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Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations for Potassium Salts of Hops Beta 

acids (K-HBAs)

Docket ID Number: EPA-HQ-OPP-2014-0374 (NOF),

Date: July 15, 2015

Section 408(c)(2)(A)(i) of FFDCA allows the U.S. Environmental Protection Agency (EPA or the Agency)

to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical 

residue in or on a food) only if the EPA determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of 

FFDCA 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. Pursuant to FFDCA section 408(c)(2)(B), 

in establishing or maintaining in effect an exemption from the requirement of a tolerance, the EPA must 

take into account the factors set forth in FFDCA section 408(b)(2)(C), which require the EPA to give 

special consideration to exposure of infants and children to the pesticide chemical residue in establishing a 

tolerance exemption, and to “ensure that there is a reasonable certainty that no harm will result to infants 

and children from aggregate exposure to the pesticide chemical residue....” Additionally, FFDCA section 

408(b)(2)(D) requires that the EPA consider “available information concerning the cumulative effects of [a 

particular pesticide's] . . . residues and other substances that have a common mechanism of toxicity.”

The EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide 

residues. First, the EPA determines the toxicity of pesticides. Second, the EPA examines exposure to the 

pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in 

residential settings.

I. Summary of Petitioned-for Tolerance Exemption

In the Federal Register of September 05, 2014 (79 FR 53012) (FRL-9914-98), EPA issued a notice 

pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 

petition (PP 3E8217) by Interregional Research Project Number 4, on behalf of BetaTec Hop Products, Inc. 

(the Petitioner), 500 College Road East, Suite 201W, Princeton, New Jersey, 08540. The petition requested 

that 40 CFR part 180 be amended by establishing an exemption from the requirement of a tolerance for 

residues of potassium salts of hops beta acids (K-HBAs) in or on honey and honeycomb. The notice 

referenced a summary of the petition prepared by the Petitioner, which is available in Docket ID Number 

EPA-HQ-OPP-2014-0374 via http://www.regulations.gov.

II. Toxicological Profile

Consistent with section 408(b)(2)(D) of FFDCA, the EPA reviewed the available scientific data and other 

relevant information on K-HBAs, and considered its validity, completeness, and reliability, as well as the 

relationship of this information to human risk. The EPA also considered available information concerning 

the variability of the sensitivities of major identifiable subgroups of consumers, including infants and 

children.

A. Overview of Potassium Salts of Hops Beta Acids

K-HBAs are derived from the resin components of the cones of female hop plants, Humulus lupulus. The 

three major components of hop beta acids (HBA) are lupulone (30-55% with an isopropyl side chain), 

colupulone (20-55% with an isobutyl side chain); and adlupulone (5-10% with a secbutyl side chain). K-
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HBAs are classified as a biochemical pesticide because they are naturally occurring, have a non-toxic mode 

of action against the target pest(s), and are structurally similar, and/or functionally identical to a naturallyoccurring active ingredient. K-HBAs are intended to be applied inside bee hives to the brood supers via

plastic strips. The strips will be treated with a 16% solution of K-HBAs (two strips per hive; 1.92 g/strip). 

There is a long history of safe use of HBA. Humans are exposed to HBA from its use as a preservative on 

meats (estimated range 4.4 mg/kg of cooked meat - 5.5 mg/kg of frankfurter) (Ref 10,) and the presence of 

HBAs in the beer brewing process (Ref 14). HBAs are considered to be Generally Recognized As Safe 

(GRAS) by FDA (Ref 10). In addition, HBAs have been shown to inhibit inflammations in mice and 

exhibit anticarcinogenic activity without any known side effects (Ref 2).

EPA granted a Section 18 Emergency Exemption in 2011 for K-HBA in over 20 States to control Varroa 

mites (Varroa destructor) in honeybee hives. The Section 18 was renewed in 2012 and 2013 in up to 37 

States to control Varroa mites (Ref 3).

Based on the data submitted in support of this petition (summarized in Unit II. B., below) and the 

comprehensive risk assessment conducted by the Agency (References 1-3, below), EPA concludes that 

there is a reasonable certainty of no harm from aggregate exposures to potassium salts of hops beta acids, 

including the consumption of food treated with this active ingredient in accordance with label directions 

and good agricultural practices. EPA has made this determination because available toxicology data 

indicate that the active ingredient is of low acute toxicity and is not a developmental toxicant, a mutagen, or 

toxic via repeat oral exposure.

B. Biochemical Pesticide Toxicology Data Requirements

All applicable mammalian toxicology data requirements supporting the request for an exemption from the 

requirement of a tolerance for residues of K-HBAs in or on honey and honeycomb have been fulfilled with 

data submitted by the petitioner. The following is a summary of EPA’s review of the toxicity profile of this 

biochemical:

 

Acute Toxicity: The applicant did not submit any Guideline studies in support of the Tier I toxicity data 

requirements for the TGAI/EP. In lieu of Guideline studies, the applicant submitted rationales submitted by

data and information from the technical literature. 

1. In lieu of an acute oral toxicity study, the registrant submitted a rationale supported by toxicity and 

exposure information obtained from the technical literature in fulfillment of the acute oral toxicity

data requirement for the TGAI/EP. A single intragastric (oral gavage) administration of hops beta 

acids (as lupulon) to mice and rats resulted in LD50s of 1500 mg/kg and 1800 mg/kg, respectively. 

These data classify HBA in Toxicity Category III for acute oral toxicity (Ref 2).

2. In lieu of an acute dermal toxicity study, the applicant submitted a rationale supported by toxicity

and exposure information (Ref 2) obtained from the technical literature in fulfillment of the acute 

dermal toxicity data requirement for the TGAI. Much of the information was not useable in that it 

did not specifically address the acute dermal toxicity route of exposure. The submitted information 

(Ref 2 and Ref 8) did not specifically address the acute dermal toxicity route of exposure. In 

addition, humans were used as the test subjects and the study was not submitted to the Human 

Studies Review Board (HSRB) for a review of its suitability for use in supporting a pesticide 

registration. In the absence of this information, the Biochemical Pesticides Branch (BPB) reviewer 
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notes that acute dermal exposure to Hops Beta Acids is highly unlikely and would only occur to the 

beekeeper/applicator, as the end use product is for Commercial applicators only. There are no 

residential uses and therefore, based on the method of application (manually applied via plastic 

strips inside beehives), non-occupational exposure to Hops Beta Acids will be minimal. 

Commercial/Occupational exposure is mitigated by protective clothing normally worn by

beekeepers, including gloves, protective suits, and a hat with a face mask or netting. Precautionary

statements on the label must require the use of gloves and eye protection for beekeepers/applicators. 

3. In lieu of an acute inhalation study, the registrant did not generate or submit Guideline studies for 

either the TGAI or the EP but addressed the data requirement with information from the open 

literature. Inhalation exposure to the active ingredient is highly unlikely based on the non-volatile 

nature of the active ingredient and method of application (manual application of treated plastic 

strips into beehives. Inhalation exposure to the active ingredient will be minimal. The applicant

also provided the following exposure rationale: “HopGuard (the end-use product containing 16% 

Hops Beta Acids), is non-volatile, viscous, is not sprayed, and there is no dust associated with the 

strips so inhalation exposure is highly unlikely.” Based on these data, K-HBAs are classified as 

Toxicity Category IV for acute inhalation toxicity.

4. A guideline primary eye irritation study was conducted using potassium salts of Hops Beta Acids 

(the TGAI) on rabbits. The normal pH of the test substance is pH 11 and was adjusted to pH 9 prior 

to use. Each of three test rabbits was administered a 0.1 mL of the test substance to the conjunctival 

sac of the right eye; the left eyes were used as the controls. Test and control eyes were observed for 

signs of irritation for 21 days post treatment. Corneal opacity, iritis, and conjunctivitis were 

observed a 1-hour post treatment. By Day 21 post treatment, none of the ocular responses had 

completely resolved in any of the test eyes. Based on these data, K-HBAs are classified as 

Corrosive, Toxicity Category I, for primary eye irritation. 

5. In lieu of a primary dermal irritation study, the applicant submitted the following rationale 

supported by toxicity and exposure information (Ref 2) obtained from the technical literature in 

fulfillment of the primary dermal irritation data requirement for the TGAI/EP: “Contact with 

growing hop plants is known to cause an allergic contact dermatitis and is attributed to the 

myrcene oil in fresh hop oil. Growing hop plants can also cause a mechanical dermatosis attributed 

to the rough climbing hairs on the stem and secretions of the yellow glandular hairs on hops. It is 

hypothesized that the hop maturing process may turn certain hop proteins into allergens, in rare 

cases leading to a diagnosis of immunological contact urticaria. Hops Beta Acids were not 

implicated in this process (Ref 2). Based on the rationale (Ref 2) submitted above, and the 

mitigation of exposure with appropriate PPE, it is recommended that Toxicity Category I PPE 

precautionary language for acute dermal toxicity be placed on the label. More importantly, oils, 

rough climbing hairs and secretions from the yellow glandular hairs of fresh hops are not present in 

the final, extracted hops beta acids active ingredient. 

6. In response to the hypothesis described above, EPA believes that any potential proteins that may 

hypothetically turn into allergens by the hops plant maturing process would be removed during the 

hops beta acids extraction process. Furthermore, hops beta acids do not contain protein and even in 

the unlikely event that proteins were present in the hops beta acids as a result of the extraction 

process, the proteins would likely be denatured and therefore would not pose the threat of 

developing into a potential allergen. 
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7. In lieu of a dermal sensitization study, the applicant submitted a rationale supported by toxicity and 

exposure information (Ref 2) obtained from the technical literature in fulfillment of the dermal 

sensitization data requirement for the TGAI/EP but addressed the data requirement with information 

from the open literature. Much of the information was not useable in that it did not specifically 

address primary dermal sensitization. However, the applicant did provide the following exposure 

rationale: “Contact with growing hop plants is known to cause an allergic contact dermatitis and is 

attributed to the myrcene oil in fresh hop oil. Growing hop plants can also cause a mechanical 

dermatosis attributed to the rough climbing hairs on the stem and secretions of the yellow glandular 

hairs on hops. It is hypothesized that the hop maturing process may turn certain hop proteins into 

allergens, in rare cases leading to a diagnosis of immunological contact urticaria. Hops Beta Acids 

were not implicated in this process (Ref 2). Based on the rationale (Ref 2) and the mitigation of 

exposure with appropriate PPE. It is recommended that Toxicity Category I PPE precautionary

language for acute dermal toxicity be placed on the label, based on the results of the Primary

Dermal Irritation study. Commercial/Occupational exposure is mitigated by protective clothing 

normally worn by beekeepers, including gloves, protective suits, and a hat with a face mask or 

netting. Precautionary statements on the label must require the use of gloves and eye protection for 

beekeepers/applicators. More importantly, oils, rough climbing hairs and secretions from the 

yellow glandular hairs of fresh hops are not present in the final, extracted hops beta acids active 

ingredient. In response to the hypothesis described above, EPA believes that any potential proteins 

that may hypothetically turn into allergens by the hops plant maturing process would be removed 

during the hops beta acids extraction process. Furthermore, hops beta acids do not contain protein 

and even in the unlikely event that proteins were present in the hops beta acids as a result of the 

extraction process, the proteins would likely be denatured and therefore would not pose the threat of 

developing into a potential allergen. 

 

Mutagenicity: Mutagenicity studies and information were not submitted by the applicant. However, the 

Agency does not consider mutagenicity studies or information to be required. HBAs are not structurallyrelated to known mutagens, nor are they in a chemical class known to contain a known mutagen. 

Significant exposure (occupational and non-occupational) to female humans is highly unlikely, based on 

the method of product application (manual insertion of HBA-treated strips into beehives), the requirement 

for appropriate PPE (gloves and eye protection worn by workers/applicators), 

low application rate (two strips per hive; 1.92 g/strip), and appropriate PPE (gloves and eye protection) 

worn by workers/applicators. Moreover, residues of HBA have been shown not to exceed 0.44 ppm in 

honey (observed in only one sample in three field studies between 2010 and 2012). When fed to rats in 

drinking water at up to 50 ppm daily for 7 months, HBAs have been shown to have potent anticarcinogenic 

activity against experimentally-induced colon cancers with no observed toxic effects (Ref 13). This 

subchronic exposure in drinking water (50 ppm) is approximately 114X greater than the residues detected 

in one sample of honey (0.44 ppm). Mutagenicity resulting from exposure, if any, to HBAs is considered 

by the Agency to be highly unlikely.

Subchronic Toxicity: In fulfilling the 90-day oral data requirement, the applicant did not submit Guideline 

studies for the TGAI. Repeated, subchronic exposure to the active ingredient is highly unlikely based on 

the method of application (manual application of treated plastic strips into beehives). Dietary exposure 

also, is highly unlikely, based on the lack of residues in edible honey (see residue studies above). In three 

different studies conducted over three years, only one honey sample from one honey super was shown to 

have residues of hops beta acids (0.44 ppm), and the residue level was only slightly above the analytical 

limits of detection (0.41 ppm) and well below the Limit of Quantitation (1.2 ppm). Additional information 

provided by the registrant (Ref 2; discussed in paragraphs 1-4 below), supports the rationale that HBAs
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have minimal subchronic toxicity:

1. When fed to rats in drinking water at up to 50 ppm daily for 7 months, HBAs have been shown to 

have potent anticarcinogenic activity against experimentally-induced colon cancers with no 

observed toxic effects (Ref 13). This subchronic exposure in drinking water (50 ppm) is 

approximately 114X greater than the residues detected in one sample of honey (0.44 ppm).

2. Hops beta acids are approved by the USDA/FSIS for use on ready to eat meat products at up to 5.5 

mg/kg (Ref 1, Ref 2 and Ref 3) to control pathogens, and has been approved for use on control 

Listeria moncytogenes on frankfurters at up to 2.5 mg/pound on cooked meat and poultry products 

(Ref 1, Ref 2. and Ref 3).

3. In a review of information used to support FDA GRAS status, it was stated that there is a long 

history of dietary exposure to HBAs [comprised primarily of lupulone (C26H38O4), adlupulone 

(C25H37O4), and colupulone (C28H38O4)], via beer consumption (FDA, 2001). The same notice 

provided estimates of dietary intake, via the use of hops beta acids as antimicrobial agents in cooked 

ready-to-eat meats and on frankfurters, to be up to 0.27 mg per person per day. A review of the 

literature in support of the FDA GRAS status demonstrated that no estrogenic activity was observed 

for polarity extracts of hops beta acids (FDA, 2001). 

4. The active ingredient occurs naturally in the lupulin glands of the flowers (cones) of hops (Humulus 

lupulus and contain up to 10% hops beta acids (Ref 14). Hops are used extensively in the brewing 

of beer and have been used to inhibit acute localized inflammations in mice at concentrations of up 

to 0.4 ppm (intravenous injection) with no side effects (Ref 6). 

In lieu of a Guideline study, the applicant submitted a rationale supported by toxicity and exposure 

information obtained from the technical literature (Ref 2) in fulfillment of the 90-day dermal toxicity data 

requirement for the TGAI/EP: “Contact with growing hop plants is known to cause an allergic contact 

dermatitis and is attributed to the myrcene oil in fresh hop oil. Growing hop plants can also cause a 

mechanical dermatosis attributed to the rough climbing hairs on the stem and secretions of the yellow 

glandular hairs on hops. It is hypothesized that the hop maturing process may turn certain hop proteins 

into allergens, in rare cases leading to a diagnosis of immunological contact urticaria. Hops Beta Acids 

were not implicated in this process (Ref 2). HBAs is highly unlikely based on the method of application 

(manually inserted into beehives), low application rate, lack of appreciable residues in honey, and 

appropriate PPE (gloves and eye protection) worn by beekeepers/applicators. 

The applicant did not submit Guideline studies for the 90-day inhalation data requirement for either the 

TGAI. However, the Agency does not consider 90-day inhalation studies or information to be required. 

Repeated, subchronic inhalation exposure to the active ingredient is highly unlikely based on the nonvolatile nature of the active ingredient and method of application (manual application of treated plastic 

strips into beehives. Non-occupational exposure to the active ingredient does not occur. The applicant also 

provided the following exposure rationale: “HopGuard (the end-use product containing 16% Hops Beta 

Acids), is non-volatile, viscous, is not sprayed, and there is no dust associated with the strips so inhalation 

exposure is highly unlikely.” 

Developmental Toxicity: The applicant did not submit Guideline studies for the TGAI. Based on 40 CFR 

part 158.2050, if the use of the product under widespread and commonly recognized practice will not result 

in significant exposure to female humans or susceptible populations for the following reasons (discussed in 

detail under mutagenicity): Occupational and non-occupational exposure is expected to be minimal due to 
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the method of application and the lack of appreciable residues in honey. Hops Beta Acids are applied inside 

the hive to the brood supers, on plastic strips treated with a 16% solution of Hops Beta Acids (two strips 

per hive; 1.92 g/strip). Residues have been shown not to exceed 0.44 ppm in honey (see residues studies 

above), well below any known acute (1500 mg/kg; Ref 5) or subchronic (50 ppm in drinking water (; Ref 

13) endpoints for Hops Beta Acids. No additional data are required at this time. Developmental toxicity

resulting from exposure, if any, to Hops Beta Acids is considered by the Agency to be highly unlikely.

III. Aggregate Exposure

In examining aggregate exposure, FFDCA section 408 directs the EPA to consider available information

concerning exposures from the pesticide residue in food and all other non-occupational exposures, 

including drinking water from ground water or surface water and exposure through pesticide use in 

gardens, lawns, or buildings (residential and other indoor uses).

Food Exposure: Dietary exposure is highly unlikely based on the lack of residues in edible honey. In three 

different studies conducted over three years, only one honey sample from one honey super was shown to 

have residues of HBAs (0.44 ppm), and the residue level was only slightly above the analytical limits of 

detection (0.41 ppm) and well below the Limit of Quantitation (1.2 ppm). The acute oral toxicity LD50 = 

1500 mg/kg (Chin and Anderson, 1950), a level that is approximately 3409X the level found in one sample 

of honey. According to the National Honey Board (NHB, 2014), annual U.S. per capita honey consumption 

was approximately 1.3 lbs (approximately 0.6 kg or 600 mg) in 2013. Assuming a 70 kg standard human 

and the lower acute oral toxicity endpoint (LD50 = 1500 mg/kg), and a honey residue level of 0.44 mg/kg, a 

human would need to consume [(1500 mg/kg x 70 kg)/0.44 mg/kg) = 2.39 x 106kg] (approximately 5 lbs) 

of honey in one serving to reach the acute toxicity endpoint of 1500 mg/kg. The 5 lb level of honey

consumption is approximately 3.9X greater than the annual U.S. per capita consumption of honey in 2013. 

When fed to rats in drinking water at up to 50 ppm daily for 7 months, HBAs have been shown to have 

potent anticarcinogenic activity against experimentally-induced colon cancers with no observed toxic 

effects (Lamy et. al., 2007). This subchronic exposure in drinking water (50 ppm) is approximately 114X 

greater than the residues detected in one sample of honey (0.44 ppm). 

HBAs are approved by the USDA/FSIS for use on ready to eat meat products at up to 5.5 mg/kg to control 

pathogens, and have been approved for use on control Listeria moncytogenes on frankfurters at up to 2.5 

mg/pound on cooked meat and poultry products (Ref 2). 

There is a long history of oral/dietary exposure of humans to K-HBAs via its use as a preservative on meats 

and its presence in beer making, without any reported toxic effects. HBAs are considered to GRAS by Ref 

10). HBAs have been shown to inhibit inflammations in mice and exhibit anticarcinogenic activity without 

any known side effects (Ref 2).

Drinking Water Exposure: K-HBAs are formulated into a viscous liquid and coated on fiber strips which 

are placed inside the beehive. The product is not sprayed or applied in any way that it would be expected to 

contact any source of drinking water. When fed to rats in drinking water at up to 50 ppm daily for 7 

months, HBAs have been shown to have potent anticarcinogenic activity against experimentally-induced 

colon cancers with no observed toxic effects (Ref 2). 

Other Non-occupational Exposure: Non-occupational exposure to K-HBAs is not expected because this 

biochemical is formulated into a viscous liquid and coated on fiber strips which are placed inside the 

beehive. The product is not sprayed or applied in any way that it would be expected to contact any 

beekeepers directly or through any type of drift. Exposure to applicators us also limited and mitigated 
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through personal protective equipment when handling bees. There is no anticipated exposure to other 

agricultural workers because the strip would be on the inside of the hive. However, minimal to no risk is 

expected for the general population, including infants and children, due to the low toxicity of this chemical.

IV. Cumulative Effects from Substances with a Common Mechanism of Toxicity

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke 

a tolerance, the EPA consider “available information concerning the cumulative effects of [a particular 

pesticide’s] . . . residues and other substances that have a common mechanism of toxicity.”

The EPA has not found K-HBAs to share a common mechanism of toxicity with any other substances, and 

K-HBAs do not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

tolerance action, therefore, the EPA has assumed that K-HBAs do not have a common mechanism of 

toxicity with other substances. Following from this, the EPA concludes that there are no cumulative effects 

associated with K-HBAs that need to be considered. For information regarding the EPA’s efforts to 

determine chemicals that have a common mechanism of toxicity and to evaluate the cumulative effects of 

such chemicals, see the EPA’s website at http://www.epa.gov/pesticides/cumulative.

V. Determination of Safety for the United States Population, 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, the EPA shall assess the available information about 

consumption patterns among infants and children, special susceptibility of infants and children to pesticide 

chemical residues, and the cumulative effects on infants and children of the residues and other substances 

with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that the 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 the 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, the EPA either retains the default value of 10X, or uses a different additional or 

no safety factor when reliable data are available to support a different additional or no safety factor. 

Because there are no threshold effects associated with this biochemical, an additional margin of safety for 

infants and children is not necessary. 

EPA has determined that there are no foreseeable dietary risks to the U.S. population, including infants and 

children, from the use of K-HBAs as a pesticide (miticide) in or on honey and honeycomb when label 

instructions and good agricultural practices are followed. The available data and information indicate that 

the chemical is of minimal toxicity and not a developmental toxicant. Therefore, EPA concludes that there 

is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from 

aggregate exposure to the residues of K-HBAs when it is used as labeled and in accordance with good 

agricultural practices. Such exposure includes all anticipated dietary exposures and all other exposures for 

which there is reliable information. EPA has arrived at this conclusion because the data and information 

available on K-HBAs do not demonstrate significant toxic potential to mammals, including infants and 

children. 

VI. Conclusions

EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including 
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infants and children, from aggregate exposure to residues of K-HBAs. Therefore, an exemption is 

established for residues of the biochemical pesticide potassium salts of hops beta acids when used in or on 

honey and honeycomb in accordance with label directions and good agricultural practices.

VII. References

1. EPA (2015) Science Review of a Response to Product Chemistry Deficiencies in Support of the 

Registration of HopGuard TGAI, HopGuard Liquid, and HopGuard. US EPA. U.S. Environmental 

Protection. May 21, 2015

2. EPA (2014) Science Review in Support of the Registration of HopGuard TGAI, HopGuard Liquid, 

and HopGuard, Hops Beta Acids Resin, a New Active Ingredient. Review of Residue Studies, Tier I 

Toxicity and Tier I Non-Target Organism Studies and Rationales. US EPA. U.S. Environmental 

Protection. December 04, 2014. 

3. EPA (2014) Science Review in Support of the Registration of HopGuard TGAI, HopGuard Liquid, 

and HopGuard, Hops Beta Acids Resin, a New Active Ingredient. Review of a TGAI, an MP, an 

EP, and a Tolerance Exemption for the New Active Ingredient. US EPA. U.S. Environmental 

Protection. September 02, 2014. 

4. Breed, M. D., E. Guzman-Nova, and G. J. hunt. 2004. Defensive behavior of honey bees: 

organization, genetics, and comparisons with other bees. Annual Review of Entomology 49: 271-

296. 

5. Chin, Y-C., and H. H. Anderson. 1950. Toxicology and pharmacology of lupulon. Arch. Int. 

Pharmacodyn. 82(1): 1-15. 

6. Cleemput, M. V., A. Heyerick, C. Libert, K. Swerts, J. Philippe, D. D. Keukeleire, G. Haegeman, 

and K. D. Bosscher. 2009. Hop bitter acids efficiently block inflammation independent of GRalpha, PPAR-alpha, or PPAR-gamma. Molecular Nutrition and Food Research 53: 1143-1155. 

7. Dong, N. T. K and R. B. Ogle. 2003. Effect of brewery waste replacement of concentrate on the 

performance of local and crossbred growing Muscovy ducks. Asian-Australian Journal of Animal 

Science 16(10): 1510-1517. 

8. Dumas, E. R., A. E. Mchaud, C. B. Bergeron, J. L. LaFrance, S. Mortillo, and S. Gafner. 2009. 

Deodorant effects of a supercritical hops extract: antibacterial activity against Corynebacterium 

xerosis and Staphylococcus epidermidis and efficacy testing of a hops/zinc ricinoleate stick in 

humans through the sensory evaluation of axillary deodorancy. Journal of Cosmetic Dermatology

8: 197-204. 

9. Estrada, J. L., F. Gorzalo, C. Cecchini, and E. Casqueta. 2002. Contact urticaria from hops 

(Humulus lupus) in a patient with previous urticaria-angiodema from peanut, chestnut, and banana. 

Contact Dermatitis 48: 127. 

10. FDA, 2001. Agency response letter GRAS Notice No. GRN 000063. CFSAN/Office of Premarket 

Approval. March 15, 2001. 

11. Huszcza, E., A. Bartmanska, M. Aniol, W. Maczka, A. Zolnierczyk, and C. Wawrzenczyk. 2008. 
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Degradation of hop bitter acid by fungi. Waste management 28(8): 1406-1410.

12. Krings, A. 2002. Keys to the vines of Carolina wetlands. Vulpia 1: 23-40.

13. Lamy, V., S. Roussl, M. Chaabi, F. Gosse’, N. Schall, A. Lobstein, and F. Raul. 2007. 

Carcinogenesis 28: 1575-1581.

14. Moir, M. M. 2000. Journal of the American Society of Brewery Chemists 58(4): 131-146.