UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

Background Material Provided to the 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 Unpublished data from Syngenta Crop Protection, Inc. .................. 12 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 Unpublished data from Syngenta ................................................................................. 12 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Unpublished data from Syngenta............................................................................................ 12 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 Unpublished data 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 Luteinizing Hormone (LH) Surge in AtrazineExposed Female Sprague-Dawley Rats--(Final) 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 Unpublished study prepared by Corning 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 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............................................................ 12 

2. FIFRA Scientific Advisory Panel (SAP). (2003). “Characterization of Epidemiology 

Data Relating to Prostate Cancer and Exposure to Atrazine.” Report from the FIFRA 

Scientific Advisory Panel Meeting of July, 2003. FIFRA Scientific Advisory Panel, Office 

of Science Coordination and Policy, Office of Prevention, Pesticides 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.” Report from the FIFRA Scientific Advisory 

Panel Meeting of June 27-29, 2000. FIFRA Scientific Advisory Panel, Office of Science 

Coordination and Policy, Office of Prevention, Pesticides and Toxic Substances, U.S. 

Environmental Protection Agency. Washington, DC............................................................ 12 

4. FIFRA Scientific Advisory Panel (SAP). (1988). “A set of issues being considered by 

the Agency in connection with the peer review classification of atrazine a class 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, Pesticides and Toxic Substances, U.S. Environmental Protection Agency. 

Washington, DC...................................................................................................................... 13 
Page 2 of 25 

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5. U.S. Environmental Protection Agency. (2010). DRAFT Framework for Incorporating 

Human Epidemiologic & Incident Data in Health Risk Assessment (Draft 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 (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. ...................................................................................................... 13 

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 (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................................. 13 

8. U.S. Environmental Protection Agency (USEPA). 2007a. Acetochlor 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 (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. ...................................................................................................... 13 

11. US EPA. (2006). Decision Documents for Atrazine. Atrazine IREDs (January and 

October 31, 2003) and Atrazine RED (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 Forum, Washington, DC. EPA/630/P-03/001F. 

Federal Register 70(66):17765-17817. ................................................................................... 13 

13. US EPA. (2003). Interim Re-registration Eligibility Decision (IRED)...................... 13 

3. FIFRA SAP Reference Materials - Post 2003 References................................................. 14 

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 Receptor 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 ..

 ........................................................................................................14 

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 effects induced by atrazine in 

ovarian cancer cells. Environ Health 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 during the growing season. J Expo Sci Environ 

Epidemiol, Sep; 19(6):544-54................................................................................................. 14 

4. Belloni V, Alleva E, et al. (2007). Effects of low 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 endocrine disrupters alone and in combination. 

Toxicol Appl Pharmacol, Jul 15; 222(2): 129-40. .................................................................. 14 
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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. Reprod 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 juvenile exposure of mice to 

arsenate and atrazine in drinking water modulates gene expression and clonogenicity of 

myeloid progenitors. Toxicol Lett, Jul 30; 180(1): 59-66. .................................................... 14 

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. ..................................................................................................................... 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 function: mode and mechanism of action studies. 

Birth Defects Res B Dev Reprod Toxicol, Apr; 80(2): 98-112. ............................................ 14 

11. Crawford, C.G. (2004). Sampling Strategies 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., 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............................................................................... 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 pituitary glands and LbetaT2 rat pituitary cells. 

Chem Res Toxicol, Apr, 21(4): 844-51. ................................................................................. 15 

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. ..................................................... 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 Research 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: implications for endocrine disruption in wildlife 

and reproductive cancers in humans. Environ Health Perspect, May, 115(5): 720-7. .......... 15 
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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 striatal slices. Toxicol, Mar 22; 232(1-2): 68-78..... 15 

22. Foradori, C., Hinds, L., Hanneman, W., & Handa, R. (2009a). Effects of atrazine 

and its withdrawal on gonadotropin-releasing hormone neuroendocrine function in the adult 

female Wistar rat. Biol Reprod, Dec, 81(6): 1099-105.......................................................... 16 

23. Foradori, C., Hinds, L., Hanneman, W., Legare, M., Clay, C., & Handa, R. (2009b). 

Atrazine inhibits pulsatile luteinizing hormone release without altering pituitary sensitivity to 

a gonadotropin-releasing hormone receptor agonist 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-Pituitary-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). 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.................................................................................................. 16 

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 atrazine and nonylphenol 

on 7,2-dimethylbenz[a]anthracene-induced mammary 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 accounts for a dimorphic 

somatostatinergic neuronal expression pattern in mice. Toxicol Sci, Jan; 89(1): 257-64. .... 16 

29. Gojmerac, T., Pleadin, J., Zuric, M., Rajkovic-Janje, R., & Korsic, M. (2004). Serum 

luteinizing hormone response to administration 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 mitochondrial function in sperm. Biochem Biophys Res Commun, Feb 

1; 366(1): 66-72. ..................................................................................................................... 16 

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................................................................................................... 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., Turner N., Hoy A., Maghzal G., Socker 

R., Van Remmen H., Kraegen E., Cooney G., Richardson A., James D. (2009). Insulin 
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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 for Targeted Testing Prioritization - The Tox 

Cast Project. Environ Health 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: morphological alterations in ovarian follicles and 

immunocytochemical labeling of 90 kDa heat shock protein. Micron, 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 carcinogenesis in probasin/SV40 T 

antigen transgenic rats. Cancer 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., 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. ........................................................ 17 

42. Kmetic, I., Gaurina Srcek, V., Silvac, I., Simic, B., Kniewald, Z., & Kniewald, J. 

(2008). Atrazine exposure decreases cell proliferation in Chinese Hamster Ovary (CHO-K1) 

cell line. Bull Environ Contam Toxicol., Aug, 81(2): 205-9................................................. 17 

43. Kniewals, J., Kmetič, I., Gaurina Srček, V., Šimiċ,B., & Kniewald, Z. (2003). 

Cytotoxicity of Herbicide Atrazine On Chinese 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 (WARP) for estimating atrazine concentration 

distributions in streams. U.S. Geological Survey Water-Resources Investigations Report 03–

4047, 68 p................................................................................................................................ 18 

45. Laville, N., Balaguer, P., Brion, F., Hinfray, N., Casellas, C., Porcher, J.M., & AitAissa, S. (2006). Modulation of aromatase activity 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., & Cooper, R.L. (2003). Pubertal development 

in female Wistar rats following exposure to propazine and atrazine biotransformation byproducts, diamino-S-chlorotriazine and hydroxyatrazine. Toxicol Sci, Nov; 76(1): 190-200. .

 .....................................................................................................18 

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 ACTH-Dependent Release of Corticosterone in Male Wistar Rats. Tox. Sci., 

112(1): 78-87. ......................................................................................................................... 18 
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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 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 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................................................. 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 atrazine and fenoxaprop-ethyl on capacitation and the 

acrosomal reaction in boar sperm. Int. J. Toxicol., Jan-Feb, 28(1): 24-32............................ 18 

54. McMullin T.S. (2003). Pharmacokinetic modeling of disposition and time-course 

studies with [14C]-atrazine. J. Toxicol. Environ. Health, May 23;66(10):941-64. ................. 18 

55. McMullin, T.S., Andersen, M.E., Hanneman, W.H., Nagahara, A., Lund, T.D., Pak, 

T., & Handa, R.J. (2004). Evidence that atrazine and diaminochlorotriazine inhibit the 

estrogen/progesterone induced surge of luteinizing 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 carcinogenic modes of action. Crit Rev Toxicol, 33(6): 

591-653. .................................................................................................................................. 19 

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. ........................................................................................................... 19 

59. Modic, MW. (2004). The role of testicular 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). Testicular toxicity and mechanisms of 

chlorotoluron compounds in the mouse. Toxicology 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 dendritic 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 downregulates 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: characterization of a quantitative 
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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 acute exposure to chemical or physical stressors 

and their relevance with regard to the role of stress and with regard 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 acetochlor 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 alterations after transplacental and/or lacational 

exposure in male Long-Evans rats. Toxicol 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 development 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-signalling 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 loss of neurons in brain 

monoamine systems. Environmental Health 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: effects 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-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. ................................................................. 20 

73. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2008). Developmental 

immunotoxicity of atrazine in rodents. Basic Clin Pharmacol Toxicol, Feb; 102(2): 139-45...

 .....................................................................................................20 

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 Pharmacol, Jun 1; 

221(2): 179-88. ....................................................................................................................... 20 

75. Rowe, A.M., Brundage, K.M., Schafer, R., & Barnett, J.B. (2006). 

Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice. Toxicol 

Appl Pharmacol, July 1; 214(1): 69-77................................................................................... 20 

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. .... 20 

77. Sanderson, J.T., Boerma, J., Gideon, W.A., Lansbergen, G.W. & van den Berg, M. 

(2002). Induction 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. .............................................................................................................................. 20 
Page 8 of 25 

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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

78. Santen R.J., Brodie H., Simpson E.R., Siiteri 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 work on evaluation of 

ovarian toxicity. 14) Two- or four-week repeated-dose 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 effects 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 vitamin 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). Distribution of 14C-atrazine following an acute 

lactational exposure in the Wistar rat. Reprod Toxicol, Jun; 23(4):607-10........................... 21 

86. Stone, W.W. & Gilliom, R.J. (2009). Update of watershed regressions 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 Annual 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-dimethylbenz(a)anthracene-induced ovarian 

carcinogenesis in rats. Cancer Lett, Jul 16; 210(2): 129-37. ................................................. 21 

90. Tinfo, N., & Laws, S.C. (2009). Understanding 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 atrazine on growth of 7,12-dimethylbenze(a) 

anthracene-induced mammary tumors in ovariectomized 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....................................................................................... 22 
Page 9 of 25 

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93. Whalen M.M., Loganathan B.G., Yamashita, N., Saito, T. (2003). 

Immunomodulation of human natural killer cell cytotoxic function 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 genotoxicity evaluation in 

different mouse organs by comet assay. Periodicum Biologorum, 106(2):, 155-9. .............. 22 

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 using a 

comet and DNA diffusion assay. Toxicol 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 Neuronal 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., 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 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., Parrish, M.B, & Tyrey, L. (1996). Effect of 

atrazine on ovarian function in the rat. Reprod Toxicol, 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 Software 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 chronic atrazine administration. Reprod Toxicol, Nov-Dec; 

13(6): 491-9. ........................................................................................................................... 23 

7. Friedmann, A.S. (2002). Atrazine inhibition of testosterone production in rat males 

following peripubertal exposure. Reprod. 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 steroidogenic capacity of purified rat Leydig cells 

in vitro. Endocrinology, May; 137(5):1714-8........................................................................ 23 

9. ILSI (International Life Sciences Institute), (1999). A Framework for Estimating 

Pesticide Concentrations in Drinking Water for Aggregate Exposure Assessments. 

International Life Sciences Institute Risk Science Institute Working Group Report, 

Washington, D.C., 61 pp......................................................................................................... 23 

10. Isaaks, E.H., and R.M. Srivastava. (1989). Applied 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............................................................................ 23 
Page 10 of 25 

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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 Protocol for Assessing 

Pubertal Development and Thyroid Function. Toxicol Sci, 58: 366-76................................ 23 

13. Lyons, W.R., Berlin, I., and Friendlander, S. (1942) Cornification of balano-preputial 

epithelium in normal rats and castrated rats treated with testosterone proprionate. 

Endocrinology, 31(6): 659-63................................................................................................. 23 

14. Marshall, F. (1966) Marshall’s Physiology 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 mechanism 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., Bailey 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, Ostby J, Gray LE Jr. (1999). Peripubertal 

exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the 

development of androgen-dependent tissues, and alters androgen receptor function in the 

male rat. Toxicol Ind Health, Jan-Mar; 15(1-2): 65-79. ........................................................ 23 

18. Ojeda, S.R., and Urbanski, H.F. (1994). Puberty in the rat. In E. Knobil and J.D. 

Neill (Eds.): The Physiology of Reproduction, 2nd ed. New York, Raven Press................... 23 

19. Rivest, .S & Rivier, C. (1995). The role of corticotropin-releasing factor and 

interleukin-1 in the regulation of neurons controlling reproductive functions. Endocr Rev, 

16(2): 177-99. ......................................................................................................................... 23 

20. Rivier, C. & Rivest, S. (1991). Effect of stress on the activity of the hypothalamicpituitary-gonadal axis: peripheral and central mechanisms. Biol Reprod., October 1, 1991; 45 

(4): 523-532. ........................................................................................................................... 24 

21. Rivier, C., Rivier, J., & Vale, W. (1986). Stress-induced inhibition of reproductive 

functions: role of endogenous corticotropin-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 various 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 vitellogenin production in male carp hepatocytes. 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) activity in H295R human adrenocortical carcinoma 

cells: a novel mechanisms for estrogenicity? 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., Boon, 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). Minireview: aromatase and the regulation of 

estrogen biosynthesis – some new perspectives. 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 for chemical carcinogenesis. Regul Toxicol Pharmacol, Oct; 

34(2):146-52. .......................................................................................................................... 24 
Page 11 of 25 

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29. Stoker, T.E., Guidici, D.L., Laws, S.C. & Cooper, R.L. (2002). The Effects of 

Atrazine Metabolites on Puberty and Thyroid Function in the Male Wistar Rat: An 

Evaluation in the Male Pubertal Protocol. Toxicol. Sci., 67: 198-206. ................................. 24 

30. Stoker, T.E., Laws, S.C., Guidici, D., & Cooper, R.L. (2000). The effects of atrazine 

on puberty and thryroid function in the male wistar rat: An evaluation of a protocol for the 

assessment of pubertal development and thyroid function. Toxicol. 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., Friedmann, A.S., Youker, R.T., Breckenridge, C.B. & Zirkin, B.R. 

(2001). Atrazine effects on testosterone levels and androgen-dependent reproductive organs 

in peripubertal male rats. J. Androl, Jan-Feb; 22(1): 142-8................................................... 24 
Page 12 of 25 

*These materials are subject to FIFRA 10(g) and therefore are provided on a separate disc For assistance contact Hamaad Syed 

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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-dependent-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 the 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 NOAEL 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 Project 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 Considered 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 FIFRA Scientific Advisory Panel 

Meeting of July, 2003. FIFRA Scientific Advisory Panel, Office of 

Science Coordination and Policy, Office of Prevention, Pesticides 

and Toxic Substances, U.S. Environmental Protection Agency. 

Washington, DC. 

Web Link

3. FIFRA Scientific Advisory Panel (SAP). (2000). “Atrazine: 

Hazard and Dose-Response Assessment and Characterization.” 

Report from the FIFRA Scientific Advisory Panel Meeting of June 

27-29, 2000. FIFRA Scientific Advisory Panel, Office of Science 

Web Link
Page 13 of 25 

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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 (SAP). (1988). “A set of issues 

being considered by the Agency in connection with the peer review 

classification of atrazine a class 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, Pesticides 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 January 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 (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. 

Web Link

8. U.S. Environmental Protection Agency (USEPA). 2007a. 

Acetochlor Registration Agreement and Monitoring Program. 

Documents are available through the 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 Documents for Atrazine. Atrazine IREDs 

(January and October 31, 2003) and 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-registration Eligibility Decision 

(IRED) Web Link
Page 14 of 25 

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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 Receptor 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 effects 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 development of mice. Ethology Ecology & 

Evolution, 19: 309-22. 

Web Link

5. Benachour, N., Moslemi, S., Sipahutar, H., & Seralini G.E. (2007). 

Cytotoxic effects and aromatase inhibition by xenobiotic endocrine 

disrupters alone and in combination. Toxicol Appl Pharmacol, Jul 

15; 222(2): 129-40. 

Web Link

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. Reprod 

Toxicol, Oct, 22(3): 508-12. 

Web Link

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. 

Web Link

8. Cimino-Reale, G., Ferrario, D., Casati, B., Brustio, R., Diodovich, C., 

Collotta, A., Vahter, M., & Gribaldo, L. (2008). Combined in utero 

and juvenile exposure of mice to arsenate and atrazine in drinking 

water modulates gene expression 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). Atrazine and reproductive function: 

mode and mechanism of action studies. Birth Defects Res B Dev 

Web Link
Page 15 of 25 

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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

Reprod Toxicol, Apr; 80(2): 98-112. 

11. Crawford, C.G. (2004). Sampling Strategies for Estimating Acute and 

Chronic Exposures of Pesticides in Streams. Journal of the American 

Water Resources Association (JAWRA) 40(2):485-502. 

Web Link

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. 

Web Link

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, 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 diaminocholorotriazine adducts in Wistar rat 

pituitary glands and LbetaT2 rat pituitary cells. Chem Res Toxicol, 

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18. Fan, W., Yanase, T., Morinaga, H., Gonda, S., Okabe, T., Nomura, 

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20. Filipov, N.M., Pinchuk, L.M., Boyd, B.L., & Crittenden P.L. 

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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

Dopaminergic toxicity of the herbicide atrazine in rat striatal slices. 

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23. Foradori, C., Hinds, L., Hanneman, W., Legare, M., Clay, C., & 

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24. Fraites, M.J.P., Cooper, R.L., Buckalew, A., Jayaraman, S., Mills, 

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27. Gilliom R.J., Barbash, J.E., Crawford, C.G., Hamilton, P.A., Martin, 

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Thelin, G.P. & Wolock, D.M. (2006). The quality of our Nation’s 

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28. Giusi, G., Facciolo, R.M., Canoaco, M., Alleva, E., Santucci, D., 

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29. Gojmerac, T., Pleadin, J., Zuric, M., Rajkovic-Janje, R., & Korsic, 

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30. Hase, Y., Tatsuno, M., Nishi, T., Kabe, Y., Yamaguchi, Y., Hanada, 

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31. Heneweer, M., Van den Berg, M., & Sanderson, J.T. (2004). A 

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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 

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33. Hocking, B. (2009). Melamine-contaminated powdered formula 

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34. Hoehn K., Salmon A., Hohnen-Behrens C., Turner N., Hoy A., 

Maghzal G., Socker R., Van Remmen H., Kraegen E., Cooney G., 

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35. Holloway, A.C., Anger, D.A., Crankshaw, D.J., Wu, M., & Foster, 

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36. Hossain, M. M. & Filipov, N. M. (2008). Alteration of dopamine 

uptake into rat striatal vesicles and synaptosomes caused by an in 

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37. Judson R.S., Houck K.A., Kavlock R.J., Knudsen T.B., Martin 

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38. Juliani, C.C., Silva-Zacarin, E.C., Santos, D.C., & Boer, P.A.(2008). 

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39. Kandori, H., Suzuki, S., Asamoto, M., et al. (2005). Influence of 

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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. 

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41. Kirby E.D., Geraghty A.C., Ubuka T., Bentley G.E., Kaufer D. 

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42. Kmetic, I., Gaurina Srcek, V., Silvac, I., Simic, B., Kniewald, Z., & 

Kniewald, J. (2008). Atrazine exposure decreases cell proliferation 

in Chinese Hamster Ovary (CHO-K1) cell line. Bull Environ 

Contam Toxicol., Aug, 81(2): 205-9. 

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43. Kniewals, J., Kmetič, I., Gaurina Srček, V., Šimiċ,B., & Kniewald, 

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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 Regressions for Pesticides (WARP) 

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Geological Survey Water-Resources Investigations Report 03–4047, 

68 p. 

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45. Laville, N., Balaguer, P., Brion, F., Hinfray, N., Casellas, C., 

Porcher, J.M., & Ait-Aissa, S. (2006). Modulation of aromatase 

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108. 

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46. Laws, S.C., Ferrell, J.M., Stoker, T.E., & Cooper, R.L. (2003). 

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propazine and atrazine biotransformation by-products, diamino-Schlorotriazine and hydroxyatrazine. Toxicol Sci, Nov; 76(1): 190-

200. 

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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 Corticosterone in Male Wistar Rats. Tox. 

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48. Laws, S.C., Stoker, T.E., Ferrell, J.M., Hotchkiss, M.G., & Cooper 

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51. Malik, S.I., Terzoudi, G.I., & Pantelias, G.E. (2004). SCE analysis 

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19. 

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52. Manske, M., Beltz, L, and Dhanwada, K. (2004). Low-Level 

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53. Maravilla-Galvan, R., Fierro, R., Gonzalez-Marquez, H., GomezArroyo, S., Jimenez, I., & Betancourt, 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. 

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54. McMullin T.S. (2003). Pharmacokinetic modeling of disposition 

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Health, May 23;66(10):941-64. 

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55. McMullin, T.S., Andersen, M.E., Hanneman, W.H., Nagahara, A., 
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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 female Sprague-Dawley rats without 

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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 

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57. Meek, M.E., J.R. Bucher, S.M. Cohen et al. (2003). A framework 

for human relevance analysis of information on carcinogenic modes 

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58. Mizota, K. & Ueda, H. (2006). Endocrine disrupting chemical 

atrazine causes degranulation through Gq/11 protein-coupled 

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59. Modic, MW. (2004). The role of testicular aromatase in the atrazine 

mediated changes in estrone and estradiol in the male wistar rat. 

North Carolina State University. 

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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. 

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61. Pinchuk, L.M., Lee, S.R., & Filipov, N.M. (2007). In vitro atrazine 

exposure affects the phenotypic and functional maturation of 

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62. Pogrmic, K., Fa, S., Dakic, V., Kaisarevic, S. & Kovacevic, R. 

(2009). Atrazine oral exposure of peripubertal male rats 

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63. Pruett, S.B., Fan, R., Zheng, Q., Myers, L.P., & Hebert, P.(2003). 

Modeling and predicting immunological effects of chemical 

stressors: characterization of a quantitative biomarker for 

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Sci., Oct, 75(2):, 343-54. 

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64. Pruett, S.B., Fan, R., Zheng, Q., & Schwab, C. (2009). Patterns of 

immunotoxicity associated with chronic as compared with acute 

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testing. Toxicological Sciences, Jun, 109(2): 265-75. 

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65. Rayburn, A.L., Moody, D.D., and Freeman, J.L. (2005). 

Cytotoxicity of technical grade versus formulations of atrazine and 

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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 lacational exposure in male Long-Evans 

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67. Rayner, J. L., Wood, C., Fenton, S. E. (2004). Exposure parameters 

necessary for delayed puberty and mammary gland development in Web Link
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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

Long-Evans rats exposed in utero to atrazine. Toxicol Appl 

Pharmacol, Feb 15; 195(1): 23-34. 

68. Rivest, P. & Sanderson, J. (2010). Effects of pesticides on 

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3BETA/BETA-signalling in LNCAp human prostate cancer cells. 

The Toxicologist 114, 405. 

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available yet 

69. Rodriguez, V.M., Thiruchelvam, M., & Cory-Slechta, D.A. (2005). 

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71. Rosenberg, B.G., Chen, H., Folmer, J., Liu, J., Papadopoulos, V., & 

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72. Ross, M.K., Jones, T.L., and Filipov, M.N. (2009). Disposition of 

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73. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2008). 

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74. Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2007). In vitro 

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78. Santen R.J., Brodie H., Simpson E.R., Siiteri P.K., Brodie A.. 

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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 

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81. Shibayama, H., Kotera, T., Shinoda, Y., Hanada, T., Kajhara, T., 

Ueda, M., Tamura, H., Ishibashi, S., Yamashita, Y., & Ochi, S. 

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82. Singh, M., Kaur, P., Sandhir, R., & Kiran, R. (2008a). Protective 

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83. Singh, M., Sandhir, R., & Kiran, R.(2008b). Atrazine-induced 

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703-305-0502 syed.hamaad@epa.gov or 

Bill Zerfas 703-305-5445 zerfas.william@epa.gov

Sci., Jan, 96(1): 19-25. 

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4. FIFRA SAP Reference Materials - Pre-2003 References 

1. Blomquist, J.D., Denis, J.M., Cowles, J.L., Hetrick, J.A., Jones, R.D. & 

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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

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Bill Zerfas 703-305-5445 zerfas.william@epa.gov

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703-305-0502 syed.hamaad@epa.gov or 

Bill Zerfas 703-305-5445 zerfas.william@epa.gov

33. Wetzel L.T., Luempert L.G., III Breckenridge C.B., Tisdel M.O., 

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