Cyfluth rin an d Beta

- Cyfluthrin : R esponse to Comments on Human Health Scoping Document

Page 2 of 6 The HED Cyflu thrin and Beta

- Cyfluthrin Ris k Assessment T eam has received comments on the Cyfluthrin and beta

- Cyfluthrin Registration Review Scoping Document and Preliminary Workplan (EPA Docket ID: EPA

- HQ

- OPP

- 2010

- 06 84 ). Comments relevant to HED’s scoping document were provided by Bayer CropScience. The comments all fall within the following categories: hazard assessment, dietary exposure, residential exposure, and aggregate risk

assessment

. A summary of each comment and HED’s response to each comment follows.

Comments Related to Hazard Assessment

Comment 1

. Comment Concerning Assessment of the 10x FQPA Safety Factor

The Agency did not retain the FQPA Safety Factor for the previous cyfluthrin risk assessment. However, the Agency recently reviewed the pyrethroid toxicity databa se and current literature, and decided to retain the FQPA Safety Factor because of potential age

- dependent pharmacokinetics and pharmacodynamics. Bayer CropScience disagrees with the Agency’s decision to retain the FQPA Factor.

HED’s Response:

HED add ressed this issue in July 2010 when it presented to a Scientific Advisory Panel (SAP) of
experts a study proposal to characterize pyrethroid juvenile susceptibility . As a result of this SAP, the Agency is anticipating receiving additional data from which to make an informed decision. Furthermore, the Agency commends Bayer’s role as a leader in providing data to
assist in this effort.

During registration review, t he Agency will reassess the need for the 10x FQPA Safety Factor

. In doing so, it will consider the advice of the SAP, along with a ll information relevant to cyfluthrin FQPA Safety Factor assessment.

Comment 2 . Comment Concerning the Dermal Absorption F actor

Bayer CropScience stated that EPA used a dermal absorption factor of 5% in a review

conducted in 2002

. Bayer has conducted a dermal absorption study using beta

- cyfluthrin. T he amount absorbed was 0.8% of the applied high dose and 1.3% of the applied low dose. Bayer requested that HED review the report and consi der using the values in future risk assessments.

HED’s Response:

HED welcomes chemical

- specific data submitted by registrants. HED will review the study (MRID 48290901) for future actions. If the study is acceptable, HED will use the dermal absorption values in the final risk assessment for the registration review decision

.Cyfluth rin an d Beta

- Cyfluthrin : R esponse to Comments on Human Health Scoping Document

Page 3 of 6 Comment 3 . Comment Concerning the Agency’s Request for an Immunotoxicity Study:

Bayer CropScience acknowledged that an immunotoxicity study in rats and/or mice is now a requirement. Bayer further stated that it has submitted guideline toxicology studies in rats and mice that address immunotoxicological properties. Bayer believes that these studies satisfy the requirement for an immunotoxicit y study.

HED’s Response:

Although immunotoxicological information provided in the studies that HED has required in the past helps to elucidate immunotoxic potential, the information is not adequate to make a complete assessment of immunotoxicity. As a result, the Agency continues to require the

submission o f an acceptable immunotoxicity study.

Comments Related to Dietary Exposure Assessment

Comment 4

. Comment from Bayer CropScience Concerning Tolerance Expression

Bayer CropScience stated that there was an error in the executive summary of the scoping

document. The executive summary state s that compliance with the tolerances for beta

- cyfluthrin should be determined by measuring beta

- cyfluthrin only. Bayer feels that compliance with the

tolerances for beta

- cyfluthrin should be determined by measuring cyfluthrin only.

HED’s Response:

The current analytical enforcement method for cyfluthrin and beta

- cyfluthrin does not distinguish between the four isomers. At the time of registratio n review, the tolerance enforcement method might be one that does distinguish between the isomers. At that time, the Agency should specify which compounds nee d to be analyzed to determine compliance with the

tolerance levels.

Comments Related to Residential Exposure Assessment

Comment 5

. Comment Concerning Residential Risk Estimates Reported in the Scoping

Document

Bayer CropScience stated that there were discrepancies between some residential risk estimates reported in Table 1 and Appendix 4 of the scoping document. Bayer further stated that the residential risk assessment is not mentioned in the residential exposure section of the scoping

document or in the table of references. The results of the residential risk assessment should be

summar ized and included in the references list.Cyfluth rin an d Beta

- Cyfluthrin : R esponse to Comments on Human Health Scoping Document

Page 4 of 6 HED’s Response

HED acknowledges the discrepancies in the reported risk estimates. The values given in Appendix 4 are the correct ones. The scoping document does not need to be revised because the discrepancies do not change HED’s conclusion that the residential risks are not of concern. During registration review, HED will put the risk assessment through its standard secondary review process to ensure that all values in the risk assessment are correct and inter nally consistent. In addition, documents will be summarized and referenced as appropriate.

Comment 6

. Comment Concerning the Agency’s Use of Probabilistic Models for Conducting Resident ial Exposure Assessments

Bayer CropScience stated that the Agency does not use probabilistic models for residential exposure assessment, but instead uses methodology that overestimates residential exposures. Bayer encouraged the Agency to replace the current conservative deterministic algorithms that

assume worst

- case scenarios with population based, longitudinal, probabilistic assessments. The Agency should do this by revising existing exposure algorithms, using parameter distributions, incorporatin g use probabilities, or by conducting probabili stic modeling. Assessment of postapplication exposure of children following a crack and crevice application is an example of a case where unrealistic exposure estimates are generated by using deterministic methods.

HED’s Response

The Agency is in the pr ocess of revising its SOPs for residential exposure assessment. During registration review, HED will conduct an aggregate risk assessment that adheres to HED’s most

up

- to

- date models, policies, methodologies

, and procedures. When appropriate, HED will us e distributions of data in place of point estimates. In the event that Bayer submits a probabilistic assessment, HED will evaluate the inputs and, to the extent possible, incorporate the results into the cyfluthrin and beta

- cyfluthrin risk assessment.

C omment 7 . Comment Concerning the Agency’s Revision of the Residential SOPs and Cooperation with the Scientific Community and Stakeholders

Bayer CropScience acknowledged the Agency’s proposal to revise the Residential SOPs and

e xposure a lgorithms for c alc ulation of d ermal, i nhalation, and h and

- to

- m outh e xposure

. The Agency should develop scientifically based exposure algorithms by working with the scientific community and various stakeholders. Bayer stated that it was willing to work with the Agency

to d evelop these refined equations.

HED’s Response

The Agency routinely works with the scientific community. HED evaluates scientifically

- based algorithms and data submitted by the scientific community and various stakeholders. In 2009

, the public and the FIFRA S cientific Advisory Panel (S AP ) reviewed revised version s of theCyfluth rin an d Beta

- Cyfluthrin : R esponse to Comments on Human Health Scoping Document

Page 5 of 6 Residential SOPs . The SOPs were reviewed to ensure that the Agency identified state

- of

- the

- art
scientific data, formally incorporated additional exposure sources, and use d updated info rmation

in a scienti fically credible manner. The Agency is currently reviewing all SAP comments

. HED will begin to use the SOPs at such time as they are ready for use.

Comment 8

. Comment from Bayer CropScience Concerning Default Parameters Used in Residential Exposure Assessments and Data Available in the Residential Exposure Joint Venture Survey Conducted by the Consumer Specialty Products Association

Bayer CropScience stated that many of the default paramete rs used in residential exposure

assessments do not reflect exposures that would be likely to occur in residential environments

and

, therefore , the Agency’s assessments overestimate potential exposure . Bayer plans to conduct a liquid crack and crevice trea tment exposure study to quantify and refine the current

conservative transferrable residue values used in the EPA human health risk assessment. In addition, Bayer will survey pest control operators in order to refine assumptions regarding the quantity of pesticide used in one day. Bayer further stated that, in order to conduct a probabilistic temporal exposure assessment, one must have information concerning how, where, when, and the quantity of each pesticide used. The most recent data are a vailable thr ough the Residential Exposure Joint Venture Survey conducted by the Consumer Specialty Products

Association (CSPA) in 2001 and 2002. The CSPA is proposing to conduct a new survey to update product use information. The Agency should support this work and use the data in residential exposure assessments.

HED’s Response:

During registration review, t he Agency will evaluate all chemical

- specific data submitted by the registrants and will incorporate the data, as appropriate, in order to refine residential and aggregate human health risk assessments. HED notes that

, if any of the proposed studies involve potential exposure to human subjects , then protocols for these studies m ight be subject to review by the Agency’s Human Studies Review Board (H SRB) . If the review is necessary

, it must occur prior to the initiation of the studies.

Comments Related to Aggregate Risk Assessment

Comment 9

. Comment Concerning Probabilistic Aggregate Assessment:

B ayer CropS cience stated that the Agency has not performed a complete probabilistic aggregate risk assessment that incorporates monitoring residue data, residential event

- based probabilities, residential parameter distributions, and population

- based longitudinal exposure modeling. Bayer

further stated that it would submit a probabilistic assessment performed with the CARES Model. It will include an analysis of various biomonitoring conducted on children and adults using a compound

- specific metabolite that is produced only by cyfluthrin. HED’s Response:Cyfluth rin an d Beta

- Cyfluthrin : R esponse to Comments on Human Health Scoping Document

Page 6 of 6 D uring registration review, HED will perform an aggregate assessment that adheres to HED’s

most up

- to

- date models, policies, methodologies, and procedures. In the event that Bayer

submit s a probabilistic assessment, HED will evaluate the assessment to determine its adequacy

for use in risk assessment

. HED will also evaluate any chemical

- specific data that are submitted in support of the risk assessment. As stated above, if any of the proposed studies involve potential exposure to human s ubjects, then protocols for these studies might be subject to review by the Agency’s HSRB. If the review is necessary, it must occur prior to the initiation of the

studies.