Page 2 of 20 I. In vitro and In vivo Laboratory Studies

For the July SAP meeting, the Agency’s scientific r eview of atrazine experimental toxicology studies involves the following: 1) devel opment of the mammary gland and 2) relevant literature studies published from July 15, 2010 to the present using the same search strategy as for the September SAP. Some new studies were identified from the open literature. Other new experimental toxicology data come from EPA’s laboratories and new studies submitted by Syngenta Crop Protecti on. The data from EPA’s Office of Research and Development includes luteinizing hormo ne data following 1- to 4-day atrazine exposures , the effects of atrazine follow ing gestational exposures, and the effects of atrazine on steroidogenesis. In total, EPA has evaluated more than 15 new experimental toxicology studies for this upcoming S AP meeting. A list of these and other relevant references is attached (Attachment 1).

II. Cancer Epidemiology Studies

For the July 2011 FIFRA SAP, cancer-related epidemi ology studies are being considered. To identify the epidemiological invest igations of the association between atrazine exposure and carcinogenic effects, EPA sea rched major biomedical databases, performed citation mapping, and hand-searched selec ted reference lists of pertinent articles. Approximately 50 epidemiology studies were identified on potential carcinogenic effects of atrazine exposure. The Age ncy is including these in the July SAP review. An updated epidemiological study of sp ecific cancer types among atrazine-exposed pesticide applicators from the Nat ional Cancer Institute’s Agricultural Health Study is anticipated to be published in spri ng 2011 and will also be part of this review. A bibliography of these references is prov ided in Attachment 2.

III. Water Monitoring/Modeling Studies

Attachment 3 provides a list of relevant references related to water monitoring/modeling. This list contains all of the previously cited references, which are still relevant, in addition to sources mentioned by the September 2010 SAP either in their remarks or in their written report. Certain articles have also been added that have general relevance to or show specific applications of topics addressed at the September 2010 Meeting. Since potential directions for next steps will be discussed at the July Meeting, citing these sources was deemed to be more important than an exhaustive search of the literature for this current bibliogra phy.Page 3 of 20

IV. Exposure White Paper Studies

At the February, 2010 SAP, the Agency presented a p roposed plan for a collaborative project with investigators from the A HS to evaluate approaches for estimating exposure to pesticide applicators. At t he July, 2011 meeting, the Agency will discuss the status of the collaborative project (wh ich includes a case study involving atrazine) and solicit comment from the Panel on the overall direction of the project and the methods development aspects of this effort. The references related to this project are provided in Attachment 4. This project is part of a larger effort by OPP to improve the incorporation of epidemiology in human health r isk assessment. The feedback from the SAP may not be used for atrazine risk assessmen t per se but will inform EPA’s continued efforts to improve risk assessment approa ches and methodologies.Page 4 of 20 Attachment 1: In vitro and In vivo Experimental Toxicology

1. Andre LeBlanc, L. S. (2011). Atrazine Metabolite Screening in Human

Microsomes: Detection of Novel Reactive Metabolites and Glutathione Adducts by LC-MS. Chemical Research in Toxicology. 24, 329- 339.

2. Bardullas, U., Giordano, M., Rodríguez, V.M. (20 10). Chronic atrazine exposure causes disruption of the spontaneous locomotor acti vity and alters the striatal dopaminergic system of the male Sprague-Dawley rat. Neurotoxicol Teratol. 2010 doi:10.1016/j.ntt.2010.09.001.

3. Belloni, V., Dessì-Fulgheri, F., Zaccaroni, M., Di Consiglio, E., De Angelis, G., Testai, E., Santochirico, M., Alleva, E., Santucci, D. (2010). Early exposure to low doses of atrazine affects behavior in juvenile and adult CD1 mice. Toxicology. 2010 doi:10.1016/j.tox.2010.07.002

4. Campbell, J., Anderson, M., Clewell, H. (2011). PBPK model for atrazine and chlorinated metabolites. Sponsor: Syngenta Crop Pro tection, LLC.

5. Coder, P. (2011a). A Study of the Effects of Sho rt-Term Atrazine Exposure on the Estrogen-Induced Luteinizing Hormone (LH) Surge in Ovariectomized YoungAdult Sprague-Dawley Female Rats. Unpublished study from Syngenta Crop Protection, Inc. Report Number WIL-639091. MRID 48 470002

6. Coder, P. (2011b). An Oral (Gavage and Dietary) Study Evaluating the Pharmacokinetics of Atrazine in Female Sprague-Dawl ey Rats: Final Report. Project Number: WIL-0639081, TK0033836. Unpublished study prepared by WIL Research Laboratories, Inc. MRID 48373101

7. Coder, P. (2011c). An Oral (Gavage and Dietary) Study of the Effects of Atrazine on the Spontaneous Luteinizing Hormone Surge in Fem ale Sprague-Dawley Rats. Unpublished study from Syngenta Crop Protect ion, Inc. Report Number

WIL-639080.

8. Coder, P. (2011d). An Oral (Gavage and Dietary) Study of the Effects of Atrazine on Fertility and Reproductive Performance in Female Long Evans and SpragueDawley Rats. Unpublished study from Syngenta Crop P rotection, Inc. Report

Number WIL-639090. MRID 48470001

9. Coder, P. (2011e). An Oral (Gavage) Study of the Effects of Atrazine on the Estrous Cycle and the Estrogen-Induced Luteinizing Hormone Surge in Female Rats: Final Report. Project Number: WIL-639060, TK0 023168. Unpublished study prepared by WIL Research Laboratories, Inc. M RID 48381001Page 5 of 20

10. Davidson, I. (1987) Metabolism and Kinetics of Atrazine in Man: Lab Project Number: 101947. Unpublished study prepared by Bowma n School of Medicine.

MRID 43598603

11. Davis, L.K., Nurr, A.S., Best, D.S., Fraites, M .J.P., Zorrilla, L.M., Narotsky, M.G., Stoker, T.E., Goldman, J.M., and Cooper, R.L. (2011 ). The Effects of Prenatal Exposure to Atrazine on Pubertal and Postnatal Repr oductive Indices in the

Female Rat.

12. FIFRA Scientific Advisory Panel (FIFRA SAP). (2 010a). A Set of Scientific Issues Being Considered by the Environmental Protection Ag ency Regarding: ReEvaluation of Human Health Effects of Atrazine: Rev iew of Experimental Animal and In Vitro Studies and Drinking Water Monitoring Frequency, FIFRA Office of Science Coordination and Policy, Office of Preventi on, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Available at: http://www.epa.gov/scipoly/sap/meetings/2010/042610 meeting.html SAP Minutes

No. 2010-04

.

13. FIFRA Scientific Advisory Panel (FIFRA SAP). (2 010b). A Set of Scientific Issues Being Considered by the Environmental Protection Ag ency Regarding: ReEvaluation of Human Health Effects of Atrazine: Rev iew of Non-cancer Effects and Drinking Water Monitoring Frequency, FIFRA Offi ce of Science Coordination and Policy, Office of Prevention, Pesticides and To xic Substances, U.S. Environmental Protection Agency. Available at: http://www.epa.gov/scipoly/sap/meetings/2010/042610 meeting.html SAP Minutes

No. 2010-07

.

14. Fraites, M.J.P., Narotsky, M.G., Best, D.S., St oker, T.E., Davis, L.K., Goldman, J.M., Hotchkiss, M.G., Klinefelter, G.R., Kamel, A. , Qian, Y., Podhorniak, L., Cooper, R.L. (2011). Gestational Atrazine Exposure Effects on Male Reproductive Development and Metabolite Distributio n in the Dam, Fetus, and

Neonate.

15. Goldman, J., Davis, L., Murr, A., Cooper, R.L. (2011) The Influence of 1, 2, and 4 Days of Atrazine Treatments on the LH Surge in Ovar iectomized / Estradiolprimed Rats: Preliminary Report to the Office of Ch emical Safety and Pollution Prevention. Internal ORD report to OCSPP.

16. Hovey, R.C., Coder, P.S., Wolf, J.C., Sielken, R.L. Jr., Tisdel, M.O., Breckenridge, CB. (2011). Quantitative assessment o f mammary gland development in female Long Evans rats following in utero exposure to atrazine. Toxicol. Sci. 119(2), 380-390.

17. Hyun Joo, K.C., and Hodgson, E. (2010). Human m etabolism of atrazine. Pesticide Biochemistry and Physiology. 98, 73-79.Page 6 of 20

18. McMullin, T.S., Brzezicki, J.M., Cranmer, B.K., Tessari, J.D., and Andersen, M. E. (2003). Pharmacokinetic modeling of disposition and time-course studies with [14C] atrazine. J Toxicol Environ Health A. 66, 941 -964.

19. McMullin, T.S., Hanneman, W.H., Cranmer, B.K., Tessari, J.D., and Andersen, M.E. (2007). Oral absorption and oxidative metaboli sm of atrazine in rats evaluated by physiological modeling approaches. Tox icology. 240, 1-14.

20. Paul, H., Dunsire, J., Hedley, D. (1998). The A bsorption, Distribution, Degradation and Excretion of (U-carbon 14) Trizine G 30027 in the Rat: Lab Project Number: 9523: 523-92: 153138. Unpublished s tudy prepared by Inveresk

Research International. MRID 44713802

21. Pogrmic-Majkic, K., Fa, S., Dakic, V., Kaisarev ic, S., Kovacevic, R. (2010). Upregulation of peripubertal rat Leydig cell steroi dogenesis following 24 h in vitro and in vivo exposure to atrazine. Toxicol Sci. 118(1), 52-60.

22. Simoneaux, B. (1985) Metabolism of [Carbon 14]- Atrazine in Orally Dosed Rats: (General Metabolism): Laboratory Study No.: ABR- 85 104. Unpublished study prepared by Ciba-Geigy Corp. MRID 40431309

23. Stanko, J., Enoch, R., Rayner, J., Davis, C., W olf, D., Malarkey, D., and Fenton, S. (2010). Effects of Prenatal Exposure to a Low D ose Atrazine Metabolite Mixture on Pubertal Timing and Prostate Development of Male Long Evans Rats. Reproductive Toxicology 30, 540-549.

24. Thede, B. (1987). Study of [Carbon 14]-Atrazine Dose/Response Rela- tionship in the Rat: (General Metabolism): Laboratory Study No. ABR-87087. Unpublished study prepared by Ciba-Geigy Corp. MRID 40431305

25. Thomas, J. (2011) In vitro Metabolism of Atrazi ne in Rat and Human Hepatocytes: Final Report. Project Number: 639084, TK0042000. Unpublished study prepared by WIL Research Laboratories, Inc. M RID 48373102

26. Timchalk, C., Dryzga, M. D., Langvardt, P. W., Kastl, P. E., and Osborne, D. W. (1990) Determination of the effect of tridiphane on the pharmacokinetics of [14C]- atrazine following oral administration to male Fisc her 344 rats, Toxicology 61, 27-

40.

27. Tinfo, N.S., Hotchkiss, M.G., Buckalew, A.R., Z orrilla, L.M., Cooper, R.L., Laws, S.C. (2011). Understanding the Effects of Atrazine on Steroidogenesis in Rat

Granulosa and H295R Adrenal Cortical Carcinoma Cell s. Reproductive Toxicology. 31, 184-193.Page 7 of 20

28. Xiaoying Hui, R.C.W.a.H.I.M. (2011). Pharmacoki netics of [14C]-atrazine in rhesus monkeys, single-dose intravenous and oral ad ministration, Toxicological and Enviromental Chemistry. 93, 370-382.

29. Zhoumeng Lin, J.W.F., Ross, M.K., and Filipov, N.M. (2011). A physiologically based pharmacokinetic model for atrazine and its ma in metabolites in the adult male C57BL/6 mouse. Toxicology and Applied Pharmaco logy. 251, 16-31.Page 8 of 20 Attachment 2: Cancer Epidemiology

1. Alavanja, M.C., Dosemeci, M., Samanic, C., Lubin , J., Lynch, C.F., Knott, C., et al. (2004). Pesticides and lung cancer risk in the agricultural health study cohort. Am J Epidemiol, 160(9), 876-885.

2. Alavanja, M.C., Samanic, C., Dosemeci, M., Lubin , J., Tarone, R., Lynch, C.F., et al. (2003). Use of agricultural pesticides and pros tate cancer risk in the Agricultural Health Study cohort. Am J Epidemiol, 1 57(9), 800-814.

3. Andreotti, G., Freeman, L.E., Hou, L., Coble, J. , Rusiecki, J., Hoppin, J.A., et al. (2009). Agricultural pesticide use and pancreatic c ancer risk in the Agricultural Health Study Cohort. Int J Cancer, 124(10), 2495-25 00.

4. Baris, D., Zahm, S.H., Cantor, K.P., and Blair, A. (1998). Agricultural use of DDT and risk of non-Hodgkin's lymphoma: pooled analysis of three case-control studies in the United States. Occupational and Envi ronmental Medicine, 55(8),

522-527.

5. Brown, L.M., Blair, A., Gibson, R., Everett, G.D ., Cantor, K.P., Schuman, L. M., et al. (1990). Pesticide exposures and other agricultu ral risk factors for leukemia among men in Iowa and Minnesota. Cancer Res, 50(20) , 6585-6591.

6. Brown, L.M., Burmeister, L.F., Everett, G.D., an d Blair, A. (1993). Pesticide exposures and multiple myeloma in Iowa men. Cancer Causes Control, 4(2),

153-156.

7. Burmeister, L.F. (1990). Cancer in Iowa farmers: recent results. Am J Ind Med, 18(3), 295-301.

8. Cantor, K.P., Blair, A., Everett, G., Gibson, R. , Burmeister, L.F., Brown, L.M., et al. (1992). Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota. Cancer Re s, 52(9), 2447-2455.

9. Carreon, T., Butler, M.A., Ruder, A.M., Waters, M.A., Davis-King, K.E., Calvert, G.M., et al. (2005). Gliomas and farm pesticide exp osure in women: The Upper Midwest Health Study. Environmental Health Perspect ives. 113(5), 546-551.

10. Clavel, J., Hemon, D., Mandereau, L., Delemotte , B., Severin, F., and Flandrin, G. (1996). Farming, pesticide use and hairy-cell le ukemia. Scandinavian Journal of Work Environment & Health. 22(4), 285-293.

11. De Roos, A., Zahm, S., Cantor, K., Weisenburger , D., Holmes, F., Burmeister, L., et al. (2003). Integrative assessment of multiple p esticides as risk factors for nonHodgkin's lymphoma among men. Occup Environ Med. 60 (9), E11.Page 9 of 20

12. Delancey, J., Alavanja, M., Coble, J., Blair, A ., Hoppin, J., Austin, H., et al. (2009). Occupational exposure to metribuzin and the incidence of cancer in the Agricultural Health Study. Ann Epidemiol. 19(6), 38 8-395.

13. Dennis, L.K., Lynch, C.F., Sandler, D.P., and A lavanja, M.C. (2010). Pesticide use and cutaneous melanoma in pesticide applicators in the agricultural heath study. Environ Health Perspect. 118(6), 812-817.

14. Donna, A., Crosignani, P., Robutti, F., Betta, P., Bocca, R., Mariani, N., et al. (1989). Triazine herbicides and ovarian epithelial neoplasms. Scand J Work Environ Health. 15(1), 47-53.

15. Engel, L.S., Hill, D.A., Hoppin, J.A., Lubin, J .H., Lynch, C.F., Pierce, J., et al. (2005). Pesticide use and breast cancer risk among farmers' wives in the agricultural health study. Am J Epidemiol. 161(2), 121-135.

16. Hessel, P., Kalmes, R., Smith, T., Lau, E., Min k, P., and Mandel, J. (2004). A nested case-control study of prostate cancer and at razine exposure. J Occup Environ Med. 46(4), 379-385.

17. Hoar, S.K., Blair, A., Holmes, F.F., Boysen, C. , and Robel, R.J. (1985). Herbicides and colon cancer. Lancet. 1(8440), 1277- 1278.

18. Hoar, S.K., Blair, A., Holmes, F.F., Boysen, C. D., Robel, R.J., Hoover, R., et al. (1986). Agricultural herbicide use and risk of lymp homa and soft-tissue sarcoma. JAMA. 256(9), 1141-1147.

19. Hoar Zahm, S., Weisenburger, D., Cantor, K., Ho lmes, F., and Blair, A. (1993). Role of the herbicide atrazine in the development o f non-Hodgkin's lymphoma. Scand J Work Environ Health. 19(2), 108-114.

20. Hopenhayn-Rich, C., Stump, M., and Browning, S. (2002). Regional assessment of atrazine exposure and incidence of breast and ov arian cancers in Kentucky. Arch Environ Contam Toxicol. 42(1), 127-136.

21. Kettles, M.A., Browning, S.R., Prince, T.S., an d Horstman, S.W. (1997). Triazine herbicide exposure and breast cancer incidence: An ecologic study of Kentucky counties. Environmental Health Perspectives. 105(11 ), 1222-1227.

22. Landgren, O., Kyle, R.A., Hoppin, J.A., Beane F reeman, L.E., Cerhan, J.R., Katzmann, J.A., et al. (2009). Pesticide exposure a nd risk of monoclonal gammopathy of undetermined significance in the Agri cultural Health Study. Blood. 113(25), 6386-6391.

23. Lee, W.J., Sandler, D.P., Blair, A., Samanic, C ., Cross, A.J., and Alavanja, M.C. (2007). Pesticide use and colorectal cancer risk in the Agricultural Health Study.Page 10 of 20

Int J Cancer. 121(2), 339-346.

24. Lynch, S., Rusiecki, J., Blair, A., Dosemeci, M ., Lubin, J., Sandler, D., et al. (2006). Cancer incidence among pesticide applicator s exposed to cyanazine in the agricultural health study. Environ Health Persp ect. 114(8), 1248-1252.

25. MacLennan, P., Delzell, E., Sathiakumar, N., an d Myers, S. (2003). Mortality among triazine herbicide manufacturing workers. J T oxicol Environ Health A. 66(6), 501-517.

26. MacLennan, P.A., Delzell, E., Sathiakumar, N., Myers, S.L., Cheng, H., Grizzle, W., et al. (2002). Cancer incidence among triazine herbicide manufacturing workers. Journal of Occupational and Environmental Medicine. 44(11), 1048-

1058.

27. McElroy, J., Gangnon, R., Newcomb, P., Kanarek, M., Anderson, H., Brook, J., et al. (2007). Risk of breast cancer for women living in rural areas from adult exposure to atrazine from well water in Wisconsin. J Expo Sci Environ Epidemiol. 17(2), 207-214.

28. McElroy, J.A., Andersen, L.D., Trentham-Dietz, A., Kirby, R.S., Clayton, M.K., and Remington, P.L. (2001). Assigning atrazine expo sure levels in a case-control study using spatial analysis of well water testing data. American Journal of Epidemiology. 153(11), 452.

29. McElroy, J.A., Gangnon, R.E., Trentham-Dietz, A ., Newcomb, P.A., and Remington, P.L. (2002). Using geostatistics to asse ss atrazine exposure in a population-based case control study of breast cance r. Epidemiology. 13(4), 727.

30. Mills, P. (1998). Correlation analysis of pesti cide use data and cancer incidence

rates in California counties. Arch Environ Health. 53(6), 410-413.

31. Mills, P., and Yang, R. (2006). Regression anal ysis of pesticide use and breast

cancer incidence in California Latinas. J Environ H ealth. 68(6), 15-22; quiz 43-14.

32. Mills, P. K., and Yang, R. (2003). Prostate can cer risk in California farm workers. Journal of Occupational and Environmental Medicine. 45(3), 249-258.

33. Mills, P. K., and Yang, R. C. (2007). Agricultu ral exposures and gastric cancer risk in Hispanic farm workers in California. Enviro n Res. 104(2), 282-289.

34. Muir, K., Rattanamongkolgul, S., Smallman-Rayno r, M., Thomas, M., Downer, S., and Jenkinson, C. (2004). Breast cancer incidence a nd its possible spatial association with pesticide application in two count ies of England. Public Health. 118(7), 513-520.Page 11 of 20

35. Neuberger, J., Martin, J., Pierce, J., Mayo, M. , and Jewell, W. (2004). Cancer cluster investigations: use of a hybrid approach in a rural county. J Public Health Manag Pract. 10(6), 524-532.

36. Orsi, L., Delabre, L., Monnereau, A., Delval, P ., Berthou, C., Fenaux, P., et al. (2009). Occupational exposure to pesticides and lym phoid neoplasms among men: results of a French case-control study. Occup Environ Med. 66(5), 291-298.

37. Reynolds, P., Hurley, S.E., Goldberg, D.E., Yer abati, S., Gunier, R.B., Hertz, A., et al. (2004). Residential proximity to agricultura l pesticide use and incidence of breast cancer in the California Teachers Study coho rt. Environ Res. 96(2), 206-

218.

38. Ruder, A.M., Waters, M.A., Butler, M.A., Carreó n, T., Calvert, G.M., Davis-King, K.E., et al. (2004). Gliomas and farm pesticide exp osure in men: the upper midwest health study. Arch Environ Health. 59(12), 650-657.

39. Rull, R.P., Gunier, R., Von Behren, J., Hertz, A., Crouse, V., Buffler, P.A., et al. (2009). Residential proximity to agricultural pesti cide applications and childhood acute lymphoblastic leukemia. Environmental Researc h. 109(7), 891-899.

40. Rusiecki, J.A., De Roos, A., Lee, W.J., Dosemec i, M., Lubin, J.H., Hoppin, J.A., et al. (2004). Cancer incidence among pesticide app licators exposed to atrazine in the agricultural health study. Journal of the Na tional Cancer Institute. 96(18),

1375-1382.

41. Sathiakumar, N., Delzell, E., and Cole, P. (199 6). Mortality among workers at two triazine herbicide manufacturing plants. Am J Ind M ed. 29(2), 143-151.

42. Sathiakumar, N., MacLennan, P.A., Mandel, J., a nd Delzell, E. (2011). A review of epidemiologic studies of triazine herbicides and cancer. Crit Rev Toxicol. 41 Suppl 1, 1-34. MRID 48470004

43. Schroeder, J.C., Olshan, A.F., Baric, R., Dent, G.A., Weinberg, C.R., Yount, B., et al. (2001). Agricultural risk factors for t(14;1 8) subtypes of non-Hodgkiin's lymphoma. Epidemiology. 12(6), 701-709.

44. Thorpe, N., and Shirmohammadi, A. (2005). Herbi cides and nitrates in groundwater of Maryland and childhood cancers: a ge ographic information systems approach. J Environ Sci Health C Environ Ca rcinog Ecotoxicol Rev. 23(2), 261-278.

45. van Balen, E., Font, R., Cavallé, N., Font, L., Garcia-Villanueva, M., Benavente, Y., et al. (2006). Exposure to non-arsenic pesticid es is associated with lymphoma among farmers in Spain. Occup Environ Med. 63(10), 663-668.Page 12 of 20

46. Van Leeuwen, J., Waltner-Toews, D., Abernathy, T., Smit, B., and Shoukri, M. (1999). Associations between stomach cancer inciden ce and drinking water

contamination with atrazine and nitrate in Ontario (Canada) agroecosystems, 1987-1991. Int J Epidemiol. 28(5), 836-840.

47. Weisenburger, D. (1990). Environmental epidemio logy of non-Hodgkin's lymphoma in eastern Nebraska. Am J Ind Med. 18(3), 303-305.

48. Young, H., Mills, P., Riordan, D., and Cress, R . (2005). Triazine herbicides and epithelial ovarian cancer risk in central Californi a. J Occup Environ Med, 47(11),

1148-1156.

49. Zahm, S., and Blair, A. (1992). Pesticides and non-Hodgkin's lymphoma. Cancer Res, 52(19 Suppl), 5485s-5488s.

50. Zahm, S.H., Weisenburger, D.D., Saal, R.C., Vau ght, J.B., Babbitt, P.A., and Blair, A. (1993). The role of agricultural pesticid e use in the development of nonHodgkin's lymphoma in women. Arch Environ Health. 4 8(5), 353-358.Page 13 of 20 Attachment 3: Water Monitoring/Modeling

1. Aspinall, R., and Pearson, D. (2000). Integrated geographical assessment of

environmental condition in water catchments: Linkin g landscape ecology, environmental modeling, and GIS. Journal of Environ mental Management. 59,

299-319.

2. Battaglin, W.A. and Goolsby, D.A. (1998). Regres sion models of herbicide

concentrations in outflow from reservoirs in the Mi dwestern USA, 1992–1993. J
Amer Water Res Assoc. 34, 1369–1390.

3. Blomquist, J.D., Denis, J.M., Cowles, J.L., Hetr ick, J.A., Jones, R.D., and Birchfield, N.B. (2001). Pesticides in Selected Wat er-Supply Reservoirs and Finished Drinking Water, 1999-2000: Summary of Resu lts from a Pilot Monitoring Program. U.S. Geological Survey Open-File Report 0 1-456. Published in cooperation with the U.S. Environmental Protection Agency.

4. Brown, L.C., and Berthouex, P.M. (2002). Statis tics for Environmental Engineers. CRC Press.

5. Coles, S. (2001). An Introduction to Statistical Modeling of Extreme Values. New York: Springer.

6. Coupe, R.H., and Blomquist, J.D. (2004). Water-s oluble pesticides in finished water of community water supplies. AWWA. 96(10), 5 6-68.

7. Conover, W.J. (1980). Practical Nonparametric St atistics. New York: Wiley.

8. Crawford, C.G. (2004). Sampling Strategies for E stimating Acute and Chronic Exposures of Pesticides in Streams. Journal of the American Water Resources Association (JAWRA). 40(2), 485-502.

9. de Haan, L., and Ferreira, A. (2006). Extreme Va lue Theory: An Introduction. New York: Springer.

10. Deutsch, C.V., and Journel, A.G. (1998). GSLIB : Geostatistical Software Library

and User’s Guide. Second Edition. Oxford Universit y Press (New York, Oxford).

11. FIFRA Scientific Advisory Panel (FIFRA SAP). (2 009). A Set of Scientific Issues Being Considered by the Environmental Protection Ag ency Regarding: The Ecological Significance of Atrazine Effects on Prim ary Producers in Surface Water Streams in the Corn and Sorghum Growing Regio n of the United States (Part II). SAP Minutes No. 2009-06. May 12 – 14, 2 009 FIFRA Scientific Advisory Panel. Document available at http://www.epa.gov/scipoly/sap/meetings/2009/051209 meeting.htmlPage 14 of 20

12. FIFRA Scientific Advisory Panel (FIFRA SAP). (2 010a). A Set of Scientific Issues Being Considered by the Environmental Protection Ag ency Regarding: ReEvaluation of Human Health Effects of Atrazine: Rev iew of Experimental Animal and In Vitro Studies and Drinking Water Monitoring Frequency, FIFRA Office of Science Coordination and Policy, Office of Preventi on, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Available at: http://www.epa.gov/scipoly/sap/meetings/2010/042610 meeting.html SAP Minutes

No. 2010-04

.

13. FIFRA Scientific Advisory Panel (FIFRA SAP). (2 010b). A Set of Scientific Issues Being Considered by the Environmental Protection Ag ency Regarding: ReEvaluation of Human Health Effects of Atrazine: Rev iew of Non-cancer Effects and Drinking Water Monitoring Frequency, FIFRA Offi ce of Science Coordination and Policy, Office of Prevention, Pesticides and To xic Substances, U.S. Environmental Protection Agency. Available at: http://www.epa.gov/scipoly/sap/meetings/2010/042610 meeting.html SAP Minutes

No. 2010-07

.

14. Gilbert, R.O. (1987). Statistical Methods for E nvironmental Pollution Monitoring. New York: Wiley & Sons.

15. Gilliom, R.J., Barbash, J.E., Crawford, C.G., H amilton, P.A., Martin, J.D., Nakagaki, N., Nowell, L.H., Scott, J.C., Stackelber g, P.E., Thelin, G.P., and Wolock, D.M. (2006). The quality of our Nation’s wa ters—Pesticides in the Nation’s streams and ground water, 1992–2001. U.S. Geological Survey Circular 1291, 172 p. Available at http://pubs.usgs.gov/circ /2005/1291/pdf/circ1291.pdf

16. Gramacy, R.B. and Lee, H.K.H. (2008). Bayesian treed Gaussian process models with an application to computer modeling. J ournal of the American Statistical Association. 103, 1119-1130.

17. Higdon, D., Kennedy, M., Cavendish, J., Cafeo, J., and Ryne, R.D. (2004). Combining field observations and simulations for ca libration and prediction. SIAM Journal of Scientific Computing. 26, 448-466.

18. Huang, Y., and Batterman, S. (2003). An Extre me Value Analysis of Pollutant Concentrations in Surface Soils Due to Atmospheric Deposition. Human and Ecological Risk Assessment. 9, 1729-1746.

19. International Life Sciences Institute (ILSI). (1999). A Framework for Estimating Pesticide Concentrations in Drinking Water for Aggr egate Exposure

Assessments. International Life Sciences Institute Risk Science Institute Working Group Report, Washington, D.C., 61 pp. Available at http://www.ilsi.org/ResearchFoundation/Publications /Estimating%20Pesticide%2 0Concentrations.pdfPage 15 of 20

20. Isaaks, E.H., and Srivastava, R.M. (1989). An Introduction to Applied Geostatistics. Oxford University Press (New York, Oxford).

21. Kennedy, M., and O'Hagan, A. (2001). Bayesian Calibration of Computer Models. J R Stat Soc, Series B. Stat Methodol. 63, 425-464.

22. Kroll, C., and Vogel, R. (2002). Probability Di stribution of Low Streamflow Series in the United States. Journal of Hydrologic Enginee ring. 7(2), 137-146.

23. Kyriakidis, P.C. and Journel, A.G. (2001). Stoc hastic modeling of atmospheric pollution: a spatial time-series framework. Part I: Methodology. Atmospheric Environment. 35, 2331-2337.

24. Lall, U., and Sharma, A. (1996). A Nearest Neig hbor Bootstrap for Resampling Hydrologic Time Series. Water Resources Research. 3 2(3), 679-693.

25. Larson, S.J., Crawford, C.G., and Gilliom, R.J. (2004). Development and application of Watershed Regressions for Pesticides (WARP) for estimating

atrazine concentration distributions in streams. U. S. Geological Survey WaterResources Investigations Report 03–4047, 68 p. Ava ilable at http://pubs.usgs.gov/wri/wri034047/

26. Lee, H.K. (2004). Bayesian Nonparametrics via Neural Networks. Philadelphia:

ASA/SIAM.

27. Mao D., Miller, P.S., Davidson, P.C., Prenger, J.J., Zwilling, L.F., Cox, M.J., Harbourt, C.M., and Hendley, P. (2011). Methodology for Compiling a Database of Atrazine Monitoring Program Community Water Syst em Facilities, Watersheds, and Their Characteristics. Unpublished study from Syngenta Crop
Protection, Inc. MRID 48470008

28. Miller, P.S., Northcott, W.J., Andrus, J. M., Z willing, L.F., Cheplick, J. M., Harbourt, C.M., and Hendley, P. (2011). Atrazine - Development of the PRZMHybrid Watershed Exposure Modeling System, Unpublis hed study from Syngenta Crop Protection, Inc. MRID 48470007

29. Mosquin, P., Whitmore, R., and Chen W. (2011a). Estimation of statistical confidence in upper centile concentrations of histo rical atrazine monitoring data of Community Water Systems. Unpublished study from Syngenta Crop
Protection, Inc. MRID 48470005

30. Mosquin, P., Whitmore, R., and Chen W. (2011b). Impact of Alternative Monitoring Frequencies on Estimation of Atrazine Ro lling Average Environmental Concentrations. Unpublished study from Syngenta Cro p Protection, Inc. MRID

48470006Page 16 of 20

31. Ott, W.R. (1995). Environmental Statistics and Data Analysis. CRC Lewis
Publishers, New York.

32. Padoan, S., Ribatet, M., and Sisson, S. (2010). Likelihood-Based Inference for

Max-Stable Processes. Journal of the American Stati stical Association. 105(489),

263-277.

33. Park, H., and Sohn, H. (2006). Parameter Estima tion of the Generalized Extreme Value Distribution for Structural Health Monitoring . Probabilistic Engineering Mechanics. 21, 366-376.

34. Pereira, H.G., J. Ribeiro, A.J. Sousa, L. Ribei ro, A. Lopez, and J. Sperodio. (2000). Geostats 2000 edited by W.J. Klei ngeld and D.G. Krige.

35. Ramsey, J.O. and Silverman, B.W. (2002). Applie d Functional Data Analysis, Second Edition. Springer-Verlag, New York, NY.

36. Ramsey, J.O. and Silverman, B.W. (2005). Functi onal Data Analysis, Second Edition. Springer-Verlag, New York, NY.

37. Reiss, R., and Thomas, M. (2007). Statistical A nalysis of Extreme Values: with Applications to Insurance, Finance, Hydrology, and Other Fields. Basel: Birkhauser-Verlag.

38. Rouhani, S. and Myers, D.E. (1990). Problems in space-time kriging of geohydrological data. Mathematical Geology. 22, 611 -622.

39. Santner, T.J., Williams, B.J., and Notz, W.I. ( 2003) The Design and Analysis of Computer Experiments. Springer-Verlag, New York, NY

.

40. Stone, W.W., and Gilliom, R.J. (2009). Update o f watershed regressions for pesticides (WARP) for predicting atrazine concentra tion in streams. U.S. Geological Survey Open-File Report 2009–1122. Avai lable at http://pubs.usgs.gov/of/2009/1122/

41. Stone, W.W., Gilliom, R.J., and Crawford, C.G. (2008). Watershed Regressions for Pesticides (WARP) for Predicting Annual Maximum and Maximum MovingAverage Concentrations of Atrazine in Streams. U.S. Geological Survey OpenFile Report 08-1186. Available at http://pubs.usgs. gov/of/2008/1186/

42. Sullivan, D.J., Vecchia, A.V., Lorenz, D.L., Gi lliom, R.J., and Martin, J.D. (2009).

Trends in Pesticide Concentrations in Corn-Belt Str eams, 1996-2006: U.S. Geological Survey Scientific Investigations Report 2009-5132.

43. Terrrado, M, Kuster, M., Raldua, D., Lopez de A lda, M., Bacelo, D., and Tauler, R. (2007). Use of chemometric and geostatistical m ethods to evaluate pesticidePage 17 of 20

pollution in the irrigation and drainage channels o f the Ebro river delta during rice-growing season. Anal Bioanal Chem. 387, 1479-1 488.

44. U.S. Environmental Protection Agency (USEPA). ( 2000). FIFRA Scientific Advisory Panel Briefing Document for a Consultation on: Monitoring Strategies for Pesticides in Surface Derived Drinking Water. P repared for June 6-9, 2000 FIFRA Scientific Advisory Panel. Document available at http://www.epa.gov/scipoly/sap/meetings/2000/june/d rinkingwatersurvey.pdf

45. U.S. Environmental Protection Agency (USEPA). ( 2002). Organophosphate

Pesticides: Revised Cumulative Risk Assessment. Cu rrent as of June 10, 2002. Documents available through the USEPA Office of Pes ticide Programs web site at http://www.epa.gov/pesticides/cumulative/rra-op/

.

46. U.S. Environmental Protection Agency (USEPA). ( 2007a). Acetochlor Registration Agreement and Monitoring Program. Doc uments are available through the Federal docket. Docket ID: EPA-HQ-OPP- 2007-0725. Available at http://www.regulations.gov/search/Regs/home.html#do cketDetail?R=EPA-HQOPP-2007-0725

47. U.S. Environmental Protection Agency (USEPA). (2007b). N-methyl Carbamate

Revised Cumulative Risk Assessment. Available thro ugh the USEPA Office of Pesticide Programs web site at http://www.epa.gov/oppsrrd1/REDs/nmc_revised_cra.pd f

.

48. U.S. Environmental Protection Agency (USEPA). (2007c). Preliminary Interpretation of the Ecological Significance of At razine Stream-Water Concentrations Using a Statistically-Designed Monit oring Program. Prepared for the December 4 – 7, 2007 FIFRA Scientific Advisory Panel. Document available at http://www.epa.gov/scipoly/sap/meetings/2007/120 407_mtg.htm

49. U.S. Environmental Protection Agency (USEPA). ( 2009a). The Ecological Significance of Atrazine Effects on Primary Produce rs in Surface Water Streams in the Corn and Sorghum Growing Region of the Unite d States (Part II). Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel. Document available at http://www.epa.gov/scipoly/sap/meetings/2009/051 209meeting.html

50. U.S. Environmental Protection Agency (USEPA). ( 2009b). The Ecological Significance of Atrazine Effects on Primary Produce rs in Surface Water Streams in the Corn and Sorghum Growing Region of the Unite d States (Part II). Addendum to Section VI: Additional Analysis of the 40 AEEMP Sampling Sites to Identify Additional Areas That May Exceed the LOC. Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel. Document available at http://www.epa.gov/scipoly/sap/meetings/2009/051209 meeting.htmlPage 18 of 20

51. Varljen, M.D., Barcelona, M.J. and Wehrmann, H. A. (1999). A jackknife approach to examine uncertainity and temporal change in the spatial correlation of a VOC plume. Environmental Monitoring and Assessment. 59, 31-46.

52. Vecchia, A.V. and Crawford, C.G. (2006). Simula tion of daily pesticide

concentrations from watershed characteristics and m onthly climatic data: U.S. Geological Survey Scientific Investigations Report 2006-5181.

53. Vecchia, A.V., Martin, J.D., and Gilliom, R.J. (2008). Modeling Variability and

Trends in Pesticide Concentrations in Streams. Jou rnal of the American Water Resources Association (JAWRA). 44(5), 1308-1324.

54. Ver Hoeff, J., and Peterson, E. (2010). A Movi ng Average Approach for Spatial

Statistical Models of Stream Networks. Journal of t he American Statistical Association (JASA). 105(489), 6-18.

55. Whitmore, R.W., and Mosquin, P.L. (2010). Inv estigation of Statistical Confidence in Upper Quantiles and “Peak” Concentrat ions of Currently Available Atrazine Drinking Water Monitoring Data. RTI Inter national report Submitted to the U.S. Environmental Protection Agency by Syngent a Crop Protection, Inc.

MRID 47972804

56. Wilks, D.S. (1999). Interannual Variability an d Extreme-Value Characteristics of Several Stochastic Daily Precipitation Models. Agri cultural and Forest Meteorology. 93, 153-169.

57. Williams, B., Higdon, D., Gattiker, J., Moore, L., McKay, M., and Keller-McNulty, S. (2006). Combining Experimental Data and Computer Simulations, With an Application to Flyer Plate Experiments. Bayesian A nalysis. 1, 765-792.

58. Williams R., and Merritt A. (2011). Summary of Site Selection and Monitoring Plan for Atrazine Daily Monitoring in Selected Comm unity Water Systems. Unpublished study from Syngenta Crop Protection, In c. MRID 48470009

59. Yiou, P., Goubanova, K., Li, Z., and Nogaj, M. (2008). Weather Regime Dependence of Extreme Value Statistics for Summer T emperature and Precipitation. Nonlinear Processes in Geophysics. 15, 365-378.

60. Zhang, Q., Xu, C., Chen, Y., and Liu, C. (2009) . Extreme Value Analysis of

Annual Maximum Water Levels in the Pearl River Delt a, China. Front. Earth Sci. China. 3(2), 154-163.Page 19 of 20 Attachment 4: Exposure White Paper

1. Aschengrau, A., and Seage, G.R. (2003). Essentia ls of Epidemiology in Public Health. Jones and Bartlett Publishers. Sudbury, Mas sachusetts. Science and Decisions Advancing Risk Assessment. The National A cademies of Sciences.

2. Bakke, B., De Roos, A.J., Barr, D.B., Steward, P .A., Blair, A., Beane-Freeman, L., Lynch, C.F., Allen, R.H., Alavanja, M.C.R., and Vemeulen, R. (2008). Exposure to atrazine and selected non-persistent pe sticides among corn farmers during a growing season. Journal of Exposure Scienc e and Environmental Epidemiology. 1-11.

3. Caulderon R.L. (2000). Measuring risks in human s: the promise and practice of epidemiology. Food and Chemical Toxicology, 38, S59 -S63.

4. Coble, J., Arbuckle, T., Lee, W., Alavanja, M., and Dosemeci, D. (2005). The Validation of a Pesticide Exposure Algorithm Using Biological Monitoring Results. Journal of Occupational and Environmental Hygiene. 2, 194-201.

5. Hackathorn, D.R. and Eberhart, D.C. (1985). Data base proposal for use in predicting mixer/loader/applicator exposure. Americ an Chemical Society Symposium Series. 273, 341-355.

6. Hertz-Picciotto, I. (1995). Epidemiology and Qua ntitative Risk Assessment: A Bridge from Science to Policy. American Journal of Public Health. 85(4).

7. Montgomery, M.P., Kamel, F., Hoppin, J.A., Beane -Freeman, L.E., Alavanja, M.C.R., and Sandler, D.P. (2010). Effects of self-r eported health conditions and pesticide exposures on probability of follow-up in a prospective cohort study. Am J Ind Med. 53(5), 486-96.

8. Nieuwenhuijsen M.J. (2003). Exposure Assessment in Occupational and Environmental Epidemiology. Oxford University Press , New York.

9. Shore, R.E. (1995). Editorial: Epidemiology Data in Risk Assessment- Imperfect

but Valuable. American Journal of Public Health. 85(4).

10. Tarone, R.E., Alavanja, M.C., Zahm, S.H., Lubin , J.H., Sandler, D.P., McMaster, S.B., Rothman, N., and Blair, A. (1997). The Agricu ltural Health Study: factors affecting completion and return of self-administere d questionnaires in a large prospective cohort study of pesticide applicators. Am J Ind Med. 31(2), 233-242.

11. Thomas K.W., Dosemeci, M., Hoppin, J.A., Sheldo n, L.S. , Croghan, C.W., Gordon, S.M., Jones, M.L., Reynolds, S.J., Raymer, J.H., Akland, G.G., Lynch, C.F., Knott, C.E., Sandler, D.P., Blair, A.E., and Alavanja, M.C.R. (2009). UrinaryPage 20 of 20

biomarker, dermal, and air measurement results for 2,4-D and chlorpyrifos farm applicators in the Agricultural Health Study. Journ al of Exposure Science and Environmental Epidemiology, epub ahead of print, do i:10.1038/jes.2009.6

12. U.S. EPA. (1995). PHED: Pesticide Handlers Expo sure Database Reference

Manual V1.1

13. U.S. EPA. (2002). Atrazine: Revised Occupationa l and Residential Exposure Assessment and Recommendations for the Reregistrati on Eligibility Decision

Document.

14. U.S. EPA. (2010). Agency’s Framework for Incorp orating Human Epidemiology &

Incident Data in Health Risk Assessment. Available at http://www.epa.gov/scipoly/sap/meetings/2010/020210 meeting.html

15. U.S. EPA. (2010). Office of Pesticide Programs & The Agricultural Health Study Comparison of Exposure Assessment Approaches (Adden dum to Case Study B). Available at http://www.epa.gov/scipoly/sap/meeting s/2010/020210meeting.html

16. U.S. EPA; FR Vol. 57, No. 104; May 29, 1992; http://cfpub.epa.gov/ncea/raf/recordisplay.cfm?deid =15263 ).

17. van den Brandt, P., Voorrips, L., Hertz-Picciot to, I., Shuker, D., Boeing, H., Speijers, G., Guittard, C., Kleiner, J., Knowles, M ., Wolk, A., and Goldbohm, A. (2002). The contribution of epidemiology. Food Che m Toxicol. Feb-Mar, 40(2-3),

387-424.

18. Zartarian, V., Bahadori, T., McKone, T. (2005). Adoption of an official ISEA Glossary. Journal of Exposure Analysis and Environm ental Epidemiology, 15, 1-

5.