[Federal Register Volume 76, Number 217 (Wednesday, November 9, 2011)]
[Notices]
[Pages 69715-69716]
[FR Doc No: 2011-29004]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings 2

    Take notice that the Commission received the following electric
corporate filings:

    Docket Numbers: EC12-20-000.
    Applicants: Duke Energy Ohio, Inc., Duke Energy Kentucky, Inc.
    Description: Application of Duke Energy Ohio, Inc. and Duke Energy
Kentucky, Inc.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5094.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: EC12-21-000.
    Applicants: ITC Midwest LLC.
    Description: ITC Midwest Section 203 Application regarding Huxley
Substation Transmission Assets.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5096.
    Comment Date: 5 p.m. ET on 11/23/2011.
    Take notice that the Commission received the following electric
rate filings:

    Docket Numbers: ER10-1478-003.
    Applicants: Pennsylvania Electric Company.
    Description: Revised MBR Power Sales Tariff to be effective 11/2/
2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5069.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER10-2834-001; ER10-2821-001.
    Applicants: Munnsville Wind Farm, LLC, Stony Creek Wind Farm, LLC.
    Description: Notice of Change in Status of Munnsville Wind Farm,
LLC and Stony Creek Wind Farm, LLC.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5117.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER11-3614-004
    Applicants: Glacial Energy Holdings.
    Description: Substitute Baseline Tariff to be effective 11/1/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5008.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER11-4214-000.
    Applicants: PacifiCorp.
    Description: NV Energy Refund Report to be effective N/A.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5068.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER11-4596-001.
    Applicants: South Carolina Electric & Gas Company.
    Description: Amendment of Pending Tariff Filing Attachment C to be
effective 1/1/2012.
    Filed Date: 11/01/2011.
    Accession Number: 20111101-5095.
    Comment Date: 5 p.m. ET on 11/22/2011.

    Docket Numbers: ER11-4677-001
    Applicants: NextEra Energy Montezuma II Wind, LLC.
    Description: NextEra Energy Montezuma II Wind, LLC Amendment to MBR
Application and Revision to be effective 11/2/2011.
    Filed Date: 11/01/2011.
    Accession Number: 20111101-5182.
    Comment Date: 5 p.m. ET on 11/15/2011.

    Docket Numbers: ER12-52-001.
    Applicants: Windpower Partners 1993, L.P.
    Description: Windpower Partners 1993, L.P. Amendment to MBR
Application and Revision to be effective 11/2/2011.
    Filed Date: 11/01/2011.
    Accession Number: 20111101-5183.
    Comment Date: 5 p.m. ET on 11/15/2011.

    Docket Numbers: ER12-129-001.
    Applicants: Spindle Hill Energy LLC.
    Description: Supplement to October 20, 2011 Market-Based Rate
Tariff Filing to be effective 12/20/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5009.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-323-000.
    Applicants: San Joaquin Cogen, LLC.
    Description: SJC First Revised MBR to be effective 9/10/2010.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5070.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-324-000
    Applicants: PJM Interconnection, L.L.C.
    Description: Queue No. W1-105; Original Service Agreement No. 3090
to be effective 10/4/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5071.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-325-000.
    Applicants: Florida Power & Light Company.
    Description: FPL and Lee County Electric Cooperative, Inc. First
Revised SA No. 266 to be effective 1/1/2012.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5072.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-326-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Queue No. W1-106; Original Service Agreement No. 3091
to be effective 10/4/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5077.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-327-000
    Applicants: L&L Energy LLC.
    Description: Baseline refile to be effective 11/3/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5080.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-328-000.
    Applicants: Stony Creek Wind Farm, LLC.
    Description: Application For Category 1 Seller Designation In
Southeast Region to be effective 1/1/2011.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5097.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-329-000.
    Applicants: Ontario Power Generation, Inc.
    Description: Refund Report of Ontario Power Generation, Inc.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5098.
    Comment Date: 5 p.m. ET on 11/23/2011.

    Docket Numbers: ER12-330-000.
    Applicants: Florida Power & Light Company.
    Description: FPL and Seminole Electric Cooperative, Inc. Ninth
Revised SA. No. 162 to be effective 1/1/2012.
    Filed Date: 11/02/2011.
    Accession Number: 20111102-5103.
    Comment Date: 5 p.m. ET on 11/23/2011.

    The filings are accessible in the Commission's eLibrary system by
clicking on the links or querying the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and 385.214) on or before 5
p.m. Eastern time on the specified comment date. Protests may be
considered, but intervention is necessary to become a party to the
proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings

can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER> (toll free). For
TTY, call<PHONE_NUMBER>.

    Dated: November 2, 2011.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2011-29004 Filed 11-8-11; 8:45 am]
BILLING CODE 6717-01-P


UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

DATE:		November 27, 2007

SUBJECT:		Organic Esters of Phosphoric Acid:  Toxicology Disciplinary
Chapter for the Issuance of the Reregistration Eligibility Decision
(RED) Document

			Case No.:  4122

			PC Code: 111286, 129079, 129080

			DP Barcode:  347014

FROM:		Jenny J. Tao, Toxicologist

 		Risk Assessment and Science Support Branch (RASSB)

	 		Antimicrobials Division (7510P)

TO:			Heather Garvie, Chemical Review Manager

Diane Isbell, Team Leader

Mark Hartman, Chief

			Regulatory Management Branch II

			Antimicrobials Division (7510P)

THROUGH:		Nader Elkassabany, Team Leader

			Team Two

And

Norm Cook, Chief

	 		Risk Assessment and Science Support Branch

	 		Antimicrobials Division

REGISTRANT:	Interface Research Corporation

Attached is the Toxicology Disciplinary Chapter for Phosphoric Acid
Esters for the purpose of issuing a Reregistration Eligibility Decision
(RED).

Organic Esters of Phosphoric Acid

PC Code: 111286, 129079, 129080

Toxicology Disciplinary Chapter for

the Reregistration Eligibility Decision (RED) Document

11/27/2007

TABLE OF CONTENTS

0.0
BACKGROUND……………………………………………………
………………………..4

1.0 HAZARD
CHARACTERIZATION………………………………………………
………..5

2.0 TOXICOLOGY DATA
REQUIREMENTS..……………………………………………...7

3.0 DATA
GAP(S)………………………….……………………………
…………………….....8

4.0 HAZARD
ASSESSMENT……………………………………………………
……………...9

 	4.1 Acute
toxicity………………………………………………………
………………….9

	4.2 Subchronic
toxicity………………………………………………………
…………….9

	4.3 Prenatal developmental
toxicity……….…………………………..…………………1
0

	4.4 Reproductive
toxicity………………………………………………………
………...11

	4.5 Chronic
toxicity………………………………………………………
……………....12

	4.6
Carcinogenicity…………………………………………………
…………………….12

	4.7
Mutagenicity……………………………………………………
…………………….12

	4.8
Neurotoxicity…………………………………………………
……………………....15

	4.9 Metabolism and
pharmacokinetics……………………..…………………………
….15

5.0 TOXICITY ENDPOINT
SELECTION…………………….……………………………..15

	5.1 Toxicological Doses and Endpoint
Selection..……….…….………………………...15

	5.2 Dermal
Absorption…………………………………….………………
……………...21

	5.3 Classification of Carcinogenic
Potential…...……..…………………………………..21

6.0 FQPA
CONSIDERATIONS……………….…………………………………
……………..23

	6.1 Developmental Toxicity Study
Conclusions……………………………………….....23

	6.2 Reproductive Toxicity Study
Conclusions……………………………………………24

	6.3 Recommendation for Developmental Neurotoxicity
Study………….……………….25

7.0
REFERENCES..............................................................
..........................................................26

8.0
APPENDICES……………………………………………………
……………………….....28

8.1 Toxicity Profile
Summary………………………………………………………
……	.29

		8.1.1	Acute Toxicity
Table…………………………….………………………..29

8.1.2	Subchronic, Chronic and Other Toxicity
Table..……………………….....29

0.0	BACKGROUND

Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric acid consists of a
mixture of three active ingredients: Phosphoric acid, mono(2-ethylhexyl)
ester; Phosphoric acid, bis(2-ethylhexyl) ester, compound with
2,2'-(cocoalkylimino) bis(ethanol); and Phosphoric acid,
mono(2-ethylhexyl) ester, compounds with diethanolamine N-coco alkyl
derivatives (1:1).  Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric
acid are approved for use primarily as a fungicide and a bacteriostat as
materials preservative in carpets; epoxy flooring and tile; vinyl
products, synthetic and non-woven textile products, including wall
coverings, car tops, awnings, tarpaulins, tents, sails, drapes, shower
curtains, cubicle curtains, and film (to be used for purposes other than
food storage and flooring products) and polymeric packaging film (to be
used for purposes other than food storage); plastic furniture (excluding
used for food service and food storage); polymeric laminates (excluding
laminates used for food preparation surfaces); polymer concrete; water,
oil, solvent based paints, stains, other coating systems (for use on
interior and exterior surfaces), substrates, machinery and equipment,
including heating and ventilating and air conditioning systems (HVAC),
molded polymeric and polymer concrete bath tubs, showers, bathroom
sinks, bathroom countertops and bathroom accessories, various molded
polymer, and polymer concrete products for general household,
industrial, commercial and health care use; natural and synthetic
polymeric sealants, adhesives and caulking compounds; textile and vinyl
upholstery, mattresses, mattresses ticking and mattress covers; air
filters to be used in furnaces, air conditioners, air purification
devices; automobiles and re-circulating air handling systems, and human
clothing.  The three components and structure(s) of Organic esters of p
SEQ CHAPTER \h \r 1 hosphoric acid are shown in Table 1 below.

Table 1.  Active Ingredients in Organic Esters of P  SEQ CHAPTER \h \r 1
hosphoric Acid

PC

Code	CAS RN	Name	Structure

111286	1070-03-7	Phosphoric acid, mono(2-ethylhexyl) ester

129079	68649-38-7	Phosphoric acid, bis(2-ethylhexyl) ester, compound
with 2,2'-(cocoalkylimino) bis(ethanol)	Not available

129080	120579-32-0	Phosphoric acid, mono(2-ethylhexyl) ester, compounds
with diethanolamine N-coco alkyl derivatives	Not available

1.0	HAZARD CHARACTERIZATION

Organic esters of phosphoric acid was found to be low toxic (Toxicity
Category IV) with an observed lethal dose greater than 5000 mg/kg for
both acute oral and dermal toxicity.  Mortality was observed at all
concentrations in rabbits in an acute inhalation toxicity study,
resulting in an LD50 determination of 1.48 mg/L (combined) (Toxicity
Category III).  Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric acid
was shown to be mildly irritating to the eyes (Toxicity Category III)
and is not a dermal irritant (Toxicity Category IV).

Significant decrease in body weight, body weight gain and food
consumption were observed in a 90-day oral toxicity study in rats.
Males were affected more severely and at a lower dose level than
females.  Treatment-related histopathologic findings of lenticular
degeneration and forestomach lesions were found in high-dose females and
in intermediate- and high-dose males, respectively.  Changes in a few
hematologic and clinical parameters were also reported.  However, these
changes, while statistically significant, were relatively small and
likely not biologically relevant because they were not correlated with
any histopathologic findings.  Increases in organ weight (kidney, testes
and liver) with no histopathologic changes were considered to be likely
related to decreases in body weight.

In the developmental toxicity study in rats, treatment-related deaths
were reported in the high-dose group.  Clinical signs of toxicity
(salivation with red stain around the mouth and nose, hypoactivity,
urine and fecal stains) were also observed at this dose level.
Significant reduced absolute body weight and body weight gain were
reported in maternal animals in the high-and mid-dose groups.  There
were significant increases in total resorptions, early resorptions, and
postimplantation losses in the high-dose group.  Significant decrease in
live mean fetal weight was also observed at the high dose level.  There
were dose-related increases in the number of litters with fetuses with
visceral and skeletal malformations at the dose level at which maternal
toxicity was seen.

  SEQ CHAPTER \h \r 1 Organic esters of phosphoric acid was found to be
negative in the absence or presence of S9 in Salmonella strains TA98,
TA100, TA1535, TA1537 and TA1538.  There was no evidence of chromosome
aberration induction in the absence or presence of S9 in a chromosome
aberration test using Chinese Hamster Ovary cells.  No evidence of
sister chromatid exchange (SCEs) induced was shown in a sister chromatid
exchange assay using Chinese hamster ovary CHO-WBL cell cultures.

  SEQ CHAPTER \h \r 1 From the available repeated-dose toxicity studies,
there was no evidence of neurotoxicity of Organic esters of phosphoric
acid.  The Antimicrobial Division Toxicology Endpoint Selection
Committee (ADTC) concluded that there is no concern for neurotoxicity
resulting from exposure to Organic esters of phosphoric acid for its
currently registered uses.

No data are available for reproductive toxicity of Organic esters of
phosphoric acid.  The data for in vivo mammalian micronucleus test and
SEQ CHAPTER \h \r 1 pharmacokinetic and metabolism studies are also not
available.

Additional studies are required to assess exposure in the occupational
and residential settings for the use of Organic esters of phosphoric
acid: a dermal sensitization study, a 90-day dermal and inhalation
toxicity study in rat, a 2-generational reproductive toxicity study and
an in vivo mammalian micronucleus test.

2.0	TOXICOLOGY DATA REQUIREMENTS

  SEQ CHAPTER \h \r 1 The Toxicology database for Organic esters of
phosphoric acid is listed in the following table.

Table 2.  Toxicologic Data Requirements for Organic Esters of Phosphoric
Acid

Test

	MRID	Technical

Required	Satisfied

870.1100	Acute Oral Toxicity (Rat)

870.1200	Acute Dermal Toxicity (Rabbit)

870.1300	Acute Inhalation (Rat)

870.2400	Primary Eye Irritation (Rabbit)

870.2500	Primary Dermal Irritation (Rabbit)

870.2600	Dermal Sensitization  	42907901

42907902

40423801

44858903

44858904

n/a	yes

yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

no

870.3100	90-Day Oral (Rat)

870.3250     90-Day Dermal (Rat)

870.4365     90-Day Inhalation	41083601

	yes

yes

no?	yes

no

n/a?

870.3700	Developmental Toxicity (Rat)

870.3700     Developmental Toxicity (Rabbit)

870.3800	Reproduction	41151601

	yes

no

yes	yes

n/a

no

870.4100a   Chronic (Rat)

870.4100b   Chronic (Mouse)

870.4200a   Carcinogenicity (Rat)

870.4200b   Carcinogenicity (Mouse)

	no

no

no

no	n/a

n/a

n/a

n/a

870.5100	Mutagenicity – Bacterial Reverse                      Gene
Mutation assay

870.5375	Mutagenicity – Chromosome
aberrations  (CHO) MRID

870.5375    Mammalian Cytogenetics (sister
chromatid Exchange) assay                                (hamster)

870.5395	Mutagenicity – Mammalian
erythrocyte micronucleus test                             (Mouse)

870.5550	Mutagenicity – Unscheduled DNA                    synthesis
in primary rat hepatocytes 	40564601 and 40564602

40564603

40564604

	yes

yes

no

yes

no	yes

yes

no

n/a

3.0	DATA GAPS

  SEQ CHAPTER \h \r 1 The ADTC determined that there are data gaps in
the hazard database for Organic esters of phosphoric acid based on the
current use patterns.  Due to the potential dermal and inhalation
exposure in the occupational as well as residential settings, a 90-day
dermal and inhalation toxicity study must be performed with Organic
esters of phosphoric acid.

  SEQ CHAPTER \h \r 1 There are no data on the reproductive toxicity of
Organic esters of phosphoric acid.  The data for characterizing the
developmental and reproductive toxicity are limited to one developmental
toxicity study in rats.  A reproductive toxicity study is necessary to
assess any effects on fertility and reproduction, and is required to
support the current uses of Organic esters of phosphoric acid.

No dermal sensitization study or in vivo mammalian micronucleus test is
submitted to the Agency. In order to fully characterize the hazard
concerns of Organic esters of phosphoric acid, thess study are required.

In conclusion, the following studies are required to complete the hazard
database for Organic esters of phosphoric acid to support its current
uses: 1) a dermal sensitization study; 2) a 90-day dermal and inhalation
toxicity study in rat; 3) a reproductive toxicity study; and 4) an in
vivo mammalian micronucleus test.

4.0	HAZARD ASSESSMENT

Acute Toxicity

Adequacy of Database for Acute Toxicity:  The acute toxicity profile for
Organic esters of phosphoric acid is considered incomplete.  No study is
available for dermal sensitization.

Except for the dermal sensitization study, all other acute studies were
available for Organic esters of phosphoric acid.  However, many of the
acute studies were not tested at the technical grade level.  From the
available acute toxicity data, it was found that Organic esters of
phosphoric acid is low toxic (Toxicity Category IV) for acute oral and
dermal toxicity, with an observed lethal dose greater than 5000 mg/kg
(MRIDs 42907901 and 42907902).  The acute inhalation toxicity   SEQ
CHAPTER \h \r 1 was examined in rabbits (MRIDs 40423801, purity 60%),
and mortality was observed at all concentrations during the study (1.27,
2.32, 2.82, or 4.75 mg/L), resulting in an LD50 determination of 1.48
mg/L (combined) (Toxicity Category III).  Organic esters of p  SEQ
CHAPTER \h \r 1 hosphoric acid was shown to be mildly irritating to the
eyes (Toxicity Category III), and it is not a dermal irritant (Toxicity
Category IV).

The acute toxicity data on Organic esters of phosphoric acid are
summarized below in Table 4.1.

Table 4.1.  Acute Toxicity Profile for Organic Esters of Phosphoric Acid

Guideline Number	Study Type/

Test substance (% a.i.)	MRID Number	Results	Toxicity Category

870.1100	Acute oral, rat

(Purity not reported)	42907901	  SEQ CHAPTER \h \r 1 LD50 (M/F) > 5000
mg/kg (observed)	IV

870.1200	Acute dermal, rabbit

(Purity not reported)	42907902	LD50 (M/F) > 5000 mg/kg (observed)	IV

870.1300	Acute inhalation, rat

(Purity 60%)	40423801, supplements 41365401 & 41365402	LC50 (M/F) = 1.48
mg/L

LC50 (M) = 1.43 mg/L

LC50 (F) = 1.53 mg/L	III

870.2400	Primary eye irritation, rabbit

(Purity not reported)	44858903	mildly irritating   SEQ CHAPTER \h \r 1
III

870.2500	Primary dermal irritation, rabbit

(Purity not reported)	44858904	Not irritating	IV

870.2600	Dermal sensitization	No study available

Subchronic Toxicity

Adequacy of Database for Subchronic Toxicity:  The database for
subchronic toxicity is considered incomplete.    SEQ CHAPTER \h \r 1
Only a 90-day oral toxicity study in the rat (MRID 41083601) is
available for addressing subchronic toxicity.

870.3100	90-Day Oral Toxicity – Rat

In a 90-day subchronic oral toxicity study (MRID 41083601), groups of 10
male and 10 female Sprague-Dawley rats were given Intersept (100% a.i.,
Lot/Batch #3.791) administered in the diet at 0, 62.5, 200 and 625
(weeks 1-6)/375 (weeks 7-13) mg/kg/day in males and 0, 37.5, 120 and 375
mg/kg/day in females.  Doses were determined from a 14-day dietary
range-finding study in rats (MRID 41665301).

No deaths occurred during this study, but the high dose in males was
reduced from 625 mg/kg/day to 375 mg/kg/day after six weeks due to
increasing weight loss in this group.  The report stated that clinical
signs were observed in mid- and high-dose rats, which included
piloerection (which progressed to rough haircoat) and fur staining.
Actual data were not provided.  Ophthalmoscopic examination revealed
lenticular degeneration in 3/10 high-dose males and 7/10 high-dose
females vs. 0/20 in control.  Treatment-related histopathologic findings
were forestomach lesions (gastritis/ulcer-erosion/squamous hyperplasia
hyperkeratosis) in intermediate- and high-dose males and lenticular
degeneration in 5/10 high-dose females and 1/10 high-dose males (0/20
control).

Small, statistically significant changes in a few hematologic parameters
(increased platelets, decreased hemoglobin, MCV, MCH and PCV) were
reported, primarily in high-dose females but these values were within
reference ranges established previously at the test site. Changes in
clinical chemistry parameters included decreased GPT in high-dose males
(-28%) and low-, mid- and high-dose females (-17%, -15%, and -27%,
respectively), total bilirubin in mid- and high-dose males (-42% and
-47%, respectively) and high-dose females (-42%), and phosphorus in mid-
and high-dose females (-22% and -11%, respectively).  In addition,
creatinine was decreased in high-dose males only (-7%, p ( 0.05).  These
changes, while statistically significant, were relatively small and were
likely not biologically relevant because they were not correlated with
any histopathologic findings.

Body weight was statistically significantly decreased in mid-dose males
(-9 to -15%) and high-dose males (-15 to -29%) and females (-10 to -13%)
during the study.  Total body weight gain was also decreased in mid-dose
males (-22%), and in high-dose males (-42%) and females (-32%).
Concomitant decreased food consumption was observed in mid-dose males
(-14%) and high-dose males (-27%) and females (-17%).

Increases in kidney weight relative to body weight in both high-dose
males and females (+15%), and testes weight relative to body weight in
mid- and high-dose males (+13% and +26%, respectively) were likely
related to decreases in body weight.  Liver weight relative to body
weight was increased only in mid- and high-dose females (+12% and +25%,
respectively), however, these increases were moderate and of unknown
toxicologic significance in the absence of other toxic liver findings.

The systemic LOAEL in males is 200 mg/kg/day based on decreased body
weights, body weight gain, and food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis); the NOAEL
in males is 62.5 mg/kg/day.  The LOAEL in females is 375 mg/kg/day based
on decreased body weight, body weight gain, food consumption, and
lenticular degeneration; the NOAEL in females is 120 mg/kg/day.

It is noted that the high dose of 625 mg/kg/day should never have been
tested in males, based upon the results of the range-finding study (MRID
41665301).  Decreased body weight gain and food consumption were
observed in male rats after 14 days at a dose of 500 mg/kg/day.  An
initial reduction in body weight gain was also observed at the dose of
625 mg/kg/day although no decrease and rats were treated only for 10
days at this higher dose.

Despite this obvious error in dose selection for the main study, this
study is classified as Acceptable – Guideline.

4.3	Prenatal Developmental Toxicity

Adequacy of Database for Prenatal Developmental Toxicity:  The database
for prenatal developmental toxicity is considered adequate for the
currently registered uses.    SEQ CHAPTER \h \r 1 Developmental toxicity
assessment for Organic esters of phosphoric acid is based on a
developmental study in the rat (MRID 41151601).

870.3700	Prenatal Developmental Toxicity (Gavage) Study – Rat

In a developmental toxicity study (MRID 41151601), 25 presumed pregnant
Charles River rats (Crl: CD®BR) per group were administered Intersept®
(100.0% a.i.) by gavage at doses of 0, 125, 250 or 500, mg/kg/day on
gestation days (GD) 6-15, inclusive.  The controls were given vehicle
(corn oil) only for the same dosing period.  On GD 20, all dams were
sacrificed, necropsied to assess gross pathology, and uteri and ovaries
were removed.  All fetuses were sexed, weighed, and examined for
external malformations/variations prior to sacrifice.  Approximately
one-half of the fetuses were fixed in ethanol and the remainder were
placed in Bouin’s fixative and examined for visceral
malformations/variations.  The ethanol-fixed fetuses were further
processed, stained, and examined for skeletal malformations/variations.

Four treatment-related deaths occurred at 500 mg/kg/day.  Clinical signs
of toxicity observed at 500 mg/kg/day were salivation with red stain
around the mouth (7) and nose (10), hypoactivity (8), urine stains (17),
and fecal stains (4) compared to 0/25 control dams.  Urine stains were
also observed on one low-dose animal and four mid-dose animals.  There
were no statistically or biologically significant gross necropsy
observations at maternal sacrifice.  Absolute body weights were
statistically significantly reduced (p(0.05 or 0.01) for 250 and 500
mg/kg/day dams during GD 8, 12, 16, and 20 and statistically
significantly reduced body weight gain was observed for both treatment
groups during GD 6-8 and GD 0-20 (11.1 and 20.6%, respectively during GD
0-20).  Net body weight change from GD 0 was also statistically
significantly reduced at 250 and 500 mg/kg/day (17.2 and 21.1%,
respectively), compared to controls.  Food consumption was not
monitored.  No treatment-related maternal changes were noted at
125 mg/kg/day.

The maternal toxicity LOAEL is 250 mg/kg/day based on clinical signs of
toxicity and reduced absolute body weights and weight gains.  The
maternal toxicity NOAEL is 125 mg/kg/day.

There were statistically significant increases (p(0.01) in total
resorptions, early resorptions, and postimplantation losses at 500
mg/kg/day compared to controls.  One high-dose dam had complete litter
resorption of two implantation sites.  The increase in postimplantation
loss resulted in slightly (n.s.) decreased number of fetuses per litter
for the high-dose group.  Also at 500 mg/kg/day there were
statistically significant decreases (p(0.01) in live mean fetal weight
(9.5%) and live female fetal weight (10.1%) compared to controls.
Gravid uterine weights were also lower than controls at 250 and 500
mg/kg/day (6.2 and 20.3%, respectively) but did not reach statistical
significance.

The total fetuses (litters) with major external, visceral or skeletal
malformations was 0 (0), 1 (1), 4 (2), and 17 (9) (p(0.05), in the
control, low-, mid-, and high-dose groups, respectively.  A positive
trend for certain skeletal variations (delayed ossification of the
hyoid, skull, pelvic girdle, vertebrae, sternebrae, and metatarsals) was
also evident with increasing doses of Intersept® with the 500 mg/kg/day
group generally statistically significantly increased (p(0.05) compared
to controls.  A dose-related increase was also observed in the number of
litters containing fetuses with increased renal pelvic cavitation and
dilation of lateral ventricles of the brain.

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with
external malformations were 0/0, 1/1, 4/2, and 8/6 (litter rate,
p(0.05), respectively.  External malformations at 500 mg/kg/day
consisted of one fetus each with cleft palate and anophthalmia;
umbilical hernia; umbilical hernia, microphthalmia, exencephaly, and
spina bifida; extra hind limb; malformed head; humpback; and 2 with
anophthalmia.  At 250 mg/kg/day, malformations consisted of one fetus
with gnathocephaly, and, from a different litter, a fetus with
microphthalmia and two fetuses with umbilical hernia.

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with
skeletal malformations were 0/0, 1/1, 1/1, and 6/4 (litter rate,
p(0.05), respectively.  Wavy or bent ribs were seen in 2 fetuses from 2
litters at 250 mg/kg/day and in 15 fetuses from 8 litters at 500
mg/kg/day compared to none in controls.  Skeletal malformations at 500
mg/kg/day consisted of vertebral anomaly with or without associated rib
anomaly in 3 fetuses from 2 litters; cervical vertebrae fused in 2
fetuses from 2 litters; and single incidences of exencephaly,
forked/fused ribs, and supernumerary limbs.

No treatment-related fetal effects were observed at 125 mg/kg/day.

The developmental toxicity LOAEL is 250 mg/kg/day based on dose-related
increases in the number of litters with fetuses with skeletal and
visceral abnormalities.  The developmental toxicity NOAEL is 125
mg/kg/day.

This study is classified as Acceptable – Guideline.

4.4	Reproductive Toxicity

Adequacy of Database for Reproductive Toxicity:  The database for
reproductive toxicity is considered incomplete.    SEQ CHAPTER \h \r 1
There are no reproductive toxicity data for Organic esters of phosphoric
acid.  The assessment for the reproductive and developmental toxicity of
Organic esters of phosphoric acid can not be completed with only one
developmental toxicity study in rats.  A 2-generational reproductive
toxicity study is required to assess any effects on fertility and
reproduction and to support the current uses of this chemical.

Chronic Toxicity

Adequacy of Database for Chronic Toxicity:  The assessment for chronic
toxicity is considered to be unnecessary for the currently registered
uses of Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric acid.  And no
chronic toxicity studies are required at this time.

Carcinogenicity

Adequacy of Database for Carcinogenicity:  The assessment for
carcinogenicity is considered to be unnecessary for the currently
registered uses of Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric
acid.  Negative findings were reported in the available genetic toxicity
studies.  No carcinogenicity studies are required at this time.

Mutagenicity

Adequacy of Database for Mutagenicity:  The database for mutagenicity is
considered incomplete.  There is no in vivo mammalian micronucleus assay
is available, and it is considered a data gap.  Therefore, an in vivo
mammalian micronucleus assay (870.5395) is required to support the
current uses of Organic esters of p  SEQ CHAPTER \h \r 1 hosphoric acid.
 Several other mutagenicity studies have been submitted and reviewed by
the Office of Pesticide Programs (OPP) and found acceptable.  The
summaries of these studies are provided below.

	Gene Mutation

 provided) in DMSO at concentrations of 0.005, 0.01, 0.05, 0.1 and 0.5
μL/plate in the presence and absence of mammalian metabolic activation
(S9-mix).

 due to excess cytotoxicity.  Cytotoxicity was not apparent at lower
concentrations.  In the presence of S9-mix, there was a slight reduction
in the number of revertants per plate at 0.5 μg/plate compared to the
solvent control values, in all TA-strains but particularly in TA1535.
There was no reduction in the number of revertants per plate at lower
concentrations and no thinning of the background lawn of bacteria at any
concentration in any tester strain.  There was no increase in the number
of revertants per plate over solvent control values in any tester strain
at any evaluated concentration of Intersept®, with or without S9-mix.
The solvent and positive control values were appropriate for the
respective strains.  There was no evidence of induced mutant colonies
over background.

This study is classified as Acceptable – Guideline.

 not provided) in DMSO at concentrations of 0.01, 0.05, 0.1, 0.5 and 1.0
μL/plate in the presence and absence of mammalian metabolic activation
(S9-mix).

Intersept® was tested up to cytotoxic concentrations.  Concentrations
of 0.5 and 1.0 μg/plate were excessively cytotoxic to all five tester
strains in the absence of S9-mix and thus not evaluated for
mutagenicity.  In the presence of S9-mix, 1.0 μg/plate was excessively
cytotoxic to all five tester strains and 0.5 μg/plate was excessively
cytotoxic to TA1535, TA1537 and TA1538.  There was no increase in the
number of revertants per plate over solvent control values in any tester
strain at any evaluated concentration of Intersept®, with or without
S9-mix.  The solvent and positive control values were appropriate for
the respective strains.  There was no evidence of induced mutant
colonies over background.

This study is classified as Acceptable – Guideline.

	Cytogenetics

In a mammalian cell cytogenetics assay (chromosomal aberrations) (MRID
40564603), Chinese hamster ovary CHO-WBL cell cultures were exposed to
Intersept® (Lot No. P2991, purity not provided) in DMSO at
concentrations of 2.5, 5.0, 7.5, 10.0 μg/mL with a 10 hour harvest time
without S9-mix and at concentrations of 10, 20, 30 and 40 μg/mL at a 20
hour harvest time without S9-mix.  Cells were exposed to concentrations
of 5, 7.5 10, 25, 50, 75 and 100 μg/mL with a 10 hour harvest time with
S9-mix.

Intersept® was tested up to cytotoxic concentrations.  In the absence
of S9-mix, all four concentrations of Intersept® tested using a 20 hour
harvest time (10, 20, 30 and 40 μg/mL) were completely cytotoxic and no
results were obtained.  Four lower concentrations (2.5, 5, 7.5 and 10
μg/mL) were tested using a 10 hour harvest time.  There were reductions
in cell monolayer confluency of 15% and 30% at 7.5 and 10 μg/mL,
respectively.  In the presence of S9-mix, Intersept® concentrations of
50, 75 and 100 μg/mL were completely cytotoxic at a 10 hour harvest
time while  no cytotoxicity was apparent at 25 μg/mL.  Concentrations
of 5, 7.5, 10 and 25 μg/mL were evaluated for chromosomal aberration
inducing potential.  There was no statistically significant increase in
the percentage of cells with aberrations, the number of aberrations per
cell or the percentage of cells with > 1 aberration per cell at any
Intersept® concentration compared to the solvent control.  Positive and
solvent controls induced the appropriate response.  There was no
evidence of chromosomal aberrations induced over background levels.

This study is classified as Acceptable – Guideline.

In a mammalian cell cytogenetics assay (sister chromatid exchange) (MRID
40564604), Chinese hamster ovary CHO-WBL cell cultures were exposed to
Intersept® (Lot No. P2991, purity not provided) in DMSO at
concentrations of 0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3, 100, 333,
1000 μg/mL with and without mammalian metabolic activation (S9-mix).
Cells were treated for 25 hours without S9-mix and for 2 hours with
S9-mix and harvested 25.5 hours after termination of treatment without
S9-mix and 2.5 hours after treatment with S9-mix.  The S9-fraction was
obtained from Aroclor 1254 induced male Sprague-Dawley rat liver.

city was seen at concentrations of 33.3 μg/mL and higher and a
precipitate was apparent at 1000 μg/mL.  In the presence of S9-mix,
concentrations of 100, 333 and 1000 μg/mL were completely cytotoxic and
a precipitate was seen at 1000 μg/mL.  Four concentrations, 0.333, 1.0,
3.33 and 10.0 μg/mL, were evaluated for SCE induction without S9-mix.
No effect on cell confluency was seen at these four concentrations but a
delay in cell cycle kinetics was apparent at 10 μg/mL.  There was no
significant increase in SCE frequency at any evaluated concentration
over the solvent control mean value of 7.42 ± 0.44 SCE/cell.  Four
concentrations, 1.0, 3.33, 10 and 33.3 μg/mL, were evaluated for SCE
induction with S9-mix.  No cytotoxicity or cell cycle delay was seen at
any of these four concentrations.  There was no significant increase in
SCE frequency at any evaluated concentration over the solvent control
mean value of 9.04 ± 0.41 SCE/cell.  Positive and solvent controls
induced the appropriate response with and without S9-mix.  There was no
evidence of SCEs induced over background levels.

This study is classified as Acceptable – Guideline.

4.8	Neurotoxicity

Adequacy of Database for Neurotoxicity:  These studies are not required
at this time.

  SEQ CHAPTER \h \r 1 From the available repeated-dose toxicity studies,
there was no evidence of neurotoxicity of Organic esters of phosphoric
acid.  It is concluded that there is no concern for neurotoxicity
resulting from exposure to Organic esters of phosphoric acid for its
currently registered uses.

	4.9	Metabolism and Pharmacokinetics

Adequacy of Database for Metabolism and Pharmacokinetics:    SEQ CHAPTER
\h \r 1   SEQ CHAPTER \h \r 1 Pharmacokinetics and metabolism studies
are not available for Organic esters of phosphoric acid.  These studies
are required to support its registered uses.

5.0	Toxicity Endpoint Selection

Toxicological Doses and Endpoint Selection

5.1.1	Acute Reference Dose (aRfD) tc \l2 "1. Acute Reference Dose (aRfD)
 –all populations

No endpoint is required for the currently registered uses.

5.1.2	Chronic Reference Dose (cRfD) tc \l2 "3. Chronic Reference Dose
(cRfD)

No endpoint is required for the currently registered uses.

5.1.3	Incidental Oral Exposure:  tc \l2 "4. Incidental Oral Exposure:
Short- and Intermediate-Term (1-30 days and 30 days-6 months)

Study Selected:  90-Day Oral Toxicity in Rats

MRID No.:  41083601

Executive Summary:  In a 90-day subchronic oral toxicity study (MRID
41083601), groups of 10 male and 10 female Sprague-Dawley rats were
given Intersept (100% a.i., Lot/Batch #3.791) administered in the diet
at 0, 62.5, 200 and 625 (weeks 1-6)/375 (weeks 7-13) mg/kg/day in males
and 0, 37.5, 120 and 375 mg/kg/day in females.  Doses were determined
from a 14-day dietary range-finding study in rats (MRID 41665301).

No deaths occurred during this study, but the high dose in males was
reduced from 625 mg/kg/day to 375 mg/kg/day after six weeks due to
increasing weight loss in this group.  The report stated that clinical
signs were observed in mid- and high-dose rats, which included
piloerection (which progressed to rough haircoat) and fur staining.
Actual data were not provided.  Ophthalmoscopic examination revealed
lenticular degeneration in 3/10 high-dose males and 7/10 high-dose
females vs. 0/20 in control.  Treatment-related histopathologic findings
were forestomach lesions (gastritis/ulcer-erosion/squamous hyperplasia
hyperkeratosis) in intermediate- and high-dose males and lenticular
degeneration in 5/10 high-dose females and 1/10 high-dose males (0/20
control).

Small, statistically significant changes in a few hematologic parameters
(increased platelets, decreased hemoglobin, MCV, MCH and PCV) were
reported, primarily in high-dose females but these values were within
reference ranges established previously at the test site. Changes in
clinical chemistry parameters included decreased GPT in high-dose males
(-28%) and low-, mid- and high-dose females (-17%, -15%, and -27%,
respectively), total bilirubin in mid- and high-dose males (-42% and
-47%, respectively) and high-dose females (-42%), and phosphorus in mid-
and high-dose females (-22% and -11%, respectively).  In addition,
creatinine was decreased in high-dose males only (-7%, p ( 0.05).  These
changes, while statistically significant, were relatively small and were
likely not biologically relevant because they were not correlated with
any histopathologic findings.

Body weight was statistically significantly decreased in mid-dose males
(-9 to -15%) and high-dose males (-15 to -29%) and females (-10 to -13%)
during the study.  Total body weight gain was also decreased in mid-dose
males (-22%), and in high-dose males (-42%) and females (-32%).
Concomitant decreased food consumption was observed in mid-dose males
(-14%) and high-dose males (-27%) and females (-17%).

Increases in kidney weight relative to body weight in both high-dose
males and females (+15%), and testes weight relative to body weight in
mid- and high-dose males (+13% and +26%, respectively) were likely
related to decreases in body weight.  Liver weight relative to body
weight was increased only in mid- and high-dose females (+12% and +25%,
respectively), however, these increases were moderate and of unknown
toxicologic significance in the absence of other toxic liver findings.

The systemic LOAEL in males is 200 mg/kg/day based on decreased body
weights, body weight gain, and food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis); the NOAEL
in males is 62.5 mg/kg/day.  The LOAEL in females is 375 mg/kg/day based
on decreased body weight, body weight gain, food consumption, and
lenticular degeneration; the NOAEL in females is 120 mg/kg/day.

It is noted that the high dose of 625 mg/kg/day should never have been
tested in males, based upon the results of the range-finding study (MRID
41665301).  Decreased body weight gain and food consumption were
observed in male rats after 14 days at a dose of 500 mg/kg/day.  An
initial reduction in body weight gain was also observed at the dose of
625 mg/kg/day although no decrease and rats were treated only for 10
days at this higher dose.

Despite this obvious error in dose selection for the main study, this
study is classified as Acceptable – Guideline.

Dose and Endpoint for Risk Assessment:  The systemic NOAEL in males is
62.5 mg/kg/day based on decreased body weights, body weight gain, and
food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis) at 200
mg/kg/day dose level.

Uncertainty Factor(s):  100 (10x for interspecies extrapolation, 10x for
intra species variations).

Comments about Study/Endpoint:  None.

5.1.4	Dermal Exposure:  Short- and Intermediate-Term (1-30 days and 30
days-6 months)

Study Selected:  90-Day Oral Toxicity in Rats

MRID No.:  41083601

Executive Summary:  In a 90-day subchronic oral toxicity study (MRID
41083601), groups of 10 male and 10 female Sprague-Dawley rats were
given Intersept (100% a.i., Lot/Batch #3.791) administered in the diet
at 0, 62.5, 200 and 625 (weeks 1-6)/375 (weeks 7-13) mg/kg/day in males
and 0, 37.5, 120 and 375 mg/kg/day in females.  Doses were determined
from a 14-day dietary range-finding study in rats (MRID 41665301).

No deaths occurred during this study, but the high dose in males was
reduced from 625 mg/kg/day to 375 mg/kg/day after six weeks due to
increasing weight loss in this group.  The report stated that clinical
signs were observed in mid- and high-dose rats, which included
piloerection (which progressed to rough haircoat) and fur staining.
Actual data were not provided.  Ophthalmoscopic examination revealed
lenticular degeneration in 3/10 high-dose males and 7/10 high-dose
females vs. 0/20 in control.  Treatment-related histopathologic findings
were forestomach lesions (gastritis/ulcer-erosion/squamous hyperplasia
hyperkeratosis) in intermediate- and high-dose males and lenticular
degeneration in 5/10 high-dose females and 1/10 high-dose males (0/20
control).

Small, statistically significant changes in a few hematologic parameters
(increased platelets, decreased hemoglobin, MCV, MCH and PCV) were
reported, primarily in high-dose females but these values were within
reference ranges established previously at the test site. Changes in
clinical chemistry parameters included decreased GPT in high-dose males
(-28%) and low-, mid- and high-dose females (-17%, -15%, and -27%,
respectively), total bilirubin in mid- and high-dose males (-42% and
-47%, respectively) and high-dose females (-42%), and phosphorus in mid-
and high-dose females (-22% and -11%, respectively).  In addition,
creatinine was decreased in high-dose males only (-7%, p ( 0.05).  These
changes, while statistically significant, were relatively small and were
likely not biologically relevant because they were not correlated with
any histopathologic findings.

Body weight was statistically significantly decreased in mid-dose males
(-9 to -15%) and high-dose males (-15 to -29%) and females (-10 to -13%)
during the study.  Total body weight gain was also decreased in mid-dose
males (-22%), and in high-dose males (-42%) and females (-32%).
Concomitant decreased food consumption was observed in mid-dose males
(-14%) and high-dose males (-27%) and females (-17%).

Increases in kidney weight relative to body weight in both high-dose
males and females (+15%), and testes weight relative to body weight in
mid- and high-dose males (+13% and +26%, respectively) were likely
related to decreases in body weight.  Liver weight relative to body
weight was increased only in mid- and high-dose females (+12% and +25%,
respectively), however, these increases were moderate and of unknown
toxicologic significance in the absence of other toxic liver findings.

The systemic LOAEL in males is 200 mg/kg/day based on decreased body
weights, body weight gain, and food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis); the NOAEL
in males is 62.5 mg/kg/day.  The LOAEL in females is 375 mg/kg/day based
on decreased body weight, body weight gain, food consumption, and
lenticular degeneration; the NOAEL in females is 120 mg/kg/day.

It is noted that the high dose of 625 mg/kg/day should never have been
tested in males, based upon the results of the range-finding study (MRID
41665301).  Decreased body weight gain and food consumption were
observed in male rats after 14 days at a dose of 500 mg/kg/day.  An
initial reduction in body weight gain was also observed at the dose of
625 mg/kg/day although no decrease and rats were treated only for 10
days at this higher dose.

Despite this obvious error in dose selection for the main study, this
study is classified as Acceptable – Guideline.

Dose and Endpoint for Risk Assessment:  The systemic NOAEL in males is
62.5 mg/kg/day based on decreased body weights, body weight gain, and
food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis) at 200
mg/kg/day dose level.

Uncertainty Factor(s):  100 (10x for interspecies extrapolation, 10x for
intra species variations).

Comments about Study/Endpoint:  None.

5.1.5	Dermal Exposure:  Long-Term (>6 months) tc \l2 "7. Dermal
Exposure: All Durations  Exposure

Study Selected:  90-Day Oral Toxicity in Rats

MRID No.:  41083601

Executive Summary:  See Short-and Intermediate-term Dermal Exposure
Endpoints.

Dose and Endpoint for Risk Assessment:  The systemic NOAEL in males is
62.5 mg/kg/day based on decreased body weights, body weight gain, and
food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis) at 200
mg/kg/day dose level.

Uncertainty Factor(s):  300 (10x interspecies extrapolation, 10x
intraspecies variation, 3x for use of subchronic endpoint for long-term
endpoint).

Comments about Study/Endpoint:  None.

5.1.6	Inhalation Exposure:  Short- and Intermediate-Term (1-30 days and
30 days-6 months)

Study Selected:  90-Day Oral Toxicity in Rats

MRID No.:  41083601

Executive Summary:  In a 90-day subchronic oral toxicity study (MRID
41083601), groups of 10 male and 10 female Sprague-Dawley rats were
given Intersept (100% a.i., Lot/Batch #3.791) administered in the diet
at 0, 62.5, 200 and 625 (weeks 1-6)/375 (weeks 7-13) mg/kg/day in males
and 0, 37.5, 120 and 375 mg/kg/day in females.  Doses were determined
from a 14-day dietary range-finding study in rats (MRID 41665301).

No deaths occurred during this study, but the high dose in males was
reduced from 625 mg/kg/day to 375 mg/kg/day after six weeks due to
increasing weight loss in this group.  The report stated that clinical
signs were observed in mid- and high-dose rats, which included
piloerection (which progressed to rough haircoat) and fur staining.
Actual data were not provided.  Ophthalmoscopic examination revealed
lenticular degeneration in 3/10 high-dose males and 7/10 high-dose
females vs. 0/20 in control.  Treatment-related histopathologic findings
were forestomach lesions (gastritis/ulcer-erosion/squamous hyperplasia
hyperkeratosis) in intermediate- and high-dose males and lenticular
degeneration in 5/10 high-dose females and 1/10 high-dose males (0/20
control).

Small, statistically significant changes in a few hematologic parameters
(increased platelets, decreased hemoglobin, MCV, MCH and PCV) were
reported, primarily in high-dose females but these values were within
reference ranges established previously at the test site. Changes in
clinical chemistry parameters included decreased GPT in high-dose males
(-28%) and low-, mid- and high-dose females (-17%, -15%, and -27%,
respectively), total bilirubin in mid- and high-dose males (-42% and
-47%, respectively) and high-dose females (-42%), and phosphorus in mid-
and high-dose females (-22% and -11%, respectively).  In addition,
creatinine was decreased in high-dose males only (-7%, p ( 0.05).  These
changes, while statistically significant, were relatively small and were
likely not biologically relevant because they were not correlated with
any histopathologic findings.

Body weight was statistically significantly decreased in mid-dose males
(-9 to -15%) and high-dose males (-15 to -29%) and females (-10 to -13%)
during the study.  Total body weight gain was also decreased in mid-dose
males (-22%), and in high-dose males (-42%) and females (-32%).
Concomitant decreased food consumption was observed in mid-dose males
(-14%) and high-dose males (-27%) and females (-17%).

Increases in kidney weight relative to body weight in both high-dose
males and females (+15%), and testes weight relative to body weight in
mid- and high-dose males (+13% and +26%, respectively) were likely
related to decreases in body weight.  Liver weight relative to body
weight was increased only in mid- and high-dose females (+12% and +25%,
respectively), however, these increases were moderate and of unknown
toxicologic significance in the absence of other toxic liver findings.

The systemic LOAEL in males is 200 mg/kg/day based on decreased body
weights, body weight gain, and food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis); the NOAEL
in males is 62.5 mg/kg/day.  The LOAEL in females is 375 mg/kg/day based
on decreased body weight, body weight gain, food consumption, and
lenticular degeneration; the NOAEL in females is 120 mg/kg/day.

It is noted that the high dose of 625 mg/kg/day should never have been
tested in males, based upon the results of the range-finding study (MRID
41665301).  Decreased body weight gain and food consumption were
observed in male rats after 14 days at a dose of 500 mg/kg/day.  An
initial reduction in body weight gain was also observed at the dose of
625 mg/kg/day although no decrease and rats were treated only for 10
days at this higher dose.

Despite this obvious error in dose selection for the main study, this
study is classified as Acceptable – Guideline.

Dose and Endpoint for Risk Assessment:  The systemic NOAEL in males is
62.5 mg/kg/day based on decreased body weights, body weight gain, and
food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis) at 200
mg/kg/day dose level.

Comments about Study/Endpoint:  A total uncertainty factor of 1000 is
applied to the oral endpoint selected for inhalation risk determination
(10x for interspecies extrapolation, 10x for intra species variations,
and 10x for route-to-route extrapolation).  The Agency may request a
confirmatory inhalation toxicity study, if the calculated MOE is below
the target value of 1000.  In addition, a 100% inhalation absorption
value must be applied for route-to-route extrapolation.

Dermal Absorption

Dermal Absorption Factor:    SEQ CHAPTER \h \r 1 A dermal absorption
factor of 100% is used since no dermal toxicity study is available.

Classification of Carcinogenic Potential

  SEQ CHAPTER \h \r 1 The carcinogenicity data for Organic esters of
phosphoric acid are not required at this time for the currently
registered uses.

The toxicological doses and endpoints selection are summarized below in
Table 5.1.

Table 5.1. Summary of Toxicological Doses and Endpoints for Organic
Esters of Phosphoric Acid

Exposure Scenario	Dose Used in

Risk Assessment

(mg/kg/day)	Target MOE, UF, for Risk Assessment	Study and

 Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(all populations)	This risk assessment is not currently required

Chronic Dietary

(all populations)	This risk assessment is not currently required

Non-Dietary Risk Assessments

Incidental Oral

Short-Term

(1-30days) and Intermediate-Term

(30 days-6 months)  	NOAEL (males) = 62.5 	MOE = 100 (10x inter-species
extrapolation, 10x intra-species variation)	90-Day (Oral) Subchronic
Toxicity Study in Rats (MRID 41083601)

LOAEL (males) = 200 mg/kg/day based on decreased body weights and body
weight gain and food consumption.

Dermal

Short-Term

(1-30days) and Intermediate-Term

(30 days-6 months)  	NOAEL (males) = 62.5	MOE = 100 (10x inter-species
extrapolation, 10x intra-species variation)	90-Day (Oral) Subchronic
Toxicity Study in Rats (MRID 41083601)

LOAEL (males) = 200 mg/kg/day based on decreased body weights and body
weight gain and food consumption.

Dermal

Long-Term

(> 6 months)	NOAEL (males) = 62.5	MOE = 300 (10x inter-species
extrapolation, 10x intra-species variation, 3x for use of a subchronic
endpoint for the long-term endpoint) 	90-Day (Oral) Subchronic Toxicity
Study in Rats (MRID 41083601)

LOAEL (males) = 200 mg/kg/day based on decreased body weights and body
weight gain and food consumption.

Inhalation

Short-Term

(1-30days) and Intermediate-Term

(30 days-6 months)  	NOAEL (males) = 62.5	MOE = 1000 (10x inter-species
extrapolation, 10x intra-species variation, 10x route-to-route
extrapolation)	90-Day (Oral) Subchronic Toxicity Study in Rats (MRID
41083601)

LOAEL (males) = 200 mg/kg/day based on decreased body weights and body
weight gain and food consumption.

Cancer

(oral, dermal, inhalation)	No carcinogenicity data available for Organic
Esters of Phosphoric Acid.

NOAEL = no observed adverse effect level, LOAEL = lowest observed
adverse effect level, MOE = margin of exposure, UF = uncertainty factor

FQPA Considerations

There are no currently registered food-related uses for Organic esters
of phosphoric acid; therefore, no FQPA concerns will be assessed.
However, there are some uses (e.g., as material preservative in carpets,
flooring and tile, textile products, shower curtains, human clothing,
etc.) that may result in mouth contacting with the materials/products by
young children.  Therefore, a FQPA equivalent evaluation is conducted.
There is only one developmental toxicity study in rats and no data on
reproductive toxicity available for Organic esters of phosphoric acid.

	6.1	Developmental Toxicity Study Conclusions

In a developmental toxicity study (MRID 41151601), 25 presumed pregnant
Charles River rats (Crl: CD®BR) per group were administered Intersept®
(100.0% a.i.) by gavage at doses of 0, 125, 250 or 500, mg/kg/day on
gestation days (GD) 6-15, inclusive.  The controls were given vehicle
(corn oil) only for the same dosing period.  On GD 20, all dams were
sacrificed, necropsied to assess gross pathology, and uteri and ovaries
were removed.  All fetuses were sexed, weighed, and examined for
external malformations/variations prior to sacrifice.  Approximately
one-half of the fetuses were fixed in ethanol and the remainder were
placed in Bouin’s fixative and examined for visceral
malformations/variations.  The ethanol-fixed fetuses were further
processed, stained, and examined for skeletal malformations/variations.

Four treatment-related deaths occurred at 500 mg/kg/day.  Clinical signs
of toxicity observed at 500 mg/kg/day were salivation with red stain
around the mouth (7) and nose (10), hypoactivity (8), urine stains (17),
and fecal stains (4) compared to 0/25 control dams.  Urine stains were
also observed on one low-dose animal and four mid-dose animals.  There
were no statistically or biologically significant gross necropsy
observations at maternal sacrifice.  Absolute body weights were
statistically significantly reduced (p(0.05 or 0.01) for 250 and 500
mg/kg/day dams during GD 8, 12, 16, and 20 and statistically
significantly reduced body weight gain was observed for both treatment
groups during GD 6-8 and GD 0-20 (11.1 and 20.6%, respectively during GD
0-20).  Net body weight change from GD 0 was also statistically
significantly reduced at 250 and 500 mg/kg/day (17.2 and 21.1%,
respectively), compared to controls.  Food consumption was not
monitored.  No treatment-related maternal changes were noted at
125 mg/kg/day.

The maternal toxicity LOAEL is 250 mg/kg/day based on clinical signs of
toxicity and reduced absolute body weights and weight gains.  The
maternal toxicity NOAEL is 125 mg/kg/day.

There were statistically significant increases (p(0.01) in total
resorptions, early resorptions, and postimplantation losses at 500
mg/kg/day compared to controls.  One high-dose dam had complete litter
resorption of two implantation sites.  The increase in postimplantation
loss resulted in slightly (n.s.) decreased number of fetuses per litter
for the high-dose group.  Also at 500 mg/kg/day there were
statistically significant decreases (p(0.01) in live mean fetal weight
(9.5%) and live female fetal weight (10.1%) compared to controls.
Gravid uterine weights were also lower than controls at 250 and 500
mg/kg/day (6.2 and 20.3%, respectively) but did not reach statistical
significance.

The total fetuses (litters) with major external, visceral or skeletal
malformations was 0 (0), 1 (1), 4 (2), and 17 (9) (p(0.05), in the
control, low-, mid-, and high-dose groups, respectively.  A positive
trend for certain skeletal variations (delayed ossification of the
hyoid, skull, pelvic girdle, vertebrae, sternebrae, and metatarsals) was
also evident with increasing doses of Intersept® with the 500 mg/kg/day
group generally statistically significantly increased (p(0.05) compared
to controls.  A dose-related increase was also observed in the number of
litters containing fetuses with increased renal pelvic cavitation and
dilation of lateral ventricles of the brain.

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with
external malformations were 0/0, 1/1, 4/2, and 8/6 (litter rate,
p(0.05), respectively.  External malformations at 500 mg/kg/day
consisted of one fetus each with cleft palate and anophthalmia;
umbilical hernia; umbilical hernia, microphthalmia, exencephaly, and
spina bifida; extra hind limb; malformed head; humpback; and 2 with
anophthalmia.  At 250 mg/kg/day, malformations consisted of one fetus
with gnathocephaly, and, from a different litter, a fetus with
microphthalmia and two fetuses with umbilical hernia.

At 0,125, 250, and 500 mg/kg/day, the number of fetuses/litters with
skeletal malformations were 0/0, 1/1, 1/1, and 6/4 (litter rate,
p(0.05), respectively.  Wavy or bent ribs were seen in 2 fetuses from 2
litters at 250 mg/kg/day and in 15 fetuses from 8 litters at 500
mg/kg/day compared to none in controls.  Skeletal malformations at 500
mg/kg/day consisted of vertebral anomaly with or without associated rib
anomaly in 3 fetuses from 2 litters; cervical vertebrae fused in 2
fetuses from 2 litters; and single incidences of exencephaly,
forked/fused ribs, and supernumerary limbs.

No treatment-related fetal effects were observed at 125 mg/kg/day.

The developmental toxicity LOAEL is 250 mg/kg/day based on dose-related
increases in the number of litters with fetuses with skeletal and
visceral abnormalities.  The developmental toxicity NOAEL is 125
mg/kg/day.

This study is classified as Acceptable – Guideline.

	6.2	Reproductive Toxicity Study Conclusions

  SEQ CHAPTER \h \r 1 There are no data on the reproductive toxicity of
Organic esters of phosphoric acid.  For the current registered uses of
this chemical, this study is required and is considered a data gap in
the absence of the study.

6.3	Recommendation for a Developmental Neurotoxicity Study

6.5.1	Evidence of Neurotoxicity

From the available repeated-dose toxicity studies, there was no evidence
of neurotoxicity for Organic esters of phosphoric acid.  Developmental
toxicity effects were shown at the dose level at which maternal toxicity
was seen.  Based on the available data, it is   SEQ CHAPTER \h \r 1
concluded that there is not a concern for developmental neurotoxicity
resulting from exposure to Organic esters of phosphoric acid for its
currently registered uses.

7.0	REFERENCES

MRID 40423801	Unknown (1986) Intersept(: Acute inhalation toxicity in
rats.  American Biogenics Corporation, Decatur, IL.  Laboratory Study
No.: 420-2344, January 16, 1986.  Unpublished.

MRID 40564601	Lavelle, G.C. (1986) Gene mutation test on Intersept® -
The Salmonella/microsomal assay for bacterial mutagenic activity of
Compound A: Intersept® (Pomostat 941), Lot No. K13508 RJ. Hill Top
Biolabs, Inc., Main & Mile Streets, Miamiville, Ohio 45147. Laboratory
Project ID 85-1704-15, January 31, 1986.  Unpublished.

MRID 40564602	Buehler, E.V. (1987) Gene mutation test on Intersept® -
The Salmonella/microsomal assay for bacterial mutagenic activity of
Intersept®, Lot #2991. Hill Top Biolabs, Inc., Main & Mile Streets,
Miamiville, Ohio 45147. Laboratory Project ID 87-0795-11, October 19,
1987. Unpublished.

MRID 40564603	Murli, H. (1987) Mutagenicity test on Intersept® in an in
vitro cytogenetic assay measuring chromosomal aberration frequencies in
Chinese hamster ovary (CHO) cells. Hazleton Laboratories America, Inc.,
5516 Nicholson Lane, Suite 400, Kensington, Maryland 20895. Laboratory
Project ID HLA Study No. 9845-0-437, October 1, 1987. Unpublished.

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r chromatid exchange frequencies in Chinese hamster ovary (CHO) cells.
Hazleton Laboratories America, Inc., 5516 Nicholson Lane, Suite 400,
Kensington, Maryland 20895. Laboratory Project ID HLA Study No.
9845-0-438, October 1, 1987. Unpublished.

MRID 41083601	Pickersgill, N. (1989) Intersept: 90 day (dietary
administration) sub-chronic toxicity study in the rat.  Hazelton, UK,
Otley Road, Harrogate, North Yorkshire, England, HG3 1PY. Study #
5843-640/2. February 9, 1989.  Unpublished.

MRID 41151601	Morseth, S.L. (1989) Teratology study with Intersept® in
rats.  Hazleton Laboratories America, Inc., 9210 Leesburg Turnpike,
Vienna, VA 22182.  HLA Study No. 2535-100, May 19, 1989.  Unpublished.

MRID 42907901	Harrod, K.J. (1993) Portercept( HVAC with Intersept(
acrylic primer/finish: Acute oral toxicity in rats – Limit test.  Hill
Top Biolabs, Inc., Miamiville, OH.  Laboratory Project No.: 93-9025-21,
July 1, 1993. Unpublished.

MRID 42907902	Harrod, K.J. (1993) Portercept( HVAC with Intersept(
acrylic primer/finish: Acute dermal toxicity in rabbits.  Hill Top
Biolabs, Inc., Miamiville, OH.  Laboratory Project No.: 93-9025-21, July
1, 1993.   Unpublished.

MRID 44858903	Moore, G.E. (1999) Antimicrobial drip pad, 2%:  Primary
eye irritation study in rabbits.  Product Safety Labs, East Brunswick,
NJ.  Laboratory Project ID: 7217, March 31, 1999.  Unpublished.

MRID 44858904	Moore, G.E. (1999) Antimicrobial drip pad, 2%:  Primary
dermal irritation study in rabbits.  Product Safety Labs, East
Brunswick, NJ.  Laboratory Project ID: 7218, March 30, 1999.
Unpublished.

8.0  APPENDICES

Toxicity Profile Summary

Toxicity Profile Summary Tables

8.1.1  Acute Toxicity Table – See Section 4.1

8.1.2  Subchronic, Chronic and Other Toxicity Table

Table 8.1.  Subchronic, Chronic and Other Toxicity for Organic Esters of
Phosphoric Acid

Guideline Number/

Study Type/

Test Substance (% a.i.)	MRID Number (Year)/

Classification/Doses	Results

870.3250

90-day oral - Rat

Purity 100% (Intersept®)

	MRID 41083601/41665301 (1989)

Acceptable - Guideline

Rat, oral/diet (10/sex/group)

0, 62.5, 200, or 375/625 mg/kg/day (male);

0, 37.5, 120 or 375 mg/kg/day (female), 90 days

	Systemic Toxicity

Male:

NOAEL = 62.5 mg/kg/day

LOAEL = 200 mg/kg/day, based on decreased body weights, body weight
gain, and food consumption and forestomach lesions
(gastritis/ulcer-erosion/squamous hyperplasia hyperkeratosis);

Female:

NOAEL = 120 mg/kg/day

LOAEL = 375 mg/kg/day, based on decreased body weight and weight gain
and lenticular degeneration.

870.3700

Developmental (gavage) - Rat

Purity 100%	MRID  41151601/40679502 (1989)

Acceptable - Guideline

Females rats (25/dose)

0, 125, 250, or 500 mg/kg/day, GD 6-15, inclusive	Maternal toxicity:

NOAEL = 125 mg/kg/day

LOAEL = 250 mg/kg/day, based on clinical signs of toxicity and reduced
absolute body weight and weight gain;

Developmental toxicity:

NOAEL = 125 mg/kg/day

LOAEL = 250 mg/kg/day based on dose-related increases in the number of
litters with fetuses with skeletal and visceral abnormalities.

870.5265

Bacterial reverse mutation test

Purity not provided	MRID 40564601 (1986)

Acceptable - Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.005, 0.01, 0.05, 0.1, or 0.5 µL/plate with and without S9 metabolic
activation

	Negative

870.5265

Bacterial reverse mutation test

Purity not provided	MRID 40564602 (1987)

Acceptable - Guideline

Strains TA98, TA100, TA1535, TA1537 and TA1538

0.01, 0.05, 0.1, 0.5 or 1.0 µL/plate with and without S9 metabolic
activation

	Negative

870.5375

In Vitro mammalian chromosome aberration test (hamster)

Purity not provided	MRID 40564603 (1987)

Acceptable - Guideline

2.5, 5.0, 7.5, 10.0 µg/mL (10-hr harvest time) without S9 metabolic
activation;

10, 20, 30, 40 µg/mL (20-hr harvest time) without S9 metabolic
activation;

5, 7.5, 10, 25, 50, 75, 100 µg/mL (10-hr harvest time) with S9
metabolic activation

	Negative

870.5900

Mammalian cytogenetics (sister chromatid exchange) assay (hamster)

Purity not provided	MRID 40564604 (1987)

Acceptable - Guideline

0.033, 0.10, 0.333, 1.00, 3.33, 10.0, 33.3, 100, 333, 1000 µg/mL with
and without S9 metabolic activation

	Negative

Page   PAGE  1  of   NUMPAGES  30

Page   PAGE  30  of   NUMPAGES  30


[Federal Register Volume 80, Number 249 (Tuesday, December 29, 2015)]
[Notices]
[Pages 81340-81341]
[FR Doc No: 2015-32724]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-4170]

Establishment of a Public Docket; Clinical Trial Designs in
Emerging Infectious Diseases

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of docket; request for comments.

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

SUMMARY: The Food and Drug Administration (FDA) is establishing a
public docket to receive input on clinical trial designs in emerging
infectious diseases. Interested parties are invited to submit comments,
supported by research and data, regarding clinical trial designs.

DATES: Submit either electronic or written comments on the collection
of information by January 28, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2015-N-4170 for ``Clinical Trial Designs in Emerging Infectious
Diseases.'' Received comments will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' publicly viewable
at http://www.regulations.gov or at the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments

received, go to http://www.regulations.gov and insert the docket
number, found in brackets in the heading of this document, into the
``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

SUPPLEMENTARY INFORMATION: FDA held a workshop on ``Clinical Trial
Designs in Emerging Infectious Diseases'' in partnership with the
National Institute of Allergy and Infectious Diseases, the HHS Office
of the Assistant Secretary for Preparedness and Response, and the
Centers for Disease Control and Prevention as a step in collecting
information. The objectives of the workshop were to: (1) Discuss the
deployment of investigational products in the context of emerging
infectious diseases, drawing on the lessons learned in the Ebola virus
epidemic; (2) explore the strengths and weaknesses of different
clinical trial designs for establishing the safety and efficacy of
investigational products for the treatment and/or prevention of life-
threatening emerging infectious diseases (EID) in resource-limited
settings from scientific, ethical, and operational perspectives; (3)
identify areas of consensus and areas needing further discussion, with
the goal of formulating acceptable options for the deployment of
investigational products in clinical trials for future EIDs; and (4)
discuss planning and other factors that can impact on the ability to
establish clinical trials in a timely fashion to evaluate
investigational therapies. The meeting agenda, transcripts, and web
cast recordings are available on the FDA Web site at http://www.fda.gov/emergencypreparedness/counterterrorism/medicalcountermeasures/aboutmcmi/ucm466153.htm. The meeting agenda and
transcripts will also be available in the docket.
    FDA is opening this docket to provide an avenue for the public to
submit additional information that may be relevant to the design and
conduct of clinical trials for establishing the safety and efficacy of
investigational products for the treatment and/or prevention of life-
threatening emerging infectious diseases. Individuals submitting
comments are specifically invited to address the scientific, ethical,
and practical considerations that should be taken into account when
designing and implementing clinical trials for future emerging
infectious diseases in resource-limited settings.

    Dated: December 23, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-32724 Filed 12-28-15; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register: June 28, 2011 (Volume 76, Number 124)]
[Rules and Regulations]
[Page 37634-37636]
[DOCID:fr28jn11-6]

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

DEPARTMENT OF COMMERCE

Bureau of Industry and Security

15 CFR Part 748

[Docket No. 110519290-1298-01]
RIN 0694-AF25

Revision to the Validated End-User Authorization for CSMC
Technologies Corporation in the People's Republic of China

AGENCY: Bureau of Industry and Security, Commerce.

ACTION: Final rule.

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

SUMMARY: In this final rule, the Bureau of Industry and Security (BIS)
amends the Export Administration Regulations (EAR) to revise the
validated end-user authorization for CSMC Technologies Corporation
(CSMC) in the People's Republic of China (PRC) by adding an item to the
list of items that may be exported, reexported, or transferred (in-
country) to CSMC's eligible destinations under Authorization Validated
End-User (VEU).

DATES: This rule is effective June 28, 2011.

FOR FURTHER INFORMATION CONTACT: Karen Nies-Vogel, Chair, End-User
Review Committee, Office of the Assistant Secretary, Export
Administration, Bureau of Industry and Security, U.S. Department of
Commerce, Phone:<PHONE_NUMBER>, Fax:<PHONE_NUMBER>, E-mail:
<EMAIL_ADDRESS>

SUPPLEMENTARY INFORMATION:

Background

Authorization Validated End-User (VEU): The List of Approved End-Users,
Eligible Items and Destinations in the PRC

    BIS amended the EAR in a final rule on June 19, 2007 (72 FR 33646),
creating a new authorization for ``validated end-users'' (VEUs) located
in eligible destinations to which eligible items may be exported,
reexported, or transferred (in-country) under a general authorization
instead of a license, in conformance with section 748.15 of the EAR. On
January 18, 2011, BIS identified CSMC as a Validated End-User (76 FR
2802).
    VEUs may obtain eligible items that are on the Commerce Control
List, set forth in Supplement No. 1 to Part 774 of the EAR, without
having to wait for their suppliers to obtain export licenses from BIS.
Eligible items may include commodities, software, and technology,
except those controlled for missile technology or crime control
reasons.
    The VEUs listed in Supplement No. 7 to Part 748 of the EAR were
reviewed and approved by the U.S. Government in accordance with the
provisions of section 748.15 and Supplement Nos. 8 and 9 to Part 748 of
the EAR. The End-User Review Committee (ERC), composed of
representatives from the Departments of State, Defense, Energy and
Commerce, and other agencies, as appropriate, is responsible for
administering the VEU program. A unanimous vote by the ERC is required
to authorize VEU status for a candidate or to add any eligible items to
an existing authorization. Majority vote of the ERC is required to
remove VEU authorization or to remove eligible items from an existing
authorization.
    In addition to U.S. exporters, Authorization VEU may be used in
accordance with the provisions of the EAR by foreign reexporters and by
persons transferring in-country, and it does not have an expiration
date. VEUs are subject to regular reviews, based on information
available to the United States government, to ensure that items shipped
under Authorization VEU are used for civilian purposes. In addition,
VEUs are subject to on-site reviews as warranted.
    As of the date of this rule, pursuant to section 748.15(b) of the
EAR, VEUs are only located in the PRC and India.

Revisions to CSMC Technologies Corporation's ``Eligible Items (By
ECCN)''

    This final rule amends Supplement No. 7 to Part 748 of the EAR to
add most items classified under Export Control Classification Number
(ECCN) 3B001.h (``Multi-layer masks with a phase shift layer'') to the
list of items that may be exported, reexported, or transferred (in-
country) to CSMC's ``Eligible Destinations'' under Authorization VEU.
Multilayer masks with a phase shift layer designed to produce ``space
qualified'' semiconductor devices are excluded from those items
eligible for shipment under Authorization VEU to CSMC. The ERC reviewed
CSMC's request to add these items to its VEU Authorization and
concluded the proposed addition is appropriate.
    The complete list of items by ECCN, as revised, that may be
exported, reexported, or transferred (in-country) to CSMC's eligible
destinations under Authorization VEU is as follows:

Eligible Items that may be exported, reexported, or transferred (in-
country) to the three ``Eligible Destinations'' under CSMC Technologies
Corporation's Validated End-User Authorization

    Items classified under Export Control Classification Numbers
1C350.c.3, 1C350.c.11, 2B230.a, 2B230.b, 2B350.f, 2B350.g, 2B350.h,
3B001.c.1.a, 3B001.c.2.a, 3B001.e, 3B001.h (except for multilayer masks
with a phase shift layer designed to produce ``space qualified''
semiconductor devices), 3C002.a, and 3C004.

    Since August 21, 2001, the Export Administration Act (the Act) has
been in lapse and the President, through Executive Order 13222 of
August 17, 2001 (3 CFR, 2001 Comp., p. 783 (2002)), as extended most
recently by the Notice of August 12, 2010 (75 FR 50681 (August 16,
2010)), has continued the EAR in effect under the International
Emergency Economic Powers Act. BIS continues to carry out the
provisions of the Act, as appropriate and to the extent permitted by
law, pursuant to Executive Order 13222.

Rulemaking Requirements

    1. Executive Orders 13563 and 12866 direct agencies to assess all
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety effects, distributive impacts, and equity). Executive
Order 13563 emphasizes the importance of quantifying both costs and
benefits, of reducing costs, of harmonizing rules, and of promoting
flexibility. This rule has been determined to be not significant for
purposes of Executive Order 12866.
    2. This rule involves collections previously approved by the Office
of Management and Budget (OMB) under Control Number 0694-0088, ``Multi-
Purpose Application,'' which carries a burden hour estimate of 58
minutes to prepare and submit form BIS-748; and for recordkeeping,
reporting and review requirements in connection with Authorization VEU,
which carries an estimated burden of 30 minutes per submission. This
rule is expected to result in a decrease in license applications
submitted to BIS because this rule expands the list of items that do
not require an individually validated license for exports, reexports,
or transfers (in-country) to eligible CSMC destinations. Total burden
hours associated with the Paperwork Reduction Act of 1995 (44 U.S.C.
3501 et seq.) (PRA) and OMB Control Number 0694-0088 are not expected
to increase significantly as a result of this rule.
    Notwithstanding any other provisions of law, no person is required
to respond nor be subject to a penalty for failure to comply with a
collection of information, subject to the requirements of the PRA,
unless that collection of information displays a currently valid OMB
Control Number.
    3. This rule does not contain policies with Federalism implications
as that term is defined under Executive Order 13132.
    4. Pursuant to the Administrative Procedure Act (APA), 5 U.S.C.
553(b)(B), BIS finds good cause to waive requirements that this rule be
subject to notice and the opportunity for public comment because such
notice and comment here are unnecessary. In determining whether to
grant VEU designations, a committee of U.S. Government agencies
evaluates information about and commitments made by candidate
companies, the nature and terms of which are set forth in 15 CFR part
748, Supplement No. 8. The criteria for evaluation by the committee are
set forth in 15 CFR 748.15(a)(2).
    The information, commitments, and criteria for this extensive
review were all established through the notice of proposed rulemaking
and public comment process (71 FR 38313, July 2, 2006, and 72 FR 33646,
June 19, 2007). Given the similarities between the authorizations
provided under the VEU program and export licenses (as discussed
further below), the publication of this information does not establish
new policy; in publishing this final rule, BIS simply amends an
authorization by adding an eligible ECCN to the list of items approved
for export, reexport, or transfer (in-country)

to the VEU's approved facilities. This has been done within the
established regulatory framework of the VEU program. Further, this rule
does not abridge the rights of the public or eliminate the public's
option to export under any of the forms of authorization set forth in
the EAR.
    Publication of a proposed rule is unnecessary because the
authorization granted in the rule is consistent with the authorizations
granted to exporters for individual licenses (and amendments or
revisions thereof), which do not undergo public review. Just as license
applicants do, VEU authorization applicants provide the U.S. Government
with confidential business information. This information is extensively
reviewed according to the criteria for VEU authorizations, as set out
in 15 CFR 748.15(a)(2). Additionally, just as the interagency reviews
license applications, the authorizations granted under the VEU program
involve interagency deliberation and result from review of public and
non-public sources, including licensing data, and the measurement of
such information against the VEU authorization criteria. Given the
thorough nature of the review, and in light of the parallels between
the VEU application review process and the review of license
applications, public comment on this authorization and subsequent
amendments prior to publication is unnecessary. Moreover, because, as
noted above, the criteria and process for authorizing and administering
VEUs were developed with public comments; allowing additional public
comment on this amendment to an individual VEU authorization, which was
determined according to those criteria, is unnecessary.
    Section 553(d) of the APA generally provides that rules may not
take effect earlier than thirty (30) days after they are published in
the Federal Register. However, section 553(d)(1) of the APA provides
that a substantive rule which grants or recognizes an exemption or
relieves a restriction, may take effect earlier. Today's final rule
grants an exemption from licensing procedures and thus is effective
immediately.
    No other law requires that a notice of proposed rulemaking and an
opportunity for public comment be given for this final rule. Because a
notice of proposed rulemaking and an opportunity for public comment are
not required under the APA or by any other law, the analytical
requirements of the Regulatory Flexibility Act (5 U.S.C. 601 et seq.)
are not applicable and no regulatory flexibility analysis has been
prepared.

List of Subjects in 15 CFR Part 748

    Administrative practice and procedure, Exports, Reporting and
recordkeeping requirements.

    Accordingly, part 748 of the EAR (15 CFR parts 730-774) is amended
as follows:

PART 748--[AMENDED]

0
1. The authority citation for 15 CFR part 748 continues to read as
follows:

    Authority:  50 U.S.C. app. 2401 et seq.; 50 U.S.C. 1701 et seq.;
E.O. 13026, 61 FR 58767, 3 CFR, 1996 Comp., p. 228; E.O. 13222, 66
FR 44025, 3 CFR, 2001 Comp., p. 783; Notice of August 12, 2010, 75
FR 50681 (August 16, 2010).

0
2. Supplement No. 7 to Part 748 is amended by revising the ``Eligible
Items (by ECCN)'' for ``CSMC Technologies Corporation'', for ``China
(People's Republic of)'' to read as follows:

  Supplement No. 7 to Part 748--Authorization Validated End-User (VEU); List of Validated End-Users, Respective
                   Items Eligible for Export, Reexport and Transfer, and Eligible Destinations
----------------------------------------------------------------------------------------------------------------
              Country                 Validated end-user    Eligible items (by ECCN)      Eligible destination
----------------------------------------------------------------------------------------------------------------
China (People's Republic of)......                                                     .........................

                                                  * * * * * * *
                                    CSMC Technologies      1C350.c.3, 1C350.c.11,      CSMC Technologies Fab 1
                                     Corporation.           2B230.a, 2B230.b,           Co., Ltd, 14 Liangxi
                                                            2B350.f, 2B350.g 2B350.h,   Road, Wuxi, Jiangsu
                                                            3B001.c.1.a, 3B001.c.2.a,   214061, China.
                                                            3B001.e 3B001.h (except    CSMC Technologies Fab 2
                                                            for multilayer masks with   Co., Ltd., Block 86, 87,
                                                            a phase shift layer         Wuxi National Hi-New
                                                            designed to produce         Tech Industrial
                                                            ``space qualified''         Development Zone, Wuxi,
                                                            semiconductor devices),     Jiangsu 214061, China.
                                                            3C002.a, and 3C004.        Wuxi CR Semiconductor,
                                                                                Wafers and Chips Co.,
                                                                                Ltd., 14 Liangxi Road,
                                                                                Wuxi, Jiangsu 214061,
                                                                                China.

                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------

    Dated: June 22, 2011.
Kevin J. Wolf,
Assistant Secretary for Export Administration.
[FR Doc. 2011-16156 Filed 6-27-11; 8:45 am]
BILLING CODE 3510-33-P