Hop Beta Acids 

PC Codes: 005115 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAl SAFETY & POUUTIOI PIEVEITIOI 

MEMORANDUM 

DATE: 12/04/2014 

SUBJECT: Science Review in Support of the Registration of HopGuard TGAI, HopGuard 

Liquid, and HopGuard, Respectively Containing 48.02%, 16%, and 16% Hops 

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

Toxicity and Tier I Non-Target Organism Studies and Rationales. 

FROM: 

TO: 

EPA Reg. No.: 

Petition No.: 

Decision Nos.: 

DP Nos.: 

Chemical Class: 

PC Codes: 

CAS No. 

MRIDs: 

83623-G, -R & -E 

3E8217 

484728, 484725&484727 

417759,417758,417760 

Biochemical 

005115 

None Assigned 

492519-0 I to -05 

Russell S. Jones, Ph.D., Senior Biologist Is/ 12/04/2014 

Biochemical Pesticides Branch 

Biopesticides & Pollution Prevention Division (7511 P) 

Menyon Adams, Regulatory Action Leader Is/ 12/04/2014 

Biochemical Pesticides Branch 

Biopesticides & Pollution Prevention Division (7511 P) 

ACTION REQUESTED 

The BetaTec Division of John I. Haas, Inc. requests registration ofthree products containing the 

new active ingredient, Hops Beta Acids Resin: A technical grade of the active ingredient (TGAI) 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 4 17759 

EPA File No.: 83623-G, -R, & -E 

Hopguard TGAI, (EPA File Symbol No. 83623-G); a manufacturing use product (MP), 

Hopguard Liquid (83623-R); and an end use product (EP), Hopguard II (EPA File Symbol No. 

83623-E). Simultaneously, M. Braverman (IR-4 Project) submitted a petition for an exemption 

from the requirement of tolerances for the active ingredient, Hops Beta Acids Resin (aka 

Potassium Beta Resin, or KBR). In support of the registration and tolerance exemption petition, 

the registrant submitted product chemistry information for each product (MRJD 49251901 ), field 

residue studies (MRJD 49251902), scientific rationales in support of the Tier I human health data 

requirements (MRJD 49251904), a guideline study for primary eye irritation (OCSPP 870.2400; 

MRID 49251903), and scientific rationales in support of non-target organism data requirements 

(MRJD 49251905). 

Product chemistry studies and data have been reviewed under a separate Memorandum (See 

Memorandum from R. S. Jones toM. Adams, dated 09/03/2014). This portion of the review 

addresses the residue studies, Tier I human health information, and Tier I non-target organisms 

information. 

The EPA granted a Section 18 Emergency Exemption in 201 I in over 20 States to control Varroa 

mites (V arroa destructor) in honeybee hives. The Section 18 was renewed in 2012 and 2013 in 

up to 37 States to control Varroa mites. It also is noted that in a literature review conducted in 

support of a GRAS determination by FDA (FDA, 2001 ), the safety of all extracted acids of hops 

(including Hops Beta Acids) is supported by a long history of safe use in foods, especially beer, 

throughout recorded history. The literature review (FDA, 2001) demonstrated that no 

information was available that was inconsistent with the safety determination for the proposed 

uses. 

EXECUTIVE SUMMARY 

There are no concerns for human health when Potassium Salts of Hops Beta Acids (Hops Beta 

Acids) are used in accordance with Agency-approved product use directions. In three years of 

field residue studies, Hops Beta Acids were detected in only one sample of consumable honey 

(from the honey supers) at a level that was barely above the limit of detection (LOD = 0.41 ppm); 

the residues were present in the one sample at 0.44 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 Ibs (approximately 0.6 kg or 600 mg) in 2013. 

Assuming a 70 kg standard human and the lower acute oral toxicity endpoint (LDso = 1500 

mg!kg), and a honey residue level of0.44 mg/kg, a human would need to consume [(1500 mg/kg 

x 70 kg)/0.44 mglkg) = 2.39 x 106 kg] (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. It is noted here that 

2 
Hop Beta Acids 

PC Codes: 005 I I 5 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 4 I 7758 & 4 I 7759 

EPA File No.: 83623-G, -R, & -E 

the 0.44 ppm residue level for Hops Beta Acids was detected in only one honey sample in three 

studies conducted between 20 10 and 2012. If averaged over all honey samples, the residue level 

would be far below the limits of detection. When fed to rats in drinking water at up to 50 ppm 

daily for 7 months, Hops Beta Acids 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). 

There is a long history of oral/dietary exposure of humans to Hops Beta Acids via 

its use as a preservative on meats (FDA, 200 1; USDA/FSIS, 2013) and its presence in beer 

making (Moir, 2000; Verzele & De Keukelele, 1991 ), without any reported toxic effects. Hops 

Beta Acids are considered to be Generally Recognized As Safe (GRAS) by FDA (200 1 ). Hops 

Beta Acids have been shown to inhibit inflammations in mice and exhibit anticarcinogenic 

activity without any known side effects (Cleemput et. al. 2009; Lamy et. al., 2007). Hops beta 

acids are approved by the USDA/FSIS for use on read-to-eat meat products at up to 5.5 mglkg 

(cited by Shen et. al., 2009) 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 (USDA/FSIS, 20 13). 

Acute, subchronic, and chronic exposure to Hop Beta Acids via inhalation and ocular routes of 

exposure also is not expected and is highly unlikely. The TGAIIEP containing 16% Hops Beta 

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

inhalation and ocular exposure is highly unlikely. Hand-to-eye contact is mitigated by a label 

requirement for eye protection. The most likely exposure to humans would result from dermal 

exposure to applicators when inserting the product-treated strips into the bee hives. Dermal 

exposure will be mitigated by precautionary statements on the label requiring the use of gloves 

and eye protections when applying the product. Bee keepers already wear extensive PPE to 

protect themselves from bee stings, gloves, protective suits, and a hat with a face mask or netting. 

There are no concerns for non-target organisms, including threatened and endangered species 

when the product is used in accordance with EPA-approved product labeling. Based on a lack of 

exposure, effects of Hops Beta Acids on non-target organisms, including threatened and 

endangered species, are highly unlikely and not anticipated. Runoff into ground and surface 

waters is not anticipated. The product (plastic strips treated with a 16% solution of Hops Beta 

Acids) is manuaJiy inserted into beehives. It is highly unlikely that organisms external to the 

hive will have access to the treated strips, and li ttle or no likelihood that the active ingredient wi ll 

migrate from the hive to the external environment. In the highly unlikely event that Hops Beta 

Acids would migrate out of the beehive to the externaJ environment, environmental fate data 

indicate that Hops Beta Acids would degrade rapidly, with 100% degradation in 36 hours in the 

light and 4 days in the dark (Huszcza, 2008). Based on little or no likelihood of exposure to any 

3 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 4 17759 

EPA File No.: 83623-G, -R, & -E 

non-target organism, the Agency makes a "No Effect" determination for threatened and 

endangered species. 

RECOMMENDATIONS AND CONCLUSIONS 

1. The petition for an exemption of Potassium Salts of Hops Beta Acids from the 

requirement of tolerances is supported. 

2a. Except for Primary Eye Irritation, a substantial amount of the information submitted in 

support of the data requirements for Tier I Human Health Assessment was not useable in 

that it did not specifically address the respective routes of exposure. An Acceptable 

Primary Eye Irritation study was submitted in support of the TGAI and the EP. 

2b. Sufficient, acceptable information (obtained from the technical literature) as well as 

credible exposure rationales were available, however, to support all of the Tier I Data 

requirements for both the TGAI and the EP. No additional human health data are 

required at this time. 

2c. Based on selected acceptable information obtained from the technical literature, and/or 

acceptable minimal exposure rationales for each route of exposure for both the TGAJ and 

the EP, no human health concerns are anticipated when Hops Beta Acids are used in 

accordance with product label use directions. 

3a. Based on the method of application (manual insertion of treated strips into the brood 

supers of bee hives), there is little or no likelihood of any exposure to Hops Beta Acids to 

terrestrial and aquatic non-target organisms. No additional non-target organism data are 

required at this time. 

3b. Based on the lack of exposure to non-target organisms, a "No Effect'. determination is 

made for threatened and endangered species 

STUDY SUMMARIES 

Residue Data (40 CFR 158.2040) 

The registrant submitted residue chemistry data in support of a request for an exemption from the 

requirements of tolerances for Hops Beta Acids (PP 3E8217). Residue chemistry data are not 

4 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 4 17758 & 417759 

EPA File No.: 83623-G, -R, & -E 

typically required unless Tier II or Tier III toxicology studies are required and when numerical 

tolerances are required. 

Tier II or Tier III toxicology studies are not required for Hops Beta Acids and numerical 

tolerances are not required for Hops Beta Acids at this time, although the registrant elected to 

submit burden of the residue studies and analytical methods for review. 

Three residue studies were submitted in support of the residue data requirements. The ftrst two 

studies were previously submitted and reviewed in support of Section 18 Emergency Exemption 

requests (10ID06, 100Rl2, and 10WA06) in 2010. 

Chemical Identity (OCSPP 880.1 00): 

Hops Beta Acids (HBAs) are derived from the resin components of the cones of female hop 

plants. The three major components of Hop Beta acids are the structurally-similar ofLupulone 

(30-55% with a isopropyl side chain), Colupulone (20-55% with an isobutyl side chain); and 

Adlupulone (5-1 0% with a secbutyl side chain). See structures below. The components differ 

only in the R-side chain attached (see Table 2). 

Lupulone Colupulone Adlupulone 

Table 2. Identity of Three Primary Hops Beta Acids Components 

Component CAS No. Mol. Formula Mol. Weight R-Side chain 

Lupulone (30-55%) 1

• 

2 468-28-0 C26l-bs04 414.58 -CH2CH(CH3)2 

Colupulone (20-55%) 1

• 

3 468-27-9 C2sl-b604 400.55 -CH(CHJh 

Adlupulone (5-10%) 1

• 

4 31769-60-5 C21H3s04 414.58 -CH(CH3)CH2CH3 .. 1 Percentages may vary according to variety and growmg cond1t10ns 

2 3,5-dihydroxy-2-(3-methylbutanoyl}-4,6,6-tris(3-methylbut-2-enyl)cyclohexa-2,4-dien-l-one 3 3 ,5-d ihydroxy-4,6,6-tris(3-methy lbut-2-eny 1)-2-(2-methylpropanoy l)cyclohexa-2,4-dien- 1-one 4 3,5-dihydroxy-2,6,6-tris(3-methyl-2-butenyl)-4-(2-methyl-1-oxobutyl)-2,4-cyclohexadien-l -one 

5 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R. & -E 

The nominal concentration of Hops Beta Acids (Potassium Beta Resin, or KBR) in the TGAT is 

48.02% by weight of product, the remainder being co-extracted impurities (see Table 1) and 

intentionally added inert ingredients [see Confidential Statement of Formula, for HopGuard® 

Technical Grade Active Ingredient (Potassium Beta Resin= KBR), dated 10/2112013; p 188 of 

225 in MRID 49251901]. 

The nominal concentration of Hops Beta Acids respectively in the MP [HopGuard® Liquid 

(Manufacturing-use Product, MP)] and EP [HopGuard® (End-use Product)) is 16.01% and 

16.0% (see CSFs dated 10/2 1/2013 and 07123/2014). 

Deficiencies: None 

Classification: ACCEPT ABLE 

Residue Analytical Method (OCSPP 860.1340): The registrant submitted a method entitled, 

"QAM 05.14 Identification and assay for beta acids in honey and pollen" (See MRID 4925 1902, 

pp. 28-48 for an analytical summary, description of methods, sample preparation, representative 

chromatograms, standard curves, determination of minimum detection levels in honey (MDLs), 

and calculations for limits of detection (LOD) and limits of quantitation (LOQ) in honey). The 

general scope of the method is to adsorb the beta acids found in honey and pollen onto a solidphase extraction column and selectively desorb the components for analysis by HPLC. The 

method is based upon a published analytical method for hops beta acids (American Society of 

Brewing Chemists. Methods of Analysis, 8

1

h Edition. Beer-23-C Iso-a.-Acids by Solid Phase 

Extraction and HPLC; & European Brewery Convention, Analytica-Section 9 Beer Method). 

The LOD for the method is 0.41 ppm; the LOQ for the method is 1.2 ppm. 

Magnitude of the Residue in Honey (No OCSPP Number): In support of a request for an 

exemption from the requirements of tolerances for potassium salts of hops beta acids inion honey 

(PP 3E8217), the registrant submitted data from two field studies conducted in 2010 and a third 

in 2012. The first study was conducted during honey flow during late April/May 2010; the 

second study was conducted during honey flow during late June/July 201 0; and the third study 

was conducted during nectar flow from July 26-August 23,2012. In the first two studies (2010), 

single HopGuard applications were used. In the third study, three consecutive HopGuard 

applications were used. The first study was conducted at the bee yard of the USDAIARS Carl 

Hayden Bee Research Center (Tucson, AZ). Studies two and three were conducted at the Casa 

Grande honey Bee Apiary in (Tucson, AZ) by personnel from the USDA! ARS Carl Hayden Bee 

Research Center. Analyses of residues in honey and pollen were conducted at John I. Haas 

Laboratories (Yakima, W A). Specific details of product application, honey collection, sample 

6 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

handling, storage conditions, and data for individual samples of each study are presented in 

MRID 49251902, pp. 49-66. The three studies are summarized below: 

2010 ApriVMay Study: The first study was conducted in Arizona in commercial honey bee hives 

during late April and Early May 2010. There were 8 colonies per trial with 6 treatment and 28 

untreated control colonies. Four treated colonies had only one box with brood and the remaining 

two treated colonies had one honey box on top of the brood (bottom) box. HopGuard was 

applied to hives on cardboard strips (1.92 g a.i./strip). Two strips were hung over the brood 

frame in the bottom box only within each hive (3.84 g a.i./hive). After 35 days of exposure, 

honey samples were collected from each of the six top (honey) boxes and from the two bottom 

(brood) boxes. Honey samples were stored at -20 °C until shipment to at John I. Haas 

Laboratories (Yakima, W A) for analysis. 

All adult bees and brood remained healthy and exhibited normal bee behavior throughout the 35-

day exposure period. All strips were dry and had evidence of substantial chewing by bees. 

Residues were detected in 4 of 6 bottom (brood) boxes after 35 days exposure to HopGuardtreated cardboard strips. Residues ranged from 0.27 ppm to 9.52 ppm in 9 of 30 samples from 

the brood boxes, and were not detectable in the remaining 21 samples. The average residue 

content of all 30 brood box samples was 0.51 ppm. Hops beta acid residues in pollen obtained 

from treated frames contained an average of3.6 ppm over the 35-day exposure period. 

Residues were not detected in any samples obtained from the two top (honey) boxes (the ones 

used for human honey consumption). Residues were not detected in the untreated colonies. 

2010 June/July Study: The second study was conducted in Arizona in commercial honey bee 

hives during late June and early July 2010. There were 20 colonies per trial with two boxes of 10 

frames each and a honey super. Ten colonies were treated with four HopGuard-treated strips 

(1.92 g a. i./strip; two strips per box) in the bottom (brood) boxes for one week. Traps were 

monitored daily for dead bees during the one week exposure period and for 1, 2, 3, and 7 days 

post treatment. Honey supers (not containing brood), specifically designed for honey collection, 

were placed in the hive during nectar flow, and were removed from the hives after the one-week 

exposure period and set aside for analysis of residues in the honey. Honey samples were stored 

at -20 °C until shipment to at John I. Haas Laboratories (Yakima, WA) for analysis. According 

to the study author, 2010 was notable for an unseasonably low nectar flow, and only five treated 

colonies and one control colony produced sufficient honey for sampling. 

Except for the fust day (12 dead bees in treated hives, 6 dead bees in the controls), numbers of 

dead bees were approximately the same in treated and control hives (6-8 dead bees per colony 

per day). The first day observations were considered to be not treatment related. Residues of 

Hop Beta Acids were not detected in any honey samples obtained from the honey supers of 

7 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

treated and untreated colonies. Analysis of a spent strip at the end of the study, showed that after 

35-days the HopGuard® strip contained 505 ug beta acids/in2

, whereas a fresh strip just out of 

the package contained 30,000 ug/in2

. 

2012 July/August Study: The third study was conducted in Arizona in commercial honey bee 

hives during late July through late August 2012. There were 20 colonies used in the study, each 

containing a similar number of frames of bees and brood, a queen, food storage and empty 

frames for the queen to lay eggs. In mid-July, each colony was set up with honey supers. On 

July 26, two HopGuard® strips (1.92 g a. i./strip) were applied to each brood chamber in 10 of 

the colonies. At one week post treatment, honey samples were collected from the honey supers, 

and the original HopGuard® strips were replaced with new ones. At the end of the second week 

of treatment, a second honey sample was obtained from the honey supers of the treated colonies. 

This process was repeated for a third week, for a total of three weekly HopGuard® applications 

immediately followed by weekly sampling of honey from the honey supers. Honey samples were 

stored at -20 °C until shipment to at John I. Haas Laboratories (Yakima, WA) for analysis. 

Colony activities (worker bee tasks of foraging, queen tending, brood rearing, cleaning, 

thermoregulation, guarding, comb building. etc.), as well as queen egg laying were remained 

undisturbed by the treatments with HopGuard® throughout the study. Hops beta acids were not 

detectable in 21 of22 samples; in one sample, residues were present 0.44 ppm which is barely 

above the Limit of Detection (0.41 ppm) but below the Limit of Quantitation ( 1.2 ppm). 

CONCLUSIONS: When used in accordance with EPA-approved labeling, it is highly unlikely 

that the use ofHopGuard® on the brood boxes of honey bee hives will result in detectable 

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 hops beta acids, and the residue 

level was only slightly above the analytical limits of detection. HopGuard® is practically nontoxic to honey bees and was not observed to adversely affect normal honeybee behavior. 

Classification: ACCEPT ABLE 

Review of Tier I Toxicity Data 

The registrant did not submit any Guideline studies in support of the Tier I toxicity data 

requirements for the TGAIIEP. In lieu of Guideline studies, the registrant submitted rationales 

submitted by data and information from the technical literature. These rationales are summarized 

below 

8 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

Technical Grade Active Ingredient/End-Use Product (TGAI/EP): Potassium Salts of Hops 

Beta Acids 

Reviewer's Note: The TGAl is defmed as Potassium salts of Hops Beta Acids and is present in 

the TGAl at 16% (w/w). The end-use product consists of plastic strips coated with the 16% 

Hops Beta Acids solution and are contained in a sealed pouch until use. The plastic strips are 

considered to be the delivery system into the beehives (above the brood super), and not an 

integral part of the formulation. The Agency considers the TGAl and the EP to be identical for 

purposes of human health hazard and risk assessment. 

A: Acute Oral Toxicity (OCSPP 870.1100): The registrant did not submit Guideline studies 

for either the TGAI or the EP, although none are required at this time. In lieu of an acute oral 

toxicity study, the registrant submitted a rationale supported by toxicity and exposure 

information obtained from the technical literature (MRJD 49251904, pp. 5-7; and 27-29) in 

fulfillment of the acute oral toxicity data requirement for the TGAliEP; the relevant information 

is presented below: 

1. A single intragastric (oral gavage) administration of hops beta acids (as lupulon) to mice 

and rats resulted in LDsos of 1500 mg/kg and 1800 mg/kg, respectively (Chin and 

Anderson, 1950). These data classify Hops Beta Acids in Toxicity Category III for acute 

oral toxicity. 

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 (cited by Shen et. al., 2009) to control pathogens, and has been approved 

for use on control Listeria moncytogenes on frankfurters at up to 2.5 mg/products on 

cooked meat and poultry products at up to 2.5 mg/pound (USDA/FSIS, 2013). According 

to the NHDSC (2014), US per capita consumption is approximately 70 hotdogs with an 

average weight of 1.6 oz ( 45 g) per hot dog (Nutrition Facts, 20 14) or approximately 7 lbs 

of hot dogs per year. For hot dogs alone, this would be equivalent to a dietary intake of 

17.5 mg Hops Beta Acids/person/year or an estimated daily dietary intake of0.048 

mg/person/day. 

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 Hops Beta Acids [comprised primarily of lupulone 

(C26H3&0 4), adlupulone (C2sH37Q4), and colupulone (C2sH3s04)], 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 polar extracts of hops 

beta acids (FDA, 2001). 

9 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

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 (Moir, 2000; Verzele & De 

Keukelele, 1991 ). 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 (Cleemput et. al. 2009). 

5. When fed to rats in drinking water at up to 50 ppm, hops beta acids have been shown to 

have potent anticarcinogenic activity against colon cancers with no observed toxic effects 

(Lamy et. al., 2007). 

Conclusions: Hops Beta Acids can be classified in Toxicity Category III for acute oral toxicity, 

based on studies where mice and rats were dosed with Hops Beta Acids by oral gavage; 

Observed LD50s ranged between 1500 to 1800 mg/kg (Chin and Anderson, 1950). 

ln addition, acute oral exposure to Hops Beta Acids is highly unlikely. 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 

(detected in only one sample of edible honey in three years of studies; see residues studies 

above), well below any known endpoints for Hops Beta Acids (1500 mg/kg). No additional data 

are required at this time. 

There is a long history of oral/dietary exposure of humans to Hops Beta Acids via its use as a 

preservative on meats (FDA, 2001; USDA/FSIS, 20 13) and its presence in beer making (Moir, 

2000; Verzele & De Keukelele, 1991 ). Hops Beta Acids are considered to be Generally 

Recognized As Safe (GRAS) by FDA (200 I). Hops Beta Acids have been shown to inhibit 

inflammations in mice and exhibit anticarcinogenic activity without any known side effects 

(Cleemput et. al. 2009; Lamy et. a!., 2007). 

Classification: ACCEPT ABLE 

B: Acute Dermal Toxicitv (OCSPP 870.1200): The registrant did not submit Guideline 

studies for either the TGAI or the EP, although none are required at this time. Dermal exposure 

to the active ingredient is highly unlikely based on the method of application (manual application 

of treated plastic strips into beehives), and the requirement of worker/applicators to wear gloves 

when applying the end-use product. Non-occupational exposure to the active ingredient does not 

occur. 

10 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

However, in lieu of an acute dermal toxicity study, the registrant submitted a rationale supported 

by toxicity and exposure information (MRID 49251904, p. 8; and 30-31) obtained from the 

technical literature in fu lfillment 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. One study (Dumas, et. al., 2009) reported the effects of a deodorant 

study whereby 0.4 g of a mixture of Hops Alpha Acids (50%), Hops Beta Acids (26%), and other 

substances (zinc, ricinoleate) present at unknown concentrations, were applied to human 

underarms as a deodorant stick. Preliminary studi es demonstrated that the extract inhibited the 

growth ofunderann odor causing bacteria in Petri dish cultures. Each subject received two 

applications of the deodorant stick, although the precise amount ofl·lops Beta Acids applied is 

uncertain. Dermal irritation and toxicity were not observed in any test subject. Due to the 

mixture of substances used as the test substance, this study cannot be used to fulfill the data 

requirement for acute dermal toxicity. 

REVIEWER'S NOTE and Conclusions: The submitted information (MRJD 49251904, pp. 8; 

and 30-31; and Dwnas, et. al., 2009) 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. 

The BPB reviewer notes that acute dermal exposure to Hops Beta Acids is highly unlikely and 

would only occur to the worker/applicator. Based on the method of application (manually 

applied via plastic strips inside beehives), non-occupational exposure to Hops Beta Acids will 

not occur. Occupational exposure is mitigated by protective clothing nonnally 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 

workers/applicators. 

Classification: ACCEPTABLE, based on a lack of acute exposure via the dermal route of 

exposure. It is recommended that precautionary statements requiring the use of gloves and eye 

protection for workers/applicators be placed on the product label, based on the results of the 

Primary Eye Irritation study (see below). 

C: Acute Inhalation Toxicitv (OCSPP 870.1300): The registrant did not submit Guideline 

studies for either the TGAI or the EP, although none are required at this time. 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. 

Non-occupational exposure to the active ingredient does not occur. The registrant also provided 

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

II 
Hop Beta Acids 

PC Codes: 005 1 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 4 17758 & 4 17759 

EPA File No.: 83623-G, -R, & -E 

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

inhalation exposure is highly unlikely. " 

The registrant also submitted toxicity and exposure information (MRIO 4925 1904, p. 9; and 32-

33) obtained from the technj calliterature in fulfillment of the acute inhalation toxicity data 

requirement for the TGAI/EP. However, much of the information was not useable in that it did 

not specifically address the acute inhalation toxicity route of exposure. 

Conclusions: Due to the lack of volatility and the method of product application (manual 

insertion of Hops Beta Acids-treated strips into beehjves), occupational and non-occupational 

inhalation exposure is hlghly unlikely. No additional data are required at this time. 

Classification: ACCEPT ABLE, based on a lack exposure via the inhalation route of exposure 

D: Primary Eve Irritation (OCSPP 870.2400): A Guideline primary eye irritation study 

(MRID 49251903) was conducted using potassium salts of Hops Beta Acids (the TGAI) on 

rabbits. The normal pH of the test substance is pH II 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 2 1 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. 

Conclusions: Based on the data, Potassium Salts of Hops Beta Acids are classified as Corrosive, 

Toxicity Category I. 

Classification: ACCEPT ABLE 

E: Primary Dermal Irritation (OCSPP 870.2500): The registrant did not submit Guideline 

studies for either the TGAf or the EP, although none are required at this time. Dermal exposure 

to the active ingredient is highly unlike ly based on the method of application (manual application 

of treated plastic strips into beehives), and the requirement of worker/applicators to wear gloves 

when applyi ng the end-use product. Non-occupational exposure to the active ingredient does not 

occur. 

However, In lieu of a primary dermal irritation study, the registrant submitted a rationale 

supported by toxicity and exposure information (MRID 49251904, pp. 11-12; and 35-36) 

obtained from the techn ical literature in fulfillment of the primary dermal irritation data 

12 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DPNumbers: 417758&417759 

EPA File No.: 83623-G, -R, & -E 

requirement for the TGAl!EP. Much of the information was not useable in that it did not 

specifically address the primary dermal irritation route of exposure. The registrant also provided 

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, I rare cases leading to a 

diagnosis of immunological contact urticaria. Hops Beta Acids were not implicated in this 

process (Estrada et. a/., 2002). 

In addition, one study (Dumas, et. al., 2009) reported the effects of a deodorant study whereby 

0.4 g of a mixture of Hops Alpha Acids (50%), Hops Beta Acids (26%), and other substances 

(zinc, ricinoleate) present at unknown concentrations, were applied to human underarms as a 

deodorant stick. Each subject received two applications of the deodorant stick, although the 

precise amount of Hops Beta Acids applied is uncertain. Dermal itTitation and toxicity were not 

observed in any test subject. Due to the mixture of substances used as the test substance, this 

study cannot be used to fulfill the data requirement for primary dermal irritation, although it does 

provide supplemental information. 

REVIEWER'S NOTE and Conclusions: The submitted information (MRID 49251904, pp. 

11-12; and 35-36; Dumas, et. al., 2009; and Estrada et. al., 2002) did not specifically address the 

dermal irritation route of exposure. In addition, humans were used as the test subjects in both 

cited studies and they were not submitted to the Human Studies Review Board (HSRB) for a 

review of its suitability for use in supporting a pesticide registration. 

The BPB reviewer notes that dermal exposure to Hops Beta Acids is highly unlikely and would 

only occur to the worker/applicator. Based on the method of application (applied via plastic 

strips inside beehives), non-occupational exposure to Hops Beta Acids will not occur. 

Occupational exposure is mitigated by protective clothing normally worn by beekeepers, 

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

Classification: ACCEPT ABLE, based on the rationale (Estrada et. al., 2002) 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, based on the results 

of the Primary Eye Irritation study (see above). 

E: Dermal Sensitization (OCSPP 870.2600): The registrant did not submit Guideline studies 

for either the TGAI or the EP, although none are required at this time. Dermal exposure to the 

active ingredient is highly unlikely based on the method of application (manual application of 

13 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 4 17758 & 417759 

EPA File No.: 83623-G, -R, & -E 

treated plastic strips into beehives), and the requirement of worker/applicators to wear gloves 

when applying the end-use product. Non-occupational exposure to the active ingredient does not 

occur. 

However, in lieu of a dermal sensitization study, the registrant submitted a rationale supported by 

toxicity and exposure information (MRlD 49251904, p. 13; and 37-38) obtained from the 

technical literature in fulfillment of the dermal sensitization data requirement for the TGAl/EP. 

Much of the information was not useable in that it did not specifically address primary dermal 

sensitization. However, the registrant 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 

altributed 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, I rare cases leading to a diagnosis of immunological contact urticaria. Hops Beta 

Acids were not implicated in this process (Estrada et. a!., 2002). 

Similar to the conclusions reached for primary dermal irritation (see above), the BPB reviewer 

notes that dermal exposure to Hops Beta Acids is highly unlikely and would only occurto the 

worker/applicator. Based on the method of application (applied via plastic strips inside 

beehives), non-occupational exposure to Hops Beta Acids will not occur. Occupational exposure 

is mitigated by protective clothing normally worn by beekeepers, including gloves, protective 

suits, a hat with a face mask or netting. Precautionary statements on the label must require the 

use of gloves and eye protection for workers/applicators. 

Classification: ACCEPT ABLE, based on the rationale (Estrada et. al., 2002) submitted above 

and the mitigation of exposure with appropriate PPE. It is recommended that Toxicity Category 1 

PPE precautionary language for acute dermal toxicity be placed on the label, based on the results 

of the Primary Eye l rri tation study (see above). 

F: 90-Day Oral Toxicity (OCSPP 870.3100): The registrant did not submit Guideline studies 

for either the TGAI or the EP, although none are required at this time. 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). 

14 
Hop Beta Acids 

PC Codes: 005 II 5 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R. & -E 

In addition, the registrant submitted a rationale supported by toxicity and exposure information 

obtained fi·om the technical literature (MRJD 49251904, pp. 14-16; and 39-41) in fulfillment of 

the 90-day oral toxicity data requirement for the TGAIIEP. The relevant information, much of 

which is similar to that presented in support of the acute oral toxicity data requirement, is 

presented below: 

1. Hops beta acids are approved by the USDNFSIS for use on ready to eat meat products at 

up to 5.5 mglkg (cited by Shen et. al., 2009) 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 (USDAJFSIS, 2013). 

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

long history of dietary exposure to Hops Beta Acids [comprised primarily of lupulone 

(C26HJs04), adlupulone (C2sH37Q4), and colupulone (C2sH3s04)], 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). 

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

(Humulus lupulus and contain up to 10% hops beta acids (Moir, 2000; Verzele & De 

Keukelele, 1 991 ). 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 (Cleemput et. al. 2009). 

5. When fed to rats in drinking water at up to 50 ppm daily for 7 months, hops beta acids 

have been shown to have potent anticarcinogenic activity against experimentally-induced 

colon cancers with no observed toxic effects (Lamy et. al., 2007). 

Conclusions: There is a long history of oraVdietary exposure of humans to Hops Beta Acids via 

its use as a preservative on meats (FDA, 2001 ; USDA!FSIS, 2013) and its presence in beer 

making (Moir, 2000; Verzele & De Keukelele, 1991), without any reported toxic effects. Hops 

Beta Acids are considered to be Generally Recognized As Safe (GRAS) by FDA (2001). Hops 

Beta Acids have been shown to inhibit inflammations in mice and exhibit anticarcinogenic 

activity without any known side effects (Cleemput et. al. 2009; Lamy et. al., 2007). 

It is also noted that rats have been administered Hops Beta Acids in drinking water at levels up to 

50 ppm with no observed toxic effects. Tllis subchronic exposure in drinking water (50 ppm) is 

Approximately 114X greater than the residues detected in one sample of honey (see residue 

15 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

studies above). 

Classification: ACCEPT ABLE 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

G: 90-Dav Dermal Toxicity (OCSPP 870.3250): The registrant did not submit Guideline 

studies for either the TGAI or the EP, although none are required at this time. Repeated dermal 

exposure to the active ingredient is highly unlikely based on the method of application (manual 

application of treated plastic strips into beehives), and the requirement of worker/applicators to 

wear gloves when applying the end-use product. Non-occupational exposure to the active 

ingredient does not occur. 

The registrant submitted a rationale supported by toxicity and exposure information obtained 

from the technical literature (MRID 49251904, p. 16; and 42-43) in fulfillment ofthe 90-day 

dermal toxicity data requirement for the TGAI/EP. Much of the information was not useable in 

that it did not specifically address subchronic (90-day) dermal toxicity. However, the registrant 

did provide the following exposure rationale: "Contact with growing hop plants is known to 

cause an allergic contact dermatitis and is allributed to the rnyrcene oil in .fresh hop oil. 

Growing hop plants can also cause a mechanical dermatosis allributed 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, I rare cases leading to a 

diagnosis of immunological contact urticaria. Hops Beta Acids were not implicated in this 

process (Estrada et. a!. , 2002). 

REVIEWER'S NOTE and Conclusions: The submitted information (MRlD 49251904, p. 16; 

and 42-43; and Estrada et. al., 2002) did not specificall y address subchronic dermal toxicity. 

However, the BPB reviewer notes that repeated, subchronic exposure to Hops Beta Acids 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 workers/applicators. 

Classifica tion: ACCEPT ABLE, based on minimal exposure and a ru story of exposure with no 

observed toxicity. 

H: Acute Inhalation Toxicity (OCSPP 870.3465): The registrant did not submit Guideline 

studies for either the TGAI or the EP, although none are required at this time. Repeated, 

subchronic inhalation exposure to the active ingredient is rughly 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. 

16 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA Fi le No.: 83623-G, -R, & -E 

The registrant 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. " 

The registrant also submitted toxicity and exposure information (MRJD 49251904, p. 17; and 44-

45) obtained from the technical literature in fulfillment of the acute inhalation toxicity data 

requirement for the TGAIIEP. However, much of the infom1ation was not useable in that it did 

not specifically address the acute inhalation toxicity route of exposure. 

Conclusions: Due to the lack of volatility and the method of product application (manual 

insertion of Hops Beta Acids-treated strips into beehives), repeated, subchronic occupational and 

non-occupational inhalation exposure is highly unlikely. No additional data are required at this 

time. 

Classification: ACCEPT ABLE, based on a lack exposure via the inhalation route of exposure. 

1: Pre-Natal Development-Rat (OCSPP 870.3700): The registrant did not submit Guideline 

studies for either the TGAI or the EP, although none are required at this time. Use of the product 

under widespread and commonly recognized practice will not result in significant exposure to 

female humans. Occupational and non-occupational exposure is not expected due to the method 

of application and the lack of appreciable residues in honey (see residue studies above). 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; Chin and Anderson, 1950) or subchronic (50 ppm in drinking water; Lamy et. al., 2007) 

endpoints for Hops Beta Acids. No additional data are required at this time. 

The registrant also submitted toxicity and exposure information (MRID 49251904, p. 18-19; and 

45-47) obtained from the technical literature in fulfillment ofthe acute inl1alation toxicity data 

requirement for the TGAIIEP. However, much of the information was not useable in that it did 

not specifically address pre-natal development. 

Conclusions: Based on the method of product application (manual insertion of Hops Beta 

Acids-treated strips into beehives), a lack of acute or subchronic exposure, lack of significant 

exposure to female humans, and lack of appreciable residues in edible honey (see residue studies 

above), pre-natal developmental toxicity is highly unlikely. No additional data are required at this 

time. 

Classification: ACCEPTABLE 

17 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Srudies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 4 17759 

EPA File No.: 83623-G, -R, & -E 

1: Mutagenicity Testing (OCSPP 870.5100,870.5300, & 870.5375): The registrant did not 

submit Guideline studies for either the TGAl or the EP, although none are required at this time. 

Occupational and non-occupational exposure is not expected due to the method of application 

and the lack of appreciable residues in honey (see residue studies above). 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; Chin and 

Anderson, 1950) or subchronic (50 ppm in drinking water; Larny et. al., 2007) endpoints for 

Hops Beta Acids. No additional data are required at this time. 

The registrant also submitted toxicity and exposure information (MRID 49251904, p. 18-19; and 

48-54) obtained from the technical literature in fulfillment of the mutagenicity data requirements 

for the TGAI/EP. However, much of the information was not useable in that it did not 

specifically address mutagenicity. 

Conclusions: Based on the method of product application (manual insertion of Hops Beta 

Acids-treated strips into beehives), lack of acute or subchronic exposure, long history of 

exposure to Hops Beta Acids in food preservation and in the making ofbeer, lack of appreciable 

residues in edible honey, and the lack of any structural or chemical similarity to known 

mutagens, mutagenicity is highly unlikely. No ociditional data are required at this time. 

Classification: ACCEPT ABLE 

QUALITATIVE HUMAN HEALTH RISK ASSESSMENT 

Acute, subchronic, and chronic exposure to Hop Beta Acids via the oral route of exposure is not 

expected and is highly unlikely. Residue data submitted by the applicant indicate that residues of 

Hop Beta Acids will likely not be present in edible honey, when only the brood boxes (supers) of 

a honey bee colony/hive are treated with the end-use product (a plastic strip coated with 1.92 g a.i 

with two strips/brood box). Brood box honey is not used for human consumption. A series of 

three field studies conducted between 201 0 and 2012 demonstrated that when the product is 

applied according to label use directions, honey obtained from the honey boxes (supers), honey 

used for human consumption, was virtually residue free. Only one sample of honey (out of the 

three field studies) had residues of Hops Beta Acids present at 0.44 ppm, barely above the Limit 

of Detection of (0.4 1 ppm) and substantially below the Limit ofQuantitation (1.2 ppm). 

Measured acute oral toxicity endpoints (LDsos) for Hops Beta Acids range from 1500 mg!kg to 

1800 mg/kg in mice and rats by oral gavage (Chin and Anderson, 1950). The lower acute oral 

toxicity endpoint is 3409X greater than the single measured residue level in honey (0.44 ppm). A 

18 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

subchronic study wherein rats were administered Hops Beta Acids at 50 ppm daily for 7 months 

in drinking water reported no toxic effects (Lamy et. al., 2007). The same study also observed 

substantial anti-carcinogenic effects in rats that were chemically-induced to have colon tumors. 

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 LDso acute oral toxicity endpoint of 1500 mg/kg, and a honey 

residue level of 0.44 mglkg, a human would need to consume ((1500 mg/kg x 70 kg)/0.44 mg/kg) 

= 2.39 x I 06 kg (approximately 5 lbs) of honey to reach the acute toxicity endpoint of 1500 

mg/kg. The 5 lb level of honey consumption is approximately 3.9X greater than the U.S. per 

capita consumption of honey in 2013. It is noted here that the 0.44 ppm residue level for Hops 

Beta Acids was detected in only one honey sample in three studies conducted between 20 I 0 and 

2012. If averaged over all honey samples, the residue level would be far below the limits of 

detection. 

Acute, subchronic, and chronic exposure to Hop Beta Acids via inhalation and ocular routes of 

exposure also is not expected and is highly unlikely. The TGAI/EP containing 16% Hops Beta 

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

inhalation and ocular exposure is highly unlikely. Hand-to-eye contact is mitigated by a label 

requirement for eye protection. 

The most likely exposure to humans would result from dermal exposure to applicators when 

inserting the product-treated strips into the bee hives. Dermal exposure will be mitigated by 

precautionary statements on the label requiring the use of gloves and eye protections when 

applying the product. Bee keepers already wear extensive PPE to protect themselves from bee 

stings, gloves, protective suits, and a hat with a face mask or netting. 

CONCLUSIONS: When the product is used according to label use directions, there are no 

human health concerns with the use of Hop Beta Acids in bee hives to control Varroa mites at 

this time. 

Review of Tier I Non-Target Organism and Environmental Fate Data 

The registrant 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 registrant submitted rationales 

submitted by data and information from the technical literature. These rationales are summarized 

below 

19 
Hop Beta Acids 

PC Codes: 005 I I 5 

Review Type: Residue Stud ies, Tier l Tox, Tier I Non-targets 

DP Numbers: 4 I 7758 & 4 I 7759 

EPA File No.: 83623-G, -R, & -E 

Technical Grade Active Ingredient/End-Usc Product (TGAI/EP): Potassium Salts of Hops 

Beta Acids 

Reviewer's Note: The TGAI is defined as Potassium salts of Hops Beta Acids and is present in 

the TGAI at 16% (w/w). The end-use product consists of plastic strips coated with the 16% 

Hops Beta Acids solution and are contained in a sealed pouch until use. The plastic strips are 

considered to be the delivery system into the beehives (above the brood super), and not an 

integral part of the formulation. The Agency considers the TGAI and the EP to be identical for 

purposes of non-target organism hazard and risk assessment. 

Overall, the rationales are based on a lack of exposure to the active ingredient due to the manner 

in which the end-use product is applied to control Varroa mites in beehives. Hop Beta Acidstreated are applied to the inside of honey bee hives (colonies) on product-treated cardboard strips. 

The two strips each (four per hive) are placed on brood frames (bottom boxes of the commercial 

bee hive). This method of application, as well as the low application rate (1.92 g a.i./cardboard 

strip), precludes any significant exposure to any non-target organisms or the environment 

external to the bee hive. In the highly unlikely event that Hops Beta Acids would migrate out of 

the beehive to the external environment, environmental fate data indicate that Hops Beta Acids 

would degrade rapidly, with I 00% degradation in 36 hours in the light and 4 days in the dark 

(Huszcza, 2008). 

Avian Acute Oral & Avian Dietary Toxicitv (OCSPP 850.2100 & 850.2200): It is highly 

unlikely that there will be any acute oral or dietary exposure of hops beta acids to birds via the 

application ofHopGuard® (16.0% a.i.) to the insides of commercial beehives. There is little or 

no opportunity for a bird to gain access to the active ingredient-treated cardboard strips inside a 

beehive, nor is there a likelihood that the active ingredient will migrate outside of the hive after 

application. 

In the unlikely event that hops beta acids would migrate outside the beehive, they would be 

rapidly degraded by soil fungi. In laboratory experiments, Trametes versicolor was shown to 

fully degrade humulones and lupulones in commercial hop extract and sterilized spent hops after 

4 days incubation in the dark and 36 hours in the light (Huszcza, 2008). In addition, limited 

testing data indicate that chickens administered up to 250 ppm of a hops beta acid (lupulone) in 

drinking water for 13 to 22 days post hatching had no effects on bird behavior or weight gain 

(Siragusa et. a!., 2008), and improved their health by inhibiting pathogenic clostridia in the 

chicken intestinal tract. In experiments designed to evaluate the effects of brewery waste in the 

diets of Muscovy ducks, it was observed that brewery waste (known to contain hops beta acids) 

could replace up to 50% of the diet without reducing daily weight gains (Dong and Ogle, 2003). 

The Agency has granted Section 18 Emergency Exemptions in 20 I I in over 20 States to control 

20 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

Varroa mites (Va.rroa destructor) in honeybee hives, whjch were renewed in 2012 and 2013 in up 

to 37 States to control Varroa mites. No adverse effects have ever been reported for birds. 

Conclusion: Based upon a lack of exposure to birds via the use of the end-use product in 

beehives, no adverse effects are expected in birds as a result of the use of HopGuard® (16.0% 

potassium salts of hops beta acids). No toxicity is expected in the unlikely event that birds are 

orally exposed to hops beta acids. There are no concerns for non-target birds. 

Classification: ACCEPTABLE 

Freshwater Fish Acute Toxicity & Freshwater Aquatic Invertebrate Toxicity (OCSPP 

850.1085 & 850.1010): It is highly unlike ly that there will be any exposure of potassium salts of 

hops beta acids to aquatic organisms via the application of HopGuard® ( 16.0% a.i.) to the 

insides of commercial beehives. There is little or no opportunity for an aquatic organism to gain 

access to the active ingredient-treated cardboard strips inside a beehive, nor is there a likelihood 

that the active ingredient will migrate outside of the hive and into aquatic environments after 

application. 

In the unlikely event that hops beta acids would migrate outside the beehive, they would be 

rapidly degraded by soil fungi. In laboratory experiments, Trameles versicolor was shown to 

fully degrade humulones and lupulones in commercial hop extract and sterilized spent hops after 

4 days incubation in the dark and 36 hours in the light (Huszcza, 2008). Hops (Humulus spp.) 

have been observed to grown as a wetland species in North Carolina, indicating that there may be 

some level of natural background exposure of aquatic organisms to hops beta acids (Krings, 

2002). 

Conclusion: Based upon a lack of exposure to aquatic environments via the use of the end-use 

product in beehives, no adverse effects are expected in aquatic organisms as a result of the use of 

HopGuard® (16.0% potassium salts ofhops beta acids). There are no concerns for non-target 

aquatic organisms. 

Classification: ACCEPT ABLE 

Terrestrial Plant Toxicity, Seedling Emergence & Vegetative Vigor (OCSPP 850.4100 & 

850.4150): It is highly unlikely that there will be any exposure of potassium salts of hops beta 

acids to plants via the application ofHopGuard® ( 16.0% a.i.) to the insides of commercial 

beehives. In the unlikely event that hops beta acids would migrate outside the beehive, they 

would be rapidly degraded by soil fungi. In laboratory experiments, Trametes versicolor was 

2 1 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R, & -E 

shown to fully degrade humulones and Jupulones in commercial hop extract and sterilized spent 

hops after 4 days incubation in the dark and 36 hours in the light (Huszcza, 2008). 

Based upon a lack of exposure to terrestrial environments via the use of the end-use product in 

beehives, no adverse effects are expected in plants as a result ofthe use ofHopGuard® (16.0% 

potassium salts of hops beta acids). There are no concerns for non-target plants. 

Non-Target Insect Testing (OCSPP 880.4350): It is highly unlikely that there will be any 

exposure of potassium salts of Hops Beta Acids to non-target insects via the application of 

HopGuard® ( 16.0% a.i.) to the insides of commercial beehives. Three years of residue studies 

using Hops Beta Acids in beehives to control Varroa mites demonstrated that there were no 

adverse effects on bees. It is highly unlikely that non-target insects will gain access to the treated 

strips inside the hive due to the vigorous defense of hives by the honey bees against invaders 

(Breed et. al., 2004). 

QUALITATIVE ENVIRONMENTAL RISK ASSESSMENT 

Non-target organism studies and environmental fate data were not submitted for review. In lieu 

of Guideline studies, the registrant submitted rationales in support of the Tier I non-target 

organism data requirements. 

Based on a lack of exposure, effects of Hops Beta Acids on non-target organisms, including 

threatened and endangered species, are highly unlikely and not anticipated. Runoff into ground 

and surface waters is not anticipated. The product (plastic strips treated with a 16% solution of 

Hops Beta Acids) is manually inserted into beehives. It is highly unlikely that organisms 

external to the hive will have access to the treated strips, and little or no likelihood that the active 

ingredient will migrate from the hive to the external environment. In the highly unlikely event 

that Hops Beta Acids would migrate out of the beehive to the external environment, 

environmental fate data indicate that Hops Beta Acids would degrade rapidly, with 100% 

degradation in 36 hours in the light and 4 days in the dark (Huszcza, 2008). 

22 
Hop Beta Acids 

PC Codes: 005115 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 4 17759 

EPA File No.: 83623-G, -R, & -E 

CONCLUSIONS: There are no concerns for non-target organisms, including threatened and 

endangered species when the product is used in accordance with EPA-approved product labeling. 

Based on little or no li kelihood of exposure to any non-target organism, the Agency makes a "No 

Effect" determination for threatened and endangered species. 

NO DERs WERE WRITTEN FOR THIS REVIEW 

cc: R. S. Jones, M. Adams, BPPD Subject File/BPB File/IHAD/Archives 

R. S. Jones, Ph.D., Sr. Biologist, FT, OPY: 12/04/2014 

23 
Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

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DP Numbers: 417758 & 417759 

EPA Fi le No.: 83623-G, -R, & -E 

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Hop Beta Acids 

PC Codes: 0051 15 

Review Type: Residue Studies, Tier I Tox, Tier I Non-targets 

DP Numbers: 417758 & 417759 

EPA File No.: 83623-G, -R. & -E 

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25