UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

OFFICE OF  PREVENTION, PESTICIDES,  AND TOXIC SUBSTANCES

DATE:  August 29, 2008

MEMORANDUM

SUBJECT: Creosote- Toxicology Disciplinary Chapter for the
Reregistration Eligibility

                    Decision Document (RED) for creosote.

FROM:        Timothy F. McMahon, Ph.D.

        Senior Toxicologist, Antimicrobials Division (7510P)

TO:	        Jackie McFarlane, Chemical Review Manager

        Regulatory Management Branch I

                    Antimicrobials Division (7510P)

Attached to this cover memorandum is the Toxicology Disciplinary Chapter
for the creosote RED document in support of the reregistration of
creosote.

1.0	Executive
Summary.................................................................
...............................4

2.0	Hazard
Assessment..............................................................
...................................7

2.1	Acute
Toxicity................................................................
.............................7

2.2	Subchronic
Toxicity................................................................
....................8

2.3	Prenatal Developmental
Toxicity..............................................................11

2.4	Reproductive
Toxicity................................................................
...............13

2.5	Carcinogenicity
........................................................................
................14

2.6	Dermal
Absorption..............................................................
.......................17

2.7
Mutagenicity............................................................
..................................19

2.8
Neurotoxicity...........................................................
...................................20

3.0	Dose-Response Assessment
Summary.................................................................
...21

4.0	Cumulative
Risk....................................................................
..................................23

5.0	Endocrine Disruption
........................................................................
.....................23

6.0
References..............................................................
..................................................25

	CREOSOTE - TOXICOLOGY

1.0 EXECUTIVE SUMMARY

Creosote is a fungicide, insecticide, and sporicide used as a wood
preservative for above and below ground wood protection treatments as
well as treating wood in marine environments.  All 21 Creosote products
currently registered are Restricted Use Pesticides; 20 are End-Use
Products and 1 is a Manufacturing-Use Product for formulating industrial
end-use wood preservative products.  Creosote wood preservatives are
used primarily to pressure treat railroad ties/crossties (represents
close to 70% of all Creosote use) and utility poles/crossarms
(represents 15 - 20% of all Creosote use).  Assorted creosote-treated
lumber products (e.g., timbers, poles, posts and groundline-support
structures) represent the remaining uses for this wood preservative.
These applications of creosote occur through the use of mechanical
sprayers, mechanical dip devices, and hand equipment.  The industry
refers to different blends of creosote [based on the wood treatment
standards set by the American Wood-Preservers’ Association (AWPA)], as
P1/P13, P2, and P3.  Typically, railroad ties/crossties are treated with
a P2 blend,  which is more viscous than the P1/P13 blend used for
treating utility poles.  The AWPA cites P3 as “Creosote-petroleum”.

The acute toxicity of both the P1/P13 and P2 blends of creosote is
moderate by the oral, dermal, and inhalation routes of exposure in
experimental animals (Toxicity Categories III and IV).  Median lethal
doses by the oral and dermal routes are above 2000 mg/kg, and median
lethal doses by the inhalation route are above 4mg/L, which are
considered limit doses in acute toxicity tests as set by Agency
guidelines. The P1/P13 blend displays eye and skin irritation potential
in experimental animals (eye irritation clearing in 8-21 days, skin
irritation up to 14 days post-dosing).  The P2 blend appears to show
somewhat less potential for skin and eye irritation (eye irritation
clearing within 7 days, skin irritation clearing after 72 hours) but
data are incomplete. Dermal sensitization studies reviewed for both the
P1/P13 blend and the P2 blend were inconclusive as to dermal
sensitization potential based on  the choice of doses for the induction
and challenge phases of the experiment, which require further
discussion.

Subchronic dermal testing with both the P1/P13 and P2 blends of creosote
showa minimum of toxic effects in experimental animals (rats).  Using
the P2 blend, one mortality of questionable significance was observed at
a dose of 400 mg/kg/day, while testing of the P1/P13 blend produced
decreases in body weight gain.  Effects on the skin in both studies were
minimal to moderate.

Subchronic inhalation testing with creosote produced a wider spectrum of
effects.  At a dose of 0.049 mg/L, exposure to the P1/P13 blend produced
myocardial pathology (degeneration, hemorrhage, cardiomyopathy) in males
and females. Altered hematological parameters (decreased hemoglobin,
hematocrit, erythrocytes; increased reticulocytes, polychromasia,
poikilocytosis, anisocytosis) were also observed in males and females.
Testing of the P2 blend by the inhalation route also produced altered
hematological parameters, and  resulted in increased absolute and
relative liver and thyroid weights. Follicular cell hypertrophy was
observed. Lesions of the nasal cavity were also observed with the P2
blend.

Developmental and reproductive testing of creosote showed potential
sensitivity of offspring to the P1/P13 blend.  Decreased body weight
gain and decreased food consumption were observed in maternal animals at
a dose of 175 mg/kg/day, and at this same dose, increased
post-implantation loss, increased mean resorptions, and decreased live
fetuses per litter were also observed. An overall significant increase
in incidence of developmental malformations was also observed at the 175
mg/kg/day dose.  Testing of the P2 blend did not show any apparent
susceptibility of developing offspring to creosote, and reproductive
testing of P1/P13 creosote did not show any apparent susceptibility, but
the reproductive toxicity study contained several deficiencies that
compromised interpretation of the data, such as a low fertility and
pregnancy index for F1 female parental rats. Thus, there is some
uncertainty associated with concluding that creosote is devoid of any
reproductive effects.  In this light, the additional 10-fold safety
factor mandated by FQPA was employed to account for this uncertainty as
well as for the effects observed from developmental toxicity testing of
P1/P13 creosote.

In consideration of the available evidence that creosote is a positive
mutagen, the Agency waived the requirement for the standard mutagenicity
battery, and instead required dominant lethal testing of both the P1/P13
and P2 blends.  The results of testing of both the P1/P13 blend and P2
blend of creosote showed that, at doses toxic to the dosed animals
(330.5  mg/kg for the P1/P13 blend, and 194 mg/kg for the P2 blend),
there was no evidence of a dominant lethal effect of either creosote
blend.

There are no reliable metabolism data on creosote, as the chemical is a
complex mixture of several classes of polycyclic aromatic chemicals.
Assays are in development to identify marker compounds to determine
exposure to creosote.

Submitted studies on the dermal absorption of creosote have been
submited and consist of an in vivo dermal absorption study in the rat as
well as an in vitro dermal absorption study using both rat and human
skin (MRIDs 47179501 and 47179502). The results of these studies support
the conclusion that dermal abshuman skin is approximately 8-fold lower
than that of rat skin. The results of the submitted studies also support
a value for dermal absorption of creosote in rat skin of approximately
34%. Thus, estimated dermal absorption of creosote in human skin is
determined to be 5% (34% value divided by 8 and rounded to 5%).  A
smaller value was not concluded on the basis of the lack of data on
solubility limit of the creosote mixture itself in the in vitro test
system, and the continued absorption of creosote observed after 8 hours
in the in vivo study suggesting the availability of creosote within the
skin for absorption.

A large body of experimental evidence exists which shows a positive
relationship between exposure to creosote and development of tumors in
experimental animals.  In addition to its tumor-promoting potential, the
ability of creosote to induce lung tumors after dermal application was
examined. Dermally applied creosote  (0.25ml undiluted, twice weekly for
8 months) induced 5.8 lung adenomas per mouse in mice housed in
stainless steel cages, while untreated controls showed 0.5 lung
adenomas/mouse (Roe et al, Cancer Res. 18: 1176-1178, 1958).
Carcinogenicity of two high-temperature derived creosote oils was
studied by Poel and Kammer (JNCI 18: 41-55, 1957).  The light creosote
fraction is composed mainly of benzene, toluene, xylene, and solvent
naphtha, while the blended oil is composed of creosote oil, anthracene
oil, and oil drained from recovery of naphthalene. Oils were applied by
drops to the skin of mice at concentrations of 20%, 50%, or 80% three
times a week for life.  By weeks 21-26, both oils had induced skin
tumors.  Several mice exhibited metastases to the lungs or regional
lymph nodes.

In an oral carcinogenicity study conducted by  Culp et al. (1996), the
carcinogenicity of two coal tar mixtures and pure benzo[a]pyrene (BaP)
was studied.  Coal tar mixture 1 (CTM-1) was a composite of coal tar
samples from seven coal gasification plant waste sites and was dosed at
0.0, 0.01, 0.03, 0.1, 0.3, 0.6, and 1.0% of diet.  Coal tar mixture 2
(CTM-2) was a composite of coal tars from three waste sites with high
BaP content and was dosed at 0.0, 0.01, 0.03, 0.1, 0.3% of diet.  An
additional group was dosed with pure BaP at 0, 0.0005, 0.0025, and 0.01
% in diet.  A control group received solvent control in diet.  Each
group consisted of 48 mice.

In mice exposed to coal tar, coal tar acted as a systemic carcinogen and
induced a dose-related increase in hepatocellular adenomas and
carcinomas, alveolar/bronchiolar adenomas and carcinomas, forestomach
squamous epithelial papillomas and carcinomas, small intestine
adenocarcinomas, histiocytic sarcomas, hemangiosarcomas in multiple
organs, and sarcomas in several tissues.

The incidence of forestomach tumors increased sharply between the 0.1
and 0.3% doses.  However, there was not a proportional increase in
forestomach tumors above 0.3% because these mice died from
adenocarcinomas of the small intestine.  Tumors of the esophagus,
observed in BaP treated mice, were not observed in the CTM1 or CTM-2
treated groups.  Lung and hepatocellular tumors observed in the CTM1 and
CTM2 groups were not observed in BaP treated animals.

Multiple neoplasms were noted in liver, lung, forestomach, and the small
intestines of exposed mice.  Liver neoplasms occurred in 1, 0,  and 4
mice fed 0.03, 0.1 and 0.3% CTM-1, respectively.  Lung neoplasms
occurred in 21, 11 and 13 mice fed 0.3% , 0.6% , 1.0% CTM-1,
respectively.  Eight mice in the 0.3% CTM-2 group had multiple lung
neoplasms.  Forestomach carcinomas were found in 2 and 1 mice fed 0.6%
or 1.0% CTM-1, respectively.  Adenocarcinomas were found in the small
intestines (jejunum) of 2 and 12 mice fed 0.6% and 1.0% CTM-1,
respectively.  Groups dosed with (0.3% CTM-1 or CTM-2 had significantly
reduced survival.

quivalent to 20.5 and 104 μg BaP/day.  Tumors of the esophagus were not
observed in the CTM1 or CTM-2 treated groups.  Lung and hepatocellular
tumors, observed in CTM treated mice, were not observed in mice fed BaP.

Multiple neoplasms of the forestomach occurred in 8 and 21 mice fed 25
and 100 ppm BaP, respectively.  Multiple neoplasms of the esophagus and
tongue were noted in 6 and 3 mice, respectively, fed 100 ppm BaP.  It
should be noted that all animals in 100 ppm group died before
termination of the study.

In humans, evidence for carcinogenicity of creosote varies. Several
studies have associated occupational exposure to creosote with
development of skin cancer, with a latency period of 20-25 years. These
studies are very old (1920's to 1940's), when occupational safety
practices were much more lax than today.  More recent reports (1980)
show no increase in risk of skin, bladder, or lung cancer in wood
treatment plant workers, or after treatment for 4 years with coal-tar
medicinal therapy for treatment of dermatitis.  These reports, however,
were limited in scope. Those reports associated with therapeutic use of
coal tar did not mention the fact that the composition of the coal tar
used therapeutically is different than that used for wood treatment.  In
the report on wood treatment workers, the population studied was small,
and the follow-up period was too short to allow a long enough latency
for tumor development.

The Agency in 1988 acknowledged limitations on conducting a quantitative
risk assessment from use of a single component of creosote (Guidance for
the Reregistration of Pesticide Products Containing Coal Tar/Creosote As
the Active Ingredient, USEPA, 1988), but it was also observed that
creosote mixtures are “complex mixtures with known synergistic
effects” on carcinogenicity.

In conjunction with the Pest Management Regulatory Agency, Health
Canada, a  quantitative risk assessment on carcinogenicity of creosote
has been performed using the data of Culp et al. (1998). A dermal
carcinogenicity study by Bushmann et al. (1997) was also available, but
was determined not suitable for quantitative assessment of
carcinogenicity. Ulceration of the skin was significant finding of the
study which potentially affected tumor response. In addition, systemic
toxicity was not examined, and complete histopathology data were not
available. Based upon the analysis of the Culp et al. data, an oral
cancer potency factor of 6.28 x 10-6 (µg/kg/day)-1 for the coal tar
mixture 1 tested in this study was selected, on the basis of forestomach
tumors observed.

 2.0 Hazard Assessment

2.1 Acute Toxicity

Results of acute toxicity studies, primary eye and dermal irritation
studies and dermal sensitization study with Creosote P1/P13 and Creosote
P2  are summarized in Table 1.

Table 1a.  Acute Toxicity of   Creosote P1/P13

Study Type

Animal

Results

Tox Cat

MRID No

81-1:  Acute Oral

Rat

LD50	Male	 2451 mg/kg

Female	 1893  mg/kg

III

43032101

81-2:  Acute Dermal

Rabbit

LD50	Male	> 2000 mg/kg

Female	> 2000 mg/kg

III

43032102

81-3:  Acute Inhalation

Rat

LC50	> 5  mg/L

IV

43032103

81-4:  Primary Eye Irritation

Rabbit

Irritation clearing in 8-21 days

II

43032104

81-5:  Primary Dermal Irritation

Rabbit

erythema to day 14

III

43032105

81-6: Dermal Sensitization

Guinea Pig

study unacceptable

N/A

43032106

Table 1b.  Acute Toxicity of   Creosote P2

Study Type

Animal

Results

Tox Cat

MRID No

81-1:  Acute Oral

Rat

LD50	Male	 2524 mg/kg

Female	 1993  mg/kg

III

43032301

81-2:  Acute Dermal

Rabbit

LD50	Male	> 2000 mg/kg

Female	> 2000 mg/kg

III

43032302

81-3:  Acute Inhalation

Rat

LC50	> 5.3  mg/L

IV

43032303

81-4:  Primary Eye Irritation

Rabbit

Irritation clearing within 7 days

III

43032304

81-5:  Primary Dermal Irritation

Rabbit

no irritation  after 7 days

III

43032305

81-6: Dermal Sensitization

Guinea Pig

study unacceptable

N/A

43032306

2.2. Subchronic Toxicity

Reference:   R.A. Hilaski;  April 13, 1995;  North American P1/P13
Creosote CTM: 90-Day Subchronic Dermal Toxicity Study In Rats.    IRDC,
Mattawan, MI.;  Report No. 671-013. Sponsored by The Creosote Council
II.  MRID # 43616101 Unpublished. Study I.D. : IRDC 671-013

Executive Summary:    In a 90-day dermal toxicity study (MRID #
43616101),  10 Charles River Crl:CD BR rats (10/sex/dose) were given
dermal applications of P1/P13 creosote in corn oil mixture at dosage
levels of 0, 4, 40 or 400 mg/kg bw/day.  There were no treatment-related
effects from dermal application of P1/P13 creosote on body weight, food
consumption, ophthalmology, hematology, clinical chemistry, or organ
weights at any dose level tested. Mortality (death of one male rat at
400 mg/kg/day) was observed on day 79 of the study. No test-article
related microscpoic lesions were noted at the application site on the
skin at any dose level.   Based on the results of this study, the
systemic LOAEL was determined to be 400 mg/kg bw/day for both male and
female rats, based on mortality.   The systemic NOAEL was determined to
be 40 mg/kg/day.

This study is classified as acceptable and satisfies the guideline
requirement (OPPTS 870.3250;  OPP 82-3) for a subchronic dermal toxicity
study in rats for P1/P13 creosote

Reference:  R.A. Hilaski; April 13, 1993;   North American P2 Creosote
CTM:  90-Day  Subchronic Dermal Toxicity Study in Rats.   IRDC,
Mattawan, MI.;   Report No. 671-014. Sponsored by The Creosote Council
II.  MRID # 43616201.

Executive Summary: In a 90-day dermal toxicity  study (MRID # 43616201),
Charles River rats ( 10/sex/dose) were given dermal applications of P2
creosote in corn oil at dosage levels of 0, 4, 40 or 400 mg/kg bw/day.
There was no mortality observed in this study at any dose level. Body
weight in high dose males was decreased 7-8% during weeks 9-12 of the
study, and bodyweight gain decreased 15% in high dose males for the
treatment period. Food consumption in high dose males was decreased
during weeks 2-4 and week 6 by 4-10% vs control. Only slight dermal
irritation was observed in high dose males. No effects were observed on
hematology or clinical chemistry. Treated skin in the 400 mg/kg/day dose
groups (male and female) was observed with increased incidence of dermal
inflamation.  Based on the results of this study, the systemic LOAEL is
400 mg/kg/day, based on decreased body weight gain in male rats. The
systemic NOAEL is 40 mg/kg/day.  For females,  the NOAEL is set at 400
mg/kg bw/day since no systemic toxic effects were noted in any of the
treated groups.

Reference: R.I. Hilaski, March 28, 1995: Thirteen week subchronic
inhalation toxicity study on North American P1/P13 Creosote CTM in
rats.;  International Research and Development Corp., Mattawan, MI
49071;  Project No. 671-016;   Creosote Council II;  MRID # 43601001;
Unpublished

Executive Summary:  In a subchronic inhalation toxicity study with
P1/P13 creosote (MRID # 43601001),  20 Sprague-Dawley rats/sex/group
were treated for thirteen weeks, five days a week, six hours per day
with P1/P13 Creosote CTM  via whole body exposure at doses of 0, 5.4, 49
and 106 mg/m3 (0.005, 0.049 and 0.106 mg/L in air, respectively)
measured gravimetrically.  The aerosol MMAD was between 2.2 and 3.0
microns with a geometric standard deviation between 1.91 and 1.99.
Subsequent to the exposure period  10 animals/sex/group were allowed to
recover for  6 weeks.

During the study one male rat of the mid dose group (49 mg/m3) died
from myocardial degeneration that resulted in heart failure.  One male
and one female rat in the highest dose group had similar lesions
observed at terminal necropsy.   Cardiac pathology (ie: hemorrhage,
lymphocytic infiltration and cardiomyopathy) was noted in all animals of
all groups (including controls) and this condition may have been
exacerbated by treatment with creosote in the mid and high dose animals.
 Significant treatment-related findings in the mid and high dose animals
after the exposure period included decreased body weight gains of both
sexes (resolved by the end of recovery period), altered hematological
parameters (decreased hemoglobin, hematocrit, numbers of erythrocytes,
increased numbers of reticulocytes, polychromasia, poikilocytosis,
anisocytosis -both sexes) and biochemical parameters (increased serum
cholesterol levels - both sexes,  phosphorous levels - males only).
Macroscopic discolouration of the lungs, which persisted throughout the
recovery period, was correlated with the presence of black pigment
granules within alveolar macrophages of animals of all treatment groups.
 An increase in liver/brain weights (statistically significant only in
the females), increased lung/trachea/body weight ratios and the presence
of small cystic spaces containing basophilic mucoid material in the
nasal cavity epithelium was still evident after the recovery period in
both sexes.

Male and female rats of the low dose group were observed to have mild
poikilocytosis and anisocytosis while the females only showed the
occasional cyst of the epithelium in the nasal cavity.  All
hematological findings in low dose animals showed recovery.

Based on the  results of this study, the systemic LOAEL is 49 mg/m 3
for both sexes, based on cardiac pathology,  decreased body weight gain,
altered hematology and clinical chemistry, and gross pathological
findings in the lungs. The systemic NOAEL is  5.4 mg/m3  (0.005 mg/L)
for P1/P13.

This study is classified as acceptable (guideline) ans satisfies the
guideline requirement (OPPTS 870.3465;  OPP 82-4) for a subchronic
inhalation toxicity study in rats.

Reference:  R. J. Hilaski;  March 27, 1995;  Thirteen week subchronic
inhalation toxicity study on North American P2 Creosote CTM in rats.;
International Research and Development Corp., Mattawan, MI 49071;
Project No. 671-018;   Creosote Council II;  MRID # 43600901.
Unpublished.

Executive Summary: In a 13-week inhalation toxicity study (MRID #
43600901), 20 Sprague-Dawley rats/sex/group were treated for 5
days/week, 6 hours/day with P2 Creosote CTM via whole body exposure at
doses of 0, 4.7, 48 or 102 mg/m3 (0, 0.005, 0.048 or 0.102 mg/L ) in air
measured gravimetrically.  The aerosol size MMAD was between 2.4 and 2.9
microns with a geometric standard deviation between 1.85 and 1.91.
Subsequent to the exposure period 10 rats/sex/group were allowed to
recover from treatment for 6 weeks.

During the exposure period, two animals (low dose female; mid dose
male) were sacrificed in extremis and the cause of morbidity was not
related to treatment.  Significant treatment-related findings in mid and
high dose animals included decreased terminal body weight and body
weight gain (m/f), altered hematological parameters (decreased
hemoglobin content, hematocrit, erythrocyte and platelet counts;
increased reticulocyte counts and mild poikilocytosis, m/f) and
biochemical parameters (increased serum cholesterol levels, m/f).  In
both sexes macroscopic discolouration of the lungs persisted through the
recovery period and correlated with the presence of black pigment
granules within alveolar macrophages.  Both sexes showed increased
absolute and relative liver and thyroid weights and increased
lung/trachea/body weight ratios.  Absolute and relative thyroid weights
of high dose animals actually increased after the recovery period.  An
increased incidence of lesions of the nasal cavity epithelium (chronic
inflammation) was noted following treatment (all treatment groups, m/f)
but appeared to lessen in incidence and severity during the recovery
period (mainly the high dose group, m/f).  During exposure an increased
incidence of thyroid follicular epithelial cell hypertrophy occurred in
all male groups including control and in the high dose female group.  At
recovery the male incidence remained similar to that observed at
exposure while the incidence in females of the high dose group had
declined.  The incidence of thyroid follicular cell hypertrophy was
slightly increased in low and mid dose females after the recovery
period. Slightly increased incidence of mild poikilocytosis was observed
in all treatment groups (m/f) including the low dose group and control,
which persisted through the recovery period. Low dose animals exhibited
lesions of the nasal cavity epithelium which had resolved after the
recovery period.  Based on the results of this study, the systemic LOAEL
is 48 mg/m3  , based on  decreased body weight and weight gain, altered
hematology ad clinical chemistry, increased absolute and relative weight
of the liver ad thyroid, and increased incidence of lesions of the nasal
cavity. The systemic NOAEL is set at 4.7 mg/m3 (0.0047 mg/L )  for P2
Creosote CTM in rats.

This study is classified as acceptable (guideline) and satisfies the
guideline requirement (OPPTS 870.3465;  OPP 82-4) for a subchronic
inhalation toxicity study in rats for P2 creosote.

2.3 Developmental Toxicity

Reference: Raymond York, (March 10, 1995).  Developmental Toxicity Study
In Rats: North American P1/P13 Creosote.  IRDC, 500 North main Street,
Mattawan, MI, Report number 671-020, The Creosote Council II, Mellon
Hall, Duquesne University, Pittsburgh, U.S.A. MRID # 43584201.
Unpublished.

In a developmental toxicity study using P1/P13 creosote (MRID #
43584201), pregnant female Sprague-Dawley rats (30/dose) were
administered P1/P13 creosote at dose levels of 0, 25, 50, and 175
mg/kg/day on gestation days 6 through 15 inclusive.  Decreased body
weight and food consumption were observed in dams at the 175 mg/kg/day
dose level.   Decreased uterine weight was observed in dams at the high
dose, which is reflected partly by the decreased live fetuses per litter
at the high dose (although mean fetal weight was not affected).
Cesarean section observations showed significantly increased resorptions
and post-implantation loss as well as decreased number of live fetuses
per litter at the 175 mg/kg/day dose.   Based on the results of this
study, the maternal NOAEL is 50 mg/kg/day, and the maternal LOAEL is 175
mg/kg/day, based on decreased body weight gain and food consumption
during the study.

No treatment-related malformations (external, visceral or skeletal)
were observed in any of the fetuses at 25 mg/kg bw/day. At 50 mg/kg
bw/day, the overall incidence of malformations on a fetal and litter
basis were statistically elevated compared to controls. However, these
individual malformations were not seen at higher dose levels and/or fell
within the range of historical control data. At 175 mg/kg/day there was
(i) an overall significant increased incidence of developmental
malformations, (ii) increased incidence of cardiovascular, vertebral and
digital malformations, compared to lower dose levels, concurrent
controls or historical controls (2429 and 2898 fetuses examined
viscerally and skeletally respectively) and (iii) an increased incidence
of malformations at this dose level in spite of increased fetal loss
(resorptions) (Beck and Lloyd, 1963) thus resulting in fewer fetuses
available for teratogenic examination.  Although the incidence of fetal
malformations observed at 175 mg/kg/day dose level in rats was low and
could be related to maternal stress (decreased body weight gain and food
consumption), the teratogenic potential of P1/P13 Creosote cannot be
ruled out. Based on these data, the developmental toxicity NOAEL is 50
mg/kg/day, and the developmental toxicity LOAEL is 175 mg/kg/day, based
on increased post-implantation loss, increased mean resorptions,
decreased live fetuses per litter, and increased developmental
malformations.

This study is classified as acceptable and satisfies the guideline
requirement (83-3) for a developmental toxicity study in rats with
P1/P13 creosote.

Reference:  Developmental Toxicity Study In Rats: North American P2
Creosote.  Raymond G. York (March 10, 1995), IRDC, 500 North Main
Street, Mattawan, MI, Report number 671-022, The Creosote Council II,
Mellon Hall, Duquesne University, Pittsburgh, U.S.A. MRID # 43584202.
Unpublished.

Executive Summary: In a developmental toxicity study (MRID # 43584202),
pregnant female Sprague-Dawley rats (30/dose) were administered P2
creosote by gavage  on gestation days 6 through 15 inclusive at dose
levels of 0, 25, 75, and 225 mg/kg/day. Although decreases in body
weight and food consumption were observed at all dose levels, food
efficiency appeared affected only at the high dose of 225 mg/kg/day.
Thus, the cesarean section effects observed at this dose (decreased
implantations/dam, increased pre- and post-implantation loss, increased
resorptions, decreased uterine weight) could be secondary to the
decreased food efficiency observed at this dose.  This distinction is a
fine one, however, based on results with P1/P13 creosote in which no
decrease in food efficiency was observed at a dose of 175 mg/kg, but
increased resorptions, increased post-implantation loss, and decreased
live fetuses per litter were observed at 175 mg/kg.  The Maternal NOAEL
in this study is determined to be 75 mg/kg/day, and the LOAEL 225
mg/kg/day, based on decreased food efficiency observed in maternal rats
at 225 mg/kg/day.

With regards to assessing the teratogenic potential of P2 Creosote in
rats, no treatment-related malformations (external, visceral or
skeletal) were observed at the 25 mg/kg bw/day dose level. The single
incidences of malformations [craniorachischisis, hydrocephaly and
malpositioned eye (same pup)] observed at the 75 mg/kg bw/day dose
level, and hydrocephaly at the 225 mg/kg bw/day dose level compared to
none observed in lower dose levels, concurrent controls or historical
controls (2429 and 2898 fetuses examined viscerally and skeletally
respectively) were considered treatment-related. It should be noted that
at 225 mg/kg bw/day one whole litter was resorbed and the number of
fetuses examined at this level for visceral and skeletal malformations
was approximately 50% of those examined at the mid-dose level. The
developmental toxicity NOAEL is determined to be 25 mg/kg/day in this
study, based on the incidences of malformations observed at 75 mg/kg/day
which exceeded both concurrent and historical control incidence.

Reference: York, R. (1994): Developmental Toxicity Study in New Zealand
White Rabbits: Creosote P1/P13. Laboratory Project number 672-002. Study
conducted by IRDC.  Unpublished.

In a developmental toxicity study in rabbits (MRID 44839802),
artificially inseminated New Zealand White Rabbits (20/dose) were
administered creosote P1/P13 in corn oil by gavage on gestation days 6
through 18. Doses were 0, 1, 9, and 75 mg/kg/day. At the 75 mg/kg/day
dose level, increased abortions (3 rabbits vs. 0 control), reduced live
fetuses (28 vs. 50 in control), and decreased implantation sites were
noted in maternal rabbits.  There was no significant effect of creosote
P1/P13 treatment on offspring in this study.  The Maternal NOAEL in this
study is determined to be 9 mg/kg/day based on effects noted at 75
mg/kg/day.  The Developmental NOAEL is determined to be 75 mg/kg/day,
and the LOAEL > 75 mg/kg/day.

2.4 Reproductive Toxicity

Reference: Marcinowski, J. (1993).  Two-Generation
Reproduction/Fertility Study in Rats: Lab Project Number: 672-006.
Unpublished study prepared by International Research & Development Corp.

In a two-generation reproduction toxicity study (MRID 42893201),
Charles River Crl:CD rats, 26/sex/group, were dosed by gavage with
P1/P13 creosote in corn oil at doses of 0, 25, 75, and 150 mg/kg/day.
Pre-mating treatment phase lasted approximately 17 weeks, which may have
contributed to the decreased fertility observed in this study.  Systemic
effects observed in this study for parental animals included a
dose-related decrease in body weight during the pre-mating period at all
dose levels.  Salivation was  observed at 75 mg/kg/day and above in the
F1 generation.  Effects in offspring included a dose-related decrease in
growth of  the F0 generation starting at 25 mg/kg/day (as shown by
decreased pup weight). For the F0 pups, mean number of live pups per
litter was decreased at 75 and 150 mg/kg/day, and percent live pups at
175 mg/kg/day was also decreased. In the F1 pups, the percent live pups
was decreased at 75 and 150 mg/kg/day, but pup growth was affected only
at 150 mg/kg/day as shown by decreased mean pup weight. Decreased
fertility and pregnancy indices were observed in the F1 female parental
rats at all dose levels, but this was not interpreted as a
treatment-related effect, as it was more likely related to the fact that
the critical weight for fertility was exceeded by the 17-week pre-mating
interval. Based on the results of this study, the Parental Systemic
NOAEL is < 25 mg/kg/day, and the parental systemic LOAEL is 25
mg/kg/day, based on decreased pre-mating body weight.  The developmental
NOAEL in this study is < 25 mg/kg/day, and the developmental LOAEL is 25
mg/kg/day, based on a dose-related decrease in pup body weight for the
F0 pups from days 14-21. The reproductive NOAEL is < 25 mg/kg/day, and
the reproductive LOAEL is 25 mg/kg/day, based on reduced pregnancy and
fertility indices in F1 female parental rats.

2.5 Chronic Toxicity/Carcinogenicity

The chronic toxicity/carcinogenicity data base submitted to the Agency
for creosote consists of a six-month initiation/promotion study of
creosote conducted in mice.  This study was not designed for purposes of
deriving a quantitative risk estimate of carcinogenic potency. However,
a recently conducted study by Culp et al. (Carcinogenesis vol. 19, no.1,
pp. 117-124) did examine tumors induced by coal tar mixtures and is also
summarized in this section.

Reference:  Naas, D.J.  (1996) A 6-month dermal oncogenicity study of
creosote in mice.  WIL Research Laboratories, Inc., 1407 George Road,
Ashland, OH  44805-9281, Project No. WIL-100005, January 11, 1996.  MRID
44844401. Unpublished.

EXECUTIVE SUMMARY:  In a dermal oncogenicity study (MRID 44844401),
North American P1/P13 creosote composite (100.0%, lot no. P1/13-009-A)
was administered to groups of 30 male Crl:CD-1® mice by applying 50
µL aliquots of 1%, 50% or 100% corresponding to 10 µg/µL, 500
µg/µL, or undiluted creosote to the shaved backs of the mice.  Acetone
was utilized as a solvent throughout the study and was used as the
solvent control.  9,10-Dimethyl-1,2-benzanthracene (DMBA) was utilized
as a positive tumor initiator, and 12-0-tetradecanoylphorbol-13-acetate
(TPA) was used as a positive tumor promoter in the study.  Creosote was
tested as a tumor initiator with TPA as promotor, as a promotor with
DMBA as initiator, and as both initiator and promotor (complete
carcinogen).  A positive control group with DMBA and TPA, and acetone
controls groups with DMBA and TPA were included.  The initiation phase
consisted of 5 applications/week for 2 weeks followed by a two week rest
period, and then promotion ( 2 applications/week for 26 weeks).

Creosote treatment at 50% and 100% especially during the promotion phase
caused skin irritation and clinical signs including severe erythema,
slight edema, eschar, and exfoliation. Increased incidences of thickened
skin (7-11/30, p < 0.01), scabbing (16-20/30, p < 0.01), acute
inflammation (12-18/30, p < 0.01), ulceration (6-10/30, p < 0.05-0.01),
and epithelial hyperplasia (13-23/30, p < 0.01) were seen at the
application site during necropsy compared to the DMBA/acetone controls
(0/30).  Dermal treatment with Creosote did not result in a significant
decrease in survival, although 6 mice died during treatment in the
DMBA/100% creosote group compared to none in the acetone control groups.
 Group mean body weights of males treated with 100% creosote during the
initiation phase were decreased by 6-8% by the end of the 2-week
treatment regimen; however, they gained weight rapidly over the next
week and no further decreases in weight or weight gain were seen with
creosote treatment compared to the acetone controls.  Food consumption
in the experimental groups was generally greater than in the solvent
control groups.

Increased incidences of enlarged lymph nodes were seen with 50% (6/30,
p < 0.05), and 100% creosote (5-9/30, p < 0.05-0.01) during the
promotion phase with DMBA as initiator and with 100% creosote as both
initiator and promotor (6-9/30, p < 0.05-0.01) compared to 0/30 in the
solvent controls.  Incidences of enlarged spleen were also increased
(15-19/30, p < 0.01) with 50% and 100% creosote in the promotion phase
compared to the controls (1/30).

The LOAEL is 50 µL of 50% or 25,000 µg/day twice/week applied to the
skin for 26 weeks, based on skin toxicity, enlarged lymph nodes and
enlarged spleen. The NOAEL was 50 µL of 1% or 500 µg/day applied to
the skin twice/week for 26 weeks.

Topical treatment of male Crl:CD-1® mice for 2 weeks in the initiation
phase of the study with all concentrations of creosote followed by
treatment with TPA resulted in increased incidences of neoplasms,
chiefly skin papillomas (acetone/TPA control, 0%; creosote/TPA treated,
80-90%, p < 0.01).  Treatment twice a week for 26 weeks during the
promotion phase with 50 µL of  500 µg/µL or undiluted creosote
following the DMBA initiation phase resulted in tumor incidences of 100%
compared to 3% in the DMBA/acetone control.  Topical treatment with
undiluted creosote in both the initiation and promotion phases resulted
in a 100% tumor incidence compared to 0% in the acetone control group.
Creosote acted as an initiator, promoter, and complete carcinogen under
the conditions of this study.

This oncogenicity study in the mouse is Acceptable/Nonguideline.  The
study had numerous deficiencies that limited the information obtainable
on possible systemic toxic effects, but the data demonstrated
unequivocally the oncogenic nature of creosote when applied to the skin
of Crl CD-1® mice.  The deficiencies did not affect this outcome of the
study, which was designed to assess the skin tumor initiating,
promoting, and complete carcinogenicity of creasote.

Reference: Culp, S.J., Gaylor, D.W., Sheldon, W.G., Goldstein, L.S., and
Beland, F.A. (1998): A comparison of the tumors induced by coal tar and
benzo(a)pyrene in a 2-year bioassay. Carcinogenesis 19:1, pp. 117-124

Summary: In an oral carcinogenicity study conducted by  Culp et al.
(1996), the carcinogenicity of two coal tar mixtures and pure
benzo[a]pyrene (BaP) was studied.  Coal tar mixture 1 (CTM-1) was a
composite of coal tar samples from seven coal gasification plant waste
sites and was dosed at 0.0, 0.01, 0.03, 0.1, 0.3, 0.6, and 1.0% of diet.
 Coal tar mixture 2 (CTM-2) was a composite of coal tars from three
waste sites with high BaP content and was dosed at 0.0, 0.01, 0.03, 0.1,
0.3% of diet.  An additional group was dosed with pure BaP at 0, 0.0005,
0.0025, and 0.01 % in diet.  A control group received solvent control in
diet.  Each group consisted of 48 mice.

In mice exposed to coal tar, coal tar acted as a systemic carcinogen and
induced a dose-related increase in hepatocellular adenomas and
carcinomas, alveolar/bronchiolar adenomas and carcinomas, forestomach
squamous epithelial papillomas and carcinomas, small intestine
adenocarcinomas, histiocytic sarcomas, hemangiosarcomas in multiple
organs, and sarcomas in several tissues.

The incidence of forestomach tumors increased sharply between the 0.1
and 0.3% doses.  However, there was not a proportional increase in
forestomach tumors above 0.3% because these mice died from
adenocarcinomas of the small intestine.  Tumors of the esophagus,
observed in BaP treated mice, were not observed in the CTM1 or CTM-2
treated groups.  Lung and hepatocellular tumors observed in the CTM1 and
CTM2 groups were not observed in BaP treated animals.

Multiple neoplasms were noted in liver, lung, forestomach, and the small
intestines of exposed mice.  Liver neoplasms occurred in 1, 0,  and 4
mice fed 0.03, 0.1 and 0.3% CTM-1, respectively.  Lung neoplasms
occurred in 21, 11 and 13 mice fed 0.3% , 0.6% , 1.0% CTM-1,
respectively.  Eight mice in the 0.3% CTM-2 group had multiple lung
neoplasms.  Forestomach carcinomas were found in 2 and 1 mice fed 0.6%
or 1.0% CTM-1, respectively.  Adenocarcinomas were found in the small
intestines (jejunum) of 2 and 12 mice fed 0.6% and 1.0% CTM-1,
respectively.  Groups dosed with (0.3% CTM-1 or CTM-2 had significantly
reduced survival.

d 25 ppm, equivalent to 20.5 and 104 μg BaP/day.  Tumors of the
esophagus were not observed in the CTM1 or CTM-2 treated groups.  Lung
and hepatocellular tumors, observed in CTM treated mice, were not
observed in mice fed BaP.

Multiple neoplasms of the forestomach occurred in 8 and 21 mice fed 25
and 100 ppm BaP, respectively.  Multiple neoplasms of the esophagus and
tongue were noted in 6 and 3 mice, respectively, fed 100 ppm BaP.  It
should be noted that all animals in 100 ppm group died before
termination of the study.

2.6 Dermal Absorption

CITATION:	Fasano, W. (2007) AWPA P1-P13 Creosote: In vivo dermal
absorption in the rat. E.I. du Pont de Nemours and Company, HaskellSM
Laboratory for Health and Environmental Sciences, Newark, Delaware.
Laboratory Project ID:  DuPont-19622, July 2, 2007. MRID 47179501.
Unpublished.

EXECUTIVE SUMMARY:  In a dermal penetration study (MRID 47179501) AWPA
P1-P13 Creosote (98.5% a.i.) spiked with eight radiolabeled target
chemicals (approx. 43% of the chemicals in creosote) was applied to the
clipped dorso-lumbar skin (10.5 cm2) of eight male Sprague-Dawley rats
at a dose of 10.7 mg/cm2 skin (10 µL/cm2, total radioactivity 16.7
µCi). The exposure duration was 8 hours.  At the end of 8 hours,
animals were removed from the metabolism cages, and the application
sites were washed with 2% Ivory soap solution followed by a water rinse
and then a dry natural sponge. Four rats were then euthanized (0 hours
post-exposure) while the other 4 rats were  returned to the metabolism
cages for further excreta collection. These 4 rats were sacrificed at
496 hours post-exposure.

The mean percent recovery of the radioactivity in the applied dose was
95.009% (±2.569%) and 96.609% (±3.628%) at 0 and 496 hours
post-exposure, respectively. The majority of the administered dose was
recovered from the skin wash sponges; the mean percent recovery was
59.283% (±12.54%) for the 0-hr post-exposure group and 56.822%
(±8.294%) for the 496-hr post-exposure group. The mean percent absorbed
dose was 6.342% (±0.808%) at 0 hours post-exposure and 33.959%
(±8.445%) at 496 hours post-exposure, with a mean percent of 1.553%
(±0.299%) and 0.005% (±0.003%), respectively, present in the skin
after removal of the stratum corneum. Most of the absorbed dose had been
excreted by 496 hours post-exposure, with a mean of 18.97% (±4.97%) of
the dose eliminated in the urine and 12.60% (±4.11%) eliminated in the
feces.

In a supplemental dermal penetration study intended to clarify the
results for the 496 post-exposure group in the initial main study, AWPA
P1-P13 Creosote (98.5% a.i.) spiked with eight radiolabeled target
chemicals was applied to the shaved dorsal skin (10.5 cm2) of four male
Sprague-Dawley rats at a dose of 10.7 mg/cm2 skin (10 µL/cm2, total
radioactivity 18.9 µCi). The exposure duration was 8 hours. Animals
were sacrificed at 496 hrs post-exposure (504 hrs post-dosing). In the
supplemental absorption study, the O-ring, which demarcated the
application area, was applied without glue following the dose
application, and was removed at the end of the 8-hr exposure. In the
main study, the O-ring had been glued to the skin one day prior to dose
application and remained in place until study termination.

In the supplemental study, the mean percent recovery of the
radioactivity in the applied dose was 92.775% (±2.70%) at 496 hours
post-exposure. The majority of the administered dose was recovered from
the body wrap (34.228±6.328%), skin wash (22.240±7.818%), and O-ring
(27.452±3.680%).   Although the mean percent absorbed dose was reported
in this supplemental experiment as 8.853±1570%, with a mean percent of
0.005% present in the skin after removal of the stratum corneum, the
presence of a significant amount of radioactivity in the body wrap after
8 hours adds uncertainty as to the actual available dose.  In addition,
in the first experiment, dermal absorption was still evident after
washing of the skin at 8 hours and monitoring of urinary and fecal
excretion of radioactivity from 8 hours onward. Therefore, the data are
not conclusive of a reduced dermal absorption based on the contention
that the O-ring or the glue had an influence on dermal absorption.

In a preliminary plasma kinetic (dermal bioavailability) study, neat
creosote was applied to the clipped dorso-lumbar skin (10.5 cm2) of four
male Sprague-Dawley rats (10 µL/cm2) for an exposure duration of 8
hours; animals were sacrificed 168 hours post-dosing (160 hours
post-exposure). None of the twelve target creosote chemicals analyzed in
the plasma were detected above their detection limit.

This study in the rat is ACCEPTABLE-NON-GUIDELINE  Although only one
exposure duration and one exposure concentration were evaluated, this
was part of an agreement in study design between the Antimicrobials
Division and the registrant.

CITATION:	Fasano, W. (2007) AWPA P1-P13 Creosote: In vitro kinetics in
rat and human skin. E.I. du Pont de Nemours and Company, HaskellSM
Laboratory for Health and Environmental Sciences, Newark, Delaware.
Laboratory Project ID:  DuPont-21647, April 30, 2007. MRID
47179502.Unpublished.

EXECUTIVE SUMMARY:  In an in vitro dermal absorption study using rat and
human skin preparations (MRID 47179502), AWPA P1-P13 Creosote (98.5%
a.i.) spiked with eight radiolabeled target chemicals was applied to 6
rat and 6 human skin preparations mounted in individual static diffusion
cells at a nominal dose of 10,700 µg creosote/cm2 (1 µCi/skin).
Samples were collected from the receptor chambers at 0.5, 1, 2, 4, and 8
hours post-application. The skin was washed 8 hours post-application and
the study terminated. The amount of the applied dose absorbed was
considered to be the amount of radioactivity measured in the receptor
fluid.

The mean total recovery of the applied dose for the rat and human skin
was 78.3% and 83.9%, respectively. The mean absorbed dose was 15.1% for
the rat skin and 3.34% for the human skin. The mean rate of penetration
was 85.3 µg equiv/cm2/hr for the rat skin and 19.7µg equiv/cm2/hr for
the human skin. The mean rate of penetration and the mean total
penetration for the rat skin were approximately 4.3 times and 4.4 times
greater than that for the human skin, respectively.

Based on (1) the lack of data demonstrating that the concentration of
the creosote solution did not exceed solubility limits and therefore did
not have an artefactual influence on the magnitude of absorption in the
in vitro test system, and (2) the continued absorption observed after 8
hours in the in vivo study [the O-ring influence could not be
conclusively demonstrated to be acting as a depot for radioactivity]),
the conclusion was to use the value of 34% from the in vivo absorption
study and recognize the 8-fold difference in absorption between human
and rat skin. Therefore, a value of 5% for dermal absorption was used
(34% divided by 8 and rounded upward).

2.7 Mutagenicity

In consideration of the available evidence that creosote is a positive
mutagen, the Agency waived the requirement for the standard mutagenicity
battery, and instead required dominant lethal testing of both the P1/P13
and P2 blends. The executive summaries of these studies are shown below.

In a  rat dominant lethal assay (MRID not available), male
HSD:Sprague-Dawley CD rats were treated orally once per day for five
consecutive days with Cresosote P1/P13 at target doses of 725, 362.5 or
181.25 mg/kg body weight/day in a volume of 2.5 mL/kg.  Actual doses
determined by chemical analysis were 857.5, 330.5 and 230.8 mg/kg/day.
Twenty-one rats were dosed at the two lower doses and 26 rats at the
highest dose.  The vehicle was corn oil.  Seven days after the initial
dosing, each male was mated with two untreated females per week for 10
weeks. Females were sacrificed 13 days after the midweek of the
presumptive mating day and the following data collected:  total
implantations per female, corpora lutea per female, preimplantation
losses per female, live implantations per female, dead implantations per
female, proportion of females with one or more dead implantations,
proportion of females with two or more dead implantations and dead
implantations/total implantations (expressed as a percentage).  The
fertility index, computed as the number of fertile females (with corpora
lutea present) per number of mated females, was also determined.

Creosote P1/P13 was tested to toxic doses.   In the dominant lethal
study, all rats in the top two treatment groups but none in the low dose
group showed decreased activity following dosing and all rats in the
high dose group had dyspnea.  Two animals in the low dose group and two
in the high dose group had material around the nose and mouth. Other
pharmacotoxic signs were limited to a few animals in the high dose group
and included lacrimation, deposition of the test material around the
eyes, increased salivation and anogenital staining.  One high dose rat
died following the fourth dose.  A dose-related decrease in body weight
in the low-, mid-, and high-dose animals, compared to the solvent
controls, was seen during the dosing period, and this initial weight
loss was not recovered in mid- and high-dose rats during the ten week
mating period.   Statistically significant differences from control
values were seen in a number of endpoints throughout the study;;
however, with the exception of results from mating group nine, none were
endpoints indicative of a dominant lethal effect.  In mating group nine,
statistically significant increases were seen in dead implantations per
female, the percentage of females with ( one implantation, the
percentage of females with ( two implantations and the percent dead
implantations per total implantations. These increases were seen at the
low and mid doses but not at the high dose.  Also, the vehicle control
values in mating group nine were unusually low compared to those in the
other weekly mating groups (there were fewer preimplantation losses
(0.85 per female) and fewer dead implantations (0.41 per female) than
seen for the vehicle controls in the other mating groups (1.53 ± 0.37
and 0.85 ± 0.20 per female, respectively) and values for percentage of
females with ( one and two dead implantations and the percent dead
implantations per total implantations were depressed).  The  results,
although statistically significant, are thus not considered biologically
significant.  Positive and solvent control values were appropriate
except where noted for the vehicle controls in mating group nine.  Based
on the results of this study, there was no evidence that Creosote P1/P13
induced dominant lethals in any germ cell stage in male rats as tested
in this study.

In a  rat dominant lethal assay (MRID not available), male
HSD:Sprague-Dawley CD rats were treated orally once per day for five
consecutive days with Creosote P2 at target doses of 775, 387.5 or
193.75 mg/kg body weight/day in a volume of 2.5 mL/kg.  Actual doses by
chemical analysis were 866.3, 431, or 199.3 mg/kg body weight/day.
Twenty-one rats were dosed at the two lower doses and 26 rats at the
highest dose.  The vehicle was corn oil.  Seven days after the initial
dosing, each male was mated with two untreated females per week for 10
weeks. Females were sacrificed 13 days after the midweek of the
presumptive mating day and the following data collected:  total
implantations per female, corpora lutea per female, preimplantation
losses per female, live implantations per female, dead implantations per
female, proportion of females with one or more dead implantations,
proportion of females with two or more dead implantations and dead
implantations/total implantations (expressed as a percentage). The
fertility index, computed as the number of fertile females (with corpora
lutea present) per number of mated females, was also determined.

Creosote P2 was tested to an adequate dose.  All rats in all treatment
groups showed decreased activity following dosing.  Other clinical
signs, limited to a few animals in which there was a back-up of test
material during dosing, were lacrimation, deposition of the test
material around the eyes and increased salivation in one high-dose male,
labored breathing in one low-dose male and two high-dose males, and
material around nose and mouth in two low-dose, one medium-dose and four
high-dose males.  Reduced food consumption was seen in all high-dose
rats.  No dosing- or test material-related deaths occurred during the
study.  A dose-related decrease in body weight in the low-, mid-, and
high-dose animals, compared to the solvent controls, was seen during the
dosing period, and this initial weight loss was not recovered in mid-
and high-dose rats during the ten week mating period.  Statistically
significant differences from solvent control values (p ( 0.05) were seen
for a number of endpoints during the first nine weekly mating intervals
but, with one exception, not in endpoints considered indicative of
dominant lethality.  The one exception was a significant increase in the
number of dead implants over the solvent control value in the sixth
mating group at the lowest Creosote P2 dose.  This increase was not
considered biologically relevant because no significant increases were
seen at higher doses or in other endpoints concerning dead implants.  In
the tenth mating group (exposure to the test material at the
spermatogonial stem cell stage), an apparently dose-related increase was
seen in the number of dead implantations per female, the percentage of
females with ( 1 dead implant, the percentage of females with ( 2 dead
implants and the percentage of dead implantations per total
implantations.  The increases reached statistical significance at the
highest dose for the first two endpoints.   Positive and solvent control
values were appropriate.  The data in this study, while indicating a
positive effect at week 10 of treatment, are not considered to be
treatment-related, based on the conclusion that while dead implantations
per female was significantly increased at the highest dose tested at
mating week 10, the number of live implants/female was not significantly
reduced (<5% lower than control).  In addition,  no dominant lethal
effects were seen at weeks 8 or 9, which would also sample
spermatogonial cells.   Therefore, creosote P2 is considered to be
negative for dominant lethal effects in rats.

2.8 Neurotoxicity

There are no current Agency guideline neurotoxicity studies available
for creosote.  Of the existing studies available, there is no evidence
of neurotoxicity for either the P1/P13 or P2 blends of creosote,
although there is valid concern for some of the components of creosote,
which are known to be neurotoxic (i.e. naphthalene).  Data  from the
ATSDR Toxicological profile for Creosote  showed increased brain-to-body
weight ratios after exposure of male and female rats to beechwood
creosote (used therapeutically in the past as a disinfectant and
expectorant, and composed mainly of phenol, cresols, guaicol, xylenol,
and creosol)  to 257 mg/kg/day in the diet for 3 months in male rats, or
exposure of female rats for 52 weeks to 297 mg/kg/day in the diet, or
exposure of male and female rats for 96 weeks in the diet to 143 and 394
mg/kg/day, respectively. Acute exposure of male and female rats to 600
and 313 mg/kg beechwood creosote resulted in  convulsions. Although
signs of neurologic involvement were evident,  no treatment-related
pathological findings of the central nervous system were noted at
necropsy in these studies.

 Based on the above data, and realizing that creosote is currently
registered only for non -food use and is a restricted use pesticide, no
additional neurotoxicity testing will be required at this time.

3.0  Dose-Response Assessment

On April 1, 1999, the Health Effects Division's Hazard Identification
Assessment Review Committee (HIARC) evaluated the toxicological
endpoints selected  for occupational and residential (dermal and
inhalation) exposure risk assessments for Creosote.  On September 3,
2003, the Antimicrobials Division Toxicity Endpoint Selection Committee
(ADTC) met to verify the selected endpoints for long-term dermal risk
assessments for creosote and  inhalation risk assessment, and also
discussed whether dermal and inhalation Margins of Exposure should be
combined for creosote risk assessment.  The toxicological endpoints
selected for various exposure scenarios are summarized in Table 2.
below.

Table 3.  Summary of Doses and Endpoints Selected for Creosote  Risk
Assessments.

EXPOSURE

SCENARIO

Endpoint (mg/kg/day) and Margin of Exposure (MOE)

ENDPOINT

STUDY

Acute and Chronic Dietary

 Acute and Chronic Dietary risk assessment not required

Carcinogenicity

(dermal)

Creosote has been shown to exert positive mutagenic effects in vitro,
and has been shown to be positive for carcinogenicity in an
initiation/promotion study.  Creosote  has been classified as a B1
carcinogen in IRIS. An oral cancer slope factor of 6.28 x 10-6  (µg
CTM1/kg/day)-1 was selected for creosote using the data of Culp et al
(1998) for the coal tar mixture 1 (CTM1) on the basis of forestomach
tumors.

Short-Term  (Dermal)

Oral NOAEL=50

MOE = 100

 decreased body weight gain at 175 mg/kg/day

 Developmental Toxicity - Rat

Intermediate-term

(Dermal)

Dermal NOAEL = 40

MOE=100

Decreased body weight gain at 400 mg/kg/day

90-Day Dermal Toxicity Study in the Rat

Long-Term (Dermal)a

Oral  LOAEL = 25 mg/kg/day

MOE = 300

decreased pre-mating body weight

2-generation reproduction study - Rat

Inhalation-creosote

(any  time period)b

NOAEL = 0.0047mg/m3

MOE = 100

decreased body  weight, body weight gain, altered hematology

90-day Inhalation Study in the Rat with P2 creosote (MRID 43600901)

Inhalation-naphthalenec (any time period)

HEC = 52 mg/m3

MOE = 300

nasal effects: hyperplasia and metaplasia in respiratory and olfactory
epithelium respectively

Two year inhalation toxicity study - mouse (USEPA, IRIS)

Dermal absorption d

5%, determined from the results of in vivo / in vitro testing in rats
and in vitro testing using human skin (MRIDs 47179501 and 47179502).

  aafter re-examination of the toxicology data, the ADTC concluded that
the 2-generation reproduction toxicity study was appropriate for
long-term dermal risk assessment for the following reasons: the duration
of the 2-generation reproduction study is more representative of the
time frame (i.e. long-term) than the 90-day dermal study, and is
consistent with OPP policy regarding duration of the study vs.  route of
exposure;  body weight gain decreases in the 2-generation reproduction
toxicity study were observed in the F2 generation, supporting  the time
frame for the long-term endpoint (i.e. > 6 months).  The 90-day dermal
study effects are not as representative of the time frame for the
long-term dermal risk assessment.  However, the two studies can be
considered co-critical studies for this endpoint. Correction of the
LOAEL from the 2-generation reproduction toxicity study for dermal
absorption (50%) and use of a LOAEL (3x extra UF) yields a MOE and
endpoint (300 and 50 mg/kg/day) similar to the 90-day dermal toxicity
study (40 mg/kg/day and MOE of 300 [extra 3x to extrapolate to long-term
endpoint]).

bthe ADTC re-examined the use of the inhalation toxicity study selected
for inhalation risk assessment for creosote and concluded that a
developmental toxicity study, as used for the oral and dermal risk
assessments of creosote, is not appropriate for inhalation risk
assessment because: (1) the inhalation toxicity study showed significant
effects on body weight gain early in the study (one week) and is
therefore relevant for short-term assessment (2)  it is also a
route-specific study; and (3) the inhalation NOAEL is more sensitive
than the developmental NOAEL.   Therefore, the inhalation study will
remain as the study for the short-term inhalation endpoint.

ddermal absorption of creosote was determined from submitted in vivo and
in vitro studies on creosote (MRIDs 47179501 and 47179502).

4.0  Cumulative Risk

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether
to establish, modify, or revoke a tolerance, the Agency consider
available information concerning the cumulative effects of a particular
pesticide’s residues and other substances that have a common mechanism
of toxicity. As there are no tolerances for creosote, the Agency is not
considering whether creosote has a common mechanism of toxicity with any
other chemicals. However, based on the complex nature of the creosote
mixture, components of this mixture may act in similar ways to produce
the adverse effects noted for creosote.

5.0  Endocrine Disruption

EPA is required under FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances ( including all active
pesticides or other ingredients) “may have an effect in humans that is
similar to an effect produced by a naturally occurring estrogen, or
other such endocrine effects as the Administrator may
designate.”Following the recommendations of its Endocrine Disruptor
Screening and Testing Advisory Committee (EDSTAC), the EPA  has
determined that there was scientific bases for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the
estrogen hormone system. EPA also adopted EDSTAC recommendation, that
program include evaluations of potential effects in wildlife may. For
pesticide chemicals, EPA will use FIFRA and, to some extent that effects
in wildlife may help determine whether a substance may have an effect on
humans, FFDCA authority to require the wildlife evaluations. As the
science develops and resources allow, screening additional hormone
systems may be added to the Endocrine Disruptor Screening Program.

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, creosote may be subjected
to additional screening and/or testing to better characterize effects
related to endocrine disruption.

6.0 References

MRID 43032101: North American P1/P13 Creosote: Acute Oral Toxicity Study
in Rats. Study                    conducted by IRDC, Mattawan, MI for
the Creosote Council II.  Unpublished.

      HED document no. 011033.

MRID 43032102: North American P1/P13 Creosote: Acute Dermal Toxicity
Study in Rats.                                         Study conducted
by IRDC, Mattawan, MI for the Creosote Council II.
                       Unpublished. HED document no. 011033.

MRID 43032103: North American P1/P13 Creosote: Acute Inhalation Toxicity
Study in Rats.                        Study conducted by IRDC, Mattawan,
MI for the Creosote Council II.
Unpublished. HED document no. 011033.

MRID 43032104: North American P1/P13 Creosote: Eye Irritation Study in
Rabbits. Study                                          conducted by
IRDC, Mattawan, MI for the Creosote Council II.

                               Unpublised. HED document no. 011033.

MRID 43032105: North American P1/P13 Creosote: Primary Dermal Irritation
Test in Rabbits.                                   Study conducted by
IRDC, Mattawan, MI for the Creosote Council II.
               Unpublished. HED document no. 011033.

MRID 43032106: North American P1/P13 Creosote: Dermal Sensitization
Study (Buehler) in the                                Albino Guinea Pig.
Study conducted by IRDC, Mattawan, MI for the

                               Creosote Council II.  Unpublished. HED
document no. 011033.

MRID 43032301: North American P2 Creosote: Acute Oral Toxicity Study in
Rats. Study                                            conducted by
IRDC, Mattawan, MI for the Creosote Council II.

                               Unpublished. HED document no. 011033.

MRID 43032302: North American P2 Creosote: Acute Dermal Toxicity Study
in Rats. Study                                      conducted by IRDC,
Mattawan, MI for the Creosote Council II.

                               Unpublished.

MRID 43032303: North American P2 Creosote: Acute Inhalation Toxicity
Evaluation in Rats.                                    Study conducted
by IRDC, Mattawan, MI for the Creosote Council II.
                   Unpublished. HED document no. 011033.

MRID 43032304: North American P2 Creosote:Eye Irritation Study in Rats.
Study conducted

                 by IRDC, Mattawan, MI for the Creosote Council II.
Unpublished.

     HED document no. 011033.

MRID 43032305: North American P2 Creosote: Primary Dermal Irritation
Test in Rabbits.Study                                conducted by IRDC,
Mattawan, MI for the Creosote Council II.

                            Unpublished. HED document no. 011033.

MRID 43032306: North American P2 Creosote: Dermal Sensitization Study
(Buehler) in the                                      Albino Guinea Pig.
Study conducted by IRDC, Mattawan, MI for the

                              Creosote Council II.  Unpublished. HED
document no. 011033.

MRID 43601001: North American P1/P13 Creosote: Thirteen Week Subchronic
Inhalation                             Toxicity Study on North American
P1/P13 Creosote CTM in Rats:                                     Study
conducted by IRDC, Mattawan, MI for the Creosote Council II.

                               Report   No. 671-016 (1995). Unpublished.

MRID 43600901: North American P2 Creosote: Thirteen Week Subchronic
Inhalation                    		     Toxicity Study on North American P2
Creosote CTM in Rats:  Study
conducted by IRDC, Mattawan, MI for the Creosote Council II. Report No.
                                671-018 (1995).  Unpublished.

MRID 43616101: North American P1/P13 Creosote: 90-Day Subchronic Dermal
Toxicity Study                                in Rats.   Study
conducted by IRDC, Mattawan, MI for the Creosote Council
              II.  Report No. 671-013 (1995). Unpublished.

MRID 43616201: North American P2 Creosote: 90 Day Subchronic Dermal
Toxicity Study in                        Rats. Study  conducted by IRDC,
Mattawan, MI for the Creosote Council                            II.
Report No. 671-014 (1993). Unpublished.

MRID 43584201: North American P1/P13 Creosote: Developmental Toxicity
Study in Rats.                                     Study  conducted by
IRDC, Mattawan, MI for the Creosote Council
                 II.  Report No. 671-020 (1995). Unpublished.

MRID 43584202: North American P2 Creosote: Developmental Toxicity Study
in Rats.                                            Study  conducted by
IRDC, Mattawan, MI for the Creosote Council
                II.  Report No. 671-022 (1995). Unpublished.

MRID 47179501: Fasano, W. (2007) AWPA P1-P13 Creosote: In vivo dermal
absorption in the

      rat. E.I. du Pont de Nemours and Company, HaskellSM Laboratory for
Health

                             and Environmental Sciences, Newark,
Delaware. Laboratory Project ID:

                             DuPont-19622, July 2, 2007.

MRID 47179502: Fasano, W. (2007) AWPA P1-P13 Creosote: In vitro kinetics
in rat and human

                             skin. E.I. du Pont de Nemours and Company,
HaskellSM Laboratory for Health

                             and Environmental Sciences, Newark,
Delaware. Laboratory Project ID:

                             DuPont-21647, April 30, 2007.

York, Raymond G. (1994): Developmental Toxicity Study in New Zealand
White Rabbits. Study                                  conducted by IRDC,
Mattawan, MI for Koppers Inductries, Pittsburgh, PA.
             Report no. 672-002. Unpublished.

York, Raymond G. (1995): Two Generation Reproduction/Fertility Study in
Rats. Study                                              conducted by
IRDC, Mattawan, MI for Koppers Inductries, Pittsburgh, PA.
                   Report no. 672-006. Unpublished.

MRID 44844401: A 6-Month Dermal Oncogenicity Study of Creosote in Mice.
Study conducted                  by WIL Research Laboratories, Ashland,
OH for Koppers Industries,

                             Pittsburgh, PA. Report no. WIL-100005.
Unpublished.

McMahon, Timothy F.: Creosote: Endpoint Selection Report. February 2008.
Unpublished.

USEPA, 1984: Wood Preservative Pesticides: Creosote, Pentachlorophenol,
Inorganic

                       Arsenicals.  Position Document 4

Agency for Toxic Substances and Disease Registry (1990): Toxicological
Profile for Creosote. U.S. Department of Health and Human Services:
Public Health Service.

Culp, S.J., Gaylor, D.W., Sheldon, W.G., Goldstein, L.S., and Beland,
F.A. (1996): DNA adduct measurements in relation to small intestine and
forestomach tumor incidence during the chronic feeding of coal tar or
benzo[a]pyrene to mice.
Po祬祣汣捩䄠潲慭楴潃灭畯摮⁳ㄱ㘱ⴱ㘱⸸ഠ䌍汵
Ɒ匠䨮Ⱞ䜠祡潬Ⱳ䐠圮Ⱞ匠敨摬湯⹗⹇潇摬瑳楥Ɱ
䰠匮Ⱞ愠摮䈠汥湡Ɽ䘠䄮ㄨ㤹⤸›⁁潣灭牡獩湯漠
桴畴潭獲椠摮捵摥戠⁹潣污琠牡愠摮戠湥潺慛灝特湥
湩愠㈠礭慥⁲楢慯獳祡慃捲湩杯湥獥獩ㄠ⠹⤱›ㄱ
ⴷ㈱⸴ഠ

V

W

X

m

Ï

ã

/

‚

…

†

—

ò

W

X

Ð

Ñ

‚

ò

ó

 h+<

  h+<

 h+<

 h+<

 h+<

 h+<

 h+<

 h+<

 h+<

  h+<

³ð h+<

@

@

@

@

öîæÚÌÚ¾Ú¾Ú°Ú¾Ú¾Úæî©Ú©ÌÚ¾Ú¾Ú¾Úöî©žöžö
ž°žöî©žöî©žöî©æö“öæö©ö  h+<

  h+<

 h+<

 h+<

 h+<

 h+<

 h+<

 h+<

 h+<

 h+<

@

 h+<

  h+<

 h+<

  h+<

³ð h+<

  h+<

 h+<

 h+<

 h+<

 h+<

@

³ð h+<

 h+<

 h+<

 h+<

 h+<

 h+<

  h+<

  h+<

 h+<

  h+<

 h+<

 h+<

 h+<

@

 h+<

h+<

 h+<

 h+<

³ð h+<

 h+<

£ð h+<

 h+<

h+<

@

@

@

{

š

¢

£

h·~

  h+<

 h+<

 h+<

摧纷

L

摧纷

摧纷

 h+<

 h+<

 h+<

 h+<

฀Gaylor, D.W.,  Culp, S.J.,  Goldstein, L.S., and  Beland, F.A.
(2000): Cancer Risk Estimation for Mixtures of Coal Tars and
Benzo[a]pyrene. Risk Analysis 20(1): 81-85.

Schneider, K., Roller, M., Kalberlah, F., and Schumacher-Wolz, U.
(2002): Cancer Risk Assessment for Oral Exposure to PAH Mixtures. J.
Appl. Toxicol. 22: 73-83.

 PAGE  27


This is to notify the public that a website containing information pertaining to the National Surface Transportation Financing Commission can be accessed at http://financecommission.dot.gov/index.htm.


[Federal Register Volume 88, Number 120 (Friday, June 23, 2023)]
[Proposed Rules]
[Pages 41056-41058]
[FR Doc No: 2023-13229]

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R01-OAR-2023-0297; FRL-11046-01-R1]

Air Plan Approval; Rhode Island; Organic Solvent Cleaning
Regulation

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Environmental Protection Agency (EPA) is proposing to
approve a State Implementation Plan (SIP) revision submitted by the
State of Rhode Island. This SIP amendment consists of revisions to the
Rhode Island Air Pollution Control Regulation No. 36, currently
codified in Title 250 Department of Environmental Management, Chapter
120 Air Resources, Subchapter 05 Air Pollution Control, Part 36 Control
of Emissions from Organic Solvent Cleaning (Part 36). The proposed SIP
revisions include minor regulatory changes that were necessary to
provide consistency with the federal regulations for National Emissions
Standards for Hazardous Air Pollutants (NESHAP) for Halogenated Solvent
Cleaning. This action is being taken under the Clean Air Act.

DATES: Written comments must be received on or before July 24, 2023.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-R01-
OAR-2023-0297 at https://www.regulations.gov, or via email to
[email protected]. For comments submitted at Regulations.gov,
follow the online instructions for submitting comments. Once submitted,
comments cannot be edited or removed from Regulations.gov. For either
manner of submission, the EPA may publish any comment received to its
public docket. Do not submit electronically any information you
consider to be Confidential Business Information (CBI) or other
information whose disclosure is restricted by statute. Multimedia
submissions (audio, video, etc.) must be accompanied by a written
comment. The written comment is considered the official comment and
should include discussion of all points you wish to make. The EPA will
generally not consider comments or comment contents located outside of
the primary submission (i.e. on the web, cloud, or other file sharing
system). For additional submission methods, please contact the person
identified in the FOR FURTHER INFORMATION CONTACT section. For the full
EPA public comment policy, information about CBI or multimedia
submissions, and general guidance on making effective comments, please
visit https://www.epa.gov/dockets/commenting-epa-dockets. Publicly
available docket materials are available at https://www.regulations.gov
or at the U.S. Environmental Protection Agency, EPA Region 1 Regional
Office, Air and Radiation Division, 5 Post Office Square--Suite 100,
Boston, MA. EPA requests that if at all possible, you contact the
contact listed in the FOR FURTHER INFORMATION CONTACT section to
schedule your inspection. The Regional Office's official hours of
business are Monday through Friday, 8:30 a.m. to 4:30 p.m., excluding
legal holidays and facility closures due to COVID-19.

FOR FURTHER INFORMATION CONTACT: Michele Kosin, Physical Scientist, Air
Quality Branch, Air & Radiation Division (Mail Code 5-MI), U.S.
Environmental Protection Agency, Region 1, 5 Post Office Square, Suite
100, Boston, Massachusetts 02109-3912;<PHONE_NUMBER>;
[email protected].

SUPPLEMENTARY INFORMATION: Throughout this document whenever ``we,''
``us,'' or ``our'' is used, we mean EPA.

 Table of Contents

I. Background and Purpose
II. Description and Review of Submittals
III. Proposed Action
IV. Incorporation by Reference
V. Statutory and Executive Order Reviews

I. Background and Purpose

    On September 3, 2020 (85 FR 54924), EPA approved a SIP revision
demonstrating that Rhode Island meets the requirements of reasonably
available control technology (RACT) for the two precursors for ground-
level ozone, oxides of nitrogen (NOX) and volatile organic
compounds (VOCs), set forth by the Clean air Act (CAA or Act) with
respect to the 2008 and 2015 ozone National Ambient Air Quality
Standard (NAAQSs or standards). Additionally, the 2020 action approved
specific regulations that implement RACT requirements by limiting air
emissions of NOX and VOC pollutants from solvent cleaning
operations sources within the state. As part of this action, EPA
approved the Rhode Island Air Pollution Control Regulation No. 36,
currently codified in Title 250 Department of Environmental Management,
Chapter 120 Air Resources, Subchapter 05 Air Pollution Control, Part
36--Control of Emissions from Organic Solvent Cleaning (Part 36) into
the SIP. Prior to the 2020 action, EPA last approved the Part 36
regulations into the SIP on in 2012. See 77 FR 14691
    On February 4, 2022, the Rhode Island Department of Environmental
Management's Office of Air Resources (RI DEM) proposed minor revisions
to Part 36 to make the rule fully consistent with the National
Emissions Standards for Hazardous Air Pollutants (NESHAP) for
Halogenated Solvent Cleaning (40 CFR part 63, subpart T) eliminating
any inconsistencies between the federal regulation and the current
state rule. On May 3, 2022, the RI DEM Deputy Administrator Office of
Air Resources signed the amended Part 36, and it was filed with the
Rhode Island Secretary of State on May 24, 2022, with an effective date
of June 13, 2022. The amended regulation was authorized pursuant to
R.I. General Laws Sec.  42-17.1-2(19) and R.I. General Laws Chapter 23-
23, as amended, and has been promulgated pursuant to the procedures set
forth in the R.I. Administrative Procedures Act, R.I. General Laws
Chapter 42-35. On June 9, 2022, the RI DEM submitted a request for EPA
to incorporate the revisions to Part 36 into the Rhode Island SIP.

II. Description and Review of Submittals

    On June 9, 2022, the RI DEM submitted to EPA an amended version of
Part 36, Control of Emissions from Organic Solvent Cleaning, as a
revision to the Rhode Island State Implementation Plan. The revisions
to the Part 36 regulation ensure that Part 36 is fully consistent with
the Halogenated Solvent Cleaning NESHAP at 40 CFR part 63, subpart T.
Part 36 was revised to include the addition or amendment of several
definitions consistent with the federal rule. In addition, RI DEM
clarified the applicability of the rule.
    Rhode Island made several minor changes to the Part 36 Organic
Solvent Cleaning Rule. Specifically, RI DEM amended and added
definitions to Section 36.5 in order to be consistent with the NESHAP,
including definitions for air blanket, consumption, contaminants,
cover, halogenated hazardous air pollutant solvent, high precision
products, hoist, industrial solvent cleaning, janitorial cleaning,
overall control device efficiency, part, soils, solvent/air interface
area, sump heater, and vapor cleaning. The applicability section of
Section 36.6 was also slightly revised at 36.6(C) to clarify the
applicability for cold solvent cleaning machines and at 36.6(D) to
clarify applicability for industrial solvent cleaning, consistent with
the NESHAP. In addition, several other minor clerical revisions were
made to correct formatting and other references as a result of the
changes above.
    The revisions discussed above serve to clarify the existing
regulation and are not intended to significantly impact its original
meaning. The revisions to Part 36 are generally non-substantive changes
to ensure consistency between the state and federal rule. We have
scrutinized the changes as described above and find that these do not
unfavorably affect the stringency of the State's program or impact
previous EPA SIP approvals for Part 36. We thus propose to find that
Rhode Island's amended 250-RICR-120-05-36 (Part 36) submittal remains
consistent with the Clean Air Act.

III. Proposed Action

    EPA is proposing to approve the Rhode Island SIP revision requests
as described above. The SIP revisions meet section 110(l) of the CAA
because the revisions will not interfere with any applicable
requirement concerning attainment and reasonable further process, or
any other applicable requirement of the CAA. EPA is soliciting public
comments on the issues discussed in this notice or on other relevant
matters. These comments will be considered before taking final action.
Interested parties may participate in the Federal rulemaking procedure
by submitting written comments to this proposed rule by following the
instructions listed in the ADDRESSES section of this Federal Register.

IV. Incorporation by Reference

    In this rule, the EPA is proposing to include in a final EPA rule
regulatory text that includes incorporation by reference. In accordance
with requirements of 1 CFR 51.5, the EPA is proposing to incorporate by
reference amended Rhode Island regulation Part 36, Control of Emissions
from Organic Solvent Cleaning. The proposed changes are described in
sections I. and II. of this document. The EPA has made, and will
continue to make, these documents generally available through https://www.regulations.gov and at the EPA Region 1 Office (please contact the
person identified in the FOR FURTHER INFORMATION CONTACT section of
this preamble for more information).

V. Statutory and Executive Order Reviews

    Under the Clean Air Act, the Administrator is required to approve a
SIP submission that complies with the provisions of the Act and
applicable Federal regulations. See 42 U.S.C. 7410(k); 40 CFR 52.02(a).
Thus, in reviewing SIP submissions, EPA's role is to approve state
choices, provided that they meet the criteria of the Clean Air Act.
Accordingly, this proposed action merely approves state law as meeting
Federal requirements and does not impose additional requirements beyond
those imposed by state law. For that reason, this proposed action:
     Is not a significant regulatory action subject to review
by the Office of Management and Budget under Executive Orders12866 (58
FR 51735, October 4, 1993) and 13563 (76 FR 3821, January 21, 2011);
     Does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     Is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     Does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     Does not have federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     Is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);

     Is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001); and
     Is not subject to requirements of section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the Clean Air Act.
     In addition, the SIP is not approved to apply on any
Indian reservation land or in any other area where EPA or an Indian
tribe has demonstrated that a tribe has jurisdiction. In those areas of
Indian country, the rule does not have tribal implications and will not
impose substantial direct costs on tribal governments or preempt tribal
law as specified by Executive Order 13175 (65 FR 67249, November 9,
2000).
    Executive Order 12898 (Federal Actions To Address Environmental
Justice in Minority Populations and Low-Income Populations, 59 FR 7629,
Feb. 16, 1994) directs Federal agencies to identify and address
``disproportionately high and adverse human health or environmental
effects'' of their actions on minority populations and low-income
populations to the greatest extent practicable and permitted by law.
EPA defines environmental justice (EJ) as ``the fair treatment and
meaningful involvement of all people regardless of race, color,
national origin, or income with respect to the development,
implementation, and enforcement of environmental laws, regulations, and
policies.'' EPA further defines the term fair treatment to mean that
``no group of people should bear a disproportionate burden of
environmental harms and risks, including those resulting from the
negative environmental consequences of industrial, governmental, and
commercial operations or programs and policies.''
    The RI DEM did not evaluate environmental justice considerations as
part of its SIP submittal; the CAA and applicable implementing
regulations neither prohibit nor require such an evaluation. EPA did
not perform an EJ analysis and did not consider EJ in this action. Due
to the nature of the action being taken here, this action is expected
to have a neutral to positive impact on the air quality of the affected
area. Consideration of EJ is not required as part of this action, and
there is no information in the record inconsistent with the stated goal
of E.O. 12898 of achieving environmental justice for people of color,
low-income populations, and Indigenous peoples.

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Ozone, Reporting and recordkeeping requirements, Volatile
organic compounds.

    Dated: June 14, 2023.
David Cash,
Regional Administrator, EPA Region 1.
[FR Doc. 2023-13229 Filed 6-22-23; 8:45 am]
BILLING CODE 6560-50-P