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Comment: Piperonyl Butoxide Task Force II. The HED Scoping Document states that,

“ The dietary exposure assessment (including food and water) needs to be updated to reflect current methodologies. ” This statement is not supported by any specific examples of changes in current methodologies for exposure from food/water that have taken place

since the RED was completed in 2006. It would be helpful if more information could be provided. It suggests that there may be substantive changes in policy or methods that have been adopted in this area in the past 5 years. If so, these policies and methods

should be ref

erenced.

HED Response : OPP’s efforts to improve, update, and refine i ts risk assessment methodologies are ongoing. A large part of the purpose of registration review is to update and/or refine assessments to incorporate changes that have occurred since t he previous risk assessment was conducted. These changes may involve revisions to Agency policies, updated modeling methodologies, receipt of new data and/or

reevaluation of exis t ing data. Any policy or other changes that have been finalized and

are in effect at the time that the reg istration review assessment is conducted will be incorporated into the assessment. Following are some examples of specific updates required for the piperonyl butoxide dietary and drinking water exposure assessment.
With the exception of new toxicity data requirements, t he updates are internal to OPP and do not require data from the r egistrant for implementation.

- As noted in the HED scoping document, FQPA requires that anticipated residues (ARs) be updated every five years . This involves revising the ARs

– and the food

and water assessment

– to incorporate updated information on percent crop treated and pesticide data program (PDP) residues.

- For the 2006 dietary exposure assessment

, d rinking water levels of concern (D WLOCs) were calculated and compared with the estimated drinking water concentrations (EDWCs) of piperonyl butoxide in ground water and surface water. Since that time, OPP’s Dietary Exposure Evaluation Model DEEM

- FCIDTM has been updated to incorporate EDWCs directly into the dietary assessment. The updated

DEEM

- FCIDTM model will be used for the dietary assessment conducted for registration review.

- As stated in the E nvironmental F ate and Effects Division ’s (EFED) Registration

Review Problem Formulation for Piperonyl Butoxide, an updated water assessment will be conducted considering the following: new data submitted to the agency; changes in the label uses and rates; any mitigation that has been proposed in the previous assessments; n ew models that have been developed for use in drinking water assessment. The updated EFED drinking water assessment will be used for the food

and water assessment conducted for R egistration R eview.

- An immunotoxicity study is required under 40 CFR Part 158 as a part of the new d ata requirements for registration of a pesticide for food and non

- food uses. Newly required toxicity data may result in revised points of departures (PODs) for dietaryPage 3 of 4

exposure assessment. If so, the revised PODs will be used for the updated dietary

asse ssment.

Comment: PBTF II. The Scoping Document states that

, “ The residential exposure assessment is adequate but should be updated to reflect current standard operating procedures. ” It is unclear what current SOPs are being referenced. Are these the residential SOPs that EPA proposed in 2009, but has not yet formally adopted. Or is EPA referring to policy changes in the way that the 2001 SOPs are being interpreted at

the time of t his writing. Is EPA referencing changes to be made at some future time that corresponds with timing of a new RED?

HED Response: The HED R esidential SOPs are undergoing significant revis ion to incorporate any/all available new data and any other changes r esulting from HEDs reevaluation of existing data. As noted above, any changes to risk assessment methodology and/or exposure assumptions that have been finalized and are in effect at the time that the registration review assessment is conducted will be in corporated into the residential exposure assessment. These updates are internal to OPP and do not require data from the registrant to implement. Any changes to the Residential SOPs and the

rationales for those changes will be made publicly available prio r to their implementation

.

Comment: PBTF II. The Scoping Document states that, “ The occupational exposure assessment is adequate but needs to be updated to reflect current standard operating procedures. ” We are not aware of changes in SOPs for occupat ional exposure assessment. Is EPA referring to use of the AHED data, policy changes in policies for acute versus chronic exposures or something else. This statement does not provide enough detailed information to assist registrants.

HED Response: As pa rt of OPP’s ongoing reevaluation and refinement of its risk assessment process, the Pesticide Handler Exposure Database ( PHED ) occupational handler unit exposures are being replaced with unit exposures based on data provided by

the A gricultural Handler Exp osure Task Force (AHETF) . In addition the transfer

coefficients established in HED ExpoSAC P olicy 3 are being updated to reflect the complete set of data available in the A gricultural Re

- entry Task Force (ARTF)

submission. These updates are internal to OPP and do not require data from the registrant to implement. Any changes to the occupational handler and post

- application exposure assumptions and the rationales for those changes will be made publicly available prior to

the ir implementation.

Comment: PBTF II. The Scoping Document states that, “ A number of residential and/or occupational exposure studies requested in the RED have not been submitted. The outstanding data must be submitted for registration review. ” It wou ld be helpful to provide more details regarding the basis for these studies and their specific nature.

HED Response: The Agency issued, and the registrant(s) should have received data call

in (DCI) notices for the following studies and/or information:Page 4 of 4

- OP PTS GLN 875.1400: Inhalation Exposure

– Metered Release Devices

- OPPTS GLN 875.1700: Use Data

– Metered Release Devices

- OPPTS GLN 875.1400: Inhalation Exposure Indoors (ultra low volume (ULV) Cold Fogger

Descriptions and rationales for these studies were p rovided with the DCIs.

Comment: PBTF II. The Scoping Document states that, “ The aggregate risk assessment is adequate but may need to be updated to incorporate any changes to dietary and/or residential exposure assessments. ” This statement needs cla rification. What specific changes to the dietary and residential assessments does EPA anticipate?

HED Response: Specific changes to the dietary and residential assessments outlined above will be incorporated into the updated aggregate risk assessment as appropriate.

Comment: Physicians Committee for Responsible Medicine (PCRM) . The following two studies could be used to aid or fulfill the data requirements for the Acute and Subchronic Neurotoxicity studies (870.6200) and should be further investigat ed by the Agency: Anticonvulsant activity and neurotoxicity of piperonyl butoxide in mice and In vitro neurotoxicity of the antitumor agent 9

- methoxy

- N2

- methylellipticinium acetate (MMEA): role of brain cytochrome P

- 450

.

HED Response: HED will investi gate these studies as part of the toxicological

evaluation of piperonyl butoxide conducted for Registration Review.

Comment: PCRM. A study conducted in 2010, which analyzed i n duced immunotoxi ci ty via apoptosis in murin sp l enocytes in vitro was conducted using malathion, lindane, and piperonyl butoxide, individually or in combined mixtures, may be used to either waive or direct the conduct of the Immunotoxicity requirement (870.7800) in terms of dose level.

HED Response: Again, HED will i nvestigate these studies as part of the toxicological evaluation of piperonyl butoxide conducted for Registration Review.