0.0010
                                   0.000013
                                    1.4E-06
                      Grass Grown for Seed and CRP Areas
                                     0.21
                                     Full
                           Mowing, pruning, weeding
                                      500
                                       0
                                     0.12
                                    0.0011
                                   0.000016
                                    1.6E-06
1 Transfer Coefficients from HED Policy No. 3.0.
2 DFR (ug/cm[2])= application rate x 20% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2],
3 TTR (for Grass use sites) (ug/cm[2])= application rate x 5% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2]
4 Dermal Dose (mg/kg/day) = DFR(t) or TTR (ug/cm[2]) x TC (cm[2]/hr)x hr/day (8 hours) x (1/1000 ug/mg) x (1/ 60 kg bw) where DFR(t)is dislodgeable foliar residue at time t
5 LADD= (Dermal PPE Dose+Inhalation Baseline Dose) x average days of exposure (10/365) x (35 years/70 years).
6 Cancer Risk Estimates = LADD x Q1*, where Q1*=1.03E-1 (mg/kg/day)[-1].

Existing Use Sites
The short-and intermediate-term dermal non-cancer MOEs for all occupational post-application scenarios ranged from 45 to 1,400 on the day of application; and therefore, some post-application activities are of concern.  Risk from occupational contact with full foliage wheat, small grains and mint is not of concern 8 days after application, risk from sod harvesting is not of concern 5 days after application, and risk from occupational contact with full foliage corn, sorghum and cotton is not of concern 4 days after application.  The estimated cancer risks on the day of application ranged from 2.3x10[-6] to 1.4x10[-4].

Table <IP_ADDRESS>. Post Application Exposure from Bromoxynil to Registered Use Sites
                                     Crop
                      Maximum Application Rate (lb ai/A)
                                   Activity
                              Foliage Development
                                     TC[1]
                          Transferrable Residue[2,3]
                            Daily Dose (mg/kg/d)[4]
                                 Day 0 MOE[5]
                  Days After Treatment to Reach
MOE > LOC
                                    MOE[5]
                                     Corn
                                      0.5
                             Irrigation, Scouting
                                     Full
                                     1,000
                                    1.1032
                                   0.147096
                                      68
                                       4
                                      104

                                      0.5
                                   Scouting
                                    Minimum
                                      400
                                    1.1032
                                   0.0588384
                                      170
                                      N/A
                                    Sorghum
                                      0.5
                             Irrigation, Scouting
                                     Full
                                     1,000
                                    1.1032
                                   0.147096
                                      68
                                       4
                                      104

                                      0.5
                                   Scouting
                                      Low
                                      100
                                    1.1032
                                   0.0147096
                                      680
                                      N/A
                                     Wheat
                                      0.5
                                   Scouting
                                     Full
                                     1,500
                                    1.1032
                                   0.220644
                                      45
                                       8
                                      105

                                      0.5
                             Irrigation, Scouting
                                      Min
                                      100
                                    1.1032
                                   0.0147096
                                      680
                                      N/A
                              Other Small Grains
                                      0.5
                                   Scouting
                                     Full
                                     1500
                                    1.1032
                                   0.220644
                                      45
                                       8
                                      105

                                      0.5
                             Irrigation, Scouting
                                      Min
                                      100
                                    1.1032
                                   0.0147096
                                      680
                                      N/A
                                    Cotton
                                      0.5
                                   Scouting
                                     Full
                                     1,000
                                    1.1032
                                   0.147096
                                      68
                                       4
                                      104
                               Seedling Alfalfa
                                     0.375
                             Irrigation, Scouting
                                      Min
                                      100
                                    0.8274
                                   0.0110322
                                      910
                                      N/A
                                     Flax
                                     0.25
                                   Scouting
                                      Min
                                      100
                                    0.5516
                                   0.0073548
                                     1,400

                                    Garlic
                                      0.5
                      Irrigation, scouting, hand weeding
                                      Min
                                      300
                                    1.1032
                                   0.0441288
                                      230

                                     Mint
                                      0.5
                         irrigation, scouting, weeding
                                     Full
                                     1,500
                                    1.1032
                                   0.220644
                                      45
                                       8
                                      105

                                      0.5
                         irrigation, scouting, weeding
                                    Minimum
                                      100
                                    1.1032
                                   0.0147096
                                      680
                                      N/A
                                    Onions
                                     0.375
                      Irrigation, scouting, hand weeding
                                      Min
                                      300
                                    0.8274
                                   0.0330966
                                      300

                              Grass Grown for Sod
                                      0.5
                                  Harvesting
                                     Full
                                     5800
                                   0.275805
                                   0.2132892
                                      47
                                       5
                                      102
       Grass Grown for Seed, Non Residential Turf, Non-Industrial Sites
                                      0.5
                                    Mowing
                                     Full
                                      500
                                    0.2758
                                   0.018387
                                      540
                                      N/A
1 Transfer Coefficients from HED Policy No. 3.0
2 DFR (ug/cm[2])= application rate x 20% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2], TTR (for Grass use sites) (ug/cm[2])= application rate x 5% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2]
3 TTR (for Grass use sites) (ug/cm2)= application rate x 5% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2]
4 Dermal Dose (mg/kg/day) = DFR(t) (ug/cm[2]) x TC (cm[2]/hr)x hr/day (8 hours) x (1/1000 ug/mg) x (1/ 60 kg bw) where DFR(t)is dislodgeable foliar residue at time t
5 Dermal Short-Term MOE = NOAEL (10 mg/kg/day)/Dermal Daily Dose (mg/kg/day)

Table <IP_ADDRESS>. Post Application Exposure and Cancer Risk to Workers from Bromoxynil Treatment to Registered Use Sites
                                     Crop
                      Maximum Application Rate (lb ai/A)
                                   Activity
                              Foliage Development
                                     TC[1]
                                 Exposure Days
                             Days After Treatment
                          Transferrable Residue[2,3]
                            Daily Dose (mg/kg/d)[4]
                                    LADD[5]
                            Cancer Risk Estimate[6]
                                     Corn
                                      0.5
                             Irrigation, Scouting
                                     Full
                                     1000
                                      30
                                       0
                                    1.1214
                                    0.0218
                                    0.00090
                                    9.2E-05

                                      0.5
                                   Scouting
                                    Minimum
                                      400
                                      30
                                       0
                                    1.1214
                                    0.0087
                                    0.00036
                                    3.7E-05
                                    Sorghum
                                      0.5
                             Irrigation , Scouting
                                     Full
                                     1000
                                      10
                                       0
                                    1.1214
                                    0.0218
                                    0.00030
                                    3.1E-05

                                      0.5
                                   Scouting
                                      Low
                                      100
                                      10
                                       0
                                    1.1214
                                    0.0022
                                    0.00003
                                    3.1E-06
                                     Wheat
                                      0.5
                                   Scouting
                                     Full
                                     1500
                                      30
                                       0
                                    1.1214
                                    0.0327
                                    0.00134
                                    1.4E-04

                                      0.5
                             Irrigation, Scouting
                                      Min
                                      100
                                      30
                                       0
                                    1.1214
                                    0.0022
                                    0.00009
                                    9.2E-06
                              Other Small Grains
                                      0.5
                                   Scouting
                                     Full
                                     1500
                                      10
                                       0
                                    1.1214
                                    0.0327
                                    0.00045
                                    4.6E-05

                                      0.5
                             Irrigation, Scouting
                                      Min
                                      100
                                      10
                                       0
                                    1.1214
                                    0.0022
                                    0.00003
                                    3.1E-06
                                    Cotton
                                      0.5
                                   Scouting
                                     Full
                                     1000
                                      10
                                       0
                                    1.1214
                                    0.0218
                                    0.00030
                                    3.1E-05
                                    Alfalfa
                                     0.375
                             Irrigation, Scouting
                                      Low
                                      100
                                      10
                                       0
                                    0.8410
                                    0.0016
                                    0.00002
                                    2.3E-06
                                     Flax
                                     0.75
                                   Scouting
                                      Min
                                      100
                                      10
                                       0
                                    1.6821
                                    0.0033
                                    0.00004
                                    4.6E-06
                                    Garlic
                                      0.5
                      Irrigation, scouting, hand weeding
                                      Min
                                      300
                                      10
                                       0
                                    1.1214
                                    0.0065
                                    0.00009
                                    9.2E-06
                                     Mint
                                      0.5
                         irrigation, scouting, weeding
                                     Full
                                     1500
                                      10
                                       0
                                    1.1214
                                    0.0327
                                    0.00045
                                    4.6E-05

                                      0.5
                         irrigation, scouting, weeding
                                    Minimum
                                      100
                                      10
                                       0
                                    1.1214
                                    0.0022
                                    0.00003
                                    3.1E-06
                                    Onions
                                     0.375
                      Irrigation, scouting, hand weeding
                                      Min
                                      300
                                      10
                                       0
                                    0.8410
                                    0.0049
                                    0.00007
                                    6.9E-06
                              Grass Grown for Sod
                                      0.5
                                  Harvesting
                                     Full
                                     5800
                                      10
                                       0
                                    0.2803
                                    0.0316
                                    0.00043
                                    4.5E-05
       Grass Grown for Seed Non Residential Turf, Non-Industrial Sites
                                      0.5
                                    Mowing
                                     Full
                                      500
                                      10
                                       0
                                    0.2803
                                    0.0027
                                   0.000037
                                    3.8E-06
1 Transfer Coefficients from HED Policy No. 3.0
2 DFR (ug/cm[2])= application rate x 20% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2]
3 TTR (for Grass use sites) (ug/cm[2])= application rate x 5% dissipation x 4.54 x10[8] ug/lb x 2.47 x 10[-8]A/cm[2]
4 Dermal Dose (mg/kg/day) = DFR(t) (ug/cm[2]) x TC (cm[2]/hr)x hr/day (8 hours) x Dermal Absorption (17%) x (1/1000 ug/mg) x (1/ 70 kg bw) where DFR(t)is dislodgeable foliar residue at time t
5 LADD= (Dermal PPE Dose+Inhalation Baseline Dose) x average days of exposure (30/365) x (35 years/70 years)
6 Cancer Risk Estimates = LADD x Q1*, where Q1*=1.03E-1 (mg/kg/day)[-1]

Occupational Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative occupational post-application inhalation exposure assessment was not performed for bromoxynil at this time.  However, there are multiple potential sources of post-application inhalation exposure to individuals performing post-application activities in previously treated fields.  These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides.  The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009.  The Agency received the SAP's final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The Agency is in the process of evaluating the SAP report as well as available post-application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational
post-application inhalation exposure assessment for bromoxynil.

      9.3 Occupational Exposure Data Requirements & Label Changes
To characterize post-application exposure and reduce uncertainty for late applications of bromoxynil, HED is requesting the registrant submit a dislodgeable foliar residue (DFR) study on a representative row crop (e.g. corn).  HED suggests using corn for the study site because in the U.S., 57% of bromoxynil is applied exclusively to corn and the label allows for bromoxynil application to corn later in the growth cycle (post emergence to tassel emergence), resulting in potentially higher exposures.

Based on email correspondence with the registrant (dated 11/01/2010), Huskie(TM) Herbicide (EPA Reg. No. 264-1023) is not intended for application with chemigation or aerially to grain sorghum, grass grown for seed and CRP areas.  The label should restrict aerial and chemigation explicitly from these use sites.

Existing labels should clarify that products containing bromoxynil are restricted from use on golf course turf.

Under the WPS for Agricultural Pesticides, a 24-hr REI is required for chemicals classified under Toxicity Category II.  Therefore, the REI on the Huskie(TM) Herbicide label should be 24 hours.  Other bromoxynil product labels should also require a 24-hr REI, except for the specific use sites of wheat, small grains and mint which require an REI of 8 days, sod harvesting which require an REI of 5 days, and corn, sorghum and cotton which require an REI of 4 days.

10.0 Environmental Justice Considerations
Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well-established procedures.  In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup's food and water consumption, and activities in and around the home that involve pesticide use in a residential setting.  Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide.  These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country.  Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant.  Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post-application are evaluated.  Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

11.0 References
Alsadek, J., 07/08/2010, DP# 378991, Usage Report Package in Support of Registration for the Herbicide Bromoxynil, (035302).

Dodd, N., 2/15/2011, DP# 378614, Bromoxynil.  Petition for Tolerances in Support of New Uses on Grass and Grain Sorghum.  Summary of Analytical Chemistry and Residue Data.

Goodlow, T., 8/17/2010, DP# 380770, Bromoxynil: Review of HUSKIE HERBICIDE  -  Magnitude of the Residue in/on Sorghum and Grass

Grube, A., 10/22/2010, DP# 382833, Usage Report Package in Support of Registration for the Herbicide Bromoxynil, (035301).

Mason, T., 12/16/2010, DP# 374620, Drinking water assessment for ground and aerial application of bromoxynil on grass grown for seed and ground application of sorghum.

Rury, K., 04/07/2011, DP# 378616, Bromoxynil:  Occupational and Residential Exposure Assessment for Proposed Field Uses of Bromoxynil on Sorghum, Grass Grown for Seed, Conservation Reserve Program Areas, and Existing Use sites of Bromoxynil.

Walls, C., 03/22/2011, DP#378615, Bromoxynil:  Acute, Chronic, and Cancer Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the New Uses on Grass and Grain Sorghum.

Appendix A.  Toxicology Profile and Executive Summaries

A.1	Toxicology Data Requirements
The requirements (40 CFR 158.340) for non-food use for Bromoxynil are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

                                     Study
                                   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
                                      yes
                                       -
                                       -
870.3700a  Developmental Toxicity (rodent)
870.3700b  Developmental Toxicity (nonrodent)
870.3800    Reproduction
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
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
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
870.5100    Mutagenicity -- Gene Mutation - bacterial
870.5300    Mutagenicity -- Gene Mutation - mammalian
870.5xxx    Mutagenicity -- Structural Chromosomal Aberrations
870.5xxx    Mutagenicity -- Other Genotoxic Effects
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
870.6100a  Acute Delayed Neurotox. (hen)
870.6100b  90-Day Neurotoxicity (hen)
870.6200a  Acute Neurotoxicity Screening Battery (rat)
870.6200b  90-Day Neurotoxicity Screening Battery (rat)
870.6300    Developmental Neurotoxicity
                                      no
                                      no
                                      yes
                                      yes
                                      no
                                       -
                                       -
                                      no
                                      no
                                       -
870.7485    General Metabolism
870.7600    Dermal Penetration
870.7800    Immunotoxicity
                                      yes
                                      yes
                                      yes
                                      yes
                                      yes
                                      no

A.2	Toxicity Profiles

Table A.2.1.  Acute Toxicity Profile
Guideline
Study
Species
Results
Tox. Category
MRID No.
                          Bromoxynil Phenol Technical
870.1100
Acute oral toxicity
Rat
LD50 = 81 mg/kg  M
LD50 = 93 mg/kg  F)
II
00124758
870.1200
Acute dermal toxicity
Rat
LD50 >= 2000 mg/kg (M, F)
III
00124758
870.1300
Acute inhalation toxicity
Rat
LC5O = 0.269 mg/L  M
LC5O = 0.150 mg/L F
II
43014701
870.2400
Primary eye irritation
Rabbit
Corneal opacity resolved within 3 days; iritis resolved within 4 days; conjunctival irritation persisted for 10 days.
II
00124758
870.2500
Primary skin irritation
Rabbit
Not an irritant
IV
00124758
870.2600
Dermal sensitization
Guinea Pig
Not a sensitizer
Negative
42718701
                        Bromoxynil Octanoate Technical
870.1100
Acute oral toxicity
Rat
LD50 = 400 mg/kg  M
LD50 = 238 mg/kg  F
II
00124112
870.1100
Acute dermal toxicity
Rabbit
LD50> 2000 mg/kg  M
  abraded skin.
LD50 1310 mg/kg  F
  with intact skin.
LD50 = 1660 mg/kg  F
  with abraded skin.
II
00124112
870.1300
Acute inhalation toxicity
Rat
LC5O = 0.810 mg/L  M
LC5O = 0.720 mg/L  F
III
42167101
870.2400
Primary eye irritation
Rabbit
Corneal opacity and irritation lasting 24-72 hrs. Cleared by 96 hrs.
II
00124112
870.2500
Primary skin irritation
Rabbit
Erythema for 72 hrs. No edema.,
IV
00124112
870.2600
Dermal sensitization
Guinea Pig
Contact sensitizer in modified Draize test.
Positive
41879801

Table A.2.2	Subchronic, Chronic and Other Toxicity Profile for Bromoxynil Phenol Technical
                                Guideline No.
                                  Study Type
                    MRID No. (year)/ Classification /Doses
                                    Results
870.3100

90-Day oral toxicity (rat)
MRID 41469101 (1985)

0, 400, 755 or 1456 ppm
0, 28, 58, 168 mg/kg/day M
0, 35, 76,250 mg/kg/day F
Dietary

Supplementary
NOAEL:  M = 28 mg/kg/day,  F  not established
LOAEL
  M = 58 mg/kg/day), based on decreased body weight gain, increased ALT, increased AST and increased alkaline phosphates.
  F = 35 mg/kg/day), based on decreased body weight gain.  This study is of limited usefulness because a NOAEL was not determined for females, excessive mortality occurred in males and females at the highest dose level tested, and an insufficient number of tissues was microscopically examined.
870.3100

90-Day oral toxicity (mouse)
MRID 42553401 (1992)

0, 10, 30, 100, 300, 1000 or 3000 ppm
0, 1.3, 3.9, 13, 39, 130 or 390 mg/kg/day M, F
Dietary

Supplementary
(Range-finding)
NOAEL:  M = 3.9 mg/kg/day, F = 13 mg/kg/day
LOAEL:
  M = 13 mg/kg/day), based on increased liver weights and HC hypertrophy
  F = 39 mg/kg/day, based on increased liver weights, heptatocellular (HC) hypertrophy, HC degeneration and HC vacuolization.
870.3150

90-Day oral toxicity rodents (dog)
MRID 43166701 (1988)

1, 5, 8, 12, 16, 20, 30, 40 or 50 mg/kg/day
Capsule

Supplementary
(Range-finding)
NOAEL:  M  not established, F = 1 mg/kg/day
LOAEL:
  M = 1 mg/kg/day for males, based on decreased body weight gain.
  F = 5 mg/kg/day, based on decreased body weight gain, panting and liquid feces.

At doses above the LOAELs M and/or F, the following  additional effects were observed: panting, liquid feces, salivation, unsteady gait, decreased erythrocyte count, decreased hemoglobin, decreased packed cell volume, increased urea nitrogen, vomiting and mortality.

Toxicities observed during the first day of the study (single dose effects) were elevated rectal temperatures, panting and death.

Single dose NOAEL = 8.0 mg/kg
Single dose LOAEL = 12 mg/kg based on panting.  Elevated rectal temperatures occurred at 16 mg/kg and above, and death occurred at 30 mg/kg and above
870.3200

21-Day dermal toxicity (rabbit)
MRID 42272301 (1992)

0, 30, 300 or 1000 mg/kg/day

Minimum
Dermal
  NOAEL = not established
  LOAEL = 1000 mg/kg/day
Systemic
  NOAEL = not established
  LOAEL = 1000 mg/kg/day
870.3700a

Prenatal developmental in rats
(MRID 40466802 (1992)

0, 4, 12.5 or 40 mg/kg/day on gestation days 6-15
Gavage
Sprague-Dawley

Supplementary
Maternal NOAEL = 12.5 mg/kg/day

Maternal LOAEL =  40 mg/kg/day based on decreased body weight gain throughout most of the treatment and post-treatment period and decreased food consumption during the treatment period.

Developmental NOAEL = 4 mg/kg/day

Developmental LOAEL = 12.5 mg/kg/day based on increased incidence of supernumerary (14th) ribs and Increased post-implantation loss.  At 40 mg/kg/day, the following additional effects were observed in the offspring:  reduced fetal weight, increased numbers of small fetuses, and increased incidences of soft tissue and skeletal abnormalities (including anophthalmia, microphthalmia, short renal papilla, and spinal and thoracic bone abnormalities).
870.3700a

Prenatal developmental in rats
MRID 00116558 (1981)
(00070894, 00071084)

0, 5, 15 or 35 mg/kg/day on gestation days 5-17
Gavage
Sprague-Dawley

Supplementary
Maternal NOAEL = 5 mg/kg/day
Maternal LOAEL = 15 mg/kg/day based on decreased body weight gain.  At 35 mg/kg/day, 6/28 dams died between days 7 and 14 of gestation.

Developmental NOAEL = not established.
Developmental LOAEL = 5 mg/kg/day based on increased incidence of 14th ribs.  At the high dose of 35 mg/kg/day, additional effects included an increased incidence of late intrauterine deaths, decreased fetal body weights and an increase in the total incidence of minor anomalies.
870.3700a

Prenatal developmental in rats
Rogers, Francis, Barbee et al. (1991)

0, 1.7, 5 or 15 mg/kg/day on gestation days 6-15
Gavage
Sprague-Dawley

Not classified.
Maternal NOAEL = 5 mg/kg/day
Maternal LOAEL = 15 mg/kg/day, based on decreased body weight gain and increased liver weights.

Developmental NOAEL = 5 mg/kg/day
Developmental LOAEL = 15 mg/kg/day, based on an increased incidence of supernumerary ribs.
870.3700a

Prenatal developmental in rats - dermal
MRID 40881201, 40883601 (1988)

0, 5, 10, 50 or 100 mg/kg/day for 6 hours/day on gestation days 6-15.

Sprague-Dawley

Supplementary
Maternal dermal NOAEL = 100 mg/kg/day
Maternal dermal LOAEL not established

Maternal systemic NOAEL = 50 mg/kg/day
Maternal systemic LOAEL = 100 mg/kg/day based on decreased body weight gain and decreased food consumption during the treatment period..

Developmental NOAEL = 10 mg/kg/day
Developmental LOAEL = 50 mg/kg/day, based on increased 14th ribs
870.3700b

Prenatal developmental in (rats)
[MRID 00138149 (1983)

0, 15, 30 or 60 mg/kg/day on gestation days 5-20

Gavage
New Zealand White

Guideline
Maternal NOAEL = 15 mg/kg/day
Maternal LOAEL = 60 mg/kg/day, based on reduced body weight gain and reduced food consumption during the treatment period.  There were no deaths or clinical signs of toxicity associated with treatment..

Developmental NOAEL = not established
Developmental LOAEL = 15 mg/kg/day, based on an increased incidence of supernumerary ribs. At 60 mg/kg/day, the following additional effects were also observed:  increased post-implantation loss (due primarily to 5 totally resorbed litters), decreased fetal weights, and increased numbers of litters and numbers of fetuses with major malformations (including hydrocephalus, anophthalmia, microphthalmia and defects in skull ossification).  The incidence of total minor anomalies was also increased at 60 mg/kg/day.
870.3700b
Prenatal developmental in nonrodents (rabbit)
MRID 00142779 (1983)

0, 30, 45 or 60 mg/kg/day on gestation days 6-18

Gavage
New Zealand White

Supplementary
Maternal NOAEL = 15 mg/kg/day
Maternal LOAEL = 60 mg/kg/day, based on increased mortality (7/23 dams died at this dose level) and other clinical signs of toxicity, such as anorexia and discharge of blood.

Developmental NOAEL = not established
Developmental LOAEL = 15 mg/kg/day, based on decreased fetal body weights. At 45 and 60 mg/kg/day, a dose-related increase in extra or rudimentary 14th ribs also was observed. At 60 mg/kg/day, several vertebral and thoracic bone abnormalities, including fused ribs, scoliosis, extra ribs, thoracic centrum misshapen and incomplete ossification of sternebrae, were observed.
870.3700b
Prenatal developmental in nonrodents (rabbit) dermal
MRID 40935101, 41307801 (1988)

0, 10, 50 or 150 mg/kg/day for 6 hours/day on gestation days 6-18.

New Zealand White

Supplementary
Maternal dermal NOAEL = 150 mg/kg/day
Maternal dermal LOAEL not established

Maternal systemic NOAEL = 50 mg/kg/day
Maternal systemic LOAEL = 150 mg/kg/day based on decreased body weight gain.

Developmental NOAEL = 10 mg/kg/day
Developmental LOAEL = 50 mg/kg/day, based on an apparent increase in agenesis of the intermediate lobe of the lung and on an increase in holes in the parietal portion of the skull.
870.3700a

Prenatal developmental in mice  -  oral
Rogers, Francis, Barbee et al. 1991

0, 11, 32 or 96 mg/kg/day on gestation days 6-15

Gavage
Swiss Webster (CD-1)

Not Classified
Maternal NOAEL = 11 mg/kg/day
Maternal LOAEL = 32 mg/kg/day, based on increased mortality and increased liver weights.

Developmental NOAEL = 32 mg/kg/day
Developmental LOAEL = 96 mg/kg/day, based on increased incidence of 14th ribs, decreased fetal weights and decreased numbers of fetuses with ossified vertebrae.
870.3800

Reproduction and fertility effects
(2-generation rat)
MRID 41149301 (1989)

0, 10, 50 or 250 ppm (approximately 0, 0.8, 4 or 21 mg/kg/day during 14 weeks prior to mating)

Sprague-Dawley

Minimum
Parental NOAEL = 4 mg/kg/day
Parental LOAEL = 21 mg/kg/day based on decreased body weight gain in F0 and F1 females before mating, during gestation and lactation and at study termination.  In addition, possibly increased liver weights were observed in both male and female adults.

Reproductive NOAEL = 21 mg/kg/day
Reproductive LOAEL = not established

Offspring NOAEL = 4 mg/kg/day
Offspring LOAEL = 21 mg/kg/day based on decreased body weight gain during lactation and delayed eye opening.
870.3800

Reproduction and fertility effects
(3-generation rat)
MRID 00064815 (1978)
(00242060)

0, 30, 100 or 300 ppm (equivalent to 0, 1.5, 5 or 15 mg/kg/day)

Wistar

Supplementary

Parental NOAEL = 1.5 mg/kg/day
Parental LOAEL = 5.0 mg/kg/day based on decreased body weight gain in F1 and F2 parents

Reproductive NOAEL = 15 mg/kg/day
Reproductive LOAEL = not established.

Offspring NOAEL = 5 mg/kg/day
Offspring LOAEL = 15 mg/kg/day based on decreased body weight particularly in F2 generation.
870.4100a

Chronic toxicity
(rat)
See 870-4300

870.4100b

Chronic toxicity (dog)
MRID 40780301, 41304701 (1988)

0, 0.1, 0.3, 1.5 or 7.5 mg/kg/day
Capsule

Guideline
Threshold dose = 1.5 mg/kg/day, (slightly decreased body weight gain in males)
LOAEL = 7.5 mg/kg/day, M & F, based on increased incidences of salivation, panting, liquid feces and pale gums;  statistically significant decreased body weight gain over entire duration of study, but particularly during first 8 weeks of study;  statistically significant decreased erythrocytes (RBC), hemoglobin (Hb) and packed cell volume (PCV);  statistically significant increased urea nitrogen; increased absolute liver weights and liver/body weight ratios.
870.4200

Carcinogenicity
(mice)
MRID 00068077 (1982)

0, 10, 30 or 100 ppm
0, 1.3, 3.9 or 13 mg/kg/day.

Dietary
Swiss albino

Guideline for chronic feeding study.

NOAEL
   M = 3.9 mg/kg/day
   F = 13 mg/kg/day
LOAEL
   M = 13 mg/kg/day based on a dose-related increased incidence of liver adenomas/carcinomas combined, the incidence being statistically significant at 13 mg/kg/day
   F = not established.

Carcinogenicity:
   M  Positive evidence of neoplasms in males as stated above
   F  No tumors were observed in females; CARC (1991) concluded dose levels in females were not sufficiently high to assess tumorigenic potential.
870.4200

Carcinogenicity
(mice)
MRID 43245501 (1994)

0, 20, 75 or 300 ppm
0, 3.1, 12, 46 mg/kg/day M
0, 3.7, 14, 53 mg/kg/day F

CD-1

Acceptable for chronic feeding and for oncogenicity

NOAEL = 12 mg/kg/day M, 14 mg/kg/day F
LOAEL = 46 mg/kg/day M, 53 mg/kg/day F, based on increased liver weights, increased incidences of diffusely dark livers, and increased incidences of non-neoplastic microscopic lesions in liver.  Histopathologic lesions in the liver included hepatocellular centrilobular hypertrophy, hepatocellular degeneration/necrosis, and pigment in hepatocytes and Kupffer cells.

Carcinogenicity:
  Males: treatment-related increased incidences of hepatocellular adenomas, carcinomas, and adenomas/carcinomas combined were observed in the male mice at all dose levels in this study.
  Females: slightly increased incidences of hepatocellular carcinomas and of adenomas/carcinomas combined was observed at the high dose level only.
870.4300

Combined Chronic/Carcinogenicity (rats)
MRID 00096521 (1982)
(00064815)

0, 10, 30,100 ppm
0, 0.5, 1.5, 5 mg/kg/day)
Dietary

Supplementary for chronic feeding and for oncogenicity
NOAEL = 5 mg/kg/day, M & F
LOAEL = not established

Carcinogenicity:
No evidence of an increased incidence of neoplasms in males or females.  Dose levels used in this study were determined to be insufficiently high to assess carcinogenic potential.
870.4300

Combined Chronic/Carcinogenicity (rats)
MRID 40612501, 41374801 (1988)

0, 60, 190 or 600 ppm 0, 2.6, 8.2 or 28 mg/kg/day M
0, 3.3, 11.0 41 mg/kg/day F
Dietary

Minimum for chronic feeding and for oncogenicity
NOAEL = 2.6 mg/kg/day M,  3.3 mg/kg/day F
LOAEL:
   M = 8.2 mg/kg/day, based on an increased incidence of spongiosis hepatis in the liver.
   F: 11.0 mg/kg/day, based on decreased body weight gain.

Carcinogenicity:
No evidence of an increased incidence of neoplasms in males or females.  Dose levels used in this study were determined to be sufficiently high to assess carcinogenic potential.
870.5100

Bacterial reverse mutation test (Salmonella)
MRID 41995701 (1991)

Strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations ranging from 3.33 to 1000 ug/plate and with metabolic activation (rat S9 mixture) at concentrations ranging from 10.0 to 3330 ug/plate.

Acceptable
Negative.

Bromoxynil phenol, without and with metabolic activation, did not induce a genotoxic effect in this assay system.
870.5375

In vitro mammalian chromosome aberration test
MRID 00115651 (1982)

Cultures of Chinese hamster ovary (CHO) cells were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations ranging from 100 to 1500 ug/ml (8 hour exposure) and from 50 to 500 ug/ml (20 hour exposure).

Acceptable
Negative without activation

Positive with activation at >= 1200 ug/ml

Bromoxynil phenol did not induce a genotoxic effect in the non-activated portion of this assay, but the significant increase in chromosome damage in the activated portion of this assay at concentrations equal to and above 1200 ug/ml was considered to be a positive genotoxic response.
870.5395

In Vivo mammalian (mouse) erythrocyte micronucleus test
MRID 00124803  (1982)

Bromoxynil phenol was administered orally by gavage on two consecutive days to groups of 5 male and 5 female CD-1 mice at dose levels of 0 (control), 21.6, 69.0 or 215.5  mg/kg/day.

Acceptable
Negative at dose levels up to 215.5 mg/kg/day which produced target cell toxicity as well as death

Bromoxynil phenol did not induce a clastogenic effect in this assay system.
870.5395

In vivo Mammalian erythrocyte micronucleus test
MRID 42092301 (1991)

Single doses of technical grade bromoxynil phenol were administered orally by gavage to groups of 5 male and 5 female CD-1 mice at dose levels of 0 (control), 35, 70 or 105 mg/kg.

Acceptable
Negative

Bromoxynil phenol did not induce a clastogenic effect in this assay system.

870.5550

Unscheduled DNA synthesis in mammalian cells
MRID 00115646 (1982)

Cultures of primary rat hepatocytes were exposed to technical grade bromoxynil phenol at concentrations ranging from 0.1 to 50 ug/ml.

Acceptable
Negative

Bromoxynil phenol did not induce a genotoxic effect in this assay system

870.5xxx

In vitro transformation assay
MRID 00115647 (1982)

Cultures of mouse C3H/10T (1/2) C18 cells were exposed to technical grade bromoxynil phenol at concentrations ranging from 32.5 to 390 ug/ml.

Acceptable
Negative

Bromoxynil phenol did not induce a genotoxic effect in this assay system.

870.5xxx

Sister Chromatid Exchange
MRID 00115648 (1982)

Cultures of Chinese hamster ovary (CHO) cells were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations ranging from 4.67 to 18.7 ug/ml and with metabolic activation (rat S9 mixture) at concentrations ranging from 500 to 900 ug/ml.

Acceptable
Negative

Bromoxynil phenol did not induce a genotoxic effect in this assay system.
870-5xxx

Forward mutation
Mouse lymphoma cells
MRID 00115649 (1982)

Cultures of L5178Y TK+/- cells were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations ranging from 15.6 to 250 ug/ml and with metabolic activation (rat S9 mixture) at concentrations of 3.9, 7.8, 15.6, 31.3 or 62.5 ug/ml.

Acceptable
Negative without activation

Positive with activation at 31.3 and 63 ug/ml.

Bromoxynil phenol did not induce a genotoxic effect in the non-activated portion of this assay, but the dose-related increase in mutant colonies in the activated portion of this assay was considered to be a positive genotoxic response.

870-5xxx

Forward mutation
Mouse lymphoma cells
MRID 41995702  (1991)

Cultures of Chinese hamster ovary (CHO)/HGPRT locus cells were exposed to technical grade bromoxynil phenol without and with metabolic activation (rat S9 mixture) at concentrations ranging from 100 to 1000 ug/ml.

Acceptable
Negative

Bromoxynil phenol, without and with metabolic activation, did not induce a genotoxic effect in this assay system.
870-5xxx

DNA Repair Test
(E. coli)
MRID 00115650 (1982)

Cultures of both indicator strains (Escherichia coli indicator strains pol A+ (W3110) and pol A- (p3478)) on agar plates were exposed to technical grade bromoxynil phenol without and with metabolic activation (rat S9 mixture) at concentrations ranging from 1.0 to 10000 ug/plate.

Acceptable
Positive without activation at >= 1000 ug/plate

Positive with activation at >= 1000 ug/plate

Bromoxynil phenol induced a positive genotoxic response in both the non-activated and activated portions of this assay.
870.7485

Metabolism and pharmacokinetics
(species)
Please see 870.7485 data for bromoxynil octanoate.

870.7600
Dermal penetration (species)
MRID 40854602

[14]C-Bromoxynil phenol, solubilized in water with sodium hydroxide, was topically applied to the skin of male Sprague Dawley rats at doses of 0.10, 1.0 or 10.0 mg/rat for durations of exposure of 0.5, 1, 2, 4, 10 or 24 hours (4 rats/dose/duration of exposure).

Acceptable
Percent dermal absorption at 10 hours was 1.92%, 1.74% and 1.24% for doses of 0.10, 1.0 and 10.0 mg/rat respectively.  Following a soap and water wash (at 10 hours), 22.64%, 10.79% and 3.79% of the respective doses remained in/on the skin.

Percent dermal absorption at 24 hours was 3.12%, 3.24% and 3.02% for doses of 0.10, 1.0 and 10.0 mg/rat respectively.  Following a soap and water wash (at 24 hours), 18.99%, 7.84% and 2.03% of the respective doses remained in/on the skin.

Table A.2.3 Toxicity Profile for Bromoxynil Octanoate
                                 Guideline No.
                                  Study Type
                    MRID No. (year)/ Classification /Doses
                                    Results
870.3100

13-Week oral toxicity
(rat)
MRID 42411901 (1992)

0, 150, 600, 1100 ppm 0, 11, 45, 91 mg/kg/day M
0, 13, 55, 111 mg/kg/day F
Dietary

Minimum
NOAEL:  M = 45 mg/kg/day, F = 13.mg/kg/day
LOAEL
M = 91 mg/kg/day, based on decreased body weight gain, decreased serum total protein, decreased globulins and increased degeneration/necrosis of cardiac myofibers and possibly increased thymic lymphocyte necrosis.  F = 55 mg/kg/day, based on decreased body weight gain and increased liver weights
870.3150

13-Week oral toxicity dog
MRID 42869701, 43700201 (19)

0, 0.43, 1.43 or 7.14 mg/kg/day
Capsule

Supplementary
NOAEL = 0.43 mg/kg/day, M & F
LAAEL = 1.43 mg/kg/day, M & F, based on decreased body weight gain
870.3150

13-Week oral toxicity dog
MRID 00061179 (1965)
(00090653, 00111190)
0, 1, 5 or 25 mg/kg/day

Capsule

Supplementary
NOAEL = 1.0 mg/kg/day, M & F
LOAEL = 5.0 based on occasional panting (considered a threshold dose).  At 25 mg/kg/day, additional signs of toxicity, observed in both males and females, were panting (after each dose) throughout the study; decreased body weight gain; possibly decreased erythrocyte counts, hemoglobin, and packed cell volume; and increased serum urea nitrogen.
870.3200

21-Day dermal toxicity (rabbit)
MRID 42346201 (19--)

0, 30, 300 or 1000 mg/kg/day

Minimum
Dermal
  NOAEL = 30 mg/kg/day, M & F
  LOAEL = 300 mg/kg/day, M & F, based on significant dermal irritation consisting of slight to moderate redness and swelling, cracking and flaking of the skin

Systemic
  NOAEL = not established
  LOAEL = 1000 mg/kg/day
870.3150

90-Day oral toxicity in nonrodents (dog)
No study data are currently available

870.3700a

Prenatal developmental in rodents (rat) - oral
Rogers, Francis, Barbee et al. 1991

0, 2.4, 7.3 or 21.8 mg/kg/day on gestation days 6-15
Gavage
Sprague-Dawley

Not classified
Maternal NOAEL = 7.3 mg/kg/day
Maternal LOAEL = 21.8 mg/kg/day, based on decreased body weight gain and increased liver weights.

Developmental NOAEL = 7.3 mg/kg/day
Developmental LOAEL = 21.8 mg/kg/day, based on an increased incidence of 14th ribs and on reduced fetal weights.
870.3700a

Prenatal develop-mental in rodents (rat) - dermal
MRID 41163301 (1989)

0, 2, 5, 10, 15, 20 or 75 mg a.i./kg/day for 6 hours/day on gestation days 6-15
Gavage
Sprague-Dawley

Supplementary

Maternal dermal NOAEL = 20 mg/kg/day
Maternal dermal LOAEL = 75 mg/kg/day based on skin irritation,

Maternal systemic NOAEL = 15 mg/kg/day
Maternal systemic LOAEL = 20 mg/kg/day based on decreased body weight gain and decreased food consumption during the treatment period.,

Developmental NOAEL = 10 mg/kg/day
Developmental LOAEL = 15 mg/kg/day based on increased incidence of supernumerary (14th) ribs. At 20 and 75 mg a.i./kg/day, the incidences of supernumerary ribs were increased still further.
870.3700b

Prenatal
developmental in
non-rodents (rabbit) - dermal
MRID 41471901, 42183901 (1990)

0, 5, 10, 15, 20, 40 or 80 mg a.i./kg/day for 6 hours/day on gestation days 6-18

New Zealand White

Supplementary

Maternal dermal NOAEL = not established
Maternal dermal LOAEL = 5.0 mg/kg/day based on skin irritation. At 15 mg/kg/day and higher, a majority of treated animals manifested erythema, fissuring and desquamation.

Maternal systemic NOAEL = 80 mg/kg/day
Maternal systemic LOAEL =  not established

Developmental NOAEL = 80 mg/kg/day
Developmental LOAEL = not observed
870.3700a

Prenatal developmental in rodents (rabbit) - oral
No study available
No study is necessary (Fifth Developmental Toxicity Peer Review Committee, 4/21, 1992)
870.3800

Reproduction and fertility effects -  Rat
Oral
No study available

870.3800

Reproduction and fertility effects -  Rat
Dermal
MRID 41667401 (1990)

Male rats treated with 0, 25, 50 or 100 mg a.i./kg/day for 21 days, then mated with unexposed female rats on days 1, 7, 14, 21, 35, 56 or 113 post-exposure.

Supplementary
Special study.
Male dermal NOAEL =50 mg/kg/day
Male dermal LOAEL = 100 mg/kg/day, based on significant skin irritation.

Male systemic NOAEL = 25 mg/kg/day
Male systemic LOAEL = 50 mg a.i./kg/day, based on decreased body weight gain.  At 100 mg a.i./kg/day, possibly increased liver weights were also observed.

Male reproductive NOAEL = 50 mg/kg/day
Male reproductive LOAEL = 100 mg a.i./kg/day (tentative), based on possibly decreased prostate gland weight.

Offspring NOAEL =100 mg/kg/day
Offspring LOAEL = not established
870.4100b

Chronic toxicity dogs
No study data are currently available.  Please refer to 870.4100b for bromoxynil phenol

870.4200

Carcinogenicity rats
No study data are currently available.  Please refer to 870.4200 for bromoxynil phenol

870.4300

Carcinogenicity mice
No study data are currently available.  Please refer to 870.4300 for bromoxynil phenol

870.5100

Bacterial reverse mutation test
Salmonella/mammalian microsome

MRID 43022701 (1993)

Strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to technical grade bromoxynil octanoate without and with metabolic activation (rat S9 mixture) at concentrations ranging from 33 to 10000 ug/plate.

Acceptable
Negative.

Bromoxynil octanoate, without and with metabolic activation, did not induce a genotoxic effect in this assay system.

870.5395

Mammalian in vivo erythrocyte micronucleus test
MRID 41930802 (1991)

Single doses of technical grade bromoxynil octanoate were administered orally by gavage to groups of 5 male CD-1 mice at dose levels up to 183 mg/kg and to groups of 5 female CD-1 mice at dose levels up to 267 mg/kg.

Acceptable
Negative.

Bromoxynil octanoate did not induce a clastogenic effect in this assay system.

870.5550

Unscheduled DNA synthesis in mammalian cells
Cultures of primary rat hepatocytes were exposed to technical grade bromoxynil octanoate at concentrations ranging from 0.98 to 15.63 ug/ml.  Higher concentrations (> 31.25 ug/ml) were cytotoxic.

Acceptable
 Negative

Bromoxynil octanoate did not induce a genotoxic effect in this assay system.   (MRID 42078901)

870.6300

Developmental neurotoxicity rats
No study available

870.7600

Dermal Absorption - rat
MRID 40854603 (1988)

[14]C-Bromoxynil octanoate, incorporated into the end-use product Buctril, which contained 33.4% bromoxynil octanoate as the active ingredient, was topically applied to the skin of male Sprague Dawley rats at doses of 0.08, 0.4 or 3.4 mg/rat for durations of exposure of 0.5, 1, 2, 4, 10 or 24 hours (4 rats/dose/duration of exposure).

Acceptable
Percent dermal absorption at 10 hours was 10.32%, 7.07% and 4.51% for doses of 0.08, 0.4 and 3.4 mg/rat respectively.  Following a soap and water wash (at 10 hours), 6.46%, 8.06% and 6.13% of the respective doses remained in/on the skin.

Percent dermal absorption at 24 hours was 17.58%, 18.43% and 10.88% for doses of 0.08, 0.4 and 3.4 mg/rat respectively.  Following a soap and water wash (at 24 hours), 7.91%, 9.50% and 4.97% of the respective doses remained in/on the skin.

870.7485

Metabolism -rat
MRID 00154756, 00154757 (1984), 42901001 (1993)

The absorption, distribution, excretion and metabolism of bromoxynil octanoate were studied in male and female Sprague Dawley rats given single oral doses of [14]C-bromoxynil octanoate by gavage at dose levels of 2 or 20 mg/kg or at a dose level of 2 mg/kg following 14 days of unlabeled bromoxynil octanoate administered by oral gavage at a dose level of 2 mg/kg/day.

Minimum
Results were similar regardless of dosing regimen.  Rate of absorption was moderate in both males and females; peak plasma concentrations of radioactivity were not reached until 7-10 hours after dosing.

Radioactivity was widely distributed in most tissues; highest concentrations were observed in blood, plasma, liver, kidneys and thyroid (especially in females).  Levels of radioactivity in tissues were generally higher in females than in males.  Most radioactivity was excreted in the urine (about 84-89% in males and 76-80% in females at 7 days) and considerably lesser amounts in the feces (about 6-10% in both males and females at 7 days).

Excretion was more rapid in males than in females.  Retention of radioactivity in tissues after 7 days was about 2-3% in males and 7-9% in females.  Essentially all bromoxynil octanoate was rapidly and nearly completely converted to bromoxynil phenol via ester hydrolysis.

In special studies, the only chemical species identified in tissues was bromoxynil phenol per se; no bromoxynil octanoate was identified in tissues.  In urine, the only major species was free and conjugated bromoxynil phenol with no bromoxynil octanoate being present.  In feces, however, some bromoxynil octanoate was identified.

A.3	HAZARD IDENTIFICATION AND ENDPOINT SELECTION
A.3.1	Acute Reference Dose (aRfD)  -  General Population (Including Infants and Children)
Study Selected: Subchronic Study in Dogs
MRID No.:  43166701
Executive Summary:  In a 13-week range-finding study, technical grade bromoxynil phenol was administered orally in gelatin capsules to groups of 2 male and 2 female beagle dogs at dose levels of 0 (control), 1, 5, 8, 12, 16, 20, 30, 40 or 50 mg/kg/day.  Treatment-related decreased body weight gain was observed in males at all dose levels tested.  At 5 mg/kg/day, occasional panting and liquid feces were also noted and at 8 and 12 mg/kg/day, frequent panting, occasional salivation, unsteady gait, decreased erythrocyte count, decreased hemoglobin, decreased packed cell volume, and increased urea nitrogen were observed.  Dose levels of 16 mg/kg/day and higher were clearly excessive and caused mortality and/or signs of severe toxicity.  Decreased body weight gain, occasional panting and liquid feces were observed in females at 5 mg/kg/day.  At 8 mg/kg/day and higher, effects in females were the same as in males.  For males, no NOAEL was determined in this study (<1 mg/kg/day).  The LOAEL is 1 mg/kg/day for males, based on decreased body weight gain.  For females, the NOAEL is 1 mg/kg/day and the LOAEL is 5 mg/kg/day, based on decreased body weight gain, panting and liquid feces.  This study was a range-finding study.  Only 2 dogs/sex/dose level were used and an insufficient number of tissues was microscopically examined in the control group and at dose levels of 12 mg/kg/day and lower.
Dose and Endpoint for Establishing aRfD:  The NOAEL of 8 mg/kg/day is based on an effect attributed to a single dose (panting) at the LOAEL of 12 mg/kg/day. The study NOAELs and LOAELS based on decreased body weight gain are not attributable to a single dose.  In addition to panting, elevated rectal temperature occurred at 16 mg/kg/day and above, and death occurred at 30 mg/kg/day and above after a single dose on day One.
UF(s):  A UF of 100 was applied to account for interspecies extrapolation (10X) and intraspecies variation (10X).
Comments on Study/Endpoint/UFs:  This study provides the lowest NOAEL in the database (most sensitive endpoint) and is expected to be protective for any potential single-dose adverse effects in humans.  In the dog, increased panting can be an adaptive, compensatory response to elevated body temperature, vs. an adverse effect.  In this study, the cascade of events beginning with panting on day one, followed by a progression of elevated rectal temperature and eventually death, were considered adverse responses.

      aRfD = 8 mg/kg/day (NOAEL) = 0.08 mg/kg/day
                            100 (UF)

A.3.1a	Acute Reference Dose (aRfD)  -  Females 13+
Study Selected: Developmental Toxicity in Rats (Oral)
MRID No.:  40466802, 00116558
Executive Summary:  In an oral developmental toxicity study (MRID 40466802), technical grade bromoxynil phenol was administered to groups of 22 pregnant Sprague Dawley rats by gavage at doses of 0 (control), 4, 12.5 or 40 mg/kg/day on gestation days 6-15, inclusive.  The developmental toxicity NOAEL is 4 mg/kg/day.  A dose-related increased incidence of supernumerary (14th) ribs was observed at the developmental toxicity LOAEL of 12.5 mg/kg/day.  Increased post-implantation loss was also observed at 12.5 mg/kg/day.  At 40 mg/kg/day, the following additional effects were observed in the offspring:  reduced fetal weight, increased numbers of small fetuses, and increased incidences of soft tissue and skeletal abnormalities (including anophthalmia, microphthalmia, short renal papilla, and spinal and thoracic bone abnormalities).  The maternal toxicity NOAEL is 12.5 mg/kg/day and the maternal toxicity LOAEL is 40 mg/kg/day, based on decreased body weight gain throughout most of the treatment and post-treatment period and decreased food consumption during the treatment period.

In an oral developmental toxicity study (MRID 00116558), groups of 28 pregnant Sprague Dawley rats received 0 (control), 5, 15 or 35 mg/kg/day of technical grade bromoxynil phenol by gavage on gestation days 5-17, inclusive.  No developmental toxicity NOAEL was determined in this study (below 5 mg/kg/day).  At the LOAEL of 5 mg/kg/day, a dose-related increased incidence of 14th ribs was observed.  At the high dose of 35 mg/kg/day, additional effects included an increased incidence of late intrauterine deaths, decreased fetal body weights and an increase in the total incidence of minor anomalies.  The maternal toxicity NOAEL is 5 mg/kg/day and the maternal toxicity LOAEL is 15 mg/kg/day, based on decreased body weight gain.  At 35 mg/kg/day, 6/28 dams died between days 7 and 14 of gestation.

Dose and Endpoint for Establishing aRfD:  The NOAEL of 4 mg/kg/day (MRID 40466802) is based on an increase of supernumerary ribs seen at the LOAEL of 5 mg/kg/day in a co-critical study (MRID 00116558).

UF(s):  A UF of 100 was applied to account for interspecies extrapolation (10X) and intraspecies variation (10X).
Comments on Study/Endpoint/UFs:  These studies provide the lowest NOAEL in the database (most sensitive endpoint) and is expected to be protective for any potential single-dose adverse effects in humans.  The LOAEL derived from a co-critical study is very close to the NOAEL and suggests a steep dose-response curve.  While the BMD data (benchmark dose = 13.66 mg/kg/day) suggest that the dose-response curve is not as steep as the observed effects would indicate, HED has taken the most protective approach and used the observed effects in the risk assessment.
      aRfD = 4 mg/kg/day (NOAEL) = 0.04 mg/kg/day
                            100 (UF)

A.3.2	Chronic Reference Dose (cRfD)  -  All Populations
Study Selected:  Chronic (1-year) Study in Dogs
MRID No.: 40780301 and 41304701
Executive Summary:   In a 12-month chronic oral toxicity study, technical grade bromoxynil phenol was administered in gelatin capsules to groups of 6 male and 6 female beagle dogs at dose levels of 0 (control), 0.1, 0.3, 1.5 or 7.5 mg/kg/day.  At the highest dose level tested (7.5 mg/kg/day), the following treatment-related effects were observed in both male and female dogs:  increased incidences of salivation, panting, liquid feces and pale gums;  statistically significant decreased body weight gain over entire duration of study, but particularly during first 8 weeks of study;  statistically significant decreased erythrocytes (RBC), hemoglobin (Hb) and packed cell volume (PCV);  statistically significant increased urea nitrogen; increased absolute liver weights and liver/body weight ratios.  At 1.5 mg/kg/day, a statistically significant decreased body weight gain over the entire duration of study was observed in the male dogs.  Other "effects" at this same dose level were marginal, inconsistent and of equivocal toxicological significance.  These effects included panting; decreased RBC, Hb and PCV; increased urea nitrogen; and increased absolute and relative liver weights in males and panting and increased absolute and relative liver weights in females.  No treatment-related gross or histo-pathological changes were observed in any organs in this study.  The dose level of 1.5 mg/kg/day is considered to be a threshold NOAEL/LOAEL for both male and female dogs in this study.

Dose and Endpoint for Establishing cRfD:  The NOAEL of 1.5 mg/kg/day is based on increased incidences of salivation, panting, liquid feces and pale gums; statistically significant decreased body weight gain over the entire duration of the study, but particularly during the first 8 weeks of the study; statistically significant decreased erythrocytes (RBC), hemoglobin (Hb) and packed cell volume (PCV); statistically significant increased urea nitrogen; increased absolute liver weights and liver/body weight ratios seen at the LOAEL of 7.5 mg/kg/day in both sexes.
UF(s):  A UF of 100 was applied to account for interspecies extrapolation (10X) and intraspecies variation (10X).
Comments about Study/Endpoint/UF:  This study provides the lowest NOAEL in the database (most sensitive endpoint) that reflects chronic (long-term) exposure which is the duration relevant to human dietary exposure.
      cRfD = 1.5 mg/kg/day (NOAEL) = 0.015 mg/kg/day
                      100 (UF)

A.3.3	Dermal Short-Term (1-30 days) and Intermediate-Term (1-6 Months)
Study Selected:  Rat Dermal Developmental Toxicity Study
MRID No.: 40881201, 40883601
Executive Summary:   In a dermal developmental toxicity study, bromoxynil phenol (solubilized in water containing 50 mg/ml sodium hydroxide and 20% triethylene glycol) was applied to groups of 23 pregnant Sprague Dawley rats at dose levels of 0 (control), 5, 10, 50 or 100 mg/kg/day for 6 hours/day on gestation days 6-15, inclusive.  A dose-related increased incidence of supernumerary (14th) ribs was observed in this study at 10, 50 and 100 mg/kg/day.  At 10 mg/kg/day, however, the increased incidence was not statistically significant compared to the concurrent control group and was within the historical control range.  The developmental toxicity NOAEL is 10 mg/kg/day and the developmental toxicity LOAEL is 50 mg/kg/day, based on increased 14th ribs.  The maternal toxicity NOAEL is 50 mg/kg/day and the maternal toxicity LOAEL is 100 mg/kg/day, based on decreased body weight gain and decreased food consumption during the treatment period.  No deaths or clinical signs, including skin irritation, were attributed to treatment with the test material in this study.

Dose and Endpoint for Risk Assessment:  The developmental NOAEL of 10 mg/kg/day is based on increased incidence of supernumerary (14[th]) ribs seen at the LOAEL of 50 mg/kg/day.
Comments about Study/Endpoint/Margins of Exposure:  This study provides the lowest NOAEL in the database (most sensitive endpoint) that reflects the route and duration of exposure relevant to occupational and/or residential scenarios. The reference value for this risk assessment scenario is a margin of exposure (MOE) of 100 based on 10X interspecies and 10X intraspecies uncertainty factors.
The lowest NOAEL from an oral study appropriate for use for this endpoint is 4 mg/kg/day from the developmental toxicity study (see Acute Reference Dose, Females 13+).  If this study were used along with the dermal absorption factor of 17% for extrapolation between the dermal and oral routes, the extrapolated NOAEL 4.0 / 0.17) would be 23.5 mg/kg/day, which is higher and less protective than the NOAEL from the route-specific study used.  Thus, using the route-specific study would be protective of the developmental effects noted after oral exposure

A.3.3	Inhalation Short-Term (1-30 days) and Intermediate-Term (1-6 Months)
Study Selected:  Rat Oral Developmental Toxicity Study
MRID No.: 00116558 and 40466802
Executive Summary:  See above: Acute Reference Dose Females 13+
Dose and Endpoint for Risk Assessment:  The NOAEL of 4 mg/kg/day (MRID 40466802) is based on an increase of supernumerary ribs seen at the LOAEL of 5 mg/kg/day in a co-critical study (MRID 00116558).
Comments about Study/Endpoint/Margins of Exposure:  This study provides the lowest NOAEL in the database (most sensitive endpoint) and reflects the duration of exposure relevant to occupational and/or residential exposure scenarios.  Although there are uncertainties associated with the use of an oral study for the inhalation route of exposure, the assumption is made in this risk assessment that oral and inhalation absorption rates are equivalent (100%) (The actual absorption by the oral route is 76  -  89%). The reference value for this risk assessment scenario is a margin of exposure (MOE) of 100 based on 10X interspecies and 10X intraspecies uncertainty factors.

Appendix B.  Chemical Names and Structures of Bromoxynil, its Esters and Metabolite.

Common name
Chemical name
Chemical structure
bromoxynil
3,5-dibromo-4-hydroxybenzonitrile

bromoxynil octanoate
2.6-dibromo-4-cyanophenyl octanoate

bromoxynil heptanoate
2.6-dibromo-4-cyanophenyl heptanoate

DBHA
3,5-dibromo-4-hydroxybenzoic acid

Appendix C.  Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure.  Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as PHED and the Outdoor Residential Exposure Task Force (ORETF).  EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted.  All applicable requirements of EPA's Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.
Appendix D.  International Residue Limit Status Sheet

Bromoxynil (035301; 09/15/2010)
Summary of US and International Tolerances and Maximum Residue Limits
Residue Definition:
US
Canada
Mexico[2]
Codex[3]
40 CFR 180.324:
Plant: bromoxynil (3,5-dibromo-4-hydroxybenzonitrile)
Livestock: bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and its metabolite 3,5-dibromo-4-hydroxybenzoic acid (DBHA)
3,5-dibromo-4-hydroxybenzonitrile, including the metabolite 3,5-dibromo-4-hydroxybenzoic acid

None
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

                                      US
Canada
Mexico[2]
Codex
Grain, aspirated grain fractions
1.2

Grass, forage
18

Grass, hay
5.0

Milk
0.4
0.1

Sorghum, grain, forage
0.8

Sorghum, grain, grain
0.2
0.1

Completed:  M. Negussie;09/16/2010
[1] Includes only commodities of interest for this action.  Tolerance values should be the HED recommendations and not those proposed by the applicant.
2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains.  PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.


[Federal Register: October 14, 2010 (Volume 75, Number 198)]
[Rules and Regulations]
[Page 63064-63066]
[DOCID:fr14oc10-12]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2010-0676; Directorate Identifier 2010-NM-095-AD;
Amendment 39-16479; AD 2010-21-19]
RIN 2120-AA64

Airworthiness Directives; Learjet Inc. Model 45 Airplanes

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final rule.

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

SUMMARY: We are adopting a new airworthiness directive (AD) for the
products listed above. This AD requires replacing aluminum fire
extinguisher discharge tubes with new, improved tubes; checking the
fire extinguisher container for certain serial numbers; replacing fire
extinguisher containers that have affected serial numbers; inspecting
the pressure indicator on certain fire extinguisher containers for
discrepancies; and performing corrective action if necessary. This AD
was prompted by a report of accidental discharge of a fire extinguisher
container and damage to an aluminum discharge tube. Investigation
revealed that following the discharge an inaccurate pressure
indication, due to the indicator dial being incorrectly staked, showed
that the container was fully charged. We are issuing this AD to prevent
inaccurate pressure readings and subsequent damage to the discharge
tubes during operation, which could result in failure of the fire
extinguisher system and an uncontained fire in an emergency situation.

DATES: This AD is effective November 18, 2010.
    The Director of the Federal Register approved the incorporation by
reference of certain publications listed in the AD as of November 18,
2010.

ADDRESSES: For service information identified in this AD, contact
Learjet, Inc., One Learjet Way, Wichita, Kansas 67209-2942; telephone
316-946-2000; fax<PHONE_NUMBER>; e-mail<EMAIL_ADDRESS>
Internet http://www.bombardier.com. You may review copies of the
referenced service information at the FAA, Transport Airplane
Directorate, 1601 Lind Avenue, SW., Renton, Washington. For information
on the availability of this material at the FAA, call<PHONE_NUMBER>.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://
www.regulations.gov; or in person at the Docket Management Facility
between 9 a.m. and 5 p.m., Monday through Friday, except Federal
holidays. The AD docket contains this AD, the regulatory evaluation,
any comments received, and other information. The address for the
Docket Office (phone:<PHONE_NUMBER>) is Document Management Facility,
U.S. Department of Transportation, Docket Operations, M-30, West
Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE.,
Washington, DC 20590.

FOR FURTHER INFORMATION CONTACT: James Galstad, Aerospace Engineer,
Systems and Propulsion Branch, ACE-116W, FAA, Wichita Aircraft
Certification Office, 1801 Airport Road, Room 100, Mid-Continent
Airport, Wichita, Kansas 67209; telephone<PHONE_NUMBER>; fax (316)
946-4107; e-mail<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Discussion

    We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR
part 39 to include an airworthiness directive (AD) that would apply to
the specified products. That NPRM was published in the Federal Register
on July 7, 2010 (75 FR 38941). That NPRM proposed to require replacing
aluminum fire extinguisher discharge tubes with new, improved tubes;
checking the fire extinguisher container for certain serial numbers;
replacing fire extinguisher containers that have affected serial

numbers; inspecting the pressure indicator on certain fire extinguisher
containers for discrepancies; and performing corrective action if
necessary.

Comments

    We gave the public the opportunity to participate in developing
this AD. We received no comments on the NPRM or on the determination of
the cost to the public.

Conclusion

    We reviewed the relevant data and determined that air safety and
the public interest require adopting the AD as proposed.

Costs of Compliance

    We estimate that this AD affects 322 airplanes of U.S. registry. We
also estimate that it will take 5 work-hours per product to comply with
this AD. The average labor rate is $85 per work-hour. Required parts
cost is minimal. Where the service information lists required parts
costs that are covered under warranty, we have assumed that there will
be no charge for these costs. As we do not control warranty coverage
for affected parties, some parties may incur costs higher than
estimated here. Based on these figures, we estimate the cost of this AD
to the U.S. operators to be $136,850, or $425 per product.

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. Subtitle VII: Aviation Programs,
describes in more detail the scope of the Agency's authority.
    We are issuing this rulemaking under the authority described in
Subtitle VII, Part A, Subpart III, Section 44701: ``General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.

Regulatory Findings

    This AD will not have federalism implications under Executive Order
13132. This AD will not have a substantial direct effect on the States,
on the relationship between the national government and the States, or
on the distribution of power and responsibilities among the various
levels of government.
    For the reasons discussed above, I certify that this AD:
    (1) Is not a ``significant regulatory action'' under Executive
Order 12866,
    (2) Is not a ``significant rule'' under DOT Regulatory Policies and
Procedures (44 FR 11034, February 26, 1979),
    (3) Will not affect intrastate aviation in Alaska, and
    (4) Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

Adoption of the Amendment

0
Accordingly, under the authority delegated to me by the Administrator,
the FAA amends 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

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

Sec.  39.13  [Amended]

0
2. The FAA amends Sec.  39.13 by adding the following new airworthiness
directive (AD):

2010-21-19 Learjet Inc: Amendment 39-16479; Docket No. FAA-2010-
0676; Directorate Identifier 2010-NM-095-AD.

Effective Date

    (a) This AD is effective November 18, 2010.

Affected ADs

    (b) None.

Applicability

    (c) This AD applies to Learjet Inc. Model 45 airplanes,
certificated in any category; as identified in Bombardier Service
Bulletins 40-26-05 and 45-26-9, both Revision 2, both dated May 4,
2009.

Subject

    (d) Air Transport Association (ATA) of America Code 26: Fire
protection.

Unsafe Condition

    (e) This AD results from a report of accidental discharge of a
fire extinguisher container and damage to an aluminum discharge
tube. Investigation revealed that following the discharge an
inaccurate pressure indication, due to the indicator dial being
incorrectly staked, showed that the container was fully charged. The
Federal Aviation Administration is issuing this AD to prevent
inaccurate pressure readings and subsequent damage to the discharge
tubes during operation, which could result in failure of the fire
extinguisher system and an uncontained fire in an emergency
situation.

Compliance

    (f) You are responsible for having the actions required by this
AD performed within the compliance times specified, unless the
actions have already been done.

Replacement, Check, Inspection, Corrective Action

    (g) Within 12 months after the effective date of this AD:
Replace the aluminum fire extinguisher discharge tubes with new,
improved stainless steel tubes; check the fire extinguisher
container for any serial number specified in Table 1 of Bombardier
Service Bulletin 40-26-05 or 45-26-9, both Revision 2, both dated
May 4, 2009, as applicable; replace any containers that have
affected serial numbers, do a weight check of all containers,
including the replacement container, if applicable; and inspect the
pressure indicator on the containers for discrepancies; by doing all
applicable actions in accordance with the Accomplishment
Instructions of Bombardier Service Bulletin 40-26-05 or 45-26-9,
both Revision 2, both dated May 4, 2009; as applicable. If any
discrepancy is found, replace the container before further flight in
accordance with the Accomplishment Instructions of Bombardier
Service Bulletin 40-26-05 or 45-26-9, both Revision 2, both dated
May 4, 2009; as applicable.
    (h) Actions done before the effective date of this AD in
accordance with the applicable service information listed in Table 1
of this AD are acceptable for compliance with the corresponding
requirements in paragraph (g) of this AD.

            Table 1--Credit for Actions Accomplished in Accordance With Previous Service Information
----------------------------------------------------------------------------------------------------------------
                                     Bombardier
    Affected Serial Numbers--          Service                Revision--                      Dated--
                                     Bulletin--
----------------------------------------------------------------------------------------------------------------
For Model 45 airplanes having             40-26-05  Basic Issue..................  November 24, 2008.
 serial numbers 2001 through
 2114, inclusive.
For Model 45 airplanes having             40-26-05  1............................  December 22, 2008.
 serial numbers 2001 through
 2114, inclusive.
For Model 45 airplanes having              45-26-9  Basic Issue..................  November 24, 2008.
 serial numbers 006 through 383,
 inclusive.

For Model 45 airplanes having              45-26-9  1............................  December 22, 2008.
 serial numbers 006 through 383,
 inclusive.
----------------------------------------------------------------------------------------------------------------

Alternative Methods of Compliance (AMOCs)

    (i)(1) The Manager, Wichita Aircraft Certification Office (ACO),
FAA, has the authority to approve AMOCs for this AD, if requested
using the procedures found in 14 CFR 39.19. In accordance with 14
CFR 39.19, send your request to your principal inspector or local
Flight Standards District Office, as appropriate. If sending
information directly to the manager of the ACO, send it to the
attention of the person identified in the Related Information
section of this AD.
    (2) Before using any approved AMOC, notify your Principal
Maintenance Inspector or Principal Avionics Inspector, as
appropriate, or lacking a principal inspector, your local Flight
Standards District Office.

Related Information

    (j) For more information about this AD, contact James Galstad,
Aerospace Engineer, Systems and Propulsion Branch, ACE-116W, FAA,
Wichita Aircraft Certification Office, 1801 Airport Road, Room 100,
Mid-Continent Airport, Wichita, Kansas 67209; telephone (316) 946-
4135; fax<PHONE_NUMBER>; e-mail<EMAIL_ADDRESS>
Material Incorporated by Reference

    (k) You must use the service information contained in Table 2 of
this AD, as applicable, to do the actions required by this AD,
unless the AD specifies otherwise.

               Table 2--Material Incorporated by Reference
------------------------------------------------------------------------
             Document                 Revision             Date
------------------------------------------------------------------------
Bombardier Service Bulletin 40-26-            2  May 4, 2009.
 05.
Bombardier Service Bulletin 45-26-            2  May 4, 2009.
 9.
------------------------------------------------------------------------

    (1) The Director of the Federal Register approved the
incorporation by reference of the service information contained in
Table 2 of this AD under 5 U.S.C. 552(a) and 1 CFR part 51.
    (2) For service information identified in this AD, contact
Learjet, Inc., One Learjet Way, Wichita, Kansas 67209-2942;
telephone<PHONE_NUMBER>; fax<PHONE_NUMBER>; e-mail
<EMAIL_ADDRESS>Internet http://www.bombardier.com.
    (3) You may review copies of the service information at the FAA,
Transport Airplane Directorate, 1601 Lind Avenue SW., Renton,
Washington. For information on the availability of this material at
the FAA, call<PHONE_NUMBER>.
    (4) You may also review copies of the service information that
is incorporated by reference at the National Archives and Records
Administration (NARA). For information on the availability of this
material at an NARA facility, call<PHONE_NUMBER>, or go to http://
www.archives.gov/federal_register/code_of_federal_regulations/
ibr_locations.html.

    Issued in Renton, Washington, on October 5, 2010.
Ali Bahrami,
Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. 2010-25599 Filed 10-13-10; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register Volume 79, Number 231 (Tuesday, December 2, 2014)]
[Notices]
[Pages 71504-71505]
[FR Doc No: 2014-28365]

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DEPARTMENT OF TRANSPORTATION

Federal Railroad Administration

[Docket No. FRA-2012-0033]

Notice of Intent To Grant Buy America Waivers to National
Railroad Passenger Corporation and California High-Speed Rail Authority
for the Non-Domestic Final Assembly of Four ``Prototype'' Tier III
High-Speed Rail Trainsets

AGENCY: Federal Railroad Administration (FRA), United States Department
of Transportation (DOT).

ACTION: Notice of intent to grant Buy America waivers.

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

SUMMARY: FRA is issuing this notice to advise the public that it
intends to grant the National Railroad Passenger Corporation (Amtrak)
and California High-Speed Rail Authority (Authority) waivers from FRA's
Buy America requirement for the non-domestic final assembly of up to
four (two for Amtrak; two for the Authority) ``prototype'' Tier III
high-speed rail (HSR) trainsets in connection with the procurement of
HSR trainsets. These waivers apply only to the final assembly of up to
two prototype HSR trainsets each for Amtrak and the Authority. Each
waiver is subject to the following condition: Before issuing a ``Notice
To Proceed'' to any selected supplier, Amtrak and the Authority each
must certify and provide support to FRA that its selected supplier
still has not established domestic manufacturing facilities capable of
assembling the prototypes and delivering them within a reasonable time.
All components used in the prototypes must still be domestically
manufactured or separate waivers for components requested and granted
before assembly of the prototypes can commence.

DATES: Written comments on FRA's determination to grant Amtrak's and
the Authority's Buy America waiver requests should be provided to the
FRA on or before December 17, 2014.

ADDRESSES: Please submit your comments by one of the following means,
identifying your submissions by docket number FRA-2012-0033. All
electronic submissions must be made to the U.S. Government electronic
site at http://www.regulations.gov. Commenters should follow the
instructions below for mailed and hand-delivered comments.
    (1) Web site: http://www.regulations.gov. Follow the instructions
for submitting comments on the U.S. Government electronic docket site;
    (2) Fax:<PHONE_NUMBER>;
    (3) Mail: U.S. Department of Transportation, 1200 New Jersey Avenue
SE., Docket Operations, M-30, Room W12-140, Washington, DC 20590-0001;
or
    (4) Hand Delivery: Room W12-140 on the first floor of the West
Building, 1200 New Jersey Avenue SE., Washington, DC 20590, between 9
a.m. and 5 p.m., Monday through Friday, except Federal holidays.
    Instructions: All submissions must make reference to the ``Federal
Railroad Administration'' and include docket number FRA-2012-0033. Due
to security procedures in effect since October 2001, mail received
through the U.S. Postal Service may be subject to delays. Parties
making submissions responsive to this notice should consider using an
express mail firm to ensure the prompt filing of any submissions not
filed electronically or by hand. Note that all submissions received,
including any personal information therein, will be posted without
change or alteration to http://www.regulations.gov. For more
information, you may review DOT's complete Privacy Act Statement in the
Federal Register published on April 11, 2000 (65 FR 19477), or visit
http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Mr. John Johnson, Attorney-Advisor,
FRA Office of Chief Counsel, 1200 New Jersey Avenue SE., Mail Stop 25,
Washington, DC 20590,<PHONE_NUMBER><EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:
    FRA is issuing this notice to advise the public that it intends to
grant Amtrak's and the Authority's requests for waivers from FRA's Buy
America requirement, 49 U.S.C. 24405(a), for the non-domestic final
assembly of up to four (two for Amtrak; two for the Authority)
``prototype'' Tier III high-speed rail (HSR) trainsets in connection
with the procurement of HSR trainsets. These ``prototype'' Tier III HSR
trainsets will be delivered to Amtrak and the Authority for use in
passenger (revenue) service. Please note that the Federal Transit
Administration (FTA) would use the term ``pilot'' to describe these
vehicles. Because some time may elapse between granting these waivers
and construction of prototype HSR trainsets, each waiver has the
following condition: Before issuing a ``Notice To Proceed'' to any
selected supplier, Amtrak and the Authority each must certify and
provide support to FRA that its selected supplier still has not
established domestic manufacturing facilities capable of assembling the
prototypes and delivering them within a reasonable time. In addition,
all components used in the prototypes must still be domestically
manufactured or separate waivers for components requested and granted
before assembly of the prototypes can commence.
    The larger projects underlying these waiver requests are Amtrak's
and the Authority's plans to advance HSR on the Northeast Corridor and
in California, respectively. In near identical waiver requests Amtrak
and the Authority asserted that the projects require the purchase and
use of high-quality, service-proven FRA Tier III Next Generation
Trainsets, including two prototype HSR trainsets for each project.
    FRA's Buy America requirement for rolling stock, including HSR
trainsets, requires domestic final assembly of the trainsets and that
all of the components be manufactured in the United States. More
information about FRA's Buy America requirement is available at http://www.fra.dot.gov/Page/P0185. Section 24405(a)(2) also permits the
Secretary of Transportation (delegated to the FRA Administrator) to
waive the Buy America requirements if the Secretary finds that: (A)
applying paragraph (1) would be inconsistent with the public interest;
(B) the steel, iron, and goods manufactured in the United States are
not produced in sufficient and reasonably available amount or are not
of a satisfactory quality; (C) rolling stock or power train equipment
cannot be bought or delivered to the United States within a reasonable
time; or (D) including domestic material will increase the cost of the
overall project by more than 25 percent.
    FRA believes a waiver is appropriate under 49 U.S.C. 24405(a)(2)(C)
because domestically-produced HSR trainsets meeting the specific
technical, design, and schedule needs of Amtrak and the

Authority are not currently available in the United States. There is no
assembly or testing facility for HSR trainsets operating at speeds
greater than 160 mph in the United States. Moreover, FRA estimates that
it could take HSR trainset manufacturers a minimum of one-and-a-half to
two years to establish the required facilities to support a domestic
HSR trainset assembly capability. This includes any HSR trainset
manufacturers that currently have passenger railcar manufacturing
facilities in the United States. For example, in addition to acquiring
specialized machinery and training and hiring the workforce, these
manufacturers' plants are currently customized for steel railcars, and
HSR trainsets use aluminum, which requires different manufacturing
techniques.
    In addition, Tier III HSR is a significant new technology for the
U.S. market, and safety is a significant factor. Allowing final
assembly of the prototype HSR trainsets at the manufacturer's existing
non-domestic facilities is necessary to ensure that expected safety
benefits of ``service-proven'' systems are secured, to enable training
of domestic workers, and to assure successful technology transfer. For
example, rather than attempting to establish new manufacturing and
assembly processes at a domestic facility while simultaneously
integrating and testing HSR trainset designs, the selected
manufacturer(s) can focus on identifying and remedying any defects in
the designs specific to Amtrak and the Authority and their operations
in the United States. FRA concludes that integrating manufacturing,
assembly, and labor resources into the prototype production, among
other suggested actions by Amtrak and the Authority, will facilitate
the development of domestic HSR production facilities. This same
``human technology transfer'' has been successful in other global HSR
installations in South Korea, China, Taiwan, and Spain.
    On March 14, 2014, FRA published on its Web site public notice of
Amtrak's and the Authority's waiver requests. FRA received 13 online
comments and one mailed response to this notice. None of the commenters
identified a domestic source for HSR trainsets. Of the 14 comments, 10
commenters indicated they were against granting the waiver; four were
for granting the waiver. Of the 10 comments ``against,'' four were not
responsive to the notice. Of the six remaining dissenters, they mainly
disagreed with Amtrak's and the Authority's argument that HSR trainsets
cannot be delivered in a reasonable time because Amtrak and the
Authority could wait for domestic assembly. While this is theoretically
possible, significant capacity and technology transfer problems are
probable, and FRA believes that the one-and-a-half to two-year minimum
delay could negatively impact the schedules proposed by Amtrak and the
Authority. In addition, as noted above, FRA believes that allowing the
prototypes to be assembled at the manufacturers' non-domestic factories
will facilitate the successful technology transfer and training of U.S.
workers. Finally, because FRA is limiting the waivers to final assembly
of up to four prototypes with the expectation that the training of
domestic resources will occur simultaneously, FRA is not delaying or
preventing the establishment of the selected supplier's domestic
assembly facilities. FRA finds that this delay to provide ``service-
proven'' systems makes the prototypes not available within a
``reasonable time.'' Therefore, waivers are appropriate.
    FRA will publish the letters granting Amtrak's and the Authority's
waiver requests on its Web site at: http://www.fra.dot.gov/eLib/Details/L16035 and http://www.fra.dot.gov/eLib/Details/L16036,
respectively.

    Issued in Washington, DC on November 26, 2014.
Melissa L. Porter,
Chief Counsel.
[FR Doc. 2014-28365 Filed 12-1-14; 8:45 am]
BILLING CODE 4910-06-P