Page 2 of 4 Comment: MGK Insect Control Solutions. With respect to the uncertainty factor of 1000 for the short-term and intermediate-term inhalation endpoints rela ted to respiratory tract lesions, we disagree with the Agen cy’s position on metaplasia. A number of research studies on the respiratory tract prov ide evidence that a wide variety of factors (including chemical exposure) can bring about the histopathologica l transformation of squamous metaplasia of the la rynx. Other factors that s uggest squamous metaplasia in the larynx of rats should not be viewed as a toxicological response, but rather an adaptive one. We provided more detail in formation during the Reregistration process and plan to revisit this issue duri ng the Registration Review process.

HED Response: With respect to the short-term i nhalation endpoint, HED points out that it is based on tremors, labored breathing, hyperactivity, secretory signs, matted coat, and decreased body weight/body weight gain, wh ich were observed during the first few weeks of the subchronic inhalation study. The intermediate-term inhalation endpoint is not based solely on metaplasia. The LOAEL in the subchronic inhalation study is based on hypertrophy/hyperplasia in the mucosal seromucous glands of the larynx, pseudostratified ciliated/nonciliated column ar epithelial hyperkeratosis of the larynx (both sexes), goblet cell hyperpla sia in the nasopharynx and na soturbinates (males), and epithelial intracytoplasmic eosinophilic materi al in the nasoturbinates, which were

observed at all dose levels at the end of the study.

Comment: MGK Insect Control Solutions

. Under Hazard Characterization, second bullet. EPA has made a gross error in th is document and quoted the incorrect cancer classification for pyrethrins. After review of the mechanism of action data of the PJV, in the EPA HED report “PYRETHRINS: Fourth Re port of the Cancer Assessment Review Committee”, TXR No.: 0054822, dated Februar y 14, 2008, HED reclassified pyrethrins as “Not Likely to be Carcinogenic to Hum ans” at doses that do not cause a mitogenic response in the liver /cell proliferation.

HED Response: The Agency acknowledges this error. MGK Insect Control Solutions is correct in pointing out that the can cer classification for pyrethrins is “ Not Likely to be Carcinogenic to Human s” at doses that do not cause a mit ogenic response in the liver/cell proliferation.

Comment: MGK Insect Control Solutions

. In addition, as a member of the Residential Exposure Joint Venture (REJV), the origi nal survey database, and the new one just getting underway, will provide highly refine d use and usage information for consumer products containing pyrethrins. We strongly ur ge the Agency to use the Surveys not only for Human Health risk assessments, but also the surveys can be mined for detailed information that can refine ecological risk assessments for outdoor products.

HED Response: HED looks forward to reviewing revised REJV survey to inform residential human health exposure and risk assessment when that survey data is submitted to the Agency. That data is anticipated to be useful for assessing residential exposure, from a deterministic and probabilistic perspective.Page 3 of 4 Comment: MGK Insect Control Solutions

. The large number of in cidents reported in the time period of 2006 to 2011, is misleadi ng with respect to products containing pyrethrins. Many of the pr oducts with pyrethrins also contain more toxic residual pyrethroids which are more likely to have caused effects, if they were attributable to the pesticide exposure (many reportable incidents are deemed unrelated to exposure to the product.) The PJV is mid way through a 5 year product stewardship program with the Agency providing information to clarify any role pyrethrins may have in adverse effects, particularly possible allergic reactions. So fa r, the results indicate many fewer effects directly related to pyrethrins exposure. This program is fu rther described in bullet three

in the EPA document.

HED Response: EPA acknowledges that when an incident involves more than one pesticide, it is difficult to determine which e ffects are attributed to the pesticide being considered. However, because pyrethrins ar e usually co-formulated with other active ingredients, and because there is about a 50-fold difference between the frequency of incidents involving pyrethrins al one versus pyrethrins and othe r chemicals, it is important to attend to the incidents involving multiple chemicals. Consequently, based on the frequency of exposures and the potential fo r exposures to resu lt in high severity outcomes, these incident data warrant further analysis in the preliminary risk assessment phase of Registration Review. EPA agrees it will be importa nt to consider Pyrethrins Joint Venture (PJV) product st ewardship program during the preliminary risk assessment phase of Registration Review.

Comment: MGK Insect Control Solutions

. With respect to the Immunotoxicity study requirement, MGK points EPA to the ongoing effort between CropLife America and EPA OPP’s Health Effects Division review of all of the existing immunotox icity data submitted to date. This effort brings out the fact that no toxico logical endpoints have changed or been further informed by this data require ment. We look forward to EPA’s review and further dialog in hopes that clear criteria fo r waiving out of the data requirement can be identified to prevent the unn ecessary sacrifice of animals from unnecessary studies.

HED Response: OPP is conducting an independent retr ospective analysis of more than 150 immunotoxicity studies submitted to Ag ency. Preliminary findings of OPP’s retrospective analysis suggest that immunotoxicity studies have not yet provided lower PoDs than are selected from other guideline experimental toxicology studies and thus, so far, immunotoxicity studies w ould not have impacted the Agency’s risk assessments. The OPP retrospective analysis is anticipated to be completed in the summer of 2012. In the interim, HED recommends that the imm unotoxicity continue to be required for registration and registra tion review chemicals.

Comment: PCRM. The Physician’s Committee for Responsible Medicine raised two studies that may be relevant for bridging pyrethroid (and in this case, pyrethrins) data in regard to immunotoxicology. The two citati ons for the two studies are as follows:

• Zhang Y et al. 2010. Immunotoxicity of pyrethroid metabolites in an in vitro model. Environ Toxicol Chem. Nov;29(11):2505-10.Page 4 of 4 • Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of

Health. and Human Services. EPA To xicological Profile for Pyrethri ns and Pyrethro ids. Pg. 77. September 2003.

HED Response: HED will investigate these studies as part of the toxicological evaluation of pyrethrins conduc ted for Registration Review.