DCN 5 4069 Site Visit for EPRI Grant/ Alden Laboratory Thomas, D., EPA Placeholder for pages 3 & 4. Pages not available in electronic format. Please see the hard copy at the USEPA Water Docket.


[Federal Register: March 15, 2006 (Volume 71, Number 50)]
[Notices]
[Page 13387]
[DOCID:fr15mr06-107]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2006-0222; FRL-7769-2]

Pesticide Program Dialogue Committee Spray Drift Work Group;
Notice of Public Meeting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: Pursuant to the Federal Advisory Committee Act (Pub. L. 92-
463), the U.S. Environmental Protection Agency (EPA) gives notice of a
public meeting of the Pesticide Program Dialogue Committee (PPDC) Spray
Drift Work Group on March 29 and 30, 2006. An agenda for this meeting
is being developed and will be posted on EPA's Web site. The work group
is developing input and advice concerning spray drift for EPA's Offices
of Water and Pesticide Programs.

DATES: The meeting will be held on Wednesday, March 29 and Thursday,
March 30, 2006. The meeting is tentatively scheduled for 9 a.m. to 4:30
p.m. on Wednesday and from 9 a.m. to noon on Thursday; please check the
agenda posted on EPA's Web site for any revision to the scheduled
times.

ADDRESSES: The meeting will be held in EPA's offices at Crystal Mall
2, 1801 S. Bell Street, Arlington, VA in room 1126 (the
``Fishbowl'').

FOR FURTHER INFORMATION CONTACT: Pat Cimino, Office of Pesticide
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number<PHONE_NUMBER>; fax number
(703) 308-4776; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general, and may be of
particular interest to persons who work in agricultural settings or
persons who are concerned about implementation of the Clean Water Act
(CWA); the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA);
the Federal Food, Drug, and Cosmetic Act (FFDCA); and the amendments to
both of these major pesticide laws by the Food Quality Protection Act
(FQPA) of 1996. Potentially affected entities may include, but are not
limited to: Farmers and agricultural workers; pesticide industry and
trade associations; environmental, consumer, and farm worker groups;
pesticide users and growers; pest consultants; State, local and Tribal
governments; academia; public health organizations; food processors;
and the public. If you have questions regarding the applicability of
this action to a particular entity, consult the person listed under FOR
FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established a docket for this action under
Docket identification number EPA-HQ-OPP-2006-0222; FRL-7769-2. Publicly
available docket materials are available either electronically at
http://www.regulations.gov or in hard copy at the Public Information

and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1801 S. Bell St., Arlington, VA. This Docket Facility is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
Docket telephone number is<PHONE_NUMBER>.
    2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.

II. Background

    The Office of Pesticide Programs is entrusted with responsibility
to help ensure the safety of the American food supply, the education
and protection from unreasonable risk of those who apply or are exposed
to pesticides occupationally or through use of products, and general
protection of the environment and special ecosystems from potential
risks posed by pesticides.
    The Office of Water is responsible for protecting public health by
ensuring safe drinking water and for protecting water quality and
restoring impaired waterways.

III. How Can I Request to Participate in the Meeting?

    PPDC meetings are open to the public and seating is available on a
first-come basis. Persons interested in attending do not need to
register in advance of the meeting. For information on facilities and
services for the handicapped or to request special assistance at the
meeting, contact Pat Cimino at the phone number listed under FOR
FURTHER INFORMATION CONTACT.

List of Subjects

    Environmental protection, Agriculture, Agricultural workers,
Chemicals, Foods, Growers, Pesticides and pests, Pesticide applicators,
Public health, Risk assessment, Tolerance reassessment, Water quality.

    Dated: March 8, 2006.
 James Jones,
Director, Office of Pesticide Programs.
[FR Doc. E6-3726 Filed 3-14-06; 8:45 am]

BILLING CODE 6560-50-S


[Federal Register Volume 76, Number 20 (Monday, January 31, 2011)]
[Notices]
[Pages 5366-5368]
[FR Doc No: 2011-1921]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OAR-2004-0077; FRL-9259-4]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Significant New Alternatives Policy (SNAP) Program
Final Rulemaking Under Title VI of the Clean Air Act Amendments of
1990; EPA ICR No. 1596.08, OMB Control No. 2060-0226

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: In compliance with the Paperwork Reduction Act (PRA) (44
U.S.C. 3501 et seq.), this document announces that EPA is planning to
submit a request to renew an existing approved Information Collection
Request (ICR) to the Office of Management and Budget (OMB). This ICR is
scheduled to expire on June 30, 2011. Before submitting the ICR to OMB
for review and approval, EPA is soliciting comments on specific aspects
of the proposed information collection as described below.

DATES: Comments must be submitted on or before April 1, 2011.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-
OAR-2004-0077, by one of the following methods:
     http://www.regulations.gov: Follow the on-line
instructions for submitting comments.
     E-mail<EMAIL_ADDRESS>     Mail: Environmental Protection Agency, EPA Docket Center
(EPA/DC), Mailcode 6102T, Attention Docket ID No. OAR, 1200
Pennsylvania Avenue, NW., Washington, DC 20460
     Hand Delivery: Public Reading Room, Room 3334, EPA West
Building, 1301 Constitution Avenue, NW., Washington, DC.
    Such deliveries are only accepted during the Docket's normal hours
of operation, and special arrangements should be made for deliveries of
boxed information.
    Instructions: Direct your comments to Docket ID No. EPA-HQ-OAR-
2004-0077. EPA's policy is that all comments received will be included
in the public docket without change and may be made available online at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through http://www.regulations.gov or e-mail. The http://www.regulations.gov Web site
is an ``anonymous access'' system, which means EPA will not know your
identity or contact information unless you provide it in the body of
your comment. If you send an e-mail comment directly to EPA without
going through http://www.regulations.gov your e-mail address will be
automatically captured and included as part of the comment that is
placed in the public docket and made available on the Internet. If you
submit an electronic comment, EPA recommends that you include your name
and other contact information in the body of your comment and with any
disk or CD-ROM you submit. If EPA cannot read your comment due to
technical difficulties and cannot contact you for clarification, EPA
may not be able to consider your comment. Electronic files should avoid
the use of special characters, any form of encryption, and be free of
any defects or viruses. For additional information about EPA's public
docket visit the EPA Docket Center homepage at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Melissa Fiffer, Stratospheric
Protection Division, Alternatives and Emissions Reduction Branch, Mail
Code 6205J, Environmental Protection Agency, 1200 Pennsylvania Ave.,
NW., Washington, DC 20460; telephone number:<PHONE_NUMBER>; fax
number:<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

How can I access the docket and/or submit comments?

    EPA has established a public docket for this ICR under Docket ID
No. EPA-HQ-OAR-2004-0077, which is available for online viewing at
http://www.regulations.gov, or in person viewing at the Air and
Radiation Docket in the EPA Docket Center (EPA/DC), EPA West, Room
3334, 1301 Constitution Ave., NW., Washington, DC. The EPA/DC Public
Reading Room is open from 8 a.m. to 4:30 p.m., Monday through Friday,
excluding legal holidays. The telephone number for the Reading Room is
202-566-1744, and the telephone number for the Air and Radiation Docket
is<PHONE_NUMBER>.
    Use http://www.regulations.gov to obtain a copy of the draft
collection of information, submit or view public comments, access the
index listing of the contents of the docket, and to access those
documents in the public docket that are available electronically. Once
in the system, select ``search,'' then key in the docket ID number
identified in this document.

What information is EPA particularly interested in?

    Pursuant to section 3506(c)(2)(A) of the PRA, EPA specifically
solicits comments and information to enable it to:
    (i) Evaluate whether the proposed collection of information is
necessary for the proper performance of the functions of the Agency,
including whether the information will have practical utility;
    (ii) evaluate the accuracy of the Agency's estimate of the burden
of the proposed collection of information, including the validity of
the methodology and assumptions used;
    (iii) enhance the quality, utility, and clarity of the information
to be collected; and
    (iv) minimize the burden of the collection of information on those
who are to respond, including through the use of appropriate automated
electronic, mechanical, or other technological collection techniques or
other forms of

information technology, e.g., permitting electronic submission of
responses. In particular, EPA is requesting comments from very small
businesses (those that employ less than 25) on examples of specific
additional efforts that EPA could make to reduce the paperwork burden
for very small businesses affected by this collection.

What should I consider when I prepare my comments for EPA?

    You may find the following suggestions helpful for preparing your
comments:
    1. Explain your views as clearly as possible and provide specific
examples.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used
that support your views.
    4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
    5. Offer alternative ways to improve the collection activity.
    6. Make sure to submit your comments by the deadline identified
under DATES.
    7. To ensure proper receipt by EPA, be sure to identify the docket
ID number assigned to this action in the subject line on the first page
of your response. You may also provide the name date, and Federal
Register citation.

What information collection activity or ICR does this apply to?

    Docket ID No. EPA-HQ-OAR-2004-0077.
    Affected entities: Entities potentially affected by this action are
manufacturers, importers, formulators and processors of substitutes for
ozone-depleting substances.
    Title: Significant New Alternatives Policy (SNAP) Program Final
Rulemaking Under Title VI of the Clean Air Act Amendments of 1990.
    ICR numbers: EPA ICR No. 1596.08, OMB Control No. 2006-0226.
    ICR status: This ICR is currently scheduled to expire on June 30,
2011. An Agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information, unless it displays
a currently valid OMB control number. The OMB control numbers for EPA's
regulations in title 40 of the CFR, after appearing in the Federal
Register when approved, are listed in 40 CFR part 9, and are displayed
either by publication in the Federal Register or by other appropriate
means, such as on the related collection instrument or form, if
applicable. The display of OMB control numbers in certain EPA
regulations is consolidated in 40 CFR part 9.
    Abstract: Information collected under this rulemaking is necessary
to implement the requirements of the Significant New Alternatives
Policy (SNAP) program for evaluating and regulating substitutes for
ozone-depleting chemicals being phased out under the stratospheric
ozone protection provisions of the Clean Air Act (CAA) and globally
under the Montreal Protocol on Substances That Deplete the Ozone Layer.
Under CAA Section 612, EPA is authorized to identify and restrict the
use of substitutes for class I and class II ozone-depleting substances
where EPA determines other alternatives exist that reduce overall risk
to human health and the environment. The SNAP program, based on
information collected from the manufacturers, formulators, and/or
sellers of such substitutes, identifies acceptable substitutes.
Responses to the collection of information are mandatory under Section
612 for anyone who sells or, in certain cases, uses substitutes for an
ozone-depleting substance after April 18, 1994, the effective date of
the final rule. Measures to protect confidentiality of information
collected under the SNAP program are based on EPA's confidentiality
regulations (40 CFR 2.201 et seq., or Subpart B). Submitters may
designate all or portions of their forms or petitions as confidential.
EPA requires the submitters to substantiate their claim of
confidentiality. Under CAA Section 114(c), emissions information may
not be claimed as confidential.
    To develop the lists of acceptable and unacceptable substitutes,
the Agency must assess and compare ``overall risks to human health and
the environment'' posed by use of substitutes in the context of
particular applications. EPA requires submission of information
covering a wide range of health and environmental factors. These
include intrinsic properties such as physical and chemical information,
ozone depleting potential, global warming potential, toxicity, and
flammability, and use-specific data such as substitute applications,
process description, environmental release data, exposure data during
use of a substitute, environmental fate and transport, and cost
information. Once a completed submission has been received, a 90 day
review period under the SNAP program will commence. Any substitute
which is a new chemical must also be submitted to the Agency under the
Premanufacture Notice program under the Toxic Substances Control Act
(TSCA). Alternatives that will be used as sterilants must be filed
jointly with EPA's Office of Pesticide Programs and with SNAP.
    Burden Statement: The annual public reporting and recordkeeping
burden for this collection of information is estimated to average 30
hours per response. Burden means the total time, effort, or financial
resources expended by persons to generate, maintain, retain, or
disclose or provide information to or for a Federal agency. This
includes the time needed to review instructions; develop, acquire,
install, and utilize technology and systems for the purposes of
collecting, validating, and verifying information, processing and
maintaining information, and disclosing and providing information;
adjust the existing ways to comply with any previously applicable
instructions and requirements which have subsequently changed; train
personnel to be able to respond to a collection of information; search
data sources; complete and review the collection of information; and
transmit or otherwise disclose the information.
    The ICR provides a detailed explanation of the Agency's estimate,
which is only briefly summarized here:
    Estimated total number of potential respondents: 221.
    Frequency of response: Annual.
    Estimated total annual burden hours: 6,517 hours.
    Estimated total annual costs: $465,450. This includes an estimated
burden cost of $443,170 in labor costs, $22,070 in capital costs, and
$210 in maintenance and operational costs.

Are there changes in the estimates from the last approval?

    There is a decrease of 1,687 hours in the total estimated
respondent burden compared with that identified in the ICR currently
approved by OMB. The development of new substitutes caused the number
of persons filing a SNAP Information Notice or TSCA/SNAP addendum to
increase slightly, but also resulted in fewer respondents keeping
records for alternatives that are subject to narrowed use limits. In
addition, respondents filing a SNAP Information Notice reported a
decrease in total annual burden of hours when collecting data to
complete the form and when responding to requests for additional
information. This decrease may be attributable to increased respondent
familiarity with EPA's forms, more examples in the public record for
respondents to research and use in preparing responses, and general
increased availability of computer software and information via the
Internet.

What is the next step in the process for this ICR?

    EPA will consider the comments received and amend the ICR as
appropriate. The final ICR package will then be submitted to OMB for
review and approval pursuant to 5 CFR 1320.12. At that time, EPA will
issue another Federal Register notice pursuant to 5 CFR
1320.5(a)(1)(iv) to announce the submission of the ICR to OMB and the
opportunity to submit additional comments to OMB. If you have any
questions about this ICR or the approval process, please contact the
technical person listed under FOR FURTHER INFORMATION CONTACT.

    Dated: January 24, 2011.
Elizabeth Craig,
Acting Director, Office of Atmospheric Programs.
[FR Doc. 2011-1921 Filed 1-28-11; 8:45 am]
BILLING CODE 6560-50-P


1 Date: December 8, 1997 MEMORANDUM SUBJECT: PENTACHLOROPHENOL:  Report of the Hazard Identification Assessment Review Committee.

FROM: Jess Rowland Branch Senior Scientist, Science Analysis Branch, Health Effects Division ( 7509C)

THROUGH: K. Clark Swentzel, Chairman, Hazard Identification Assessment Review Committee Toxicology Branch II, Health Effects Division ( 7509C)

TO: Norm Cook, Chief Risk Assessment and Science Support Branch Antimicorbial Division ( 7505W)

PC Code: 063001 On November 25, 1997, the Health Effects Division's Hazard Identification Review committee evaluated the toxicology data base of Pentachlorophenol, selected doses and endpoints for acute dietary, chronic dietary ( RfD) as well as occupational and residential exposure risk assessments, assessed the carcinogenic potential and addressed the sensitivity of infants and children from exposure to Pentachlorophenol as required by the Food Quality Protection Act ( FQPA). 2 Committee Members in Attendance Members in attendance were Karl Baetcke, William Burnam, George Ghali, Karen Hamernik, Susan Makris, Melba Morrow, Nancy McCarroll, Kathy Raffale, John Redden, Jess Rowland and Clark Swentzel. Data was presented by Tim McMahon of the Antimicrobial Division.

Report Preparation: Jess Rowland, M. S 3 I. INTRODUCTION On November 25, 1997, the Health Effects Division's Hazard Identification Review committee evaluated the toxicology data base of Pentachlorophenol, selected doses and endpoints for acute dietary, chronic dietary ( RfD) as well as occupational and residential exposure risk assessments, assessed the carcinogenic potential and addressed the sensitivity of infants and children from exposure to Pentachlorophenol as required by the Food Quality Protection Act ( FQPA).

II. HAZARD IDENTIFICATION A. Acute Dietary ( one day)

Study Selected: Developmental Toxicity  Rat § 83 3a MRID No. 43091702 Executive Summary: In a developmental toxicity study, pregnant Crl: CD BR VAF/ plus rats ( 25/ dose) received oral administration of Pentachlorophenol ( 88.9%) at doses of 0, 10, 30 or 80 mg/ kg/ day during gestation days 6 through 15. For maternal toxicity, the NOEL was 30 mg/ kg/ day and the LOEL was 80 mg/ kg/ day based on reduced body weight gain during the dosing period ( 79% of control) and for the entire gestation period ( 88% of controls). Developmental toxicity observed at 80 mg/ kg/ day included: significant increase in the number of resorptions ( mainly early) with a corroborative decrease in litter size; . reduced mean fetal weights; significant increase in the number of fetuses with external, visceral and/ or skeletal malformation/ variations ( hydrocephaly, diaphragmatic hernia, and dilation of the renal pelvis); and significant increase in the number of litters ( 22 of 23) that contained fetuses ( 6 of 22) with skeletal anomalies. The most common were vertebral structural variations and incomplete ossification. For developmental toxicity, the NOEL was 30 mg/ kg and the LOEL was 80 mg/ kg/ day based on increased resorptions, reduced fetal weight and skeletal malformations/ variations.

Dose and Endpoint for Risk Assessment: Developmental NOEL= 30 mg/ kg/ day based on increased resorptions, reduced fetal weight and skeletal malformations/ variations at 80 mg/ kg/ day ( LOEL).

Comments about Study and Endpoint: The skeletal malformations/ variations are presumed to occur after a single exposure ( dose) and thus were considered to be appropriate for this risk assessment.

This risk assessment is required. 4 Acute Dietary Risk Assessment: The Committee determined that the 10 x factor to account for enhanced sensitivity of infants and children ( as required by FQPA) should be reduced to 3 x. For acute dietary risk assessment, a Margin of Exposure ( MOE) of 300 is required for the protection of the general U. S. population including infants and children from exposure to Pentachlorophenol.

Although developmental toxicity studies showed no increased sensitivity in fetuses as compared to maternal animals following in utero exposures in rats and rabbits a MOE of 300 is required because of the lack of an acceptable two generation reproductive toxicity study in rats which would have enabled an evaluation of sensitivity between adults and pups.

B. Chronic Dietary [ Reference Dose ( RfD)]

Study Selected: Chronic Toxicity  Dog Guideline § 82 1b MRID No. 43982701 Executive Summary: In a chronic toxicity study, Pentachlorophenol ( 90.9%) was administered to beagle dogs ( 4/ sex/ dose) in gelatin capsules at dose levels of 0, 1.5, 3.5, or 6.5 mg/ kg/ day for 52 weeks. Treatment related effects observed at the lowest dose level ( 1.5 mg/ kg/ day) were increases in liver weights ( females) and alkaline phosphatase activity ( males) as well as increases in the incidences of granular cytoplasmic pigment accumulation of the liver ( both sexes) and lymphocytic mucosal inflammation of the stomach. For systemic toxicity, the LOEL was 1.5 mg/ kg/ day based on the hepatotoxicity discussed above; a NOEL was not established.

Dose and Endpoint for establishing the RfD: LOEL= 1.5 mg/ kg/ day based on hepatotoxicity characterized as increases in liver weights and alkaline phosphatase activity, increased incidences of granular cytoplasmic pigment accumulation in the liver as well as increased incidence of lymphocytic mucosal inflammation in the stomach.

Comments about Study and Endpoint: Pigment accumulation seen in dogs has also been seen in rats.

For chronic risk assessment, an UF of 1000 was applied to derive the RfD. The UF of 1000 includes: 10 x for inter species variation; 10 x for intra species variation; 3 x for the use of a LOEL ( under FIFRA); and an additional 3 x for the data gap of a 2 generation reproductive toxicity study ( under FQPA).

RfD = 1.5 mg/ kg/ day ( LOEL)= 0.0015 mg/ kg/ day 1000 ( UF) 5 C. Occupational Exposure There are no registered residential use for Pentachlorophenol at the present time and therefore residential risk assessments are not required..

1. Dermal Absorption MRID No 00259257 Executive Summary: In a dermal absorption study 14 C Pentachlorophenol ( 5% solution in P 9 oil) was applied to the skin of yound adult Sprague Dawley rats for 0.25, 1, 4, 8 and 24 hours. The calculated absorption was 40% at 8 hours and 60% at 24 hours.

Dermal Absorption Factor: A dermal absorption factor of 40% should be used for correcting oral dosing to dermal dosing.

2. Short Term Dermal  ( 1 7 days)

Study Selected: Developmental Toxicity  Rat § 83 3a MRID No. 43091702 Executive Summary: See Acute Dietary Dose and Endpoint for Risk Assessment: Developmental NOEL= 30 mg/ kg/ day based on increased resorptions, reduced fetal weight and skeletal malformations/ variations at 80 mg/ kg/ day ( LOEL). Comments about Study and Endpoint: Since an oral NOEL was selected, a dermal absorption rate of 40% should be used for correcting the oral dose to a dermal dose for risk assessmeents.

Although a 90 dermal toxicity study in rats ( MRID No. 43182301) was available in the data base, it was not considered to be appropriate for this risk assessment because of the concern for the developmental effects that were seen in rats which were not evaluated in the dermal study. Also, the oral NOEL of 30 mg/ kg/ day is supported by the NOEL of 100 mg/ kg/ day established in the 90 day dermal study when the dermal absorption rate is used for correcting the oral dose to a dermal dose. A comparable dermal dose of 75 mg/ kg/ day is obtained when used in conjunction with a dermal absorption factor of 40% ( i. e., oral NOEL 30 mg/ kg/ day ÷ 40% DA = 75 mg/ kg/ day).

This risk assessment is required. 6 3. Intermediate Term Dermal ( 7 Days to Several Months)

Study Selected: Developmental Toxicity  Rat § 83 3a MRID No. 43091702 Executive Summary: See Acute Dietary Dose and Endpoint for Risk Assessment: Developmental NOEL= 30 mg/ kg/ day based on increased resorptions, reduced fetal weight and skeletal malformations/ variations at 80 mg/ kg/ day ( LOEL).

Comments about Study and Endpoint: Since an oral LOEL was selected, a dermal absorption rate of 40% should be used for correcting the oral dose to a dermal dose for risk assessmeents.

Although a 90 dermal toxicity study in rats ( MRID No. 43182301) was available in the data base, it was not considered to be appropriate for this risk assessment because of the concern for the developmental effects that were seen in rats which are not evaluated in the dermal study. Also, the oral NOEL of 30 mg/ kg/ day is supported by the NOEL of 100 mg/ kg/ day established in the 90 day dermal study when the dermal absorption rate is used for correcting the oral dose to a dermal dose. A comparable dermal dose of 75 mg/ kg/ day is obtained when used in conjunction with a dermal absorption factor of 40% ( i. e., oral NOEL 30 mg/ kg/ day ÷ 40% DA = 75 mg/ kg/ day).

This risk assessment is required.

4. Long Term Dermal ( Several Months to Life Time)

Study Selected: Chronic Toxicity Dog Guideline § 83 1b MRID No 43982701 Executive Summary: See Chronic Dietary Dose and Endpoint for Risk Assessment: LOEL= 1.5 mg/ kg/ day based on hepatoxicity characterized as increases in liver weights and alkaline phosphatase activity, increased incidences of granular cytoplasmic pigment accumulation in the liver as well as increased incidence of lymphocytic mucosal inflammation in the stomach. 7 Comments about Study and Endpoint: Since an oral LOEL was selected, a dermal absorption rate of 40% should be used for correcting the oral dose to a dermal dose for risk assessmeents. This dose was used in establishing the RfD.

This risk assessment is required.

5. Inhalation Exposure ( Any Time period)

Inhalation toxicity studies with the technical material were available in the toxicology data base and the available studies with the formuation products are all classified as Supplementary. Therefore, the Committee determined that Pentachlorophenol should be placed in Toxicity Category I, a respirator must be worn during use and a Data Call In notice should be issued for an acute inhalation toxicity study with the technical material.

Due to the lack of an appropriate inhalation toxicity study, doses and endpoints were not selected for inhalation risk assessments.

D Margin of Exposure for Occupational Exposures:

For Short and Intemediate Term dermal risk assessment, a MOE of 100 is adequate because a NOEL was used for these risk assessments. For Long Term dermal risk assessment, however, a MOE of 300 is required because of the use of a LOEL for this risk assessment. The additional UF of 3 is applied under FIFRA ( i. e., lack of a NOEL in the critical study) and NOT under FQPA. The latter ( FQPA) does not apply for these risk assessments, since there are no registered residential uses at the present time and thus infants and childern are not expected to be exposed to Pentachlorophenol.

III. CARCINOGENICITY CLASSIFICATION The National Toxicology Program ( NTP) conducted a toxicity/ carcinogenicity study with two composition of Pentachlorophenol: TG Penta and Dowicide EC 7. Both preparations contained 90% penta, but differed in the level and nature of impurities. Male and female B6C3F1 mice were fed diets containing TG Penta at 100 or 200 ppm and EC 7 at 100, 200 or 600 ppm for 2 years. Statistically significant increases in the incidences of multiple biologically significant tumor types ( hepatocellular adenomas and carcinomas, adrenal medulla pheochrocytomas and malignant pheochrocytomas, and/ or hemangiosarcomas and hemangiomas) were observed in one or both sexes.

The NTP has also just completed a toxicology/ carcinogenesis study in rats. The Agency is awaiting the receipt of a draft copy of the Technical Report. 8 Based on the observance of increased tumors in the mouse study and the pending results of the rat study, the Committee recommended that the carcinogenic potential of Pentachlorophenol should be evaluated by the Cancer Assessment Review Committee.

IV. FQPA CONSIDERATIONS 1. Determination of Sensitivity The oral perinatal and prenatal data demonstrated no indication of increased sensitivity of rats or rabbits to in utero exposure to Pentachlorophenol.

In a prenatal developmental toxicity study, Sprague Dawley rats ( at least 22/ group) received oral administrations of Pentachlorophenol ( 88.9%) in corn oil at doses of 0, 10, 30, or 80 mg/ kg/ day during gestation days 6 through 15. Cesarean sections were performed on gestation day 20. For maternal toxicity, the NOEL was 30 mg/ kg/ day and the LOEL was 80 mg/ kg/ day, based on reduced bodyweight gains. For developmental toxicity, the NOEL was 30 mg/ kg/ day and the LOEL was 80 mg/ kg/ day based on increased resorptions ( mainly early) with corollary reductions in litter size, reduced fetal weight, and increased litter incidences of external, visceral, and/ or skeletal malformations and variations. These findings included hydrocephaly, diaphragmatic hernia, dilatation of the renal pelvis, vertebral structural variations, and incomplete ossification of the sternebrae. ( MRID No. 43091702)

Apparently in other older developmental toxicity studies in rodents found in the literature, maternal and developmental effects were observed at 30 mg/ kg/ day, with a NOEL of 3 mg/ kg/ day. Although the NOELs for these studies may have been lower than the 1994 study, no special sensitivity was noted for the offspring.

The IRIS Data Base referenced a study by Larsen et al. ( 1975) which demonstrated that Pentachlorophenol does not cross the placenta. No data were provided in the package to allow adequate review of this hypothesis at the time of this review.

There was discussion of the possibility that developmental effects noted in rodents following in utero exposure to Pentachlorophenol were related to impurities in the test substance ( including hexadioxin). Apparently, there were some studies conducted to pursue these effects, and one by Schwetz and Gehring ( 1973) was discussed in the 1990 RfD report. Additionally, elevation of maternal body temperature was cited as a cause of developmental toxicity. This is feasible since pentachlorophenol uncouples oxidative phosphorylation and increases body temperature, and maternal heat stress is known to result in developmental toxicity. 9 In a prenatal developmental toxicity study, New Zealand White rabbits ( 20/ group) received oral administrations of Pentachlorophenol ( 88.9%) in corn oil at doses of 0, 7.5, 15, or 30 mg/ kg/ day in corn oil ( 1 ml/ kg) on gestation days 6 18. For maternal toxicity, the NOEL was 15 mg/ kg/ day, and the LOEL was 30 mg/ kg/ day based on minimally reduced body weight gain and consistent reductions in food consumption during the treatment period. No unequivocal treatment related developmental effects were noted; therefore, the developmental NOEL was > 30 mg/ kg/ day ( HDT) ( MRID No. 43091701)

A one generation reproduction study in rats was described in the literature. No data or adequate DER were provided for review. Various accounts of this study in the data package do not provide a clear description of the study design, although it was apparently conducted as part of a two year chronic study. Dietary levels for the chronic study are described as 0, 8, 23, 77, or 231 ppm ( equivalent to 0, 1, 3, 10, or 30 mg/ kg/ day, respectively). According to the 1990 RfD report, a significant decrease in percent pups born alive, and significant decreases in survival throughout lactation were observed at 30 mg/ kg/ day. Apparently, there was also a developmental segment to the study since increased variations in lumbar spurs and vertebrae with unfused centra were described for the same dose level. Based on these findings, it is assumed that the NOEL for effects on the offspring was 10 mg/ kg/ day, and the LOEL was 30 mg/ kg/ day. For the adults, the NOEL for chronic systemic toxicity was 3 mg/ kg/ day, with a LOEL of 10 mg/ kg/ day, based on liver and kidney pathology. It appears that the major flaw of this study is the lack of a second generation. ( Schwetz, et al., 1978)

2. Recommendation for a developmental neurotoxicity study Based on the following weight of the evidence review of the available data, the Committee determined that a developmental neurotoxicity study is not required.

# There was no evidence of frank, unequivocal neurotoxicity in the database, including changes in brain weight or incidence of neuropathology in the central or peripheral nervous system tissues ( nonperfused). The nervous system has not been generally considered a target tissue ( NTP Technical Report, 1989).

# No evidence of abnormalities in the development of the fetal nervous system were observed in the prenatal developmental toxicity studies in either rats or rabbits, at maternally toxic oral doses up to 30 mg/ kg/ day. Incidences of hydrocephaly in the prenatal rat study were seen in only 2 fetuses of 2 litters and were within published historical control ranges.

# There was minimal clinical evidence of nonspecific neurobehavioral effects such as salivation, ataxia, or convulsions.

VII. DATA GAPS Two Generation Reproductive Toxicity  Rat ( § 83 4) 10


[Federal Register: November 14, 2008 (Volume 73, Number 221)]
[Notices]
[Page 67511-67512]
[DOCID:fr14no08-82]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2008-0343; FRL-8389-3]

Naphthalene Reregistration Eligibility Decision

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the availability of EPA's Reregistration
Eligibility Decision (RED) for the pesticide naphthalene. The Agency's
risk assessments and other related documents also are available in the
naphthalene Docket. Naphthalene is an insecticide used primarily as a
moth repellant. EPA has reviewed naphthalene through the public
participation process that the Agency uses to involve the public in
developing pesticide reregistration and tolerance reassessment
decisions. Through these programs, EPA is ensuring that all pesticides
meet current health and safety standards.

FOR FURTHER INFORMATION CONTACT: Molly Clayton, Special Review and
Reregistration Division (7508P), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number:<PHONE_NUMBER>; fax
number:<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general, and may be of
interest to a wide range of stakeholders including environmental, human
health, and agricultural advocates; the chemical industry; pesticide
users; and members of the public interested in the sale, distribution,
or use of pesticides. Since others also may be interested, the Agency
has not attempted to describe all the specific entities that may be
affected by this action. If you have any questions regarding the
applicability of this action to a particular entity, consult the person
listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established a docket for this action under
docket identification (ID) number EPA-HQ-OPP-2008-0343. Publicly
available docket materials are available either in the electronic
docket at http://www.regulations.gov, or, if only

available in hard copy, at the Office of Pesticide Programs (OPP)
Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Bldg.),
2777 S. Crystal Dr., Arlington, VA. The hours of operation of this
Docket Facility are from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
    2.  Electronic access. You may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr.

II. Background

A. What Action is the Agency Taking?

    Under section 4 of the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA), EPA is reevaluating existing pesticides to
ensure that they meet current scientific and regulatory standards. EPA
has completed a RED for the pesticide, naphthalene under section
4(g)(2)(A) of FIFRA. Naphthalene is an insecticide used as a moth
repellant for the protection of wool clothing and as an animal
repellant against nuisance vertebrate pests. Naphthalene products are
formulated as moth balls, flakes, dusts, and granules. All pesticidal
uses of naphthalene are residential; no food or occupational uses are
registered.
    EPA has determined that the database to support reregistration is
substantially complete and that products containing naphthalene are
eligible for reregistration, provided the risks are mitigated in the
manner described in the RED. Upon submission of any required product
specific data under section 4(g)(2)(B) of FIFRA and any necessary
changes to the registration and labeling (either to address concerns
identified in the RED or as a result of product specific data), EPA
will make a final reregistration decision under section 4(g)(2)(C) of
FIFRA for products containing naphthalene.
    EPA is applying the principles of public participation to all
pesticides undergoing reregistration and tolerance reassessment. The
Agency's Pesticide Tolerance Reassessment and Reregistration; Public
Participation Process, published in the Federal Register on May 14,
2004, (69 FR 26819) (FRL-7357-9) explains that in conducting these
programs, EPA is tailoring its public participation process to be
commensurate with the level of risk, extent of use, complexity of
issues, and degree of public concern associated with each pesticide.
Due to its uses, risks, and other factors, naphthalene was reviewed
through the modified 4-Phase public participation process. Through this
process, EPA worked extensively with stakeholders and the public to
reach the regulatory decisions for naphthalene.
    The reregistration program is being conducted under congressionally
mandated time frames, and EPA recognizes the need both to make timely
decisions and to involve the public. Few comments were received during
the earlier comment period for this pesticide, and all issues related
to this pesticide were resolved through consultations with
stakeholders. The Agency therefore is issuing the naphthalene RED
without a comment period.

B. What is the Agency's Authority for Taking this Action?

    Section 4(g)(2) of FIFRA, as amended, directs that, after
submission of all data concerning a pesticide active ingredient, ``the
Administrator shall determine whether pesticides containing such active
ingredient are eligible for reregistration,'' before calling in product
specific data on individual end-use products and either reregistering
products or taking other ``appropriate regulatory action.''

List of Subjects

    Environmental protection, Pesticides and pests.

    Dated: November 5, 2008.
Steven Bradbury,
Director, Special Review and Reregistration Division, Office of
Pesticide Programs.
[FR Doc. E8-26966 Filed 11-13-08; 8:45 am]

BILLING CODE 6560-50-S


[Federal Register Volume 80, Number 3 (Tuesday, January 6, 2015)]
[Notices]
[Pages 500-501]
[FR Doc No: 2014-30946]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings #1

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

    Docket Numbers: EC15-57-000.
    Applicants: Kay Wind, LLC, Southern Power Company.
    Description: Joint Application for Authorization for Disposition of
Jurisdictional Facilities of Kay Wind, LLC, et. al.
    Filed Date: 12/29/14.
    Accession Number: 20141229-5206.
    Comments Due: 5 p.m. ET 1/20/15.

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

    Docket Numbers: ER10-1484-010.
    Applicants: Shell Energy North America (U.S.), L.P.
    Description: Updated Market Power Analysis for the Southeast Region
of Shell Energy North America (U.S.), L.P.
    Filed Date: 12/29/14.
    Accession Number: 20141229-5201.
    Comments Due: 5 p.m. ET 2/27/15.

    Docket Numbers: ER10-2743-006; ER12-995-004; ER12-637-004; ER10-
2793-006; ER10-2755-007; ER10-2739-010; ER10-1892-006; ER10-1886-006;
ER10-1872-006; ER10-1859-006.
    Applicants: Bluegrass Generation Company, L.L.C., Calhoun Power
Company, LLC, Cherokee County Cogeneration Partners, LLC, Columbia
Energy LLC, Decatur Energy Center, LLC, DeSoto County Generating
Company, LLC, Las Vegas Power Company, LLC, Mobile Energy L L C, Santa
Rosa Energy Center, LLC, LS Power Marketing, LLC.
    Description: Updated Market Power Analysis in Southeast Region of
the LS Power Development, LLC subsidiaries.
    Filed Date: 12/29/14.
    Accession Number: 20141229-5192.
    Comments Due: 5 p.m. ET 2/27/15.

    Docket Numbers: ER10-2870-005; ER14-2548-004; ER11-3013-004; ER10-
2872-004; ER10-2868-004; ER10-2865-005; ER10-2860-006.
    Applicants: TransCanada Power Marketing Ltd, TransCanada Hydro
Northeast Inc., Ocean State Power LLC, TransCanada Maine Wind
Development Inc., TC Ravenswood, LLC, TransCanada Energy Sales Ltd.,
Coolidge Power LLC.
    Description: Notice of Non-Material Change in Status of TransCanada
Entities.
    Filed Date: 12/29/14.
    Accession Number: 20141229-5179.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER11-4498-008; ER14-325-004; ER13-2409-004; ER12-
979-008; ER12-2542-005; ER12-2448-008; ER12-128-005; ER11-4507-007;
ER11-4501-009; ER11-4500-007; ER11-4499-008; ER11-4363-005.
    Applicants: Smoky Hills Wind Farm, LLC, Smoky Hills Wind Project
II, LLC, Enel Cove Fort, LLC, Enel Stillwater, LLC, Canastota
Windpower, LLC, EGP Stillwater Solar, LLC, Caney River Wind Project,
LLC, Rocky Ridge Wind Project, LLC, Prairie Rose Wind, LLC, Chisholm
View Wind Project, LLC, Buffalo Dunes Wind Project, LLC, Osage Wind,
LLC.
    Description: Notice of Change in Status of Smoky Hills Wind Farm,
LLC, et. al.
    Filed Date: 12/29/14.
    Accession Number: 20141229-5211.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER13-67-003.
    Applicants: NorthWestern Corporation.
    Description: Compliance filing per 35: Order No 1000 Fourth
Regional Compliance Filing--Montana OATT to be effective 10/1/2013.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5012.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER13-136-003; ER13-135-003; ER13-137-003; ER13-138-
003; ER13-141-003; ER13-142-003.
    Applicants: Georgia-Pacific Brewton LLC, Brunswick Cellulose LLC,
Georgia-Pacific Cedar Springs LLC, Georgia-Pacfic Consumer Operations
LLC, Palatka, Georgia-Pacific Consumer Products LP, Naheola, Georgia-
Pacific Consumer Products LP, Savannah.
    Description: Updated Market Power Analysis in Southeast Region of
the Georgia-Pacific Entities.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5028.
    Comments Due: 5 p.m. ET 3/2/15.

    Docket Numbers: ER15-747-000.
    Applicants: Midcontinent Independent System Operator, Inc.
    Description: Sec.  205(d) rate filing per 35.13(a)(2)(iii): 2014-
12-29 Sub-Regional Constraints in the PRA Filing to be effective 3/1/
2015.

    Filed Date: 12/29/14.
    Accession Number: 20141229-5165.
    Comments Due: 5 p.m. ET 1/20/15

    Docket Numbers: ER15-748-000.
    Applicants: Garrison Energy Center LLC.
    Description: Baseline eTariff Filing per 35.1: Application for
Market-Based Rate Authorization to be effective 12/31/2014.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5002.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER15-749-000.
    Applicants: Wheelabrator Ridge Energy Inc.
    Description: Compliance filing per 35.37: compliance to be
effective 2/28/2015.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5026.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER15-750-000.
    Applicants: Wheelabrator South Broward Inc.
    Description: Compliance filing per 35.37: Compliance South to be
effective 2/28/2015.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5027.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER15-751-000.
    Applicants: Wabash Valley Power Association, Inc.
    Description: Sec.  205(d) rate filing per 35.13(a)(2)(iii):
Amendment to Rate Schedule--NREMC and SDI to be effective 1/1/2015.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5054.
    Comments Due: 5 p.m. ET 1/20/15.

    Docket Numbers: ER15-752-000.
    Applicants: Southwestern Public Service Company.
    Description: Sec.  205(d) rate filing per 35.13(a)(2)(iii): 12-30-
14_RS135 SPS-GSEC_Amended Op Proc to be effective 1/1/2015.
    Filed Date: 12/30/14.
    Accession Number: 20141230-5064.
    Comments Due: 5 p.m. ET 1/20/15.

    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 5:00
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: December 30, 2014.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2014-30946 Filed 1-5-15; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 84, Number 132 (Wednesday, July 10, 2019)]
[Notices]
[Pages 32915-32916]
[FR Doc No: 2019-14675]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. AC19-171-000]

Spire Storage West LLC; Notice of Filing

    Take notice that on June 28, 2019, Spire Storage West LLC (Spire
Storage) filed a request as Successor to Clear Creek Storage Company,
L.L.C. (Clear Creek) for waiver or clarification of any

continuing obligation to file FERC Form Nos. 3-Q and 2-A covering Clear
Creek's activities in the months of January and February 2019
immediately before its combination into Spire Storage.
    Any person desiring to intervene or to protest this filing must
file in accordance with Rules 211 and 214 of the Commission's Rules of
Practice and Procedure (18 CFR 385.211, 385.214). Protests will be
considered by the Commission in determining the appropriate action to
be taken, but will not serve to make protestants parties to the
proceeding. Any person wishing to become a party must file a notice of
intervention or motion to intervene, as appropriate. Such notices,
motions, or protests must be filed on or before the comment date.
Anyone filing a motion to intervene or protest must serve a copy of
that document on the Applicant.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper using the eFiling link at http://www.ferc.gov. Persons unable to file electronically should submit an
original and 5 copies of the protest or intervention to the Federal
Energy Regulatory Commission, 888 First Street NE, Washington, DC
20426.
    This filing is accessible on-line at http://www.ferc.gov, using the
eLibrary link and is available for review in the Commission's Public
Reference Room in Washington, DC. There is an eSubscription link on the
website that enables subscribers to receive email notification when a
document is added to a subscribed docket(s). For assistance with any
FERC Online service, please email<EMAIL_ADDRESS>or call
(866) 208-3676 (toll free). For TTY, call<PHONE_NUMBER>.
    Comments: 5:00 p.m. Eastern Time on August 2, 2019.

    Dated: July 3, 2019.
Kimberly D. Bose,
Secretary.
[FR Doc. 2019-14675 Filed 7-9-19; 8:45 am]
 BILLING CODE 6717-01-P


[Federal Register Volume 77, Number 219 (Tuesday, November 13, 2012)]
[Rules and Regulations]
[Pages 67557-67559]
[FR Doc No: 2012-27517]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 25

[Docket No. FAA-2012-0959; Special Conditions No. 25-473-SC]

Special Conditions: ATR-GIE Avions de Transport Regional, Models
ATR42-500 and ATR72-212A Airplanes; Aircraft Electronic System Security
Protection From Unauthorized External Access

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final special conditions; request for comments.

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SUMMARY: These special conditions are issued for the ATR-GIE Avions de
Transport Regional Models ATR42-500 and ATR72-212A airplanes. These
airplanes will have novel or unusual design features associated with
the architecture and connectivity capabilities of the airplanes'
computer systems and networks, which may allow access to or by external
computer systems and networks. Connectivity to, or access by, external
systems and networks may result in security vulnerabilities to the
airplanes' systems. The applicable airworthiness regulations do not
contain adequate or appropriate safety standards for these design
features. These special conditions contain the additional safety
standards that the Administrator considers necessary to establish a
level of safety equivalent to that established by the existing
airworthiness standards.

DATES: The effective date of these special conditions is November 5,
2012. We must receive your comments by December 13, 2012.

ADDRESSES: Send comments identified by docket number FAA-2012-0959
using any of the following methods:
     Federal eRegulations Portal: Go to http://www.regulations.gov/and follow the online instructions for sending your
comments electronically.
     Mail: Send comments to Docket Operations, M-30, U.S.
Department of Transportation (DOT), 1200 New Jersey Avenue SE., Room
W12-140, West Building Ground Floor, Washington, DC, 20590-0001.
     Hand Delivery or by Courier: Take comments to Docket
Operations in Room W12-140 of the West Building Ground Floor at 1200
New Jersey Avenue SE., Washington, DC, between 8 a.m. and 5 p.m.,
Monday through Friday, except federal holidays.
     Fax: Fax comments to Docket Operations at<PHONE_NUMBER>.
    Privacy: The FAA will post all comments it receives, without
change, to http://www.regulations.gov/, including any personal
information the commenter provides. Using the search function of the
docket web site, anyone can find and read the electronic form of all
comments received into any FAA docket, including the name of the
individual sending the comment (or signing the comment for an
association, business, labor union, etc.). DOT's complete Privacy Act
Statement can be found in the Federal Register published on April 11,
2000 (65 FR 19477-19478), as well as at http://DocketsInfo.dot.gov/.
    Docket: Background documents or comments received may be read at

http://www.regulations.gov/at any time. Follow the online instructions
for accessing the docket or go to the Docket Operations in Room W12-140
of the West Building Ground Floor at 1200 New Jersey Avenue SE.,
Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday,
except federal holidays.

FOR FURTHER INFORMATION CONTACT: Varun Khanna, FAA, Airplane and Flight
Crew Interface Branch, ANM-111, Transport Airplane Directorate,
Aircraft Certification Service, 1601 Lind Avenue SW., Renton,
Washington 98057-3356; telephone<PHONE_NUMBER>; facsimile<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: The FAA has determined that notice of, and
opportunity for prior public comment on, these special conditions are
impracticable because these procedures would significantly delay
issuance of the design approval and thus delivery of the affected
aircraft. In addition, the substance of these special conditions has
been subject to the public comment process in several prior instances
with no substantive comments received. The FAA therefore finds that
good cause exists for making these special conditions effective upon
issuance.

Comments Invited

    We invite interested people to take part in this rulemaking by
sending written comments, data, or views. The most helpful comments
reference a specific portion of the special conditions, explain the
reason for any recommended change, and include supporting data.
    We will consider all comments we receive by the closing date for
comments. We may change these special conditions based on the comments
we receive.

Background

    On January 22, 2009, ATR-GIE Avions de Transport Regional
(hereafter referred to as ``ATR-GIE'') applied for a change to FAA Type
Certificate No. A53EU to install a new avionics suite that includes
connectivity capabilities between airplane computer systems and
networks and external systems and networks in their Models ATR42-500
and ATR72-212A airplanes. Both airplanes are two-engine, turbo-
propeller driven. The Model ATR42-500 has a maximum takeoff weight of
41,005 pounds and an emergency exit arrangement to support a maximum of
60 passengers. The Model ATR72-212A has a maximum takeoff weight of
49,603 pounds and an emergency exit arrangement to support a maximum of
72 passengers.

Type Certification Basis

    Under the provisions of Title 14, Code of Federal Regulations (14
CFR) 21.101, ATR-GIE must show that the Models ATR42-500 and ATR72-
212A, as changed, continue to meet the applicable provisions of the
regulations incorporated by reference in Type Certificate No. A53EU or
the applicable regulations in effect on the date of application for the
change. The regulations incorporated by reference in the type
certificate are commonly referred to as the ``original type
certification basis.'' In addition, the certification basis includes
certain special conditions, exemptions, and equivalent safety findings
that are not relevant to these special conditions.
    If the Administrator finds that the applicable airworthiness
regulations (i.e., 14 CFR part 25) do not contain adequate or
appropriate safety standards for the Models ATR42-500 and ATR72-212A
airplanes because of a novel or unusual design feature, special
conditions are prescribed under the provisions of Sec.  21.16.
    Special conditions are initially applicable to the model for which
they are issued. Should the type certificate for that model be amended
later to include any other model that incorporates the same novel or
unusual design features, or should any other model already included on
the same type certificate be modified to incorporate the same novel or
unusual design features, the special conditions would also apply to the
other model.
    In addition to the applicable airworthiness regulations and special
conditions, the Models ATR42-500 and ATR72-212A airplanes must comply
with the fuel vent and exhaust emission requirements of 14 CFR part 34
and the noise certification requirements of 14 CFR part 36.
    The FAA issues special conditions, as defined in 14 CFR 11.19, in
accordance with Sec.  11.38, and they become part of the type
certification basis under Sec.  21.101.

Novel or Unusual Design Features

    The Models ATR42-500 and ATR72-212A airplanes will incorporate the
following novel or unusual design features: Digital systems
architecture composed of several connected networks. The proposed
architecture and network configuration may be used for, or interfaced
with, a diverse set of functions, including:
     Flight-safety related control, communication, display,
monitoring, and navigation systems (aircraft control functions);
     Airline business and administrative support (airline
information services);
     Passenger information and entertainment systems (passenger
entertainment services); and,
     The capability to allow access to or by systems external
to the airplane.

Discussion

    The Models ATR42-500 and ATR72-212A architecture and network
configuration may allow increased connectivity to, or access by,
external airplane sources, airline operations, and maintenance systems
to the aircraft control functions and airline information services. The
aircraft control functions and airline information services perform
functions required for the safe operation and maintenance of the
airplane. Previously these functions and services had very limited
connectivity with external sources. The architecture and network
configuration may allow the exploitation of network security
vulnerabilities resulting in intentional or unintentional destruction,
disruption, degradation, or exploitation of data, systems, and networks
critical to the safety and maintenance of the airplane. The existing
regulations and guidance material did not anticipate these types of
airplane system architectures. Furthermore, 14 CFR regulations and
current system safety assessment policy and techniques do not address
potential security vulnerabilities, which could be exploited by
unauthorized access to airplane systems, data buses, and servers.
Therefore, these special conditions are issued to ensure that the
security (i.e., confidentiality, integrity, and availability) of
airplane systems is not compromised by unauthorized wired or wireless
electronic connections.

Applicability

    As discussed above, these special conditions are applicable to the
ATR-GIE Avions de Transport Regional Models ATR42-500 and ATR72-212A
airplanes. Should ATR-GIE apply at a later date for a change to the
type certificate to include another model incorporating the same novel
or unusual design feature, the special conditions would apply to that
model as well.

Conclusion

    This action affects only certain novel or unusual design features
on two models of airplanes. It is not a rule of general applicability.
    The substance of these special conditions has been subjected to the
notice and comment period in several prior instances and has been
derived

without substantive change from those previously issued. It is unlikely
that prior public comment would result in a significant change from the
substance contained herein. Therefore, because a delay would
significantly affect the certification of the airplane, the FAA has
determined that prior public notice and comment are unnecessary and
impracticable, and good cause exists for adopting these special
conditions upon issuance. The FAA is requesting comments to allow
interested persons to submit views that may not have been submitted in
response to the prior opportunities for comment described above.

List of Subjects in 14 CFR Part 25

    Aircraft, Aviation safety, Reporting and recordkeeping
requirements.
    The authority citation for these special conditions is as follows:

    Authority: 49 U.S.C. 106(g), 40113, 44701, 44702, 44704.

The Special Conditions

    Accordingly, pursuant to the authority delegated to me by the
Administrator, the following special conditions are issued as part of
the type certification basis for ATR-GIE Avions de Transport Regional
Models ATR42-500 and ATR72-212A airplanes.
    1. Airplane Electronic System Security Protection from Unauthorized
External Access. The applicant must ensure airplane electronic system
security protection from access to or by unauthorized sources external
to the airplane, including those possibly caused by maintenance
activity.
    2. The applicant must ensure that electronic system security
threats are identified and assessed, and that effective electronic
system security protection strategies are implemented to protect the
airplane from all adverse impacts on safety, functionality, and
continued airworthiness.
    3. The applicant must establish appropriate procedures to allow the
operator to ensure that continued airworthiness of the aircraft is
maintained, including all post-type-certification modifications that
may have an impact on the approved electronic system-security
safeguards.

    Issued in Renton, Washington, on November 5, 2012.
Ali Bahrami,
Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. 2012-27517 Filed 11-9-12; 8:45 am]
BILLING CODE 4910-13-P


Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 1 Chapter I. Executive Summary This document is an addendum to the Final Draft for the Drinking Water Criteria Document on Chlorinated Acids/ Aldehydes/ Ketones/ Alcohols ( U. S. EPA, 1994) and provides an update for trichloroacetic acid ( TCA) and monochloroacetic acid ( MCA). This addendum provides study descriptions for newer studies for TCA or MCA that have been published between 1994 and 2000, as well as a few key studies published prior to 1994 or in 2001. Brief summaries of the older literature are introduced as appropriate in this addendum as a means to put the newer data into perspective and for synthesis of the discussion on the derivation of the Health Advisories for TCA and MCA.

MCA and TCA are hygroscopic crystals in pure form, soluble and miscible in water,

respectively, and usually exist in the environment in aqueous solutions. The molecular weights of TCA and MCA are 163.4 and 94.5, respectively. Chlorinated acetic acids are formed during chlorination of water that contains organic matter, primarily humic and fulvic acids. Formation of chlorinated acetic acids is higher in the presence of humic acid fractions of water than in the presence of fulvic acid.

TCA is readily absorbed by the oral route in rats and by the dermal and oral routes in humans. Once absorbed, TCA is available for systemic distribution, based on the detection of TCA in blood after oral exposure. Tissue distribution appears to be time dependent; following Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 2 intravenous administration of radiolabelled TCA; the highest concentrations were in plasma followed by kidney, and liver for the first 3 hours following exposure. In contrast; radioactivity in the liver exceeded that in plasma at 24 hours following exposure, perhaps reflecting the slow rate of elimination from the liver. Intermediate levels of radioactivity were measured in other tissues and were lowest in fat. TCA appears to bind plasma proteins, which might be an important determinant of partitioning of TCA from the plasma to target tissues. In one study, the unbound fraction of TCA in plasma was 0.53, with a blood: plasma concentration ratio of 0.76,

suggesting that most of the TCA distributed in the blood would be available for uptake and distribution to tissues. No studies were identified on the tissue distribution of TCA in humans,

but the appearance of TCA in blood and urine of humans orally exposed to chlorinated solvents or chloral hydrate indicates that it is present in the systemic circulation as a downstream metabolite.

No studies investigating the toxicokinetics or degree of maternal to fetus or blood to breast milk transfer of TCA were located in the literature.

TCA is not readily metabolized, based on minimal first pass metabolism in the liver following oral dosing, and limited amounts of radioactivity excreted in exhaled air, or present as non extractable radiolabel in plasma and liver, following i. v administration of radiolabeled TCA.

Some studies suggest that TCA is metabolized to DCA. The enzymes involved in TCA metabolism have not been determined; some in vitro studies suggest that biotransformation is likely to be mediated by cytochrome P450s metabolic pathways. In contrast, the primary route of Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 3 DCA metabolism has recently been shown to be NADPH and glutathione transferase dependent.

The significance of these metabolic routes for TCA biotransformation is not known.

The primary route of excretion of TCA is in the urine ( 57 84% of administered dose is excreted after 24 48 hours), with exhalation of CO 2 and fecal excretion contributing to a lesser extent. In one study, the elimination half life following a single TCA dose was approximately 8 hours in rats. The elimination of TCA from the blood appears to be considerably slower in humans than in rodents exposed to chlorinated solvents, suggesting that chronic exposure to high doses might result in an increase in the internal dose of TCA. However, data on the rates of TCA elimination are based on studies of trichloroethylene and its downstream metabolites, including TCA. Thus, species differences might be due to differences in the internal dose of the parent compound ( resulting from differences in systemic absorption) and/ or in the rate of formation of TCA. On the other hand, rapid urinary clearance was observed in humans who were dermally exposed to low doses of TCA by walking or swimming in chlorinated pool water for 30 minutes.

Urinary TCA levels were elevated in the 10 minute period following exposure ( approximately 1.1 to 3.9 fold greater than background excretion levels), and generally returned to pre exposure levels within 3 hours. Higher exposures resulted in higher amounts of urinary TCA, adjusted to the subjects' body surface area, suggesting a dose response relationship. TCA pool water concentrations ranged from 57 to 871 µ g/ L, with a mean of 420 µ g/ L and a median of 278 µ g/ L,

resulting in dermal doses of approximately 1 µ g. The rapid elimination rate observed in the swimming pool study, relative to oral and inhalation animal studies, appeared to result from Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 4 route dependent and dose dependent differences in TCA kinetics, and it has been suggested that the potential for TCA bioaccumulation at environmentally relevant human exposures is likely to be limited.

Based on human case studies following accidental dermal exposure to concentrated solutions of MCA, absorption occurs rapidly and distributes to a diversity of target organs.

Similar findings were observed in orally dosed animal studies. In one animal study, radioactivity following an i. v. dose of radiolabeled MCA distributed into tissues rapidly, resulting in minimal concentrations in the plasma at 45 minutes following dosing. Radioactivity in the liver, heart,

lungs, and brown fat paralleled levels in plasma. However, radioactivity in the brain displayed different kinetics from plasma, with levels remaining relatively constant from 15 minutes to 16 hours post exposure. Similarly, high levels of radioactivity were observed in the thymus gland from 2 to 16 hours following exposure. No studies investigating the toxicokinetics or degree of maternal to fetus or blood to breast milk transfer of MCA were located.

The metabolism of MCA is not well understood. MCA can undergo dehalogenation reactions, leading to the formation of oxalate and glycine. Some in vivo animal studies and in vitro assays with liver tissue slices support the hypothesis that MCA may form glutathione conjugates. It has been suggested that the primary metabolic pathway involves glutathione conjugation and that the rate limiting step in MCA toxicity is liver detoxification; adverse effects occur at high doses due to metabolic saturation of detoxification pathways. This would suggest Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 5 that the parent MCA is the active toxic moiety. However, other investigators have hypothesized that MCA toxicity is associated with the formation of conjugates with proteins and/ or membrane lipids, resulting from the metabolism of the parent compound. This hypothesis is based on data showing increased retention of radiolabeled MCA in plasma protein, as well as liver, heart and lung, although the type of metabolites was not specified. MCA has also been shown to bind with lipids, as evidenced by the appearance of cholesteryl chloroacetate in neutral lipid fractions from hepatic lipid extracts from treated rats.

MCA is excreted primarily in urine in rats, with excretion by this route accounting for 50% or more of orally or intravenously administered doses within 16 or 17 hours. Based on one case report of dermal poisoning, MCA appears to be rapidly cleared from the blood in humans.

Limited animal data suggest that MCA and/ or its metabolites might accumulate in body tissue,

particularly the brain, depending on dose and/ or exposure duration.

No physiologically based pharmacokinetic ( PBPK) models have been developed for either MCA or TCA alone ( i. e., as parent compound). However, PBPK models for TCA and DCA in B6C3F1 mice exposed to trichloroethylene via oral dosing ( by gavage in corn oil) or inhalation have been elucidated by several investigators. The main trichloroethylene PBPK model was linked to five TCE metabolite sub models, for chloral hydrate, trichloroethanol, trichloroethanol glucuronide, DCA, and TCA, respectively. Each sub model contained compartments for the liver,

lung, kidney, and body. The tissue: blood partition coefficients for all five TCE metabolites were Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 6 experimentally determined. The model was developed using literature values for V max and K m for trichloroethylene, literature values for physiological parameters, and the experimentallydetermined tissue partition coefficients. Other parameters were fit using data for trichloroethylene and metabolites obtained from male B6C3F1 mice receiving a single gavage dose of 1200 mg/ kg trichloroethylene. The model was validated using other doses in the oral study ( 300, 600, and 2000 mg/ kg). For the inhalation model, additional parameters were developed using data from male B6C3F1 mice exposed for 4 hours to 600 ppm trichloroethylene; the model was validated with data from a separate inhalation mouse study, with exposure concentrations ranging from 110 748 ppm trichloroethylene.

The TCA models adequately described the TCA concentrations in the liver, lungs,

kidneys, and blood following trichloroethylene exposure, as well as urinary excretion of TCA following oral and inhalation exposure to trichloroethylene. But, the DCA models did not fit the experimental data as well as the TCA models. TCA and DCA observed in the model validation studies came either from either trichloroethylene metabolism or conversion of other trichloroethylene metabolites. Thus, the results of direct administration of either TCA or DCA could not be determined. In addition, the first order metabolic rate constants for the conversion of TCA to DCA, and for conversion of DCA to other metabolites were markedly different in the oral and inhalation models, suggesting that there might be route dependency in the metabolism of of these two chlorinated acetic acids. However, the metabolic rate constants for TCA and DCA Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 7 were derived from oral versus inhalation exposure to trichloroethylene. Thus, differences in these rate constants might be secondary to upstream differences in TCE metabolism.

A human PBPK model developed for trichloroethylene included two sub models to account for metabolism and excretion   one for TCA and one for trichloroethanol. The submodel for TCA was constructed in order to model concentrations of TCA in human blood and urine following human volunteer inhalation exposure to 50 or 100 ppm trichloroethylene, using sex specific metabolic rate constants and partition coefficients. Predicted TCA concentrations in the blood and urine were similar to those observed in trichloroethylene exposed males and females. However, TCA modeled in this study resulted from trichloroethylene metabolism, not from direct exposure. Thus, the usefulness of the model for understanding the toxicokinetics of TCA following direct exposures is limited.

EPA's Information Collection Rule ( ICR) database contains extensive information on concentrations of MCA and TCA in drinking water systems, and how those concentrations vary with input water characteristics and treatment methods. The database contains information from 6 quarterly samples from 7/ 97 to 12/ 98, from approximately 300 large systems covering approximately 500 plants. Based on these data, the mean concentrations of MCA and TCA are consistently lower in groundwater than surface water, with TCA > MCA in both water sources.

The mean concentrations of TCA were 3.28 and 13.25

g/ L in groundwater and surface water, Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 8 respectively, whereas the mean concentrations of MCA were 0.76 and 1.28

g/ L in groundwater and surface water, respectively.

For all chemical disinfection treatments for surface water and groundwater, the mean concentrations of TCA were significantly higher than MCA. Statistical examination of the data for surface water plants showed that the mean concentrations of TCA were significantly reduced when treatment with chlorine was followed by chloramine than when only free chlorine was used.

There were no significant differences in the mean concentrations of TCA among the common disinfection methods ( non ozonation) in groundwater, or for MCA for surface water or ground water. However, ozone in the water treatment plant and free chlorine or free chloramine in the distribution system may result in a statistically significant reduction in the formation of TCA compared to that observed using the common ( non ozonation) chemical disinfection processes in treating surface water. However, the use of ozone in treating surface water as compared to the common ( non ozonation) chemical disinfection processes did not result in statistically significant difference in MCA concentrations. In addition, there were no statistically significant differences in MCA and TCA concentrations using ozonation in treating surface water.

Statistical analysis of the ICR data indicated that, in general, for a given influent bromide concentration range in plants treating surface water or groundwater, the mean concentrations of TCA are significantly higher than MCA. Regression analysis showed that there is a statistically significant correlation between influent Total Organic Carbon ( TOC) concentration and the mean Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 9 concentration of MCA in surface water, but not between influent TOC concentration and the mean concentration of MCA in groundwater, or between influent TOC concentration and the mean concentration of TCA in surface or groundwater. Further, no consistently significant differences between the mean seasonal concentrations of MCA and TCA in groundwater or surface water were observed..

MCA and TCA have been used in industry, pharmaceutical preparations, and in hospitals.

Between 1981 to 1983, 10,912 workers were potentially exposed to MCA and 35,124 workers were potentially exposed to TCA.

In addition to MCA and TCA concentrations in drinking water, there are some limited data on MCA and TCA concentrations in air and food. Concentrations of MCA and TCA in the food appear to be comparable to those in drinking water and may contribute significantly to the overall dose. With regard to inhalation exposure, the reported annual average ambient air concentration for TCA is 7

g/ m3 and the estimated annual time weighted average ambient air concentration for MCA is 63

g/ m3. However, additional air monitoring data are needed to evaluate whether inhalation exposure is a significant route of human exposure. Dermal absorption of TCA contributes less than 1% of total doses from routine household uses of drinking water,

and dermal exposure from MCA is likely to be similarly low. Although available data suggest that food and air may be significant sources of human exposure to TCA and MCA, these data are inadequate to quantify the contributions of each of these sources for an overall assessment of Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 10 human exposure. Thus, the default relative source contribution ( RSC) from drinking water ( i. e.,

20%) is used to estimate lifetime health advisories for these chlorinated acetic acids.

No data are available on the body burden of MCA. Very limited data are available on the levels of TCA in blood or urine resulting from direct exposure to TCA. Some data have shown that exposure to chlorinated solvents such as tetrachloroethylene and trichloroethylene contribute to the total TCA body burden. However, these data are not useful in estimating total body burden because neither environmental intake nor the kinetics of TCA absorption and distribution are taken into account when TCA is a downstream metabolite from a chlorinated solvent.

In short term oral toxicity studies with TCA, high doses of approximately 600 mg/ kg/ day resulted in decreased food consumption and body weight loss. Alterations in intermediary carbohydrate metabolism ( e. g., decreased lactate levels in several tissues) have also been observed.. The liver has consistently been identified as a target organ for TCA toxicity in shortterm and longer term studies. Indicators of peroxisome proliferation have been primary endpoints evaluated, with mice reported to be more sensitive to induction of peroxisome proliferation than rats. In B6C3F1 mice exposed for 10 weeks to drinking water doses  125 mg/ kg/ day, TCA induced peroxisome proliferation ( in the absence of effects on liver weight); the No Observable

Adverse Effects Level ( NOAEL) was 25 mg/ kg/ day. In F344 rats exposed to TCA in drinking water for up to 104 weeks, peroxisome proliferation was observed at 364 mg/ kg/ day, but not at 32.5 mg/ kg/ day. Increased liver weight and significant increases in hepatocyte proliferation have Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 11 been observed in short term studies in mice at doses as low as 100 mg/ kg/ day, but no increase in hepatocyte proliferation was noted in rats given TCA at similar doses. More clearly adverse livertoxicity endpoints, including increased serum levels of liver enzymes ( indicating leakage from cells) and/ or histopathological evidence of necrosis, have been reported in rats, but generally only at high doses. For example, in a 2 year chronic drinking water bioassay with F344 rats, increased hepatocyte necrosis was observed only at the highest dose tested, 364 mg/ kg/ day.

The potential reproductive toxicity of TCA has not been adequately tested. No animal studies were identified that evaluated this endpoint. The results of an in vitro fertilization assay indicated that TCA might have the potential to decrease fertilization. The available data suggest that TCA is a developmental toxicant at maternally toxic doses. In the presence of maternal toxicity, TCA increased resorptions, decreased implantations, and increased cardiovascular malformations at 291 mg/ kg/ day in one drinking water study, and decreased fetal weight and length, and increased cardiovascular malformations at 330 mg/ kg/ day in another gavage study.

Neither of these studies identified a NOAEL. Developmental toxicity screening level assays,

including in vitro mouse and rat whole embryo culture and the nonmammalian Xenopus assay system ( frog embryo teratogenesis assay) have demonstrated adverse developmental effects. In contrast, testing using Hydra ( freshwater invertebrate hydrozoa) as a predictive model has shown that TCA is not likely to be a developmental toxicant. The Hydra system is an assay that determines the degree to which a test chemical can perturb embryonic development at maternally subtoxic doses, and is designed to overestimate developmental hazard potential. Its primary Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 12 utility is as a prescreening assay for developmental toxicity, and it is considered to be more sensitive to developmental toxicity than most in vitro mammalian test systems.

TCA was not mutagenic in the Ames assay in Salmonella typhimurium strain TA100 in the absence of metabolic activation. In modified Ames assays with Salmonella typhimurium,

mixed results were reported. TCA was weakly mutagenic in a mouse lymphoma assay. Studies reporting the effect of TCA on DNA strand breaks have also yielded mixed results. A recent study found that chromosome damage is not induced by TCA at neutralized pH; in contrast,

another study showed evidence of TCA induced clastogenicity ( small colonies) in mouse lymphoma cells at neutralized pH.

In carcinogenic gavage bioassays, TCA induces liver tumors in mice but not in rats. This observation has also been reported in more recent drinking water studies. One mouse study showed an increased incidence of hepatic adenomas in female B6C3F1 mice at drinking water doses of 262 mg/ kg/ day and higher. In contrast, no increase in liver lesions was found in F344 rats given drinking water doses up to 364 mg/ kg/ day. In addition, a variety of recent studies investigating epigenetic and genetic mechanisms of carcinogenicity have observed either TCAinduced or TCA promoted liver tumors in mice. Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 13 No animal studies were identified on the potential systemic toxicity of TCA following dermal or inhalation exposures. However, concentrated solutions of TCA applied topically to shave rabbit skin are corrosive.

In short term MCA toxicity studies, effects in mice included neurotoxicity and decreased body weight at high doses near the LD 50 of 260 mg/ kg. In lower dose studies, increased nasal discharge and lacrimation were observed in rats at  7.5 mg/ kg/ day, but no adverse effects were observed in mice treated with similar doses. Subchronic and chronic oral dosing studies suggest that the primary targets for MCA induced toxicity include the heart and nasal epithelium. In a 13 week oral gavage study, decreased heart weight was observed at 30 mg/ kg/ day ( equivalent to 21.4 mg/ kg/ day after adjustment for intermittent dosing) and cardiac lesions progressed in severity with increasing dose at  60 mg/ kg/ day. Liver and kidney toxicity were only observed at higher doses. In a two year chronic bioassay, MCA administered by gavage decreased survival and increased the incidence of nasal and forestomach hyperplasia in B6C3F1 mice at  50 mg/ kg/ day ( NTP, 1992). In a two year drinking water carcinogenic bioassay with F344 rats,

increased spleen weight was noted at 3.5 mg/ kg/ day. Decreased body weight, decreased liver and kidney weights, decreased spleen weight, and increased testes weight were observed at doses  26.1 mg/ kg/ day; these changes were interpreted by study authors as being associated with dosedependent decreases in body weight. Myocardial degeneration and inflammation of the nasal cavities were also observed in rats exposed to 59.9 mg/ kg/ day during the 104 week drinking water study, confirming the nasal cavities and heart as target organs of MCA induced toxicity. Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 14 No studies were located on the reproductive toxicity of MCA, and the potential developmental toxicity of MCA has not been adequately tested. In one developmental toxicity study, markedly decreased maternal weight gain were reported in pregnant rats exposed to 193 mg/ kg/ day MCA during gestation days ( GD) 1 22, without evidence of developmental toxicity.

However, fetal histopathology was limited to the heart. In contrast, an increase in cardiovascular malformations in pregnant rats exposed to 140 mg/ kg/ day during GD 6 15 was reported in a published abstract. This dose was also the Low Observable Adverse Effects Level ( LOAEL) for maternal toxicity, based on marked decreases in dam weight gain. However, a full report of this study has not been published. In non mammalian screening assays using the Hydra test system,

MCA was predicted to be a potential development toxicant in mammals. This test system is designed to overestimate developmental hazard potential and is considered to be more sensitive to developmental toxicity than most in vitro mammalian test systems; its primary utility is to identify compounds for in vivo developmental toxicity testing. Based on findings in the Hydra test system, MCA would be considered a priority compound for further testing in vivo.

Genotoxicity assays with MCA has yielded mixed results. Two year oral gavage cancer bioassays with male and female F344 rats and B6C3F1 mice, and a two year drinking water study with male F344 rats, have not shown evidence of MCA induced carcinogenicity. Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 15 No animals studies on the potential systemic toxicity of MCA following dermal or inhalation exposures were identified. However, concentrated solutions of MCA applied topically to shaved rabbit skin are corrosive.

There are no epidemiology or clinical studies investigating the potential human health effects of either TCA or MCA by any route of exposure.. Human health effects data for TCA and MCA are limited largely to case reports of accidental dermal poisonings and dermal injury caused by the use of TCA in chemical skin peeling applications and topical treatment of warts. TCA is corrosive to human skin. This characteristic has been used clinically in chemical skin peeling treatments for many years, in which concentrated solutions ( ranging from 16.9% to 50% TCA)

have been employed. No studies investigating the toxicity of TCA in humans via the inhalation route were located.

Case reports following accidental skin exposure to concentrated solutions demonstrate that MCA is a systemic metabolic poison in humans, resulting in a characteristic progression of toxicity that can be fatal. The skin burn typically intensifies 1 to 3 hours following exposure,

reaching a severity of second or third degree. Typical clinical signs include vomiting, neurological symptoms such as convulsions, and cardiovascular shock, which often progress to coma. Clinical signs include severe acidosis with hyperglycemia and hypokalemia, low urinary output, and elevated creatinine phosphokinase. Nonspecific organ lesions of the liver, grain, heart, and kidney have been reported. The onset of acidosis is thought to result from inhibition of the Kreb's cycle. Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 16 No studies investigating the toxicity of MCA in humans via the oral or inhalation routes were located.

TCA induces systemic, non cancer effects in animals and humans that can be grouped into three categories: metabolic alterations, liver toxicity, and developmental toxicity. The primary site of TCA toxicity is the liver. It has been suggested that TCA disrupts regulation of pyruvate dehydrogenase activity, leading to altered carbohydrate metabolism, although the precise mechanisms are unknown. Other hypotheses include TCA induced. dysregulation of protein kinases that modulate glycogen phosphorylase activity, resulting in TCA induced glycogen accumulation in the liver. However, in a study with dichloroacetic acid ( DCA), no alterations in glycogen phosphorylase activity associated with glycogen accumulation were observed, and the authors suggested that TCA might also not be acting in this manner. Proposed alternative mechanisms include alterations in the molecular structure of glycogen leading to sequestration of the glycogen in a form that is difficult to mobilize, or changes in serum glucose or insulin levels resulting in glucose accumulation. Peroxisome proliferation, as indicated by changes in markers of peroxisomal proliferation such as cyanide insensitive palmitoyl CoA oxidase ( PCO) and increased 12 hydroxylation of lauric acid, is thought to play a role in at least some of the observed liver effects induced by TCA. Although TCA induces developmental toxicity in rats at maternally toxic doses and in a number of in vitro test systems, the mechanism for the developmental toxicity is not known. Physiologically based pharmacokinetic modeling has suggested that TCA behaving as a weak acid might induce developmental toxicity by changing the intracellular pH in the Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 17 fetal/ embryo compartment Alternately, peroxisome proliferation might be involved in TCA's developmental toxicity; however, the mode of action is unknown.

A variety of mechanisms have been suggested as contributing to TCA induced liver tumorigenesis. Of these, peroxisome proliferation and altered regulation of cell growth have the most supporting data. There is little evidence for a role of direct genotoxicity of TCA itself,

oxidative DNA damage, or regenerative hyperplasia. The role of peroxisome proliferation is unclear, in part because liver tumors are only induced in mice, and peroxisome proliferative response are activated in both mice and rats. Further, humans have been reported to be less affected by exposure to peroxisomal proliferators than either mice or rats, and thus the relevance of this mode of tumor induction to human carcinogenesis may be low or non existent. A more convincing argument case can be made for altered regulation of cell growth and proliferation in subpopulations of cells, thus providing a selective growth advantage in chemically or spontaneously initiated cells.

Acute high doses of MCA cause metabolic acidosis in humans, hypothesized to be due to a build up of endogenously formed acids that results from inhibition of a key enzyme in the Kreb's cycle. MCA exposure also induces cardiovascular, kidney, and liver damage in fatal cases of MCA poisoning in humans, with the spectrum of effects being similar to that observed in rodents following subchronic or chronic oral toxicity studies. The mechanism for the apparent targeting of the heart has not been well characterized but may involve inhibition of the enzyme activity of Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 18 mitochondrial aconitase in heart muscle; aconitase is an important enzyme in the citric acid energy cycle ( Kreb's cycle). Mechanisms of liver and kidney damage have also been largely unexplored.

There is limited evidence that glutathione depletion might be important in cellular protection from MCA; one suggestion is that depletion of cellular thiols might be related to the observed targetorgan effects. However, the results of in vitro studies investigating this mechanism are mixed.

Nasal discharge and lacrimation were reported in rats following short term MCA gavage exposures. In chronic bioassays, MCA induced inflammation and hyperplasia in the nasal epithelium of mice when administered by gavage and chronic nasal inflammation in rats when given in drinking water. These findings might reflect the irritant properties of MCA; however, the possibility of nasal effects occurring secondarily to an alternative mechanism cannot be excluded.

The Health Advisory ( HA) values for TCA and MCA are summarized in Table I 1. For TCA, no suitable studies were identified for derivation of the One Day HA. A NOAEL of 25 mg/ kg/ day for increased relative liver weight, accompanied by increases in indicators of peroxisomal proliferation in B6C3F1 mice given TCA in drinking water for 21 days was used to derive a Ten Day HA of 3 mg/ L ( 3000 µ g/ L) for a 10 kg child. This Ten Day HA was used as a conservative value for the One Day HA. A NOAEL of 36.5 mg/ kg/ day, based on liver histopathological changes observed in Sprague Dawley rats given TCA in drinking water for 90 days, was used to derive a Longer Term HA of 0.4 mg/ L ( 400 µ g/ L) for a 10 kg child and 1 mg/ L ( 1000 µ g/ L) for a 70 kg adult. A NOAEL of 32.5 mg/ kg/ day, based on liver Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 19 histopathological changes in F344 rats exposed to TCA in drinking water for 2 years, was used to calculate a DWEL of 1 mg/ L ( 1000 µ g/ L) and a Lifetime HA value of 0.02 mg/ L ( 20 µ g/ L),

assuming an RSC of 20%.

According to EPA's1999 Draft Guidelines for Cancer Risk Assessment, TCA is classified as " suggestive evidence of carcinogenicity", because the evidence from animal data is suggestive of carcinogenicity, which raises a concern for carcinogenic effects, but is not sufficient for a conclusion regarding human carcinogenic potential.

For MCA, no suitable studies were identified for derivation of the One Day HA. Based on the observation of nasal discharge in rats exposed by gavage for 12 days in a 16 day period, a LOAEL of 7.5 mg/ kg/ day ( adjusted to 5.6 mg/ kg/ day to account for intermittent exposure) was used to derive a Ten Day HA of 0.2 mg/ L ( 200 µ g/ L) for a 10 kg child. This Ten Day HA was used as a conservative value for the One Day HA. Based on decreased relative heart weight in rats given MCA by gavage 5 days/ week for 13 weeks, a LOAEL of 30 mg/ kg/ day ( adjusted to 21.4 mg/ kg/ day to account for intermittent exposure) was used to derive a Longer Term HA of 0.2 mg/ L ( 200 µ g/ L) for a 10 kg child and 0.7 mg/ L ( 700 µ g/ L) for a 70 kg adult. A LOAEL of 3.5 mg/ kg/ day ( DeAngelo et al., 1997) for increased absolute and relative spleen weight in rats exposed to MCA for 104 weeks in Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 20 According to EPA's 1999 Draft Guidelines for Carcinogen Risk Assessment, MCA is best described as " inadequate for an assessment of human carcinogenic potential". Although well conducted chronic cancer bioassays performed in male and female B6C3F1 mice and F344 rats did not demonstrate evidence of carcinogenicity, the route of compound administration was via oral gavage, only two doses were tested, and significant mortality was observed in high dose male rats, high dose male mice, and low and high dose female rats. These high mortality rates may have compromised the power and sensitivity of the study to detect MCA associated tumor effects, should they have occurred. In the drinking water carcinogenesis bioassay with male F344 rats, no tumorigenic effects were noted; however, female rats, potentially more sensitive to MCAassociated effects, were not tested, and the group sample sizes were limited. Thus, this descriptor is appropriate for MCA carcinogenicity. Addendum to Drinking Water Criteria Document for Monochloroacetic Acid and Trichloroacetic Acid EPA/ OW/ OST/ HECD Draft, do not cite or quote I 21 Table I 1. Summary of Health Advisory Values for Drinking Water ( a)

Longer Term HA Lifetime HA Chemical One Day HA Ten Day HA Child Adult TCA 3 3 0.4 1 0.02 MCA 0.2 0.2 0.2 0.7 amg/ L