EPA Reviewer: Linda L. Taylor, Ph.D.
Risk Assessment Branch VII, Health Effects Division (7509C)
EPA Secondary Reviewer: Elizabeth Mendez, Ph.D.
Immediate Office, Health Effects Division (7509C)
TXR# 0050697

                   DATA EVALUATION RECORD  -  SUPPLEMENT # 1
                  see TXR# 0055341 (root) for previous review

STUDY TYPE: F1-Extended One Generation Toxicity Study  -  rat
                          OCSPP 870.3800, 870.6300, 870.7800/OECD 416
P.C. CODE: 030001
CAS NO.: 94-75-7
DP Barcode: D386909
TEST MATERIAL (PURITY) : 2, 4-D [97.85- 98.6% a.i.]
SYNONYMS: 2, 4-dichlorophenoxyacetic acid; 2, 4-D acid
SPONSOR: Industry Task Force II on 2, 4-D Research Data

CITATION: Marty, MS; Zablotny, CL; Andrus, AK; et al. (2010) 2, 4-D: An Extended One Generation Dietary Toxicity Study in Crl:CD(SD) Rats. Toxicology & Environmental Research and Consulting.  The Dow Chemical Company. Laboratory Project Study ID 081104, January 30, 2010. MRID 47972101. Unpublished.

EXECUTIVE SUMMARY: In an extended dietary one-generation reproductive toxicity study (MRID 47972101), 2,4-dichloro phenoxyacetic acid (2,4-D; 97.85%-98.6% a.i.; lot # 2006 2433 8006-USA) was administered to 27 Crl:CD(SD) young adult rats/sex/dose via the diet at dose levels of 0, 100, 300, or 600 (females)/800 (males) ppm [equivalent to 0, ≈5, 15, or 30 (females)/40 (males) mg/kg bw/day] for approximately four weeks prior to mating and continuing through mating (up to 2 weeks), gestation, and lactation.  P1 males were exposed for a minimum of 11 weeks including 7 weeks from the initiation of the mating phase. P1 females were exposed until lactation day 22 (LD22). A satellite group of P1 females (12/dose) were subject to the same exposures as the P1 females on the main study (exposure for 4 weeks during the pre-mating, up to 2 weeks during the mating period and during gestation until termination on gestation day 17 (GD 17). Satellite males were not exposed to dietary 2, 4-D except during co-housing with satellite females during the mating period.

P1 Generation: A comprehensive evaluation of P1 male and P1 female reproductive system was conducted, including an evaluation of gonadal function, the estrous cycle, sperm parameters, mating performance, conception, gestation, parturition and lactation, as well as survival, growth and development of the offspring. Selected systemic toxicity parameters were also evaluated in the P1 males and P1 females.

Satellite GD 17 Females: A satellite group of P1 females (12/dose) was included for assessments of selected systemic toxicity parameters, clinical chemistry/hematology, thyroid hormone levels, thyroid weights, plasma  2, 4-D levels, histopathology, and selected reproductive parameters during gestation (corpora lutea and implantation numbers).

F1 Generation: F1 offspring were evaluated for potential effects on the nervous system, immune system, reproductive and endocrine systems, thyroid function, and other systemic toxicity parameters. 2, 4-D plasma levels were also assessed in the F1 offspring. In-life parameters in all F1 offspring included clinical observations, body weights, feed consumption, anogenital distance, nipple retention and puberty onset. Selected F1 offspring were divided into three different groups (Sets 1, 2, and 3) at weaning (postnatal day 21; PND 21). Each set of F1 offspring was maintained on the test diet until PND 60 (Set 1b F1 offspring), ≈PND 70 (Sets 1a and 2a F1 offspring), or ≈PND 90-139 (Sets 2b and 3 F1 offspring).

   Set 1a (10/sex/dose): assessment of general systemic and thyroid toxicity, which included clinical chemistry/hematology parameters, thyroid hormone assessment, and urinalysis (males only). Post-mortem evaluations in Set 1a (PND70) included gross pathology, organ weights and histopathology on a wide range of tissues, including thyroids.

   Set 1b (10/sex/dose): developmental neurotoxicity (DNT) assessment, which included functional observational battery (FOB), motor activity and acoustic startle response (ASR). On PND 60, Set 1b animals were perfused for central nervous system (CNS) and peripheral nerve neuropathology evaluation and brain morphometry. A special stain (Luxol Fast Blue) was used to evaluate brain myelination.

Set 2a (10sex/dose): assessment of potential developmental immunotoxicity (DIT): examination of humoral immune function using the sheep red blood cell (SRBC) antibody-forming cell (AFC) assay on PND 70-74.
Set 2b (10/sex/dose): assessment of potential developmental immunotoxicity (DIT): examination of innate cellular immunity using the natural killer cell (NK) assay on PND 87-93.

   Set 3 (23-27/sex/dose): assessment of reproductive/endocrine toxicity, which included estrous cycle evaluation and post-mortem evaluations that focused on reproductive organs, sperm assessment, and ovarian follicle counts on PND 139. TK analyses were conducted on Set 3 males and females on PND 63 and 84 to determine plasma 2, 4-D levels.

In addition, selected pups culled on PND 4 were used to assess thyroid hormone levels. Additional data were gathered from F1 offspring not assigned to Sets 1-3. On PND 22, unselected weanlings were either perfused for examination of neuropathology (12/sex/dose) or euthanized for assessment of systemic toxicity, which included thyroid hormone assessment, organ weights, and post-mortem examinations (gross pathology and histopathology) in 10/sex/dose.

Reproductive and selected data from the F1 generation were used to assess whether a second generation would be produced. None of the criteria were met (Table 1), and a second generation was not assessed in this study.

P1 Adult Rats: There were no treatment-related deaths or clinical signs of toxicity in either sex of P1 adults. Body weights and body-weight gains were comparable among the groups during the pre-mating and mating phases (both sexes) and during gestation and the latter part of lactation (dams). Prior to dietary adjustment of 2, 4-D concentration during the second week of lactation, the 600 ppm dams displayed a decrease in body weight (LD 7; ↓5%) and body-weight gain (LD 1-4; ↓64%), which is consistent with reduced food intake during the first week of lactation. The reduction in food intake can be attributed to the increase in the actual dose (≈65 mg/kg/day) above the targeted level (30 mg/kg/day) during this time. After dietary adjustment, food intake for the 600 ppm dams was above control levels.

There were no apparent treatment-related effects on hematology, differential white blood cell counts, and prothrombin time, and clinical chemistry and urinalysis parameters were comparable among the groups (both sexes). P1 males displayed increased kidney weights (absolute and relative) at 800 ppm, which were accompanied by histopathological findings (degenerative lesion in the proximal convoluted tubules in the outer zone of the medulla) and are consistent with previous findings that the kidney is a target organ. There were no treatment-related findings in the P1 female kidney. Decreased reproductive and accessory sex gland weights were observed at 300 ppm and/or 800 ppm.  These changes, however, are related to the concurrent control being outside of the laboratory historical control range. P1 females at 600 ppm displayed increased uterine weights (↑17%, both absolute and relative), although statistical significance was not attained. There were no alterations in estrous cycle pattern in the 600 ppm P1 females compared to the control, and no significant difference in mean estrous cycle length in P1 females at any dose level compared to the control. There were no significant, treatment-related effects on sperm motility or progressive motility, no differences in testicular spermatid and epididymal sperm counts, and no differences in the proportion of abnormal sperm. Male and female mating, conception, fertility, and gestation indices were comparable among the groups, and post-implantation loss was comparable among the groups. Both the time to mating and gestation length were comparable among the groups.

GD 17 Satellite Females: All P1 satellite females survived to scheduled sacrifice, and body weights were comparable among the groups. Hematology and clinical chemistry parameters were comparable among the groups. Reproductive indices and the numbers of corpora lutea and implantations were comparable among the groups. There was a slight increase in resorptions at 600 ppm (0.9 vs 1.5), although there was wide variability (standard deviations exceed the means). There was a slight increase in post-implantation loss at 600 ppm (9.2 vs 5.5). It should be noted that this observation was not corroborated since post-implantation losses in the P1 adults of the definitive study were comparable amongst all dose groups.   Both the 100 ppm and 600 ppm females displayed an increase in thyroid weight (↑9%), but there was no dose-response. There were no statistically significant, treatment-related differences in serum T3, T4, or TSH in the GD 17 satellite females. Although the 600 ppm GD 17satellite females displayed the predicted pattern of thyroid hormone changes (↓ T3 and ↓ T4 with ↑TSH levels) that suggest 2, 4-D exposure may adversely affect thyroid function at doses above the renal saturation clearance, the thyroid effects noted below renal saturation are not considered sufficiently robust to be adverse.

 F1 Offspring: There were no treatment-related effects on the numbers of live or dead F1 pups born/litter or on pup survival or sex ratio. Slightly lower body weights were observed in the 600 ppm pups during early lactation, which coincided with the dams decreased food intake LD 1-4 and LD 4-7). Pup body weight (600 ppm) remained lower in the 600 ppm pups (↓6%) during PND 14-21. There was no significant, treatment-related difference in absolute or relative anogenital distance in either sex and no differences in nipple/areolae retention between control and high-dose groups in either sex. F1 males at 800 ppm displayed a 1.6 days delay in preputial separation (well within normal variability), which was accompanied by a very slight reduction in body weight compared to the control (↓2.1 grams; 99% of control). The age at vaginal opening was comparable among the groups of F1 females.

F1 Offspring Thyroid Assessments: PND 4 - There were no statistically-significant differences in serum T3, T4, or TSH in PND 4 culled pups. T4 was reduced to a similar extent in both sexes at the 300 ppm (↓14%-15%) and 600 ppm/800 ppm (↓12%-14%) dose levels, and female PND 4 pups showed an increase in TSH (↑19%) at 600 ppm. F1 PND 22 Weanlings - F1 PND 22 males displayed a statistically-significant reduction (↓28%) in T4 at 800 ppm, and F1 PND 22 females displayed a non-statistically significant reduction (↓20%) in T4 at 600 ppm. T3 was reduced in the males at 300 ppm (↓19%) and 800 ppm (↓13%), but there was no dose response. F1 PND 62-64 - Both sexes displayed increased TSH at 300 ppm (↑26%) and at 800 ppm (males ↑23%))/600 ppm (females ↑24%)), although the increase in males was not dose-related and none of the differences in thyroid hormone levels were statistically significant. T4 was decreased at 800 ppm in males (↓13%). Though these findings suggest that 2, 4-D exposure may adversely affect thyroid function at doses above the renal saturation clearance, the thyroid effects noted below renal saturation are not considered sufficiently robust to be adverse.

F1 Unselected Offspring (PND 22 weanlings): There were no effects on survival of the unselected weanlings used for systemic toxicity (non-perfused). All treated males displayed a decrease in body weight (↓9%-10%) compared to the control males. Decreased adrenal weights were observed in males at 800 ppm (absolute ↓37% and relative ↓29%). The decreases in kidney (↓15%), liver (↓18%), testes (↓15%), and thyroid (↓14%) weights observed in males at 800 ppm were slightly greater than the body-weight deficit of 10%. Organ weights were comparable among the groups of females. There were no significant differences in perfused absolute brain weights, cerebral lengths and widths or cerebellar lengths and widths in perfused F1 PND 22 weanlings of either sex. There were no neuropathological observations attributed to treatment in the perfused F1 PND 22 weanlings, and no treatment-related changes in myelin in either males at 800 ppm or females at 600 ppm.

F1 Offspring Set 1a (PND 70): All Set 1a pups survived to scheduled sacrifice. Males at 800 ppm displayed decreased body weight (↓11%-17%) and body-weight gains (↓11%-25%) throughout the study period, with the magnitude of the reduction lessening with time of exposure. Females displayed comparable body weight/gain among the groups. Platelet counts were reduced in the 800 ppm males but not in the females at any dose level. Both sexes displayed a slight increase in ALT (↑18%/25%) and an increase in triglyceride (↑31%/43%) levels. Although some of the decreases in organ weights observed in the 800 ppm males may be attributed to the 10% decrease in body weight at termination, the decreases in liver (↓16%), pituitary (↓14%), and adrenal glands (↓12%) might be related to treatment.  Increased uterine weights (↑31% absolute and ↑32% relative) were observed at 600 ppm. Although statistical significance was not attained, the finding is considered treatment-related since a similar increase was observed at 600 ppm in the P1 and Set 3 F1 females. Increased ovarian weight (↑9%) was observed in the 600 ppm F1 Set 1a females, although statistical significance was not attained. Increased kidney weights (↑9% absolute and ↑11% relative) were observed in the females at 300 ppm and 600 ppm, although there was no dose-response and kidney weights were comparable among the male groups.  Decreased thymus weights (↓12% absolute and ↓10% relative) were observed in females at 600 ppm and in Set 3 females at 600 ppm (↓14% absolute and ↓13% relative). An increased incidence of degeneration of the proximal convoluted tubule in the kidney was observed in males at 300 ppm and 800 ppm and in females at 600 ppm. Regarding the terminal stage of estrous, 2 of 10 females at 300 ppm and 3 of 10 females at 600 ppm displayed proestrus, whereas none of the 10 females in the control and 100 ppm groups displayed proestrus.

F1 Offspring Set 1b (PND 54-56): There were no significant differences in body weight/gain in either sex. There was an increase in the level of urination in all treated male groups compared to the control group, but there was no dose response. There was a 10% reduction in hind limb grip strength at 800 ppm in males and at 600 ppm in females. Males at 800 ppm displayed a decrease in total motor activity (↓10%), whereas females at 600 ppm showed an increase (↑12%). During the first half of the session, all male groups displayed a similar motor activity level (were within 6%), whereas the 800 ppm males showed a progressive lessening of activity with increased time; i. e., the 800 ppm males displayed decreased activity compared to the control (↓11%, ↓16%, ↓30%, and ↓34% in Epochs 5, 6, 7, and 8, respectively). Males at 800 ppm displayed a different acoustic startle response (ASR) initially compared to the control males. There was no apparent difference in ASR in females. There were no significant differences in perfused absolute brain weights, cerebral lengths and widths, or cerebellar lengths and widths in either sex (PND 60). There were no treatment-related (1) microscopic changes in the central or peripheral nervous system in the perfused offspring; (2)  changes in myelin; or (3) changes in microscopic measurements of structures in the cerebral cortex, cerebellum, thalamus, or hippocampus.

F1 Offspring Set 2a (PND 67-73): Developmental Immunotoxicity (Primary Immune Response to Sheep Red Blood Cells): There were no deaths. Slight decreases in body weights and body-weight gains were observed in males at 800 ppm (↓6%-10% and ↓15%) and females at 600 ppm (↓8%-9% and ↓10%). Terminal body weights were comparable among the male and female groups. Both absolute (↓10%) and relative (↓8%) thymus weight decreases were observed in the males at 800 ppm and in the females at 600 ppm [absolute (↓13%) and relative (↓10%)]. Males at 300 ppm showed a 17% decrease in thymus weight but no dose response. Spleen weights were slightly lower in females at 600 ppm [absolute (↓13%) and relative (↓14%)]. There was no significant difference in response for AFC/spleen and AFC/106  splenocytes among the male groups. Females at 600 ppm displayed a non-significant decrease of 54% for AFC/spleen and 27% for the AFC/106  splenocytes.

F1 Offspring Set 2b (PND 67-73): Developmental Immunotoxicity (Natural Killer Cell Activity): There were no deaths, and body weights/gains showed a similar slight reduction in males at 800 ppm as observed in the other offspring groups. Female body weights/gains were comparable among the groups. Terminal body weights (PND 87-93) were comparable among the groups (both sexes). There were no significant treatment-related effects on absolute or relative spleen or testes weights in males, and no significant treatment-related effects on spleen weights in females (only organs weighed). There were no significant, treatment-related differences in the percent target cell cytotoxicity at any dose level compared to control (both sexes), and 2, 4-D did not alter the cytotoxic ability of splenic NK-cells in male or female rats at any dose level.

F1 Offspring Set 3 (PND 90 or 139): Reproductive Toxicity: There were no treatment-related deaths or clinical signs of toxicity. Terminal body weights were comparable among the groups (both sexes). No significant differences were observed in mean estrous cycle length at any dose level compared to the control. There were no significant, treatment-related effects on the numbers of small follicles, growing follicles, or total follicles. There were no significant, treatment-related effects on sperm motility or progressive motility, no differences in testicular spermatid and epididymal sperm counts, and no differences in the proportion of abnormal sperm between the control and 800 ppm males. Absolute (↓9%) and relative (↓8%) pituitary gland weights were significantly lower in the 800 ppm males and absolute (↓9%) and relative (↓10%) pituitary gland weights were non-significantly lower in the 600 ppm females. There was no associated histopathology in the pituitary glands. Uterine weights were increased at 300 ppm (↑10% absolute and ↑10% relative) and 600 ppm (↑10% absolute and ↑11% relative) compared to the controls. Thymus weights were decreased (↓14% absolute and ↓13% relative) in females at 600 ppm, although statistical significance was not attained. No histopathological changes were observed in the pituitary or thymus in either sex. A degenerative lesion was observed in the kidney (proximal convoluted tubule) in both sexes at 300 ppm and at 600 ppm/800 ppm. Ovarian follicle counts were comparable between the control and 600 ppm females (PND 139).

The parental systemic LOAEL is 800 ppm (45.3 mg/kg bw/day in males), based on nephrotoxicity manifested as increased kidney weights, and degenerative lesions in the proximal convoluted tubules in the main study P1 rats. The parental systemic NOAEL is 300 ppm (16.6 mg/kg bw/day in males).   No toxicologically relevant effects were identified in P1 females or in the GD 17 satellite female groups at the highest dose tested (600 ppm; 40.2 mg/kg/day).

The thyroid toxicity NOAEL is established at 800/600 ppm (45.3 mg/kg/day in males and /40.2 mg/kg/day in females), the highest dose tested.  The thyroid effects noted in the database were considered to be adaptive.

The offspring (F1 adults) LOAEL is 800/600 ppm (55.6 mg/kg bw/day in males and 46.7 mg/kg/day in females), based on kidney toxicity manifested as increased kidney weights and increased incidence of degeneration of the proximal convoluted tubules.  The offspring NOAEL is 300 ppm (20.9/ mg/kg bw/day in males and 23.3 mg/kg/day in females).

The F1 offspring (PND 22) LOAEL is 800/600 ppm, based on decreased body weight observed throughout lactation. The offspring NOAEL is 300 ppm. The dose on a mg/kg/day basis for the PND 22 F1 offspring was not calculated.
The DNT offspring (PND 21-60) LOAEL is >800/600 ppm (81.7 mg/kg bw/day in males, 59.2 mg/kg bw/day in females), based on the lack of evidence of DNT (FOB parameters, motor activity, and acoustic startle response).  The DNT offspring NOAEL is 800 ppm/600 ppm (81.7 mg/kg bw/day in males, 59.2 mg/kg bw/day in females).

The DIT offspring (PND 139) LOAEL is >800/600 ppm (71.8 mg/kg bw/day in males, 55.3 mg/kg bw/day in females), based on the lack of evidence of DIT [SRBC antibody-forming cell assay (PND 66-70) and Natural Killer Cell assay (PND 87-93)].  The DIT offspring NOAEL is 800/600 ppm (71.8 mg/kg bw/day in males and 55.3 mg/kg bw/day in females), the highest dose tested.

The reproductive LOAEL is > 800/600 ppm (45.3 mg/kg bw/day in males, 40.2 mg/kg bw/day in females), based on the lack of effect on estrous cyclicity, (P1 females, satellite GD 17 dams, Set 3 F1 offspring) or reproductive indices (mating, fertility, time to mating, gestation length, pre-and post-implantation loss, number of corpora lutea (satellite GD 17 dams), sperm parameters, ovarian follicle counts, and reproductive organ histopathology).  The reproductive NOAEL is 800/600 ppm (45.3 mg/kg bw/day in males, 40.2 mg/kg bw/day in females), the highest dose tested.

This study is classified acceptable/non-guideline. The study does not satisfy a guideline requirement for 2, 4-D. It satisfies the data call-in requirements for 2, 4-D for OCSPP 870.3800 (Reproduction and Fertility Effects), OCSPP 870.6300 (Developmental Neurotoxicity),  OCSPP 870.7800 (Immunotoxicity). The study is in accordance with the OECD extended one-generation reproductive toxicity study guideline (November, 2010).

COMMENT:  The major change is a change in the offspring (F1 adults) LOAEL from 300 ppm to 600 ppm, making the new NOAEL 300 ppm.  Both the PMRA and EPA do not consider the kidney effects occurring at PND 70 and PND 139 to be adverse at the 300 ppm dose level in either sex.  Although there was some degeneration in the males at 300 ppm on PND 70, this did not correlate with increased kidney weight and was not really different from controls on PND 139.  One would expect the degeneration to be worse after a prolonged exposure.  There is clear correlation in both sexes at 800/600 ppm and at both time points.

A few typos were identified subsequent to  the finalization of the DER, which include: (1) in the paragraph for P1 adult rats on page 3, it should have indicated that no alterations were observed in estrous cycle pattern in the P1 females rather than F1 females; (2) page 50, first line should read from PND 21-69 (not PND 21-56).


[Federal Register Volume 77, Number 87 (Friday, May 4, 2012)]
[Notices]
[Pages 26554-26555]
[FR Doc No: 2012-10819]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-E-0113]

Determination of Regulatory Review Period for Purposes of Patent
Extension; GILENYA

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) has determined the
regulatory review period for GILENYA and is publishing this notice of
that determination as required by law. FDA has made the determination
because of the submission of an

application to the Director of Patents and Trademarks, Department of
Commerce, for the extension of a patent which claims that human drug
product.

ADDRESSES: Submit electronic comments to
http:[sol][sol]www.regulations.gov. Submit written petitions along with
three copies and written comments to the Division of Dockets Management
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Beverly Friedman, Office of Regulatory
Policy, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, rm. 6284, Silver Spring, MD 20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: The Drug Price Competition and Patent Term
Restoration Act of 1984 (Pub. L. 98-417) and the Generic Animal Drug
and Patent Term Restoration Act (Pub. L. 100-670) generally provide
that a patent may be extended for a period of up to 5 years so long as
the patented item (human drug product, animal drug product, medical
device, food additive, or color additive) was subject to regulatory
review by FDA before the item was marketed. Under these acts, a
product's regulatory review period forms the basis for determining the
amount of extension an applicant may receive.
    A regulatory review period consists of two periods of time: A
testing phase and an approval phase. For human drug products, the
testing phase begins when the exemption to permit the clinical
investigations of the drug becomes effective and runs until the
approval phase begins. The approval phase starts with the initial
submission of an application to market the human drug product and
continues until FDA grants permission to market the drug product.
Although only a portion of a regulatory review period may count toward
the actual amount of extension that the Director of Patents and
Trademarks may award (for example, half the testing phase must be
subtracted as well as any time that may have occurred before the patent
was issued), FDA's determination of the length of a regulatory review
period for a human drug product will include all of the testing phase
and approval phase as specified in 35 U.S.C. 156(g)(1)(B).
    FDA recently approved for marketing the human drug product GILENYA
(fingolimod). GILENYA is indicated for treatment of patients with
relapsing forms of multiple sclerosis to reduce the frequency of
clinical exacerbations and to delay the accumulation of physical
disability. Subsequent to this approval, the Patent and Trademark
Office received a patent term restoration application for GILENYA (U.S.
Patent No. 5,604,229) from Novartis Pharmaceuticals Corp., and the
Patent and Trademark Office requested FDA's assistance in determining
this patent's eligibility for patent term restoration. In a letter
dated April 25, 2011, FDA advised the Patent and Trademark Office that
this human drug product had undergone a regulatory review period and
that the approval of GILENYA represented the first permitted commercial
marketing or use of the product. Thereafter, the Patent and Trademark
Office requested that FDA determine the product's regulatory review
period.
    FDA has determined that the applicable regulatory review period for
GILENYA is 4,296 days. Of this time, 4,021 days occurred during the
testing phase of the regulatory review period, while 275 days occurred
during the approval phase. These periods of time were derived from the
following dates:
    1. The date an exemption under section 505(i) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 355(i)) became
effective: December 19, 1998. The applicant claims December 25, 1998,
as the date the investigational new drug application (IND) became
effective. However, FDA records indicate that the IND effective date
was December 19, 1998, which was 30 days after FDA receipt of the IND.
    2. The date the application was initially submitted with respect to
the human drug product under section 505(b) of the FD&C Act: December
21, 2009. The applicant claims December 18, 2009, as the date the new
drug application (NDA) for GILENYA (NDA 22-527) was initially
submitted. However, FDA records indicate that NDA 22-527 was submitted
on December 21, 2009.
    3. The date the application was approved: September 21, 2010. FDA
has verified the applicant's claim that NDA 22-527 was approved on
September 21, 2010.
    This determination of the regulatory review period establishes the
maximum potential length of a patent extension. However, the U.S.
Patent and Trademark Office applies several statutory limitations in
its calculations of the actual period for patent extension. In its
application for patent extension, this applicant seeks 5 years of
patent term extension.
    Anyone with knowledge that any of the dates as published are
incorrect may submit to the Division of Dockets Management (see
ADDRESSES) either electronic or written comments and ask for a
redetermination by July 3, 2012. Furthermore, any interested person may
petition FDA for a determination regarding whether the applicant for
extension acted with due diligence during the regulatory review period
by October 31, 2012. To meet its burden, the petition must contain
sufficient facts to merit an FDA investigation. (See H. Rept. 857, part
1, 98th Cong., 2d sess., pp. 41-42, 1984.) Petitions should be in the
format specified in 21 CFR 10.30.
    Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) electronic or written comments and written petitions.
It is only necessary to send one set of comments. However, if you
submit a written petition, you must submit three copies of the
petition. Identify comments with the docket number found in brackets in
the heading of this document.
    Comments and petitions that have not been made publicly available
on http:[sol][sol]www.regulations.gov may be viewed in the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: April 16, 2012.
Jane A. Axelrad,
Associate Director for Policy, Center for Drug Evaluation and Research.
[FR Doc. 2012-10819 Filed 5-3-12; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register Volume 85, Number 179 (Tuesday, September 15, 2020)]
[Notices]
[Pages 57203-57204]
[FR Doc No: 2020-20322]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings #1

    Take notice that the Commission received the following electric
rate filings:
    Docket Numbers: ER20-2069-000.
    Applicants: Wheatridge Wind Energy, LLC.
    Description: Second Amendment to June 16, 2020 Wheatridge Wind
Energy, LLC tariff filing.
    Filed Date: 9/3/20.
    Accession Number: 20200903-5212.
    Comments Due: 5 p.m. ET 9/14/20.

    Docket Numbers: ER20-2070-000.
    Applicants: Wheatridge Wind II, LLC.
    Description: Second Amendment to June 16, 2020 Wheatridge Wind II,
LLC tariff filing.
    Filed Date: 9/3/20.
    Accession Number: 20200903-5213.
    Comments Due: 5 p.m. ET 9/14/20.

    Docket Numbers: ER20-2108-001.
    Applicants: Great Bay Solar II, LLC.
    Description: Tariff Amendment: Deficiency Response (ER20-2108) to
be effective 8/18/2020.
    Filed Date: 9/4/20.
    Accession Number: 20200904-5152.
    Comments Due: 5 p.m. ET 9/25/20.

    Docket Numbers: ER20-2611-001.
    Applicants: Southwest Power Pool, Inc.
    Description: Tariff Amendment: 3723 Southwestern Power Admin/WFEC
Inter Agr-Amended Filing to be effective 8/1/2020.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5059.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2816-000.
    Applicants: PacifiCorp.
    Description: Supplemental Information in Compliance with September
4, 2020 Order on Emergency Waiver Petition of PacifiCorp.
    Filed Date: 9/8/20.
    Accession Number: 20200908-5223.
    Comments Due: 5 p.m. ET 9/29/20.

    Docket Numbers: ER20-2837-000.
    Applicants: Public Service Company of Colorado.
    Description: Sec.  205(d) Rate Filing: KEPCO_effective 1.1.21 to be
effective 1/1/2021.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5000.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2838-000.
    Applicants: California Independent System Operator Corporation.
    Description: Sec.  205(d) Rate Filing: 2020-09-09 Transferred
Frequency Response Agreement--Tucson Electric Power to be effective 12/
1/2020.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5003.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2839-000.
    Applicants: Inova Energy LLC.
    Description: Baseline eTariff Filing: Inova Energy LLC Market Based
Rate Filing to be effective 11/8/2020.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5005.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2840-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Sec.  205(d) Rate Filing: Original ISA No. 5744; Queue
No. AF1-324 to be effective 8/10/2020.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5069.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2841-000.
    Applicants: Southern California Edison Company.
    Description: Sec.  205(d) Rate Filing: Second Amended LGIA Maverick
Solar Maverick Solar 4 EDF Renewables Almasol Gen to be effective 9/10/
2020.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5077.
    Comments Due: 5 p.m. ET 9/30/20.

    Docket Numbers: ER20-2842-000.
    Applicants: Thunderhead Wind Energy LLC.

    Description: Request for Prospective Tariff Waiver, et al. of
Thunderhead Wind Energy LLC.
    Filed Date: 9/9/20.
    Accession Number: 20200909-5107.
    Comments Due: 5 p.m. ET 9/30/20.
    The filings are accessible in the Commission's eLibrary system
(https://elibrary.ferc.gov/idmws/search/fercgensearch.asp) by querying
the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and 385.214) on or before 5:00
p.m. Eastern time on the specified comment date. Protests may be
considered, but intervention is necessary to become a party to the
proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER>
(toll free). For TTY, call<PHONE_NUMBER>.

    Dated: September 9, 2020.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2020-20322 Filed 9-14-20; 8:45 am]
BILLING CODE 6717-01-P


  SEQ CHAPTER \h \r 1 ICR SUPPORTING STATEMENT OUTLINE

Part A

1.  Introduction to Part A  TC \l2 "Introduction to Part A
Identification of the Information Collection

1(a) Title of the Information Collection

Confidential Financial Disclosure Form 3110.48 for Special Government
Employees (SGE) Serving on Federal Advisory Committees at the
Environmental Protection Agency

1(b) Short Characterization/Abstract

The purpose of this information collection request is to assist the
United States Environmental Protection Agency (EPA or the Agency) in
selecting Federal advisory committee members who will be appointed as
Special Government Employees (SGEs), mostly to EPA’s scientific and
technical committees.  To select SGE members as efficiently and cost
effectively as possible, the  Agency needs to evaluate potential
conflicts of interest before a candidate is hired as an SGE and
appointed as a member to a committee by EPA’s Administrator or Deputy
Administrator.

 Agency officials developed  the “Confidential Financial Disclosure
Form for Special Government Employees Serving on Federal Advisory
Committees at the U.S. Environmental Protection Agency,” also referred
to as Form 3110-48, for a greater inclusion of information to discover
any potential conflicts of interest as recommended by the Government
Accountability Office.

2. Need for and use of the Collection

2(a) Need/Authority for the Collection

In June 2001, the Government Accountability Office (GAO) issued a report
entitled “EPA’s Science Advisory Board Panels – Improved Policies
and Procedures Needed to Ensure Independence and Balance.”  GAO
recommended that EPA develop policies and procedures that better
identify and mitigate potential conflicts of interest and support the
development of balanced panels.  Recommendations included gathering the
required conflict of interest information before a member is selected,
specifically:

Determine whether each panel will be reviewing a “particular matter”
before selecting the panel in order to identify the financial
conflict-of-interest requirements, if any, to which the panelists will
be subject.

Obtain and evaluate relevant background information on peer review panel
candidates before appointing panel members.  The evaluation should
include explicitly discussing with potential panelists: (1) items not
adequately reported on the confidential financial disclosure form as
well as items reported that could present conflicts of interest; (2)
other information relevant to assessing impartiality, such as research
conducted and previous public statements or positions on the matter
being reviewed, interest of the employer or clients in the matter,
participation in legal proceedings, work for chemical companies or other
affected industries, and prior or current research grants that could be
affected by the matter; and (3) whether they have any potential
conflicts of interest related to the specific panel being established.
Further, pertinent information obtained from discussions with panelists
should be documented.”

As part of that effort to respond to GAO’s recommendations, EPA
developed a new and improved form for all of its scientific and
technical committee’s Special Government Employees.

	EPA’s Designated Federal Officers (DFOs) who manage EPA Federal
Advisory Committees (FACs) experienced great difficulty trying to use
the OGE Form 450 to identify actual or potential conflicts of interest
of potential candidates for Federal Advisory Committee membership.  The
OGE Form 450 was confusing for the proposed members and they did not
identify all financial interests of possible concern.  In response to
the GAO’s recommendations, EPA developed the Form 3110-48 to ensure
that all relevant financial interests are identified and considered
during the member selection process.   It is important for EPA to have
this information collection in place because we continuously need to
appoint new SGE members as new advisory committees are created or as
members’ terms of appointment expire.

The Form 3110-48 is completed by candidates for membership as SGEs on
EPA federal advisory committees.  The form is completed as part of the
member selection process and before they are invited to serve as a
member of a FAC at EPA.  The Form 3110-48 is reviewed by the
Committee’s Designated Federal Officer, and the Program Office Deputy
Ethics Official (DEO) to determine whether there is a financial conflict
of interest between the proposed member’s public responsibilities and
private interests/activities and whether there is any appearance of a
lack of impartiality.  In some cases, the Alternate Designated Agency
Ethics Official also reviews the form.  As GAO recommended, it is
important to collect this information before the potential member is
appointed to the advisory committee, because if a conflict of interest
is identified after the person is appointed, the Agency may have to
terminate the person’s membership and identify another person to serve
on the committee.  This is potentially embarrassing to both the Agency
and the appointed member. It is also important to know upfront that a
candidate could serve if appointed, as the appointment process is time
consuming and, as required by the Federal Advisory Committee Act, the
Agency must ensure that the advisory committee is balanced in the points
of view represented.  If a conflict is identified after a person is
appointed to an advisory committee as an SGE, additional time is needed
to select a replacement and the Agency loses valuable time and expertise
in receiving the advice it needs.   Also important is the fact that
finding replacement members creates a burden of additional cost and
staff hours.  Using the Form 3110-48 benefits EPA by increasing
efficiency and saving time and money.

Currently nine of EPA’s 22 Federal Advisory Committees (FACs) appoint
members as SGEs and have need to use the Form 3110-48.  This number may
increase as new committees are added, or decrease as committees are
terminated.  EPA anticipates averaging approximately 257 SGEs during the
next 3 years.

Again, it is imperative that Form 3110-48 be approved to satisfy the GAO
recommendations that EPA gather the required Conflict of Interest
information before a member is selected to improve the EPA’s policies
and procedures to better identify and mitigate potential conflicts of
interest and support the development of balanced membership.  EPA must
have this information collection in place so that the EPA doesn’t lose
continuity in appointing new Special Government (SGE) members, as new
advisory committees are created, or as members’ terms of appointment
expire.  If a conflict is identified after an SGE is appointed to an
advisory committee, the SGE and the EPA face embarrassment and
additional time is needed to select a replacement while EPA loses
valuable time and expertise.  Using the Form 3110-48 before member
appointments are made benefits EPA by increasing efficiency, thus saving
time and money.

Confidentiality of Information provided on the Form 3110-48:

Title I of the Ethics in Government Act of 1978 (the Act), 5 USC App.,
Executive Order 12674, and 5 CFR Part 2634, Subpart I, of the Office of
Government Ethics regulations require the reporting of financial
information that is relevant to the administration and application of
the criminal financial conflict of interest laws, administrative
standards of conduct, and agency-specific statutory and program-related
restrictions.  The primary use of the information collected on this form
is to allow EPA to conduct the conflicts reviews in accordance with
applicable Federal laws and regulations.  The information reported on
the Form 3110-48 is “confidential” and required to be withheld from
the public pursuant to Section 107(a) of the Act.  Agency personnel
shall not publicly release the reports on the information contained
therein except that disclosures may be pursuant to (1) a Federal, State
or local law enforcement agency if the disclosing agency becomes aware
of a violation or potential violation of law or regulation; (2) a court
or party in a court or Federal administrative proceeding if the
Government is a party or in order to comply with a judge-issued
subpoena; (3) a source when necessary to obtain information relevant to
a conflict of interest investigation or decision; (4) the National
Archives and Records Administration or the General Services
Administration in records management inspections; (5) the Office of
Management and Budget during legislative coordination on private relief
legislation; and (6) in response to a request for discovery or for the
appearance of a witness in a judicial or administrative proceeding, if
the information is relevant to the subject matter. The confidential
report will not be disclosed to any requesting person unless authorized
by law.

EPA requires SGEs who are new to a federal advisory committee to
complete parts 2-9 of Form 3110-48 before participating in a Committee
activity.  Subsequently, SGEs must file reports annually to report on
the previous calendar year.  For these annual reports, the SGEs must
complete parts 2-8.  In addition, they must complete Part 1
(“Statement regarding any change since annual submission of the
form”) and Part 9 (“Identification of any other information related
to conflicts of interest or appearance of a lack of impartiality”)
before participating in any new advisory activity.  Filers must provide
sufficient information about outside interests and activities so that
EPA DFOs and ethics officials can make an informed judgment regarding
any conflict of interest or appearance of lack of impartiality. EPA
staff may contact proposed SGEs to obtain additional information if
necessary to determine whether there is a conflict between an SGE’s
public responsibilities and his /her or his/her spouse's private
interests and activities.

EPA seeks to collect the information in “Attachment A,” which is the
Confidential Financial Disclosure for Special Government Employees
Serving on Federal Advisory Committees at the U.S. Environmental
Protection Agency (Form 3110-48).  This information collection request
will be needed on a continual basis.

Again, it is imperative that Form 3110-48 be approved to satisfy the GAO
recommendations that EPA gather the required Conflict of Interest
information before a member is selected to improve the EPA’s policies
and procedures to better identify and mitigate potential conflicts of
interest and support the development of balanced membership.  EPA must
have this information collection in place so that the EPA doesn’t lose
continuity in appointing new Special Government (SGE) members, as new
advisory committees are created, or as members’ terms of appointment
expire.  If a conflict is identified after an SGE is appointed to an
advisory committee, the SGE and the EPA face embarrassment and
additional time is needed to select a replacement while EPA loses
valuable time and expertise.  Using the Form 3110-48 before member
appointments benefits EPA by increasing efficiency, thus saving time and
money.

2(b) Practical Utility/Users of the Data

	Information gathered from Form 3110-48 will continuously help EPA to
evaluate relevant background information on Special Government Employee
candidates before appointing members.  By using the form, EPA DFOs are
allowed to expedite the process of selecting viable candidates for
membership on EPA’s federal advisory committees.

3. Non duplication, Consultations, and Other Collection Criteria

3(a) Non duplication

	Almost all information request from respondents under this ICR is
personal in nature and, in most cases, is not available from other
sources.

3(b) Public Notice Required Prior to ICR submission to OMB

	On November 24, 2010 (75 FR 71687) EPA sought comments on this ICR
pursuant to 5 CFR 1320.8(d).  EPA received no comments. A second comment
will be opened for 30-days once this ICR is submitted to OMB.

3(c) Consultations

	In accordance with OMB’s Terms of Clearance on the previous approval
of this ICR, EPA has reviewed the actual number of SGE confidential
disclosure forms received over the last three years and consulted with
various agency staff to determine trends in expected committee
membership over the next three years. While committee membership can
vary year to year, EPA anticipates that the number of SGEs completing
the form during the period of this ICR will not vary significantly from
the previous three-year average, which was 257 per year.

3(d) Effects of Less Frequent Collection

	The form is required to be updated once a year.  The form allows
Government officials to determine whether there is a statutory conflict
between Special Government Employees public responsibilities and private
interests and activities, or the appearance of a lack of impartiality,
as defined by federal regulation.

18 U.S.C. 208: “An employee is prohibited from participating
personally and substantially in an official capacity in any particular
matter in which, to his knowledge, he or any person whose interests are
imputed to him under this statute has a financial interest, if the
particular matter will have a direct and predictable effect on that
interest.”

5 C.F.R. 2635.502: Appearance of lack of impartiality: “Where an
employee knows that a particular matter involving specific parties is
likely to have a direct and predictable effect on the financial interest
of a member of his household, or knows that a person with whom he has a
covered relationship is or represents a party to such matter, and where
the person determines that the circumstances would cause a reasonable
person with knowledge of the relevant facts to question his impartiality
in the matter, the employee should not participate in the matter unless
he has informed the agency designee of the appearance of a problem and
received authorization from the agency designee".

3(e) General Guidelines

	This ICR complies with OMB’s general guidelines for the collection of
information.

3(f) Confidentiality

Confidentiality of Information provided on the Form 3110-48:

 Title I of the Ethics in Government Act of 1978 (the Act), 5 USC App.,
Executive Order 12674, and 5 CFR Part 2634, Subpart I, of the Office of
Government Ethics regulations require the reporting of financial
information that is relevant to the administration and application of
the criminal financial conflict of interest laws, administrative
standards of conduct, and agency-specific statutory and program-related
restrictions.  The primary use of the information collected on this form
is to allow EPA to conduct the conflicts reviews in accordance with
applicable Federal laws and regulations.  The information reported on
the Form 3110-48 is “confidential” and required to be withheld from
the public pursuant to Section 107(a) of the Act.  Agency personnel
shall not publicly release the reports on the information contained
therein except that disclosures may be pursuant to (1) a Federal, State
or local law enforcement agency if the disclosing agency becomes aware
of a violation or potential violation of law or regulation; (2) a court
or party in a court or Federal administrative proceeding if the
Government is a party or in order to comply with a judge-issued
subpoena; (3) a source when necessary to obtain information relevant to
a conflict of interest investigation or decision; (4) the National
Archives and Records Administration or the General Services
Administration in records management inspections; (5) the Office of
Management and Budget during legislative coordination on private relief
legislation; and (6) in response to a request for discovery or for the
appearance of a witness in a judicial or administrative proceeding, if
the information is relevant to the subject matter. The confidential
report will not be disclosed to any requesting person unless authorized
by law.

EPA requires SGEs who are new to a federal advisory committee to
complete parts 2-9 of Form 3110-48 before participating in a Committee
activity.  Subsequently, SGEs must file reports annually to report on
the previous calendar year.  For these annual reports, the SGEs must
complete parts 2-8.  In addition, they must complete Part 1
(“Statement regarding any change since annual submission of the
form”) and Part 9 (“Identification of any other information related
to conflicts of interest or appearance of a lack of impartiality”)
before participating in any new advisory activity.  Filers must provide
sufficient information about outside interests and activities so that
EPA DFOs and ethics officials can make an informed judgment regarding
any conflict of interest or appearance of lack of impartiality. EPA
staff may contact proposed SGEs to obtain additional information if
necessary to determine whether there is a conflict between an SGE’s
public responsibilities and his /her or his/her spouse's private
interests and activities.

EPA seeks to collect the information in “Attachment A,” which is the
Confidential Financial Disclosure for Special Government Employees
Serving on Federal Advisory Committees at the U.S. Environmental
Protection Agency (Form 3110-48).  This information collection request
will be needed on a continual basis.

Again, it is imperative that Form 3110-48 be approved to satisfy the GAO
recommendations that EPA gather the required Conflict of Interest
information before a member is selected to improve the EPA’s policies
and procedures to better identify and mitigate potential conflicts of
interest and support the development of balanced membership.  EPA must
have this information collection in place so that the EPA doesn’t lose
continuity in appointing new Special Government (SGE) members, as new
advisory committees are created, or as members’ terms of appointment
expire.  If a conflict is identified after an SGE is appointed to an
advisory committee, the SGE and the EPA face embarrassment and
additional time is needed to select a replacement while EPA loses
valuable time and expertise.  Using the Form3110-48 before member
appointments benefits EPA by increasing efficiency, thus saving time and
money.

3(g) Sensitive Questions

Title I of the Ethics in Government Act of 1978 (the Act), 5 USC App.,
Executive Order 12674, and 5 CFR Part 2634, Subpart I, of the Office of
Government Ethics regulations require the reporting of financial
information that is relevant to the administration and application of
the criminal financial conflict of interest laws, administrative
standards of conduct, and agency-specific statutory and program-related
restrictions.  The primary use of the information collected on this form
is to allow EPA to conduct the conflicts reviews in accordance with
applicable Federal laws and regulations.  The information reported on
the Form 3110-48 is “confidential” and required to be withheld from
the public pursuant to Section 107(a) of the Act.  Agency personnel
shall not publicly release the reports on the information contained
therein except that disclosures may be pursuant to (1) a Federal, State
or local law enforcement agency if the disclosing agency becomes aware
of a violation or potential violation of law or regulation; (2) a court
or party in a court or Federal administrative proceeding if the
Government is a party or in order to comply with a judge-issued
subpoena; (3) a source when necessary to obtain information relevant to
a conflict of interest investigation or decision; (4) the National
Archives and Records Administration or the General Services
Administration in records management inspections; (5) the Office of
Management and Budget during legislative coordination on private relief
legislation; and (6) in response to a request for discovery or for the
appearance of a witness in a judicial or administrative proceeding, if
the information is relevant to the subject matter. The confidential
report will not be disclosed to any requesting person unless authorized
by law.

4. The Respondents and the Information Requested

4(a) Respondents/SIC Codes

A Special Government Employee (SGE) is a person who is retained,
designated, appointed, or employed to perform, with or without
compensation, for a period not to exceed 130 days during any period of
365 consecutive days, temporary duties for the Federal Government either
on a full-time or intermittent basis.  SGEs who provide advice to EPA
are required to file the Form 3110-48 in lieu of the Office of
Government Ethics Form 450 to disclose confidential financial
information.  Form 3110-48 has already been reviewed and approved for
use by the Office of Government Ethics.

4(b) Information Requested

(i)  Data items, including record keeping requirements

The Agency will maintain records of the Form 3110-48.  Designated
Federal Officers from Offices sponsoring federal advisory committees
will retain files of the completed form.  The Agency does not anticipate
any record keeping activities on the part of the respondents under this
ICR.

	(ii) Respondent Activities

After being nominated by an outside party or themselves, respondents
will be asked to

Complete the Form 3110-48.  Forms may be mailed or e-mailed to
candidates.  Although candidates may type their information on the form
on-line, they must then print the form and sign it.  They may return the
form by mail, but may not return the form by e-mail as an original
signature is required.   Each form will involve reading instructions and
completing the form.   The form will require one hour to complete.
Subsequent forms filed annually should take less time to complete as
respondents gain familiarity with its information requirements and may
only need to make slight changes to information filed previously.

5. The Information Collected–Agency Activities, Collection
Methodology,

and Information Management

5(a) Agency Activities

To respond to this ICR, we estimated that Designated Federal Officers
(DFOs) spend one hour reviewing each Form 3110-48 (sometimes calling and
asking for further clarification or to address areas not filled out
completely).  EPA currently pays an estimated labor cost of GS 14 Step
10, which in 2011 was $65.53 per hour, rounded to $66 per hour according
to the Office of Personnel Management (  HYPERLINK
"http://www.opm.gov/oca/11tables/html/dcb_h.asp"
http://www.opm.gov/oca/11tables/html/dcb_h.asp ). Due to the 2011
federal employee pay freeze for the next 2 years and possibly beyond, we
anticipate no cost increase for the next 3 years of this ICR (2011,
2012, 2013) the 3 year average estimated cost for the DFO is $16,962.

  The EPA Deputy Ethics Official (DEO) labor cost is estimated to be a
GS-15 Step 7, which in EPA’s Emergency ICR (2010) was $71.16, rounded
to $71 per hour at one hour per form.  Due to the 2011 federal employee
pay freeze for the next 2 years and possibly beyond, we anticipate no
cost increase for the next 3 years of this ICR (2011, 2012, 2013) the 3
year average estimated cost for the DEO is $18,247.

Both DFO and DEO total labor rates below include a factor of 1.6 (60%)
for overhead costs.

DFO Cost

EPA estimates that approximately 257 advisory committee members will
serve on EPA’s Federal Advisory Committees (FACs) as SGEs over the
next 3 years.   Multiplying the number of SGE members (257) by the 3
year average dollar amount paid to EPA’s DFOs ($66), and multiplying
the subtotal cost of $16,962 by 1.6 (60% overhead) to allow for employee
overhead costs, we estimate the subtotal to be $27,139.

Year 1 @ $66 for 1 hour x 257 = $16,962 x 1.6 = $27,139

Year 2 @ $66 for 1 hour x 257 = $16,962 x 1.6 = $27,139

Year 3 @ $66 for 1 hour x 257 = $16,962 x 1.6 = $27,139

DEO Cost

Multiplying the number of SGE members (257) by the dollar amount paid to
EPA’s DEO with a 3 year average cost ($71), and multiplying the cost
of $18,247 by 1.6 (60% overhead) to allow for employee overhead costs,
we estimate the subtotal to be $29,195.

Year 1 @ $71 for 1 hour x 257 = $18,247 x 1.6 = $29,195

Year 2 @ $71 for 1 hour x 257 = $18,247 x 1.6 = $29,195

Year 3 @ $71 for 1 hour x 257 = $18,247 x 1.6 = $29,195

Total DFO and DEO Cost Using 3 Year Average

The total 3 year average dollar burden estimate for this ICR (for both
DFOs and DEO) is approximately $56,334 each year.

DFO 3 year average $27,139 + DEO 3 year average $29,195 = $56,334

Agency (EPA) activities associated with the collection of information
include:

Designated Federal Officers (DFOs) for each committee with Special
Government Employees (SGEs), Deputy Ethics Official, Assistant Deputy
Ethics Official

First internal EPA review and approval of Form 3110-48 (completed 2003)

Second internal EPA review and approval of Form 3110-48 (completed 2007)

Taking actions to review the form, ascertain improvements, and revise
periodically (approximately 3 year intervals or more if needed)

Designated Federal Officers (DFOs) for each committee with Special
Government Employees (SGEs):

Providing copies of the mandatory form

Answering any respondent questions, follow-up

Gathering respondents completed forms

Reviewing and analyzing data

Recordkeeping/storing completed form

Forwarding form to EPA’s Ethics staff for review and analyzing

Deputy Ethics Official:

First review and approval of Form 3110-48 (completed 2003)

Second review and approval of Form 3110-48 (completed 2007)

5(b) Collection Methodology and Management

	In collecting and analyzing the information associated with this ICR,
EPA will use a telephone system, personal computers, e-mail and websites
from which the respondents can obtain blank forms, as well as using the
mail and committee meetings for distribution of the form. Although
candidates (respondents) may type their information on the form on-line,
they must then print the form and sign it.  They may return the form by
mail, but may not return the form by e-mail as an original signature is
required.

	Although EPA uses internet websites and e-mail to distribute the blank
forms, this form is not a survey instrument, and no database is
necessary to aggregate results.

This information is not available to the public.

5(c) Small Entity Flexibility

	Not applicable

5(d) Collection Schedule

After being nominated by an outside party or themselves, respondents are
asked to Complete the Form 3110-48 (No schedule – dates are variable).

After the initial completion of the Form 3110-48, respondents are asked
to update the form annually (generally during January of each year).
Respondent’s confidential financial information is not made public.

6. Estimating the Burden and Cost of the Collection

6(a) Estimating Respondent Burden and Costs

	(i) Estimating Burden and Labor Costs

The respondents for this information collection request are candidates
who are willing to serve on EPA Federal Advisory Committees as Special
Government Employees (SGE). An SGE is a person who is retained,
designated, appointed, or employed to perform, with or without
compensation, for a period not to exceed 130 days during any period of
365 consecutive days, temporary duties for the Federal Government either
on a full-time or intermittent basis.  SGEs who are currently members of
EPA advisory committees must file the Form 3110-48 once a year.  In
addition as new candidates who wish to be considered for such service
must file before they are formally appointed by the EPA Administrator or
Deputy Administrator.

To respond to this ICR, we estimated that each responding SGE candidate
will take one hour to complete the Form 3110-48.  We anticipate that EPA
will pay an estimated labor cost of $66, which including the standard
overhead factor of 1.6 produces a loaded wage rate of $105.60. We
estimate that approximately 257 members of Advisory Committees will have
to respond to this request each year.   Multiplying the estimated number
of SGE members (257) by the dollar amounts to be paid to EPA’s SGEs
each successive year, and multiplying the subtotal costs of each
successive year by 1.6 to allow for respondent overhead costs, we
estimate that the total dollar burden estimate for this ICR to be
approximately $27,139 for year 1, $27,139 for year 2 and $27,139 for
year 3.  The grand total for all 3 years is estimated at $81,417.  The
annual average cost to all respondent’s cost over the three years is
$27,139, as indicated in the following annual respondent burden and cost
table.

Annual Cost for SGE Respondents

SGE Respondent

Activities to Complete Form 3110-48	Burden Hours/

Respondent

	Burden for SGE Candidate

($66 per labor hour multiplied by 1.6 for overhead equals $105.6)	Number
of Respondents per Year

	Total

Cost per

Year

Total per Year	60 minutes

(1 hour/100%)	$105.6	257	$27,139

     Read Instructions	10 minutes

(~0.17%)	(0.17 x $105.6 =)

$17.60	($17.95 x 257 =)	$4,523.20

     Fill Out Form 	48 minutes

(~0.80%	(0.80 x $105.6 =)

$84.48	($84.48 x 257 =)	$21,711.36

     Prepare Envelope to Mail                         	2 minutes

(~0.03%)	(0.03 x $105.6 =)

$3.5	($3.17 x 257 =)	$904.64

TOTAL	60 minutes	$105.60	257	$27,139.20

	(ii) Estimating Capital and Operations and Maintenance Costs

		Not applicable.

	(iii) Capital/Start-up Operating and Maintenance (O&M) Costs

		Not applicable.

	(iv) Annualizing Capital Costs

		Not Applicable

6(b) Estimating Agency Burden and Cost

Annual Agency Burden and Cost

	Agency

Hours

	Number of Hours Per Year	Labor Cost Per Year	Overhead Cost Per Year
Subtotal Labor & Overhead Cost

	Total

Cost/

Year (rounded)

Form 3110-48

DFO Activities

For 257

Respondents	$66 per hour

	Distribute form to SGE Nominees (respondents) and answer their
questions	5 minutes

(0.0833)	257	$1,413.50	$848.10	$2,261.60

	Review and analyze data of completed form, and ask follow-up  questions
45 minutes

(0.75)	257	$12,721.50	$7,632.90	$20,354.40

	Recordkeeping/

storing form 	5 minutes

(0.0833)	257	$1,413.50	$848.10	$2,261.60

	Forward form to EPA Ethics Staff	5 minutes

(0.0833	257	$1,413.50	$848.10	$2,261.60

	       DFO Subtotal	60 min./1 hour

(1.00)	257	$16,962.00	$10,177.20	$27,139.20	$27,139

DEO Activities For 257 Respondents	$71 per hour

	Review, analyze, follow-up, and approve or disapprove	60 min./1 hour

(1.00)	257	$18,247.00	$10,948.20	$29,195.20

	       DEO Subtotal     	60 min./1 hour

(1.00)	257	$18,247	$10,948	$29,195	$29,195

EPA Grand Total

(DFO & DEO)	120 min./ 2 hours

2.00	514	$35,209.00	$21,125.40	$56,334.40	$56,334

6(c) Bottom Line Burden Hours and Cost Tables

	(i) Respondent Tally

Bottom-Line Annual Burden and Cost for SGE Respondents

SGE Respondent

Activities to Complete Form 3110-48	Burden Hours/

 Respondent

	Burden for SGE Candidate

($66 per labor hour multiplied by 1.6 for overhead equals $105.6)	Number
of Respondents per Year

	Total

Cost per

Year

Total per Year	60 minutes

(1 hour/100%)	$105.6	257	$27,139

	(ii) The Agency Tally

Bottom-Line Annual Agency Burden and Cost

	Agency

Hours For Each

Review	Number of Hours Per Year	Labor Cost Per Year	Overhead Cost Per
Year	Total Agency

Cost per

Year

Agency Total

(DFO &DEO) For 300 Respondents	120 min./ 2 hours

2.00	514	$35,209	$21,125	$56,334

6(f) Reasons for Change in Burden

	There is a decrease of 43 hours in from the currently approved burden
due to more precise estimates of the number of SGEs filling out Form
3110-48, based on the average number of forms received in the last 3
years.

6(g) Burden Statement

	Burden Statement:  The annual public reporting and recordkeeping burden
for this collection of information is estimated to average one hour per
response.  Burden means the total time, effort, or financial resources
expended by persons to generate, maintain, retain, or disclose or
provide information to or for a Federal agency.  This includes the time
needed to review instructions; develop, acquire, install, and utilize
technology and systems for the purposes of collecting, validating, and
verifying information, processing and maintaining information, and
disclosing and providing information; adjust the existing ways to comply
with any previously applicable instructions and requirements; train
personnel to be able to respond to a collection of information; search
data sources; complete and review the collection of information; and
transmit or otherwise disclose the information.  An agency may not
conduct or sponsor, and a person is not required to respond to, a
collection of information unless it displays a currently valid OMB
control number.  The OMB control numbers for EPA's regulations are
listed in 40 CFR part 9 and 48 CFR chapter 15.

	To comment on the Agency's need for this information, the accuracy of
the provided burden estimates, and any suggested methods for minimizing
respondent burden, including the use of automated collection techniques,
EPA has established a public docket for this ICR under Docket ID Number
EPA-HQ-OA-2010-0757, which is available for online viewing at
HYPERLINK "http://www.regulations.gov"  www.regulations.gov , or in
person viewing at the Office of Environmental Information Docket in the
EPA Docket Center (EPA/DC), EPA West, Room 3334, 1301 Constitution
Avenue, NW, Washington, D.C.  The EPA Docket Center Public Reading Room
is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding
legal holidays.  The telephone number for the Reading Room is (202)
566-1744, and the telephone number for the Office of Environmental
Information Docket is<PHONE_NUMBER>. An electronic version of the
public docket is available at www.regulations.gov.  This site can be
used to submit or view public comments, access the index listing of the
contents of the public docket, and to access those documents in the
public docket that are available electronically.  When in the system,
select “search,” then key in the Docket ID Number identified above.
Also, you can send comments to the Office of Information and Regulatory
Affairs, Office of Management and Budget, 725 17th Street, NW,
Washington, D.C. 20503, Attention: Desk Officer for EPA.  Please include
the EPA Docket ID Number EPA-HQ-OA-2010-0757 and OMB Control No.
2090-0029 in any correspondence.


Table 1. – Summary of Possible Options for Effective Dates of PM2.5 Increments following Promulgation of this Rule

Effective Date of Final Rule	SIP Submission Deadline	SIP approval

Deadline	Implementation Date of Final Rule	Revocation of PM10 Increment

Proposed Option 1

	Federal Program

(40 CFR 52.21)	12 months  or (Requesting comment on 60 days)

_________

_________	12 months or

(Requesting comment on 60 days) or

(Requesting comment on 25 months to make it equitable with SIP approved States)

	12 months or

(Requesting comment on 60 days) or

(Requesting comment on 25 months to make it equitable with SIP approved States)

	State Program

(40 CFR 51.166)

12 months

or (Requesting comment on 60 days)

21 months

25 months	Upon EPA’s final approval	Upon EPA’s final approval

Proposed Option 2

	Federal Program	60 days	________	_________	60 days	60 days

	State Program

≤ 36 months

(Requesting comment on 21 months to make it consistent with option 1)	12 months from complete SIP submission	Upon EPA’s final approval	Upon EPA’s final approval


                DEPARTMENT OF ENVIRONMENT AND NATURAL RESOURCES

                        WATER POLLUTION CONTROL PROGRAM

                           TOXIC POLLUTANT CRITERIA

                               Chapter 74:51:01

                                  APPENDIX B

                              SEE: § 74:51:01:55

	Source: 19 SDR 111, effective January 31, 1993; transferred from Chapter 74:03:02, Appendix C, July 1, 1996; transferred from Chapter 74:51:01, Appendix A, 24 SDR 10, effective July 20, 1997; 25 SDR 98, effective January 27, 1999; 31 SDR 29, effective September 13, 2004; 35 SDR 253, effective May 12, 2009; 41 SDR 109, effective January 12, 2015; 42 SDR 103, effective January 19, 2016.

               SOUTH DAKOTA SURFACE WATER QUALITY STANDARDS[(1)]
                     FOR TOXIC POLLUTANTS - ARSD 74:51:01

Pollutant
CAS Number
                              Human Health Value
                            Concentrations in ug/L
             Freshwater Aquatic Life Value Concentrations in ug/L
                               Uses 2-3-4-5-6-9

Use
1[(2)]
Uses
2-3-4-5-6-9[(3)]
Acute
(CMC)
Chronic
(CCC)
Acenaphthene
                                                                          83329
                                      670
                                      990

Acenaphthylene (PAH)[(6)]
                                                                         208968

Acrolein
                                                                         107028
                                       6
                                       9
                                       3
                                       3
Acrylonitrile[(][4)]
                                                                         107131
                                     0.051
                                     0.25

Aldrin[(][4][)]
                                                                         309002
                                   0.000049
                                   0.000050
                                      3.0

Anthracene (PAH)[(][5][)]
                                                                         120127
                                     8,300
                                    40,000

Antimony
                                                                        7440360
                                      5.6
                                      640

Arsenic[(4)]
                                                                        7440382
                                0.018[(4)(11)]
                                 0.14[(4)(11)]
                                      340
                                      150
Asbestos[(4)]
                                                                        1332214
                              7,000,000 fibers/L

alpha-BHC[(4)]
                                                                         319846
                                    0.0026
                                    0.0049

beta-BHC[(4)]
                                                                         319857
                                    0.0091
                                     0.017

gamma-BHC (Lindane)[(4)]
                                                                          58899
                                     0.98
                                      1.8
                                     0.95

Benzene[(4)]
                                                                          71432
                                      2.2
                                      51

Benzidine[(4)]
                                                                          92875
                                   0.000086
                                    0.00020

Benzo(a)Anthracene[(4)]
                                                                          56553
                                    0.0038
                                     0.018

Benzo(a)Pyrene[(4)]
                                                                          50328
                                    0.0038
                                     0.018

Benzo(b)Fluoroanthene[(4)]
                                                                         205992
                                    0.0038
                                     0.018

Benzo(k)Flouroanthene[(4)]
                                                                         207089
                                    0.0038
                                     0.018

Beryllium[(4)]
                                                                        7440417
                                       4

Bis(2-Chloroethyl)Ether[(4)]
                                                                         111444
                                     0.030
                                     0.53

Bis(2-Chloroisopropyl)Ether[(4)]
                                                                         108601
                                     1,400
                                    65,000

Bis(2-Ethylhexyl)Phthalate[(4)]
                                                                         117817
                                      1.2
                                      2.2

Bromoform[(5)]
                                                                          75252
                                      4.3
                                      140

Butylbenzyl Phthalate
                                                                          85687
                                     1,500
                                     1,900

Cadmium
                                                                        7440439

                                   2.0[(7)]
                                   0.25[(7)]
Carbon Tetrachloride[(4)]
                                                                          56235
                                     0.23
                                      1.6

Chlordane[(4)]
                                                                          57749
                                    0.00080
                                    0.00081
                                      2.4
                                    0.0043
Chlorine
                                                                        7782505

                                      19
                                      11
Chlorobenzene
                                                                         108907
                                      130
                                     1,600

Chlorodibromomethane[(4)]
                                                                         124481
                                     0.40
                                      13

Chloroform[(4)]
                                                                          67663
                                      5.7
                                      470

2-Chloronaphthalene
                                                                          91587
                                     1,000
                                     1,600

2-Chlorophenol
                                                                          95578
                                      81
                                      150

Chromium(III)
                                                                       16065831

                                   570[(7)]
                                    74[(7)]
Chromium(VI)
                                                                       18540299

                                      16
                                      11
Chrysene[(4)]
                                                                         218019
                                    0.0038
                                     0.018

Copper
                                                                        7440508
                                     1,300

                                    13[(7)]
                                   9.0[(7)]
Cyanide (weak acid dissociable)
                                                                          57125
                                      140
                                      140
                                      22
                                      5.2
4,4'-DDD[(4)]
                                                                          72548
                                    0.00031
                                    0.00031

4,4'-DDE[(4)]
                                                                          72559
                                    0.00022
                                    0.00022

4,4'-DDT[(4)]
                                                                          50293
                                    0.00022
                                    0.00022
                                      1.1
                                     0.001
Dibenzo(a,h)Anthracene[(4)]
                                                                          53703
                                    0.0038
                                     0.018

1,2-Dichlorobenzene
                                                                          95501
                                      420
                                     1,300

1,3-Dichlorobenzene
                                                                         541731
                                      320
                                      960

1,4-Dichlorobenzene
                                                                         106467
                                      63
                                      190

3,3'-Dichlorobenzidine[(4)]
                                                                          91941
                                     0.021
                                     0.028

Dichlorobromomethane[(5)]
                                                                          75274
                                     0.55
                                      17

1,2-Dichloroethane[(4)]
                                                                         107062
                                     0.38
                                      37

1,1-Dichloroethylene[(4)]
                                                                          75354
                                      330
                                     7,100

2,4-Dichlorophenol
                                                                         120832
                                      77
                                      290

1,2-Dichloropropane[(4)]
                                                                          78875
                                     0.50
                                      15

1,3-Dichloropropene
                                                                         542756
                                     0.34
                                      21

Dieldrin[(4)]
                                                                          60571
                                   0.000052
                                   0.000054
                                     0.24
                                     0.056
Diethyl Phthalate
                                                                          84662
                                    17,000
                                    44,000

2,4-Dimethylphenol
                                                                         105679
                                      380
                                      850

Dimethyl Phthalate
                                                                         131113
                                    270,000
                                   1,100,000

Di-n-Butyl-Phthalate
                                                                          84742
                                     2,000
                                     4,500

2-Methyl-4,6-Dinitrophenol
                                                                         534521
                                      13
                                      280

2,4-Dinitrophenol
                                                                          51285
                                      69
                                     5,300

Dioxin (2,3,7,8-TCDD)[(4)]
                                                                        1746016
                                    5.0E-9
                                    5.1E-9

2,4-Dinitrotoluene[(4)]
                                                                         121142
                                     0.11
                                      3.4

1,2-Diphenylhydrazine[(4)]
                                                                         122667
                                     0.036
                                     0.20

alpha-Endosulfan
                                                                         959988
                                      62
                                      89
                                     0.22
                                     0.056
beta-Endosulfan
                                                                       33213659
                                      62
                                      89
                                     0.22
                                     0.056
Endosulfan Sulfate
                                                                        1031078
                                      62
                                      89

Endrin
                                                                          72208
                                     0.059
                                     0.060
                                     0.086
                                     0.036
Endrin Aldehyde
                                                                        7421934
                                     0.29
                                     0.30

Ethylbenzene
                                                                         100414
                                      530
                                     2,100

Fluoranthene
                                                                         206440
                                      130
                                      140

Fluorene[(5)]
                                                                          86737
                                     1,100
                                     5,300

Heptachlor[(4)]
                                                                          76448
                                   0.000079
                                   0.000079
                                     0.52
                                    0.0038
Heptachlor epoxide[(4)]
                                                                        1024573
                                   0.000039
                                   0.000039
                                     0.52
                                    0.0038
Hexachlorobenzene[(4)]
                                                                         118741
                                    0.00028
                                    0.00029

Hexachlorobutadiene[(4)]
                                                                          87683
                                     0.44
                                      18

Hexachlorocyclopentadiene
                                                                          77474
                                      40
                                     1,100

Hexachloroethane[(4)]
                                                                          67721
                                      1.4
                                      3.3

Ideno(1,2,3-cd)Pyrene
                                                                         193395
                                    0.0038
                                     0.018

Isophorone[(4)]
                                                                          78591
                                      35
                                      960

Lead
                                                                        7439921

                                    65[(7)]
                                   2.5[(7)]
Mercury
                                                                        7439976
                                     0.050
                                     0.051
                                      1.4
                                   0.77[(8)]
Methyl Bromide
                                                                          74839
                                      47
                                     1,500

Methyl Chloride[(5)]
                                                                          74873

Methylene Chloride[(4)]
                                                                          75092
                                      4.6
                                      590

Methylmercury
                                                                       22967926

                                   0.3 mg/kg

N-Nitrosodimethylamine[(4)]
                                                                          62759
                                    0.00069
                                      3.0

N-Nitrosodi-n-Propylamine[(4)]
                                                                         621647
                                    0.0050
                                     0.51

N-Nitrosodiphenylamine[(4)]
                                                                          86306
                                      3.3
                                      6.0

Nickel
                                                                        7440020
                                      610
                                     4,600
                                   470[(7)]
                                    52[(7)]
Nitrobenzene
                                                                          98953
                                      17
                                      690

Nonylphenol
                                                                       84852153

                                      28
                                      6.6
Polychlorinated Biphenyls, PCBs[(4)(9)]

                                   0.000064

                                   0.000064

                                     0.014
Pentachlorophenol
                                                                          87865
                                     0.27
                                      3.0
                                    19[(6)]
                                    15[(6)]
Phenanthrene[(5)]
                                                                          85018

Phenol
                                                                         108952
                                    10,000
                                    860,000

Pyrene[(5)]
                                                                          12900
                                      830
                                     4,000

Selenium
                                                                        7782492
                                      170
                                     4,200
                                    [(10)]
                                   5.0[(8)]
Silver
                                                                        7440224

                                   3.2[(7)]

1,2,4-Trichlorobenzene
                                                                         120821
                                      35
                                      70

1,1,2,2-Tetrachloroethane[(4)]
                                                                          79345
                                     0.17
                                      4.0

Tetrachloroethylene[(5)]
                                                                         127184
                                     0.69
                                      3.3

Thallium
                                                                        7440280
                                     0.24
                                     0.47

Toluene
                                                                         108883
                                     1,300
                                    15,000

Toxaphene[(4)]
                                                                        8001352
                                    0.00028
                                    0.00028
                                     0.73
                                    0.0002
1,2-Trans-Dichloroethylene
                                                                         156605
                                      140
                                    10,000

1,1,1-Trichloroethane
                                                                          71556

1,1,2-Trichloroethane[(4)]
                                                                          79005
                                     0.59
                                      16

Trichloroethylene[(4)]
                                                                          79016
                                      2.5
                                      30

2,4,6-Trichlorophenol[(4)]
                                                                          88062
                                      1.4
                                      2.4

Vinyl Chloride[(4)]
                                                                          75014
                                     0.025
                                      2.4

Zinc
                                                                        7440666
                                     7,400
                                    26,000
                                   120[(7)]
                                   120[(7)]

                                 SOUTH DAKOTA
                    Surface Water Quality Standards[(][1)]
                             for Toxic Pollutants

[(1)]	The aquatic life values for arsenic, cadmium, chromium (III), chromium (VI), copper, lead, mercury (acute), nickel, selenium, silver and zinc given in this document refer to the dissolved amount of each substance unless otherwise noted. All surface water discharge permit effluent limits for metals shall be expressed and measured in accordance with § 74:52:03:16.

[(2)]	Based on two routes of exposure - ingestion of contaminated aquatic organisms and drinking water.

[(3)]	Based on one route of exposure - ingestion of contaminated aquatic organisms only.

[(4)]	Substance classified as a carcinogen with the value based on an incremental risk of one additional instance of cancer in one million persons (10[-6]).

[(5)]	Chemicals which are not individually classified as carcinogens but which are contained within a class of chemicals with carcinogenicity as the basis  for the criteria derivation for that class of chemicals; an individual carcinogenicity assessment for these chemicals is pending.

[(6)]	pH-dependent criteria.  Value given is an example only and is based on a pH of 7.8.  Criteria for each case must be calculated using the following equation taken from National Recommended Water Quality Criteria: 2002 (EPA-822-R-02-047, November 2002):

	Pentachlorophenol (PCP), ug/L
	Chronic = e[1.005(pH) - 5.134]			Acute = e[1.005(pH) - 4.869]

[(7)]	Hardness-dependent criteria in ug/L.  Value given is an example only and is based on a CaCO3 hardness of 100 mg/L.  Criteria for each case must be calculated using the following equations taken from National Recommended Water Quality Criteria: http://water.epa.gov/scitech/swguidance/standards/criteria/current/index.cfm#hhtable, June 2013:

	Cadmium, ug/L
	Chronic = (*0.909)e(0.7409[ln(hardness)]-4.719)	Acute = (*0.944)e(1.0166[ln(hardness)]-3.924)

	*Conversion factors are hardness-dependent. The values shown are with a hardness of 100 mg/L as calcium carbonate (CaCO3). Conversion factors (CF) for any hardness can be calculated using the following equations:
		Chronic:  CF = 1.101672 - [(ln hardness)(0.041838)]
		Acute:  CF = 1.136672 - [(ln hardness)(0.041838)]

	Chromium (III), ug/L
	Chronic = (0.860)e(0.8190[ln(hardness)]+0.6848)	Acute = (0.316)e(0.8190[ln(hardness)]+3.7256)

	Copper, ug/L
	Chronic = (0.960)e(0.8545[1n(hardness)]-1.702)		Acute = (0.960)e(0.9422[ln(hardness)]-1.700)

	Lead, ug/L
	Chronic = (*0.791)e(1.273[ln(hardness)]-4.705)		Acute = (*0.791)e(1.273[ln(hardness)]-1.460)

	*Conversion factors are hardness-dependent. The values shown are with a hardness of 100 mg/L as calcium carbonate (CaCO3). Conversion factors (CF) for any hardness can be calculated using the following equations:
		Acute and Chronic:  CF = 1.46203 - [(ln hardness)(0.145712)]

	Nickel, ug/L
	Chronic = (0.997)e(0.8460[ln(hardness)]+0.0584)	Acute = (0.998)e(0.8460[ln(hardness)]+2.255)

	Silver, ug/L
								Acute = (0.85)e(1.72[ln(hardness)]-6.59)

	Zinc, ug/L
	Chronic = (0.986)e(0.8473[ln(hardness)]+0.884)	Acute = (0.978)e(0.8473[ln(hardness)]+0.884)

[(8)]	These criteria are based on the total-recoverable fraction of the metal.

[(9)]	This criterion applies to total pcbs, (e.g. the sum of congener or all isomer or homolog or Aroclor analyses).

[(10)]	The (0.996)CMC = 1/[fl/CMC1) + (f2/CMC2)] where f1 and f2 are the fractions of total selenium that are treated as selenite and selenate, respectively, and CMC1 and CMC2 are 185.9 g/L and 12.82 g/L, respectively.

[(11)]	This criterion for arsenic refers to the inorganic form only.