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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 referenced.

HED Response: OPP’s efforts to improve, update, and refine its 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 the 

previous risk assessment was conducted. These changes may involve revisions to 

Agency policies, updated modeling methodologies, receipt of new data and/or 

reevaluation of existing data. Any policy or other changes that have been finalized and 

are in effect at the time that the registration 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, the updates are internal to OPP and 

do not require data from the registrant 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, drinking water levels of concern 

(DWLOCs) 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 Environmental Fate 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; new 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 Registration Review.

- An immunotoxicity study is required under 40 CFR Part 158 as a part of the new data 

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

assessment.

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 this writing. Is EPA referencing changes to be made at some future time that 

corresponds with timing of a new RED?

HED Response: The HED Residential SOPs are undergoing significant revision to 

incorporate any/all available new data and any other changes resulting 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 incorporated 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 prior 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 occupational 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 part 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 Agricultural Handler Exposure Task Force (AHETF). In addition the transfer 

coefficients established in HED ExpoSAC Policy 3 are being updated to reflect the 

complete set of data available in the Agricultural 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 

their 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 would 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:
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- OPPTS 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 provided 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 clarification. 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 investigated 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 investigate these studies as part of the toxicological 

evaluation of piperonyl butoxide conducted for Registration Review.

Comment: PCRM. A study conducted in 2010, which analyzed induced immunotoxicity 

via apoptosis in murin splenocytes 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 investigate these studies as part of the toxicological 

evaluation of piperonyl butoxide conducted for Registration Review.