[Federal Register Volume 85, Number 28 (Tuesday, February 11, 2020)]
[Proposed Rules]
[Pages 7698-7708]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-02665]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2015-0230; FRL-9998-74]
RIN 2070-ZA16


Banda de Lupinus Albus Doce (BLAD); Proposal To Revoke Exemption 
and Establish Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA or Agency).

ACTION: Proposed rule; reproposal.

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SUMMARY: On May 29, 2015, EPA proposed to revoke the current exemption 
from the requirement of a tolerance for residues of banda de Lupinus 
albus doce (BLAD) in or on all food commodities and to establish 
tolerances for residues of BLAD in or on almonds, grapes, strawberries, 
and tomatoes. Following the receipt of several comments, the Agency is 
reproposing this action in order to clarify its proposed rulemaking. In 
addition, since the publication of the initial proposal, the registrant 
has requested that the Agency establish tolerances for additional 
commodities. The Agency is undertaking this action under the Federal 
Food, Drug, and Cosmetic Act (FFDCA).

DATES: Comments must be received on or before April 13, 2020.

ADDRESSES: Submit your comments, identified by docket identification 
number EPA-HQ-OPP-2015-0230, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/where-send-comments-epa-dockets.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Anne Overstreet, Deputy Director, 
Biopesticides and Pollution Prevention Division (7511P), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave. NW, Washington, DC 20460-0001; main telephone number: (703) 305-
7090; email address: BPPDFRNotices@epa.gov.

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. What should I consider as I prepare my comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through 
regulations.gov or email. Clearly mark the part or all of the 
information that you claim to be CBI. For CBI information on a disk or 
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as 
CBI and then identify electronically within the disk or CD-ROM the 
specific information that is claimed as CBI. In addition to one 
complete version of the comment that includes information claimed as 
CBI, a copy of the comment that does not contain the information 
claimed as CBI must be submitted for inclusion in the public docket. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When preparing and submitting 
your comments, see the commenting tips at http://www.epa.gov/dockets/commenting-epa-dockets#tips.

II. This Proposal

A. What is the authority for this action?

    EPA is taking this action under section 408(e) of the FFDCA, 21 
U.S.C. 346a(e), which allows EPA to issue regulations, including 
establishing tolerances and revoking exemptions, on its own initiative. 
Under FFDCA section 408(e), the Agency applies the same standards for 
establishing tolerances and revoking exemptions found in FFDCA section 
408(b) and (c), 21 U.S.C. 346a(b) and (c). FFDCA section 
408(b)(2)(A)(i) allows EPA to establish a tolerance (the legal limit 
for a pesticide chemical residue in or on a food) only if EPA 
determines that the tolerance is ``safe.'' FFDCA section 
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including all anticipated dietary exposures 
and all other exposures for which there is reliable information.'' This 
includes exposure through drinking water and in residential settings 
but does not include occupational exposure. FFDCA section 408(b)(2)(C) 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate

[[Page 7699]]

exposure to the pesticide chemical residue. . . .''
    The relevant portion of FFDCA section 408(c)(2)(A)(i) requires the 
Agency to modify or revoke an exemption if the Agency determines it is 
not safe, where ``safe'' has the same definition as in FFDCA section 
408(b)(2)(A)(ii).
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of FFDCA section 408 and a complete description 
of the risk assessment process, see http://www.epa.gov/pesticide-tolerances/setting-tolerances-pesticide-residues-foods.

B. What action is the Agency taking?

    EPA is proposing to revoke the existing exemption from the 
requirement of a tolerance for residues of the fungicide BLAD in or on 
all food commodities that was established in the Federal Register of 
March 22, 2013 (78 FR 17600) (FRL-9380-6). In place of the exemption, 
EPA is proposing to establish tolerances for residues of the fungicide 
BLAD at the level of quantitation (LOQ), i.e., 0.02 parts per million 
(ppm), in or on the following commodities: Almond; almond, hulls; 
fruit, pome, group 11-10; fruit, stone, group 12-12; grape; hops, dried 
cones; strawberry; vegetable, cucurbit, group 9; and vegetable, 
fruiting, group 8-10.
    EPA is taking this action in response to concerns raised by the 
U.S. Food and Drug Administration (FDA) about the potential 
allergenicity of BLAD for lupin-sensitive and/or peanut-sensitive 
individuals following EPA's promulgation of the tolerance exemption of 
BLAD on all food commodities. (Ref. 1). Based on the potential 
uncertainty raised by those concerns, EPA sought additional data from 
the petitioner and reexamined the safety of the BLAD tolerance 
exemption. Following further review of BLAD and an assessment of the 
additional data that were provided, EPA has concluded that given the 
source of BLAD and the results of bioinformatics analysis, such data do 
not disprove the potential for BLAD to pose an allergenicity risk to 
lupin-sensitive and peanut-sensitive individuals. As a result, EPA no 
longer considers the existing tolerance exemption for residues of BLAD, 
which, on its face, permits unlimited residues of BLAD in or on all 
food commodities, to be safe. Nevertheless, EPA concludes that the 
available residue data and food processing information support a safety 
determination for establishing numerical tolerances at the LOQ for 
residues of BLAD in or on almond; almond, hulls; fruit, pome, group 11-
10; fruit, stone, group 12-12; grape; hops, dried cones; strawberry; 
vegetable, cucurbit, group 9; and vegetable, fruiting, group 8-10.

III. Guidance for Assessing Allergenicity

    The Agency considered the following sources of internationally 
accepted guidance in assessing the potential allergenicity of BLAD. 
Although these documents are primarily concerned with the safety of 
foods that have been genetically modified, the allergenicity analysis 
is relevant since it outlines a process for evaluating whether the gene 
(or protein) engineered into the food has introduced an allergen or 
resulted in a food that may be allergenic. EPA considers the 
recommended approaches for assessing potential allergenicity to apply 
equally to proteins that may be applied directly onto the plant as well 
as those directly incorporated into the plant via genetic engineering.

A. Report of Joint FAO/WHO Expert Consultation (2001)

    In 2001, the Joint Food and Agriculture Organization of the United 
Nations (FAO)/World Health Organization (WHO) Expert Consultation on 
Allergenicity of Foods Derived from Biotechnology was held at the 
headquarters of the FAO. The 28-expert consultation focused on the 
question of allergenicity of genetically modified foods and prepared a 
report providing scientific advice for the assessment of allergenicity 
of genetically modified foods. (Ref. 2, hereinafter ``2001 FAO/WHO 
Report''). The consultation developed a new decision tree identifying 
two paths for assessing allergenicity, depending upon whether the 
source of the gene is a known allergen. (Id. at 6, 26).
    If the source of the gene is a known allergen, the analysis focuses 
on both sequence homology and specific sera testing. (Id. at 7-8). 
Determining sequence homology to a known allergen is the first step for 
genes derived from known allergenic sources. The 2001 FAO/WHO Report 
notes that significant sequence homology is indicated (and thus a 
potential for cross-reactivity between the new protein and a known 
allergen) when there is more than 35% identity between the amino acid 
sequence of the expressed protein and the known allergen, within a 
window of 80 amino acids. (Id. at 10-11).\1\ If the sequence homology 
demonstrates similarity to a known allergen, the product is considered 
allergenic, i.e., a person sensitive to a known allergen is likely to 
be allergic to the new protein as well. (Id. at 7). The 2001 FAO/WHO 
Report notes that for proteins derived from known allergenic sources 
where sequence homology to a known allergen is demonstrated, ``the 
product is considered allergenic, and no further testing is typically 
undertaken.'' (Id.)
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    \1\ The 2001 FAO/WHO Report also recognizes that potential for 
cross-reactivity may require consideration of additional factors 
when proteins have less than 35% identity with a known allergen in a 
window of 80 amino acids. (Ref. 2 at 11). These considerations are 
not discussed in this document since the sequence homology for BLAD 
exceeds 35% identity with other known allergens.
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    The 2001 FAO/WHO Report provides that for proteins derived from 
known allergenic sources where the sequence homology analysis is 
negative, a specific serum screen is to be conducted. (Id. at 7). The 
2001 FAO/WHO Report recommends using only patients with a level of 
sensitization to the allergen source of more than 10 kilointernational 
units per liter (kIU/L) of specific immunoglobulin E (IgE), in order to 
ensure that the test is conducted with sera from patients sufficiently 
allergic to the source material, and cautions that patients who have a 
low level of sensitization may not provide useful results for assessing 
reactivity to the expressed protein. (Id.) Assuming adequately 
sensitive sera are available, the 2001 FAO/WHO Report notes that the 
degree of confidence in the results of the specific serum screening 
will depend upon the number of sera available for analysis. To achieve 
a 95% certainty that a substance is not a major allergen, a negative 
result must be obtained with at least 6 relevant sera; 99% certainty, 
at least 8 relevant sera; 99.9% certainty, at least 14 relevant sera. 
To achieve 95% certainty that a substance is not a minor allergen, a 
negative result must be obtained with at least 17 relevant sera; 99% 
certainty, at least 24 relevant sera. Larger numbers of sera are 
recommended to increase the confidence associated with negative 
immunoassay results; using fewer sera carries the risk of a false 
negative outcome. (Id.) The 2001 FAO/WHO Report notes that the in vitro 
method applied to assess the results should be a validated assay 
measuring specific IgE. (Id.)
    The 2001 FAO/WHO Report concludes that any positive results from 
the sera screen will define the product as likely to be allergenic and 
will normally lead to discontinuation of product development. (Id.) A 
negative outcome from the sera screen does not necessarily support a 
conclusion that the product is not allergenic, however;

[[Page 7700]]

rather, because of the allergenic nature of the source of the 
substance, a desire to continue with product development will normally 
prompt further analysis to rule out allergenicity concerns (i.e., 
targeted serum screening, analysis of pepsin resistance, and animal 
modeling, and in selected cases, in vivo/ex vivo testing (i.e., skin 
prick testing, basophil histamine release, and oral challenge)). (Id. 
at 7-8).
    If the source of the protein is not a known allergen, the 2001 FAO/
WHO Report decision tree advises consideration of four sets of data: 
(1) Sequence homology with known allergens; (2) targeted serum testing; 
(3) pepsin resistance; and (4) immunogenicity testing in animal models. 
(Id. at 8). If the sequence homology reveals a level of homology with a 
known allergen, the protein is ``considered to be an allergenic risk . 
. . [and n]o further evaluation for allergenicity would typically be 
necessary.'' (Id.) If the sequence homology does not identify any 
similarities, the 2001 FAO/WHO Report notes that it does not 
necessarily mean that the substance is not an allergen. Rather, because 
of potential limitations in the databases or limited information on the 
relevant allergen, the 2001 FAO/WHO Report recommends that a targeted 
serum screen be conducted to test for cross-reactivity of individual 
serum samples containing high levels of IgE antibodies specific to a 
source broadly related to the source of the substance at issue, e.g., 
if the gene is derived from a monocot, sera from individuals with 
allergies to other monocots would be used in the screen. (Id. at 12). A 
positive result with one of these sera will indicate that the substance 
is likely to be allergenic and further study would not be necessary, 
unless further confirmation is sought through in vivo/ex vivo 
approaches mentioned above. (Id. at 8). Negative results would then 
lead to the analysis of the protein for pepsin resistance (i.e., how 
completely the protein degrades in the presence of pepsin during 
digestion) and evidence of immunogenicity in appropriate animal models. 
(Id. at 12-13). The 2001 FAO/WHO Report recommends that any results of 
these analyses be taken into consideration in combination with the rest 
of the decision tree criteria. (Id. at 13.)

B. Codex Alimentarius Guidance (2009)

    The Codex Alimentarius Guidance is a ``collection of 
internationally adopted food standards, guidelines, codes of practice 
and other recommendations,'' developed by an intergovernmental body 
with more than 180 members, within the framework of the Joint Food 
Standards Programme established by the FAO and WHO. (Ref. 3, preface). 
Contained within the Codex Alimentarius Guidance, the Guideline for the 
Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA 
Plants (``Codex Guideline'') addresses safety and nutritional aspects 
of genetically altered foods and recommends an approach for assessing 
the safety of foods derived from recombinant-DNA plants and plants 
altered by other techniques. (Id. at 7-33).
    The Codex Guideline states that all newly expressed proteins in 
recombinant-DNA plants should be assessed for their potential to cause 
allergic reactions. (Id. at 15). The Codex Guideline describes stepwise 
approach to the assessment of the possible allergenicity of newly 
expressed proteins. (Id. at 20-23). The initial assessment involves 
three steps: (1) Identify the source of the protein; (2) assess the 
extent to which a protein is similar in structure to a known allergen; 
and (3) evaluate the resistance of the protein to degradation by 
pepsin. (Id. at 21-22).
    The Codex Guideline states that ``[i]t is important to establish 
whether the source is known to cause allergic reactions. Genes derived 
from known allergenic sources should be assumed to encode an allergen 
unless scientific evidence demonstrates otherwise.'' (Id. at 21). The 
Codex Guideline notes ``[t]he transfer of genes from commonly 
allergenic foods . . . should be avoided unless it is documented that 
the transferred gene does not code for an allergen. . . .'' (Id. at 
15). Because there is no single definitive test for predicting allergic 
human response, ``[k]nowledge of the source of the introduced protein 
allows the identification of tools and relevant data to be considered 
in the allergenicity assessment. These include: the availability of 
sera for screening purposes; documented type, severity and frequency of 
allergic reactions; structural characteristics and amino acid sequence; 
physicochemical and immunological properties (when available) of known 
allergenic proteins from that source.'' (Id. at 21).
    The next piece of the allergenicity assessment is the amino acid 
sequence homology, the purpose of which is to determine whether a 
protein is similar in structure to a known allergen and thus has 
allergenic potential. (Id.) Assessing similarity to known allergens is 
done by comparing the new protein to databases of known allergens, 
looking for two types of similarity. First, the sequence homology looks 
for contiguous identical amino acid segments; the Codex Guideline noted 
that ``the size of the contiguous amino acid search should be based on 
scientifically justified rationale in order to minimize the potential 
for false negative or false positive results,'' whereas the 2001 FAO/
WHO Report recommended moving from 8 to 6 identical amino acid 
segments. (Id.) Second, the sequence homology looks for whether there 
is a potential for human IgE cross-reactivity between the new protein 
and a known allergen. (Id.) The Codex Guideline incorporates the 
finding of the 2001 FAO/WHO Report, which concludes that a potential 
cross-reactivity is likely when there is more than 35% identity in a 
segment of 80 or more amino acids. (Id.) Where there is a negative 
sequence homology, it indicates that the protein is not a known 
allergen and is unlikely to be cross-reactive with known allergens. 
(Id. at 22). A positive sequence homology indicates that the protein is 
likely to be allergenic and, in order to be considered further, 
specific serum testing (i.e., testing conducted using serum of 
individuals who are sensitized to the allergenic source) should be 
conducted. (Id.)
    The Codex Guideline also recognizes that many food allergens 
exhibit resistance to pepsin digestion and thus resistance to pepsin 
digestion can be used to assess potential allergenicity. (Id.) If a 
protein is resistant to pepsin digestion, it suggests that further 
analysis should be conducted to evaluate potential allergenicity; 
however, the Codex Guideline notes that lack of resistance does not 
necessarily mean that the protein is not an allergen. (Id.)
    The Codex Guideline states that for proteins that originate from a 
known allergenic source or that have sequence homology with a known 
allergen, testing in immunological assays should be performed where 
sera are available. (Id.) The sera should be obtained from individuals 
with a ``clinically validated allergy'' to the protein source, and sera 
must be obtained from sufficient numbers of individuals to achieve the 
necessary level of confidence in the test results regarding the 
protein's allergenicity. (Id.) The 2001 FAO/WHO Report notes that, in 
the case of a major allergen, a minimum of eight relevant sera is 
required in order to achieve a 99% certainty that the new protein is 
not an allergen, while in the case of a minor allergen, a minimum of 24 
is required. (Id. at n.11). In addition, the ``quality of the sera and 
the assay procedure need to be standardized to produce a valid test 
result.'' (Id. at 23). ``[A] negative result in in vitro

[[Page 7701]]

immunoassays may not be considered sufficient, but should prompt 
additional testing, such as the possible use of skin test and ex vivo 
protocols. A positive result in such tests would indicate a potential 
allergen.'' (Id.)

IV. Regulatory Background

    BLAD is a protein fragment with fungicidal properties. More 
specifically, BLAD is a 20 kilodalton (kDa) polypeptide fragment of 
[beta]-conglutin, a main storage protein in the flowering plant sweet 
lupin (Lupinus albus). BLAD is produced by breakdown of [beta]-
conglutin during day 4 to 12 of the germination process of sweet 
lupins. BLAD degrades chitin by catalyzing and successfully removing 
the N-acetyl-D-glucosamine terminal monomers, resulting in the 
destruction of fungal cells. (Ref. 4).
    In the Federal Register of March 22, 2013 (78 FR 17600) (FRL-9380-
6), EPA established an exemption from the requirement of a tolerance 
for residues of BLAD in or on all food commodities when applied as a 
fungicide and used in accordance with label directions and good 
agricultural practices. EPA established this tolerance exemption 
following the receipt of a petition from Consumo Em Verde S.A., 
Biotecnologia De Plantas, Parque Technologico de Cantanhede (CEV) in 
2012. The Agency's safety finding was based on an assessment of 
available data and an assumption that there was a long history of safe 
use in human and animal consumption without any adverse effects.
    Although the preamble to the March 2013 final rule did not discuss 
the potential allergenicity of BLAD, EPA's supporting memorandum for 
the establishment of a tolerance exemption examined BLAD's potential 
allergenicity, based on the available information EPA had about BLAD at 
the time. (Ref. 4). Observing that (i) BLAD comprises an internal 
segment of [beta]-conglutin, (ii) [beta]-conglutin exhibits a 
relatively strong homology to the other members of the vicilin family, 
including well-known allergens contained in peanuts and soybeans, and 
(iii) there were a considerable number of studies concerning the 
allergenicity of lupin-derived products, EPA conducted an allergenicity 
assessment of BLAD. (Id.) EPA examined BLAD under the criteria in the 
2001 FAO/WHO Report and the Codex Guideline for assessing proteins not 
known to be derived from an allergenic source, which it characterized 
as follows: (la) Amino acid residue homology >35%, or (1b) identity in 
one or more sets of >6 contiguous amino acid residues, or (1c) cross-
reactivity to known allergens; (2) high resistance to proteolytic 
attack; and (3) ingestion of sufficient amounts. (Id.) Although EPA 
found that BLAD exhibited a high sequence homology with a well-
established peanut allergen, Ara h 1, EPA concluded that a tolerance 
exemption would be safe because, when used according to the proposed 
label directions, BLAD's potential exposure and harmful effects to 
humans would be negligible, and no adverse effects such as allergenic 
reactions would be expected. (Id.)
    Following EPA's establishment of this BLAD tolerance exemption, 
however, FDA expressed concerns about the potential allergenicity of 
BLAD for lupin-sensitive and/or peanut-sensitive individuals. (Ref. 1). 
FDA noted that the preamble to the March 2013 final rule did not 
discuss allergenicity and disagreed with EPA's statement in the 
tolerance exemption preamble about the long history of safe consumption 
of sweet lupins. (Id.) FDA noted that BLAD is derived from the lupin 
plant and provided information concerning the allergenicity of lupin. 
(Id.) Specifically, FDA provided scientific literature indicating that 
lupin causes allergic reactions and epidemiological evidence indicating 
that lupin is an increasingly significant allergenic hazard in Europe 
where it is consumed. (Id.) FDA also referred EPA to the 2005 European 
Food Safety Authority (EFSA) official opinion. The EFSA opinion 
examined the potential for allergenicity of lupin in response to a 
request from the European Commission, which was considering whether to 
place lupin on a list of known allergens and require lupin 
identification on food labels. (Id.; see also Ref. 5). The EFSA opinion 
noted allergic reactions to lupin have been documented in individuals 
allergic to peanuts and those with no known allergy to peanuts. (Ref. 
5).
    FDA also provided information on BLAD's bioinformatics. Using 
publicly available sequence information, FDA determined that [beta]-
conglutin, the specific protein from which BLAD is derived, is a major 
lupin allergen, Lup an 1. (Ref. 1). FDA further concluded that BLAD has 
a high amino acid sequence identity to two major allergens--Lup an 1 
and Ara h 1, a major peanut allergen. (Id.) Based on information about 
the allergenicity of the source plant and the sequence homology to 
major allergens, FDA concluded that, under the Codex Guideline and the 
2001 FAO/WHO Report, BLAD would be considered an allergen until proven 
otherwise. (Id.)
    Taking this new information concerning BLAD's source into account 
along with BLAD's bioinformatics, EPA proceeded to analyze BLAD under 
the Codex Guideline approach for assessing proteins derived from known 
allergenic sources, which emphasizes the need for specific sera testing 
to overcome the presumption that the protein will be allergenic. (Ref. 
6). This new approach differed from the approach EPA used in its 
initial assessment of BLAD; lacking information that the protein was 
derived from a known allergenic source, EPA had used the general 
assessment approach recommended for proteins that are not known to be 
derived from known allergenic sources. (Id.) In addition to using this 
new approach, EPA sought FDA's insight on evaluating food allergens as 
it evaluated BLAD's potential allergenicity.
    Applying the 2001 FAO/WHO Report and Codex Guideline processes for 
assessing substances derived from known allergenic sources, EPA 
requested that CEV submit additional data to overcome the presumption 
that BLAD would pose a potential allergenicity concern. EPA also 
required residue chemistry field trials and a residue decline study to 
determine likely residue levels of BLAD on treated commodities listed 
on the pesticide label. (Id.) Upon receipt of this new information, EPA 
reexamined the safety of BLAD.
    Based on that reexamination, on May 29, 2015, EPA proposed to 
revoke the established tolerance exemption, which, on its face, 
contains no numerical limit on permissible residues in or on all food 
commodities, and to establish tolerances for residues of BLAD in or on 
almonds, grapes, strawberries, and tomatoes at 0.005 ppm (the level of 
detection). 80 FR 30640 (May 29, 2015). In essence, the proposal noted 
that, since the available allergenicity data did not rule out the 
potential of BLAD's allergenicity, the Agency was unable to continue 
supporting the safety finding for the BLAD exemption, which set no 
numerical limits for exposures to BLAD on all food commodities, which 
facilitate the process for identifying residues that might be higher 
than expected in instances of pesticidal misuse. Nevertheless, the 
Agency determined that, because the available residue data indicate a 
lack of detectable residues on certain commodities (i.e., almonds, 
grapes, strawberries, and tomatoes), numerical tolerances set at the 
level of detection for ensuring negligible residues of BLAD on almonds, 
grapes, strawberries, and tomatoes as expected under approved label use 
conditions were safe. Id. at 30643-44.

[[Page 7702]]

    The Agency received five timely comments on the proposal, as well 
as a number of late-filed comments. Of those timely comments, many 
expressed confusion about the Agency's basis for its proposal and 
challenged whether the proposal was based on the available data. Some 
commenters also expressed concerns for the proposal's impact on farmers 
and trade. Upon further review of that proposal and following 
additional consultation with FDA regarding the commenters' scientific 
challenges to the proposal (Refs. 7, 8), the Agency recognized that the 
rationale for its May 29, 2015, proposal could have been presented more 
clearly. In addition, the registrant requested that additional 
commodities be added to this tolerance rulemaking action. Consequently, 
in response to the concerns raised in the comments and the request for 
additional commodities, the Agency has decided to repropose with 
additional explanation addressing the basis for revoking the tolerance 
exemption and establishing tolerances set at the LOQ for residues in or 
on the commodities identified in the May 29, 2015, proposal, as well as 
other commodities requested by the registrant in the interim. This 
reproposal supersedes and replaces the proposal issued on May 29, 2015.

V. Aggregate Risk Assessment and Determination of Safety

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
    As noted in the preamble to the March 22, 2013, final rule, all of 
the toxicity data requirements have been fulfilled. The toxicological 
profile of BLAD has not changed since that rule; therefore, EPA is 
relying on the toxicity findings in that document and supporting 
documents to support its continuing conclusion that BLAD does not 
present any toxic concerns. 78 FR at 17601-02 and Ref. 4.
    As noted in Unit IV., upon receiving new information about BLAD's 
source from FDA, EPA reexamined the potential allergenicity of BLAD for 
lupin-sensitive and peanut-sensitive individuals, using the approach 
recommended in the 2001 FAO/WHO Report and in the Codex Guideline: (1) 
Identify the source of the protein; (2) assess the extent to which a 
protein is similar in structure to a known allergen; and (3) for 
substances derived from a known allergenic source and that have 
sequence homology with a known allergen, test sera of a sufficient 
number of individuals who are sensitized to the allergenic source. 
(Refs. 2, 3).
    BLAD is a fragment of the [beta]-conglutin protein produced in the 
sweet lupin (Lupinus albus). There are several sources indicating that 
lupin is a major allergen. First, EFSA has issued a number of science 
opinions recognizing lupin as causing allergic reactions in peanut-
sensitive individuals and IgE sensitization in individuals with no 
known allergy to peanuts. (Refs. 5, 9). Based on the EFSA reports, the 
European Commission added lupin to the list of major allergens that 
must be identified on food labels. (Ref. 10). FDA also considers lupin 
to be a food allergen and, based on reports of allergic reactions to 
lupin (some severe), has issued advisory statements to alert consumers 
to the potential for allergic reactions to foods containing lupin, 
especially those individuals with a peanut allergy. (Refs. 8, 11, 12). 
In addition, both EFSA and FDA cite to extensive scientific literature 
indicating that exposure to lupin causes allergic reactions in peanut-
sensitive individuals (indicating cross-reactivity), as well as in the 
general population. (Refs. 1, 5, 8). After considering this 
information, EPA has concluded that lupin, from which BLAD is derived, 
is a known allergen.
    EPA also assessed BLAD for any sequence homology to known 
allergens. EPA determined that BLAD exhibits a high sequence homology 
(58%) when compared to Ara h 1, a recognized allergen known for causing 
allergic reactions (sometimes severe) in peanut-sensitive individuals. 
(Ref. 4). In addition, FDA informed EPA that BLAD is also 86% identical 
and 91% similar in amino acid sequence (with no gaps) to Lup an 1.0101, 
the [beta]-conglutin derived from Lupinus angustifolius. (Ref. 8). Lup 
an 1 has been recognized as a food allergen in the World Health 
Organization/International Union of Immunological Sciences database, 
(Ref. 13), and EFSA considers Lup an 1 to be the major lupin allergen. 
(Ref. 9 at 165). Given that BLAD is derived from a known allergen and 
has a high sequence homology to two known allergens, EPA required 
additional testing to further assess BLAD's potential allergenicity, 
consistent with the Codex Guideline recommendation to seek specific 
serum testing or immunological assays where sera are available.
    In response, CEV agreed to conduct studies that test for 
allergenicity, including a skin prick (in vivo) test on individuals 
sensitive to Ara h 1 and in vitro immunological testing on serum from 
those individuals. (Ref. 14). After identifying several patients who 
reported having an allergy, a skin prick test (SPT) was conducted in 
order to establish a sampling population that was sensitive to lupins 
and/or peanuts. (Ref. 15). Sera from 30 individuals \2\ who were found 
in the SPT to have a sensitivity to the lupin and/or peanut extract 
were used to evaluate the capacity of cross-reactivity to BLAD in these 
sensitive individuals. (Ref. 6). The IgE-specific in vitro immunoblot 
(ELISA) testing results did not indicate any IgE binding to BLAD, i.e., 
the results indicated that BLAD did not react with the tested patients' 
sera. (Id.; Ref. 15).
---------------------------------------------------------------------------

    \2\ The initial serum study selected 26 patients who reacted to 
the lupin and/or peanut in the SPT. After EPA expressed concern 
about some of the results of the study, sera from additional 
patients were included in the study. (Refs. 6, 15).
---------------------------------------------------------------------------

    While the lack of reactivity indicates that BLAD may not cause an 
allergic response in the tested patients, EPA has determined, as 
discussed below, that this study is not sufficient to overcome the 
presumption of allergenicity for BLAD among the general population of 
lupin-sensitive and/or peanut-sensitive individuals, given the 
protein's source and sequence homology. (Ref. 16). As noted in Unit 
III.B., according to the Codex Guideline, ``a negative result in in 
vitro immunoassays may not be considered sufficient, but should prompt 
additional testing, such as the possible use of skin test and ex vivo 
protocols.'' (Ref. 3 at 23). The critical issues are the availability 
of sera from a sufficient number of individuals, the quality of the 
sera, and the standardization of the assay procedure. (Id. at 22-23.)
    Both EPA and FDA have reviewed the submitted data to determine 
whether it supports a conclusion that BLAD is not an allergen. Because 
of FDA's initial concerns about BLAD and in light of FDA's experience 
evaluating food allergens, EPA discussed the submitted data with FDA 
and considered FDA's analysis of the sera testing in EPA's own 
assessment of the data. FDA identified several concerns about the 
sufficiency of the quantity and quality of the sera used in the 
testing, which raise questions about the scientific reliability of the 
data for proving that BLAD is not an allergen. As an initial matter, 
FDA noted that the sera testing method ``is not the most robust for 
disproving allergenicity to a potential allergenic food ingredient.'' 
(Ref. 8 at 4-5). FDA explained that the

[[Page 7703]]

``most reliable or `gold standard' method for assessing whether or not 
a food or food protein will be clinically reactive is clinical testing 
by oral food challenge in a well-characterized group of food allergic 
individuals.'' (Id. at 5). One of FDA's concerns about the serum test 
itself relates to the level of characterization of the recruited 
patients' clinical history. (Id.) FDA notes that it typically 
encourages submitters of in vitro sera testing to test a 
``statistically significant number of sera from well-characterized food 
allergic individuals.'' (Id.) In reviewing the BLAD sera study, FDA 
found such characterization lacking, in that characterization consisted 
of recruited patients' own clinical history of reactions to lupin or 
peanut and a skin prick test. (Id.) FDA further explained why this 
level of clinical history characterization raises uncertainty about 
whether sera were obtained from an appropriately sensitive population 
of allergic individuals:
    [W]ithout confirmation of allergy by observed positive food 
allergen challenge, there remain uncertainties about how truly reactive 
these patients are to the food allergen and how representative they are 
of the population of potential reactors to the allergen. For example, 
depending on when the last allergic reactions occurred, a patient may 
have outgrown their food allergy yet still be sensitized (having 
specific IgE) to the allergen. Also, some subjects may have associated 
non-specific reactions, e.g., an outbreak of hives/urticaria, to a food 
they had eaten or were sensitized to, even though they are not truly 
reactive to the food. Skin prick tests are also prone to false positive 
results, especially with findings of small wheal and flare responses 
(<4 mm) (Bernstein et al., 2008), which were the findings seen in a 
number of patients in the applicant's study. Inclusion of patients who 
are not validated to be clinically reactive to the allergen in question 
impacts the robustness and statistical power of the data. In the 
applicant's study, FDA found poorly characterized information about the 
recruited patients' reaction histories. (Id. at 5-6).
    In addition, FDA expressed a concern about the level of IgE 
response in the recruited patients:
    In addition, IgE-specific level responses to lupin and/or peanut 
were not found to be robust in most patients, with levels reported to 
be low (less than 2 kU/L) in the majority of subjects. In clinical 
practice to determine if a patient with mild or unclear allergic-type 
symptoms to the food is allergic, most specialists would consider food 
challenge for a patient with peanut IgE levels less than 2 kU/L, as 50% 
of peanut-allergic individuals with a median measurement of 2 kU/L are 
reported to have negative challenges (Nowak-Wegrzyn et al., 2009; Perry 
et al., 2004). Although patients could still be clinically allergic at 
low levels of IgE, for peanut, universally accepted clinical cut-off 
IgE levels to predict likely clinical peanut allergy have been reported 
at much higher levels, i.e., 14 to 15 kU/L. Patients with specific IgE 
at or above these predictive levels of 14 to 15 kU/L have a 90-95% 
likelihood of reacting to peanut during peanut challenge (Nowak-Wegrzyn 
et al., 2009; Sampson and Ho, 1997; Sampson, 2001). IgE cut-off levels 
for predicting lupin reactivity have not been established. FDA also 
found that only about one third of total patients in the applicant's 
sera study had evidence of IgE to Ara h 1 peanut protein, the relevant 
allergen in the diagnostic work-up for determining whether BLAD would 
pose a potential cross-reactive hazard for peanut-allergic individuals. 
Although BLAD was not shown to bind IgE in these subjects, the number 
of patients analyzed is too small to draw any meaningful statistical 
predictions of lack of allergenicity to BLAD for the general peanut-
allergic population. (Id. at 6).
    FDA again noted that ``[r]ecruiting patients who had gone through 
and were observed to be reactive to peanut and/or lupin by the `gold 
standard' food challenge would have helped to eliminate these 
uncertainties about the robustness of the allergic sera 
characterization.'' (Id.)
    Finally, FDA expressed concern about the quality of the testing 
data, including an inadequate description of the methodology used and 
poor quality of the sera blot analyses, which further limit the ability 
to draw conclusions about the results of the sera testing. (Id.)
    EPA gives great weight to FDA's expertise on the issue of 
allergenicity, given FDA's role in assessing food safety and their 
experience in evaluating foods for potential allergenicity concerns. As 
such, EPA has considered many of the concerns raised by FDA in its own 
analysis of the submitted data. After its initial conclusion that the 
lack of evidence of sera reactivity to BLAD provides an indication that 
BLAD may not be an allergen, EPA, taking into consideration FDA's 
concerns and the Codex Guideline warning that negative serum testing 
results may not be sufficient to disprove allergenicity, reexamined the 
adequacy of the submitted sera testing. (Ref. 6).
    According to the Codex Guideline, ``the availability of human sera 
from a sufficient number of individuals'' and the ``quality of the 
sera'' are important to ensure the validity of the test results. For 
the present situation, the quality of the sera is the more significant 
issue for the BLAD test results. In order to evaluate the quality of 
the sera, EPA looks to the 2001 FAO/WHO Report, which cautions that 
patients should be carefully selected to ensure an adequate level of 
sensitivity to the protein. (Ref. 2 at 7). If patients have a low level 
of sensitization, then the usefulness of the sera to predict reactivity 
will be compromised. (Id.) In other words, the sera must be from 
patients whose allergenicity has been verified and who are sufficiently 
sensitive so that the sera will react to the allergen. If sera used is 
taken from patients who have not had their allergy verified or who may 
have low levels of allergic reaction (i.e., are insufficiently 
sensitive to the allergens), the sera may not react to the test 
substance, giving a negative result that cannot be extrapolated to the 
larger population of allergic or sensitized individuals. This result 
would undermine the reliability of the study results for disproving 
allergenicity, which can be especially problematic for substances 
derived from known allergens or that are similar or identical to known 
allergens.
    Taking into consideration the need to ensure the quality of the 
sera and FDA's concerns about the quality of the sera used in the serum 
study, EPA has determined that the study characterization of recruited 
patients' clinical history of allergic reactions and lack of 
verification of allergenic reactivity raises uncertainties about the 
reliability of the study results to conclusively disprove BLAD's 
potential to pose an allergenic risk to lupin-sensitive and/or peanut-
sensitive individuals. (Ref. 16). The quality of the sera being used as 
a test reagent is a critical issue in ensuring the reliability of the 
study results for predicting reactivity. (Id.) The selection of test 
subjects based on self-reported clinical symptoms without a food 
challenge-confirmed allergy, as well as the potential for false 
positives in skin prick tests, raise questions about the selection 
process, the adequacy of the IgE levels, and whether the study involved 
an adequate number of patients. (Id.) In other words, these facts 
introduce uncertainty about the quality of the sera and thus the 
reliability of the study results. Consequently, EPA does not consider 
this study to be scientifically reliable to overcome the presumption of

[[Page 7704]]

allergenicity for BLAD, given the source of the protein and the 
bioinformatics analysis. (Id.)

B. Toxicological Points of Departure/Levels of Concern

    The Agency did not identify any points of departure for BLAD. The 
toxicity database does not contain any indication of toxic effects as a 
basis for any toxicological points of departure or levels of concern. 
Moreover, there is no known threshold for allergenicity to BLAD. As a 
result, the Agency is not conducting a quantitative assessment of risk 
from potential BLAD exposure. Rather, the Agency's assessment of safety 
is based on the lack of exposure to BLAD because, as discussed in Unit 
V.C., the available residue data indicate that, when applied under 
current label rates and using good agricultural practices, there will 
be negligible to no detectable residues of BLAD on treated crops.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. BLAD has been approved 
for use on several commodities; therefore, EPA evaluated the potential 
for BLAD residues on those crops in order to assess exposure.
    CEV initially submitted residue data for grape, tomato, and 
strawberry. Field trials were conducted applying PROBLAD PLUS (a 
fungicide product containing BLAD at 20%) at the maximum product-
labeled application rate (0.75 pounds of active ingredient per acre, 
five broadcast foliar applications per season, at 7-day intervals). 
Those studies showed that there were no quantifiable residues (where 
the LOQ is 0.02 ppm) on any treated grape, tomato, or strawberry 
commodities, and the majority of samples showed no residues above the 
level of detection (0.005 ppm). (Ref. 15). CEV later submitted 
additional field residue studies on cherry, cucumber, and apple that 
similarly demonstrated that application consistent with labeled rates 
resulted in residues at or below the level of detection of 0.005 ppm. 
(Ref. 17).
    The Agency also requested that CEV conduct field trials using 
exaggerated application rates of 5X and 10X to determine the rate of 
BLAD residue degradation. Since the 10X concentration would be 
phytotoxic, CEV conducted field trials on tomatoes and strawberries 
using only the 5X application rate (3.75 pounds of active ingredient 
per acre). The decline curve for the treated commodities indicated a 
half-life of 2 days. Based on the measured residue levels in the study 
and using a first order degradation model, EPA was able to calculate a 
theoretical rate of degradation of 0.4215, which was then used to 
predict BLAD residues following treatment. (Ref. 15). Applying this 
degradation rate to residue levels observed in field residue data and 
taking into consideration the required 1-day interval between 
application and harvest of treated crops, the Agency expects that there 
will be no residues of BLAD above the level of detection, if any remain 
at all, when commodities are treated in accordance with the label. 
(Id.) This rapid degradation rate is consistent with the expectation 
that BLAD, as a protein fragment, is susceptible to rapid degradation 
by environmental factors, such as microbial proteases. (Ref. 17).
    Based on the available residue data, the Agency concludes that 
residues on grape, tomato, strawberry, apple, cherry, and cucumber will 
be below levels of detection and possibly non-existent when used in 
accordance with the label at the time of consumption. The Agency has 
also concluded that the available data is mutually supportive and is 
appropriate for supporting additional tolerances for certain crop 
groupings, hops, and almonds. (Id.)
    Based on the available representative commodity data, the 
registrant requested use on and tolerances for the following crop 
groups: Vegetable, fruiting, group 8-10; vegetable, cucurbit, group 9; 
fruit, pome, group 11-10; and fruit, stone, group 12-12. Although 
residue trials on all the representative commodities for those crop 
groups were not completed, the Agency has determined that trials on the 
remaining representative commodities are not necessary. The available 
residue data are mutually supportive and support a conclusion that any 
additional residue data for the other representative commodities would 
yield the same results. Given the similarity and consistency of the 
residue levels in these studies--in particular the consistency of 
results showing residues levels near or below the level of detection--
the similarity in plant morphology between the representative commodity 
and the other commodities in the corresponding crop group, and the 
additional factors supporting the anticipated lack of exposure to 
residues of BLAD (i.e., rapid degradation rate and post-harvest 
interval), the Agency concludes that the available data are sufficient 
to support these crop groups. (Id.)
    In addition, the Agency has concluded that no separate tolerances 
are needed for processed commodities of the raw agricultural 
commodities contained in these crop groups. (Id.) The rapid degradation 
of BLAD by microbes on treated crops combined with the methods for 
processing these commodities (e.g., washing and pasteurizing) will 
reduce the already low levels of residues on the treated commodities. 
The tolerances being established are sufficient to cover residues in 
those processed commodities.
    Moreover, although no residue field trials were submitted to 
support the hops, dried cones tolerance, the Agency has assessed the 
potential for exposure to BLAD residues on hops by examining the short 
environmental persistence of BLAD and the additional processing steps 
to which hops is subject prior to consumption. Following application of 
BLAD to hops, at rates that are the same as for other labeled crops, 
initial residues of BLAD are expected to rapidly degrade during the 
drying phase. The long drying time would also allow a longer time for 
microbial degradation of the protein. Furthermore, processing of hops, 
which is used as a flavoring and preservative in fermented beverages, 
is expected to further mitigate exposure prior to consumption. All of 
these factors suggest an elimination of potential residues on hops by 
the time of consumption. (Id.)
    Because the application rates and methods are the same for grape 
and almond, the residue data can be translated to almond hulls, and the 
Agency has determined that the residues on almond hulls will be similar 
to residues found on strawberries, grapes, and tomatoes. (Ref. 18). The 
general practice for harvesting almonds, which typically involves 7-10 
days of drying before processing, is likely to further reduce residues 
on the almond hulls. Also, because BLAD is not applied directly to the 
almonds, the Agency expects residues on the almond nutmeat itself to be 
even lower.
    Because almond hulls are an animal feed item, section 180.6 of 
EPA's regulations requires that EPA consider whether residues of BLAD 
present on animal feed items will result in residues of BLAD in meat, 
milk, eggs, or poultry commodities consumed by humans. 40 CFR 180.6(a). 
If there is no reasonable expectation of residues in the livestock 
commodities, the Agency can establish a tolerance on the raw 
agricultural commodity (in this case, the almond). 40 CFR 180.6(b). 
Based on the available information, EPA has concluded that the likely 
residues on almond hulls will be at or below levels of detection. Even 
if there are any residues remaining on almond hulls that are ingested 
by animals, EPA has concluded that there

[[Page 7705]]

is not likely to be any residues in the livestock commodities. (Ref. 
18). Due to its molecular size, BLAD is not expected to pass through 
biological membranes. Moreover, it is expected to be rapidly digested 
instead of accumulating in animal tissues. (Id.) As a result, there is 
no reasonable expectation of residues in livestock commodities and thus 
no need for associated livestock commodity tolerances.
    2. Dietary exposure from drinking water. The Agency expects 
residues of BLAD in drinking water to be negligible. Because BLAD is 
applied foliarly, there is a chance that it may get into drinking 
water, but there is likely to be very little in the environment from 
applications. Moreover, what little residue may be present would likely 
be subject to potential photolysis and microbial degradation due to its 
nature as a protein.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets). BLAD is not 
registered for any specific use patterns that would result in 
residential exposure.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information concerning the cumulative 
effects of [a particular pesticide's] . . . residues and other 
substances that have a common mechanism of toxicity.''
    EPA has not found BLAD to share a common mechanism of toxicity with 
any other substances, and BLAD does not appear to degrade into any 
toxic metabolite or other substance of concern. For the purposes of 
this tolerance action, therefore, EPA has assumed that BLAD does not 
have a common mechanism of toxicity with other substances. For 
information regarding EPA's efforts to determine which chemicals have a 
common mechanism of toxicity and to evaluate the cumulative effects of 
such chemicals, see EPA's website at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

D. Safety Factor for Infants and Children

    FFDCA section 408(b)(2)(C) provides that, in considering the 
establishment of a tolerance or tolerance exemption for a pesticide 
chemical residue, EPA shall apply an additional tenfold (10X) margin of 
safety for infants and children in the case of threshold effects to 
account for prenatal and postnatal toxicity and the completeness of the 
database on toxicity and exposure, unless EPA determines that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety is commonly referred to as the Food Quality 
Protection Act Safety Factor. In applying this provision, EPA either 
retains the default value of 10X, or uses a different additional safety 
factor when reliable data are available to support the choice of a 
different safety factor.
    Because the Agency has not identified any threshold effects for 
BLAD, this additional safety factor is not applicable for assessing 
risk to infants and children.

E. Aggregate Risks and Determination of Safety

    EPA has evaluated the available toxicity, allergenicity, and 
exposure data and considered its validity, completeness, and 
reliability, as well as the relationship of the results of the studies 
to human risk. Taking into consideration all available information on 
BLAD, EPA cannot conclude that unlimited exposures to BLAD on all food 
crops would not pose a risk of allergenicity to lupin-sensitive or 
peanut-sensitive individuals. The data submitted on the potential 
allergenicity does not overcome the burden for demonstrating that BLAD 
is not an allergen, given that BLAD is derived from a known allergenic 
source and the bioinformatics analysis demonstrates sequence similarity 
with other major allergens. Based on this information, the Agency can 
no longer support a safety determination for an unlimited exemption 
from the requirement of a tolerance for residues of BLAD on all food 
commodities. As a result, EPA is proposing to revoke the current 
tolerance exemption for BLAD found in 40 CFR 180.1319.
    Although EPA can no longer support the existing tolerance exemption 
for BLAD, which, on its face, places no limits on the levels of BLAD 
residues on any food commodities, EPA has determined, based on residue 
data supporting a conclusion of negligible to no exposure to BLAD 
residues on certain crops, that certain limited tolerances would be 
safe. That is, there is a reasonable certainty that no harm will result 
to the U.S. population, including infants and children, from aggregate 
exposure to residues of BLAD when it is applied as a fungicide in 
accordance with label directions and good agricultural practices on the 
following commodities: Almond; almond, hulls; fruit, pome, group 11-10; 
fruit, stone, group 12-12; grape; hops, dried cones; strawberry; 
vegetable, cucurbit, group 9; and vegetable, fruiting, group 8-10. Such 
exposure includes all anticipated dietary exposures and all other 
exposures for which there is reliable information.
    Upon consideration of information regarding the likely levels of 
exposure to BLAD from approved use patterns, EPA concludes that the 
approved uses of BLAD are unlikely to result in residues above the 
level of detection when shipped in interstate commerce. Further, based 
on expected degradation rates, the Agency expects residue levels at the 
time of consumption to be even lower, likely non-existent. The lack of 
exposure to detectable residues of BLAD, if there are any residues at 
all, is the basis for the Agency's safety finding for these tolerances.
    While the Agency, as a general matter, expects users to follow 
label directions on pesticide products and that residue data indicate 
that application in accordance with the label results primarily in 
undetectable residues or levels at or below levels of detection, EPA is 
proposing to establish tolerances at the lowest level for measuring 
quantifiable residues of BLAD (0.02 ppm). Given the potential severity 
of allergic reactions, the Agency believes that setting numerical 
tolerances, rather than leaving in effect an unlimited exemption, is 
the appropriate regulatory mechanism for monitoring residues and 
facilitates the removal of adulterated commodities from the food supply 
if residues are found above tolerance levels on any of these 
commodities. The expectation of negligible to no residues under proper 
use conditions, subject to the mechanisms of enforcement under the 
FFDCA and the Federal Insecticide, Fungicide, and Rodenticide Act 
(FIFRA), provide assurance that consumers will not be exposed to 
residues of BLAD that may cause harm. Therefore, EPA is proposing to 
revoke the current exemption and establish tolerances for residues of 
BLAD in or on the following commodities at 0.02 ppm: Almond; almond, 
hulls; fruit, pome, group 11-10; fruit, stone, group 12-12; grape; 
hops, dried cones; strawberry; vegetable, cucurbit, group 9; and 
vegetable, fruiting, group 8-10.

VI. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (Enzyme-Linked Immunosorbent Assay 
(ELISA: EASI Method No: RA029 and

[[Page 7706]]

RA031)) is available to enforce the tolerance expression.
    The method may be requested from: Chief, Analytical Chemistry 
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 
20755-5350; telephone number: (410) 305-2905; email address: 
residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint FAO/WHO food 
standards program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established an MRL for BLAD.

C. Trade and Economic Considerations

    The Agency received comments on its May 29, 2015, proposal about 
the potential impact of the proposal on trade and farmers. The 
commenters alleged that the proposal failed to address possible impacts 
on international trade, including the potential to cause other 
countries to require or amend MRLs, to develop enforcement procedures 
consistent with international regulatory data requirements, and to 
impose new and more onerous data requirements. The commenters also 
expressed concern about the lack of harmonization with Canada, which 
has decided not to regulate residues of BLAD, and pointed to the 
potential for disruption in trade between the United States and Canada, 
or at least confusion at the border for enforcing the different 
standards, as a result. In addition, many commenters expressed concern 
that the proposal revoking the exemption would have an adverse impact 
on farmers who relied on BLAD as an effective fungicide.
    Under the FFDCA, tolerances and exemptions from the requirement of 
a tolerance may be established when EPA determines that they are safe. 
21 U.S.C. 346a(b)(2)(A)(i), (c)(2)(A)(i). The FFDCA also requires that 
EPA revoke tolerances or exemptions when it determines they are not 
safe. Id. This safety assessment is a risk-only assessment, not a risk-
benefit standard. In essence, the statute directs that whether EPA can 
leave in effect or establish a tolerance or exemption is based solely 
on the Agency's assessment of the risk to human health and not a 
balancing of other non-safety factors (e.g., impact on trade or impact 
on farmers) with the risk. The FFDCA directs EPA to consider several 
factors relevant to the safety of the pesticide residue in food 
(aggregated with other sources of exposure to the pesticide residue), 
placing particular emphasis on human dietary risk. See, e.g., 21 U.S.C. 
346a(b)(2)(B) (addressing an exception to the safety standard for 
pesticide residues as to which EPA ``is not able to identify a level of 
exposure to the residue at which the residue will not cause or 
contribute to a known or anticipated harm to human health''); 21 U.S.C. 
346a(b)(2)(C) (requiring special safety findings as to ``infants and 
children'' regarding their ``disproportionately high consumption of 
foods'' and their ``special susceptibility * * * to pesticide chemical 
residues''); 21 U.S.C. 346a(b)(2)(D)(iii) (requiring consideration of 
the relationship between toxic effects found in pesticide studies and 
human risk); 21 U.S.C. 346a(b)(2)(D)(iv), (vi), and (vii) (requiring 
consideration of available information on ``dietary consumption 
patterns of consumers,'' ``aggregate exposure levels of consumers,'' 
and the ``variability of the sensitivities of major identifiable 
subgroups of consumers''); 21 U.S.C. 346a(b)(2)(D)(vi) (requiring 
consideration of ``non-occupational'' sources of exposure); 21 U.S.C. 
346a(b)(2)(D)(viii) (requiring consideration of information bearing on 
whether a pesticide ``may have an effect in humans that is similar to 
an effect produced by a naturally occurring estrogen or other endocrine 
effects''); 21 U.S.C. 346a(l)(2) and (3) (requiring revocation or 
suspension of tolerances where associated FIFRA registration is 
canceled or suspended ``due in whole or in part to dietary risks to 
humans posed by residues of that pesticide chemical on that food'').
    The only mention of a factor relevant to trade is found in FFDCA 
section 408(b)(4), which, as noted in Unit VI.B., requires EPA to 
determine whether an MRL has been established by Codex when 
establishing a tolerance and to explain its reasons for departing from 
that level, if applicable. 21 U.S.C. 346a(b)(4). Here, as noted above, 
Codex has not established any MRLs for BLAD; therefore, there is 
nothing to harmonize and no discrepancies to explain. As a matter of 
policy and where the Agency can support the safety finding, EPA seeks 
to harmonize U.S. tolerances whenever possible with Codex MRLs and the 
MRLs of other trading partners, including Canada, consistent with U.S. 
food safety standards and agricultural practices. For BLAD, based on 
the available information, EPA can no longer maintain the safety 
finding to support the unlimited tolerance exemption for BLAD residues 
on all commodities. Harmonization with Canada's regulatory approach is 
not a legal basis for retaining the exemption under the FFDCA when EPA 
concludes that the exemption is not safe.
    Notwithstanding the substantive restrictions of the FFDCA, EPA 
recognizes the obligations of the United States to comply with the 
procedural obligations under the World Trade Organization's Sanitary 
and Phytosanitary Measures Agreement (SPS Agreement). Because the 
proposal is a regulation subject to the requirements of the SPS 
Agreement, EPA intends to comply with the provisions of that Agreement, 
including those related to notification and implementation, including 
allowing for a 6-month delay in the exemption revocation to provide 
exporting countries a period of time to adjust to the U.S. new 
tolerances. In any event, the revocation in this proposal is not 
discriminatory and is designed to ensure that both domestically 
produced and imported foods meet the food safety standard established 
by the FFDCA.

VII. Conclusion

    EPA proposes to revoke the existing tolerance exemption for 
residues of BLAD in or on all food commodities as established in the 
Federal Register of March 22, 2013 (78 FR 17600) (FRL-9380-6) under 
section 408 of the FFDCA. Based on the available information, EPA can 
no longer support the safety finding necessary to maintain the 
exemption. Notwithstanding the Agency's conclusions concerning the 
unlimited exemption, the Agency has determined that the available 
information supports a safety finding for the tolerances for residues 
of BLAD in or on almond; almond, hulls; fruit, pome, group 11-10; 
fruit, stone, group 12-12; grape; hops, dried cones; strawberry; 
vegetable, cucurbit, group 9; and vegetable, fruiting, group 8-10 at 
0.02 ppm. Therefore, EPA is proposing to establish tolerances for 
residues of BLAD on those commodities.

VIII. References

    The following is a listing of the documents that are specifically

[[Page 7707]]

referenced in this document. The docket includes these documents and 
other information considered by EPA, including documents that are 
referenced within the documents that are included in the docket, even 
if the referenced document is not physically located in the docket. For 
assistance in locating these other documents, please consult the person 
listed under FOR FURTHER INFORMATION CONTACT.

1. U.S. Food and Drug Administration (FDA). Letter from Michael A. 
Adams, Ph.D., Deputy Director of Office of Food Additive Safety 
(FAS), Center for Food Safety and Applied Nutrition (CFSAN) to 
Menyon Adams, Biopesticides and Pollution Prevention Division 
(BPPD), Office of Pesticide Programs (OPP), re: Docket Number EPA-
HQ-OPP-2011-1026. May 21, 2013.
2. Food and Agriculture Organization of the United Nations (FAO)/
World Health Organization (WHO). Evaluation of Allergenicity of 
Genetically Modified Foods: Report of a Joint FAO/WHO Expert 
Consultation on Allergenicity of Foods Derived from Biotechnology. 
January 2001.
3. WHO/FAO. Codex Alimentarius: Foods Derived from Modern 
Biotechnology. 2009.
4. U.S. Environmental Protection Agency (EPA). Memorandum from 
Miachel Rexrode, Ph.D., Senior Biologist (BPPD) to Menyon Adams, 
Regulatory Action Leader (BPPD). Request for New Product 
Registration for [beta]-Conglutin Section 3 with Tolerance. May 24, 
2012.
5. European Food Safety Authority (EFSA). Opinion of the Scientific 
Panel on Dietetic Products, Nutrition and Allergies on a Request 
from the Commission Related to the Evaluation of Lupin for Labelling 
Purposes. (Request No. EFSA-Q-2005-086). The EFSA Journal (2005) 
302, 1-11. December 6, 2005.
6. U.S. EPA. Memorandum from John L. Kough, Ph.D., Biologist (BPPD) 
to Menyon Adams, Regulatory Action Leader (BPPD). Review of 
Allergenicity Decisions on BLAD. December 9, 2015.
7. U.S. EPA. Memorandum from Robert McNally, Director, BPPD, OPP to 
Dennis M. Keefe, Ph.D., Director, CFSAN, FAS. Request for Specific 
Input from FDA to Assist EPA in Addressing Comments Received in 
Response to EPA's Proposal Regarding Banda de Lupinus alba doce 
(BLAD). December 7, 2015.
8. U.S. Department of Health and Human Services (HHS). Memorandum 
from Stefano Luccioli, MD, Medical Officer, FAS, CFSAN to Dennis 
Keefe, Ph.D., Director, FAS, CFSAN. Response to EPA Questions in 
Memorandum Dated December 7, 2015, Regarding BLAD Biopesticide. 
December 17, 2015.
9. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and 
Allergies), 2014. Scientific Opinion on the Evaluation of Allergenic 
Foods and Food Ingredients for Labelling Purposes. EFSA Journal 
2014;12(11):3894, 286 pp. doi:10.2903/j.efsa.2014.3894. November 26, 
2014.
10. Commission Directive 2006/142/EC (December 22, 2006), amending 
Annex IIIa of European Directive 2000/13/EC (March 20, 2000).
11. U.S. FDA. Allergies to a Legume Called Lupin: What You Need to 
Know. https://www.fda.gov/consumers/consumer-updates/allergies-legume-called-lupin-what-you-need-know (last checked May 31, 2019).
12. U.S. FDA. Frequently Asked Questions on Lupin and Allergenicity. 
https://www.fda.gov/food/food-additives-petitions/lupin-and-allergenicity-frequently-asked-questions (last checked May 30, 
2019).
13. World Health Organization/International Union of Immunological 
Sciences. Allergen Nomenclature. Allergen details for Lup an 1. 
http://www.allergen.org/viewallergen.php?aid=421 (last checked May 
31, 2019).
14. U.S. EPA. Memorandum from Miachel Rexrode, Ph.D., Senior 
Biologist (BPPD) to Linda Hollis, Chief, Biochemical Pesticides 
Branch (BPB), BPPD. BLAD Data Requirements. May 15, 2013.
15. U.S. EPA. Memorandum from Miachel Rexrode, Ph.D., Senior 
Biologist (BPPD) to Menyon Adams, Regulatory Action Leader (BPPD). 
Evaluation of New Serum Testing and Field Residue Decline Study for 
BLAD. June 6, 2014. As corrected by the following document: U.S. 
EPA. Memorandum from Miachel Rexrode, Ph.D., Senior Biologist (BPPD) 
to Menyon Adams, Regulatory Action Leader (BPPD). December 28, 2016.
16. U.S. EPA. Memorandum from John L. Kough, Ph.D., Biologist (BPPD) 
to Menyon Adams, Regulatory Action Leader (BPPD) and Linda Hollis, 
Branch Chief, BPB, BPPD. Review of FDA Interactions on the 
Allergenicity Assessment of Banda de Lupinus alba (BLAD) from CEV. 
August 23, 2016.
17. U.S. EPA. Memorandum from John L. Kough, Ph.D., Biologist (BPPD) 
to Menyon Adams, Regulatory Action Leader (BPPD). Review of Crop 
Groupings for PROBLAD PLUS. June 26, 2019.
18. U.S. EPA. Memorandum from Judy Facey, Ph.D., Associate Branch 
Chief (Acting), BPB, BPPD and John L. Kough, Ph.D., Senior Scientist 
(BPPD) to Menyon Adams, Regulatory Action Leader (BPPD) and Linda 
Hollis, Branch Chief, BPB, BPPD. ChemSAC Conclusion on: Potential 
BLAD Residues in Meat or Milk from Almond Hull Feed Consumption 
Resulting from Almond Treatment. January 24, 2017.
19. U.S. EPA. Memorandum from Denise Keehner, Division Director, 
Biological and Economic Analysis Division, OPP to Public Docket 
concerning Tolerance Revocation Rulemaking, Proposed or Final. RFA/
SBREFA Certification for Import Tolerance Revocation. May 25, 2001.

IX. Statutory and Executive Order Reviews

    Although this proposed action would revoke an existing exemption 
from the requirement of a tolerance, it also would establish new 
tolerances that would cover pesticide chemical residues resulting from 
existing registered uses under FFDCA section 408(e). The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Orders 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993), and 13563, entitled Improving 
Regulation and Regulatory Review (76 FR 3821, January 21, 2011). As a 
result, this action is not subject to Executive Order 13211, entitled 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). Nor does it require 
OMB review or any Agency action under Executive Order 13045, entitled 
Protection of Children from Environmental Health Risks and Safety Risks 
(62 FR 19885, April 23, 1997). Nor is this action considered a 
regulatory action subject to review under Executive Order 13771, 
entitled Reducing Regulations and Controlling Regulatory Costs (82 FR 
9339, February 3, 2017).
    This action does not contain any information collections subject to 
OMB approval under the Paperwork Reduction Act (44 U.S.C. 3501 et 
seq.); does not require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); and does not involve any technical standards that 
would require Agency consideration of voluntary consensus standards 
pursuant to section 12(d) of the National Technology Transfer and 
Advancement Act (15 U.S.C. 272 note).
    This action directly regulates growers, food processors, food 
handlers, and food retailers, but it does not regulate State or tribal 
governments. Nor does this action alter the relationships or 
distribution of power and responsibilities established in the 
preemption provisions of FFDCA section 408(n)(4). Therefore, the Agency 
has determined that Executive Orders 13132, entitled Federalism (64 FR 
43255, August 10, 1999), and 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 9, 
2000), do not apply to this action. In addition, this action does not 
impose any enforceable duty, contain any unfunded mandate, or

[[Page 7708]]

otherwise significantly or uniquely affect small governments as 
described in the Unfunded Mandates Reform Act (2 U.S.C. 1501 et seq.).
    Pursuant to the Regulatory Flexibility Act (5 U.S.C. 601 et seq.), 
the Agency previously assessed whether establishment of tolerances, 
exemptions from tolerances, raising of tolerance levels, expansion of 
exemptions, or revocations might significantly impact a substantial 
number of small entities and concluded that, as a general matter, these 
actions do not impose a significant economic impact on a substantial 
number of small entities. These analyses for tolerance establishments 
and modifications and for tolerance revocations were published in the 
Federal Register of May 4, 1981 (46 FR 24950) (FRL-1809-5) and December 
17, 1997 (62 FR 66020) (FRL-5753-1), respectively, and were provided to 
the Chief Counsel for Advocacy of the Small Business Administration. 
Taking into account this analysis, and available information concerning 
the pesticide listed in this proposed rule, the Agency hereby certifies 
that this proposed rule will not have a significant negative economic 
impact on a substantial number of small entities. In a memorandum dated 
May 25, 2001, EPA determined that eight conditions must all be 
satisfied in order for an import tolerance or tolerance exemption 
revocation to adversely affect a significant number of small entity 
importers, and that there is a negligible joint probability of all 
eight conditions holding simultaneously with respect to any particular 
revocation. (Ref. 19). Furthermore, for BLAD, the Agency knows of no 
extraordinary circumstances that exist as to the present proposed rule 
that would change EPA's previous analysis. Any comments about the 
Agency's determination should be submitted to EPA along with comments 
on the proposed rule and will be addressed prior to issuing a final 
rule.

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: January 21, 2020.
Richard Keigwin,
Director, Office of Pesticide Programs.

    Therefore, it is proposed that 40 CFR chapter I be amended as 
follows:

PART 180--[AMENDED]

0
 1. The authority citation for part 180 continues to read as follows:

     Authority: 21 U.S.C. 321(q), 346a and 371.

0
2. Add Sec.  180.707 to subpart C to read as follows:


Sec.  180.707  Banda de Lupinus albus doce (BLAD); tolerances for 
residues.

    (a) General. Tolerances are established for residues of the 
fungicide banda de Lupinus albus doce (BLAD), including its metabolites 
and degradates, in or on the commodities in the table below. Compliance 
with the tolerance levels specified below is to be determined by 
measuring only BLAD in or on the following commodities.

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
Almond......................................................        0.02
Almond, hulls...............................................        0.02
Fruit, pome, group 11-10....................................        0.02
Fruit, stone, group 12-12...................................        0.02
Grape.......................................................        0.02
Hops, dried cones...........................................        0.02
Strawberry..................................................        0.02
Vegetable, cucurbit, group 9................................        0.02
Vegetable, fruiting, group 8-10.............................        0.02
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]
0
 3. Revise Sec.  180.1319 in subpart D to read as follows:


Sec.  180.1319  Banda de Lupinus albus doce (BLAD); exemption from the 
requirement of a tolerance.

    An exemption from the requirement of a tolerance is established for 
the residues of Banda de Lupinus albus doce (BLAD), a naturally 
occurring polypeptide from the catabolism of a seed storage protein 
([beta]-conglutin) of sweet lupines (Lupinus albus), in or on all food 
commodities when applied as a fungicide and used in accordance with 
label directions and good agricultural practices. This exemption 
expires on [date 6 months after date of publication of final rule in 
the Federal Register].

[FR Doc. 2020-02665 Filed 2-10-20; 8:45 am]
BILLING CODE 6560-50-P


