Federal Register / Vol. 77, No. 201 / Wednesday, October 17, 2012 / Proposed Rules 63783 

population who, as a result of their 

location, cultural practices, or other 

factors, may have atypical or 

disproportionately high and adverse 

human health impacts or environmental 

effects from exposure to the pesticides 

discussed in this document, compared 

to the general population. 

II. What action is the Agency taking? 

EPA is announcing receipt of a 

pesticide petition filed under section 

408 of the Federal Food, Drug, and 

Cosmetic Act (FFDCA), (21 U.S.C. 346a), 

requesting the establishment or 

modification of regulations in 40 CFR 

part 180 for residues of pesticide 

chemicals in or on the food commodity, 

wheat, grain. The Agency is taking 

public comment on the request before 

responding to the petitioner. EPA is not 

proposing any particular action at this 

time. EPA has determined that the 

pesticide petition described in this 

document contains data or information 

prescribed in FFDCA section 408(d)(2); 

however, EPA has not fully evaluated 

the sufficiency of the submitted data at 

this time or whether the data supports 

granting of the pesticide petition. After 

considering the public comments, EPA 

intends to evaluate whether and what 

action may be warranted. Additional 

data may be needed before EPA can 

make a final determination on this 

pesticide petition. 

Pursuant to 40 CFR 180.7(f), a 

summary of the petition that is the 

subject of this document, prepared by 

the petitioner, is included in a docket 

EPA has created for this rulemaking. 

The docket for this petition is available 

online at http://www.regulations.gov. 

As specified in FFDCA section 

408(d)(3), (21 U.S.C. 346a(d)(3)), EPA is 

publishing notice of the petition so that 

the public has an opportunity to 

comment on this request for the 

establishment or modification of 

regulations for residues of pesticides in 

or on the food commodity, wheat, grain. 

Further information on the petition may 

be obtained through the petition 

summary referenced in this unit. 

EPA has received a pesticide petition 

(PP #1F7955) from Syngenta Crop 

Protection, LLC, P.O. Box 18300, 

Greensboro, NC 27419 proposing, 

pursuant to section 408(d) of FFDCA, 21 

U.S.C. 346a(d), to amend 40 CFR 

180.559 by amending the tolerances for 

residues of the herbicide, clodinafoppropargyl (propanoic acid, 2-[4-(5- 

chloro-3-fluoro-2- 

pyridinyl)oxy]phenoxy]-,2-propynyl 

ester, (2R)-) and its acid metabolite 

(propanoic acid, 2-[4-[5-chloro-3-fluoro2-pyridinyl)oxy]phenoxy]-, (2R)-), in or 

on the raw agricultural commodity 

wheat, grain from 0.1 parts per million 

(ppm) to 0.02 ppm. 

List of Subjects 

Environmental protection, 

Agricultural commodities, Feed 

additives, Food additives, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: October 4, 2012. 

Lois Rossi, 

Registration Division, Office of Pesticide 

Programs. 

[FR Doc. 2012–25549 Filed 10–16–12; 8:45 am] 

BILLING CODE 6560–50–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

42 CFR Part 73 

[Docket: CDC–2012–0010] 

Influenza Viruses Containing the 

Hemagglutinin from the Goose/ 

Guangdong/1/96 Lineage 

AGENCY: Centers for Disease Control and 

Prevention (CDC), Department of Health 

and Human Services (HHS). 

ACTION: Request for information and 

comment. 

SUMMARY: The Centers for Disease 

Control and Prevention (CDC) within 

the Department of Health and Human 

Services (HHS) announces the opening 

of a docket to obtain information and 

comments from the public to questions 

concerning highly pathogenic avian 

influenza (HPAI) H5N1 viruses that 

contain a hemagglutinin (HA) from the 

Goose/Guangdong/1/96 lineage, and 

their potential to pose a severe threat to 

public health and safety. This 

information will be considered in a 

determination of whether such viruses 

should be listed as HHS select agents, 

by revising the HHS Select Agent 

Regulations (42 CFR Part 73). 

DATES: Electronic or written comments 

should be received on or before 

December 17, 2012. 

ADDRESSES: You may submit comments 

identified by Docket Number CDC– 

2012–0010, by any of the following 

methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Mail: Division of Select Agents and 

Toxins, Centers for Disease Control and 

Prevention, 1600 Clifton Road NE., 

Mailstop A–46, Atlanta, Georgia 30333, 

Attn: Docket Number: CDC–2012–0010. 

Instructions: All submissions received 

must include the agency name and 

docket number (CDC–2012–0010) for 

this notice. All relevant comments 

received will be posted without change 

to www.regulations.gov, including any 

personal information provided. For 

access to the docket to read background 

documents or comments received, go to 

www.regulations.gov. 

FOR FURTHER INFORMATION CONTACT: Dr. 

Robbin Weyant, Director, Division of 

Select Agents and Toxins, Centers for 

Disease Control and Prevention, 1600 

Clifton Road NE., Mailstop A–46, 

Atlanta, Georgia 30333. Telephone: 

(404) 718–2000. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Since late 2003, the World Health 

Organization (WHO) has reported over 

600 cases of human infection with 

highly pathogenic avian influenza 

(HPAI) H5N1 viruses with a mortality 

rate that exceeds 50 percent in 

hospitalized patients (Ref 1). Current 

epidemiologic evidence indicates that, 

once transmitted into a human host, 

H5N1 viruses may result in more severe 

disease in humans than other subtypes 

of influenza. 

One important factor that can account 

for some of the increased pathogenicity 

is the hemagglutinin (HA) molecule. 

Cleavage of the HA molecule by host 

proteases (chemicals that can break 

amino acid bonds) enables influenza 

viruses to productively infect cells (i.e., 

replicate). For human influenza viruses, 

replication is restricted to the 

respiratory tract. However, HPAI H5N1 

viruses contain a polybasic amino acid 

sequence in the HA molecule that is not 

found in human influenza viruses. This 

feature allows the molecule to be 

cleaved by a wider variety of proteases 

throughout the body and consequently, 

HPAI H5N1 viruses can replicate 

systemically in avian species. 

Extrapulmonary dissemination of 

HPAI H5N1 virus has been documented 

among some fatal human HPAI H5N1 

virus infections. The HA molecule 

mediates binding of the influenza virus 

to host cells in the respiratory tract. 

Human influenza viruses preferentially 

bind to different receptors than avian 

influenza viruses (Ref 2). While human 

influenza virus receptors are more 

prevalent in the upper respiratory tract, 

the receptors that bind avian viruses are 

present in the lower respiratory tract of 

humans. The ability of H5N1 viruses to 

bind and infect cells within the lung 

may contribute to the severity of H5N1 

induced viral pneumonia (Ref 3–5). 

Furthermore, a change from avian- to 

human-type receptor-binding 

specificity, as seen with the pandemic 

strains of 1918 (H1N1), 1957 (H2N2), 


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and 1968 (H3N2), is thought to be a 

critical step in the adaptation of avian 

influenza viruses to humans and the 

ability to transmit efficiently among 

humans (Ref 6–8). In two recent 

independent studies (Ref 9 and Ref 10), 

investigators have shown that laboratory 

modified HPAI H5N1 influenza viruses 

with certain mutations can be 

transmitted via the respiratory route 

between ferrets. Ferrets are widely 

considered to provide the best animal 

model for exploring these aspects of 

influenza virus pathogenicity as they 

might relate to human infection (Ref 11). 

We recognize that all HPAI H5N1 

influenza virus clades found in humans 

to date have been derived from the 

Goose/Guangdong/1/96 lineage, and the 

HA molecule enables the virus to infect 

a host cell. Thus, we are interested in 

receiving information and comments on 

whether the influenza viruses that 

contain a hemagglutinin (HA) from the 

Goose/Guangdong/1/96 lineage have the 

potential to pose a severe threat to 

public health and safety (Ref 12). 

Currently, all HPAI H5 subtype viruses 

are regulated by the U.S. Department of 

Agriculture (USDA) Animal and Plant 

Health Inspection Service (APHIS) 

whose oversight focuses on the threat to 

animal health and safety. Listing 

influenza viruses that contain an HA 

from the goose/Guangdong/1/96 lineage 

as an HHS select agent will ensure that 

the focus of regulation will also be on 

the potential impact of these viruses on 

human health as well as agriculture. 

While USDA sets biosafety measures 

that may also be more generally 

beneficial to public health, its focus 

with respect to select agent designation 

is primarily on risks to agricultural 

animals, rather than direct effects on 

human health. There is precedence (e.g., 

Bacillus anthracis) for including agents 

that have both human and agricultural 

impacts on both the HHS and USDA 

Select Agent Lists. Designating HPAI 

containing an HA from the Goose/ 

Guangdong/1/96 lineage an HHS select 

agent, in addition to its status as a 

USDA select agent, may help to ensure 

that HPAI strains that have the greatest 

potential for major direct effects on 

human health will be regulated with a 

focus on protection of human health. 

The question of whether the influenza 

viruses that contain an HA from the 

Goose/Guangdong/1/96 lineage pose a 

severe threat to public health and safety 

was considered by HHS/CDC’s 

Intragovernmental Select Agents and 

Toxins Technical Advisory Committee 

(ISATTAC). The ISATTAC is comprised 

of Federal government scientists from 

HHS/CDC, the Biomedical Advanced 

Research and Development Authority 

(BARDA) within the Office of the 

Assistant Secretary for Preparedness 

and Response (HHS/ASPR) in HHS, the 

National Institutes of Health (HHS/NIH), 

the Food and Drug Administration 

(HHS/FDA), USDA/APHIS, the USDA/ 

Agricultural Research Service, the 

USDA/Center for Veterinary Biologics, 

the Department of Homeland Security 

(DHS), and the Department of Defense 

(DOD). The criteria used by the 

ISATTAC in its review were the degree 

of pathogenicity, communicability, ease 

of dissemination, route of exposure, 

environmental stability, ease of 

production, ability to genetically 

manipulate or alter, long-term health 

effects, acute morbidity, acute mortality, 

available treatment, status of host 

immunity, vulnerability of special 

populations, and the burden or impact 

on the health care system. ISATTAC 

made the recommendation that the 

influenza viruses containing an HA 

from the Goose/Guangdong/1/96 lineage 

do have the potential to pose a severe 

threat to public health and safety. In 

making its recommendation to HHS/ 

CDC, the ISATTAC considered both the 

historical data regarding the Goose/ 

Guangdong/1/96 lineage and data from 

current in vitro and in vivo animal 

studies. The virulence of viruses of this 

lineage, the data showing 

transmissibility of genetically modified 

H5N1 viruses among ferrets, together 

with the fact that the level of immunity 

in the general population is low were all 

considered. Further, in its 

recommendation the ISATTAC voiced 

concern that an influenza pandemic 

caused by viruses containing an HA 

from the Goose/Guangdong/1/96 

lineage, could potentially overwhelm 

the health care system. The ISATTAC 

also recognized that the study of the 

Goose/Guangdong/1/96 lineage-derived 

viruses could lead to significant public 

health benefits for understanding 

pandemic influenza, improved 

diagnostics, and the development of 

more effective countermeasures. 

Therefore, the risks posed by these 

viruses need to be weighed against any 

adverse impact that a regulation will 

have on legitimate research. 

On July 2, 2010, the President signed 

Executive Order 13546, ‘‘Optimizing the 

Security of Biological Select Agents and 

Toxins in the United States’’ that 

directed the Secretaries of HHS and 

USDA to designate a subset of the select 

agents and toxins list (Tier 1) that 

presents the greatest risk of deliberate 

misuse with the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence. The Executive Order 13546 

also established the Federal Experts 

Security Advisory Panel (FESAP) to 

advise the HHS and USDA Secretaries 

on the designation of Tier 1 agents and 

toxins. In December of 2010, the FESAP 

provided the HHS and USDA Select 

Agent regulatory programs with 

recommendations on updating the HHS 

and USDA Select Agent and Toxin lists, 

including a subset of agents and toxins 

recommended for Tier 1 designation. 

On October 3, 2011, HHS/CDC 

published a notice of proposed 

rulemaking (76 FR 61206) in which we 

proposed a list of select agents and 

toxins that should be considered Tier 1 

select agents and toxins. The proposed 

Tier 1 agents and toxins that were based 

on Executive Order 13546 and the 

recommendations from FESAP were 

scored against 20 criteria by over 60 

Subject Matter Experts representing the 

Federal life sciences, public health, law 

enforcement, security, and intelligence 

communities. The criteria included: 

• The relative ease with which a 

particular select agent or toxin might be 

disseminated or transmitted from one 

human to another or into the 

environment where it could produce a 

deleterious effect upon human health; 

• The potential for a high mortality 

rate; 

• The potential for a major human 

health impact; 

• Select agents or toxins whose 

misuse might result in public panic or 

other social or economic disruption; and 

• Select agents or toxins whose use 

might require Federal, State, and/or 

local officials to take special action in 

planning for major human health 

disasters. 

We proposed that the following agents 

should be designated as Tier 1 agents: 

Bacillus anthracis, Botulinum 

neurotoxin, Botulinum neurotoxin 

producing species of Clostridium, 

Burkholderia mallei, B. pseudomallei, 

Francisella tularensis, Marburg virus, 

Variola major virus, Variola minor virus, 

and Yersinia pestis. On the same day, 

USDA/APHIS published a companion 

rule in the Federal Register proposing 

its list of select agents and toxins that 

should be considered Tier 1 select 

agents and toxins. Although USDA/ 

APHIS regulates HPAI viruses as select 

agents, they did not propose to 

designate HPAI viruses as Tier 1 select 

agents. Given the above criteria used by 

the FESAP, we would welcome 

comment on whether HPAI H5N1 

influenza viruses containing the HA 

from the Goose/Guangdong/1/96 lineage 

should be listed as a Tier 1 select agent. 

The final determination of whether or 

not to designate this particular lineage 


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Federal Register / Vol. 77, No. 201 / Wednesday, October 17, 2012 / Proposed Rules 63785 

of H5N1 HPAI as Tier 1 would be a 

collaborative process between HHS and 

USDA. HHS and USDA would continue 

to work closely together whether or not 

both HHS and USDA designate these 

viruses as Tier 1 Select Agents. 

II. Establishment of a Docket and 

Request for Specific Input on Certain 

Topics 

We are establishing a docket to 

provide an opportunity for interested 

persons to submit comments, research 

data, and other information that will 

better inform us about the risk posed by 

HPAI H5N1 influenza viruses 

containing the HA from the Goose/ 

Guangdong/1/96 lineage to public 

health and safety. In particular, we 

welcome comment on the following 

questions: 

(1) Do HPAI H5N1 influenza viruses 

containing the HA from the Goose/ 

Guangdong/1/96 lineage pose a severe 

threat to public health and safety? 

(2) Are there other influenza strains 

containing HA from Goose/Guangdong/ 

1/96 lineage that would also pose a 

severe threat even if they were not fully 

of HPAI H5N1 origin? 

(3) Are there any other HPAI H5N1 

influenza strains that have been 

identified to pose a severe threat to 

public health and safety? 

(4) Should these viruses be regulated 

as HHS select agents? 

(5) If these viruses should be 

regulated as HHS select agents, should 

these viruses be designated as Tier 1 

select agents? 

(6) Should special precautions (i.e., 

safety and containment measures) be 

considered when working with 

diagnostic specimens suspected of 

containing HPAI H5N1 influenza 

viruses containing the HA from the 

Goose/Guangdong/1/96 lineage (i.e., any 

precautions versus none at all, 

precautions beyond those usual for 

clinical samples and/or laboratory 

microbes, etc.)? and 

(7) Should special precautions (i.e., 

safety and containment measures) be 

considered when working with strains 

of HPAI containing the HA from the 

Goose/Guangdong/1/96 lineage that 

have been shown to be transmissible 

between mammals beyond those 

recommended for non-mammalian 

transmissible HPAI (Ref 13 and Ref 14)? 

III. References 

1. WHO, Cumulative number of confirmed 

human cases for avian influenza A(H5N1) 

reported to WHO, 2003–2011; http:// 

www.who.int/influenza/human_

animal_interface/H5N1_cumulative_table_

archives/en/index.html. 

2. Fukuyama S, Kawaoka Y. The 

pathogenesis of influenza virus infections: 

The contributions of virus and host factors. 

Curr Opin Immunol. 2011 Aug;23(4):481– 

6. Epub 2011 Aug 11. 

3. Shinya K, Ebina M, Yamada S, Ono M, 

Kasai N, Kawaoka Y. Avian flu: Influenza 

virus receptors in the human airway. 

Nature. 2006 Mar 23;440(7083):435–6. 

4. Nicholls JM, Chan MC, Chan WY, Wong 

HK, Cheung CY, Kwong DL, Wong MP, 

Chui WH, Poon LL, Tsao SW., Guan Y, 

Peiris JS. Tropism of avian influenza A 

(H5N1) in the upper and lower respiratory 

tract. Nat Med. 2007 Feb;13(2):147–9. Epub 

2007 Jan 7. 

5. Van Riel D, Munster VJ, de Wit E, 

Rimmelzwaan GF, Fouchier RA, Osterhaus 

AD, Kuiken T. H5N1 Virus Attachment to 

Lower Respiratory Tract. Science. 2006 

Apr 21;312(5772):399. Epub 2006 Mar 23. 

6. Matrosovich, M., et al. Early alterations of 

the receptor-binding properties of H1, H2, 

and H3 avian influenza virus 

hemagglutinins after their introduction 

into mammals. J Virol 74, 8502–8512 

(2000). 

7. Stevens, J., et al. Glycan microarray 

analysis of the hemagglutinins from 

modern and pandemic influenza viruses 

reveals different receptor specificities. J 

Mol Biol 355, 1143–1155 (2006). 

8. Connor, R.J., Kawaoka, Y., Webster, R.G. & 

Paulson, J.C. Receptor specificity in 

human, avian, and equine H2 and H3 

influenza virus isolates. Virology 205, 17– 

23 (1994). 

9. Masaki Imai,1 Tokiko Watanabe,1, 2 

Masato Hatta,1 Subash C. Das,1 Makoto 

Ozawa,1, 3 Kyoko Shinya,4 Gongxun 

Zhong,1 Anthony Hanson,1 Hiroaki 

Katsura,5 Shinji Watanabe,1, 2 Chengjun 

Li,1 Eiryo Kawakami,2 Shinya Yamada,5 

Maki Kiso,5 Yasuo Suzuki,6 Eileen A. 

Maher,1 Gabriele Neumann1 & Yoshihiro 

Kawaoka. Experimental adaptation of an 

influenza H5 HA confers respiratory 

droplet transmission to a reassortant H5 

HA/H1N1 virus in ferrets. Nature. 2012 

May 2;486(7403):420–8. 

10. Russell CA, Fonville JM, Brown AE, 

Burke DF, Smith DL, James SL, Herfst S, 

van Boheemen S, Linster M, Schrauwen EJ, 

Katzelnick L, Mosterı ́n A, Kuiken T, Maher 

E, Neumann G, Osterhaus AD, Kawaoka Y, 

Fouchier RA, Smith DJ. The potential for 

respiratory droplet-transmissible A/H5N1 

influenza virus to evolve in a mammalian 

host. Science. 2012 Jun 22; 

336(6088):1541–7. 

11. Belser JA, Szretter KJ, Katz JM, Tumpey 

TM. Use of animal models to understand 

the pandemic potential of highly 

pathogenic avian influenza viruses. Adv 

Virus Res. 2009;73:55–97. 

12. WHO/OIE/FAO H5N1 Evolution Working 

Group. Continued evolution of highly 

pathogenic avian influenza A (H5N1): 

updated nomenclature. Influenza Other 

Respi Viruses. 2012 Jan; 6(1): 1–5. doi: 

10.1111/j.1750–2659.2011.00298.x. Epub 

2011 Oct 29. 

13. Guidelines for Avian Influenza Viruses 

(http://www.selectagents.gov/resources/

Guidelines%20for%20Avian%20

Influenza%20Viruses_2011-11-4.pdf). 

14. Biosafety in Microbiological and 

Biomedical Laboratories (http:// 

www.cdc.gov/biosafety/publications/

bmbl5/index.htm). 

Dated: October 9, 2012. 

Kathleen Sibelius, 

Secretary. 

[FR Doc. 2012–25377 Filed 10–16–12; 8:45 am] 

BILLING CODE 4163–18–P 


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