposure
low usage no exposure data-available—
11-45
-------
2. Risk Assessment for Oncogenic Effects
The National Cancer Institute bioassay study (1980) indicated
that HxCDD is oncogenic. HxCDD administered to female rats
caused a toxic hepatitis and an increase in the incidences of
neoplastic nodules and liver tumors. The chlorinated dibenzo-
furans could also be potential human oncogens as are the chlori-
nated dibenzodioxins because of the structural similarity and
functional similarity in short term testing. In the Cabral
et al. 1977 and 1979 studies, the HCB treated groups had
significantly greater incidences of hepatomas when compared
to the controls thereby indicating HCB's potential oncogenicity.
The oncogenicity risk assessment for penta on the HxCDD
Rodent Bioassays follows the method and model developed in
the Position Document 4 on the wood uses of pentachlorophenol.
The "multi-stage model" was used in calculating the risk and
the carcinogenic potency of HxCDD was taken to be the geometric
mean of the 95% upper-limit estimates from the male mouse and
the female rat. The carcinogenic potency is estimated to be
q^* = 6.2 (ug/kg/day)"1. To estimate the potential risk (R)
to humans from exposure to the HxCDD contamination in pentachloro-
phenol and its salts, the Agency used the following equation:
R = 6.2 (ug/kg/day)~1 x HxCDD exposure
where the exposure is expressed in ug/kg/day averaged over a
lifetime. This exposure value does include the appropriate
assumed absorption factors of 1% for penta and its salts, 50%
for penta in organic solvent, and 100% of inhalation. The
Agency assumes that the average work life is 30 years and
that the average life span is 70 years. When qi* is multiplied
by individual exposures an upper bound risk estimate of carcino-
genicity is obtained. Under the assumption of a linear extra-
polation model, the values derived are upper bound estimates
for which the true risk would not likely exceed the upper bound
value and may be lower.
The upper bound estimates of the cancer risks to unprotected
workers exposed to penta are presented in Table II-8.
Risk estimates are presented for: worst case daily estimates
assuming 15 ppm and 1 ppm HxCDD contamination and average daily
lifetime estimates for the 15 and 1 ppra HxCDD contaminant.
11-46
-------
The computations involved in calculating the risks are
shown below; recall that exposure is multiplied by the potency
estimate q^* = 6.2 (ug/kg/day)-1.
WCE (15 ppm) = qi* x (50% absorption x Daily Dermal + Inhal.) x
15 parts HxCDD
1,000,000
WCE (1 ppm) = qj* x (50% absorption x Daily Dermal + Daily Inhal.) x
1 part HxCDD
1 ,000.000
ADL (15 ppm) = qi* x (50% absorption x Yearly Dermal + Yearly Inha.)
x 30 work Yr. x 1 Yr. X 15 parts HxCDD
70 yr. lifetime 365 day 1,000,000
ADL (1 ppm) = qi* x (50% absorption x Yearly Dermal + Yearly Inhal.)
x 30 work Yr. x 1 Yr. x 1 part HxCDD
70 yr. lifetime 365 day 70 yr. lifetime
11-47
-------
Use
TABLE I1-8
Risk Estimates for Oncogenic Effects of HxCDD
Risk Estimates
Using Daily HxCDD Using Average Daily
Exposure Risk Lifetime HxCDD
Exposure
15 ppm 1 ppm 15 ppm 1 ppm
HERBICIDAL
low usage—no exposure data available-
ANTI-MICROBIAL
Working Solutions
1. Oil Well Water
2, Evaporative
Condensers
3. Air Washers
4. Cooling Towers
Finished Product
Preservatives
1. Adhesives/Sealant
2. Canning/Sealing
3. Gaskets
4. Photo Developing
Solutions
7 x 10-1
7 x 10-1
7 x 10-1
•negligible exposure-
5 x 10-2
5 x 10-2
5 x 10-2
3 x 10-2
3 x 10-2
3 x 10-2
2 x 10-3
2 x 10-3
2 x 10-3
1 x 10-1
1 x 10-1
8 x 10~3
8 x 10-3
3 x ID"2
3 x 10-2
2 x 10-3
2 x 10-3
low usage—no exposure data available-
5. Latex paint/Rubber, low usage—no exposure data available-
defoaming agents,
paper coatings
emulsions, zinc-
silicone dioxide
coatings feathers
Working Solutions
and Finished Product
Preservatives
1. Textile/Cordage
2. Pulp/Paper Mills
1 x 10-1 8 x 10-3 4 x iQ-2 2 x 10~3
negligible exposure
11-48
-------
TABLE I1-8
Risk Estimates for Oncogenic Effects of HxCDD
Use
4. Marine Anti-
Foul ing Agents
Marine Caulking
Manufacturing
Use
Marine Paints
Mushroom Houses
Construction
Materials
MOSSICIDE
Roofs
Mix 40%
Mix 28.2%
Application
40%
2.1%
Lawns
DEFOLIANT
Alfalfa
Risk Estimates
Using Daily HxCDD Using Average Daily
Exposure Risk Lifetime HxCDD
Exposure
15 ppm 1 ppm 15 ppm 1 ppm
3.
Leather Tannery
Soak
Pickle/Tan
Fat Liquor
Finish
Biocide/
Application
2
9
5
2
1
X
X
X
X
X
10-5
10~6
10~6
10-5
10-1
1
6
3
2
8
X
X
X
X
X
10~6
10-7
10-7
ID"6
10-3
5
2
1
6
3
X
X
X
X
X
10~6
10~6
10~6
10~6
10-2
3
2
8
4
2
X
X
X
X
X
10-7
10-7
10-8
10-7
10-3
1 x 10-1 9 x 10-3 3 x iQ-3 2 x 10~4
2 x 10-1 1 x 10-2 2 x ID"4 1 x ID"5
low usage—no exposure data available
2 x 10-1 i x 1Q-2 8 x 10-3 8 x 10"4
low usage—no exposure data available-
1.6
1 .1
4 x 10-1
2 x 10-1
1 x 10-1
7 x ID"2
3 x ID"2
1 x 10-2
2 x 10-3
1 x 10-3
4 x 10~4
2 x 10~4
1 x 10~4
7 x 10-5
3 x ID'5
1 x 10-5
•negligible exposure-
low usage—no exposure data available-
11-49
-------
F. Alternatives
This section provides a brief discussion of the toxicological
characteristics of the available alternatives of the non-wood
uses of penta. The objective of this section is to present
an overview of toxicology data derived from literature reviews
The chemicals considered as possible alternatives to penta
are presented below according to use. The suitability and
use of the alternatives is discussed in the Benefits Analysis,
Part III of this document.
11-50
-------
Use Site
Alternative
TABLE II-9
PENTACHLOROPHENOL ALTERNATIVES
Ava i lable~Data
Data Result
DEFOLIANTS/HERBICIDES
Glyphosate
Endothall
Primary Eye Irrit.
(rabbit)
Primary Derm. Irrit.
(rabbit)
Mutagenicity
Teratology
(rabbit)
Neutoxicity
(hens)
21-Dy Dermal Study
(rabbit)
26-Mo Feeding Study
(rat)
3-ten. Repro. Study
(rat)
Risk Assessment
Primary Eye Irrit.
(rabbit)
Score*= 27/110
Score= 0.0/8.0,
(Tox Cat IV)
(-) Deminant lethal,
(-) host mediated
rat & mouse assay,
(-) Ames test, (-)
recomb. assay
NOEL= 1000 mgAg (feto-
tox & maternal), LEL=
3500 mg/kg (death,
wght gain, stomach
hemorrhage), no
terata at 3500 mg/kg
IBT study, no neurotox
signs or treatment-
related leasons, body
wght depression
NOEL= 1000 mg/kg, LEL=
5000 mg/kg (slight
e rythema/edema)
NOEL= 31 mg/kg, no
increased tumor incid.
NDEL= 10 mg/kg, LEL=
30 mg/kg (renal focal
tubule dilation in
F3b gen.)
Thyroid C-cell tumor
Severe corneal involve.
some animals died,
1-4% A.I. caused
mod. irrit.
* The term "score" refers to a standardized system to measure the severity of the effect
being tested for.
11-51
-------
TABLE I1-9
PENTACHLOROPHENOL ALTERNATIVES
Use Site
Alternative
Sodium Chlorate
Cacodylic Acid
s ,sts-Tributylphos-
phorotr i th ioate
(DBF)
Available Data
Data Result
DEPOLIANTS/HERBICI DBS
(cont'd) Endothall
(cont'd)
Primary Derm. Irrit,
(rabbit)
Acute Dermal Study
(rabbit)
Primary Eye Irrit.
(28% A.I.)(rabbit)
Subchronic Drinking
Water Study
(monkey)
1% A.I. caused minimal
skin lesions, 10% A.I.
caused necrosis,
formulated product
caused some deaths
All animals died at
200 mg/kg, (Tox Cat I)
Transcient conjunctival
irritation
No adverse hematolcgical
or clinical effects to
400 ppm
Primary Eye Irrit. Nr> irritation
(1.26% A.I.)
(rabbit)
Primary Derm. Irrit. Score= 0.9/8.0
(1.26% A.I.)
(rabbit)
2-Yr Feeding Study
(rat)
2-Yr Feeding Study
(dog)
3-Gen. Repro. Study
(mouse)
NOEL= 25 ppm, LEL=
100 ppm (decreased
body vKjht, liver
cell vacuolation),
NDBL< 5 ppm (rcb
ChE inhibition)
NOEL= 50 ppm, NOEL<
5 ppm (plasma/rbc
ChE inhibition)
N3EL> 100 ppm
11-52
-------
Use Site
Alternative
TABLE I1-9
PBNTACHLOROPHENOL ALTERNATIVES
Available Data
DEPOLIANTS/HERBICI DBS
(cont'd) Ametryne
Zinc Chloride
Paraquat
Primary Eye Irrit.
(rabbit)
Primary Derm. Irrit,
(rabbit)
Mutagenicity
90-Dy Feeding Study
(rat)
90-Dy Intubation
Study (rat)
Subchronic Feeding
(rats)
Injection Studies
(rats/chickens)
Chronic Feeding
(rats)
Use Experience
Tera togen ic i ty,
(mouse)
Teratogenicity,
(rat)
Data Result
Mild Irrit.(Tox Cat IV)
Score=0.0/8.0
(Tox Cat IV)
(-) Reverse mutation,
(-) Recomb. assay
NOEL= 1000 ppm
NOEL= 100 ppm
NOEL= 660 ppm
Testicular tumors
by injection, no
oncogenic effects
by other routes
NOEL= 1500 ppm
Chemical burns, TWA
for zinc chloride
funes= 1 ppm
Nat teratogenic at
10 mg per ion/wg
(HOT)
Not teratogenic at
10 mg per
NOEL (fetotoxicity) =
1.0
LEL (fetotoxicity) =
5.0 mg/kg (reduced
wt. and retarded ossi-
fication)
11-53
-------
Use Site
TABLE II-9
PENTACHLOROPHENOL ALTERNATIVES
Alternative Available} Data
Paraquat
Zinc Sulfide
Ferric Sulfate
Zinc Sulfate
Data Result
Acute dermal
(rabbit)
Primary Eye Irrit.
NOEL (maternal tox) =
1.0 mg/kg
= 60 mg per ion/kg
Opacity, severe pannus
(Category I)
Primary Skin Irrit. PIS =2.1 (Category III)
90-day feeding
(dog)
Oncogenicity
(mouse)
Mutagenicity
Reverse mutation
in R. typhimurium
Cytogenetic (bone
marrow), rat
Dominant lethal
(mouse)
NOEL = 0.5 mg per ion/kg
LEL = 1.5 mg per ion/kg
(alveolas collapse)
Not oncogenic up to 19.0 mg
par. ion/kg
NOEL = mg per ion/kg
LEL =5.6 mg/kg (renal tubu-
lar degeneration and
weight loss).
Nagative up to 5000 ug/plate
Nagative up to 19.0 mg/kg/day
Negative up to 4.0 mg per
ion/kg
Pertinent data not available
Pertinent data not available
Pertinent data not available
11-54
-------
TABLE 11-9
PENrACHLOROPHENOL ALTERNATIVES
Use Site Alternative Available Data Data Result
ANFI-MICROBIALS
Working Solutions-
Oil Well FJLpoH Chlorine Dioxide Acute Inhalation No irritation or death
Waters " " (rat) after 4 hrs.
Primary Derm. Irrit. Score= 6.6/8.0
(rabbit)
Primary Eye Irrit. Score=l0.5/110
Chlorine Gas 1977 NIOSH Ceiling Max.cone.15min= 0.5 ppm
Working Solutions-
Cooling Towers 4-Chloro-2-phenylphenol Primary Eye Irrit. Cone.: severe corneal
(rabbit) irrit., 1% A.I.:
sight irrit.
Primary Derm. Irrit. 0.1% A.I.: no irrit.,
(rabbit) >1% A.I.: dose related
irritation
Human Sensitization No irritation or sensit.
2-benzyl-4-chlorophenol Primary Eye Irrit. Score= 104/110
(9.7% A.I.)(rabbit)
Primary Derm. Irrit. Severe irritant
(9.7% A.I.)(rabbit)
Human Sensitization None
(9.7% A.I.)
90-Dy Feeding Study Organ wght changes at
(rat) all doses, LDT=
30 ppm
dichloro-s-triazine- Primary Eye Irrit. Corneal damage, no
trione (rabbit) irrit. at 310 ppm
30-Dy Eye Irrit. MD irrit. at 100 ppm
(rabbit)
Subchronic Oral NOED= 6.8% diet
(dog)
(dog)
11-55
-------
TABLE I1-9
PENTACHLOROPHENOL ALTERATIVES
Use Site
Alternative
ANTI-MICROBIALS
(cont'd)
Finished Product
Preservat ives-
AdhesivesT
Sealants
o-Phenylphenol
Copper-8-quinolinate
Available Data
Data Result
Primary Eye Irrit.
(18% A.I.)(rabbit)
Primary Derm. Irrit.
(18% A.I.)(rabbit)
Human Derm. Irrit.
(18% A.I.)
2-Yr. Feeding Study
(rat)
Japanese Study
1-Yr.Peeding
(dog)
Mutagenicity
Acute Dermal
(rabbit)
Primary Eye Irrit.
(rabbit)
CorneaI damage
Skin damage
tto irritation
(to dose related tumor
incidence between
0.02-2.0% of diet.
Renal damage &
increased testes
at high dose.
Possible tumor incidence
No dose related histo-
pathology between
0.02-0.5 gmAg/ but
elevated kidney damage
at high dose.
Negative Ames test with
& without activation
LD5o> 2000 mgAg» no
dermal irrit. or signs
(Tox Cat III)
Slight reversible
conjunctival irrit.
(Tox Cat III)
-------
TABLE I1-9
PENTACHLOROPHENOL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICROBIALS
(cont'd)
Finished Product
Preservatives^
Adhesives &
Sealants (cont'd)
Formaldehyde
Acute Inhalation
(rat)
2-Yr. Feeding Study
(rat)
2-Yr. Feeding Study
(dog)
2 Gen. Reproduction
(rat)
Mutagenicity
Teratogenicity
(dog)
Teratogenicity
(mouse)
££50= 0.82 rng/L
(Tox Cat II)
No effects on behavior,
mortality, hematology,
blood chemistry or
organ weights at dose
between 5-2000 ppm in
diet. NOEL= 500 ppm
Dose between 10-3000 ppm
in diet. NOEL= 200
ppm, changes in liver
& lungs
Not teratogenic,
NOEL>500 ppm
Weak (4-) Ames test,
(+) mitotic recomb.,
(-) DMA repair test,
(-) micronucleus test
Not teratogenic, HDT=
375 ppm, NOEL> 375 ppm
Not teratogenic, HDT=
185 ppm, maternal
NOGL= 148 mg/kg, LEL=
185 mg/kg (mortality)
11-57
-------
TABLE I1-9
PENTACHLORCPHENDL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICROBIALS
(cont'd)
Finished Product
Preservatives-
Adhesives &
Sealants (cont'd)
Copper Sulfate
90-Dy Inhalation
(rat)
18-Mo. Onco. Inhal.
(rat)
Mutagenicity
Primary Eye Irrit.
(37% A.I. & 7%
methanol)
(rabbit)
Primary Derm. Irrit.
(37% A.I. & 7%
methanol)
(rabbit)
Primary Eye Irrit.
(18% A.I.)
(rabbit)
Primary Eye Irrit.
(99% A.I.)
(rabbit)
NOBL= 0.028 ppm, LEL=
0.82 ppm (proliferation
of lung lymphocytes &
histocytes, perivas-
cular hyperemia
Carcinomas at 15 ppm
(4-) in E.coli &
P. fluorescens,
(-) S.typhimurium
Corneal burn/opacity
Vesicle formation with
superficial necrosis
or nodules
Score= 10/110
Corrosive
11-58
-------
TABLE 11-9
PEOTACHLOROPHENDL ALTERNATIVES
Use Site
Alternative
ANTI-MICRCBIALS
(cont'd)
Finished JProduct
Preservatives-
Adhesiyes &
Sealants (cont'd)
p-Chloro-m-cresol
Available Data
Data Result
Primary Derm. Irrit.
(18% A.I.)
(rabbit)
Potable Water Toler.
Score= 0.0/8.0
I.0 ppm copper residue
in water from lakes,
reserviors, etc.
Corneal cauterized
Oorneal opacity
Primary Eye Irrit.
(rabbit)
Primary Eye Irrit.
(17% A.I.)
(rabbit)
Primary Derm. Irrit. Score= 8.0/8.0
(17% A.I.)
(rabbit)
Sensitization
(G. pig)
21-Dy Derm. Study
(rabbit)
Positive
NOEL> 10 mg/kg/dy (LOT)
(siight erythema),
NOEL= 40 mg/kg/dy
(liver)
90-Dy Feeding Study
(rat)
Mutagenicity
N3EL= 150 ppm, LEL=
500 ppm (depressed
waight gain)
(-) Micronucleus test,
(-) Ames test
11-59
-------
TABLE 11-9
PENTACHLOROPHENOL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICROBIALS
(cont'd)
Finished Product
Preservatives^-
Adhesives &.
Sealants (cont'd)
Na-trichlorophenate
Boric Acid
Primary Derm. Irrit.
(85% A. I.) (rabbit)
Primary Eye Irrit.
(85% A. I.) (rabbit)
Primary Derm. Irrit.
(100% A. I.) (rabbit)
Primary Eye Irrit.
(100% A. I.) (rabbit)
Severe irritation
Corneal injury
Irritation cleared
after 4 dys
ND irritation
Working Solution
& Finished Product
Preservatives-
Pulp and Paper Methylbisthiocyanate
Acute Derm. Study
(10% A.I.)
(rabbit)
Primary Eye Irrit.
(rabbit)
Primary Derm. Irrit.
(10% A.I.)
(rabbit)
Sensitization
(10% A.I.)
(g;pig)
Nabam (sodium dimethyl- Primary Eye Irrit.
dithiocarbanate & (rabbit)
ethylenediamine) Primary Derm. Irrit.
(rabbit)
= 1.6 gm/kg
Oorneal opacity,
(Tox Cat I)
Score= 7.6/8.0,
(Tox Cat I)
Strong, (Tox Cat I)
IBT data, corneal
opacity
IBT data, Score=
2.1/8.0
11-60
-------
TABLE I1-9
PENTACHLOROPHENOL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICROBIALS
(cont'd)
Vtorking Solution
& Finished Product
Preservatives^
Pulp & Paper
Note: Formulation
may contain ETU
(ethylene thiourea)
ETU is an oncogen
2,2-Dibromo-3-nitrilo- Primary Eye Irrit. Corneal injury
propioamide
Vtorking Solution
& Finshed Product
Preservatives-
Tanneries
Di iodomethyl-p-tolyl
sulfone (Amical 48)
2-thiocyanmethyLthio-
benzothiazole
(TCMFB, Busan 44)
(5% A.I. in poly-
glycol E-200)
(rabbit)
Primary Derm. Irrit.
(rabbit)
90-Dy Drinking Water
(rat)
Mutagenicity
Primary Eye Irrit.
(Busan 44)(rabbit)
Primary Derm. Irrit.
(Busan 44)(rabbit)
Sonsitization (10%
A.I. TCMTBMrabbit)
Mutagenicity
Necrosis, (Tox Cat I)
NOEL=500 ppm
ttegative
Corrosive
Necrosis
Strong sensitizer
(+) with E.coli
11-61
-------
TABLE I1-9
PENTACHLOROPHBNOL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICRGBIALS
(cont'd)
Working Solution
& Finshed Product
Preseryat ives-
Tanneries (cont'd)
90-Dy Feeding Study
(rat)
90-Dy Feeding Study
(dogs)
IBT study/NOEL> 500 ppm
IBT Sttriy/NOEL> 500 ppm
Alkyl dimethyl benzyl
ammonium chloride
(Hyamine 3500)
90-Dy Feeding Study
(rats)
Primary Derm. Irrit.
(rabbit)
Primary Eye Irrit.
(rabbit)
Teratology
(80% A.I.)
(rabbit)
6-Mo. Drinking Water
Study (dogs)
6-Mo. Feeding Study
(dogs)
1-Yr. Feeding Study
(g.pig)
2-Yr. Feeding Study
(rats)
NOEL= 278 ppm, LEL=
448 ppm (gastric
ulceration)
Score= 6.5/8.0
Corrosive
ttot a teratogen, NOEL=
10 mg/kg/dy(fetotox),
LEL= 30 rog/kg/dy
(fetotox), NOEL< 10
mg/kg/dy (maternal)
NOEL= 1:5000 dilution
in water
NOEL= 200 ppm, (single
dose tested)
NOEL= 625 ppm, (single
dose tested)
NDEL= 5000 ppm, LEL=
10,000 ppm
11-62
-------
TABLE I1-9
PENrACHLOROPHENOL ALTERNATIVES
Use Site
Alternative
ANFI-MICROBIALS
(cont'd)
Marking Solution
& Finshed Product
Preservatives-
Tanneries (cont'd)
p-Nitrophenol
Available Data
Data Result
Primary Eye Irrit.
(rabbits)
Primary Dsrm. Irrit.
(rabbits)
Sensitization
(g.pig)
Human Patch Test
Mutagenicity
Teratology
(rats)
Severe corneal injury
Score= 1.6/8.0
Nagative
Mild irritation from
treated leather
applied directly to
skin
(-) Ames and yeast tests
Nagative
l-(3-Chloroallyl)-
3,5,7-triaza-l-
azoniaadamantane
chloride
Primary Eye Irrit.
(rabbit)
Primary Derm. Irrit.
(10% Aqueous soln)
(rabbit)
Human Irrit. &
Sensitization
(0.5% A.I.)
Sensitization
(10% A.I. in
Dowanol*/Tween
80)(g.pig)
Minimal Irritation
Irritatant
Man-irritant &
non-sensitizer
Moderate Sensitizer
11-63
-------
TABLE I1-9
PENTACHLOROPHENOL ALTERNATIVES
"Use" Site
Alternative
Data Result
ANTI-MICROBIALS
(cont'd)
Vbrking Solution
& Finshed Product
Preservat i ves-
Tanneries (cont'd)
Mutagenicity
21-Dy & 30-Dy Dermal
Study (20% A.I.
Aqueous soln)
(rabbit)
90-Dy Feeding Study
(rat)
90-Dy Feeding Study
(dog)
6-Acetoxy-2,4-dimethyl- [to data available
m-dioxane
Potassium Sorbate
Dichlorophene
(rat)
(-) Ames test
NOEL= 25 mg/kg, LEL=
50 rag/kg (depressed
liver wght), LEL=
BO rag/kg (decreased
spermatcgenesis)
NOEL= 2 mg/kg, LEL=
4 mg/kg (cerebral
edema)
NOEL= 7.5 mg/kg, LEL=
15 mg/kg (decreased
heart wght)
Liver tumors after
oral administration
Food & Drug Admin. GRAS List
Acute Dermal
LD50> 10,000 mg/kg
Primary Derm. Irrit. Score= 0.3/8.0
Human Patch Test
Teratology
(rat)
No irritation or
sensitization
NOEL= 5.0 mg/kg (terata,
fetotox, maternal),
LEL= 25.0 mg/kg (terata
microphthatmia), LEL=
75.0 mg (fetotox v^ht,
length, resorption),
LEL= 25.0 mg/kg (mater-
nal wght gain & food
consumption)
11-64
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TABLE II-9
PENTACHLOROPHBNOL ALTERNATIVES
Use Site
Alternative
Available Data
Data Result
ANTI-MICROBIALS
(cont'd)
VJbrking Solution
& Finshed Product
Preservatives-
Tanneries (cont'd)
2,3,4,6-tetrachlorc— Human Eye Irrit.
phenol Primary Derm. Irrit.
(10% A.I.)(rabbit)
Human Sensitization
20-Dy Oral Toxicity
(rabbit)
Possible Dioxin
Contamination
2-(hydroxymethyl)-2- Primary Eye Irrit.
nitro-1,3-propanediol (rabbit)
Human Sensitization
Hexahydro-l,3,5-tris-
(2-hydroxyethyl-s-
triazine)
Bioban P-1487
Finished Product Cuprous Oxide
Preservat ives-
Marine Paints
Primary Derm. Irrit.
(rabbit)
Primary Eye Irrit.
(rabbit)
Acute Derm. Study
(rabbit)
Sensitization
(g.pig)
Sensitization
Acute Dermal
(57% A.I.)(rabbit)
Primary Eye Irrit.
(36% A.I. +
Irritating & injurious
Minor Irritant, chemical
burn from repeated
contact
Mild Irritant, no sensit.
NOEL= 1.0 mg/kg, LEL=
10.0 mg/kg (liver dmg)
Mild irritation
ND irritation or sensit.
Severe irritant with
necrosis
Severe irritant with
opacity
LD5Q= 854 mg/kg
(Tox Cat II)
(+) Sensitizer
Strong irritant &
sensitizer
LD5Q= 8600 mg/kg
No cornea! opacity
11-65
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TABLE 11-9
PEOTACHLOROPHENDL ALTERNATIVES
Available Data
Use Site
Alternative
Data Result
ANTI-MICRCBIALS
(cont'd)
Finished Product
Preservatives-
Marine Paints
Bis(tributyltin) Oxide
0.5% tributyltin
fluoride)(rabbit)
Primary Derm. Irrit.
(36% A.I. +
0.5% tributyltin
fluoride)(rabbit)
Acute Dermal
(rabbit)
Acute Inhalation
(rat)
Primary Eye Irrit.
(rabbit)
Primary Derm. Irrit.
(rabbit)
Derm. Sensit.(g.pig)
21-Day Dermal
(rabbit)
30-Day Feeding
(rat)
Mutagenicity
Clinical Studies
Draize-Shelanski
Schwartz-Peck
Score= 0.05/8.0
(Tox Cat IV)
11.7 gm/kg
(Tox Cat III)
= 0.48 ppn
(Tox Cat II)
Extreme irritant with
corneal damage
Desquamation, slight
fissuring, atonia,
edema
Sensitizer
tot irritating at
1200 ppn
Growth suppression at
32, 100 & 320 ppn,
40% survival at 320
ppn
Nagative Ames test
with E.coli &
S.cervisiae
Nsgative
fto "untoward" reaction
at 1200 ppm
11-66
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TABLE I1-9
Use Site
PENFACHLOROPHENDL ALTERNATIVES
Alternative Available Data
Data Result
ANTI-MICRCBIALS
(cont'd)
Finshed Product
-- .
Mar i ne Bedd i ng Copper Naphthenate
& Double Planking
MOSS ICI IDES
Ferrous Sulfate
Heptahydrate
Ferrous Ammonium
Sulfate
Zinc Chloride
Ferric Sulfate
Zinc Sulfate
Copper Sulfate
Acute Dermal
(rabbit)
Primary Derm. Irrit.
(rabbit)
Primary Eye Irrit
(10.9% A.I.)
(rabbit)
Primary Derm
(10.9% A.I.)
(rabbit)
Subchronic Feeding
(rats)
Injection Studies
(rats/chickens)
Chronic Feeding
Use Experience
Pertinent data not
Pertinent data not
See P. 11-58
LD50= 16
(Tox Cat III)
Maderate irrit. &
erythema
(Tox Cat III)
Corneal Cpacity
Irrit. Score= 0.0/8.0
Primary Eye Irrit.
(15.35% A.I.)
(rabbit)
Primary Derm. Irrit.
(15.35% A.I.)
(rabbit)
Iritis, chemosis
Score= 0.5/8.0
NOEL= 660 ppm
Testicular tumors
by injection, no
oncogenic effects
by other routes
NCEL= 1500 ppm (rats)
Chemical burns, TWA
for zinc chloride
funes= 1 ppm
available
available
11-67
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III. BENEFITS ANALYSIS
A. Introduction
Part III contains the benefit analysis for the non-wood
preservative uses of pentachlorophenol and its sodium and
potassium salts. This analysis is based on material presented
in the following reports: Biological Data Base for Exposure
Analysis and Preliminary Benefits Analysis of Pentachlorophenol
and Sodium Pentachlorophenol (March 30, 1984); An Overview
of the Use of Pentachlorophenol at Various Industrial Sites
(MTR-81W258) prepared by the Mitre Corporation; The Biologic
and Economic Assessment of Pentachlorophenol, Inorganic
Arsenicals and Creosote, Volume II: Non-Wood Preservatives
(Technical Bulletin 1658-11) prepared by the United States
Department of Agriculture; Preliminary Benefit Analysis of
2,4,5-Trichlorophenol and Pentachlorophenol in Rayon Spinning
and Textile Finishing (MTR-79W00295) prepared by the Mitre
Corporation; Preliminary Benefit Analysis of 2,4,5-Trichloro-
phenol and Pentachlorophenol in Tanneries (MTR-79W00264)
prepared by the Mitre Corporation; Use Profile and Exposure
Assessment of Pentachlorophenol at Industrial Sites (MTR-81W213)
prepared by the Mitre Corporation; Preliminary Benefits
Analysis of 2,4,5-Trichlorophenol and Pentachlorophenol
for Industrial Water Treatment (MTR-79W00311) prepared by
the Mitre Corporation; Use Profiles and Alternatives Assessment
for 2,4,5-Trichlorophenol and Pentachlorophenol in Adhesives
and Polyvinyl Acetate Emulsions (Working Paper 80W00042)
prepared by Mitre Corporation).
Pentachlorophenol and its salts, formed by direct chlorination
of phenol, are broad-spectrum pesticides. These chemicals
are used as herbicides, antimicrobials, mossicides, and
defoliants. The following information is presented for each
specific use within each category: usage information, alternative
chemicals (each chemical and comparative efficacy, where
available), and a qualitative assessment of the economic
impact if that specific use of penta were cancelled by the
Agency.
B. Herbicidal Uses
Pentachlorophenol is a non-specific, nonresidual contact
herbicide used for control of broadleaf weeds, grasses, algae
and moss. Most herbicidal formulations are not used to
control larger woody plants such as trees and brush sprouts.
Pentachlorophenol offers no residual control because it is
not translocated into roots and stems of wood and perennial
plants. The combination of residual herbicides with penta-
chlorophenol overcomes this problem and provides control of
vegetation.
III-l
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1. Greenhouses
Pentachlorophenol is sprayed by hand on walkways, under
benches and canned plant areas to control weeds.
2. Ornamental Lawns
Pentachlorophenol is used to control weeds in dormant
ornamental grass lawns (bent, blue, fineleaf fescue, tall
fescue and bermuda) by spray application. Pentachlorophenol
is also used to control moss on ornamental lawns and turf.
Turf edging around driveways and house foundations is usually
accomplished with handheld equipment.
3. Rights-of-Way
Pentachlorophenol is used only when total vegetation control
is desired along rights-of-way such as roadways, firebreaks,
pipelines/ etc. Pentachlorophenol, which provides a quick
burn of vegetation, is usually applied in an oil spray with
other herbicides to provide full season weed and grass control.
Perennial plants usually require repeated treatments unless
other longer lasting herbicides are used.
4. Commercial and Industrial Non-Crop Areas
Pentachlorophenol is sprayed as a herbicide in areas such as
lumber yards, oil refineries, around fences and buildings,
etc. Pentachlorophenol has been used in herbicidal mixtures
on tank farms and other industrial areas where no vegetation
is permitted due to fire hazard. This chemical is also
sprayed in areas prior to paving. These products are applied
by railroad tankcars by fixed booms calibrated to deliver a
specific volume of spray at a given speed. Truck mounted
tanks and sprayers, another method of application, are also
equipped with fixed booms or handguns with attached hoses.
Knapsack spraying is used for small areas.
5. Domestic Dwellings, Medical Facilities, Schools,
Golf Courses and Sand Traps
Pentachlorophenol is used to control weeds in golf course sand
traps, home areas (driveways, patios, paths, etc.) and established
paved and unpaved parking lots and ornamentals. The use of
suitable soil sterilants in this latter use site is necessary
as pentachlorophenol alone does not kill perennial plants.
6. Wasteland Areas
Pentachlorophenol controls weeds on wasteland areas by spray
application.
III-2
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7. Aquatic Areas (Adjacent to Water) and
Drainage Ditch Banks
Pentachlorophenol is used to control weeds in these areas.
8. Alternatives and Economic Impacts
The herbicidal uses of pentachlorophenol have numerous, less
costly alternatives of equal or greater efficacy. Alternatives
include: chloropicrin, diquat dibromide, sodium chlorate,
sodium metaborate, dicamba, paraquat and paraquat dichloride,
siduron, sodium cacodylate, ammonium sulfamate, cacodylic
acid, disodium methane arsenate, monuron and monuron-tca,
picloram, bromacil, tebuthion, dimethylamine, 2,4-D, dinoseb,
amitrole, diuron, sodium chlorate, etc. The Agency does not
expect the cancellation of the herbicidal uses to cause
significant economic impact.
C. Antimicrobial Uses
Antimicrobial use of pentachlorophenol has generally declined
between the 1978-1981 survey period. Reductions in use have
primarily resulted from efforts to reduce operating costs.
The major 1981 industrial use sites', in order of decreasing
usage, were: water treatment, adhesives, textiles, tanneries
and all other uses.
1. Working Solutions
Pentachlorophenol products are used to control microorganism
growth in solutions used in industrial situations.
a . Usage
Sodium pentachlorophenol controls microorganism growth in
oil well flood waters, evaporative condenser cooling waters,
cooling tower waters and air washers. Application in oil well
flood waters is by injection pump. Application at evaporative
condensors is by hand, drip-fed, or pumped continuously or
intermittently into recirulating waters. Application at cooling
towers is by hand, drip feed, continuously or intermittently
pumped into recirculating waters. Applications of briquets
containing this chemical into air washer systems are by hand.
b. Alternatives
There are 35 alternatives for the oil well flood water use,
including organonitrogen and carbonyl compounds as well as
compounds containing chlorine and chlorine dioxide. Comparative
on-site efficacy data are not readily available for the well
flood water use. Data indicate, though, that pentachlorophenol
is more effective against fungi than bacteria. Some alter-
natives for this use have disadvantages such as foaming and
corrosion of surfaces.
III-3
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Alternatives for cooling tower use include: chlorine, 4-chlor-
2-phenylphenol, 2-benzyl-4-chlorophenol, 6-chloro-2-phenylphenol,
2,4,6-trichlorophenol, methylene bisthiocyanate, 2,2-dibromo-
3-nitrilopropionamide, dichloro-s-tria2inetrione, and manual
cleaning of systems. Comparative efficacy data of cooling
tower alternatives are not readily available because evaluation
is qualitative rather than quantitative, and water treatment
companies consider this information to be proprietary.
Alternatives for air washer systems include those for cooling
tower systems plus carbamates. Manual cleaning and hosing is
also an alternative. Comparative efficacy data are not readily
available for the air washer use. Disadvantages of some of
these alternatives include the tendency of quaternary compounds
to foam, and the corrosiveness of chlorine-related compounds.
Alternatives for the evaporative condenser water use include
carbamate compounds, quaternary ammonium compounds, and
biocides commonly used in cooling tower water. Manual cleaning
and hosing is also an alternative. Alternative chemicals are
not as effective as sodium pentachlorophenol.
c. Economic Impact
The oil well flood water use of this compound is not considered
to be extensive. No breakdown of the amount of pentachlorophenol
evaporative condenser usage is available at this time. Evapo-
rative condenser usage is combined with usage in cooling towers
and air washers. For 1981, the usage data indicate that only
12,000 pounds of this chemical was used at all three sites.
The Agency believes the economic impacts of cancellation of
this use to be small based on low usage and the availability
of substitutes.
2. Finished Product Preservatives
a. Usage
Pentachlorophenol is used as a fungicide and preservative in
adhesives and sealants (sodium and potassium salts), latex
paints, rubber articles (sodium salt), defoaming agents
(sodium salt), paper coatings (sodium salt), polyvinyl chloride
emulsions in food related products (sodium salt), zinc-silicone
dioxide matrix coatings in reusable bulk food storage containers
(sodium salt) and water-based gasketing compounds for food
applications (sodium salt). Pentachlorophenol is incorporated
directly to the products during their manufacture. Sodium
pentachlorophenol, and some other salts, are used as
preservatives in photographic developing solutions. Sodium
pentachlorophenol is used as a preservative for cements used
in food can ends and seams. Pentachlorophenol is also registered
as a preservative of feathers.
III-4
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The 1979 usage estimates indicate that less than one million
pounds of pentachlorophenol is used as a finished product
preservative. Data indicate that pentachlorophenol is not
extensively used in polyvinyl chloride emulsions. Pentachloro-
phenol is not used in paper coatings (sodium and potassium
salts) , zinc-silicone dioxide coatings in reusable bulk food
storage containers (sodium and potassium salts), rubber
articles (sodium salt), defoamers (sodium and potassium
salts). Annual use information for the can and end seal
cements is proprietary. No viable alternatives for the
gasket use appear to be available. Data indicate that only
9 pounds of pentachlorophenol were used in photographic
solutions in 1981. No production of pentachlorophenol con-
taining products is indicated for the feather use.
b. Alternatives
Alternatives for the use of this chemical in adhesives and
latex paint include o-phenylphenate, sodium o-phenylphenate,
ammonium benzoate, boric acid, tetrahydro-3,5-dimethyl-2H-
1,3,5-thiadiazine-2-thione. Alternatives for casein adhesives
include esters of p-hydroxybenzoate, sodium fluoride and
borax. Alternatives for protein adhesives include phenyl-
phenols, copper naphthenate, tributyltin oxide and copper-8-
quinolinolate. Alternatives for starch adhesives are borax,
formaldehyde, copper sulfate, zinc sulfate, zinc benzoate
and zinc fluoride. Many of these chemicals are approved by
FDA for use in food packaging materials (21 CFR 175.105).
Comparative efficacy data are generally unavailable for
adhesives. No critical use for pentachlorophenol can be
identified at this time.
Alternatives for latex paints include mercurial biocides,
carbon disulfide-derived compounds, chlorinated alkylthio
compounds, and a quaternary salt of 1,3-dichloropropene. The
following compounds provide mildewcidal protection on painted
surfaces: barium metaborate, cuprous oxide, copper-8-
quinolinolinate, bis(tri-n-butyltin)oxide and several
phthalimides. Comparative efficacy data are generally
unavailable for paint applications. No critical use for
pentachlorophenol can be identified at this time.
Alternatives for the defoamer uses (in paper manufacturing
chemicals) include: formaldehyde, b-naphthol, parachlorometa-
cresol, potassium trichlorophenate, o-phenylphenol, sodium
2-mecaptobenzothiazole, sodium o-phenylphenate, sodium
trichlorophenate.
There are no registered alternatives for photographic solution
preservation. Control measures generally involve good house-
keeping practices, filtration of process solutions and use of
chlorinating agents. Eastman Kodak exports a formaldehyde
releasing compound for this use.
111-5
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Paraformaldehyde, sodium orthophenol tetrahydrate, and zinc
dibutyldithiocarbamate are alternatives which are permitted
by FDA for food related products (21 CFR 175.300 and 177.1210)
The only registered alternative for paper and paper board is
barium metaborate. Other non-registered alternatives for
paper coatings that are approved by FDA (21 CFR 176 170
and 176.180) include: bis-(trichloromethyl)-lauramide, borax,
boric acid, 2-brorao-4'-hydroxyacetophenone, copper-8-quinolinate,
dihydroxy dichlorodiphenyl methane, formaldehyde and sodium
o-phenylphenate. FDA-approved alternatives for use in can
end and seam cements include paraformaldehyde, sodium
o-phenolphenate tetrahydrate, and zinc dibutyldithiocarbamate.
Data indicate that FDA-approved alternatives are not as
effective as pentachlorophenol in the gasket use. Substitution
of plastisol and other gasketing material for natural rubber
latex precludes the need for biocides in certain applications.
c. Economic Impact
The Agency believes that the cancellation of these uses will
not result in significant economic impacts based on the low
usage and the small cost differences between alternatives and
pentachlorophenol.
3. Working Solutions and Finished
Product Preservatives
Pentachlorophenol controls microorganisms in working solutions
and imparts a preservative action on finished products.
a. Usage
Pentachlorophenol and its sodium salt is used to control
bacterial and fungal growth in working fluids and process
chemicals in the textile industry, including the production
of rope and cordage. These chemicals preserve starch-sized
goods in storage, starch-sized kraft cord and natural fibers
in carpeting, and textile finishing for temporary and long
term mildew protection (pentachlorophenol only) protection.
These chemicals are manually or mechanically added to process
solutions and are mechanically applied to finished products.
Sodium pentachlorophenol controls microbial growth in pulp and
paper mill solutions and in the final product. This chemical
is applied by continuous feed, intermittent feed, slug feed,
drip feed or chemical pump feed into the pulp or white water
slurry. Dry powder and briquette formulations are applied by
hand. *
Pentachlorophenol and its sodium salt control microorganisms
in leather tannery solutions and final products. While it may
be used alone, these chemicals are most commonly used in
III-6
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combination with 2,4,5-trichlorophenol to provide greater
biocidal activity, although either may be used alone. These
biocides are applied by slug dosing, gravity feeding or metered
pumping, or poured directly into various tannery industrial
process solutions. Workers, who usually wear protective
clothing in the workplace, are exposed to working tannery
solutions containing dilute concentrations of these biocides.
Textile use of sodium pentachlorophenol dropped from 150,000
pounds in 1978 to 40,000 pounds in 1981. No data are available
to indicate that pentachlorophenol is used on rope and cordage,
while pentachlorophenol and its laurate salt are utilized on
tentage, awnings and tarpaulins. Data indicate that leather
usage has dropped dramatically between 1978 and 1981.
b. Alternatives
Alternatives for the textile use include sodium-o-phenylphenate
(tetrahydrate), and 1-(3-chlorallyl)-3,5,7-triaza-l-azoniada-
mantane chloride. Alternatives for process fluids include
6-acetoxy-2,4-dimethyl-m-dioxane, and potassium sorbate.
Short-terra mildew protective alternatives include sodium-o-
phenylphenate (tetrahydrate), and potassium sorbate. Long
term protective alternatives include copper-8-quinolinolate,
dichlorophene, copper naphthenate, mercurials, copper-zirconia,
alkyl ammonium naphthenate, benzimidazole, and isothiazolinone.
Limited data indicate that the textile process fluid
alternatives are not as effective as sodium pentachlorophenate.
Chlorinated phenols and dichlorophene provide effective
microorganism control but do not have the broad spectrum
activity of the mercurials. Copper-8-quinolinolate is a
suitable alternative only for dark fabrics. Dichlorophene has
a disadvantage of crystalizing and leaching out of the treated
material.
Methylene bisthiocyanate is a widely used registered alternative
which is cleared by the Food and Drug -Administration for
contact with food. Nabam and 2,2 dibromo-3-nitrilopropionamide
are also alternatives for use in pulp and paper mills.
The most frequently used alternatives for the tannery use are
Amical 48, Busan 30, Busan 72, Kathon LP and Kito 40. Other
alternatives, which may or may not be adequate replacements
for all uses within the industry include alkyl dimethyl
benzyl ammonium chloride, Cyncal®, Hyamine 3500®, paranitro-
phenol, sodium silicoflouride, nitrobenzene and chlorine.
Comparative efficacy data suggest that no single alternative
provides equivalent efficacy against bacteria and fungi as
the pentachlorophenol/2,4,5-trichlorophenol combination.
III-7
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c. Economic Impact
Short term annual estimates in control costs are estimated
to range from $120,000 to $1,000,000 for the textile finishing
industry and $350,000 for the tannery industry. Data indicate
that tannery usage has dramatically dropped between 1978 and
1981. Neither industry would experience a major impact by
cancellation of pentachlorophenol.
4. Marine Anti-Fouling Agents
These products contain pentachlorophenol not for preservation
of the product, but for microorganism control on the treated
surface to which the product is applied.
a. Usage
Pentachlorophenol is currently registered for use in marine
anti-fouling paints and marine bedding/double planking
compounds. These formulations are applied as a coating on
treated surfaces. Usage information indicates that very
small quantities of pentachlorophenol, approximately 2800
pounds A.I., were used in the U.S. in 1981 for both marine
uses.
b. Alternatives
Chemicals which may be substituted in the anti-fouling paint
uses of these products include arsenic trioxide and
bis (tributyltin) oxide. Alternatives which may be used in
the planking compounds include copper naphthenate, bis
(tributyltin) oxide, calcium carbonate, diiodomethyl para-
tolyl sulfone and cuprous oxide. No precise data is available
on the comparative efficacy of these compounds with penta-
chlorophenol. Some industrial representatives indicate that
biocides are not needed in caulking compounds.
c. Economic Impact
There will be little to no economic impact for the affected
industries if pentachlorophenol were cancelled based on the
low usage and availability of alternatives.
5. Mushroom Houses
a. Usage
Sodium pentachlorophenate is used to control microorganisms in
mushroom houses, lofts, compost wharfs, tools and sheds of
the mushroom industry. Due to its phytotoxicity, care must
be observed in this use to avoid contact with mushrooms.
Exposure is primarily inhalation and dermal, resulting from
spraying of facilities and dipping of tools, respectively.
III-8
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b. Alternatives
Alternatives include sodium chloride for non-corrosive sites,
broad spectrum disinfectants for tools and steam for interiors,
but not lofts.
Sodium chloride is highly corrosive to equipment and metal
parts of buildings. Sodium chloride does not have the broad
spectrum activity of sodium pentachlorophenol.
Current estimates of pentachlorophenol usage in the mushroom
industry range from 7,000 to 9,000 pounds.
c. Economic Impact
Cancellation of this use would affect one-third of the U.S.
mushroom production. Both the quality and quantity of a
small portion of the mushroom crop would be affected by
cancellation. Estimates by the United States Department of
Agriculture in 1980 indicate that yield and quality losses
would amount to only 0.00045 percent of the $120 million
revenue from the affected production. The majority of the
mushroom crop is produced without this chemical. The loss of
revenue would probably have a minor impact, relative to the
value of affected produce.
6. Construction Materials
a. Usage
Pentachlorophenol and its sodium salt are currently registered
for use as a mildewicide on a variety of construction materials.
These materials include: construction boards, insulation
construction paper products, brick and concrete surfaces,
caulks and sealants, polyvinyl and acrylic latex products
(spackling), and polysulfide grouts. Construction material
usage appears to be low.
b. Alternatives
Alternatives to these uses are limited. The alternative for
sodium pentachlorophenol in the construction board use is
Amical 50. This chemical is incorporated into the construction
board. Alternatives for pentachlorophenol in insulation
include boric acid. Boric acid, while used as a fire retardant
in insulation, does have some biocidal properties.
Information available to the Agency indicates that construction
roofing products contain unspecified biocides other than
pentachlorophenol and that one manufacturer uses a mildewicidal
zinc-copper based paint. No alternatives for pentachlorophenol
are available for use on brick and concrete surfaces.
Alternatives to pentachlorophenol use in caulks and sealants
III-9
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include: Troysan 174, Amical 50, and Dowicide A. No alternatives
are available for the spackling compound, caulking or polysulfide
grout uses of pentachlorophenol. No comparative evaluation
of the efficacy of these compounds has been made at this
time.
c. Economic Impact
The Agency has no data indicating any usage of pentachlorophenol,
or its salts, for the above uses. Therefore, there is no basis
for assuming that there would be any economic impact to this
industry.
D. Mossicide Use
Areas of the northwestern United States are especially
susceptable to growth of moss because the conditions of high
humidity and low sunlight favor the growth of these organisms
in these geographic areas. The "moss" which infests roofs
is a lichen and the moss which infests lawns is a true plant.
1. Usage
A granular form of this chemical is applied by hand spreader
to control moss on dormant lawns. Moss lawn control formu-
lations usually contain fertilizer plus pentachlorophenol.
The sodium salt of pentachlorophenol is also applied by
knapsack spray and brush to control lichens on roofs, masonry
and wooden structures.
2. Alternatives
The most likely alternative for lawn moss control to the
present penta-ferrous ammonium sulfate fertilizer (FAS)
formulation are FAS-fertilizer combinations. These combinations
require an additional application, though, to obtain equivalent
effectiveness of moss control. Additional alternatives
include: ferric sulfate, ferrous sulfate heptahydrate, zinc
chloride, zinc sulfate, and copper sulfate. Alternatives
are not as efficaceous as pentachlorophenol. There are
few data on relative efficacy for non-lawn sites.
3. Economic Impact
Pentachlorophenol is still used for moss control. The extent
of use of these chemicals is believed to be limited to western
Washington and Oregon. Lawn use in these areas may be
substantial because climatic conditions favor growth of this
pest. United States Department of Agriculture (USDA) estimated
in 1980 that the maximum total additional labor cost would not
exceed $1.375 million per year. The impacts of cancellation
would be greatest in the northwestern States where infestations
are most severe. Considering the limited number of alternatives,
111-10
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cancellation of these uses may result in a locally significant
economic impact.
E. Defoliant
1. Usage
Pentachlorophenol is a seed crop harvesting aid for alfalfa
(nonfood). This chemical is also registered on clover (alsike,
ladino, red and sweet), birdsfoot trefoil, and lespedeza.
This chemical is applied with low volume tractor booms.
2. Alternatives
Alternatives include: endothall, sodium chlorate, cacodylic
acid, s,s,s-tributylphosphorotrithioate, ametryn, and paraquat.
The alternatives are as effective as pentachlorophenol.
3. Economic Impact
Several alternatives are less expensive than pentachlorophenol.
Little to no economic impact is expected from cancellation
of this use.
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IV. Development of Regulatory Options
A. Introduction
In parts II and II, the Agency identified the risks and
benefits of the non-wood uses of pentachlorophenol. As
explained in Part I, FIFRA requires the Agency to determine
if the use of a pesticide meets the statutory standard for
registration by balancing the risks and benefits of use. To
carry out this mandate, the Agency has developed a range of
regulatory measures which are intended to reduce the risks of
use for the pesticide under review. This part discusses the
factors which have been taken into account in developing the
regulatory options for the non-wood preservative uses of
pentachlorophenol and describes in detail those measures
selected for further consideration in Part V.
B. Basis and Rationale for Developing Options and
Modifications
There are three basic options for regulating all pesticides:
Option 1 - Continuation of Registration without Changes
Option 2 - Continuation of Registration with
Modifications to the Terms and Conditions
of Registration
Option 3 - Cancellation of Registration
The two extreme options, Option 1, Continuation of Registration
without Change and Option 3, Cancellation of Registration,
are at the opposite ends of the risk/benefit spectrum.
Adoption of Option 1 would be appropriate when the Agency
has concluded that the level of risk is acceptable in light
of the pesticide's benefits and that further risk reduction
measures are not necessary to assure that the use of the
pesticide meets the statutory standard for continued
registration.
Adoption of Option 3, cancellation, would be appropriate
when the Agency has concluded that the risks from a use
outweigh the benefits of that use, and that these risks cannot
be mitigated to an acceptable level, in light of the benefits,
by any other measures short of cancellation. Cancellation
prohibits the sale or the distribution of a pesticide for a
particular use or uses. The effect of cancellation is to
entirely eliminate the risks of a pesticide's use or uses as
well as the benefits. Cancellation may affect all uses of a
compound, only specific uses or specific formulations, or
specific application methods.
The middle option, Option 2, is appropriate when the risks
of a pesticide use can be reduced to an acceptable level
IV-1
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while preserving the benefits of the use. This risk reduction
is accomplished by modifying the terms and conditions of the
pesticide's registration. These modifications, which are
expressed through the pesticide's labeling are, for the most
part, changes in the way the pesticide is used. These changes
are designed to reduce exposure to the pesticide, and thereby
reduce or even eliminate the risk from the pesticide.
C. Discussion of Option 2, Modifications to the Terms and
Conditions of Registration
The specific risk reducing modifications which the Agency has
selected for further consideration are presented in this section.
a. Require Protective Clothing: Impermeable Gloves
To reduce the risk caused by dermal exposure for the non-wood
uses of pentachlorophenol, the Agency would require that all
applicators using pentachlorophenol must wear gloves impervious
to this pesticide in all situations where dermal contact with
pentachlorophenol is possible.
This modification would require applicators to wear gloves
made of material impervious to pentachlorophenol when involved
in the mixing and application of pentachlorophenol. Applicators
would also wear gloves when cleaning application equipment
such as brushes. This protective clothing modification would
apply to all non-wood uses of pentachlorophenol and all
applicators where dermal contact is expected. Acceptable
materials for gloves include polyvinyl chloride, polyvinyl
acetate, neoprene, NBR (Buna-N), and nitrile.
b. Require Protective Clothing: Coveralls
This modification would require persons applying pentachlorophenol
to wear protective clothing, such as disposable coveralls, to
reduce risks to a greater degree than the risk reduction from
gloves alone. This modification would apply to all non-wood
uses of pentachlorophenol.
c. Disposal of Protective Clothing
This modification would require applicators of pentachlorophenol
to: change protective clothing showing obvious signs of
contamination; launder non-disposable clothing separately
from other household clothing; clothing and workshoes or
boots must be disposed of in any general landfill, in the
trash, or in any other manner approved for pesticide disposal.
IV-2
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d. Require Protective Clothing: Respirators
This modification would require that applicators involved in
spraying pentachlorophenol products wear respirators. Use sites
where these products can be applied by spray are: mushroom
houses and mossicide (application to roofs).
Proper use of respirators would be expected to reduce high
inhalation exposure during application. The use of a half-
mask canister or cartridge respirator capable of trapping
pesticide particulates and vapors would reduce potential
inhalation by about 90%.
e. Prohibit Eating, Drinking and Smoking During Application
This modification would prohibit eating, drinking, and smoking
during the application of pentachlorophenol products registered
for non-wood uses.
f. Restricted Use
The Agency is concerned about the possibility of high exposure
to applicators who have not been properly trained in the safe
handling procedures for formulations of pentachlorophenol
products which could be obtained "over-the-counter." Of
concern to the Agency is the potential for high exposure to
products requiring spraying and to products requiring mixing
and/or diluting where there could be some splashing of the
formulation resulting in dermal and inhalation exposure.
To protect the applicator from these potentially high exposures
to pentachlorophenol products, the Agency would require that
the sale and use of pentachlorophenol products be restricted
to certified applicators or by persons under their direct
supervision and only for those uses covered by the certified
applicator's certification.
IV-3
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g. Reduce Contaminants in Penta
This modification would require reduction in the level of the
hexachlorodibenzo-p-dioxin (HxCDD) contaminants in all penta
products. The HxCDD contaminant, which has been shown to be
teratogenic and oncogenic in test animals, is formed in
technical penta and its salts during the manufacturing process
The Agency also would require, as it did in the PD-4 of the
Wood Preservatives document of July, 1984, that the method
used by registrants to lower the HxCDD contamination must not
increase the HCB contamination.
The Agency believes that it is prudent and reasonable to
require that registrants reduce HxCDD, and not increase the
chlorinated dibenzofurans and HCB contaminants in pentachloro-
phenol and sodium pentachlorophenate products to protect the
public from potential unreasonable adverse effects. Theoret-
ically, these three impurities can be reduced by the same
purification or extraction process during manufacturing
(Dodd, 1984). By reducing the HxCDD from 15 ppm to 1.0 ppm,
the potential oncogenic risks to applicators would be reduced
by more than an order of magnitude.
The most highly toxic dioxin is 2,3,7,8-tetrachlorodibenzo-p-
dioxin (TCDD) (Nicholson and Moore, 1979). Although it has
not been found in analyses of samples of pentachlorophenol
(Buser and Bosshardt, 1976; SAB, 1978; Rakshpal, 1980), the
Agency would require registrants to amend the confidential
statements of formula to indicate that 2,3,7,8-tetrachloro-
dibenzo-p-dioxin (TCDD) is not found in pentachlorophenol
products or products containing salts of pentachlorophenol.
IV-4
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V. Proposed Regulatory Decision
As stated in Part IV, the Agency has developed three basic
regulatory options to be considered with respect to the non-wood
uses of pentachlorophenol:
1. Continuation of registration without changes.
2. Continuation of registration with modification
to terms and conditions of registration.
3. Cancellation of registration.
A. Herbicidal Uses
Pentachlorophenol products are registered for a variety
of herbicidal uses: greenhouses, ornamental lawns and edging,
rights-of-way, commercial and industrial non-crop areas, domestic
dwellings, public facilities, golf courses and sand traps,
wasteland areas and aquatic areas.
If registrations of pentachlorophenol products were continued
without restriction both commercial applicators as well as home-
owners would continue to be exposed via spray treatments and
at risk to cancer and possible fetotoxic effects. The benefits
associated with this use are inconsequential because of the
numerous alternatives available, some of which are less costly
than pentachlorophenol and of equal or greater efficacy.
If registrations of pentachlorophenol products were continued
with amended terms and conditions the following provision would
apply: all applicators would be required to be certified and
to wear respirators and impermeable gloves. Also, HxCDD content
would be required to be reduced to 1 ppm. Exposure and
subsequent health risks would be reduced but the risks would
still outweigh the benefits for this use.
If registrations of pentachlorophenol products for this
use were cancelled, all risks to the applicators and homeowners
from these products would be eliminated. Cancellation of this
use would have no economic impact.
Although the risks cannot be quantified, they are considered
to be high based on the method of application. Although the
risks could be reduced for applicators by requiring respirators
and impermeable gloves, the virtual absence of benefits supports
the finding that the benefits are outweighed by the risks or
continued use in either Option 1 or 2. Therefore, the Agency
proposes to cancel the use of pentachlorophenol for use as a
herbicide in greenhouses, ornamental lawns and edging, rights-of way,
commercial and industrial non-crop areas, domestic dwellings,
public facilities, golf courses and sand traps, wasteland
areas and aquatic areas.
V-l
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B. Antimicrobial Uses
1. Working Solutions
a. Oil Well Water
Sodium pentachlorophenate controls microorganism growth
in oil well flood waters. Application into oil well flood
waters is by injection pump. There is negligible exposure
from this use. There are numerous alternatives to penta-
chlorophenol for this use but comparative on-site efficacy
data for the alternatives are not available.
Having evaluated the cancer and fetotoxic risk associated with
this use of pentachlorophenol products, the Agency has determined
that the benefits outweigh the risks. The Agency proposes
to continue the registration for use of pentachlorophenol as
an anti-fungal agent in oil well flood waters but amend the
terms and conditions of the registration to require that
impermeable gloves be worn during the handling of pentachlorophenol
and that the HxCDD content be required to be reduced to 1 ppm.
&• Evaporative Condensers, Air Washers,
Cooling Towers
Sodium pentachlorophenate controls microorganism growth
in evaporative condensers, cooling waters, air washers, and
cooling towers. Application for evaporative condensers is
by hand or pump system. Penta-containing briquets are applied
by hand into air washer systems while application at cooling
towers is by hand, drip feed, continuously or intermittently
pumped into recirculating waters.
Continued registration of penta for these uses without
restriction would result in dermal exposure to applicators.
The MOS for fetotoxic effects for penta is 20 and for HxCDD
the MOS values are .87 (15 ppm HxCDD) and 13 (1 ppm HxCDD).
The oncogenic risk estimates are: using daily lifetime
HxCDD exposure, 7 x 10~1 (15 ppm HxCDD) and 5 x 10~2 (1 ppm HxCDD);
using average daily lifetime HxCDD exposure, 3 x 10~2 (15 ppm HxCDD),
and 2 x 10~3 (1 ppm HxCDD). Usage data from 1981 indicate
the only 12,000 Ibs. of penta were used, at all three sites.
The Agency has determined that the economic impacts of cancellation
of this use to be small based on low usage and the availability
of alternatives.
Amending the registration of these uses to require appli-
cator certification and impermeable gloves would reduce exposure
and subsequent risks by 90%. Also, the HxCDD content would be
required to be reduced to 1 ppm. Even with this reduction,
the risks would remain significant.
If registrations of pentachlorophenol products for this use
were cancelled, all risks to the applicators would be eliminated.
Cancellation of this use would have no economic impact.
Although the risks could be reduced for applicators, the virtual
absence of offsetting benefits requires a finding that the
V-2
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benefits are outweighed by the risks of continued use in either
Option 1 or 2. Therefore, the Agency proposes to cancel the
use of penta products as antimicrobial agents in evaporative
condensers, cooling towers, and air washers.
2. Finished Product Preservatives
a. Adhesives/Sealants; Canning/Sealing
Products containing pentachlorophenol are used as fungicides
and preservatives in adhesives/sealants, and canning/sealing
operations. If registration of these products were continued with-
out restriction, applicators would continue to be exposed dermally
to this chemical. The MOS for fetotoxic effects for penta
is 120 and for HxCDD the MOS values are 5.1 (15 ppm) and 77
(1 ppm). The oncogenic risk estimates using daily HxCDD
exposure are 1 x 10~1 (15 ppm) and 8 x 10~3 (1 ppm); using average
lifetime HxCDD exposure the respective risk estimates are:
3 x 10~2 and 2 x 10~3. Also, there is potential dietary exposure
to pentachlorophenol from this use since the adhesives and
sealants are used in food packaging materials.
The Agency has determined that the economic impacts of
cancellation of this use are insignificant based on low usage
and the numerous alternatives available.
Amending the registration of these uses to require appli-
cator certification and impermeable gloves would reduce dermal
exposure and subsequent risks by 90%. Also, the HxCDD content
would be required to be reduced to 1 ppm. However, potential
dietary exposure would remain a concern.
If registrations of these products were cancelled for this
use, all risks to applicators would be eliminated and there
would be no potential dietary exposure. Cancellation of this
use would not have a significant economic impact.
Although the risks could be reduced for applicators and the
dietary risks are not capable of quantitation, the virtual
absence of offsetting benefits requires a finding that the
benefits are outweighed by the risks of continued use in
either Option 1 or 2. Therefore, the Agency proposes to
cancel the use of the pentachlorophenol products for use in
adhesives and sealants.
b. Gaskets
If unrestricted registration of this use were continued
applicators would be exposed dermally to pentachlorophenol.
Also, there is potential dietary exposure to pentachlorophenol
V-3
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from this use since the penta-treated gaskets are used in food
related products. Although exposure and risk estimates have
not been determined for this use, the Agency assumes they
would be similar to those for adhesives/sealants and the
canning/sealing use. The benefits associated with this use
are inconsequential because substitution of plastisol and
other gasketing material for natural rubber latex precludes
the need for biocides (i.e. penta). Alternatives exist and
there is a low usage of penta products in gaskets.
Amending registration of this use to require applicator
certification and impermeable gloves would reduce exposure
and subsequent risks by 90%. Also, the HxCDD content would be
required to be reduced to 1 ppm. The risks would still be
very high and would outweigh the benefits for this use.
If registrations of these products were cancelled for this
use, all risks to applicators would be eliminated. Cancellation
of this use would not have a significant economic impact based
on low usage.
Although the risks could be reduced for applicators and the
dietary risks are not capable of quantitation, the virtual
absence of offsetting benefits requires a finding that the
benefits are outweighed by the risks of continued use in
either Option 1 or 2. Therefore, the Agency proposes to
cancel this use of pentachlorophenol.
c. Photographic Developing Solutions
If unrestricted registration of this use were continued
applicators would be exposed dermally to pentachlorophenol.
Although exposure and risk estimates have not been determined
for this use, potential user exposure and subsequent risk
could be high due to the film developing process and closed
room environment. The benefits associated with this use are
not siginificant because of the low usage. Only 9 pounds of
pentachlorophenol were used in photographic solutions in
1981, the last year for which data are available.
Amending registration of this use to require applicator
certification and impermeable gloves would reduce exposure
and subsequent risks by 90%. Also, the HxCDD content would be
required to be reduced to 1 ppm. The risks would still be
high and outweigh the benefits for this use.
Cancellation of this use would eliminate all risks associated
with this use without significant economic impact.
Although the risks could be reduced for applicators through
the use of impermeable gloves, the virtual absence of offsetting
benefits requires a finding that the benefits are outweighed
by the risks of continued use in either Option 1 or 2.
The Agency proposes to cancel the use of pentachlorophenol
in photographic developing solutions.
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d. Other Uses
There is negligible usage for the remaining registered
penta uses (latex paint/rubber, defoaming agents, paper coatings,
polyvinyl chloride emulsions, zinc-silicone dioxide coatings,
and feathers). The benefits associated with the continued use
of these products are insignificant. Exposure and risk estimates
have not been determined for these uses due to a lack of usage
data. However, it is believed that there is a potential for
significant risk to applicators and users is based on the exposure
patterns for other industrial uses of penta. In view of the absence
of significant benefits, the Agency proposes to cancel the
uses of penta in or on latex paints/rubber, defoaming agents,
paper coatings, polyvinyl chloride emulsions, zinc-silicone
dioxide coatings, and feathers.
3. Working Solutions and Finished Product
Preservatives
a. Textile/Cordage
Pentachlorophenol and its sodium salt is used to control
bacterial and fungal growth in working fluids and process
chemicals in the textile industry. If registrations of these
products were continued without restriction, applicators would
continue to be exposed dermally to this chemical. The MOS
for fetotoxic effects for penta is 120 and for HxCDD the MOS
values are 5.1 (15 ppm) and 77 (1 ppm). The oncogenic risk
estimates using daily HxCDD exposure are 1 x 10~1 (15 ppm) and
8 x 10-3 (i ppm); using average lifetime HxCDD exposure the
respective risk estimates are 4 x 10~2 and 2 x 10~3.
Amending the registration of this use to require applicator
certification and impermeable gloves would reduce exposure and
subsequent risks by 90%. Also, the HxCDD content would be required
to be reduced to 1 ppm.
The benefits associated with this use are not significant
since usage is low and there are available alternatives. No
data are available to indicate that penta is used on rope and
cordage; however, it is utilized on tentage, awnings and
tarpaulins.
Cancellation of this use would eliminate all risks and
result in short term annual increases in control costs from
$120,000-31,000,000 for the entire textile finishing industry.
Although the risks could be reduced for applicators through
the use of impermeable gloves, the virtual absence of offsetting
benefits requires a finding that the benefits are outweighed
by the risks of continued use in either Option 1 or 2.
Therefore, the Agency proposes to cancel the use of pentachlorophenol
products for use in the textile/cordage industry.
V-5
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b. Pulp/Paper Mills
Sodium pentachlorophenol controls microbial growth in
pulp and paper mill solutions and in the final products. This
chemical is applied by continuous feed, intermittent feed,
slug feed, drip feed, or chemical pump feed into the pulp or
white water slurry. There is negligible exposure from this
use. Alternatives to this use are available.
Having evaluated the cancer and fetotoxic risk associated
with this use of pentachlorophenol products, the Agency has
determined that the benefits outweigh the risks. The Agency
proposes to continue the registration of pentachlorophenol
for use to control microbial growth in pulp and paper mills
but amend the terms and conditions of the registration to
require that impermeable gloves be worn during handling of
pentachlorophenol and that the HxCDD content be required to be
reduced to 1 ppm.
c. Leather Tannery
Pentachlorophenol and its sodium salts are used to control
microorganism in leather tannery solutions and final products.
Unrestricted registration of this use of pentachlorophenol
would result in dermal exposure to applicators during the
various operations in the leather tanning process. There is
also a potential for dietary exposure to penta as a result
of its use in the tanning industry. Fleshings from penta-
treated hides are sold to Tenderers who then in turn sell
the fleshings for incorporation into animal/poultry feed.
If unrestricted registration of this use were to continue,
applicators would be dermally exposed to pentachlorophenol through-
out the various operations in the leather tanning process.
The MOS values for both penta and HxCDD are greater than
10,000 for all operations except the biocide/application step.
For this process the MOS values are 120 for penta and 5.1 and 77
for 15 ppm and 1 ppm HxCDD, respectively. The oncogenic risks
range from 10~5 to 10~8 for all operations except the biocide/
applicatin step using daily lifetime exposure and average daily
lifetime exposure of HxCDD. For the biocide/application step
in the tanning process, the oncogenic risks are: using daily
lifetime HxCCD exposure, 1 x 10~1 (15 ppm) and 8 x 10~3 (i ppm); using
average daily lifetime HxCDD exposure, 3 x 10~2(i5 ppm) and
2 x 10-3 (i ppm).
If the registration of the products were amended to require
that all applicators would be required to be certified and
persons working in the tanneries wear impermeable gloves, the
exposure would be reduced by 90%. Also, the HxCDD content would
be required to be reduced to 1 ppm. However, dietary exposure
would still be a concern.
If this use of pentachlorophenol were cancelled, all exposure
and subsequent risk would be eliminated.
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Cancellation of this use would eliminate all exposure
and subsequent risk. Tannery use of sodium pentachlorophenol
dropped from 150,000 Ibs in 1978 to 40,000 in 1981. Alternatives
are available and in use. Short term annual estimates in control
costs are estimated at $350,000 for the tanning industry.
Having evaluated the fetotoxic and oncogenic risks associated with
this use of pentachlorophenol, the Agency has determined that the
risks outweigh the benefits in Options 1 and 2. The Agency
proposes to cancel the use of pentachlorophenol for use in
the tanning industry.
4. Marine Anti-Fouling Agents
Marine Caulking/Marine Paints
Pentachlorophenol is registered for microorganism control
on the treated surface to which the product is applied. These
formulations are used in marine anti-fouling paints and marine
bedding/double planking compounds. These formulations are
applied as a coating on treated surfaces. Approximately 2800
pounds AI were used in 1981 for use in both marine caulking
and marine paints.
If registration of pentachlorophenol products were continued
without restriction, applicators would continue to be exposed
dermally during the manufacturing and use of marine caulking
compounds. The MOS values for marine caulking are: 110 for
manufacturing of caulking (penta) , 4.8 and 3.2 (15 ppm HxCDD),
72 and 48 (1 ppm HxCDD). No exposure information is available
from the marine paint use. The oncogenic risks associated with
the manufacture of marine caulking are: using daily HxCDD exposure,
1 x 10"1 (15 ppm) and 9 x 10~3 (1 ppm); using average daily HxCDD
exposure, 3 x 10~3 (15 ppm) and 2 x 10~4 (1 ppm). The oncogenic
risks associated with the use of marine caulking are: using
daily HxCDD exposure, 2 x 10~1 (15 ppm) and 1 x 10~2 (1 ppm);
using average daily lifetime HxCDD exposure, 8 x 10~3 (15 ppm) and
8 x 10-4 (i
Amending the registration of this use would require
applicators to be certified and wear impermeable gloves.
Exposure and subsequent health risks would be reduced by 90%.
Also, the HxCDD content would be required to be reduced to 1 ppm.
If registration of these products were cancelled for this
use, all risks to applicators would be eliminated. Alternative
chemicals are available and in use. The economic impact would
be insignificant.
Having evaluated the fetotoxic and oncogenic risks associated
with this use of pentachlorophenol, the Agency has determined
that the risks outweigh the benefits in Options 1 and 2.
The Agency proposed to cancel the use of penta in marine
caulking and marine paints.
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5. Mushroom Houses
Sodium pentachlorophenate is used to control microorganisms
in mushroom houses, lofts compost wharfs, tools and sheds
in the mushroom industry. Exposure is primarily inhalation
and dermal, resulting from spraying facilities and dipping
of tools, respectively. Alternatives include sodium chloride
for non-corrosive sites, and broad spectrum disinfectants
for tools and steam for interiors, but not lofts. Sodium
chloride is highly corrosive to equipment and metal parts of
building nor does it have broad spectrum control activity
of sodium pentachlorophenate. Current usage estimates of sodium
pentachlorophenate in the mushroom industry range from 7000
to 9000 pounds.
If current registrations were allowed to continue, applicators
would be exposed to sodium penta dermally and through inhalation
as well. Also, potential dietary exposure to the general
population is possible through residues on mushrooms. The MOS
values for fetotoxic effects are: 9.1 (penta); 3.7 (15 ppm
HxCDD); and, 56 (15 ppm HxCDD). The oncogenic risks from
exposure to HxCDD are: using daily HxCDD exposure, 2 x 10"1
(15 ppm) and 1 x 10~2 (1 ppm); using average daily lifetime
HxCDD exposure, 8 x 10~3 (15 ppm) and 8 x 10~4 (1 ppm).
If registration of these products were continued with
amended terms and conditions, the following provisions
would apply: applicators would be required to be certified
and wear impermeable gloves and a respirator. Also, the HxCDD
content would be required to be reduced to 1 ppm. Exposure and
subsequent health risks would be reduced but potential dietary
exposure would remain a concern.
Cancellation of this use would eliminate all potential
exposure and subsequent risks and would affect one-third
of the U.S. mushroom production. However, estimates by the
United States Department of Agriculture in 1980 indicate
that yield and quality losses would amount to only 0.00045% of
the $120 million revenue from the affected population.
Having evaluated the fetotoxic and oncogenic risks associated
with this use of pentachlorophenol, the^Agency has determined
that the risks outweigh the benefits in" Options 1 and 2. Therefore,
the Agency proposes to cancel the mushroom house use of
pentachlorophenol.
6. Construction Materials
Pentachlorophenol and its sodium salt are currently
registered for use as a mildewicide on a variety of construction
materials. The Agency has no data indicating any usage of
pentachlorophenol, or its salts, for any of the following uses
in construction materials: constructions boards, insulation
construction paper products, brick and concrete surfaces,
caulks and sealants, polyvinyl and acrylic latex products
(spackling) and polysulfide grouts. Due to a lack of usage
data, exposure cannot be evaluated. A qualitative assessment
of exposure indicates potential for high exposure. Several
V-8
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alternatives for use in the various construction materials
are available.
Cancellation of the use of pentachlorophenol in construction
materials would eliminate all fetotoxic and oncogenic risk
and would have no economic impact.
Having evaluated the fetotoxic and oncogenic risks associated
with this use of pentachlorophenol, the Agency has determined
that the risks outweigh the benefits in Options 1 and 2. Therefore,
the Agency proposes to cancel the use of pentachlorophenol as
a mildewicide in construction materials.
7. Mossicide
a. Roofs
The sodium salt of pentachlorophenol is applied by knap
sack spray and brush to control on roofs, masonry and wooden
structures. The extent of use of this chemicals is believed
to be limited to western Washington and Oregon. If registration
of the pentachlorophenol products were allowed to continue
without restriction, applicators would continue to be exposed
dermally and through inhalation. Risk estimates are high
with a MOS range of .18-13.0 for the formulator and .75-75.0
for the applicator (fetotoxic effects). Oncogenic risk
estimate ranges for formulators are: using daily lifetime
HxCDD exposure, 1.1 - 7 x 10~2; using average daily lifetime,
1 x 10~3 - 7 x 10~5. The oncogenic risk estimate ranges for
applicators are: using daily lifetime HxCDD exposure,
1 x 10~2 - 3 x 10~2; using average daily lifetime, 2 x 10 4-
3 x 10-5.
If registration of these products were continued with
amended terms and conditions, the following provisions would
apply: all for formulators and applicators to be certified
and wear impermeable gloves and respirators. This would
reduce exposure by 90%. Also, the HxCDD content would be
required to be reduced to 1 ppm.
Cancellation of this use would eliminate all risk but
could result in a significant economic "impact on the north-
western U.S. A limited number of alternatives all available.
Having evaluated the fetotoxic and oncogenic risk and
benefits associated with the use of pentachlorophenol, the
Agency has determined that in the absence of quantified
economic benefits, the risks outweigh the benefits.
Therefore, the Agency proposes to cancel this use of
pentachlorophenol.
V-9
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b. Lawns
A granular form of pentachlorophenol is applied by
spreader to control moss on dormant lawns. Moss lawn
control formulations usually contain fertilizer plus
pentachlorphenol. The extent of use of this chemical
is believed to be limited to western Washington and Oregon.
If registration of the pentachlorophenol products were
allowed to continue without restriction exposure to
applicators would be negligible due to the granular of the
product and application via a lawn spreader. Exposure and
subsequent risk to homeowners using a treated yard is also
thought to be negligible, although no exposure data are available.
Alternative are available but are not as efficacious as
pentachlorophenol. Cancellation of this use would eliminate
all risk but could result in a significant economic impact in
the northwestern U.S.
Having evaluated the risks and benefits associated with
this use of pentachlorophenol, the Agency has determined that
the risks, in the absence of quantifiable economic benefits,
are significant and outweigh the benefits. The Agency proposes
cancellation of the registration of this use of pentachlorophenol,
8. Defoliant
Pentachlorophenol products are registered for use as a
seed crop harvesting aid for alfalfa (non-food), clover,
(aslike, ladino, red, and sweet), birdsfoot trefoil, and
lespedza. The benefits for this use are insignificant because
less expensive alternatives of equal or greater efficacy are
available and its low usage. Dietary exposure as a result of
this use of pentachlorophenol may result.
Cancellation of this use would eliminate exposure and
subsequent risk of fetotoxic and oncogenic effects. The
Agency proposes to cancel the use of pentachlorophenol as a
defoliant.
Having evaluated the risks and benefits associated with this use
of pentachlorophenol, the Agency has determined that the risks
outweigh the benefits in Options 1 and 2.
-------
BIBLIOGRAPHY
American Wood Preservers Institute. Response of AWPI to U.S.
EPA's PD 1, OPP 30000/29: RPAR Inorganic Arsenicals, Pg. 154-192.
1979.
Boutwell, R.K. and O.K. Bosch., The Tumor-Promoting Action of Phenol
and Related Compounds for Mouse Skin. Cancer Res., 19: 413-424. 1959.
Buser, H.R. and H.P. Bosshardt. Determination of Polychlorinated
Dibenzo-P-Dioxins and Dibenzofurans in Commercial Pentachlorophenols
by Combined Gas Chromatography-Mass Spectrometry. Jour, of the Acad.,
59(3): pp.562-569. 1976.
Cabral, J.R.P. et. al., Carcinogenic Activity of Hexachlorobenzene in
hamsters. Nature, 269: 510-511. 1977.
Cabral, J.R.P. et. al., Carcinogenesis of Hexachlorobenzene in Mice.
Int. J. Cam, 23: 47-51. 1979.
Canellos, G. and N. Zank, An Overview of the Use of Pentachloro-
phenol at various industrial sites. The MITRE Corporation, McLean,
VA. Dec. 1981
Courtney, R.D., et. al ., The Effects of Pentachloronitrobenzene,
Hexachlorobenzene, and Related Compounds on Fetal Development.
Toxicol. Appl. Pharmacol., 35: 239-256. 1976.
Czerkowicz, T., Memorandum-Transmittal of Industrial (non-wood) Uses
of Pentachlorophenol, April 26, 1984.
Fahrig, R.C. Nilsson and C. Rappe. Genetic Activity of Chlorophenols
and Chlorophenol Impurities. Pentachlorophenol; Pentachlorophene
Chemistry, Pharmacology, and Environmental Toxicology. 325-338.
Plenum Press. New York and London. 1978.
Gibb, H.J. Memo concerning a Review of the Gilbert et al. Study
of Wood Treaters in Haiwaii to Amy Rispin U.S. EPA, Washington
D.C. December 21, 1983.
Goldgraben, R. et al., Use Profile and Exposure Assessment of Penta-
chlorophenol at Industrial Sites, The MITRE Corporation, McLean, VA.
Sept., 1981.
Goldgraben, R., Preliminary Benefits Analysis of 2,4,5-Trichloro-
phenol in Rayon Spinning and Textile Finishing, The Mitre Corporation,
McLean, VA. Jan., 1980.
Goldstein et. al., Effects of Pentachlorophenol on Hepatic Drug-
metabolizing Enzymes and Porphyria Related to Contamination with
Chlorinated Dibenzo-P-Dioxins and Dibenzofurans. Biochem. Pharmacol.,
26: 1549-1557. 1977.
Goldstein, J.A. Structure-Activity Relationships for the Biochemical
Effects of Halogenated Hydrocarbons and the Relationship to Toxicity.
-------
In R. Kimbrough (Ed.), Halogenated Biphenylsf Terphenyls, Naphthalenes,
Dibenzodioxins and Related Compounds. Esdvier, Amsterdam, The Nether-
lands. (In Press) 1980.
Grant, D.L. et. al., Effect of Hexachlorobenzene on Reproduction in
The Rat. Arch. Environ. Contain. Toxicol., 5(2): 207-216. 1977.
Hildebrandt, D.V.M. Letter Concerning the Development of
Proliferative Lesions in Female Rat Livers. Tracer Jitco. Inc.
October 31, 1983.
Hinkle, O.K. Fetotoxic Effects of PCP in the Golden Syrian Hamster.
Unpublished. 8 pp. Given at the 12th Annual Meeting of the Society
of Toxicologists. 1973.
Holsapple, M.P., J.A. Munson, et al. Immunosuppression by Selected
Hexachlorodibenzo-p-dioxins (HxCDD) in Adult Female B6C3F1 Mice.
Abstract, National Meeting Society of Toxicology, Atlanta, Georqia
(1984).
Innes, J.R.M. et. al., Bioassay of Pesticides and Industrial Chemicals
for Tumor Genicity in Mice: a Preliminary Note. J. Nat. Cancer Inst.,
42:1101-1114. 1969
Josephson, H.R. Economic, Social and Environmental Benefits From
Use of Wood Preservatives. Unpublished Report to the American Wood
Preservers Institute. Representative to AWPI, McLean, Va., 1979.
Johnson, R.L., P.J. Gehring, R.J. Kociba, and B.A. Schwetz.
Chlorinated Dibenzodioxins and Pentachlorophenol. Environ. Health
Perspect.,5:171-175. 1973.
Khera, K.S. Teratogenicity and Dominant Lethal Studies on Hexachloro-
benzene in Rats. Fd. Cosmet. Toxicol., 12: 471-477. 1974.
Kimbrough, R.D. and R.E. Linder., The Effect of Technical and Purified
Pentachlorophenol on the Rat Liver. Toxicol. Appl. Pharmacol., 46: 151-
162. 1978.
Knudsen, I. et. al. Short-Term Toxicity of Pentachlorophenol in Rats.
Toxicology, 2:141-152. 1974.
Kociba, R.J. et. al. Toxicological Evaluation of Rats Maintained on
Diets Containing Pentachlorophenol Sample XD-8108.00LO for 90 Days.
Report, DOW Chemical U.S.A. 1973.
Koss, G. et. al., Studies on the Toxicology of Hexachlorobenzene. III.
Observations in a Long-Term Experiment. Arch. Toxicol., 40: 285-294.
1978.
Kozak, V.P. et. al., Studies on the Toxicology of Hexachlorobenzene.
III. Observations in a Long Term Experiment. Arch. Toxicol., 40: 285-
294. 1978.
Larsen, R.V. et. al., Placental Transfer and Teratology of Pentachloro-
phenol in Rats. Environ. Letters, 10(2): 121-128, 1975.
-------
McConnell, E.E., J.A. Moore, J.K. Baseman, and M.W. Harris. The
Comparative Toxicity of Chlorinated Dibenzo-P-Dioxin Isomers in
Mice and Guinea Pigs. Unpublished. 59 pp.
McGaughy, Robert E. Transmittal of Arsenic Risk Calculations for
Wood Preservative Exposure. EPA Memo. April 24, 1984.
The Mitre Corporation., Interum Briefing- Impact Analysis for Cancel-
lation of ACA/CCA Preservatives for Treated Wood Used in Homes. EPA
Contract 68-01-5965 Task 17. (Unpublished). 1980.
Moore, Dr. J., EPA. Internal Memo To Dr. Donald Barnes Regarding
the McConnell NIEHS/NTP Reevaluation of the NCI Bioassay of
Haxachlorodioxin. Nov. 4, 1983.
National Cancer Institute and National Toxicology Program. Bio-
assay of a Mixture of 1,2,3,6,7,8, and 1,2,3,7,8,9-Hexachlorodibenzo-
p-dioxins for Possible Carcinogenicity. Department of Health and
Human Services Publication, (NIH 80-1754). 1980.
Noren, S., Aliette Exposure Assessment, Hazard Evaluation Division,
EPA, June 29, 1983.
Parker, N.B. et. al., Preliminary Benefits Analyses of 2,4,5-
Trichlorophenol and Pentachlorophenol for Industrial Water Treatment,
The MITRE Corporation, McLean, VA. April, 1980.
Poland, Alan, W.F. Greenlee, and A.S. Kende. Studies on the
Mechanism of Action of the Chlorinated Dibenzo-P-Dioxins and Related
Compounds. Annals of the New York Academy of Sciences. Vol. 320:
214-330. 1979.
Reece, M., Position Document 1 for 2,4,5-Trichlorophenol, Special
Review Division, EPA, August 16, 1978.
Rakshpal, R., EPA memo to SPRD. Impurities in Pentachlorophenol.
March 31, 1980.
Russell, L.S., Use Profiles and Alternatives Assessment for 2,4,5-
Trichlorophenol and Pentachlorophenols j.n Adhesives and Polyvinyl
Acetate Emulsions, The MITRE Corporation, McLean, VA. April, 1980.
Russell, L.S., Preliminary Benefit Analysis of 2,4,5-Trichlorophenol
and Pentachlorophenol in Taneries, The MITRE Corporation, McLean, VA,
Jan., 1980.
Saulmon, J.G., Biological Data Base for Exposure Analyses and Pre-
liminary Benefits Analysis of Pentachlorophenol and sodium penta-
chlorophenate. U.S. E.P.A., March 30, 1984.
Schwetz B A , J.F. Quast, p.A. Keeler, C.G. Humiston, and R.J. Kociba.
lesutts'of Two Year ?oxicity and Reproduction Studies on Pentachlorophe-
nols in Rats, in K.R. Rao (Ed.), Pentachlorophenol, Chemistry,
Pharmacology and Environmental Toxicology, Plenum press, pp. 301-309.
1978.
-------
Schwetz, B.A., J.M. Norris, G.L. Sparschu, V.K. Rowe, P.J. Gehring,
J.L. Emerson, and C.G. Gerbig. Toxicology of Chlorinated Dibenzo-
P-Dioxins. Environ. Health Perspect. 5:87-99.
Schwetz, B.A., P.A. Deeler, and P.J. Gehring. The Effect of Purified
and Commercial Grade Pentachlorophenol on Rat Embryonal and Fetal
Development. Toxicol. Appl. Pharmacol., 28: 151-161. 1974.
Simon, G.S., et. al. Failure of Hexachlorobenzene to Induce Dominant
Lethal Mutations in the Rat. Toxicol. Appl. Pharmacol., 47:415-419.
1979.
Squire, R. A. An Assessment of the Experimental Evidence for Potential
Carcinogenicity of Hexachlorodibenzo-P-Dioxins. Robert A. Squire,
Assoc. June 29, 1983.
Strassman-Sundy, S.C., FSB, OPII, EPA, Personnel Communication to David
Van Ormer, 1980.
U.S. EPA, Position Document PD 1 for Wood Preservatives,
October 18, 1978.
U.S. EPA, Position Document PD 2/3 for Wood Preservatives,
January, 1980.
U.S. EPA, Position Document PD 4 for Wood Preservatives,
July, 1984.
U.S. EPA, Position Document 1 for Pentachlorophenol,
October, 1978.
U.S. EPA, Postion Document 2/3 for Non-Wood Preservative Uses,
August, 1984.
Van Ormer, D. Draft Rebuttal Analysis for PD-4. Wood Preservatives.
(Inorganic Arsenic: Terato/Mutagenicity, and Pentachlorophenol:
Teratogenicity) EPA internal memo to Amy Rispin, Jan. 25, 1982 (a).
Zendzian, R.P. Absorption estimates wood preservatives: pentachloro-
phenol, inorganic arsenicals, and creosote-coal tars. EPA
Memo to B. Day April 16, 1982.
-------
Lli/iiNC- Ot
buttal No .
1
See LA,
IB
2
3
4
5
b
7
b
9
10
11
bee 11
11A
12
13
14
15
source of
bteptoe ana Johnson, Atts.
(Rep. American Wood Pre-
servers Inst.)
Washington, D.C.
bteptoe & Johnson
Washington, D.C.
Reichhoid Chemicals, Inc.
White Plains, N.Y.
Cooperative Ext. Service
Fitzgerald, Ga.
Chapman Chemical Co.
Memphis, in.
Emerald lurfgrass Farms
beat tie, Washington
Department of the Navy
Alexandria, Va .
Agro-West, inc.
Wilder, laaho
Link Not, Wilder blag. Ctr.
Wilder, Idaho
Consolidated Companies
Cleveland, Ohio
George Brown
Idaho Falls, Idaho
Howard Larson
Eramett, Idaho
Howard Larson
Lmmett, laaho
Chas. H. Lilly Co.
Portland , Oregon
L.A. Tephson
toward Hener
Ray b. buker
Date
Comment
10/i23/78
4/27/79
11/7/78
11/3/78
11/6/78
11/16/78
11/17/78
11/1U/78
ll/lO/7b
ll/2i/7b
11/16/78
11/13/78
1/22/79
11/15/78
UNDA'iED
11/17/78
11/18/78
Date
Receivea
11/2/78
5/1/79
11/13/78'
11/13/78
11/15/78
11/20/78
li/2U/7b
11/^0/78
ll/20/7b
11/24/78
11/27/78
11/29/78
2/13/79
11/29/78
11/29/78
11/24/78
11/24/7G
Teton, Idaho
-------
43A
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
Bryan Ravenscrott
Tut tie, Idaho
Vernon Bavenscroft
Tattle, Idaho
Kansas Department of
Transportation
Topeka, Kansas
Industrial Water Chemicals
Chattanooga, Tenn.
Public Service Electric
& Gas Company
Newark, N.J.
Henry J. Bills
Manchester, N.H.
Fla. Power & Light Co.
Miami , Fla .
Os borne A. Goetz
Idaho Falls, Idaho
Midland Research Labs.
Houston, Texas
Lester Labs., Inc.
Atlanta, Georgia
Herman Ratner
Atlantic City, N.J.
Jewel Hansen
Rexburg, Idaho
Tullio Gabos
Vineland, N.J.
Chemical Treatment Co.
Ashland, N.J.
Industrial Maintenance
Corp. ,
Charlotte, N.C.
Reliance Brooks Inc.
Cleveland, Ohio
Arkansas State Plant
11/29/78
11/29/78
12/1/78
12/4/78
12/1/78
12/4/78
11/30/78
UNDATED
12/4/78
12/5/78
12/4/78
UNDATED
12/5/78
12/5/78
12/6/78
12/5/78
12/5/78
12/6/78
1 2/6/7 U
12/6/78
12/7/78
12/6/78
12/8/78
12/8/78
12/8/78
12/8/78
12/8/78
12/8/78
12/11/7U
12/11/78
12/11/78
12/11/78
12/11/78
12/11/78
Board
Little Rock, Arkansas
-------
60
61
b3
64
65
66
67
68
69
70
71
72
73
74
75
76
Harris Chemical Co., Inc. 12/5/78
Knozville, Tenn.
Chem-Masters Corp., 12/4/78
Chagrin Falls, Ohio
Water Services, Inc. 12/5/78
Knoxville, Tenn.
Dept. of Agriculture 12/5/78
Atlanta, Gerogia'
Dept. of Highways & 12/1/78
Transportation
Richamond, Virginia
Kor-Chem 12/8/78
Atlanta, Georgia
Branchemco Inc. 12/5/78
Jacksonville, Fla.
A.W. Williams Inspection 12/7/78
Company
hobile, Alabama
Allegheny Power System 12/7/78
Greensburg, Pa.
Arkansas Power & 12/4/78
Light Company
Little ROCK, Arkansas
University ot Illinois 12/5/78
at Urbana-Champaign
Urbana, Illinois
Dayton Power & Light Co. 12/1/78
Dayton, Ohio
Department of 12/7/78
Transportation
Dover, Delaware
Blumberg Co. 12/8/78
Peabody, Mass.
Watcon, inc. 12/7/78
South Bend, Indiana
Long Chemical Inc. 12/6/78
Los Angelas, California
Mac Gillis & Gibbs Co. 12/8/78
Milwaukee, Wisconsin
12/11/78
12/11/78
12/11/78
12/11/78
121178
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
12/13/78
-------
108 American Water Treatment, 12/19/78
Inc.
St. Louis, Missouri
109 Bonners Ferry Bast Co. 12/19/78
Bonners Ferry, Idaho
110 Omaha Public Power District 12/19/78
Omaha, Nebraska
111 Tri-Copunty Electric 12/22/78
Cooperative
Rushford, Minnesota
111A Tri-County Electric
Cooperative
Rushford, Minnesota
112 Otter Tail Power Co.
Fergus Falls, Minnesota
113 Southern Wood Piedmont Co
Spartanburg, S.C.
bee 113 Southern Mood Piedmont
113 A co.
Spartanburg, S.C.
114 Ohio Dept. of Agriculture
Columbus, Ohio
115 Department of the Army
Engineering Res. Ctr.,
Fort Belvoir, va.
116 Public Service Co. of 12/21/78
New Hampshire
Manchester, New Hampshire
117 Indiana State Highway 12/27/78
Indianapolis, Indiana
118 Consumers Power Company 12/29/78
Jackson, Michigan
119 Dept. of Transportation 12/28/78
Sacramento, California
120 Ohio Department of 12/26/78
Transportation
Columbus, Ohio
121 Dept. of Transportation 1/3/79
Federal Aviation Administrarton
Washington, D.C.
12/29/78
12/29/78
12/29/78
12/29/78
4/11/79
12/22/78
12/19/78
2/6/79
12/22/7 8
12/22/78
12/29/7 fa
12/29/7 U
2/13/7*
1/5/79
1/5/79
1/4/79
1/5/79
1/5/79
i/5/79
1/5/79
1/5/79
-------
122
123
123A
123B
123C
1230
123E
123F
123G
124
125
126
127
128
Maine Department ot
'iransportation
Augusta, Maine
Conroe Creosoting Company
(J.A. Ramey)
Conroe, Texas
Conroe Creosoting Company
(Charline H. Mulier)
Conroe, Texas
Conroe Creosoting Company
(James P. Lumpkin)
Conroe, Texas
Conroe Creosoting Company
(Elmer Weisinger)
Conroe Creosoting Company
(Vi.E. Kolbe)
Conroe, Texas
Conroe Creosoting Company
(George B. Brodnax)
Conroe, Texas
Conroe Creosoting Company
(Marie Henry)
Conroe, Texas
Conroe Creosoting Company
(Charline Hawthorne)
Conroe, Texas
Fla. Dept. of Agriculture
6 Consumer Services
Tallahassee, Fla.
N.C. Dept. of Agriculture
(Commissioner)
Raleigh, N.C.
Dept. of Transportation
(Pa. Ofc. of Secretary)
Harrishurg, Penna.
City Public Service Board
San Antonio, Texas
G. Carl Baton (C&B Timber)
Ashton, Idaho.
12/26/78
12/30/79
12/30/78
12/30/7C
12/30/78
12/30/78
12/30/78
12/30/78
12/30/78
12/22/78
12/29/78
1/2/79
12/29/78
12/31/78
1/5/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
1/10/79
-------
159
160
161
162
163
164
See 164 A
165
166
16 6A
167
168
169
170
171
172
173
Ha be r man Supplies 1/19/79
Owatonna, Minn.
Lyle H. Guggishery
St. Cruix, Wi.
Koppers Company Inc. 1/11/79
Denver, Col.
John J. Penning ton 1/14/79
Eugene , Oregon
Gordon A. MacGregor 1/15/79
Boise, Idaho
Interstate Power Co. 1/18/79
Dubuque , Iowa
Interstate Power Co., 8/2/79
Dubuque , Iowa
Edison Sault Electric Co. 1/16/79
Sault Ste. Marie, Michigan
Oregon State University l/lb/79
(Theodore C. Scheffer)
Corvallis, Oregon
Oregon State University 1/17/79
(R.O. Graham)
Corvallis, Oregon
Indiana Farm Bureau 1/15/79
Cooperative Assn., Inc.
Lake States Wood Preserving 1/16/79
Inc.
Munising, Michigan
C.K. Peck 1/7/79
Lexington, Oregon
Houston Wood Treating Co., 1/18/79
Inc.
Houston, Missouri
Decorator Supply Inc. UNDATED
(J.P. Schellien)
Rice Lake, Wi .
Fleet Distribution Supply 1/20/79
Thief River Falls, Minn.
Anderson Glass Co., Inc. 1/18/79
Grand Rapids, Minn.
1/24/79
1/24/79
1/25/79
1/25/79
1/25/79
1/25/79
8/16/79
1/25/79
1/25/79
1/25/79
1/25/79
1/25/79
1/24/79
1/29/79
1/26/79
1/26/79
1/26/79
-------
174
175
176
177
178
G.F. Nemitz' Sons
Hutchison, Minn.
Kenneth P. Strube
Rochester, Minn.
Gordon A. Peterson
Dresser, Wi.
Jan J. Don
Grandview, Washington
Wayne Vv. Roundy
Boise, Idaho
1/19/79
1/19/79
1/20/79
1/22/79
1/23/79
1/26/79
1/26/79
1/26/79
1/30/79
1/30/79
179
179A
179
179A
180
1BOA
J.81
182
Ibj
Ib4
Vepco 1/18/79
Richmond, Va.
Vepco 1/18/79
Richmond, Va.
Vtpco 7/12/79
Kichmond, VA.
Koppers Company Inc. (194) 1/25/79
Pittsburgh, Pa. (bee
161, 183, 188, 189, 192,
193 & 194)
Koppers Co. Inc., 2/12/79
(Gerald L. Daugherty)
Pittsburgh, Pa. (See 180)
Koppers Company Inc. (194) 1/25/79
Pittsburgh, Pa. (See
161. 183, 188, 189, 192,
193 & 194)
Kansas Gas 6 1/2.5/79
Liectric Co
Witchita, Kansas
New England Log Homes 1/22/79
Inc.
hamtien, conn.
Koppers Company Inc. UNDATED
Superior, Wi.(bee 161,
180, 188, 189, 192,
193, 194)
Julian Cchrymowych 1/2J/79
New Providence, N.J.
1/30/79
8/9/79
8/10/79
1/30/79
2/12/79
2/12/79
1/30/79
130/79
1/29/79
1/29/79
-------
215
216
217
21o
il9
220
221
J.A. uones Construction, 1/29/79
Co.
Charlotte, N.C.
R.O. Watson 2/1/79
Wilmington, Delaware
Avco New Idea (Farm 2/1/79
Equipment Division)
Coidwater, Ohio
Rogers Post & Lumber Co. 1/29/79
.ceelvilie, Missouri
Cleveland Electric 1/23/79
illuminating Lo.
Cleveland, Ohio
Robert K. Hastings 1/29/79
harbor, Oregon
Friends ot the Earth
(EriK Jansson)
Washington, D.C.
2/9/79
2/9/79
2/9/79
2/9/79
2/1/7 i»
2/12/79
222
22J
224A
bcfc 224
2^4 A
225
22b
22V
228
229
lexas Forest Service
LutKin, rix.
Web & Sons Inc.
bherburne, N.Y.
Dallas Power & Light Co.
Dallas, Texas
Duilas Power & Light
Dallas, TX.
American Electric Power
service Corp.
Public Service Co.,
ol New kexico Albuquerque,
W.C. 'umber Products,
inc. (fi.F. Clitten)
Rexburg, Idaho
Idaho Power Co.
Boise, Idaho
Public Service Co. of OK.
2/6/79
UNDATED
2/6/7'J
fc/3/79
2/6/79
2/9/79
N.M..
2/8/79
2/9/7 «#
2/U/79
2/12/79
2/12/79
2/1 2/7 9
fc/10/79
2/12/79
2/12/79
2/1 3/7 »
2/1J/79
2/13/79
lulsa, OK.
-------
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
Carolina Power & Light Co.
Raleigh, N.C.
Roof Surgeon Inc.
Honolulu, Hawaii
Texas Forestry Assoc.
Lufkin, Ix.
Portland General Electric
Co.
Portland, Oregon
Morton Buildings, Inc.
Morton, 111.
Middle South Services
Inc.
New Orleans, La .
Central Vermont Public
Service Corp.
Rutland, Vt .
Texas Electric Service Co.
Fort Worth, Tx.
Upper Peninsula Power Co.
Ho ugh ton, Michigan
Duke Power Co. (Legal
Dept.)
Charlotte, N.C.
Union Electric Co.
St. Louis, Mo.
Bill Deveny
Riggins, Idaho
Everett Van Seyke
Wilder, Id.
hark Johnson,
Idaho
Reuben H. Babcock
Moore, Idaho
Picabo Livestock Co.
Picabo, Idaho
Don He c km an
2/8/7*
2/9/7 y
2/7/7 &
2/8/79
2/7/7 y
2/8/79
2/9/79
2/5/79
2/8/79
2/9/79
2/8/79
1/22/79
UNDATED
1/21/79
2/1/79
l/ltJ/79
UNDATED
2/13/79
2/1 3/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
2/13/79
1/13/79
2/13/79
1/13/79
2/13/79
White Bird, Idaho
-------
259
260
261
262
26 2A
263
264
265
266
Pa. Electric Co. 2/12/79
Johnstown, Pa.
Nixon, Margrave, Duvans & 2/12/79
Loyle(Rep: Rochester Gas &
Elec. Corp.)
kocnester, N.Y.
Indianapolis Power & Light 2/12/79
Company
Indianapolis, Indiana
111. Power Co. 2/9/79
Decatur, 111.
Illinois Power Company 3/14/79
Decatur, 111.
Tampa Llectric Co. 2/9/79
'lampa , Fia.
Jersey Central Power & 2/6/79
Lignt Co.
Morristown, N.J.
Central & South West 2/8/79
services. Inc.
Dallas, Tx.
New York State Electric 2/8/79
& Gas Corporation
Binghamton, N.Y.
273
Corporation
Syracuse, N.Y.
Minnesota Power fc Light Co
Duluth, Mn.
2/15/79
2/15/79
2/15/79
2/15/79
3/2L/79
2/15/79
2/15/79
2/15/79
2/15/79
267
268
269
270
271
272
Pa. Power & Light Co.
Allen town, Pa.
Canal Electric Co.
Sandwich, Mass.
Cambridge Electric Light
Cambridge, Mass.
New Bedford Gas & Edison
Light Co.
Duluth, Minn.
Southern States Cooperative
Richmond , Va .
Niagra Mowhawk Power
2/9/79
2/9/79
2/9/79
2/9/79
2/5/79
2/6/79
2/15/79
2/15/79
2/15/79
2/15/79
2/15/79
2/15/79
2/8/79
2/15/79
-------
27 3A
274
275
27 5A
276
277
271*
27 8A
279
280
281
282
283
284
285
286
Minnesota Power & Light CO.2/28/79
Duluth, Minn.
Boston Edison Co. 2/5/79
Boston, Mass.
American Paper Institute 2/12/79
Washington, D.C.
Lumber River Elec.
Membership Corp.
2/12/79
2/7/79
2/8/79
2/12/79
2/12/79
287
Dept. of Transportation
Raleigh, N.C.
Delsea Exterminators
Camden, N.J.
Forshav Chemicals
Charlotte, N.C.
The Washington Water
Power Co.
Spokane, Washington
Kansas Paver & Light Co.
Topeka, Ks.
Iowa-Illinois Gas &
Electric Co.
Davenport, Iowa
National Solvent Corp., 2/11/79
Meaina, Ohio
Lincoln Electric Coopera- 2/12/79
tive Inc.
Davenport, Wash ing ton
ton Frei UNDATED
Grangeville, Idaho
Long Island lighting Co. -2/13/79
Hicksville, N.Y.
University of Idaho, Coil. 1/J1/79
of Agriculture
Dept. of Agri.,
Moscow, Idaho
Public Service Co. 2/9/79
of Colorado
Denver, Colorado
3/7/79
2/15/79
2/15/79
4/17/79
2/15/79
2/16/79
2/16/79
2/22/79
2/22/79
2/22/79
2/22/79
2/22/79
2/22/79
2/22/79
2/23/79
-------
317
318
319
320
321
3 2 In
bee 321, A
321 B
322
323
324
325
326
327
328
329
Liz Vanleeuwen 2/12/79
Halsey, Oregon
Bowater Carolina Corp. 2/23/79
Catawba, S.C.
Yampa Valley Electric 3/7/79
Association, Inc.
Steamboat Springs, Col.
Sonford Products Corp., 2/8/79
(Southern Div.)
Jackson, Miss.
Public Utility District 3/9/79
No. 1 of Klickitat Cty
Goldendale, Washington
Public Utility District 3/9/79
No. 1 of Okanogan Cty.
Okanogan, Wash ing ton
Public Util. Distr. No. 1 7/2/79
No. 1 ukanogan, MA.
Masco Electric Cooperative,
Inc.
Dalies, Oregon
Nebraska Public Power
Columbus, Nebraska
Port Authority ot New York
& New Jersey
New York, N.Y.
bavannah Electric & Power
Company
bavannah, Georgia
Power & Light Company
Eastsound, Washington
Thyrald H. Finn
Rig by , Idaho
Dixie Electric Power ASSOC.
Laurel, Ms.
Memphis Light, Gas and
Water Division
hemph is, 'ic nn .
3/12/79
3/12/79
3/14/79
UNDATED
3/19/79
3/16/79
3/19/79
3/20/79
3/7/79
3/7/79
3/13/79
3/13/79
3/13/79
3/13/79
7/9/79
3/20/79
3/20/79
3/22/79
3/22/79
3/26/79
3/26/79
3/29/79
3/JU/79
-------
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
Columbus and bouthern Ohio
Electric Co .
Columbus, Ohio
Poudre Valley Rural
Llectric Association
Fort Collins, Colorado
Public Utility District
No. 1 of Cheian County
Wenatehee, Washington
Carbon Power & Light Inc.
Saratoga, Wyoming
Lugene Vvater & Electric
Board
Eugene, Oregon
3/ly/79
3/23/79
3/23/79
3/21/79
3/26/79
Dearborn Chemical Chemed
Corp.,
Lake Zurich, 111.
Inter County Rural Elec.
Coop. Corp.,
Danville, Kentucky
Craig-Cotetourt Eltc. Coop.
New Castle, Penna.
Crow Wing Coop. Power &
Light Co.
Brainerd, Minn.
Delaware County Electric
Coop.
Delhi, New YorK
Barkers Island Elec. Corp.
Barkers, Island, N.C.
Roanoke Llectric Corp.
Rich Square, N.C.
Flint Hills Rural Elec.
Coop. Assoc. Inc.
Council Grove, Kansas
3/30/79
4/3/79
4/4/79
UNDATED
UNDATED
4/3/79
4/3/79
UNDATED
3/30/79
3/30/79
3/30/79
4/3/79
4/3/79
4/10/79
4/10/7 9
4/10/79
4/10/79
4/10/79
4/10/79
4/10/79
4/10/79
-------
373
374
375
387
Waynw-White Counties 4/4/79
Electric Cooperative
Farifield, 111.
Douglas Electric Coop., 4/6/79
inc.
Roseburg, Oregon
Missouri Public Service 3/27/79
Company
Kansas City, Mo.
Coop., Inc., Hulbert,
Oklahoma
EMC Haywood Elec.,
Membership Corp.,
Vvaynesville, N.C.
4/11/79
4/13/79
4/13/79
4/13/79
376
377
378
379
380
381
382
383
384
385
386
RSR Elec. Co-op Inc.
Milnor, N.D.
The Victory Elec. Coop.
Assoc., Inc.
Dodge City, Kansas
United Elec. Coop. Inc.
Dubois, Iowa
Howard Elec. Coop.
Fayette, Mo.
Glacier Elec. Coop., Inc.
Cut BanK, Montana
OJcefenoke Rural Elec.,
Membership Corp.,
Nahunta, GA.
Kandiyohi Coop., Elec.,
Power Association Willraar,
MN
Planters Elec., Membership
Corp., Millen, GA.
Golden Valley Elec.,
ASSOC., Inc. Fairbanks,
Alaska
Re Sand Mountain Elec.,
Coop., Rainsvilie, Alabama
Lake Region Elec.,
4/9/79
4/9/79
4/1U/79
4/9/79
4/10/79
4/9/79
4/9/79
4/5/79
4/5/79
4/9/79
4/9/79
4/17/79
4/17/79
4/17/79
4/17/79
4/17/79
4/17/79
4/17/79
4/17/79
4/1V/79
4/17/79
4/17/79
4/17/79
-------
388
Grand Elec., Coop.,
Inc., Bison, S.D,
4/9/79
4/17/79
389
Union Rural Elec., 4/10/79
Association, Inc.,Brighton,
Colorado
4/18/79
390
391
392
393
394
395
396
J97
Kotzebue Elec., Assoc.,
Inc., Kotzebue, Alaska
Alger Delta Coop.,
Llec., Association Inc.,
Gladstone, Ml
TRI-County Elec., Assoc.,
Inc., Plankinton, S.D.
C&Vs Rural Llec., Coop.,
Association Clay Center,
Kansas
Slope Llec., Coop.,
Inc., New Lnglana, N.D.
Moreau-Grand Elec., Coop.,
Inc., Timber Lake S.D.
Valley Elec., Membership
Corp., Natchitoches , LA.
Yorx Country Rural Public
4/9/79
4/12/79
4/12/79
4/13/79
4/12/79
4/J/79
Undated
4/13/79
4/18/79
4/18/79
4/18/79
4/18/79
4/18/79
4/20/79
4/20/79
4/20/79
Power District York, Nebraska
398
3i>9
40U
<»01
402
4U3
4U4
Carroll Llec., Membership
Corp., Car roll ton, GA.
San Luis Valley Rural
Llec., Coop., Inc. Monte
Vista, Coioraao
Mitchell Liec., Membership
Co rp . , Cam ilia, GA .
Fiathead Llec., Coop.,
Inc., Power & Light
Kalispeil, Montana
East Central Llec.,
ASSOC., Bra ham, MN
North-Central Elec.,
Coop., Inc. Attica, Ohio
Wells Rural Llec.,
4/12/79
4/9/79
4/11/79
4/12/79
4/11/79
4/12/79
4/12/79
4/20/79
4/20/79
4/20/79
4/20/79
4/20/79
4/20/79
4/20/79
Co., Vvelis, Nevada
-------
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
454A
Harrison County Rural
Elec., Membership Corp.,
Corydon, ind iana
Edgecombe-Martin County
Elec., Membership Corp.,
'iarboro, N.C.
Kosciusko County Rural
hJLec., Membership Corp.,
Warsaw, Indiana
Jackson Electric
Membership Corp.,
Jefterson, GA.
Fairrield Elec., Coop.,
inc., Winnsboro, S.C.
Bare Electric Coop.,
Millsboro, VA.
habershara Electric
Membership Corp.,
Clarkesvilie, GA.
Western Illinois Elec.,
Coop., Carthage, IL
Hickman-Fulton Counties
Electric Coop., Corp.,
Hickm&n, KY
United Power Association
Elk River, MN.
Blue Grass Recc
Nicholasville, KY.
Rural Elec., Convenience
Coop., Co., Auburn, IL.
Meriwether Lewis Elec.,
Coop., Centerville, TN
Washington btatc Univ.
Pullman, Washington
American Institute of
Timber Construction
Englewood, Colorado
National Rural Elec.,
Coop., Accoc., Washington,
D.C.
4/20/79
4/2b/79
4/30/79
4/27/79
5/1/79
5/4/79
5/4/79
5/4/79
4/27/79
4/30/79
4/24/79
4/24/79
4/30/79
4/23/79
Undated
4/26/79
4/27/79
5/3/79
5/2/79
5/4/79
5/4/79
5/4/79
5/4/79
5/4/79
5/4/79
5/4/79
5/4/79
5/8/79
5/9/79
5/9/79
3/29/79
5/11/79
-------
455
471
Joe Wheeler Elec.,
Membership Corp.,
Hartselle, Alabama
4/30/79
5/11/79
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
Oliver B. Wilbers
Umpqua , OR
Oairyland Power Coop.,
LA Croose t Wl
Oliver-Mercer Elec.,
Coop., Inc., Hazen, ND
Petit Jean Elec.,
Clinton, Arkansas
Eastern Iowa Light
6 Power Corp., Wilton,
Iowa
Cookson Hills Elec.,
Coop., Inc., Stigler, OK
Coos Curry Elec., Coop.,
Inc., Coguille, Oregon
Navopache Elec., Coop.,
Inc., Lakeside, Arizona
Betz Labs, Inc.,
Trevose, PA.
Green River Elec., Corp.
Owensboro , KY
Northern Lights, Inc.,
Sand point, Idaho
Dow Chemical Co.,
Midland, MI
Concordia Elec., Coop.,
Inc., Ferriday, LA.
Alabama Power Co.,
birmingham, ALA.
U.S. Dept. of Agri.
4/7/79
5/10/79
5/9/79
5/7/79
5/9/79
4/26/79
V9/79d
Undated
5/9/79
6/5/79
6/7/79
6/5/79
6/11/79
6/15/79
6/15/79
5/17/79
5/17/79
5/17/79
5/1 7/7 y
5/21/79
5/2/79
5/23/79
5/24/79
6/5/7 y
6/14/79
6/15/79
6/22/79
6/22/79
6/22/79
6/28/79
Forest Serv., Asheville,
N.C.
MS. Power Co.,
Gulfpost, MS.
6/20/79
6/28/79
------- |