3

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Type of Study: Tier I Nontarget Organisms

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460** 

**OFFICE OF CHEMICAL SAFETY & POLLUTION PREVENTION/OFFICE OF PESTICIDE PROGRAMS**  MEMORANDUM

DATE: Oct ober 7, 2015

SUBJECT : Science Review in Suppo rt of the Registrati on of Male Seal Lamprey Pheromone Technical and Male Sea Lamprey Mating Pheromone Respectively Containing 99.3% and 1.06% 3

- Ketopetromyzonal Sulfate as Their Active Ingredient. Tier I Non

- T arget Organism Hazard Assessment. BPPD Concurrence of Review by CANADA PMRA . Endangered Species Assessment Addendum.

Decision Number s : 469657 DP Number s : 410913 & 410915 EPA File Symbol Number s : 6704

- OU & 6704

- OG Chemical Class: B iochemical PC Code: 000802 CAS Number: 435327

- 06

- 3 Tolerance Exemptions: Not Applicable (Non

- Food Use)
MRID Numbers : 48936406 &

- 07 & 48936212

FROM: Russell S. Jones, Ph.D., Senior Biologist /s/ 10/07/2015 Biochemical Pesticides Branch Biopesticides & Poll ution Prevention Division (7511P )

TO : Chris Pf eifer, Regulatory Action Leader /s/ 02/17 /2014 /s/ 10/07/2015 Biochemical Pesticides Branch Biopesticides & Poll ution Prevention Division (7511P )

ACTION REQUESTED

On behalf of the Great Lakes F isheries Commission (GLFC), T. Hubert requests registration of a new active ingredient , 3

- Ketopetromyzonal Sulfate (Male Sea Lamprey Pheromone) which is int ended for use in the control of Sea Lamprey

. In lieu of Guideline studies, t he registrant has subm itted scientific rationales and published and unpublished non

- target organism study data in3

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms
support of Tier I Non

- Target Organism and Environmental Fate data requirements for the Technical Grade Active Ingredient (TGAI; EPA File Symbol No. 6704

- OU) and an End

- use Product (EP; EPA File Symbol No. 6704

- OG).

RECOMMENDATIONS AND CONCLUSION S

Rationales submitted in support of the Tier I Non

- Target Organism data requirements for the TGAI/MP and the EP may be used to support the registration of Male Sea Lamp rey Pheromone ( EPA File Symbol No. 6704

- OG). BPPD concurs with the review conducted by CANADA PMRA. There are no concerns for non

- target aquatic or terrestrial organisms resulting from the use of the EP according to proposed label use directions.

Des cription of the Active Ingredient

Male Sea Lamprey Mating Pheromone Technical (EPA File Symbol 6704

- OU) is a technical grade active ingredient/manufacturing use product (TGAI/MP) to be used to formulate end use products (EPs) to attract the sea lamprey ( Petromyzon marinus ). The TGAI/MP contains 99.3% 3

- ketopetromyzonol sulfa te, ammonium salt (3

- k PMZS), which has an active equivalent rate of 96.4% w/ w 3

- ketopetromyzonol sulf ate (3

- k PMZ S ) , as its active ingredient. The 3

- K PMZ S is one of several bile acid s produced by the male sea lamprey and used as a mating attractant. The structure of 3kPMZ, ammonium salt is shown below.

O
C h e m i c a l F o r m u l a : C 2 4 H 3 7 N O 6 S M o l e c u l a r W e i g h t : 4 6 7 . 6 2 O O S O 3 - N H 4 +

Description of the End

- Use Product

Male Sea Lampr ey Mating Pheromone (EPA File Symbol 6704

- O G ) is a n end use prod uct (EP) to be used to attract the sea lamprey ( Petromyzon marinus ) in tributaries of the Great Lakes, Lake Champlain, and the Finger Lakes. The active ingredient is 1.06 % w/w 3

- ketopetromyzon ol sulfate, ammonium salt . The two inert ingredients are present in the formulation at 43.76% w/w and 55.14% w/w, respectively (See Confidential Appendix for identity of the inert ingredients).3

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms

STUDY SUMMARIES

Rationale in Supp or t of Tier I Non

- Target O rganism Data Requirements

Due to the extremely high cost of manufacturing the test substance as well as the large quantities of test substance required for limit dose testing for Tier I non

- target organism data requirements (as specified under 40 CFR 158. 2060), the registrant (GLFC) submitted scientific rationales in lieu of providing OC S PP Guideline studies

. EPA typically requires Tier I testing only of the TGAI/MP. The EP is not subjected to additional testing unless there are inert ingredients of pote ntial human health or environmental concern present in the formulation. The EP, Male Sea Lamprey Mating Pheromone (EPA File Symbol 6704

- O G ) contains one inert ingredient of concern (See Confidential Appendix for identity of the inert ingredient of concern ).

The rationales submitted by GLFC in support the non

- target organism data requirements were for avian acute oral toxicity (TGAI and EP), avian dietary toxicity (TGAI and EP), fresh water fish toxicity (TGAI and EP), aquatic invertebrate toxicity (TGAI and EP), terrestrial plant toxicity (TGAI), and non

- target i nsect testing (TGAI). The rationales were all based on the active ingredient being applied at very l ow levels in water, and a lack observable toxicity reported historically for these organisms

. P resumed exposure to the active ingredient from its use as a Sea Lamprey attractant is not expected to exceed exposure from the naturally occurring form of the active ingredient released into natural waters by male sea lampreys during the normal spawning
p eriods. The applicant states that the pheromone is intended to be used to only enhance the concentration of the chemical already present naturally during spawning season, and will not be necessary to raise the concentration significantly above natural back ground levels

. The registrant propose d the same use pattern as described under previously EPA

- approved Experimental Use Permits (EUPs; see 75437

- EUP

- 1 through

- 4 and the respective EUP extensions)

. A summary of the rationales is as follows (see MRIDs 48 936212, 48936406, and 48936407 and their respective DERs for additional details and references) :

1. The active ingredient, 3

- ketopetromyzonol sulfate (3

- kPMZS), is a component of male lamprey mating pheromone (bile acids) that induces mating responses in ovulated female adult lamprey;

2. The EP is intended for direct application to tributaries in the upstream portions where lamprey spawning occurs at active ingredient target concentration between 1x10

- 11 to 1x10

- 13 M (4.72 to 0.0472 parts per trillio n), based on measured water flow at each time. All applications are done in conjunction with barrier

- integrated traps

.3

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms

3. The application 3kPZS to natural waters will result in a concentration (approximately 10

- 12 ) that is equal to or less than the co ncentration of naturally occurring 3kPZS that would occur during Sea Lamprey spawning season

.

4. Naturally occurring 3kPZS concentrations were found to range between 0.15 and 2.85 ng/L

- 1 (8.5 x 10

- 14 M and 1.4 x 10

- 12 M) during the spawning season in kn own sea lamprey infested segments of Great Lakes tributaries. Naturally occurring 3kPZS concentrations were measured in five streams periodically from April 12th to June 15th, 2012. In April and early May concentrations of natural 3kPZS were less than 10 ng/L, then increased from the middle of May to June . P eak spawning occurred in the middle of May and p eak concentrations of natural 3kPZS ranged from 33.4 ng/L to 120.9 ng/L. Naturally occurring concentrations of 3kPZS in the Ocqueoc River during J une and July 2011 were reported as 8.2 ± 4 ng/L and 15.3 ± 1.4 ng/L, respectively.

The applied concentration of 3kPZS as a pesticide is between 1x10

- 11 to 1x10

- 13 M (4.72 to 0.0472 parts per trillion)

5. 3kPZS is seasonal, only present during the sp ring migration and spawning period. Very low concentrations were reported (e.g. 10 ng/L) in April and early May, the start of spawning migration, then increased dramatically during the peak spawning season.

6. 3kPZS does not persist in the environment

. 3kPZS was not detected in sea lamprey infested streams by August, after the spawning migration. Since sea lampreys die after mating, synthesized 3kPZS and the 3kPZS contained in the corpus of male sea lampreys did not persist in stream water longer t han two months after the peak of spawning season. River water samples collected below sea lamprey barriers during the trapping season contained detectable levels of 3kPZS that ranged from 8.5 x 10

- 14 M in the Little Manistee River to 1.4 x 10

- 12 M in t he Betsie River. River water samples collected in late April (prior to the trapping season) above and below sea lamprey barriers did not contain detectable levels of 3kPZS. Samples collected in August (after spawning season) above and below sea lamprey barriers did not contain detectable levels of 3kPZS / Degradation data show 3kPZS degrades to the first order reaction and the average half

- life across three sample reservoirs was 26.1 h ± 1.8.

7. No observed adverse effects from 3kPZS have ever been ob served by research and field staff from 2004 to the present. The naturally occurring sea lamprey pheromones have been present in streams for over 60 years and no toxic effects from exposure to these compounds has ever been observed or reported.

8. The proposed EP contains an inert of concern at 43.8% w/w (see Confidential Appendix) . Th e inert is exempt from requirements of tolerances under 40 CFR 180.9303

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms
when applied to animals as a solvent or cosolvent. The acute toxicity of the inert ingredient fo r aquatic organisms (greater than 1000 mg/L ), many orders of magnitude above the rate at which it will be applied (0.018 mg/L). In addition, the applied concentration of this inert ingredient will be many orders of magnitude below known toxic endpoints for terrestrial organisms that may be exposed to the EP via direct dermal contact or via consumption of treated waters. Acute oral LC 50 for the inert ingredient ranges from 64,000 to 98,600 mg/L in rats, mice, and cats.

9. Terrestrial plants will n ot be exposed to the EP. Aquatic plants will not be exposed to the active ingredient applied as a Sea Lamprey attractant at levels above background levels (see above discussions). Exposure to aquatic plants to the inert ingredient will be minimal, as the inert is applied at an extremely low rate and will be rapidly diluted by running stream waters following application.

10. Efficacy studies demonstrated that non

- target species were not more likely to be captured in 3kPZS

- baited traps compared to unbaited traps (see Table 3 in DER for MRID 48936406).

Conclusions: ACCEPTABLE, no additional data are required. There are no concerns for non

target aquatic or terrestrial organisms resulting from the use of the EP according to proposed label use d irections. EPA/OPP/BPPD/BPB concurs with the hazard assessment conducted by CANADA PMRA.

Endangered Species Assessment (MRIDs 48936406 &

- 07 & 48936212 )

The active ingredient, 3

- ketopetromyzonol sulfate (3

- kPMZS), is not toxic to the target pest. It is a pheromone used to attract Sea Lamprey into traps. When applied as a pesticide in traps [ 1x10

- 11 to 1x10

- 13 M (4.72 to 0.0472 parts per trillion) ] , exposure of 3

- kPZMS to non

- target organisms is approximately the same as the range of natural background le vels of 3

- kPZMS emitted Sea Lamprey ( 8.5 x 10

- 14 M to 1.4 x 10

- 12 M ). 3kPZS does not persist in the environment and had an average half

- life across three sample reservoirs of 26.1 h ours ± 1.8 . Naturally

- occurring sea lamprey pheromones have been present in streams for over 60 years and no toxic effects from exposure to these compounds has ever been observed or reported. The Agency also conducted a search (10/14/2015) of the Ecological Incident Information System version 2.1.1 (EIIS) and did not find any r eports of detrimental exposure of 3

- ketopetromyzonol sulfate ( 3

- KPMZS) or the inert, methyl alcohol, to aquatic or terrestrial species

. In addition, efficacy studies demonstrated that non

- target species were not more likely to be captured in 3kPZS

- baited traps compared to unbaited traps

. Due to non

- toxic modes of action (pheromone) and low exposure to non

- target species (natural background levels not exceeded ) a Risk Quotient (RQ) is not typically calculated since the point estimates of either toxicity and /or exposure will usually be at or near zero.3

- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms

Based on the f act that 3

- ketopetromyzonol sulfate (3

- kPMZS) has had no known direct or indirect toxic effects to non

- target organisms

, its use pattern

, and low application rate , EPA has determined a "No E ffect" to any currently listed threatened or endangered species or any designated critical habitat.

cc: R. S. Jones, C. Pfeifer, BPPD Science Review File, IHAD/ARS Russell S. Jones, Ph.D., Sr. Scientist, FT, PY

- S: 010/08 /201 53- Ketopetromyzonal sulfate DP Number: 469657 & 469659 PC Code: 000802 EPA Reg. No.: 6704

- OU &

- OG Typ e of Study: Tier I Non

- Target Organisms

CONFIDENTIAL APPENDIX

. The inert ingredients are 43.76% w/w methyl alcohol and 55.14% w/w water.