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: October 7, 2015

SUBJECT: Science Review in Support of the Registration 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-Target Organism Hazard Assessment. BPPD Concurrence of Review by 

CANADA PMRA. Endangered Species Assessment Addendum.

Decision Numbers: 469657

DP Numbers: 410913 & 410915

EPA File Symbol Numbers: 6704-OU & 6704-OG

Chemical Class: Biochemical

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 & Pollution Prevention Division (7511P)

TO: Chris Pfeifer, Regulatory Action Leader /s/ 02/17/2014 /s/ 10/07/2015

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

On behalf of the Great Lakes Fisheries Commission (GLFC), T. Hubert requests registration of a 

new active ingredient, 3-Ketopetromyzonal Sulfate (Male Sea Lamprey Pheromone) which is 

intended for use in the control of Sea Lamprey. In lieu of Guideline studies, the registrant has 

submitted scientific rationales and published and unpublished non-target organism study data in 
3-Ketopetromyzonal sulfate DP Number: 469657 & 469659

PC Code: 000802 EPA Reg. No.: 6704-OU & -OG

Type 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 CONCLUSIONS

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 Lamprey 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. 

Description 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 sulfate, ammonium salt (3-kPMZS), which has an active equivalent rate of 

96.4% w/w 3-ketopetromyzonol sulfate (3-kPMZS), as its active ingredient. The 3-KPMZS is 

one of several bile acids produced by the male sea lamprey and used as a mating attractant. The 

structure of 3kPMZ, ammonium salt is shown below. 

 

O

Chemical Formula: C24H37NO6S

Molecular Weight: 467

.

62

O

OSO3

-

NH4

+

Description of the End-Use Product

Male Sea Lamprey Mating Pheromone (EPA File Symbol 6704-OG) is an end use product (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-ketopetromyzonol 

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

Type of Study: Tier I Non-Target Organisms 

STUDY SUMMARIES

Rationale in Support of Tier I Non-Target Organism 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 OCSPP 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 

potential human health or environmental concern present in the formulation. The EP, Male Sea 

Lamprey Mating Pheromone (EPA File Symbol 6704-OG) 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 insect testing (TGAI). The rationales were all based on the active 

ingredient being applied at very low levels in water, and a lack observable toxicity reported 

historically for these organisms. Presumed 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 

periods. 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 background levels.

The registrant proposed 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 48936212, 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 trillion), 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

Type 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 concentration 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 known 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. Peak spawning occurred in the middle of 

May and peak 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 June 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 spring 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 than 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 the 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 observed 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). The inert is exempt from requirements of tolerances under 40 CFR 180.930
3-Ketopetromyzonal sulfate DP Number: 469657 & 469659

PC Code: 000802 EPA Reg. No.: 6704-OU & -OG

Type of Study: Tier I Non-Target Organisms 

when applied to animals as a solvent or cosolvent. The acute toxicity of the inert 

ingredient for 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 LC50 for the inert ingredient

ranges from 64,000 to 98,600 mg/L in rats, mice, and cats. 

9. Terrestrial plants will not 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 nontarget aquatic or terrestrial organisms resulting from the use of the EP according to proposed 

label use directions. 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 levels 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 hours ± 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 reports 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

Type of Study: Tier I Non-Target Organisms 

Based on the fact 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 Effect" 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: 010/08/2015
3-Ketopetromyzonal sulfate DP Number: 469657 & 469659

PC Code: 000802 EPA Reg. No.: 6704-OU & -OG 

Type 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.