UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY Background Material Provided to th e Science Advisory Panel (SAP) April 2010

Contents

Transmittal memo .................................................................................................................. 12 Atrazine Issue Paper ............................................................................................................. 12 1. FIFRA SAP 10g Reference Materials ................................................................................ 12 1. Breckenridge, C.B., Yi, K.D., & Simpkins, J.W. (2010a). Cytotoxicity of atrazine and its metabolites in vitro. Unpublished data from Syngenta Crop Protection, Inc. .................. 12 2. Breckenridge, C.B., Yi, K.D., Perez, E.J., & Simpkins, J.W. (2010b). Dose and timedependent-effects of atrazine and metabolites on aromatase mRNA in multiple cell types in vitro. Unpublished data from Syngenta ................................................................................. 12 3. Breckenridge, C.B., Yi, K.D., Perez, E. J., & Simpkins, J.W. (2010c). Ex vivo assessment of the effects of atrazine or its metabolites on phosphodiesterase activity. Unpublished data from Syngenta ............................................................................................ 12 4. Kim, D., Breckenridge, C. (Syngenta) (2010). Atrazine - Derivation of the short-term inhalation NOAEL using a physiologically-based pharmacokinetic model. Unpublished data from Syngenta ......................................................................................................................... 12 5. Morseth S. (1996) Evaluation of the Lutein izing Hormone (LH) Surge in AtrazineExposed Female Sprague-Dawley Rats--(Fin al) 6-Month Interim Report: Lab Project Number: CHV 2386-111: 2386-111: 6791E. Unpublished study prepared by Corning Hazleton Inc. 727 p. MRID 44152102 .................................................................................... 12 2. Previous FIFRA SAP References ....................................................................................... 12 1. FIFRA Scientific Advisory Panel (FIFRA SAP). (2009). A Set of Scientific Issues Being Considered by the Environmental Prot ection Agency Regarding: The Ecological Significance of Atrazine Eff ects on Primary Producers in Surface Water Streams in the Corn and Sorghum Growing Region of the United St ates (Part II). SAP Minutes No. 2009-06. May 12 – 14, 2009 FIFRA Scientific Advisory Panel. ........................................................... 12 2. FIFRA Scientific Advisory Panel (SAP). (2003). “Characterization of Epidemiology Data Relating to Prostate Cancer and Expos ure to Atrazine.” Report from the FIFRA Scientific Advisory Panel Meeting of July, 2003. FIFRA Scientific Advisory Panel, Office of Science Coordination and Po licy, Office of Prevention, Pestic ides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. .................................................. 12 3. FIFRA Scientific Advisory Panel (SAP). (2000). “Atrazine: Hazard and DoseResponse Assessment and Characterization.” Re port from the FIFRA Scientific Advisory Panel Meeting of June 27-29, 2000. FIFRA Scie ntific Advisory Panel, Office of Science Coordination and Policy, Office of Preventi on, Pesticides and Toxic Substances, U.S. Environmental Protection Ag ency. Washington, DC. ........................................................... 12 4. FIFRA Scientific Advisory Panel (SAP). ( 1988). “A set of issues being considered by the Agency in connection with the peer re view classification of atrazine a class C carcinogen.” Report from the FIFRA Scientific Advisory Panel Mee ting of September 14, 1988. FIFRA Scientific Advisory Panel, Offi ce of Science Coordination and Policy, Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. ..................................................................................................................... 13Page 2 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 5. U.S. Environmental Protection Agency. ( 2010). DRAFT Framework for Incorporating Human Epidemiologic & Incident Data in Hea lth Risk Assessment (D raft dated January 7, 2010). Presented to the FIFRA Scientific Advisory Panel, February 2-4, 2010. http://www.regulations.gov (Docket EPA-HQ-OPP-2009-0851). ......................................... 13 6. U.S. Environmental Protection Agency (U SEPA). 2009a. The Ecological Significance of Atrazine Effects on Primary Producers in Su rface Water Streams in the Corn and Sorghum Growing Region of the United States (Part II). Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel. ...................................................................................................... 13 7. U.S. Environmental Protection Agency (U SEPA). 2009b. The Ecological Significance of Atrazine Effects on Primary Producers in Su rface Water Streams in the Corn and Sorghum Growing Region of the United Stat es (Part II). Addendum to S ection 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. ................................ 13 8. U.S. Environmental Protection Agency (U SEPA). 2007a. Acetoc hlor Registration Agreement and Monitoring Program. Documents are available through the Federal docket. Docket ID: EPA-HQ-OPP-2007-0725. ................................................................................... 13 9. U.S. Environmental Protection Agency (USEPA). 2007b. N-methyl Carbamate Revised Cumulative Risk Assessment. ................................................................................................. 13 10. U.S. Environmental Protection Agency (USE PA). 2007c. Preliminary Interpretation of the Ecological Significance of Atrazine Stream-Water Concentrations Using a Statistically-Designed Monitoring Program. Prepared for the December 4 – 7, 2007 FIFRA Scientific Advisory Panel. ...................................................................................................... 13 11. US EPA. (2006). Decision Documents for At razine. Atrazine IREDs (January and October 31, 2003) and Atrazine RE D (April 6, 2006). EPA-HQ-OPP-2003-0367. ............... 13 12. US EPA. (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency, Risk Assessment Foru m, Washington, DC. EPA/630/P-03/001F. Federal Register 70(66):17765-17817. ................................................................................... 13 13. US EPA. (2003). Interim Re-registra tion Eligibility Decision (IRED) ...................... 13 3. FIFRA SAP Reference Materials - Post 2003 References ................................................. 14 1. Albanito L., Madeo A., Lappano R., Vivac qua A., Rago V., Carpino A., Oprea T., Prossnitz E., Musti A.M., Andò S. & Maggiolin i, M. (2007). G Protei n–Coupled Receptor 30 (GPR30) Mediates Gene Expression Change s and Growth Response to 17ß-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells. Cancer Res., Feb 15; 67(4):1859-66

.. ........................................................................................................14 2. Albanito, L., Lappano, R., Madeo, A., Chimen to, A., Prossnitz, E.R., Cappello, A.R., Dolce, V., Abonante, S., Pezzi, V., & Maggiolin i, M. (2008). G-protein-coupled receptor 30 and estrogen receptor-alpha are involved in the proliferative effects i nduced by atrazine in ovarian cancer cells. Environ Heal th Perspect, Dec; 116(12): 1648-55. ............................... 14 3. Bakke B., De Roos A.J., Barr D.B., Stewart P.A., Blair A., Freeman L.B., Lynch C.F.,Allen R.H., Alavanja M.C., Vermeulen R. (2009). Exposure to atrazine and selected nonpersistent pesticides among corn farmers dur ing the growing season. J Expo Sci Environ Epidemiol, Sep; 19(6):544-54 ................................................................................................. 14 4. Belloni V, Alleva E, et al. (2007). Effects of lo w doses of atrazine on the neurobehavioural development of mice. Ethology Ecology & Evolution, 19: 309-22. ........ 14 5. Benachour, N., Moslemi, S., Sipahutar, H., & Seralini G.E. (2007). Cytotoxic effects and aromatase inhibition by xenobiotic endocri ne disrupters alone and in combination. Toxicol Appl Pharmacol, Jul 15; 222(2): 129-40. .................................................................. 14Page 3 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 6. Betancourt, M., Resendiz, A., & Fierro, E.C. (2006). Effects of two insecticides and two herbicides on the porcine sperm motility patterns using computer-assisted semen analysis (CASA) in vitro. Re prod Toxicol, Oct, 22(3): 508-12. ............................................ 14 7. Boobis, A.R., J.E. Doe, B. Heinrich-Hirsch et al. (2008). IPCS framework for analyzing the relevance of a noncancer mode of action for humans. Crit Rev Toxicol, 38(2):87-96. .. 14 8. Cimino-Reale, G., Ferrario, D., Casati, B ., Brustio, R., Diodovich, C., Collotta, A., Vahter, M., & Gribaldo, L. (2008). Combined in utero and juve nile exposure of mice to arsenate and atrazine in dr inking water modulates gene e xpression and clonogenicity of myeloid progenitors. Toxicol Lett, Jul 30; 180(1): 59-66. .................................................... 14 9. Coban, A., & Filipov, N.M. (2007). Dopamine rgic toxicity associated with oral exposure to the herbicide atrazi ne in juvenile male C57BL/6 mice. J. Neurochem, Mar, 100(5): 1177-87. ..................................................................................................................... 14 10. Cooper R.L., Laws S., Das P.C., Narotsky M.G., Goldman J.M., Tyrey E.L., Stoker T.E. (2007). Atrazine and reproductive functio n: mode and mechanism of action studies. Birth Defects Res B Dev Reprod T oxicol, Apr; 80(2): 98-112. ............................................ 14 11. Crawford, C.G. (2004). Sampling Strategi es for Estimating Acute and Chronic Exposures of Pesticides in Streams. Journal of the American Water Resources Association (JAWRA) 40(2):485-502. ....................................................................................................... 15 12. Devos, S., Hooghe, R., Hooghe-Peters, E.L ., De Bosscher, K., Vanden Berghe, W., Haegeman, G., Staels, B., Bauer, E., Roels, F ., & Hooghe, R. (2003). Inhibition of cytokine production by the herbicide atrazine: Search for nuclear receptor targets. Biochem Pharmacol, Jan 15; 65(2): 303-8. ............................................................................................ 15 13. Devos S., Van Den Heuvel R., et al. (2004) . Limited effect of selected organic pollutants on cytokine production by peripheral blood leukocytes. Eur Cytokine Netw, AprJun; 15(2): 145-51. .................................................................................................................. 15 15. Dooley, G., Prenni, J., Prentiss, P., Cranme r, B., Anderson, M., & Tessari, J. (2006). Identification of a novel hemoglobin adduct in Sprague-Dawly rats exposed to atrazine. Chem Res Toxicol, May; 19(5): 692-700. .............................................................................. 15 14. Dooley, G.P., Reardon, K.F., Prenni, J.E., Tjalkens, R.B., Legare, M.E., Foradori, C.D., Tessari, J.E., & Hanneman, W.H. (2008). Proteomic analysis of diaminocholorotriazine adducts in Wistar rat pitu itary glands and LbetaT2 rat pituitary cells. Chem Res Toxicol, Apr, 21(4): 844-51. ................................................................................. 15 16. Dooley, G., Hanneman, W., Carbone, D., Le gare, M., Anderson, M., & Tessari, J. (2007). Development of an immunochemist ry detection method for atrazine-induced albumin adducts. Chem Res Toxicol, Jul; 20(7): 1061-6. ..................................................... 15 17. Enoch, R.R., Stanko, J.P., Greiner, S.N ., Youngblood, G.L., Rayner, J.L., & Fenton, S.E. (2007). Mammary gland development as a sensitive end point after acute prenatal exposure to an atrazine metabolite mixture in female Long-Evans rats. Environ Health Perspect, Apr, 115(4): 541-7. .................................................................................................. 15 18. Fan, W., Yanase, T., Morinaga, H., Gonda, S., Okabe, T., Nomura, M., Hayes, T., Takayanagi, R., & Nawata, H.(2007a). Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II. Biochemical and Biophysical Resear ch Communications, 355(4): 1012-8. ......................... 15 19. Fan, W., Yanase, T., Morinaga, H., Gondo, S ., Okabe, T., Normura, M., Komatsu, T., Moroashi, K., Hayes, T.B., Takayanagi, R ., & Nawata, H. (2007b). Atrazine-induced aromatase expression is SF-1 dependent: impli cations for endocrine disruption in wildlife and reproductive cancers in humans. Envi ron Health Perspect , May, 115(5): 720-7. .......... 15Page 4 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 20. Filipov, N.M., Pinchuk, L.M., Boyd, B.L., & Crittenden P.L. (2005). Immunotoxic effects of short-term atrazine exposure in young male C57BL/6 mice. Toxicol Sci, Aug; 86(2): 324-32. ......................................................................................................................... 15 21. Filipov, N.M., Stewart, M.A., Carr, R.L., & Sistrunk, S.C. (2007). Dopaminergic toxicity of the herbicide atrazine in rat stri atal slices. Toxicol, Mar 22; 232(1-2): 68-78. .... 15 22. Foradori, C., Hinds, L., Hanneman, W., & Hand a, R. (2009a). Effects of atrazine and its withdrawal on gonadotro pin-releasing hormone neuroendoc rine function in the adult female Wistar rat. Biol Reprod, Dec, 81(6): 1099-105. ......................................................... 16 23. Foradori, C., Hinds, L., Hanneman, W., Lega re, M., Clay, C., & Handa, R. (2009b). Atrazine inhibits pulsatile luteinizing hormone release without altering pituitary sensitivity to a gonadotropin-releasing hormone receptor agonis t in female Wistar rats. Biol Reprod, Jul;81(1):40-5. ......................................................................................................................... 16 24. Fraites, M.J.P., Cooper, R.L., Buckalew, A ., Jayaraman, S., Mills, L., and Laws, S.C. (2009). Characterization of the Hypothalamic-P ituitary-Adrenal Axis Response to Atrazine and Metabolites in the Female Rat. Tox. Sci. 112(1):88-99. ................................................. 16 25. Fujimoto, N. and Honda, H. (2003). Effect s of environmental estrogenic compounds on growth of a transplanted estrogen responsive p ituitary tumor cell line in rats. Food Chem Toxicol, Dec, 41(12): 1711-7. ................................................................................................. 16 26. Fukamachi, K., Han, B.S., Kim, C.K., Ta kasuka, N., Matsuoka, Y., Matsuda, E., Yamasaki, T., and Tsuda, H. (2004). Possible enhancing effects of atrazine and nonylphenol on 7,2-dimethylbenz[a]anthracene-induced mamm ary tumor development in human c-Ha-ras proto-oncogene transgenic rats. Cancer Sci, May; 95(5): 404-10. ....................................... 16 27. Gilliom R.J., Barbash, J.E., Crawford, C.G., Hamilton, P.A., Martin, J.D., Nakagaki, N., Nowell, L.H., Scott, J.C., Stackelberg, P.E., Thelin, G.P. & Wolock, D.M. (2006). The quality of our Nation’s waters—Pesticides in the Nation’s streams and ground water, 1992– 2001. U.S. Geological Survey Circular 1291, 172 p. ............................................................. 16 28. Giusi, G., Facciolo, R.M., Canoaco, M., Alleva, E., Santucci, D., Belloni, V., & Dessi-Fulgheri, F. (2006). The endocrine disruptor atrazine a ccounts for a dimorphic somatostatinergic neuronal expression pattern in mice. Toxicol Sci, Jan; 89(1): 257-64. .... 16 29. Gojmerac, T., Pleadin, J., Zuric, M., Rajkovi c-Janje, R., & Korsic , M. (2004). Serum luteinizing hormone response to administra tion of gonadotropin-releasing hormone to atrazine-treated gilts. Vet Hum Toxicol, Oct, 6(5): 245-7. .................................................... 16 30. Hase, Y., Tatsuno, M., Nishi, T., Kabe, Y ., Yamaguchi, Y., Hanada, H., Kataoka, K., Ozawa, N., Natori, M., Handa, H., & Wantabe, H. (2008). Atrazine binds to F1F0-ATP synthase and inhibits mitoc hondrial function in sperm. Biochem Biophys Res Commun, Feb 1; 366(1): 66-72. ..................................................................................................................... 16 31. Heneweer, M., Van den Berg, M., & Sanders on, J.T. (2004). A comparison of human H295R and rat R2C cell lines as in vitro screening tools for e ffects on aromatase. Toxicol. Lett., Jan 15; 146(2): 183-94. .................................................................................................. 16 32. Higley, E.B., Newsted, J.L., Zhang, X., Giesy, J.P., & Hecker, M. (2010). Assessment of chemicals effects on aromatase activity using the H295R cell line. Environ Sci Pollut Res Int., Jan, 20, Epub ahead of print ................................................................... 16 33. Hocking, B. (2009). Melamine-contaminated powdered formula and urolithiasis. N Engl J Med., June 18, 360(25): 2676-7. .................................................................................. 17 34. Hoehn K., Salmon A., Hohnen-Behrens C., Tu rner N., Hoy A., Maghzal G., Socker R., Van Remmen H., Kraegen E., Cooney G., Richardson A., James D. (2009). InsulinPage 5 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov resistance is a cellular antioxidant defense mechanism. Proc Natl Acad Sci U S A, Oct 20 106(42):17787-92. .................................................................................................................. 17 35. Holloway, A.C., Anger, D.A., Crankshaw, D.J., Wu, M., & Foster, W.G. (2008). Atrazine-induced changes in aromatase activity in estrogen sensitive target tissues. J. Appl. Toxicol., Apr, 28(3): 260-70................................................................................................... 17 36. Hossain, M. M. & Filipov, N. M. (2008). Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites. Toxicology, Jun 3; 248(1): 52-8. ....................................................................... 17 37. Judson R.S., Houck K.A., Kavlock R.J., Knudsen T.B., Martin M.T., et al. (2009). In Vitro Screening of Environmental Chemicals fo r Targeted Testing Pr ioritization - The Tox Cast Project. Environ Hea lth Perspect, doi:10.1289/ehp.0901392 ........................................ 17 38. Juliani, C.C., Silva-Zacarin, E.C., Santos, D.C., & Boer, P.A.(2008). Effects of atrazine on female Wistar rats: morphologi cal alterations in ovarian follicles and immunocytochemical labeling of 90 kDa heat shock protein. Micr on, Jul, 39(5): 607-16. .. 17 39. Kandori, H., Suzuki, S., Asamoto, M., et al. (2005). Influence of atrazine administration and reduction of calorie intake on prostate carcinogene sis in probasin/SV40 T antigen transgenic rats. Ca ncer Sci, Apr; 96(4): 221-6. ......................................................... 17 40. Karrow, N.A., McCay, J.A., Brown, R.D ., Musgrove, D.L., Guo, T.L., Germolec, D.R., & White, K.L. Jr (2005). Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice. Toxicology, Apr 1; 209(1): 15-28. .......................................................................................... 17 41. Kirby E.D., Geraghty A.C., Ubuka T., Be ntley G.E., Kaufer D. (2009). Stress increases putative gonadotropin inhibitory ho rmone and decreases luteinizing hormone in male rats. Proc Natl Acad Sci USA, 106(27): 11324-9. ........................................................ 17 42. Kmetic, I., Gaurina Srcek, V., Silvac, I., Simic, B., Kniewald, Z., & Kniewald, J. (2008). Atrazine exposure decreases cell prol iferation in Chinese Hamster Ovary (CHO-K1) cell line. Bull Environ Cont am Toxicol., Aug, 81(2): 205-9. ................................................ 17 43. Kniewals, J., Kmeti č , I., Gaurina Sr č ek, V., Šimi ċ ,B., & Kniewald, Z. (2003). Cytotoxicity of Herbicide Atrazine On Chin ese Hamster ovary cell Line In Monolayer. Toxicol Lett, Sept; 144 (Suppl 1):S111-S112. ........................................................................ 17 44. Larson, S.J., C.G. Crawford, and R.J. Gilliom. (2004). Development and application of Watershed Regressions for Pesticides (W ARP) for estimating atrazine concentration distributions in streams. U.S. Geological Surv ey Water-Resources Investigations Report 03– 4047, 68 p. ............................................................................................................................... 18 45. Laville, N., Balaguer, P., Brion, F., Hinfra y, N., Casellas, C., Porcher, J.M., & AitAissa, S. (2006). Modulation of aromatase ac tivity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line. Toxicology, Nov 10; 228(1): 98-108. ........ 18 46. Laws, S.C., Ferrell, J.M., Stoker, T.E., & C ooper, R.L. (2003). Pubertal development in female Wistar rats following exposure to propazine and atrazine biotransformation byproducts, diamino-S-chlorotriazine and hydroxyatr azine. Toxicol Sci, Nov; 76(1): 190-200. . .....................................................................................................18 47. Laws, S.C., Hotchkiss, M., Ferrell, J., Jaya raman, S., Mills, L., Modic, W., Tinfo, N., Fraites, M., Stoker, T., & Coope r, R. (2009). Chlorotriazine Herbicides and Metabolites Activate an ACTH-Dependent Rele ase of Corticosterone in Ma le Wistar Rats. Tox. Sci., 112(1): 78-87. ......................................................................................................................... 18Page 6 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 48. Laws, S.C., Stoker, T.E., Ferrell, J.M ., Hotchkiss, M.G., & Cooper R.L. (2007). Effects of Altered Food Intake During Pubert al Development in Male and Female Wistar Rats. Toxicol. Sci., Nov; 100(1): 194-202. ............................................................................. 18 49. Lee, H.K. (2004). Bayesian Nonparametrics via Neural Networks. Philadelphia: ASA/SIAM. ............................................................................................................................ 18 50. Lim, S., Ahn, S.Y., Song, I.C., Chung, M.H ., Jang, H.C., Park, K.S., Lee, K., Pak, Y.K., & Lee, H.K. (2009). Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLOS One, 4(4): 1-11. ................................................... 18 51. Malik, S.I., Terzoudi, G.I., & Pantelias, G.E. (2004). SCE analysis in G2 lymphocyte prematurely condensed chromosomes after e xposure to atrazine: th e non-dose-dependent increase in homologous recombinational events does not support its genotoxic mode of action. Cytogenet and Genome Research, 104(1-4): 315-19. ................................................ 18 52. Manske, M., Beltz, L, and Dhanwada, K. (2004). Low-Level Atrazine Exposure Decreases Cell Proliferation in Human Fibroblasts. Arch. Environ. Contam. Toxicol., 46(4): 438-44.

............................................................................................................................... ..... 18 53. Maravilla-Galvan, R., Fierro, R., Gonzalez -Marquez, H., Gomez-Arroyo, S., Jimenez, I., & Betancourt, M. (2009). Effects of atr azine and fenoxaprop-ethyl on capacitation and the acrosomal reaction in boar sperm. In t. J. Toxicol., Jan-Feb, 28(1): 24-32. ........................... 18 54. McMullin T.S. (2003). Pharmacokinetic modeling of disposition and time-course studies with [ 14 C]-atrazine. J. Toxicol. Envir on. Health, May 23;66(10):941-64. ................. 18 55. McMullin, T.S., Andersen, M.E., Hannema n, W.H., Nagahara, A., Lund, T.D., Pak, T., & Handa, R.J. (2004). Evidence that atra zine and diaminochlor otriazine inhibit the estrogen/progesterone induced surge of lutein izing hormone in female Sprague-Dawley rats without changing estrogen receptor action. Toxicol Sci, Jun; 79(2): 278-86. ....................... 18 56. McMullin, T.S., Hanneman, W.H., Cranmer, B.K., Tessari, J.D., and Andersen, M.E. (2007). Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiologically modeling approaches. Toxicol, Oct 30; 240(1-2): 1-14. .............................. 19 57. Meek, M.E., J.R. Bucher, S.M. Cohen et al. (2003). A framework for human relevance analysis of information on carcinogeni c modes of action. Crit Rev Toxicol, 33(6): 591-653.

............................................................................................................................... ... 19 58. Mizota, K. & Ueda, H. (2006). Endocrin e disrupting chemical atrazine causes degranulation through Gq/11 protein-coupled neur osteroid receptor in mast cells. Toxicol Sci., Apr, 90(2): 362-8. ........................................................................................................... 19 59. Modic, MW. (2004). The role of testicul ar aromatase in the atrazine mediated changes in estrone and estradiol in the male wistar rat. North Carolina State University. .... 19 60. Mu, H., Zhang, P., & Xu, J. (2008). Tes ticular toxicity and mechanisms of chlorotoluron compounds in the mouse. T oxicology Mechanisms and Methods, 18(5): 399- 403.

.............................................................................................................................. ....... 19 61. Pinchuk, L.M., Lee, S.R., & Filipov, N.M. ( 2007). In vitro atrazine exposure affects the phenotypic and functional maturation of dend ritic cells. Toxicol Appl Pharmacol, Sept 15, 223(3): 206-17. ................................................................................................................. 19 62. Pogrmic, K., Fa, S., Dakic, V., Kaisarevic, S. & Kovacevic, R. (2009). Atrazine oral exposure of peripubertal male rats downregulat es steroidogenesis gene expression in Leydig cells. Toxicol. Sci., Sept. 111(1): 189-97. ............................................................................. 19 63. Pruett, S.B., Fan, R., Zheng, Q., Myers, L.P., & Hebert, P.(2003). Modeling and predicting immunological effects of chemical stressors: characteriza tion of a quantitativePage 7 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov biomarker for immunological changes caused by atrazine and ethanol. Toxicol Sci., Oct, 75(2):, 343-54. ........................................................................................................................ 19 64. Pruett, S.B., Fan, R., Zheng, Q., & Schwab, C. (2009). Patterns of immunotoxicity associated with chronic as compared with acu te exposure to chemical or physical stressors and their relevance with regard to the role of stress and with re gard to immunotoxicity testing. Toxicological Sciences, Jun, 109(2): 265-75. ........................................................... 19 65. Rayburn, A.L., Moody, D.D., and Freeman, J.L. (2005). Cytotoxicity of technical grade versus formulations of atrazine and acet ochlor using mammalian cells. Bull. Environ. Contam. Toxicol., 75(4): 691-8. ............................................................................................. 19 66. Rayner, J.L., Wolf, D.C., Rayner, J.L., Enoch, J.L., Enoch, R.R., & Fenton, S.E. (2007). Atrazine-induced reproductive tract alte rations after transplacen tal and/or lacational exposure in male Long-Evans rats. Toxi col Appl Pharmacol, Feb 1, 218(3): 238-48. ......... 19 67. Rayner, J. L., Wood, C., Fenton, S. E. ( 2004). Exposure parameters necessary for delayed puberty and mammary gland developmen t in Long-Evans rats exposed in utero to atrazine. Toxicol Appl Pharmacol, Feb 15; 195(1): 23-34. ................................................... 19 68. Rivest, P. & Sanderson, J. (2010). Effects of pesticides on aromatase expression in bioluminescent mice and GSK 3BETA/BETA-signa lling in LNCAp human prostate cancer cells. The Toxicologist 114, 405. ........................................................................................... 20 69. Rodriguez, V.M., Thiruchelvam, M., & Cory-Slechta, D.A. (2005). Sustained exposure to the widely used herbicide atrazine : Altered function and lo ss of neurons in brain monoamine systems. Environmental H ealth Perspectives , Jun, 113(6): 708-15. .................. 20 70. Rooney, A.A., Matulka, R.A., & Luebke, R.W. (2003). Developmental atrazine exposure suppresses immune function in male, but not female Spragus-Dawley rats. Toxicol Sci., Dec, 76(2): 366-75. ......................................................................................................... 20 71. Rosenberg, B.G., Chen, H., Folmer, J., Liu, J., Papadopoulos, V., & Zirkin, B.R. (2008). Gestational exposure to atrazine: e ffects on the postnatal development of male offspring. J Androl., May-June; 29(3): 304-11. ..................................................................... 20 72. Ross, M.K., Jones, T.L., and Filipov, M.N. (2009). Disposition of the herbicide 2- chloro-4-(ethylamino)-6-(isopropylamino)-s-triaz ine (atrazine) and its major metabolites in mice: a liquid chromatography/mass spectrometr y analysis of urine, plasma, and tissue levels. Drug Metab. Dispos., Apr; 37(4): 776-86. ................................................................. 20 73. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2008). Developmental immunotoxicity of atrazine in rodents. Basi c Clin Pharmacol Toxicol, Feb; 102(2): 139-45.

.. .....................................................................................................20 74. Rowe, A.M., Brundage, K.M., & Barnett, J. B. (2007). In vitr o atrazine exposure inhibits human natural killer cel l lytic granule release. Toxi col Appl Pharmacol, Jun 1; 221(2): 179-88. ....................................................................................................................... 20 75. Rowe, A.M., Brundage, K.M., Schafer, R., & Barnett, J.B. (2006). Immunomodulatory effects of ma ternal atrazine exposure on male Balb/c mice. Toxicol Appl Pharmacol, Ju ly 1; 214(1): 69-77 ................................................................................... 20 76. Rusiecki, J.A., De Roos, A., Lee, W.J., Do semci, M., Lubin J.H., Hoppin, J.A., Blair, A., & Alavanja, M.C. (2004). Cancer incide nce among pesticide applicators exposed to atrazine in the Agricultural Health Study. J Natl Cancer Inst, Sept 15; 96(18): 1375-82. .... 20 77. Sanderson, J.T., Boerma, J., Gideon, W.A., Lansbergen, G.W. & van den Berg, M. (2002). Induction and inhibition of aromat ase (CYP19) activity by various classes of pesticides in H295R human adre nocortical carcinoma cells. Toxi col Appl Pharmacol. Jul 1; 182: 44-54. .............................................................................................................................. 20Page 8 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 78. Santen R.J., Brodie H., Simpson E.R., Siite ri P.K., Brodie A.. (2009). History of Aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev, Jun; 30(4): 343-75. .................................................................................................................. 20 79. Schwab, C. L., Fan R., Zheng, Q., Myers, L.P., Hébert,P., & Pruet, S.B. (2005). Modeling and predicting stress -induced immunosuppression in mice using blood parameters. Toxicol Sci, Jan; 83(1): 101-13. ............................................................................................. 20 80. Seed, J., E.W. Carney, R.A. Corley et al. (2005). Overview: Using mode of action and lifestage information to evaluate the human relevance of animal toxicity data. Crit. Rev. Toxicol., Oct-Nov; 35(8-9):664-72. ........................................................................................ 21 81. Shibayama, H., Kotera, T., Shinoda, Y., Hanada, T., Kajhara, T., Ueda, M., Tamura, H., Ishibashi, S., Yamashita, Y., & Ochi, S. (2009). Collaborative wo rk on evaluation of ovarian toxicity. 14) Two- or four-week repeated-dos e studies and fertility study of atrazine in female rats. J Toxicol Sci., 34: 147-55. ............................................................................. 21 82. Singh, M., Kaur, P., Sandhir, R., & Kiran, R. (2008a). Protective e ffects of vitamin E against atrazine-induced genotoxicity in rats. Mutat Res, Jul 31; 654(2): 145-9. ................. 21 83. Singh, M., Sandhir, R., & Kiran, R.(2008b). Atrazine-induced alterations in rat erthrocyte membranes: ameliorating efect of v itamin E. J Biochem Mol Toxicol, Sept, 225: 363-9.

............................................................................................................................... ...... 21 84. Son, H.Y., Nishikawa, A., Okazaki, K., Lee, K., Imazawa, T., & Hirose, M. (2003). Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rat pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Food Chem Toxicol, Dec; 41(12): 1811-6. ....................................................................................................................... 21 85. Stoker T.E & Cooper R.L. (2007). Distribu tion of 14C-atrazine following an acute lactational exposure in th e Wistar rat. Reprod T oxicol, Jun; 23(4):607-10. .......................... 21 86. Stone, W.W. & Gilliom, R.J. (2009). Update of watershed regressi ons for pesticides (WARP) for predicting atrazine concentration in streams. U.S. Geological Survey Open-File Report 2009–1122, 22 p. Available at http://pubs.usgs.gov/of/2009/1122/ ........................... 21 87. Stone, W.W., Gilliom, R.J. & Crawford, C.G. (2008). Watershed Regressions for Pesticides (WARP) for Predicting Annua l Maximum and Maximum Moving-Average Concentrations of Atrazine in Streams. U. S. Geological Survey Open-File Report 08-1186, 19 p.

.............................................................................................................................. ....... 21 88. Suzawa, M. & Ingraham, H.A. (2008). The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells. PloS ONE, 3(5): 1-11. ..................................................................................................................... 21 89. Tanaka, T., Kohno, H., Suzuki, R., & Sugie, S. (2004). Lack of modifying effects of an estrogenic compound atrazine on 7,12-di methylbenz(a)anthracene-induced ovarian carcinogenesis in rats. Can cer Lett, Jul 16; 210(2): 129-37. ................................................. 21 90. Tinfo, N., & Laws, S.C. (2009). Unders tanding the Effects of Atrazine on Steroidogenesis in Wistar rats. Society of Toxicology, Itinerary Planner, Baltimore, MD. . 21 91. Ueda, M., Imai, T., Takizawa, T., Onodera, H., Mitsumori, K., Matsul, T., & Hirose, M. (2005). Possible enhancing effects of at razine on growth of 7,12-dimethylbenze(a) anthracene-induced mammary tumors in ovariec tomized Sprague-Dawley rats. Cancer Sci., Jan, 96(1): 19-25. .................................................................................................................... 21 92. Victor-Costa, A.B., Carozzi Bandeira, S. M., Oliveira, A.G., Bohorquiz Mahecha, G.A. & Oliveira, C.A. (2010). Changes in testicular morphology and steroiodogenesis in adult rats exposed to atrazine. Reprod Toxicol, Jan 4. [Epub ahead of print] Doi:10.1016/j.reprotox.2009.12.006 ....................................................................................... 22Page 9 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 93. Whalen M.M., Loganathan B.G., Yamashita, N., Saito, T. (2003). Immunomodulation of human natura l killer cell cytotoxic func tion by triazine and carbamate pesticides. Chemico-Biological Interactions, Jun 15; 145(3): 311-19. .................................. 22 94. Zeljezic, D. & Garaj-Vrhovac, V. (2004a). Genotoxicity evaluation of pesticide formulations containing alachlor and atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet assay. Neoplasma, 51(3): 198-203. .................................... 22 95. Zeljeciz D, & Garaj-Vrhovac, V. (2004b). Atrazine genotoxici ty evaluation in different mouse organs by comet assa y. Periodicum Biol ogorum, 106(2):, 155-9. .............. 22 96. Zeljezic, D., Garaj-Vrhovac, V., & Perkovi c, P. (2006). Evaluation of DNA damage induced by atrazine and atrazine-based herbic ide in human lymphocytes in vitro using a comet and DNA diffusion assay. To xicol In Vitro, Sept; 20(6): 923-35. .............................. 22 97. Zorrilla, L.M., Gibson, E.K., Stoker (2009) Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Ne uronal GT1-7 Cell Line and Hypothalamic Explants

. Annual Meeting of the Society for Study of Reproduction, Pittsburgh, PA. Biol of Reprod, 81: 638. ...................................................................................................................... 22 4. FIFRA SAP Reference Materials - Pre-2003 References .................................................. 22 1. Blomquist, J.D., Denis, J.M., Cowles, J.L., He trick, J.A., Jones, R.D. & Birchfield N.B. (2001). Pesticides in Selected Water-Supply Reservoirs and Finished Drinking Water, 1999- 2000: Summary of Results from a Pilot Monito ring Program. U.S. Geological Survey OpenFile Report 01-456. Published in cooperation with the U.S. Environmental Protection Agency

............................................................................................................................... ..... 22 2. Cooper, R.L., Stoker, T.E., Goldman, J.M., Parr ish, M.B, & Tyrey, L. (1996). Effect of atrazine on ovarian function in the rat. Reprod Toxi col, Jul-Aug; 10(4): 257-64. ................ 22 3. Cooper, R.L., Stoker, T.E., Tyrey, L., Goldman, J.M., & McElroy, W.K. (2000). Atrazine disrupts the hypothalamic control of pituitary-ovarian function. Toxicol Sci., Feb; 53(2): 297-307 ........................................................................................................................ 22 4. Das, P.C., McElroy, W.K. & Cooper, R.L. (2001). Alteration of Catecholamines in Pheochromocytoma (PC12) Cells in Vitro by the Metabolites of Chlorotriazine Herbicide. Toxicol Sci, Jan; 59(1): 127-37. ............................................................................................. 22 5. Deutsch, C.V. & Journel, A.G. (1998). GSLIB: Geostatistical So ftware Library and User’s Guide. Second Edition. Oxford University Press (New York, Oxford). .................... 22 6. Eldridge, J.C., Wetzel, L.T., & Tyrey, L. (1999). Estrous cycle patterns of SpragueDawley rats during acute and ch ronic atrazine administration. Reprod Toxicol, Nov-Dec; 13(6): 491-9. ........................................................................................................................... 23 7. Friedmann, A.S. (2002). Atrazine inhibiti on of testosterone production in rat males following peripubertal exposure. Re prod. Toxicol, May-Jun; 16: 275-9. ............................ 23 8. Gao H.B., Shan L.X., Monder C., Hardy M.P. (1996). Suppression of endogenous corticosterone levels in vivo increases the st eroidogenic capacity of purified rat Leydig cells in vitro. Endocrinol ogy, May; 137(5):1714-8. ....................................................................... 23 9. ILSI (International Life Sciences Institute), (1999). A Framework for Estimating Pesticide Concentrations in Drinking Water for Aggr egate Exposure Assessments. International Life Sciences Institute Risk Science In stitute Working Group Report, Washington, D.C., 61 pp. ........................................................................................................ 23 10. Isaaks, E.H., and R.M. Srivastava. (1989). A pplied Geostatistics. Oxford University Press (New York, Oxford). ..................................................................................................... 23 11. Kalra, S.P., & Kalra, P.S.(1983). Neural regulation of luteinizing hormone secretion in the rat. Endocr Rev., Fall; 4(4): 311-51. ........................................................................... 23Page 10 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 12. Laws, S. C., Ferrell, J. M., Stoker, T. E ., Schmid, J. & Cooper, R. L. (2000). The Effects of Atrazine on Female Wistar Rats: An Evaluation of the Pr otocol for Assessing Pubertal Development and Thyroid Function. Toxicol Sci, 58: 366-76. ............................... 23 13. Lyons, W.R., Berlin, I., and Fr iendlander, S. (1942) Corn ification of balano-preputial epithelium in normal rats and castrated rats treated with testos terone proprionate. Endocrinology, 31(6): 659-63. ................................................................................................ 23 14. Marshall, F. (1966) Marshall’s Physio logy of Reproduction. Longmans, Green and Co. LTD

............................................................................................................................... ... 23 15. Matsumoto AM, Karpas AE, Southworth MB, Dorsa DM, Bremner WJ. (1986). Evidence for activation of the central nervous system-pituitary mech anism for gonadotropin secretion at the time of puberty in the male rat. Endocrinology, Jul; 119(1): 362-9. ............ 23 16. Molcrani M.C., Duval F., Crocq M.A., Ba iley P., Macher J.P. (1997). HPA axis dysfunction in depression: Correlation with monoamine system abnormalities. Psychoneuroendocrinology, 22 Suppl 1: S63-8...................................................................... 23 17. Monosson E, Kelce WR, Lambright C, Ost by J, Gray LE Jr. (1999). Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, a nd alters androgen receptor function in the male rat. Toxicol Ind Hea lth, Jan-Mar; 15(1-2): 65-79. ........................................................ 23 18. Ojeda, S.R., and Urbanski, H.F. (1994). Pube rty in the rat. In E. Knobil and J.D. Neill (Eds.): The Physiology of Reproduction, 2 nd ed. New York, Raven Press................... 23 19. Rivest, .S & Rivier, C. (1995). The role of corticotropin-releasing factor and interleukin-1 in the regulati on of neurons controlling reprodu ctive functions. Endocr Rev, 16(2): 177-99. ......................................................................................................................... 23 20. Rivier, C. & Rivest, S. (1991). Effect of stress on the activit y of the hypothalamicpituitary-gonadal axis: periphe ral and central mechanisms. Bi ol Reprod., October 1, 1991; 45 (4): 523-532. ........................................................................................................................... 24 21. Rivier, C., Rivier, J., & Va le, W. (1986). Stress-induced inhibition of reproductive functions: role of endogenous co rticotropin-releasing factor . Science, 231(4738): 607-9. ... 24 22. Sanderson J.T., Boerma J., Lansbergen G.W ., van den Berg M. (2002). Induction and inhibition of aromatase (CYP19) activity by vari ous classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol Appl Pharmacol, Jul 1; 182(1): 44-54. ................... 24 23. Sanderson J.T., Letcher R.J., Heneweer M ., Giesy J.P., van den Berg M. (2001). Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitelloge nin production in male carp hepa tocytes. Environ health Perspect, Oct; 109(10):1027-31. ............................................................................................ 24 24. Sanderson J.T., Seinen W., Giesy J.P., van den Berg M. (2000). 2-Chloro-s-triazine herbicides induce aromatase (CYP19) activit y in H295R human adrenocortical carcinoma cells: a novel mechanisms for estrogenici ty? Toxicol Sci, Mar; 54(1): 121-27. ................... 24 25. Selye, H. (1939). Effect to adaptation to various damaging agents on the female sex organs in the rat. Endocrinology, 25(4): 615-24.................................................................... 24 26. Simpson, E.R., Clyne, C.D., Rubin, G., B oon, W.C., Robertson, K., Britt, K., Speed, C., & Jones, M.E. (2002). Aromatase: a brief review. Annu Rev Physiol, 64: 93-127. ....... 24 27. Simpson , E.R., & Davis, S.R. (2001). Mi nireview: aromatase and the regulation of estrogen biosynthesis – some new perspect ives. Endocrinology, Nov; 142(11): 4589-94. .. 24 28. Sonich-Mullin, C., R. Fielder, J. Wiltse et al. (2001). IPCS conceptual framework for evaluating a mode of action fo r chemical carcinogenesis. Regul Toxicol Pharmacol, Oct; 34(2):146-52. .......................................................................................................................... 24Page 11 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 29. Stoker, T.E., Guidici, D.L., Laws, S.C. & Cooper, R.L. (2002). The Effects of Atrazine Metabolites on Puberty and Thyroi d Function in the Male Wistar Rat: An Evaluation in the Male Pubertal Pr otocol. Toxicol. Sci., 67: 198-206. ................................. 24 30. Stoker, T.E., Laws, S.C., Guidici, D., & Coope r, R.L. (2000). The effects of atrazine on puberty and thryroid function in the male wistar rat: An ev aluation of a protocol for the assessment of pubertal development and t hyroid function. Toxi col. Sci., 58: 50-9. ............. 24 31. Stoker T.E., Robinette, C.L. & Cooper, R.L. (1999). Maternal exposure to atrazine during lactation suppresses suckling- induced prolactin release and results in prostatitis in the adult offspring. Toxicol Sci, 52: 68-79 .................................................................................. 24 32. Trentacoste, S.V., Friedma nn, A.S., Youker, R.T., Breckenridge, C.B. & Zirkin, B.R. (2001). Atrazine effects on testosterone leve ls and androgen-dependent reproductive organs in peripubertal male rats. J. Androl, Jan-Feb; 22(1): 142-8. .................................................. 24Page 12 of 25

*These materials are s ubject to FIFRA 10(g) and therefore are provided on a separate disc For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov 

### Transmittal memo

Atrazine Issue Paper

1. FIFRA SAP 10g Reference Materials 

### Document Description Attachment

1. Breckenridge, C.B., Yi, K.D., & Simpkins, J.W. (2010a). Cytotoxicity of atrazine and its metabolites in vitro. Unpublished data from Syngenta Crop Protection, Inc. 10g*

2. Breckenridge, C.B., Yi, K.D., Perez, E.J., & Simpkins, J.W. (2010b). Dose and time-depende nt-effects of atrazine and metabolites on aromatase mRNA in multiple cell types in vitro. Unpublished data from Syngenta 10g*

3. Breckenridge, C.B., Yi, K.D., Perez, E.J., & Simpkins, J.W. (2010c). Ex vivo assessment of th e effects of atrazine or its metabolites on phosphodiesterase activity. Unpublished data from Syngenta 10g*

4. Kim, D., Breckenridge, C. (Syngenta) (2010). Atrazine - Derivation of the short-term inhalation NOAE L using a physiologically-based pharmacokinetic model. Unpublished data from Syngenta 10g*

5. Morseth S. (1996) Evaluation of the Luteinizing Hormone (LH) Surge in Atrazine-Exposed Female Sprague-Dawley Rats--(Final) 6- Month Interim Report: Lab Pr oject Number: CHV 2386-111: 2386- 111: 6791E. Unpublished study prepared by Corning Hazleton Inc. 727 p. MRID 44152102 10g*

2. Previous FIFRA SAP References

1. FIFRA Scientific Advisory Panel (FIFRA SAP). (2009). A Set of Scientific Issues Being Consider ed by the Environmental Protection Agency Regarding: The Ecological Significance of Atrazine Effects on Primary Producers in Surface Water Streams in the Corn and Sorghum Growing Region of the United States (Part II). SAP Minutes No. 2009-06. May 12 – 14, 2009 FIFRA Scientific Advisory Panel. Web Link

2. FIFRA Scientific Advisory Panel (SAP). (2003). “Characterization of Epidemiology Data Relating to Prostate Cancer and Exposure to Atrazine.” Report from the FI FRA Scientific Advisory Panel Meeting of July, 2003. FIFRA Scientific Advisory Panel, Office of Science Coordination and Policy, O ffice of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. Web Link

3. FIFRA Scientific Advisory Pane l (SAP). (2000). “Atrazine: Hazard and Dose-Response Assessm ent and Characterization.” Report from the FIFRA Scientific Advisory Panel Meeting of June 27-29, 2000. FIFRA Scientific Advisory Panel, Office of Science Web LinkPage 13 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Coordination and Policy, Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. 4. FIFRA Scientific Advisory Panel (S AP). (1988). “A set of issues being considered by the Agency in connection with the peer review classification of atrazine a cla ss C carcinogen.” Report from the FIFRA Scientific Advisory Panel Meeting of September 14, 1988. FIFRA Scientific Advisory Panel, Office of Science Coordination and Policy, Office of Prevention, Pe sticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. 5. U.S. Environmental Protection Agency. (2010). DRAFT Framework for Incorporating Human Epidemiologic & Incident Data in Health Risk Assessment (Draft dated Ja nuary 7, 2010). Presented to the FIFRA Scientific Advisory Panel, February 2-4, 2010. http://www.regulations.gov (Docket EPA-HQ-OPP-2009-0851). Web Link

6. U.S. Environmental Protection Agency (USEPA). 2009a. The Ecological Significance of Atrazine Effects on Primary Producers in Surface Water Streams in the Corn and Sorghum Growing Region of the United States (Part II). Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel. Web Link

7. U.S. Environmental Protection Agency (USEPA). 2009b. The Ecological Significance of Atrazine Effects on Primary Producers in Surface Water Streams in the Corn and Sorghum Growing Region of the United States (P art II). Addendum to Section VI: Additional Analysis of the 40 AEEMP Sampli ng Sites to Identify Additional Areas That May Exceed the LOC. Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel. Web Link

8. U.S. Environmental Protection Agency (USEPA). 2007a. Acetochlor Registration Agreem ent and Monitoring Program. Documents are available through th e Federal docket. Docket ID: EPA-HQ-OPP-2007-0725. Web Link

9. U.S. Environmental Protection Agency (USEPA). 2007b. N-methyl Carbamate Revised Cumulative Risk Assessment. Web Link
10. U.S. Environmental Protection Agency (USEPA). 2007c. Preliminary Interpretation of the Ecological Significance of Atrazine Stream-Water Concentrations Using a Statistically-Designed Monitoring Program. Prepared for the December 4 – 7, 2007 FIFRA Scientific Advisory Panel. Web Link

11. US EPA. (2006). Decision Document s for Atrazine. Atrazine IREDs (January and October 31, 2003) an d Atrazine RED (April 6, 2006). EPA-HQ-OPP-2003-0367. Web Link

12. US EPA. (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency, Risk Assessment Forum, Washington, DC. EPA/630/P-03/ 001F. Federal Register 70(66):17765-17817. Web Link

13. US EPA. (2003). Interim Re-regi stration Eligibility Decision (IRED) Web LinkPage 14 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 14. U.S. EPA. (1999). Guidelines for carcinogen risk assessment. Risk Assessment Forum. SAB review draft. Washington, DC: U.S. Environmental Protection Agency. Web Link

3. FIFRA SAP Reference Materials - Post 2003 References

1. Albanito L., Madeo A., Lappano R., Vivacqua A., Rago V., Carpino A., Oprea T., Prossnitz E., Musti A.M., Andò S. & Maggiolini, M. (2007). G Protein–Coupled Recepto r 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17ß-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells. Cancer Res., Feb 15; 67(4):1859-66 Web Link

2. Albanito, L., Lappano, R., Madeo, A., Chimento, A., Prossnitz, E.R., Cappello, A.R., Dolce, V., Abonante, S., Pezzi, V., & Maggiolini, M. (2008). G-protein-coupled receptor 30 and estrogen receptor-alpha are involved in the proliferative eff ects induced by atrazine in ovarian cancer cells. Environ Health Perspect, Dec; 116(12): 1648-55. Web Link

3. Bakke B., De Roos A.J., Barr D.B ., Stewart P.A., Blair A., Freeman L.B., Lynch C.F., Allen R.H., Alavanja M.C., Vermeulen R. (2009). Exposure to atrazine and selected non-persistent pesticides among corn farmers during the growing season. J Expo Sci Environ Epidemiol, Sep; 19(6):544-54 Web Link

4. Belloni V, Alleva E, et al. (2007). Effects of low doses of atrazine on the neurobehavioural developm ent of mice. Ethology Ecology & Evolution, 19: 309-22. Web Link

5. Benachour, N., Moslemi, S., Sipahut ar, H., & Seralini G.E. (2007). Cytotoxic effects and aromatase i nhibition by xenobiotic endocrine disrupters alone and in combinati on. Toxicol Appl Pharmacol, Jul 15; 222(2): 129-40. Web Link

6. Betancourt, M., Resendiz, A., & Fier ro, E.C. (2006). Effects of two insecticides and two herbicides on the porcine sperm motility patterns using computer-assisted semen analysis (CASA) in vitro. Reprod Toxicol, Oct, 22(3): 508-12. Web Link

7. Boobis, A.R., J.E. Doe, B. Hein rich-Hirsch et al. (2008). IPCS framework for analyzing the relevance of a noncancer mode of action for humans. Crit Rev Toxicol, 38(2):87-96. Web Link

8. Cimino-Reale, G., Ferrario, D., Casa ti, B., Brustio, R., Diodovich, C., Collotta, A., Vahter, M., & Gribal do, L. (2008). Combined in utero and juvenile exposure of mice to ar senate and atrazine in drinking water modulates gene expressi on and clonogenicity of myeloid progenitors. Toxicol Lett , Jul 30; 180(1): 59-66. Web Link

9. Coban, A., & Filipov, N.M. (2007) . Dopaminergic toxicity associated with oral exposure to the herbicide atrazine in juvenile male C57BL/6 mice. J. Neurochem, Mar, 100(5): 1177-87. Web Link

10. Cooper R.L., Laws S., Das P.C., Narotsky M.G., Goldman J.M., Tyrey E.L., Stoker T.E. (2007). At razine and reproductive function: mode and mechanism of action st udies. Birth Defects Res B Dev Web LinkPage 15 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Reprod Toxicol, Apr; 80(2): 98-112.

11. Crawford, C.G. (2004). Sampling Stra tegies for Estimating Acute and Chronic Exposures of Pesticides in Streams. Journal of the American Water Resources Associa tion (JAWRA) 40(2):485-502. Web Link

12. Devos, S., Hooghe, R., Hooghe-Peters, E.L., De Bosscher, K., Vanden Berghe, W., Haegeman, G., St aels, B., Bauer, E., Roels, F., & Hooghe, R. (2003). Inhibition of cytokine production by the herbicide atrazine: Search for nuclear receptor targets. Biochem Pharmacol, Jan 15; 65(2): 303-8. Web Link

13. Devos S., Van Den Heuvel R., et al . (2004). Limited effect of selected organic pollutants on cy tokine production by peripheral blood leukocytes. Eur Cytokine Netw, Apr-Jun; 15(2): 145-51. Web Link

15. Dooley, G., Prenni, J., Prentiss, P., Cranmer, B., Anderson, M., & Tessari, J. (2006). Identification of a novel hemoglobin adduct in Sprague-Dawly rats exposed to atrazine. Chem Res Toxicol, May; 19(5): 692-700. Web Link

14. Dooley, G.P., Reardon, K.F., Prenni, J.E., Tjalkens, R.B., Legare, M.E., Foradori, C.D., Tessari, J.E., & Hanneman, W.H. (2008). Proteomic analysis of diaminocholor otriazine adducts in Wistar rat pituitary glands and LbetaT2 rat p ituitary cells. Chem Res Toxicol, Apr, 21(4): 844-51. Web Link

16. Dooley, G., Hanneman, W., Carbone, D., Legare, M., Anderson, M., & Tessari, J. (2007). Development of an immunochemistry detection method for atrazine-induced albumin adducts. Chem Res Toxicol, Jul; 20(7): 1061-6. Web Link

17. Enoch, R.R., Stanko, J.P., Greiner, S.N., Youngblood, G.L., Rayner, J.L., & Fenton, S.E. (2007). Mammary gland development as a sensitive end point after acute pr enatal exposure to an atrazine metabolite mixture in female Long-Evans rats. Environ Health Perspect, Apr, 115(4): 541-7. Web Link

18. Fan, W., Yanase, T., Morinaga, H ., Gonda, S., Okabe, T., Nomura, M., Hayes, T., Takayanagi, R., & Nawata, H.(2007a). Herbicide atrazine activates SF-1 by direct affinity and concomitant coactivators recruitments to induce aromatase expression via promoter II. Biochemical and Biophysic al Research Communications, 355(4): 1012-8. Web Link

19. Fan, W., Yanase, T., Morinaga, H ., Gondo, S., Okabe, T., Normura, M., Komatsu, T., Moroashi, K., Hayes, T.B., Takayanagi, R., & Nawata, H. (2007b). Atrazine-induc ed aromatase expression is SF1 dependent: implications for endoc rine disruption in wildlife and reproductive cancers in humans. Environ Health Perspect, May, 115(5): 720-7. Web Link

20. Filipov, N.M., Pinchuk, L.M., B oyd, B.L., & Crittenden P.L. (2005). Immunotoxic effects of sh ort-term atrazine exposure in young male C57BL/6 mice. Toxico l Sci, Aug; 86(2): 324-32. Web Link

21. Filipov, N.M., Stewart, M.A., Carr, R.L., & Sistrunk, S.C. (2007).Page 16 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Dopaminergic toxicity of the herbicide atrazine in rat striatal slices. Toxicol, Mar 22; 232(1-2): 68-78. Web Link

22. Foradori, C., Hinds, L., Hanneman, W., & Handa, R. (2009a). Effects of atrazine and its w ithdrawal on gonadotropin-releasing hormone neuroendocrine function in the adult female Wistar rat. Biol Reprod, Dec, 81(6): 1099-105. Web Link

23. Foradori, C., Hinds, L., Hanneman, W., Legare, M., Clay, C., & Handa, R. (2009b). Atrazine inhibi ts pulsatile luteinizing hormone release without altering pituit ary sensitivity to a gonadotropinreleasing hormone receptor agonist in female Wistar rats. Biol Reprod, Jul;81(1):40-5. Web Link

24. Fraites, M.J.P., Cooper, R.L., Bu ckalew, A., Jayaraman, S., Mills,L., and Laws, S.C. (2009). Characterization of the HypothalamicPituitary-Adrenal Axis Response to Atrazine and Metabolites in the Female Rat. Tox. Sci. 112(1):88-99. Web Link

25. Fujimoto, N. and Honda, H. (2003). Effects of environmental estrogenic compounds on growth of a transplanted estrogen responsive pituitary tumor cell line in rats. Food Chem Toxicol, Dec, 41(12): 1711-7. Web Link

26. Fukamachi, K., Han, B.S., Kim, C. K., Takasuka, N., Matsuoka, Y., Matsuda, E., Yamasaki, T., and Tsuda, H. (2004). Possible enhancing effects of atra zine and nonylphenol on 7,2- dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene tr ansgenic rats. Cancer Sci, May; 95(5): 404-10. Web Link

27. Gilliom R.J., Barbash, J.E., Crawford, C.G., Hamilton, P.A., Martin, J.D., Nakagaki, N., Nowell, L.H., Scott, J.C., Stackelberg, P.E., Thelin, G.P. & Wolock, D.M. ( 2006). The quality of our Nation’s waters—Pesticides in the Nati on’s streams and ground water, 1992– 2001. U.S. Geological Survey Circular 1291, 172 p. Web Link

28. Giusi, G., Facciolo, R.M., Canoaco, M., Alleva, E., Santucci, D., Belloni, V., & Dessi-Fulgheri, F. (2 006). The endocrine disruptor atrazine accounts for a dimorphi c somatostatinergic neuronal expression pattern in mice. Toxicol Sci, Jan; 89(1): 257-64. Web Link

29. Gojmerac, T., Pleadin, J., Zuric, M., Rajkovic-Janje, R., & Korsic, M. (2004). Serum luteinizing ho rmone response to administration of gonadotropin-releasing hormone to atrazine-treated gilts. Vet Hum Toxicol, Oct, 6(5): 245-7. Web Link

30. Hase, Y., Tatsuno, M., Nishi, T., Kabe, Y., Yamaguchi, Y., Hanada, H., Kataoka, K., Ozawa, N., Natori , M., Handa, H., & Wantabe, H. (2008). Atrazine binds to F1F0 -ATP synthase and inhibits mitochondrial function in sperm. Biochem Biophys Res Commun, Feb 1; 366(1): 66-72. Web Link

31. Heneweer, M., Van den Berg, M ., & Sanderson, J.T. (2004). A comparison of human H295R and rat R2C cell lines as in vitro screening tools for effects on aromatase. Toxicol. Lett., Jan 15; 146(2): 183-94. Web Link

32. Higley, E.B., Newsted, J.L., Zhang, X., Giesy, J.P., & Hecker, M.Page 17 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov (2010). Assessment of chemicals effects on aromatase activity using the H295R cell line. Envir on Sci Pollut Res Int., Jan, 20, Epub ahead of print Web Link

33. Hocking, B. (2009). Melamine-contaminated powdered formula and urolithiasis. N Engl J Med., June 18, 360(25): 2676-7. Web Link

34. Hoehn K., Salmon A., Hohnen-Behr ens C., Turner N., Hoy A., Maghzal G., Socker R., Van Remmen H., Kraegen E., Cooney G., Richardson A., James D. (2009). Insulin resistance is a cellular antioxidant defense mechanism. Pr oc Natl Acad Sci U S A, Oct 20 106(42):17787-92. Web Link

35. Holloway, A.C., Anger, D.A., Cran kshaw, D.J., Wu, M., & Foster, W.G. (2008). Atrazine-induced ch anges in aromatase activity in estrogen sensitive target tissues. J. Appl. Toxicol., Apr, 28(3): 260- 70. Web Link

36. Hossain, M. M. & Filipov, N. M. (2008). Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites. Toxicology, Jun 3; 248(1): 52-8. Web Link

37. Judson R.S., Houck K.A., Kavlock R.J., Knudsen T.B., Martin M.T., et al. (2009). In Vitro Scr eening of Environmental Chemicals for Targeted Testing Prioritization - The Tox Cast Project. Environ Health Perspect, doi:10.1289/ehp.0901392 Web Link

38. Juliani, C.C., Silva-Zacarin, E.C., Santos, D.C., & Boer, P.A.(2008). Effects of atrazine on female Wist ar rats: morphological alterations in ovarian follicles and immunoc ytochemical labeling of 90 kDa heat shock protein. Micron, Jul, 39(5): 607-16. Web Link

39. Kandori, H., Suzuki, S., Asamoto, M ., et al. (2005). Influence of atrazine administration and reductio n of calorie intake on prostate carcinogenesis in probasin/SV40 T antig en transgenic rats. Cancer Sci, Apr; 96(4): 221-6. Web Link

40. Karrow, N.A., McCay, J.A., Brown, R.D., Musgrove, D.L., Guo, T.L., Germolec, D.R., & White, K.L. Jr (2005). Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice. Toxicology, Apr 1; 209(1): 15-28. Web Link

41. Kirby E.D., Geraghty A.C., Ubuka T., Bentley G.E., Kaufer D. (2009). Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proc Natl Acad Sci USA, 106(27): 11324-9. Web Link

42. Kmetic, I., Gaurina Srcek, V., Silvac, I., Simic, B., Kniewald, Z., & Kniewald, J. (2008). Atrazine expo sure decreases cell proliferation in Chinese Hamster Ovary (CHO- K1) cell line. Bull Environ Contam Toxicol., Aug, 81(2): 205-9. Web Link

43. Kniewals, J., Kmeti č , I., Gaurina Sr č ek, V., Šimi ċ ,B., & Kniewald, Z. (2003). Cytotoxicity of Herbic ide Atrazine On Chinese Hamster ovary cell Line In Monolayer. Toxicol Lett, Sept; 144 (Suppl 1):S111-S112. Web LinkPage 18 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov 44. Larson, S.J., C.G. Crawford, and R.J. Gilliom. (2004). Development and application of Watershed Regr essions for Pesticides (WARP) for estimating atrazine concentrati on distributions in streams. U.S. Geological Survey Water-Resource s Investigations Report 03–4047, 68 p. Web Link

45. Laville, N., Balaguer, P., Bri on, F., Hinfray, N., Casellas, C., Porcher, J.M., & Ait-Aissa, S. (2006). Modulation of aromatase activity and mRNA by various sele cted pesticides in the human choriocarcinoma JEG-3 cell line. Toxicology, Nov 10; 228(1): 98- 108. Web Link

46. Laws, S.C., Ferrell, J.M., Stoker, T.E., & Cooper, R.L. (2003). Pubertal development in female Wistar rats following exposure to propazine and atrazine biotrans formation by-products, diamino-Schlorotriazine and hydroxyatrazine. Toxicol Sci, Nov; 76(1): 190- 200. Web Link

47. Laws, S.C., Hotchkiss, M., Ferrell, J., Jayaraman, S., Mills, L., Modic, W., Tinfo, N., Fraites, M., Stoker, T., & Cooper, R. (2009).Chlorotriazine Herbicides and Metabolites Activate an ACTHDependent Release of Corticostero ne in Male Wistar Rats. Tox. Sci., 112(1): 78-87. Web Link

48. Laws, S.C., Stoker, T.E., Ferrell , J.M., Hotchkiss, M.G., & Cooper R.L. (2007). Effects of Altered Food Intake During Pubertal Development in Male and Female Wi star Rats. Toxicol. Sci., Nov; 100(1): 194-202. Web Link

49. Lee, H.K. (2004). Bayesian Nonparametrics via Neural Networks. Philadelphia: ASA/SIAM. Book No Link Availabe 50. Lim, S., Ahn, S.Y., Song, I.C., Chung, M.H., Jang, H.C., Park, K.S., Lee, K., Pak, Y.K., & Lee, H.K. (2009). Chronic exposure to the herbicide, atrazine, causes mito chondrial dysfunction and insulin resistance. PLOS One, 4(4): 1-11. Web Link

51. Malik, S.I., Terzoudi, G.I., & Pantel ias, G.E. (2004). SCE analysis in G2 lymphocyte prematurely condensed chromosomes after exposure to atrazine: the non- dose-dependent increase in homologous recombinational events does not support its genotoxic mode of action. Cytogenet and Genome Research, 104(1-4): 315- 19. Web Link

52. Manske, M., Beltz, L, and Dhanwada, K. (2004). Low-Level Atrazine Exposure Decreases Ce ll Proliferation in Human Fibroblasts. Arch. Environ. Contam. Toxicol., 46(4): 438-44. Web Link

53. Maravilla-Galvan, R., Fierro, R ., Gonzalez-Marquez, H., GomezArroyo, S., Jimenez, I., & Betanc ourt, M. (2009). Effects of atrazine and fenoxaprop-ethyl on capacitation and the acrosomal reaction in boar sperm. Int. J. Toxicol., Jan-Feb, 28(1): 24-32. Web Link

54. McMullin T.S. (2003). Pharmacokinetic modeling of disposition and time-course studies with [ 14 C]-atrazine. J. Toxicol. Environ. Health, May 23;66(10):941-64. Web Link

55. McMullin, T.S., Andersen, M.E., Hanneman, W.H., Nagahara, A.,Page 19 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Lund, T.D., Pak, T., & Handa, R.J. (2004). Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced surge of luteinizing hormone in fe male Sprague-Dawley rats without changing estrogen receptor action. Toxicol Sci, Jun; 79(2): 278-86. Web Link

56. McMullin, T.S., Hanneman, W.H., Cranmer, B.K., Tessari, J.D., and Andersen, M.E. (2007). Or al absorption and oxidative metabolism of atrazine in ra ts evaluated by physiologically modeling approaches. Toxicol, Oct 30; 240(1-2): 1-14. Web Link

57. Meek, M.E., J.R. Bucher, S.M. Cohe n et al. (2003). A framework for human relevance analysis of information on carcinogenic modes of action. Crit Rev Toxicol, 33(6): 591-653. Web Link

58. Mizota, K. & Ueda, H. (2006). Endocrine disrupting chemical atrazine causes degranulation through Gq/11 protein-coupled neurosteroid receptor in mast cells. Toxicol Sci., Apr, 90(2): 362-8. Web Link

59. Modic, MW. (2004). The role of test icular aromatase in the atrazine mediated changes in estrone and estr adiol in the male wistar rat. North Carolina State University. Web Link

60. Mu, H., Zhang, P., & Xu, J. (2008) . Testicular toxicity and mechanisms of chlorotoluron compounds in the mouse. Toxicology Mechanisms and Methods, 18(5): 399-403. Web Link

61. Pinchuk, L.M., Lee, S.R., & Filipov, N.M. (2007). In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells. Toxicol Appl Pharmacol, Sept 15, 223(3): 206-17. Web Link

62. Pogrmic, K., Fa, S., Dakic, V., Kaisarevic, S. & Kovacevic, R. (2009). Atrazine oral exposur e of peripubertal male rats downregulates steroidogenesis ge ne expression in Leydig cells. Toxicol. Sci., Sept. 111(1): 189-97. Web Link

63. Pruett, S.B., Fan, R., Zheng, Q., My ers, L.P., & Hebert, P.(2003). Modeling and predicting immunol ogical effects of chemical stressors: characterization of a quantitative biomarker for immunological changes caused by at razine and ethanol. Toxicol Sci., Oct, 75(2):, 343-54. Web Link

64. Pruett, S.B., Fan, R., Zheng, Q., & Schwab, C. (2009). Patterns of immunotoxicity associated with ch ronic as compared with acute exposure to chemical or physical st ressors and their relevance with regard to the role of stress a nd with regard to immunotoxicity testing. Toxicological Sciences, Jun, 109(2): 265-75. Web Link

65. Rayburn, A.L., Moody, D.D., and Freeman, J.L. (2005). Cytotoxicity of technical grade vers us formulations of atrazine and acetochlor using mammalian cells. Bull. Environ. Contam. Toxicol., 75(4): 691-8. Web Link

66. Rayner, J.L., Wolf, D.C., Rayner, J.L., Enoch, J.L., Enoch, R.R., & Fenton, S.E. (2007). Atrazine-induced reproductive tract alterations after transplacental and/or lacatio nal exposure in male Long-Evans rats. Toxicol Appl Phar macol, Feb 1, 218(3): 238-48. Web Link

67. Rayner, J. L., Wood, C., Fenton, S. E. (2004). Exposure parameters necessary for delayed puberty and mammary gland development in Web LinkPage 20 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Long-Evans rats exposed in uter o to atrazine. Toxicol Appl Pharmacol, Feb 15; 195(1): 23-34.

68. Rivest, P. & Sanderson, J. (2010). Effects of pesticides on aromatase expression in bioluminescent mice and GSK 3BETA/BETA-signalling in LNCAp human prostate cancer cells. The Toxicologist 114, 405. Link is not available yet

69. Rodriguez, V.M., Thiruchelvam, M., & Cory-Slechta, D.A. (2005). Sustained exposure to the widely used herbicide atrazine: Altered function and loss of neurons in brain monoamine systems. Environmental Health Perspectives, Jun, 113(6): 708-15. Web Link

70. Rooney, A.A., Matulka, R.A ., & Luebke, R.W. (2003). Developmental atrazine exposure suppresses immune function in male, but not female Spragus-Dawley rats. Toxicol Sci., Dec, 76(2): 366-75. Web Link

71. Rosenberg, B.G., Chen, H., Folmer , J., Liu, J., Papadopoulos, V., & Zirkin, B.R. (2008). Gestational ex posure to atrazine: effects on the postnatal development of male offspring. J Androl., May-June; 29(3): 304-11. Web Link

72. Ross, M.K., Jones, T.L., and Fili pov, M.N. (2009). Disposition of the herbicide 2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (atrazine) and its major metabolites in mice: a liquid chromatography/mass spectrometry analysis of urine, plasma, and tissue levels. Drug Metab. Dispos., Apr; 37(4): 776-86. Web Link

73. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2008). Developmental immunotoxicity of atr azine in rodents. Basic Clin Pharmacol Toxicol, Feb; 102(2): 139-45. Web Link

74. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2007). In vitro atrazine exposure inhibits human natural killer cell lytic granule release. Toxicol Appl Ph armacol, Jun 1; 221(2): 179-88. Web Link

75. Rowe, A.M., Brundage, K.M., Schafer, R., & Barnett, J.B. (2006). Immunomodulatory effects of matern al atrazine exposure on male Balb/c mice. Toxicol Appl Phar macol, July 1; 214(1): 69-77 Web Link

76. Rusiecki, J.A., De Roos, A., Lee, W.J., Dosemci, M., Lubin J.H., Hoppin, J.A., Blair, A., & Alavanja , M.C. (2004). Cancer incidence among pesticide applicators exposed to atrazine in the Agricultural Health Study. J Natl Cancer Inst, Sept 15; 96(18): 1375-82. Web Link

77. Sanderson, J.T., Boerma, J., Gideon, W.A., Lansbergen, G.W. & van den Berg, M. (2002). Induc tion and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol Appl Pharmacol. Jul 1; 182: 44-54. Web Link

78. Santen R.J., Brodie H., Simpson E.R., Siiteri P.K., Brodie A.. (2009). History of Aromatase: sa ga of an important biological mediator and therapeutic target . Endocr Rev, Jun; 30(4): 343-75. Web Link

79. Schwab, C. L., Fan R., Zheng, Q., Myers, L.P., Hébert,P., & Pruet, S.B. (2005). Modeling and predicting stress-induced immunosuppression in mice using bl ood parameters. Toxicol Sci, Web LinkPage 21 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Jan; 83(1): 101-13. 80. Seed, J., E.W. Carney, R.A. Corley et al. (2005). Overview: Using mode of action and lifestage information to evaluate the human relevance of animal toxicity data. Crit. Rev. Toxicol., Oct-Nov; 35(8-9):664-72. Web Link

81. Shibayama, H., Kotera, T., Shinoda, Y., Hanada, T., Kajhara, T., Ueda, M., Tamura, H., Ishibashi, S., Yamashita, Y., & Ochi, S. (2009). Collaborative work on eval uation of ovarian toxicity. 14) Two- or four-week repeated-dos e studies and fertility study of atrazine in female rats. J Toxicol Sci., 34: 147-55. Web Link

82. Singh, M., Kaur, P., Sandhir, R., & Kiran, R. (2008a). Protective effects of vitamin E against atrazi ne-induced genotoxicity in rats. Mutat Res, Jul 31; 654(2): 145-9. Web Link

83. Singh, M., Sandhir, R., & Kiran, R.(2008b). Atrazine-induced alterations in rat erthrocyte membranes: ameliorating efect of vitamin E. J Biochem Mol Toxicol, Sept, 225: 363-9. Web Link

84. Son, H.Y., Nishikawa, A., Okazaki, K., Lee, K., Imazawa, T., & Hirose, M. (2003). Lack of modify ing effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rat pretreated with N-bis(2- hydroxypropyl)nitrosamine (DHPN). Food Chem Toxicol, Dec; 41(12): 1811-6. Web Link

85. Stoker T.E & Cooper R.L. (2007). Distribution of 14C-atrazine following an acute lactational expos ure in the Wistar rat. Reprod Toxicol, Jun; 23(4):607-10. Web Link

86. Stone, W.W. & Gilliom, R.J. (2009). Update of watershed regressions for pesticides (W ARP) for predicting atrazine concentration in streams. U.S. Geological Survey Open-File Report 2009–1122, 22 p. Available at http ://pubs.usgs.gov/of/2009/1122/ Web Link

87. Stone, W.W., Gilliom, R.J. & Crawford, C.G. (2008). Watershed Regressions for Pesticides (WARP) for Predicting Annual Maximum and Maximum Moving-Average Concentrations of Atrazine in Streams. U.S. Geol ogical Survey Open-File Report 08- 1186, 19 p. Web Link

88. Suzawa, M. & Ingraham, H.A. (2008). The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells. PloS ONE, 3(5): 1-11. Web Link

89. Tanaka, T., Kohno, H., Suzuki, R., & Sugie, S. (2004). Lack of modifying effects of an estr ogenic compound atrazine on 7,12- dimethylbenz(a)anthracene-induced ovarian carcinogenesis in rats. Cancer Lett, Jul 16; 210(2): 129-37. Web Link

90. Tinfo, N., & Laws, S.C. (2009). Understanding the Effects of Atrazine on Steroidogenesis in Wist ar rats. Society of Toxicology, Itinerary Planner, Baltimore, MD. Web Link

91. Ueda, M., Imai, T., Takizawa, T., Onodera, H., Mitsumori, K., Matsul, T., & Hirose, M. (2005). Possible enhancing effects of atrazine on growth of 7,12-dimet hylbenze(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats. Cancer Web LinkPage 22 of 25 For assistance contact Hamaad Syed 703-305-0502 syed.hamaad@epa.gov or Bill Zerfas 703-305-5445 zerfas.william@epa.gov Sci., Jan, 96(1): 19-25. 92. Victor-Costa, A.B., Carozzi Bandeira, S.M., Oliveira, A.G., Bohorquiz Mahecha, G.A. & Oliveira, C.A. (2010). Changes in testicular morphology and steroiodoge nesis in adult rats exposed to atrazine. Reprod Toxicol, Jan 4. [Epub ahead of print] Doi:10.1016/j.reprotox.2009.12.006 Web Link

93. Whalen M.M., Loganathan B.G., Yamashita, N., Saito, T. (2003). Immunomodulation of human natural killer cell cytotoxic function by triazine and carbamate pest icides. Chemico-Biological Interactions, Jun 15; 145(3): 311-19. Web Link

94. Zeljezic, D. & Garaj-Vrhovac, V. (2004a). Genotoxicity evaluation of pesticide formulations cont aining alachlor and atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet assay. Neoplasma, 51(3): 198-203. Web Link

95. Zeljeciz D, & Garaj-Vrhovac, V. (2004b). Atrazine genotoxicity evaluation in different mouse orga ns by comet assay. Periodicum Biologorum, 106(2):, 155-9. Web Link

96. Zeljezic, D., Garaj-Vrhovac, V., & Perkovic, P. (2006). Evaluation of DNA damage induced by atrazine and atrazine-based herbicide in human lymphocytes in vitro us ing a comet and DNA diffusion assay. Toxicol In Vitro, Sept; 20(6): 923-35. Web Link

97. Zorrilla, L.M., Gibson, E.K., Stoker (2009) Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

. Annual Meeting of the Society for Study of Reproduction, Pittsburgh, PA. Biol of Reprod, 81: 638. Web Link

4. FIFRA SAP Reference Materials - Pre-2003 References

1. Blomquist, J.D., Denis, J.M., Cowles, J.L., Hetrick, J.A., Jones, R.D. & Birchfield N.B. (2001). Pesticides in Selected Water-Supply Reservoirs and Finished Drinking Water, 1999- 2000: Summary of Results from a Pilot Monitoring Program . U.S. Geological Survey Open-File Report 01-456. Published in cooperation with the U.S. Environmental Protection Agency Web Link

2. Cooper, R.L., Stoker, T.E., Goldman, J.M., Parrish, M.B, & Tyrey, L. (1996). Effect of atrazine on ovari an function in the rat. Reprod Toxicol, Jul-Aug; 10(4): 257-64. Web Link

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