[Federal Register Volume 85, Number 211 (Friday, October 30, 2020)]
[Proposed Rules]
[Pages 68801-68803]
[FR Doc No: 2020-23153]

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Proposed Rules
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains notices to the public of
the proposed issuance of rules and regulations. The purpose of these
notices is to give interested persons an opportunity to participate in
the rule making prior to the adoption of the final rules.

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Federal Register / Vol. 85, No. 211 / Friday, October 30, 2020 /
Proposed Rules

DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 25

[Docket No. FAA-2020-0720; Notice No. 25-20-08-SC]

Special Conditions: The Boeing Company Model 787 Series Airplane;
Seats With Pretensioner Restraint Systems

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed special conditions.

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SUMMARY: This action proposes special conditions for The Boeing Company
(Boeing) Model 787 series airplane. This airplane will have a novel or
unusual design feature when compared to the state of technology
envisioned in the airworthiness standards for transport category
airplanes. This design feature is pretensioner restraint systems
installed on passenger seats. The applicable airworthiness regulations
do not contain adequate or appropriate safety standards for this design
feature. These proposed 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: Send comments on or before December 4, 2020.

ADDRESSES: Send comments identified by Docket No. FAA-2020-0720 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 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 9 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 website, 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).
    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 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: Shannon Lennon, Airframe and Cabin
Safety Section, AIR-675, Transport Standards Branch, Policy and
Innovation Division, Aircraft Certification Service, Federal Aviation
Administration, 2200 South 216th Street, Des Moines, Washington 98198;
telephone and fax<PHONE_NUMBER>; email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Comments Invited

    The FAA invites 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.
    The FAA will consider all comments received by the closing date for
comments. The FAA may change these special conditions based on the
comments received.

Background

    On November 8, 2018, Boeing applied for a change to Type
Certificate No. T00021SE for pretensioner restraint systems installed
on passenger seats in the Model 787 series airplane. This airplane is a
twin-engine, transport-category airplane with passenger seating
capacity of 420 and a maximum takeoff weight of 557,000 pounds.

Type Certification Basis

    Under the provisions of title 14, Code of Federal Regulations (14
CFR) 21.101, Boeing must show that the Model 787 series airplane, as
changed, continues to meet the applicable provisions of the regulations
listed in Type Certificate No. T00021SE or the applicable regulations
in effect on the date of application for the change, except for earlier
amendments as agreed upon by the FAA.
    If the Administrator finds that the applicable airworthiness
regulations (e.g., 14 CFR part 25) do not contain adequate or
appropriate safety standards for Boeing Model 787 series airplane
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 feature, or should any other model already included on
the same type certificate be modified to incorporate the same novel or
unusual design feature, these special conditions would also apply to
the other model under Sec.  21.101.
    In addition to the applicable airworthiness regulations and special
conditions, the Boeing Model 787 series airplane 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 Boeing Model 787 series airplane will incorporate the following
novel or unusual design features:
    Forward-facing seats incorporating a shoulder harness with
pretensioner device, otherwise known as a

pretensioner restraint system, which is intended to protect the
occupants from head injuries.

Discussion

    Boeing will install, in the Model 787 series airplane, forward-
facing seats that incorporate a shoulder harness with a pretensioner
system at each seat place for head-injury protection.
    Shoulder harnesses have been widely used on flight-attendant seats,
flight-deck seats, in business jets, and in general-aviation airplanes
to reduce occupant head injury in the event of an emergency landing.
Special conditions, pertinent regulations, and published guidance exist
that relate to other restraint systems. However, the use of
pretensioners in the restraint system on transport-airplane seats is a
novel design.
    The pretensioner restraint system utilizes a retractor which
eliminates slack in the shoulder harness and pulls the occupant back
into the seat prior to impact. This has the effect of reducing forward
translation of the occupant, reducing head arc, and reducing the loads
in the shoulder harness.
    Pretensioner technology involves a step-change in loading
experienced by the occupant for impacts below and above that at which
the device deploys, because activation of the shoulder harness, at the
point at which the pretensioner engages, interrupts upper-torso
excursion. This could result in the head injury criteria (HIC) being
higher at an intermediate impact condition than that resulting from the
maximum impact condition corresponding to the test conditions specified
in Sec.  25.562. See condition 1 in these special conditions.
    The ideal triangular maximum-severity pulse is defined in Advisory
Circular (AC) 25.562-1B, ``Dynamic Evaluation of Seat Restraint Systems
and Occupant Protection on Transport Airplanes.'' For the evaluation
and testing of less-severe pulses for purposes of assessing the
effectiveness of the pretensioner setting, a similar triangular pulse
should be used with acceleration, rise time, and velocity change scaled
accordingly. The magnitude of the required pulse should not deviate
below the ideal pulse by more than 0.5g until 1.33 t1 is reached, where
t1 represents the time interval between 0 and t1 on the referenced
pulse shape as shown in AC 25.562-1B. This is an acceptable method of
compliance to the test requirements of the special conditions.
    Additionally, the pretensioner might not provide protection, after
actuation, during secondary impacts. Therefore, the case where a small
impact is followed by a large impact should be addressed. If the
minimum deceleration severity at which the pretensioner is set to
deploy is unnecessarily low, the protection offered by the pretensioner
may be lost by the time a second, larger impact occurs.
    Conditions 1 through 4 ensure that the pretensioner system
activates when intended, to provide the necessary protection of
occupants. This includes protection of a range of occupants under
various accident conditions. Conditions 5 through 10 address
maintenance and reliability of the pretensioner system, including any
outside influences on the mechanism, to ensure it functions as
intended.
    The proposed 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.

Applicability

    As discussed above, these special conditions are applicable to the
Boeing Model 787 series airplane. Should Boeing apply at a later date
for a change to the type certificate to include another model
incorporating the same novel or unusual design feature, these special
conditions would apply to that model as well.

Conclusion

    This action affects only a certain novel or unusual design feature
on one model series of airplanes. It is not a rule of general
applicability.

List of Subjects in 14 CFR Part 25

    Aircraft, Aviation safety, Reporting and recordkeeping
requirements.

Authority Citation

    The authority citation for these special conditions is as follows:

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

The Proposed Special Conditions

Sec.  25.562   Emergency landing dynamic conditions.

    Accordingly, the Federal Aviation Administration (FAA) proposes the
following special conditions as part of the type certification basis
for the Boeing Model 787 series airplane.
    In addition to the requirements of Sec.  25.562, forward-facing
passenger seats with pretensioner restraint systems must meet the
following:

1. Head Injury Criteria (HIC)

    The HIC value must not exceed 1000 at any condition at which the
pretensioner does or does not deploy, up to the maximum severity pulse
that corresponds to the test conditions specified in Sec.  25.562.
Tests must be performed to demonstrate this, taking into account any
necessary tolerances for deployment.
    When an airbag device is present in addition to the pretensioner
restraint system, and the anthropormorphic test device (ATD) has no
apparent contact with the seat/structure but has contact with an
airbag, a HIC unlimited scored in excess of 1000 is acceptable,
provided the HIC15 score (calculated in accordance with 49 CFR 571.208)
for that contact is less than 700.
    ATD head contact with the seat or other structure, through the
airbag, or contact subsequent to contact with the airbag, requires a
HIC value that does not exceed 1000.

2. Protection During Secondary Impacts

    The pretensioner activation setting must be demonstrated to
maximize the probability of the protection being available when needed,
considering secondary impacts.

3. Protection of Occupants Other Than 50th Percentile

    Protection of occupants for a range of stature from a 2-year-old
child to a 95th percentile male must be shown. For shoulder harnesses
that include pretensioners, protection of occupants other than a 50th
percentile male may be shown by test or analysis. In addition, the
pretensioner must not introduce a hazard to passengers due to the
following seating configurations:
    a. The seat occupant is holding an infant.
    b. The seat occupant is a child in a child-restraint device.
    c. The seat occupant is a pregnant woman.

4. Occupants Adopting the Brace Position

    Occupants in the traditional brace position when the pretensioner
activates must not experience adverse effects from the pretensioner
activation.

5. Inadvertent Pretensioner Actuation

    a. The probability of inadvertent pretensioner actuation must be
shown to be extremely remote (i.e., average probability per flight hour
of less than 10-7).
    b. The system must be shown to be not susceptible to inadvertent
pretensioner actuation as a result of wear and tear, nor inertia loads
resulting from in-flight or ground maneuvers likely to be experienced
in service.
    c. The seated occupant must not be seriously injured as a result of
inadvertent pretensioner actuation.

    d. Inadvertent pretensioner actuation must not cause a hazard to
the airplane, nor cause serious injury to anyone who may be positioned
close to the retractor or belt (e.g., seated in an adjacent seat or
standing adjacent to the seat).

6. Availability of the Pretensioner Function Prior To Flight

    The design must provide means for a crewmember to verify the
availability of the pretensioner function prior to each flight, or the
probability of failure of the pretensioner function must be
demonstrated to be extremely remote (i.e., average probability per
flight hour of less than 10-7) between inspection intervals.

7. Incorrect Seat Belt Orientation

    The system design must ensure that any incorrect orientation
(twisting) of the seat belt does not compromise the pretensioner
protection function.

8. Contamination Protection

    The pretensioner mechanisms and controls must be protected from
external contamination associated with that which could occur on or
around passenger seating.

9. Prevention of Hazards

    The pretensioner system must not induce a hazard to passengers in
case of fire, nor create a fire hazard, if activated.

10. Functionality After Loss of Power

    The system must function properly after loss of normal airplane
electrical power, and after a transverse separation in the fuselage at
the most critical location. A separation at the location of the system
does not have to be considered.

    Issued in Des Moines, Washington, on October 14, 2020.
James E. Wilborn,
Acting Manager, Transport Standards Branch, Policy and Innovation
Division, Aircraft Certification Service.
[FR Doc. 2020-23153 Filed 10-29-20; 8:45 am]
BILLING CODE 4910-13-P


Page 1 of 11 Appendix A: Executive Summaries and Toxicological Profile of 4 CPA The requirements ( CFR 158.340) for a food use for 4 chlorophenoxyacetic acid are in Table 1. Use of the new guideline numbers does not imply that the new ( 1998) guideline protocols were used.

Table 1: Toxicology data requirements for a food use pesticide and whether or not they have been satisfied.

Test Technical Required Satisfied 870.1100 Acute Oral Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . 870.1200 Acute Dermal Toxicity . . . . . . . . . . . . . . . . . . . . . . 870.1300 Acute Inhalation Toxicity . . . . . . . . . . . . . . . . . . . . 870.2400 Primary Eye Irritation . . . . . . . . . . . . . . . . . . . . . . . 870.2500 Primary Dermal Irritation . . . . . . . . . . . . . . . . . . . . 870.2600 Dermal Sensitization . . . . . . . . . . . . . . . . . . . . . . . . Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 870.3100 Oral Subchronic ( rodent) . . . . . . . . . . . . . . . . . . . . . 870.3150 Oral Subchronic ( nonrodent) . . . . . . . . . . . . . . . . . . 870.3200 21 Day Dermal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 870.3250 90 Day Dermal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 870.3465 90 Day Inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . Yes Yes Yes No No Yes Yes No 1 No 2 No 2 870.3700a Developmental Toxicity ( rodent) . . . . . . . . . . . . . . . 870.3700b Developmental Toxicity ( nonrodent) . . . . . . . . . . . . 870.3800 Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Yes Yes Yes Yes No 1 No 1 870.4100a Chronic Toxicity ( rodent) . . . . . . . . . . . . . . . . . . . . 870.4100b Chronic Toxicity ( nonrodent) . . . . . . . . . . . . . . . . . 870.4200a Oncogenicity ( rat) . . . . . . . . . . . . . . . . . . . . . . . . . . 870.4200b Oncogenicity ( mouse) . . . . . . . . . . . . . . . . . . . . . . . 870.4300 Chronic/ Oncogenicity . . . . . . . . . . . . . . . . . . . . . . . Yes Yes Yes Yes No3 No 1 No 1 No 1 No 1

870.5100 Mutagenicity C Gene Mutation  bacterial . . . . . . . . . 870.5300 Mutagenicity C Gene Mutation  mammalian . . . . . . 870.5395 Mutagenicity C Structural Chromosomal Aberrations 870.5xxx Mutagenicity C Other Genotoxic Effects . . . . . . . . . . Yes Yes Yes No Yes Yes Yes

870.6100a Acute Delayed Neurotox. ( hen) . . . . . . . . . . . . . . . . 870.6100b 90 Day Neurotoxicity ( hen) . . . . . . . . . . . . . . . . . . . 870.6200a Acute Neurotox. Screening Battery ( rat) . . . . . . . . . 870.6200b 90 Day Neuro. Screening Battery ( rat) . . . . . . . . . . . 870.6300 Develop. Neuro . . . . . . . . . . . . . . . . . . . . . . . . . . . . No 4 No 4 No No No

870.7485 General Metabolism/ rats . . . . . . . . . . . . . . . . . . . . . 870.7600 Dermal Penetration . . . . . . . . . . . . . . . . . . . . . . . . . Yes No No1

1 A data waiver was granted for this guideline study. 2 Not required for this use category. 3 Either 870.4200a or 870.4300 can fulfil this requirement. 4 Required only for organophosphate pesticides. Page 2 of 11 Table 2: Acute Toxicity Data on 4CPA ( Technical Grade 4 CPA)

Guideline No. Study Type MRID #( s) Results Toxicity Category 870.1100 Acute Oral 41837001 LD 50 = 2703 mg/ kg III 870.1200 Acute Dermal 42522601 LD 50 = > 2000 mg/ kg III 870.1300 Acute Inhalation 42968201 LC 50 = > 5.25 mg/ L IV 870.2400 Primary Eye Irritation 42339101 Severe irritation I 870.2500 Primary Skin Irritation 42306801 Non irritating IV 870.2600 Dermal Sensitization 42339102 Not a sensitizer NA Subchronic Toxicity Adequacy of data base for subchronic toxicity: The data base for subchronic toxicity is considered complete. No additional studies are required at this time.

870.3100 90 Day Oral Toxicity  Rat EXECUTIVE SUMMARY: In a 90 day oral toxicity study ( MRID 42902501) 4 chlorophenoxyacetic acid ( 99.8% a. i., batch/ lot # HWI TM No. 0020A4) was administered to 12 Crl: CDBR VAF/ PLUS rats/ sex/ group in diet at dose levels of 0, 100, 2000 or 8000 ppm ( equivalent to 0, 6.6, 132.4 or 516.9 mg/ kg bw/ day for males and 0, 7.99, 153 or 625.9 mg/ kg bw/ day for females). Animals were subjected to the following: ( 1) observed twice daily, ( 2) body weights measured weekly, ( 3) food consumption measured weekly, ( 4) ophthalmic examination, ( 5) hematology, clinical chemistry, urinalysis at week 5 and 14, and ( 6) at 13 weeks, fasted and sacrificed for organ weights and gross examination and microscopic examination of selected tissue and organs. Male body weights were consistently nominally lower ( 0.05% by week 7 to  1.8% by week 14) than control weights at 8000 ppm. Significantly lower body weights ( p< 0.05) were seen in females ( 9% by week 3 to  14% by week 14) at 8000 ppm. Body weight gain was significantly decreased in males and females dosed at 8000 ppm for the first week and for week 10 for males and week 5 for females. Since food efficiency was less than controls in males ( 8%) and females ( 8%) at 8000 ppm, the decrease in weight may have been due to toxicity rather than decreased food consumption. Alkaline phosphatase was slightly, but statistically elevated at 5 weeks ( 29%) and 14 weeks ( 57%) in females only. At 8000 ppm, glucose was statistically Page 3 of 11 significantly lower by 16% in females. Urine volumes were increased in males ( 17% at week 5 and 2% at week 14) and significantly increased in females ( 233% at week 5 and 198% at week 14) at 8000 ppm. The specific gravity of urine from females was decreased significantly at week 5 ( 2%) and week 14 ( 2%) in the 8000 ppm group. At histological examination, an increased number of males showed liver lymphohistiocytic infiltration ( 1 in control and 5 at 8000 ppm) and individual hepatocyte necrosis ( 0 in control and 6 at 8000 ppm). The LOAEL is 8000 ppm ( 517 mg/ kg/ day for males and 626 mg/ kg/ day for females), based on body weight decrement in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females. The NOAEL is 2000 ppm ( 132 mg/ kg/ day for males and 153 mg/ kg/ day for females). This 90 day oral toxicity study in the rodent is acceptable guideline and satisfies the guideline requirement for a 90 day oral toxicity study ( OPPTS 870.3100; OECD 408) in rodent species. The acceptability of the study is unchanged from TXR# 0010794 and the NOAEL/ LOAEL are unchanged.

870.3150 90 Day Oral Toxicity  Dog EXECUTIVE SUMMARY: In a 90 day oral toxicity study ( MRID 42968301) 4 chlorophenoxyacetic acid ( 99.8%% a. i., batch/ lot HWI 0020A4) was administered to 4 Beagle dogs/ sex/ group in the diet at dose levels of 0, 20, 100 or 500 ppm ( equivalent to 0, 0.80, 3.3 or 18.6 mg/ kg/ day for males and 0, 0.78, 4.0 or 17.4 mg/ kg/ day for females; average for males and females; 0, 0.792, 3.67 and 18.0 mg/ kg bw/ day). Doses were based on a 4 week range finding study in 2 dogs/ sex/ group dosed at 0, 40, 200, 400, 800, 1600 or 3200 ppm ( MRID 43045301). In this range finding study, the dogs were offered test material for 3 hour for 1 day followed by basal diet for 2 days; the regimen was followed subsequently at the next higher dose until the 3200 ppm dose was reached. These treated dogs were then offered 1600 ppm for the remaining ten days from day 19 to 28. In this range finding study, decreased palatability at 1600 and 3200 ppm resulted in decreased body weight and changed clinical chemistries, while absolute and relative organ weight changes were associated with decreased nutritional status of the dogs. No specific toxicity was seen grossly or microscopically. In the 90 day study, body weights and food consumption were measured weekly in the 0, 20, 100 and 500 ppm groups ( MRID 42968301). No dose related statistical differences were seen. Male body weight were nominally lower throughout the study. Males showed a nominal body weight gain decrement of 250 g week 1 13 ( 8%), but females showed a nominal 25 g body weight gain week 1 13 (+ 1%) at 500 ppm. Male food consumption was statistically significantly depressed week 9 and 12 at the 100 ppm dose level. There was no dose related differences in food consumption or food efficiency for females on study. Male dogs showed a nominal  19% decreased food efficiency for the first 4 weeks of the study, but a nominal 9% increase during the last 9 weeks of the study for no change for the entire 13 week study. Clinical observations, hematology, and clinical chemistry data showed no differences by study termination. The author stated that red feces and vomiting were seen in all dose groups, but that it appeared to be more frequent in the two top dose levels. No dose related differences were Page 4 of 11 seen in organ weights or relative organ weights or pathology at microscopic examination. Statistically significant ovarian weight increase seen in the left ovary at 20 and 500 ppm, were not seen in the combined ovarian weights. The ovarian weight changes were considered incidental and not dose related. The study showed only suggestive body weight gain decrement at 500 ppm, but no definitive toxicity in any parameter . Possibly based on the nominal male body weight gain decrement, the study author concluded that the LOAEL was 500 ppm ( HDT). It is concluded that the suggestive toxicity in male body weight gain decrement at 500 ppm ( 18.6 mg/ kg/ day) may have approached a LOAEL. However, the demonstrated NOAEL is 500 ppm ( 18.6 mg/ kg/ day for males and 17.4 mg/ kg/ day for females or an average of 18.0 mg/ kg/ day for males and females). A LOAEL was not demonstrated. The NOAEL is 500 ppm ( 18.0 mg/ kg/ day)( HDT). This 90 day oral toxicity study in the dog is acceptable/ guideline and satisfies the guideline requirement for a 90 day oral toxicity study ( OPPTS 870.3150; OECD 409) in nonrodent species. Although the study shows no definitive toxicity, repeating the study is not likely to produce meaningful information on this unpalatable test material. Dogs suffered from malnutrition at higher dose levels in a range finding study ( MRID# 43045301). This malnutrition was caused by the unpalatable test material in the diet resulting in decreased food consumption. The acceptability of the study ( MRID 42968301) is not changed from TXR# 10794, however, the NOAEL has been changed from100 ppm in TXR# 10794 to 500 ppm in the current Executive Summary, with no LOAEL.

870.3700a Prenatal Developmental Toxicity Study  Rat EXECUTIVE SUMMARY: In a developmental toxicity study ( MRID 42322602) 4 chlorophenoxyacetic acid ( 99 100% a. i., batch/ lot # HWI 0020A1 and 0020A2) was administered to 25 Crl: CDBR VAF/ PLUS rats/ group by gavage at dose levels of 0, 150, 300, 600 or 1000 mg/ kg bw/ day from days 6 through 15 of gestation. Mean body weight gains of dams were significantly decreased and were dose related during gestational days 6 through 9 ( 44%) and 6 through 16 ( 14%) at 300 mg/ kg/ day and greater. Dams at 1000 mg/ kg/ day showed yellow staining of the ano genital area, tremors, uncoordinated movements, recumbent posture, languidness, and cold to touch. Also at 1000 mg/ kg/ day, 1 dam died and 3 were killed in a moribund condition. There were no differences among control and treated groups in pre or post implantation loss, resorptions or corpora lutea. Fetal weights were significantly lower than control in the 600 ( 8%) and 1000 mg/ kg/ day groups ( 19%). There were no dose related soft tissue or skeletal malformations. Statistically significant dose related increases occurred in unossified sternebrae 5 for fetuses at all dose levels, but not for litters. Litters in the 150 mg/ kg/ day group showed the same incidence as concurrent control litters and historical control litters. The litter incidence did not reach statistical significance below the 600 mg/ kg/ day dose level. At the 1000 mg/ kg/ day dose, other variations increased, increases were seen in misaligned sternebrae and 7th cervical ribs in fetuses and litters. Page 5 of 11 The LOAEL for developmental effects in fetuses and litters was the 300 mg/ kg/ day dose level. The study author stated that the LOAEL for developmental effects was 600 mg/ kg/ day because the litter incidence was significantly increased at 600 mg/ kg/ day. Although the incidence in litters was not significantly affected until the 600 mg/ kg/ day dose level was reached, the increased fetal incidence was statistically significant at 300 mg/ kg/ day ( 27% versus 13% in control) and showed a good dose related response and the litter incidence was nominally increased at 300 mg/ kg/ day ( 52% versus 73% in control) and showed a dose related response. The response in fetuses and litters at 300 mg/ kg/ day and above suggests that the increased litter incidence was also treatment related. The maternal LOAEL is 300 mg/ kg bw/ day, based on decreased body weight between gestational days 6 and 9 and 6 to 16. The maternal NOAEL is 150 mg/ kg bw/ day. The developmental LOAEL is 300 mg/ kg bw/ day, based on unossified sternebrae 5 ( incidence was statistically significant in fetuses and nominally increased in litters). The developmental NOAEL is 150 mg/ kg bw/ day. The developmental toxicity study in the rat is classified acceptable/ guideline; and satisfies the guideline requirement for a developmental toxicity study ( OPPTS 870.3700; OECD 414) in the rat. The acceptability of the study and NOAEL/ LOAEL are not change from TXR# 009556. The developmental effect of concern is presented in the Table below.

Doses 0 150 mg/ kg/ day 300 mg/ kg/ day 600 mg/ kg/ day 1000 mg/ kg/ day Percentage with unossified sternebrae 5 in each group, * p=> 0.05, ** p=> 0.01 Fetuses 13 20* 27* 35* 81**

Litters 52 50 73 80* 100*

The range in historical control litter incidence of unossified sternebrae 5 is 0 50%.

870.3700b Prenatal Developmental Toxicity Study  Rabbit Summary of the rabbit range finding study: No definitive study was conducted. A 1965 range finding study was conducted in pregnant rabbits on 5 animals/ group at 0, 5, 10 or 25 mg/ kg/ day ( MRID# 00144733; TXR# 005712). However, since maternal weight for controls was not reported, it is impossible to determine maternal weight decrement. Total litter weight was reported but no individual fetal weights. The viability index was nominally decreased ( 11% compared with control) at the HDT, but no statistics were reported. The study was considered unacceptable/ not upgradable for these and other reasons. The study report authors however, stated that no effects were observed in fetuses or dams. A data waiver was granted for the study requirement. Page 6 of 11 Reproductive Toxicity Adequacy of data base for Reproductive Toxicity: Due to a data waiver, no additional study is required at this time.

870.3800 Reproduction and Fertility Effects  Rat EXECUTIVE SUMMARY: 4 CPA ( technical) was administered in the diet to 20 female and 10 male Sprague Dawley rat per group at 0, 25, 125 or 250 ppm for 60 days to the parental generation, mated 2: 1 to produce Fa and Fb litters for three generations ( MRID# 00083274). After weaning the F3a and F3b litters, the study was terminated. Animals were kept on diet continuously except females were rested for 10 days after weaning the first litter; the second litter was used for F1 and F2 parents. Thus females producing the litter from which parents were to be selected for the next generation were not dosed for 10 days prior to mating. No dose related effects occurred in offspring or parents. However, since the highest dose administered was only 12.5% of the NOAEL in the 90 day study in rats, the dose levels administered were too low to show any effects. The NOAEL in the 90 day study in rats 2000 ppm. A number of mothers died and/ or cannibalized their offspring. For example, from the F2a group from control to the high dose 14 to 3 mothers died with loss of their litters and 30 to 64 pups were cannibalized in control and each dose group. The pup viability index was too variable to show dose related effects, if there were any to see; it was lower in control ( 38%) than in the high dose group ( 49%) at day 21 of lactation. There appeared to be no dose relationship with variable numbers per generation and among groups. The authors speculated that a respiratory disease in the colony may have been responsible. Parts of the report that were readable suggested that no effects in parents or offspring were seen in the study at the HDT of 12.5 mg/ kg/ day. However, the parts of the submission that could verify these results were unreadable. This study is unacceptable/ not upgradable for a multi generation study of reproduction in the rat. The study was conducted at a dose that was insufficient to cause any effects. [ Note: The NOAEL/ LOAEL = 2000/ 8000 ppm ( ca. 132/ 517 mg/ kg/ day) in the 90 day subchronic study in rats.] In addition, dietary concentrations were no measured, equal numbers of males and females were not used, dosing was not continuous and the data too variable for assessment.

Mutagenicity Adequacy of data base for Mutagenicity: The data base for mutagenicity is considered adequate based on pre 1991 mutagenicity guidelines. All three studies conducted at toxic doses were negative. Page 7 of 11 Gene Mutation Guideline # 870.5100, Reverse mutation in S. typhimurium MRID 41837002 Acceptable A dose range of 0 5000

g/ plate of 4CPA was used for strains TA98, TA100, TA 1535, TA 1537, and TA 1538 of S. typhimurium. The test was negative up to cytotoxic doses of 5000

g/ plate with no activation (  S9), and up to doses of 5000

g/ plate with activation (+ S9) where no cytotoxicity was seen.

Guideline# 870.5300, Gene mutation MRID 41837004 Acceptable 4 CPA ( 99%) was evaluated for potential to induced forward mutations at the TK+/ locus in L5178Y TK+/ cells in two independently performed trials. Without S9 activation, 4 CPA was not mutagenic at doses of 100, 500, 1000, 1600, 2000, 2500, 3000, 3500, or 4000

g/ mL: higher levels ( 5000

g/ mL) were severely cytotoxic. In the presence of S9 activation at 10, 50, 100, 250, 300, 750, 1000, 1300, 1600 or 2000

g/ mL ( cytotoxic at doses  1300

g/ mL), non dose related increases in mutation frequency ( MF) were obtained in both trials. Although there was a tendency for elevated MFs at doses ranging from 300 to 1600

g/ mL + S9, doubling of the MF over concurrent controls was only seen at 600

g/ mL ( Trial 1) and 1000

g/ mL ( Trial 2). The evidence suggesting a mutagenic response, was however, insufficient to conclude the 4 CPA was positive. The test material was not mutagenic in this in vitro mammalian cell assay.

Cytogenetics Guideline # 870.5395, In vivo mammalian erythrocyte micronucleus test MRID 41837003 Acceptable In an ICR mouse bone marrow micronucleus assay, 5/ sex/ group were treated gavage with 4 chlorophenoxyacetic acid ( 99%) at doses of 0, 450, 900 or 1800 mg/ kg bw. Bone marrow cells were harvested at 24, 48 and 72 hours post treatment.

There were signs of toxicity, languidness and prostration, and most animals died within 24 hours at 1800 mg/ kg during the study. Hematopoiesis was adversely affected at 1800 mg/ kg. There were 5000 polychromatic erythrocytes and < 5 micronucleated polychromatic erythrocytes ( MPE) per group with no dose response. 4 CPA was tested at an adequate dose based on mortality. The positive control induced the appropriate response. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

Other Genotoxicity Guideline #, study type MRID 00141673 classification Dose range and brief conclusions of study ( see gene mutation summary instructions) Page 8 of 11 REFERENCES:

00083274 Booz Allen Applied Research ( 1964) The Effect of 4 Chlorophenoxyacetic Acid on Reproduction in the Rat: Project No. 4031. ( Unpublished study, including letter dated Nov 3, 1965 from R. A. Turner to Nathan G. Fox, received Nov 16, 1965 under PP0360; submitted by Chun King Corp., Duluth, Minn.; CDL: 090390 A)

00144733 Turner, R. ( 1965) A Study of the Effect of P chlorophenoxyacetic Acid on Teratogenicity in the Rabbit: BSL4054. Unpublished study prepared by Biological Science Laboratory, Foster D. Snell, Inc. 14 p.

41837001 Glaza, S. ( 1991) Acute Oral Toxicity Study of 4 Chlorophenoxyacetic Acid in Rats: Final Report: Lab Project Number: HLA/ 00801531. Unpublished study prepared by Hazleton Laboratories America, Inc. 53 p.

42306801 Glaza, S. ( 1992) Primary Dermal Irritation Study of 4 Chlorophenoxyacetic Acid in Rabbits: Lab Project Number: HWI 20200490. Unpublished study prepared by Hazleton Wisconsin, Inc. 21 p.

42322602 Henwood, SM ( 1992) Teratology Study with 4 Chlorophenoxyacetic acid. Laboratory name Hazelton Wisconsin, Inc. Laboratory report number, HWI 6341 101 ( May 14, 1992) Unpublished 42339101 Glaza, S. ( 1992) Primary Eye Irritation Study of 4 Chlorophenoxyacetic Acid in Rabbits: Lab Project Number: HWI 20200491. Unpublished study prepared by Hazleton Wisconsin, Inc. 36 p.

42339102 Glaza, S. ( 1992) Dermal Sensitization Study of 4 Chlorophenoxyacetic Acid in Guinea Pigs Closed Patch technique: Final Report: Lab Project Number: HWI 20200492. Unpublished study prepared by Hazleton Wisconsin, Inc. 33 p.

42522601 Glaza, S. ( 1992) Acute Dermal Toxicity Study of 4 Chlorophenoxyacetic Acid in Rabbits: Final Report: Lab Project Number: HWI 20700133. Unpublished study prepared by Hazleton Wisconsin, Inc. 28 p.

42902501 Henwood, SM ( 1993) 13 Week Dietary Toxicity Study with 4 Chlorophoxyacetic acid in Rats. Laboratory name Hazleton Wisconsin, Inc. Laboratory report HWI 6341 102. Unpublished 42968201 Nachreiner, D. ( 1993) 4 Chlorophenoxyacetic Acid: Acute Dust Inhalation Toxicity Study in Rats: Revised Report: Lab Project number: 92N1192 REVISED: 92N1192. Unpublished study prepared by Union Carbide and Plastics Co., Bushy Run Research Center. 58 p. Page 9 of 11 42968301 Henwood, SM ( 1993) 13 Week Dietary Study with 4 Chlorophenoxyacetic Acid in Dogs. Laboratory name Hazleton Wisconsin, Inc. Laboratory report number, HWI 6341 108. September 30,1993. Unpublished 43045301 Hewood, SM ( 1992) Dietary Escalating Dose Tolerance Study with 4 Chlorophenoxyacetic acid in Dogs. Laboratory name Hazleton Wisconsin, Inc. Laboratory report number, HWI 6341 106. September 11, 1992. Unpublished Other References:

Clock, Mary ( 1994); Memorandum to Jay Ellenburger; Dated 12/ 22/ 94. The HED Chapter of the Regististration Eligibility Decision Document ( RED) for 4 chlorophenoxyacetic acid ( 4CPA), 019401 ( TXR# 011819)

USEPA ( 1997) Regregistration Eligibility Decision ( RED) 4 Chlorophenoxyacetic Acid ( 4CPA). EPA 738 R 97 001 March 1997 Toxicity Profile Summary Tables Subchronic, Chronic and Other Toxicity Tables Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results 870.3100 90 Day oral toxicity rodents 42902501 Acceptable/ guideline 0, 100, 2000 or 8000 ppm M: 0, 6.6, 132.4, 516.9 mg/ kg/ day F: 0, 7.99, 153, 625.9 mg/ kg/ day NOAEL = M/ F; 132/ 153 mg/ kg/ day LOAEL = M/ F; 517/ 626 mg/ kg/ day based on based on body weight decrement in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females.

870.3150 90 Day oral toxicity in dogs 42968301 Acceptable/ guideline 0, 20, 100 or 500 ppm M; 0, 0.80, 3.3 and 18.6 mg/ kg/ day F; 0, 0.78, 4.0 or 17.4 mg/ kg/ day Average for males and females; 0, 0.792, 3.67 and 18.0 mg/ kg/ day. NOAEL = M/ F 18.0 mg/ kg/ day ( HDT) LOAEL = None mg/ kg/ day based on no effects at the top dose. There was a nominal body weight decrement at the top dose, which was insufficient to be considered a toxic effect. Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results Page 10 of 11 870.3200 21/ 28 Day dermal toxicity  No study available 870.3250 90 Day dermal toxicity  No study available 870.3465 90 Day inhalation toxicity  No study available 870.3700a Prenatal developmental in rats 42322602 Acceptable 0, 150, 300, 600 or 1000 mg/ kg/ day Maternal NOAEL = 150 mg/ kg/ day LOAEL = 300 mg/ kg/ day based on body weight. Developmental NOAEL = 150 mg/ kg/ day LOAEL = 300 mg/ kg/ day based on unossified sternebrae 5 ( incidence was statistically significant in fetuses and nominal in litters).

870.3700b Prenatal developmental in rabbits 00144733 Unacceptable 0, 5, 10, 25 mg/ kg/ day ( range finding study, 5 rabbits/ group) Maternal NOAEL = 25 mg/ kg/ day LOAEL = Not determined. Developmental NOAEL = 25 mg/ kg/ day LOAEL = Not determined.

870.3800 Reproduction and fertility effects 00083274 Unacceptable 0, 25, 50, 250 ppm 0, 1.25, 2.5, 12.5 mg/ kg/ day Parental/ Systemic NOAEL = 12.5 mg/ kg/ day LOAEL = Not determined. Reproductive NOAEL = 12.5 mg/ kg/ day LOAEL = Not determined. Offspring NOAEL = 12.5 mg/ kg/ day LOAEL = Not determined.

870.4100a Chronic toxicity rodents Unavailable No study available 870.4100b Chronic toxicity dogs Unavailable No study available 870.4200 Carcinogenicity rats Unavailable No study available 870.4300 Carcinogenicity mice Unavailable No study available Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results Page 11 of 11 870.5100, Gene Mutation, reverse mutation in S. typhimurium 41837002 Acceptable 0, 100, 333, 667, 1000, 3300 or 5000

g/ plate Negative without activation at cytotoxic doses and negative with activation at 5000

g/ plate.

870.5300, Gene Mutation, Mouse L5178Y lymphoma cells 41837004 Acceptable 0 4000

g/ mL  S9 0 2000

g/ mL + S9 Negative  S9 and + S9 at cytotoxic doses.

870.5395, Cytogenetics, In vivo mouse erythrocyte micronucleus test 41837003 Acceptable 0, 450, 900 or 1800 mg/ kg Negative at toxic doses.

870.6200a Acute neurotoxicity screening battery  NA 870.6200b Subchronic neurotoxicity screening battery  NA 870.6300 Developmental neurotoxicity  NA 870.7485 Metabolism and pharmacokinetics  NA 870.7600 Dermal penetration  NA Special studies  NA NA = Not available