Cyfluthrin and Beta-Cyfluthrin: Response to Comments on Human Health Scoping Document

Page 2 of 6

The HED Cyfluthrin and Beta-Cyfluthrin Risk Assessment Team has received comments on the 

Cyfluthrin and beta-Cyfluthrin Registration Review Scoping Document and Preliminary 

Workplan (EPA Docket ID: EPA-HQ-OPP-2010-0684). 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 database 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 addressed 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, the Agency will reassess the need for the 10x FQPA Safety Factor. 

In doing so, it will consider the advice of the SAP, along with all information relevant to 

cyfluthrin FQPA Safety Factor assessment.

Comment 2. Comment Concerning the Dermal Absorption Factor

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. The 

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 consider 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.
Cyfluthrin and Beta-Cyfluthrin: Response 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 immunotoxicity 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 of 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 states 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 registration review, the tolerance 

enforcement method might be one that does distinguish between the isomers. At that time, the 

Agency should specify which compounds need 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 

summarized and included in the references list.
Cyfluthrin and Beta-Cyfluthrin: Response 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 internally 

consistent. In addition, documents will be summarized and referenced as appropriate.

 

Comment 6. Comment Concerning the Agency’s Use of Probabilistic Models for 

Conducting Residential 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, 

incorporating use probabilities, or by conducting probabilistic 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 process 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 use 

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.

Comment 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 

exposure algorithms for calculation of dermal, inhalation, and hand-to-mouth exposure. 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 develop 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 Scientific Advisory Panel (SAP) reviewed revised versions of the 
Cyfluthrin and Beta-Cyfluthrin: Response 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 used updated information 

in a scientifically 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 parameters 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 treatment 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 available through 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, the 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 might be subject to review 

by the Agency’s Human Studies Review Board (HSRB). 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:

Bayer CropScience 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:
Cyfluthrin and Beta-Cyfluthrin: Response to Comments on Human Health Scoping Document

Page 6 of 6

During 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 

submits 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 subjects, 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.