Page 1 of 5 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

February 20 , 2013

SUBJECT: Acetamiprid : Summary of Hazard and Science Policy Co uncil ( HASPOC ) Meeting of January 17

, 201 3 : Revisit of r ecommendation on the need for a 28

- day inhalation stud y

.

PC Code: 099050 DP Barcode: N / A

Decision No.: N/A Registration No. : N/A

Petition No.: N/A Regulatory Action: N/A Risk Assessment Type: NA Case No.: N/A

T XR No.: 0056556 CAS No.: 135410

- 20

- 7

MRID No.: N / A 40 CFR: §180. 578

FROM: Kristin Rury , MPH

Executive Secretar y , HASPOC Health Effects Division (7509 P )

THROUGH: Jess Rowland

, Co

- Chair Anna Lowit, Ph.D

, Co

- Chair

HASPOC Health Effects Division (7509P)

TO: Elizabeth Holman

, Chemist
Christina Swartz, Chief

Risk Assessment Branch II (RAB II ) Health Effects Division (HED; 7509P)

MEETING ATTENDEES :

HASPOC Members: Anna Lowit, Elissa Reaves, Jess Rowland, John Kough, Jonathan Chen,

Julie V an Alstine, Kristin Rury, Michael Metzger, PV Shah, Ray Kent

Presenter s : Elizabeth Holman

Other Attendees: Ayaad Assad, Angela Howard, Christina Swartz, Christopher Schlosser, Jessica Kidwell, Jolene Trujillo, Kelly Lowe, Kelly O’Rourke, Matthew Lloyd, Myron Ottley, Nancy Dodd (phone) , Scott MillerPage 2 of 5 I. PURPOSE OF MEETING:

R isk A ssessment B ranch II (RAB II) prepar ed a n acet a miprid risk assessment for several new agricultural uses in 2012 and acetamiprid is currently undergoing R egistration R eview

. The Hazard Science Policy Council (HASPOC) met on March 15, 2012 to discuss the need for a 28

- day rat inhalation study to support registered and proposed uses of acetamiprid

. The HASPOC concluded based on a WOE approach that a 28

- day inhalation toxicity study was required to reduce uncertainty associated with the use of an oral point of departure (P OD ) for assessing risk

via the inhalation route based on low margins of exposure ( MOEs ) ( i.e, MOEs < 300) for some

seed treat ment uses and the toxicological profile of acetamiprid.

Since th at HASPOC meeting

, the registrant has provided additional information and requested

HED reevaluat e the need for the 28

- day inhalation study. Therefore, the HASPOC met on January 17, 2013 to reevaluate the need for an acetamiprid 28

- day inhalation study based on the information provided by the registrant

.

II. SUMMARY OF USE PROFILE & PREVIOUS RISK ASSESSMENT S :

Acetamiprid is a selective insecticide use d to control various sucking/chewing insect pests that feed upon fruit and vegetable crops. It is a member of the chloronicotinyl (neonicotinoid) class

of insecticides , with a subclass designation as a nitromethylene neonicotinoid . Acetamiprid is register ed for use on agricultural crops and ornamental plants, as seed treatments, and for use in food handling establishments. In addition, acetamiprid is registered for residential uses as crack
and crevice and mattress treatments, and as outdoor termiticide a nd perimeter treatments.

Formulations include wettable powder ( WP )

, dry flowable (DF), water

- soluble packet (WSP), emulsifiable concentrate (EC), and ready

- to

- use liquid (RTU). Occupational handlers are expected to be exposed to acetamiprid for short

- an d intermediate

- term durations; however, residential handlers are expected to be exposed for short

- term durations only. In agricultural settings, acetamiprid is applied using ground

- or aerial

- based broadcast spray equipment. In residential settings, acet amiprid is applied using handheld equipment.

In t he most recent acetamiprid risk assessment ( E. Holman

, D394322 , 04/19/2012 ) an oral point of departure ( POD ) of 10 mg/kg/day was used to assess risk via short

- and intermediate

- term inhalation exposure. The POD was based on decreased body weight and body weight gains in the offspring, decreased early pup survival on post

- natal days (PND) 0

- 1, and decreased startle response on PND 20/60 in males seen at the lowest observed adverse effect level (LOAEL) of 45 mg/kg/day in the developmental neurotoxicity

.

Inhalation MOEs from occupational activities range from 260 to 25 0 ,000 with baseline attire (no respirator). However, with the additional mitigation of a respirator for mixing/loading the WP

for aerial application

, all occupational handler inhalation MOEs range from 1 3 00 to 250,000 ( Level of Concern ; LOC = 100 )

. For residential uses, inhalation MOEs range from 3,600 for handlers applying an outdoor perimeter treatment to 560,000 for adults , post

- applica tion, following indoor crack and crevice treatment

.Page 3 of 5 III. STUDY WAIVER REQUESTS

Inhalation Study

Previously, the Office of Pesticide Programs ( OPP ) used a set of criteria to determine whether or not an inhalation study could be waived. These criteria c onsidered the scientific information

available for the chemical, including its: (1) degree of i rritation and c orrosivity ; 2) v olatility ; 3)

a erosol p article size; and 4) Acute Toxicity Category and extrapolated MOE s (e.g., MOEs 10 times higher than the target). In 2009, OPP developed an issue paper on risk assessment approaches for semi

- volatile pesticides. As part of that issue paper, an analytical comparison was conducted of oral and inhalation experimental toxic ology studies. In general, this analysis showed that the degree to which oral PODs were protective of potential inhalation toxicity varied. In many cases the oral POD was protective but in some cases the inhalation PODs were significantly more sensitive. Currently, OPP us es a weight of the evidence (WOE) approach that builds upon OPP’s experience using the criteria listed above conclusions from the 2009 SAP. As approaches for route to route extrapolation continue to evolve and improve, OPP may incorpora te additional considerations into the WOE analysis.

Inhalation exposure can be to vapors, droplets, and/or particles/dusts. The form of this exposure is determined by a number of factors including physical

- chemical properties, use pattern, and

exposur e scenario s . This interim WOE approach considers:

1. Physical

- chemical properties: Vapor pressure and Henry’s law constant are key considerations with respect to the volatilization after sprays have settled. Acetamiprid ( MW = 2 22.7 g/mol) has a low vapor pressure ( 1 x10 - 8 mm Hg at 25 ° C) and a n estimated Henry’s law constant of 6.9 x 10 - 8 atm

- cu m/mole at 25°C

. However, low vapor pressure and/or Henry’s law constant does not preclude exposure to aerosolized droplets or particles/dusts.

2. Use pattern & exposure scenarios: Any application scenario that leads to inhalation of droplets needs to be considered in the WOE analysis for an inhalation toxicolog y study waiver request. A ir blast and aerial applications are more likely to lead to higher occupational handler inhalation exp osure, particularly to droplets; and may also contribute to spray drift. In the case of acetamiprid , the highest inhalation exposure s were associated with mixing/loading the WP formulation of acetamiprid for aerial

treat ment to tree nuts

.

3. Margins of Exposure (MOEs): The MOE estimates for inhalation scenarios were calculated using the NOAEL from an oral toxicity study

, and should be considered in the WOE analysis for an inhalation toxicology study waiver. In the past, OPP has used MOEs of approximately 10 times higher than the level of concern as a benchmark for granting waiver requests (i.e., in the case of acetamiprid , h igher than 1,000) . The 2009 analysis suggests this approach is appropriate for most pesticides

, but not all. Under the

interim WOE approach , MOEs from 10

- 100 times greater than the level of concern will

be considered in combination with other factors dis cussed here. All worker exposures are

assessed as short

- and inter mediate

- term based on label

- prescribed uses and expectedPage 4 of 5 exposure durations. At the March 15, 2012 meeting, t he HASPOC note d that t he highest exposure estimate (MOE = 290) assume d the use of a respirator when treating canola and

mustard seed with a WP formulation of acetamiprid

. However, this WP formulation of acetamiprid is no t registered for use on canola and mustard seed s . T reating canola and

mustard seeds with the liquid (EC) formulation does not result in risks of concern (MOE=32,000). With the addition of a respirator for mixing/loading WP acetamiprid for aerial application

, all occupational handler MOEs are > 1300

. This is one type of mitigation the registrant could elect to put in place, although reducing the application rate to higher acreage crops may also achieve MOEs >1000. In addition , for residential exposures, the MOEs are significantly higher (inhalation MOEs range from 3,600 to 560,000)

.

4. Toxicity : Acetamiprid and its metabolites have relatively low acute toxicity via

inhalation (Toxicity Category III) and dermal (Toxicity Category III) routes of exposure in the rat and there is no evidence of dermal sensitization or eye irritation. Acetamiprid

s howed somewhat higher toxicity ( Toxicity Category II) via the oral route. Acute toxicity testing of the WP, WSP, and RTU formulations resulted in Toxicity Category III or IV designations for all routes of exposure. Overall, the toxicology data showed tha t in all species tested, generalized nonspecific toxicity was observed as decreases in body weight, body weight gain, food consumption and food efficiency. Generalized effects were also observed in the liver in the form of hepatocellular hypertrophy in bo th mice and rats and hepatocellular vacuolation in the rat. These effects are considered to be adaptive.

When considering the need for an inhalation toxicity study, the Agency will evaluate other pesticides which share the same MOA and/or are in the sa me class. These pesticides can provide important information with respect to potential inhalation toxicity. Specifically, if other similar pesticides show inhalation toxicity studies to be more sensitive, an inhalation toxicity study may be required rega rdless of MOE, depending on the exposure profile. Acetamiprid is a member of the neonicitinoid class of insecticides, which also includes the following insecticides: clothianadin, imidacloprid, dinotefuran, thiamethoxam, and thiacloprid. HASPOC recently concluded that a 28

- day inhalation study was required for clothianadin (J. VanAlstine, TXR#0055320, 03/23/2012), but was not required for thiamethoxam (K. Rury, TXR#0056482, 12/17/2012). Inhalation studies are available for imidacloprid, dinotefura n and thiacloprid . No effects were noted in the inhalation studies for imidacloprid and dinotefuran at the highest concentration tested,

and thus these studies were not used for PODs in the risk assessment. However, the thiacloprid inhalation study is the basis of inhalation PODs for that chemical. Note that the toxicological profile for thiacloprid is quite different from that of the other

neonicotinoid insecticides

.

IV. HASPOC RECOMMENDATIONS :

Based on a WOE approach considering all the available ha zard and exposure information and proposed addition of a respirator for mixing/loading WP acetamiprid for aerial application, or other appropriate mitigation, the HASPOC recommends that a subchronic inhalation toxicityPage 5 of 5 study is not required for acetamiprid at this time. This determination considered all of the available hazard and exposure information for acetamiprid , including : (1) registrant’s agreement on risk mitigation on the use of the WP label for mixing/loading; and 2) the WP formulation not used as seed treatment and 3) the use of an oral POD that results in MOEs greater than 1300 for all occupational and residential exposures. However, if the exposure profile for acetamiprid changes, the HASPOC will reevaluate the need for a subchronic inhalation toxicity study.